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Biomedical subjects

A L Gough

Publications and source records attributed to A L Gough.

14 recordsLinked to original sources

Lansoprazole versus ranitidine in the maintenance treatment of reflux oesophagitis.

AIMS: To assess the relative efficacies of lansoprazole 15 mg once daily, lansoprazole 30 mg once daily and ranitidine 300 mg b.d. in the maintenance treatment of reflux oesophagitis for 12 months. METHODS: Multicentre, out-patient, double-blind, parallel group, prospectively randomized clinical trial. Patients with grade 0, asymptomatic oesophagitis after 8 weeks of treatment with lansoprazole 30 mg once daily were randomized to receive lansoprazole 30 mg once daily (L30) (n = 75), lansoprazole 15 mg once daily (L15) (n = 86) or ranitidine 300 mg b.d. (R600) (n = 74) for 12 months. Endoscopy was repeated at 6 and 12 months, and symptomatic assessment was made every 3 months. Efficacy was primarily assessed by the time to endoscopically confirmed relapse (oesophagitis grade > or = 1) and the proportion of patients who relapsed during the 12-month study period. Severity of symptoms were secondary efficacy measures. RESULTS: For all patients randomized with at least one post-baseline endoscopy (intent-to-treat principle) both lansoprazole 15 mg (P < 0.001) and lansoprazole 30 mg (P < 0.001) were significantly superior to ranitidine 600 mg with respect to time to endoscopic relapse. There was no difference between the lansoprazole groups (P = 0.11). There was evidence of relapse in 27 of 86 (31.4%), 15 of 75 (20.0%) and 50 of 74 (67.6%) of the patients treated with lansoprazole 15 mg and 30 mg and ranitidine 600 mg, respectively. Patients receiving treatment with either lansoprazole dosages experienced significantly less severe heartburn and regurgitation than those patients treated with ranitidine. There were no differences between the treatment groups with respect to the severity or incidence of adverse events. No clinically significant laboratory changes were observed in any of the treatment groups. Serum gastrin levels were elevated in all treatment groups, and most markedly in those patients receiving lansoprazole, but there was no significant difference between the treatments. Morphological and immunohistochemical examination of the gastric biopsies revealed no clinically relevant changes from baseline in any of the treatment groups. CONCLUSION: Both lansoprazole 15 mg and lansoprazole 30 mg once daily are significantly more effective than high-dose ranitidine in maintaining reflux oesophagitis in remission.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Prevention of recurrence of oesophageal stricture, a comparison of lansoprazole and high-dose ranitidine.

OBJECTIVE: To determine the efficacy of lansoprazole 30 mg given in the morning compared with high-dose ranitidine 300 mg twice daily in the treatment of patients with oesophageal strictures. DESIGN: A multicentre, outpatient, double-blind, parallel group, prospectively randomized clinical trial. PATIENTS: One hundred and fifty-eight patients (lansoprazole 30 mg n = 78, ranitidine 600 mg n = 80) were enrolled from 19 centres in the UK over 23 months. INTERVENTIONS: Patients with an oesophageal stricture were randomized to receive either lansoprazole 30 mg once daily or high-dose ranitidine 300 mg twice daily for 12 months. Dilatation was performed at entry and repeat endoscopies were scheduled at 6 and 12 months and additionally at other times if there was symptomatic relapse. Redilatation was performed as required and according to a predefined scale. The patient's assessment of dysphagia over the previous 7 days was recorded by the investigator at 1, 3, 6, 9 and 12 months. Safety was assessed by laboratory tests, physical examination and all adverse events. MAIN OUTCOME MEASURES: Efficacy was assessed primarily by the time to redilatation, the proportion of patients requiring at least one redilatation, and the number of redilatations over 12 months. The relief of dysphagia and reduction in stricture grade were secondary efficacy measures. RESULTS: The time to redilatation was longer and the probability of no redilatation were higher in the lansoprazole group than in the ranitidine group; for all patients randomized (intention to treat principle), this difference was of borderline significance (life table, P = 0.053). The proportions of patients requiring at least one redilatation during the 12-month treatment period were 30.8% (24/78) with lansoprazole and 43.8% (35/80) with ranitidine (all patients randomized, chi 2 test, P = 0.092). Compared to ranitidine, patients receiving lansoprazole reported significantly lower dysphagia grades at 6 months (stratified Wilcoxon test, P = 0.0086) but not at 12 months (stratified Wilcoxon test, P = 0.074). A greater proportion of patients in the ranitidine group-33.8% (27/80)-withdrew prematurely compared to the lansoprazole group (26.9%, 21/78). The most frequent reasons for premature withdrawal were adverse events and protocol violations. There were no clinically significant differences in incidence or severity of adverse events between the two groups. The mean increase in gastrin levels after 12 months' treatment was significantly greater for patients in the lansoprazole group (124.2 pg/ml, P = 0.0056) than those in the ranitidine group (31.9 pg/ml). No significant changes in gastric mucosal histology were detected for patients in either group. CONCLUSION: It is concluded that lansoprazole 30 mg once daily is superior to ranitidine 300 mg twice daily in relieving dysphagia, and at least as effective in reducing the need for a repeat dilatation.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effect of an intravenous fat preparation on canine gastric secretion.

The effect of intravenous administration of a fat emulsion on canine gastric secretion stimulated by intravenous infusion of amino acids, pentagastrin or insulin was studied. The fat preparation was given at a rate of 30 ml/hour for 2 hours, and its effects were compared with those of a comparable amount of saline solution, each given on three separate occasions in each dog. Fat did not alter the Heidenhain pouch secretion stimulated by intravenous amino acids (1.10 versus 1.11 mmol of hydrogen ion, p greater than 0.9) or the gastrostomy secretion stimulated by intravenous insulin (9.22 versus 9.54 mmol of hydrogen ion, p greater than 0.7) but had a modest inhibitory effect on Heidenhain pouch secretion stimulated by pentagastrin (2.75 versus 3.54 mmol of hydrogen ion, p less than 0.05). These data provide indirect support for the contention that the inhibition of gastric secretion by fat in the gut is mediated by the release of an enterogastrone rather than by a direct effect of absorbed fat. Because gastric stimulation by intravenous fat was not observed in the dog, it seems likely that intravenous fat emulsion can be given to seriously ill patients without fear of an increased likelihood of peptic ulceration due to induced gastric hypersecretion.

Amino Acids↗

Amino acids as possible mediators of the intestinal phase of gastric secretion.

In a group of six dogs with Heidenhain pouches, the infusion of a solution of L-amino acids caused identical increases in gastric secretion when given into the jejunum as when administered directly into the portal venous system. Elevations in plasma amino nitrogen were also similar in the two circumstances. In four dogs with Heidenhain pouches and portacaval transposition, a similar infusion caused an identical increase in gastric secretion when given into the jejunum as when given into the peripheral venous system; plasma amino nitrogen levels were almost as high with the jejunal administration as with venous infusion. It is concluded that all, or almost all, of the gastric secretion evoked by amino acids in the canine intestine can be accounted for by the direct effect of absorbed amino acids on parietal cell secretion, with little or no contribution from release of an intestinal hormone.

Amino Acids↗

Computer analysis of interacting dopaminergic and cholinergic control mechanisms in the extrapyramidal system.

The experimental results of many authors suggest that the output activity of the extrapyramidal motor control system depends on a balance between the levels present of the chemical transmitters dopamine and acetylcholine. In this paper it is proposed that these results are best explained by two feedback regulatory systems interconnected with positive interaction--in the sense of the relative gain array (Bristol, 1966). Using the computer-aided design procedure CAIAD, a simple two-input two-output model is simulated so as to give responses similar to those observed when dopaminergic or cholinergic drugs are applied. The effect of reducing the gain in one control loop corresponds to the effect of lesioning part of the extrapyramidal system in the brain. In addition, the effect of an anti-schizophrenic drug such as haloperidol is interpreted as a disturbance input on one of the interacting paths.

Acetylcholine↗

Acalculous gallbladder disease: a prospective study.

A prospective study of 62 cases of acalculous gallbladder disease is reported. The clinical, radiological and pathological features are described as well as the results of cholecystectomy with a minimum follow-up of 3 years. The results compare favourably with those for calculous disease, and it is concluded that there is no clear-cut distinction between acalculous and calculous biliary disease.

Cholecystectomy↗

Radiology of acalculous gall-bladder disease - a new sign.

Radiography of excised gall-bladders, immersed in water, has shown that chronically infected gall-bladders frequently contain fat. This fat can be seen in vivo, and the frequency of the finding was assessed by reviewing 43 patients with acalculous gall-bladder disease. Other radiological signs in the cholecystograms were looked for retrospectively, and their incidence assessed. In 20 cases out of 40, no radiological abnormality was found.

Adipose Tissue↗

An assessment of the reproducibility and safety of 2-deoxy-D-glucose as a gastric acid stimulant in duodenal ulcer patients.

In studying the effects of 2-deoxy-D-glucose (2-DG) on the vagus nerve in preoperative patients with duodenal ulcer we have concluded that (1) in initiating gastric acid secretion 2-DG produces a response that is reproducible after 30 days; (2) 2-DG when given in a dose of 40 mg/kg intravenously produces a glucopenic state that appears safe in an otherwise healthy patient. We consider that 2-DG is a worthwhile agent in the investigation of the duodenal ulcer patient.

Alanine Transaminase↗