The possible existence of kinetic interactions between rifampicin and isoniazid and the effect of the concomitant presence of an impaired liver function were investigated in man. In a first study normal healthy subjects and patients with chronic liver disease received, on three different occasions, a single dose of 600 mg rifampicin or isoniazid and of rifampicin and isoniazid associated in randomized sequences. The results have shown that in both groups the serum levels, half-life values, and urinary excretion of each drug given alone are not significantly different from those observed when the other drug is associated. Serum levels and half-life of rifampicin and isoniazid were significantly higher in patients with chronically impaired liver. In a second study, rifampicin and isoniazid were given in combination at the same doses as in the first study over a period of one week. The results have shown a trend to decrease in the serum levels of rifampicin of the healthy subjects and a trend to increase in the patients with chronic liver disease on day 7 of treatment. In both groups a reduction in the half-life of rifampicin was also observed. No changes in serum isoniazid concentrations were observed between day 1 and day 7 in the healthy subjects, whereas a significant increase was observed in the patients. No significant changes in the half-life of isoniazid were observed.

Ten flatulent but otherwise healthy subjects were studied while consuming two or three different diets. Flatus collections showed that a bean-containing, high crude-fibre diet produced more flatus (mean 49.4 ml/hr) than either a diet with a restricted crude-fibre content (mean 26.7 ml/hr) or a liquid chemically defined diet (mean 10.9 ml/hr). There was a close correlation between the crude-fibre content of the diet and the production of flatus. The results are consistent with the conclusion that flatus is not the result of swallowing air, but arises mainly from bacterial fermentation of indigestible carbohydrate, eg, cellulose, passing into the colon.

A double blind comparison of conventional premedication (pethidine, promethazine, and atropine) and neuroleptanalgesia (droperidol and phenoperidine) failed to demonstrate any difference in either the comfort of the patient or ease of instrumentation in 70 upper gastrointestinal tract endoscopies. Further trials are needed before conventional premedication is abandoned.

A double-blind trial of deglycyrrhizinated liquorice was performed in 47 patients with active duodenal ulcer. Twenty-four patients received a placebo and 23 the trial medication (Caved-S) for one month. Both groups were clinically similar. No advantage of deglycyrrhizinated liquorice over placebo was found.

The effects on biliary pressure of pentazocine, morphine, pethidine, and phenazocine were compared by direct measurement through a ;T' tube after choledochotomy. In two within-patient comparisons, the mean increases in biliary pressure following intramuscular morphine were significantly greater than those following pentazocine. When pethidine and phenazocine were compared with pentazocine, the mean increases were lower following pentazocine but not to a statistically significant extent. Pentazocine appears to be the most appropriate strong analgesic in biliary and pancreatic disease.

No significant difference could be detected either by clinical impression or statistical analysis in the relief of pain afforded by 2.5 mg phenazocine hydrobromide (Narphen) and 10 mg morphine sulphate when given by intramuscular injection to patients with acute abdominal pain. Phenazocine does not cause spasm of the sphincter of Oddi and so is recommended for treating biliary or pancreatic pain.

Electrolyte solutions containing glucose, glycine, or a combination of the two were absorbed sufficiently well from the intestine to supply maintenance fluid and the electrolytes required by cholera patients. Data on net absorption and duration and volume of diarrhoea show that a solution containing both glucose and glycine provides more effective therapy than solutions containing either glucose or glycine alone.

A controlled single-blind trial has been carried out to determine the value of long-term anticholinergic therapy in duodenal ulcer. Of 106 male patients with symptomatic and radiologically proven duodenal ulcer admitted to the trial, 91 completed the study. Patients were divided randomly into three groups. They received either glycopyrronium, or 1-hyoscyamine in a sustained-release form, or inert tablets for one year. Progress was judged on the basis of frequency and severity of symptoms, monthly assessments by patients, antacid consumption, and radiology. By all criteria, glycopyrronium and 1-hyoscyamine were not significantly superior to placebo. Symptomatic improvement, both subjective and objective, occurred in approximately 80% of all patients during the year of observation; there was no significant difference between the groups.

Six normal subjects were tested with various doses of histamine acid phosphate (1, 10, 40, and 80 mug/kg/hr) and pentagastrin (0.15, 1.5, 6.0, and 12.0 mug/kg/hr), the different doses of the stimulants being administered by separate continuous intravenous infusions. In each sample of gastric juice, which was collected at 15-minute intervals, we estimated the concentrations of the H(+), Na(+), K(+), and Cl(-) and the concentration of pepsin. The drugs elicited equal maximal outputs of acid and pepsin. Pentagastrin was more potent than histamine in stimulating acid and pepsin secretion, and the rate of the responses was faster with pentagastrin than with histamine. Apart from this, however, the patterns of secretion of the various constituents of the gastric juice and the interrelationships between the concentrations of the electrolytes were identical with the two drugs. We therefore concluded that the actions of histamine acid phosphate and pentagastrin on human gastric secretion were identical.

The effects of continuous intravenous infusions of ;maximal' and ;supramaximal' doses of histamine acid phosphate and pentagastrin were assessed in a normal human volunteer. The secretory patterns in respect of the two drugs were indistinguishable over two and a quarter hours. During the steady states of acid secretion, outputs of pepsin and of electrolytes were also constant. The output of acid during the first hour of the steady state is a valid measurement of the maximal secretory capacity. The constant output of pepsin during the steady state of acid secretion suggests that both drugs are true stimulants of pepsin secretion.

The inhibitory effect of intravenous secretin and intrajejunal acid infusion on basal and pentagastrin-induced gastric acid secretion as well as the stimulatory influence of both infusions on pancreatic flow rate and bicarbonate output were compared in two groups of healthy subjects. Secretin strongly inhibited basal acid output and slightly decreased pentagastrin induced gastric secretion. Intrajejunal acid infusion did not affect the gastric secretion but resulted in an increase in pancreatic volume flow and bicarbonate output reaching about 40% of the pancreatic response to secretin(1) infused intravenously in a dose of 2 units per kilogram per hour. It is concluded that this provides evidence that secretin is a strong inhibitor of spontaneous gastric acid secretion and that acid in the jejunum causes the release of secretin in man.

This study confirms the preliminary reports that Duogastrone effectively controls the symptoms of duodenal ulceration and appears to hasten healing. In a double-blind trial, 14 patients with active duodenal ulcers were treated with Duogastrone capsules, one four times daily, half-an-hour before meals, while a comparable control group of 14 patients was treated similarly with a placebo containing magnesium trisilicate. Treatment continued for 12 weeks with clinical assessments fortnightly and a radiological assessment at the start and at the end of treatment. Only one of the 14 patients receiving Duogastrone did not respond. The remaining 13 showed marked clinical improvement with complete relief of pain and ceased to require supplementary antacids. Radiological evidence of healing or marked improvement was seen in eight of the 14 patients. None of the patients in the control group showed any marked improvement either of pain or tenderness and no changes were detectable by radiology. Patients in this group showed no reduction in their demand for supplementary antacids to relieve symptoms. No significant side effects were encountered. It is concluded that Duogastrone accelerates the healing of duodenal ulcer in ambulant patients and affords a much greater and more rapid relief of symptoms than does magnesium trisilicate.

A controlled trial of carbenoxolone sodium positioned-release capsules (Duogastrone) was carried out on a randomized series of 100 unselected male Service personnel with symptoms of active duodenal ulceration and supporting radiological evidence. Fifty-seven patients completed the trial, 29 in the carbenoxolone group and 28 in the control group. The carbenoxolone group was given capsules containing 50 mg carbenoxolone four times a day for 12 weeks while the controls received a capsule identical in every respect except that it did not contain carbenoxolone. All patients were assessed at fortnightly intervals and had clinical and radiological reassessments three and six months after commencing treatment. Review at three months and at six months revealed a slight but clinically insignificant trend in favour of the carbenoxolone group. As a corollary to this controlled trial, those patients (38 in all) who did not have an early remission of symptoms were removed from the trial and placed on capsules known to contain carbenoxolone. Subsequently these patients did not show an advantage for carbenoxolone.

Gastric secretion in man is inhibited by the presence in the duodenum of hyperosmolar and hypoosmolar solutions. Both acid and pepsin outputs are affected. There is no change in hydrogen, sodium, or potassium ion concentration in the gastric juice. Pepsin concentration, however, is reduced by all inhibitory stimuli. Inhibition is thought to act directly upon parietal and chief cells, and a possible basis for this mechanism is discussed. The response is similar in control subjects and duodenal ulcer patients; there is in particular no evidence of impaired inhibition in the ulcer group. An anomalous feature is the relatively small inhibition of acid output after hypertonic saline in control subjects compared with the duodenal ulcer patients.

A double-blind trial of a protein-free liver extract (Ripason) which was administered both orally and intramuscularly is described in 20 patients with stable cirrhosis. Control and treated groups were similar in composition except for age. Both groups showed some symptomatic improvement during the trial. Fewer patients were recorded as worse on Ripason but no significant changes in body weight, haemoglobin, or liver function tests could be detected.

Ninety patients with duodenal ulcer, divided randomly into three groups, were treated continuously for one year with either glycopyrronium, 1-hyoscyamine (as a sustained-release preparation) or inert tablets. Dosage with active tablets was so adjusted that the patient experienced definite but tolerable side-effects. Basal and maximal gastric acid secretion were measured immediately before and one week after cessation of treatment. There was no significant change in the means of these measurements in patients who received placebo or 1-hyoscyamine. In those given glycopyrronium, mean basal output was significantly increased. Mean maximal acid output in this group fell, but not significantly.Individual measurements of maximal acid output showed quite marked fluctuations in all groups. It is concluded that spontaneous changes in parietal cell mass may occur in patients with duodenal ulcer, and that prolonged anticholinergic therapy does not reduce parietal cell mass.

The effects of metoclopramide on gastric emptying and gastric secretion have been assessed in man using the double sampling test meal. Metoclopramide increases the rate of emptying of the stomach. The magnitude of the effect is directly related to the initial emptying time. Metoclopramide has no effect on the acid response to a water test meal.