SUMMARY Fifteen patients with peptic ulcer underwent 24 hour studies of gastric contents: before and on completing six weeks' treatment with oral ranitidine 150 mg bd, twice on maintenance treatment for nine to 12 months and one month after stopping the drug. For comparison, 11 patients underwent identical 24 hour studies three to 38 months after truncal vagotomy for duodenal ulcer. During treatment with ranitidine median 24 hour intragastric pH, nitrate concentration, and counts of total and nitrate reducing bacteria increased significantly regardless of dietary nitrate content; there was no significant increase in the median day time concentration of N-nitroso compounds. Despite these changes, an acid tide at some point in each 24 hour study period prevented persistent bacterial colonisation of the stomach. There were no significant differences between the biochemical and microbiological changes recorded during one year of treatment with ranitidine, and the observations on patients after truncal vagotomy. One month after stopping one year's treatment with ranitidine all variables examined returned to pretreatment levels. Treatment with ranitidine or vagotomy was associated with significant positive correlations among pH, nitrate concentration and bacterial counts. Correlations between pH and N-nitroso compound concentration and between concentrations of nitrite and N-nitroso compounds were not significant.Pernicious anaemia,'-' partial gastrectomy,l and vagotomy7-9 appear to be associated with increased risk of gastric cancer. The exact cause is unknown but a hypothetical sequence of events necessary for the development of gastric cancer in hypochlorhydric states has been postulated"" and depends on the persistence within the stomach at pH>4-0 of metabolically active bacteria capable of reducing dietary nitrate to nitrate. Nitrate may then react with amides or amines to form N-nitroso compounds, most of which are carcinogenic to animals. Concern has been expressed about a similar carcinogenic potential arising from medical treatment of ulcer using potent acid lowering drugs such as the histamine H2-receptor antagonists, particularly when treatment is prolonged in prophylaxis against ulcer recurrence.Studies of fasting gastric juice have suggested

SummaryThe response to a standard water load (20 ml/kg body weight) was studied in 20 patients with chronic obstructive airways disease and in 13 healthy subjects. The percentage of the water load excreted in four hours was significantly lower in the patients (mean 51go ) than in the controls (mean 1060' ). The maximum urine flow, osmolar clearance, free water clearance, and creatinine clearance were also significantly reduced in the patients. There was a significant inverse correlation between the percentage of load passed and the arterial Pco2 (r = -0 798). Among the several possible causes of the reduced excretion of water which are discussed is a direct effect of hypercapnia.

HertfordshireSUMMARY The effect of the specific thromboxane receptor blocking drug AH23848 was investigated in two double blind placebo controlled studies in male patients with exercise induced angina pectoris and angiographically verified coronary lesions. In the first study cardiac pacing was performed in twenty patients after coronary angiography. Patients were then randomised into two groups and received either AH23848 (70 mg orally) or placebo. One hour later cardiac pacing was repeated. Neither treatment had any significant effect upon time to angina or the ratepressure product at the onset of chest pain in these patients. In the second study twenty male patients were randomised to seven days' treatment with AH23848 (70 mg three times a day) or placebo followed by a crossover to the other treatment for a further seven days. Clinical assessment was performed before treatment and at the end of each treatment period. There was no significant difference between the placebo and AH23848 treatment periods in exercise tolerance, the rate-pressure product at angina after exercise testing, the number of ischaemic attacks as determined from 24 hour ambulatory electrocardiograms, the number of attacks of pain, or the number of glyceryl trinitrate tablets consumed. This lack of a clinical effect with AH23848 was seen despite a profound inhibition of ex vivo platelet aggregration stimulated by the thromboxane A2-mimetic U-46619. Because in experimental animals in vivo AH23848 blocks vascular thromboxane receptors as well as platelet thromboxane receptors the lack of effect of AH23848 in cardiac pacing and exercise induced angina is unlikely to be the result of inadequate blockade of -thromboxane receptors. The lack of effect of the drug is more likely to indicate that thromboxane A2 is not a factor in the aetiology of the pain experienced by these patients during exercise or cardiac pacing.

No abstract

As a short test of adrenocortical function, plasma cortisol values were determined before, and 15 and 30 minutes after, a single intravenous injection of 10 μg of a synthetic polypeptide αh1–28 ACTH (HOMACTID) given between 9 and 10 a. m. Its usefulness in a screening test to exclude primary adrenocortical insufficiency is suggested based on a single plasma corticosteroid concentration obtained 30 minutes after the HOMACTID injection, a normal response being a level of greater than 19 μg/100 ml at this time. In 30 control subjects the mean plasma cortisol level rose by 8.9 (± se 0.8) μg/100 ml at 15 minutes and 12.0 (± se 0.9) μg/100 ml at 30 minutes from a resting value of 15.5 (± se 1.1) μg/100 ml. HOMACTID can thus be used as a quick test of adrenal function in the same way as Synacthen®.