Biomedical subjects
Publications and source records attributed to M J Hayes.
In a prospective study of patients admitted to a coronary care unit, the incidence of isotopically diagnosed deep venous thrombosis was found to be related to the severity of illness rather than to the duration of bed rest. In addition, no negative correlation was found between cigarette smoking and deep venous thrombosis.
1 A decrease was found in the binding capacity of elderly people for warfarin. 2 The decrease in binding correlated with a fall in plasma albumin concentrations. 3 No changes in the association constant were observed.
1 Comparison of phenytoin clearance showed a marked increase in people over 65 years of age compared with people under 45 years of age. 2 This difference was apparent if phenytoin was given orally or intravenously. 3 Phenytoin clearance correlated inversely with phenytoin binding and plasma albumin, both of which were found to be reduced in the elderly.
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A total of 189 patients with uncomplicated myocardial infarction were selected at random for early or late mobilization and discharge from hospital. Patients were admitted to the study after 48 hours in a coronary care unit if they were free of pain and showed no evidence of heart failure or significant dysrhythmia. Randomization was achieved by monthly cross-over of the three medical wards to which the patients were discharged. One group of patients was mobilized immediately and discharged home after a total of nine days in hospital, and the second group was mobilized on the ninth day and discharged on the 16th day. Out-patient assessment was carried out six weeks after admission. No significant differences were observed between the groups in terms of mortality or morbidity, as reflected by the incidence of recurrent chest pain or myocardial infarction, heart failure, dysrhythmia, or venous thromboembolism detected either clinically or by (125)I-labelled fibrinogen scanning.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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An analytical method has been developed for the determination of a new antiepileptic drug, CGS 18416A, in human plasma. CGS 18416A is a new anticonvulsant representative of a novel class of water-soluble agents being developed for the treatment of epilepsy. Preclinical trials indicate sustained efficacy at relatively low oral doses, indicating a need for a sensitive assay. The method is based on capillary gas chromatography/mass spectrometry and utilizes stable isotope-labelled CGS 18416A as the internal standard. Samples (1 mL) are acidified, then washed with pentane/ethyl acetate, followed by liquid/liquid extraction at pH 11 with pentane/ethyl acetate. Extracts are then concentrated and analysed directly by gas chromatography/mass spectrometry. Separation is accomplished on a thick film methylsilicone capillary column. Mass spectrometry was carried out under positive ion ammonia Cl conditions with selected ion monitoring of the protonated molecular ions (m/z = 248 and 252) for CGS 18416A and the 13CD3-CGS 18416A, respectively. Specificity was demonstrated by the lack of interfering peaks at the retention time of CGS 18416A and the internal standard. Recovery and reproducibility assessments indicate good accuracy and precision over the validated concentration range of 0.2-51 ng/mL. The limit of quantification is 0.2 ng/mL and the method has sufficient sensitivity to support clinical trials. This is illustrated with an example of quantification in a normal volunteer following oral dosing.
CGS 18102A is a novel hexahydrobenzopyranopyridine that has a mixed pharmacological profile of 5-HT-1A agonist and 5-HT-2 antagonist properties. Based upon these mechanisms, the compound is predicted to have anxiolytic efficacy with possible efficacy in depression. Preclinical studies in the rat have shown the drug to be well absorbed and extensively metabolized. Because of the anticipated low plasma levels in humans a gas chromatography/mass spectrometry (GC/MS) analytical method has been developed and validated to determine plasma concentrations of CGS 18102A in early clinical studies. The method utilizes CGS 18416A as the internal standard. Samples (1 mL) were extracted with pentane:ethyl acetate (75:25, v:v). Extracts were then concentrated and analysed directly by GC/MS. Separation was accomplished on a methylsilicone capillary column (30 m x 0.32 mm i.d.). GC/MS was carried out under positive ion ammonia CI conditions, with selected ion monitoring of the [M + H]+ ions (m/z = 262 and 248) for CGS 18102A and CGS 18416A, respectively. The method was successively applied to the analysis of clinical samples from an ascending multidose safety and tolerability study conducted in six normal healthy male volunteers.
A simple receptor modeling approach has been applied to groundwater pollution studies and has shown that marker trace elements can be used effectively in source identification and apportionment. Groundwater and source materials from one coal-fired and five oil-fired power plants, and one coal-tar deposit site have been analyzed by instrumental neutron activation analysis for more than 20 minor and trace elements. In one of the oil-fired power plants, trace element patterns indicated a leak from the hazardous waste surface impoundments owing to the failure of a hypolon liner. Also, the extent and spatial distribution of groundwater contamination have been determined in a coal-tar deposit site.
BACKGROUND: Tachyphylaxis to the cardiac effects of beta-adrenoceptor stimulation after long-term beta2-agonist administration is well recognized, but the influence on global cardiac beta-adrenoceptor density has not been previously investigated in vivo. Positron emission tomography (PET) has made possible the noninvasive quantification of regional receptor density. This study assesses the effect of long-term beta2-agonist dosing on cardiac beta-adrenoceptors. METHODS AND RESULTS: Beta-adrenoceptors in the hearts of 29 healthy male subjects aged 35 +/- 8 years were imaged and quantified in vivo by means of PET and compared with the receptor density in the same subjects' lung tissue. Mononuclear leukocyte (MNL) beta-receptor density was determined in vitro by means of a radioligand binding assay. Beta-receptor density was 8.41 +/- 2.03 pmol/gm tissue in heart, 10.81 +/- 1.91 pmol/gm tissue in lung, and 38.0 +/- 17.5 fmol/mg protein on MNLs. There was a weak relationship between cardiac and pulmonary beta-receptor densities (r = 0.45, p < 0.02) but not between cardiac and MNL receptor density. In seven subjects, the measurements were repeated after 2 weeks of albuterol treatment (4 mg orally twice daily and 200 microg inhaled four times daily in the first week, with doubling of the dose during the second week). After the albuterol treatment, beta-receptor density fell on average by 19% (p < 0.05) in the heart compared with 22% (p < 0.05) in the lung and 42% (p < 0.05) in MNLs. Correlations were found between the percentage changes in receptor density in heart and lung (r = 0.98, p < 0.001) and in heart and MNLs (r = 0.99, p < 0.002). CONCLUSIONS: Two weeks of high-dose albuterol results in equivalent downregulation of beta-receptors in vivo, both in the lung and in the heart.