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Biomedical subjects

J G Mills

Publications and source records attributed to J G Mills.

At least 37 records · Page 2Linked to original sources
PubMed1989

Can higher doses of an H2-receptor antagonist accelerate duodenal ulcer healing?

Drugs that inhibit gastric acid secretion heal duodenal ulcers at a rate that correlates with the ability of individual treatment regimens to decrease 24-h intragastric acidity. As current therapeutic regimens of ranitidine decrease 24-h intragastric acidity submaximally, higher dosages may expedite duodenal ulcer healing. To test this hypothesis a randomized, double-blind clinical trial was conducted in 245 patients with duodenal ulcer to compare the effects of standard dose (300 mg nocte) and high-dose (300 mg q.d.s.) ranitidine. Patients were assessed after 2 weeks of treatment and, if unhealed, after a further 2 weeks of therapy. The therapeutic gain in ulcer healing at the 2-week endoscopy of the higher dose over the lower dose of ranitidine was 22% (68% vs 46%, P less than 0.001). The cumulative ulcer healing rates at the 4-week endoscopy were 88% and 92% for the standard and high-dose ranitidine groups, respectively (N.S.). By 2 weeks, 61% of patients treated with standard ranitidine therapy and 79% of those receiving 300 mg ranitidine q.d.s. were pain-free (P less than 0.01). A further 2 weeks of therapy enabled 88% and 97% of patients (N.S.) to become pain-free on these two regimens, respectively. The drug regimens were equally well tolerated. Thus higher-dose ranitidine can significantly accelerate the healing of duodenal ulcer with improvement in pain relief.

Adult↗
PubMed1989

The pharmacology of histamine H2-receptor antagonists.

The structure of the first histamine H2-receptor antagonist, burimamide was described in 1972. Since then, numerous compounds with diverse chemical structures have been shown to possess H2-receptor antagonist activity. Most of these compounds comprise an aromatic ring and polar group linked by a flexible chemical chain. Currently five H2-receptor antagonists are available for therapeutic use. In vitro studies have confirmed the competitive nature of the interaction between agonist and antagonist for these compounds and a comparison of the pA2 values generated shows a rank order of potency cimetidine less than nizatidine = ranitidine less than or equal to roxatidine less than famotidine. The duration of action of these agents is largely dependent upon their pharmacokinetic properties; with the possible exception of roxatidine, all have plasma elimination half-lives in the range 2-4 hours. Competitive antagonists with a high degree of selectivity for the H2-receptor and with a longer duration of action are currently being investigated, e.g., sufotidine. In addition to competitive agents, several non-competitive H2-antagonists, e.g., loxtidine, have been described. These have a prolonged duration of action. Relative potency varies between animal species and pharmacological models studied but the results of animal pharmacological studies have generally provided a good indication of the likely effects in man. Studies of 24-hour intragastric acidity represent the most physiological model available in man for evaluating the effects of different antisecretory drug regimens. Comparative studies with ranitidine 150 mg b.i.d. and cimetidine 400 mg b.i.d. have shown a reduction in 24-hour acidity of 65% and 30%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Continuous 24 hour ambulatory monitoring of intragastric pH in man.

A system has been developed which permits continuous 24 hour ambulatory recording of intragastric pH under near-physiological conditions. The system utilises a Cecar combination pH electrode connected through a pre-amplifier to an Oxford Medical Systems Medilog 4-24 cassette recorder, and the pH recorded continuously on to tape. The data is replayed at high speed, digitised and then analysed. Sources of error included system drift, system noise and the effect of changes in electrode environment due to saliva, food, loss of fluid contact, temperature variations and electrode time constant. These were found to be small. In contrast, the major changes in pH detected reflect real changes at the electrode tip. These changes can be recorded by the system. Developments in electronics and improvements in both the size and quality of pH electrodes, over the past few decades, has enabled intragastric pH recordings to be made with greater ease. However, a large number of investigators still assess gastric acidity by infrequent, intermittent sampling of gastric secretion through a naso-gastric tube. This new ambulatory system is a significant improvement and its versatility allows studies in acid secretion physiology, pharmacology and pathophysiology.

Electrodes↗
PubMed1987

Large single daily dose of histamine H2 receptor antagonist for duodenal ulcer. How much and when? A clinical pharmacological study.

The effects of single doses of cimetidine 800, 1200, and 1600 mg, given at 2300 h or 800, and 1600 mg at 1800 h, have been studied in patients with duodenal ulcer disease in symptomatic remission, and compared with cimetidine 400 mg bd (0800 h and 2300 h) and ranitidine 300 mg (given at 1800 h) respectively. A dose related reduction in intragastric acidity was seen. All single nocturnal (2300 h) doses of cimetidine produced anacidity overnight. This was not achieved with dosing at 1800 h although the duration of inhibition of gastric acidity was longer. Inhibition of overnight acid and pepsin outputs were similarly dose and timing related, but inhibition of peptic activity was much less after dosing at 1800 h. Cimetidine 1600 mg and ranitidine 300 mg were similar in their effects.

Adult↗
PubMed1985

Effect of H1- and H2-receptor antagonists on sputum volume and lung function in patients with generalized bronchiectasis.

In a placebo-controlled trial, the effect was assessed of an histamine H1-receptor antagonist, terfenadine (60 mg twice daily) and an H2-receptor antagonist cimetidine (400 mg twice daily) on the sputum production, dyspnoea score and lung function of 12 adult patients with generalized bronchiectasis. Three of these patients had cystic fibrosis. Neither drug, whether given alone or in combination, had any demonstrable effect on any of the parameters measured. It is concluded that histamine plays no significant role in the bronchial hypersecretion occurring in bronchiectasis.

Adult↗
PubMed1985

Cardiovascular responses in healthy subjects to a novel oral dopamine agonist, fenoldopam.

Two double-blind randomized crossover studies were carried out in healthy male subjects to determine the cardiovascular effects of fenoldopam and to assess whether they could be modified by metoclopramide. Blood pressure (BP) and heart rate (HR) were measured supine and upright, before and for up to 4 h after dosing. Single oral doses of fenoldopam 50, 100 or 150 mg or placebo were administered in one study. In the other study, subjects received 20 mg metoclopramide or placebo intravenously, 20 min before an oral dose of 100 mg fenoldopam or placebo. Fenoldopam produced decreases in diastolic BP and increases in HR indicative of an orally active systemic arteriolar vasodilator. Mean peak responses occurred 30-60 min after dosing and values had returned to pretreatment levels within 3-4 h. The decrease in diastolic BP was partially attenuated by pretreatment with metoclopramide. Thus, at least in part, the fall in BP following fenoldopam could be due to an interaction with dopamine receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1984

A double-blind randomized, controlled study to investigate the efficacy of cimetidine given in addition to conventional therapy in the prevention of stress ulceration and haemorrhage in patients with acute spinal injury.

The efficacy of cimetidine, 1.2 and 2.4 g/day, compared to placebo treatment given in addition to conventional therapy, which included antacids, in the prevention of gastroduodenal lesions associated with stress in 105 patients with acute spinal injury was investigated. Haematemesis was only observed in 1 placebo-treated patient. Of the 84 patients who completed the 10-day treatment and underwent endoscopy, 12 out of 43 cimetidine-treated patients and 11 out of 41 patients who received placebo were found to have gastroduodenal ulceration and/or erosions. Mean circulating concentrations of gastrin, pancreatic polypeptide and secretin were similar in all groups of patients. Whilst cimetidine has been shown to reduce the incidence of ulceration in patients suffering cranial and thermal injuries, the present study failed to demonstrate a prophylactic effect of cimetidine in the primary prevention of ulcers or erosions in patients with acute spinal injury exceeding that of conventional antacid therapy.

Adolescent↗
PubMed1984

The adaptability rating for military aeronautics: an historical perspective of a continuing problem.

Healthy candidates for military flying training may vary considerably in their ability and in their motivation to fly. A variety of tests are used to predict flying ability, but motivation may be assessed only through such subjective measures as a semi-structured interview. This paper reviews the historical background of such interviews in the U.S. Army and the U.S. Air Force, and suggests some possible improvements.

Adaptation, Psychological↗
PubMed1982

Oxmetidine: clinical pharmacological studies with a new H2-receptor antagonist.

The gastric antisecretory effects of oxmetidine, a new H2-receptor antagonist, have been studied in 33 healthy subjects. The relative potency of oxmetidine compared with that of cimetidine depended on the route of administration and the experimental conditions. Oxmetidine intravenously infused was approximately four times as potent as cimetidine, weight for weight, in inhibiting impromidine stimulated gastric acid secretion but was twice as potent when food was used as a stimulus. After oral administration there were no differences in the weight-for-weight potency of oxmetidine and cimetidine, although oxmetidine was twice as potent on a molar basis. These apparent differences according to the route of drug administration are probably due to first pass metabolism of oxmetidine. There were no differences in the duration of action of oxmetidine and cimetidine. Twenty-four hour monitoring of intragastric pH showed that oxmetidine 400 mg twice daily reduced mean hourly 24 hour intragastric pH by 59%, suggesting that a twice daily dosage regimen should be evaluated in the treatment of duodenal ulceration.

Adolescent↗
PubMed1980

Prolactin responses to histamine H2 receptor antagonists.

We have compared the effects of cimetidine and SK&F 92994, a new more potent histamine H2 receptor antagonist, on serum prolactin, and also assessed the effect of the H2 receptor agonist impromidine on the response to cimetidine. As previously reported, cimetidine 200 mg given as an iv bolus dose produced a marked rise in serum prolactin, but 50 mg and 200 mg of SK&F 92994 given by the same route had no effect. Iv infusion of impromidine 10 microgram kg-1h-1 failed to modify the prolactin response to cimetidine. It is concluded that the rise in serum prolactin following iv administration of cimetidine may be due to a specific property of cimetidine. An effect mediated via histaminergic pathways within the central nervous system, although less likely, cannot be excluded.

Cimetidine↗
PubMed1980

Histamine H2 receptors and intrinsic factor secretion.

Intrinsic factor (IF) secretion in healthy male subjects was studied in response to pentagastrin stimulation with and without cimetidine, and to impromidine, a histamine H2 receptor agonist. Peak and total IF output were reduced by cimetidine, but the concentration was unchanged and the response was unaffected by administration of the compound for 1 week. The IF secretory response to impromidine was similar to that to pentagastrin. It is suggested that the acid and IF components of the parietal cell secretory response are mediated via different intracellular pathways, that histamine H2 receptors do not fulfill and obligatory role in the secretion of IF and that synthesis of IF is probably not altered by cimetidine.

Cimetidine↗
PubMed1980

Gastric secretory studies in humans with impromidine (SK&F 92676)--a specific histamine H2 receptor agonist.

Impromidine (SK&F 92676), a potent selective histamine H2-receptor agonist in animals has been studied in healthy male volunteers. Impromidine 10 micrograms kg-1h-1 i.v. produced near maximal acid secretion and cimetidine 2 mg kg-1h-1 inhibited this output by a mean of 65% in 5 subjects. The log dose-response curve to impromidine in 5 subjects was linear over the dose range 2.5--20 micrograms kg-1h-1. Cimetidine 0.5 mg kg-1h-1 caused a highly significant parallel shift of the dose-response curve, consistent with direct competitive antagonism. The gastric secretory responses to impromidine 10 micrograms kg-1h-1 i.v., histamine acid phosphate 40 micrograms kg-1h-1 i.v., and pentagastrin 6 micrograms kg-1h-1 i.v. were similar. Cardiovascular effects of impromidine were less marked than those due to histamine. Gastric secretory and cardiovascular effects of impromidine are dose dependent. No significant difference was seen in peak acid output between impromidine 10 micrograms kg-1 and pentagastrin 6 micrograms kg-1 whether injected intramuscularly or subcutaneously. Headache which accompanied infusion with histamine occurred less frequently with impromidine, and nausea and abdominal discomfort which occurred with pentagastrin did not occur with impromidine. Impromidine will be valuable in the study of gastric secretion and the role of histamine H2 receptors in other systems.

Adolescent↗
PubMed1978

Comparative study of carbuterol and salbutamol from metered aerosols in bronchial asthma.

In a double-blind crossover trial carbuterol and salbutamol were administered by aerosol for 7 days each to 20 patients with reversible obstructive airways disease. In addition to assessment of subjective response, objective measurements were made of response of the respiratory system (FEV1, FVC, MMEFR) and cardiovascular system (pulse rate, blood pressure, ECG) to each drug. Both carbuterol and salbutamol were found to be effective, well-tolerated bronchodilators when given over a 7 day period; there was no significant difference between the drugs in any of the parameters studied. Carbuterol is a safe and effective alternative to salbutamol.

Aerosols↗
PubMed1977

Popliteal entrapment syndrome.

A probable cause of popliteal artery entrapment is proposed. The medial head of the gastrocnemius muscle during its embryological development crosses the popliteal fossa from lateral to medial. It is proposed that the migrating medial head carries the popliteal artery and vein across the fossa and entraps them against the medial condyle of the femur. Dissection of 86 anatomical specimens revealed two cases of unilateral and one case of bilateral entrapment of both popliteal vessels. Two surgical cases of popliteal entrapment are presented. This entrapment syndrome is a remedial cause of claudication and when considered, it is readily diagnosed and surgical correction is effective. Because of distal embolisation and occlusions, early recognition and treatment is desirable. Forty-seven cases from the literature are reviewed as to the entrapment type and the age and sex of the patients.

Adult↗
PubMed1975

Pharmacological evaluation of cimetidine, a new histamine H2-receptor antagonist, in healthy man.

Cimetidine, a new H2-receptor antagonist, was safely administered to eighteen healthy man by the intravenous, intraduodenal or oral route. 2 When gastric secretion was maximally stimulated by either histamine or pentagastrin, the simultaneous administration of cimetidine produced marked inhibition of both acid and pepsin secretion. 3 Cimetidine was well absorbed by mouth and had a blood half-life of 2 hours. 4 Cimetidine was rapidly excreted via the kidneys and about 70% of the excreted material was unchanged drug. 5 Clinical evaluation of cimetidine in patients with peptic ulceration is recommended.

Administration, Oral↗