Twenty patients with persistent diarrhoea participated in a randomised, double-blind trial of oral sodium cromoglycate and placebo. Eight patients noted significant improvement in their diarrhoea while taking sodium cromoglycate and this did not correlate with the presence of other atopic diseases, a history of food intolerance, or the presence of lactase deficiency. The results suggest that some patients with diarrhoea of unknown cause may have food allergy as a major contributing cause for their diarrhoea.

Fifteen patients with cystic fibrosis and pancreatic insufficiency were studied during four randomised seven day treatment periods in which they received only pancreatic supplement (Pancrelipase, 27 capsules per day) or supplement plus cimetidine (20 mg/kg body weight/24 h) or sodium bicarbonate (15 g/m2/24 h) alone or in combination. Dietary intake was not fixed but was restricted to foods of known fat and nitrogen content from which daily intakes could be computed. Faecal fat and nitrogen were calculated as g/24 h and percentage of intake. Addition of either cimetidine or bicarbonate resulted in significant improvement in fat and nitrogen excretion, which was not greater with the combination of both drugs. Cimetidine and sodium bicarbonate in these doses are therefore sufficient to produce maximal improvement in digestive activity of pancreatic supplements. Fat excretion per gram of intake fell with cimetidine and bicarbonate from 12 times the normal level, to normal, in patients consuming less than 120 g fat daily. Above this intake the dose of pancreatic supplement appeared to be inadequate. Faecal nitrogen excretion increased with nitrogen intake in all four periods, but, in contrast with fat excretion, the response to cimetidine and bicarbonate was not affected by the level of intake. Dietary intake appears to be a significant factor in determining the faecal output of fat and nitrogen in patients with pancreatic insufficiency and should be considered when determining the optimum amount of pancreatic supplementation.

Prostaglandins have been shown in animal laboratory studies to be capable of protecting the gastrointestinal tract against injury by exogenous agents. This study was conducted to determine if prostaglandin E2 (PGE2), which is native to the human gastric mucosa, could influence the increase in faecal blood loss associated with the ingestion of aspirin (ASA). A randomised double-blind study was performed on 27 healthy men. Faecal blood loss was measured by the 51Cr labelled red cell technique. ASA (600 mg four times daily) caused a significant increase in faecal blood loss. PGE2 (1 mg four times daily) had no effect on faecal blood loss when administered alone. When given in addition to ASA it resulted in a faecal blood loss not significantly different from control. No significant alteration in intestinal transit occurred. It is concluded that PGE2 protects man from the gastrointestinal injury associated with ASA.

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.

Suppositories of sulphapyridine, 5-aminosalicylic acid, and placebo were used in 45 patients with idiopathic proctitis to determine the active part of sulphasalazine. Each patient used one of the suppositories twice daily for four weeks in a double-blind controlled trial. Complete clinical remission with normal rectal mucosa on sigmoidoscopy occurred in 60% of patients given 5-aminosalicylic acid, but in only 13% and 27% of those given sulphapyridine and placebo respectively. Twelve patients were included twice. In eight of these patients 5-aminosalicylic acid was given one time and sulphapyridine (two patients) or placebo (six patients) another time. Clinical remission occurred in each patient with 5-aminosalicylic acid, but in only one patient during other therapy. The results suggest that 5-aminosalicylic acid is the active therapeutic moiety of sulphasalazine.

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.

The results of endoscopic cytology during the period 1974 to 1976 are presented. These consist of a pilot study on 76 patients and a main trial on 329 patients, of whom 61 proved to have malignant disease as the final diagnosis. Methods of cell collection, preparation, and reporting are given. Special emphasis was placed on making a definitive diagosis, especially the distinction between severe atypia and malignancy, and 'suspicious' reports were not issued. The overall accuracy achieved for all tumour types was 91.8%, with an accuracy of 98% in the diagnosis of adenocarcinoma of the stomach. There were no false positive cytology reports. Endoscopic histology on the same patients gave an accuracy of 68.9% and did not give a positive result in any of the five cases with false negative cytology. Adequate sampling, a variety of cell collection methods, and great care in technique are necessary in order to obtain optimum sensitivity and specificity in cytological diagnosis.

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.

This double-blind controlled trial compares the relapse rate in 19 duodenal ulcer patients who received cimetidine for eight weeks with that in 19 patients who received cimetidine for four weeks and inactive tablets for four weeks. Only patients who became symptom-free during the initial four weeks' treatment with cimetidine were included. The median period of remission after withdrawal of cimetidine was 50 days in patients treated with cimetidine for eight weeks and 76 days in patients treated with cimetidine for four weeks (P greater than 0.10). Six months after withdrawal of cimetidine 15 relapses had occurred in both groups. It is concluded that patients who become symptom-free during four weeks' cimetidine treatment do not benefit by continuation of treatment for another four weeks.

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.

Plasma gastrin concentrations and gastric acid output after modified sham feeding were determined in 20 duodenal ulcer patients. Sham feeding produced an acid response corresponding to 40-68% of the maximal acid output after pentagastrin stimulation, with no significant increase of plasma gastrin concentrations. In eight patients proximal gastric vagotomy almost abolished the acid responses to both insulin hypoglycaemia and sham feeding. Sham feeding in the vagotomised patients did not change the gastrin concentrations in plasma. After pretreatment with benzilonium, an anticholinergic with minimal central nervous effects, plasma gastrin concentrations increased after sham feeding. The study confirms that sham feeding is a poor stimulus for gastrin release in duodenal ulcer patients and supports a cholinergic inhibition of gastrin release. Intravenous injection of benzilonium bromide in a dose close to 70 micrograms/kg, and atropine in the low dose of 30 micrograms/kg inhibited the acid response to sham feeding by about 65%. Atropine in a dose of 50 micrograms/kg virtually abolished the acid sham feeding response, possibly owing to ganglionic or central nervous blockade. Vagal activation of the acid secretory glands does not seem to involve a purely cholinergic neurotransmission.

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.