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Biomedical subjects

B Hughes

Publications and source records attributed to B Hughes.

At least 91 records · Page 5Linked to original sources

Characterization of beta-adrenoreceptors in vivo with iodine-131 pindolol and gamma scintigraphy.

The aim of this study to was to assess the feasibility of using iodopindolol to delineate myocardial beta-adrenoreceptors in vivo. Preliminary biodistribution studies indicated that binding of 131I-d,I-pindolol in the heart was stereospecific, saturable, and displaceable by I-propranolol but not by phenoxybenzamine. However, considerable nonspecific binding was encountered. Subsequently, the stereoisomer, 131I-I-pindolol, was shown to be a high affinity beta-adrenoreceptor antagonist (Kd approximately 0.37 nM) as assessed by Scatchard analysis, and one exhibiting marked specific uptake in lung and heart in rabbits. In contrast, 131I-d-pindolol exhibited no specific binding in rabbit left ventricular membrane preparations nor specific organ uptake. Gamma camera scintigraphy with both isomers demonstrated that the I-isomer accumulated in lung and heart, and that its accumulation was blocked by I-propranolol. In contrast, d-isomer uptake was nonspecific and diffuse. The results indicate that it should be possible to externally visualize receptors by differentiating specific and nonspecific binding components of a ligand in vivo with the use of radiolabeled stereoisomers.

Animals↗

The effects of the protease inhibitor, aprotinin, on the course of shock induced by endotoxin in cats.

The administration of endotoxin derived from Escherichia coli to anaesthetized cats resulted, within the first 5 min, in an initial increase in right atrial pressure and a reduction in systemic arterial blood pressure. Over the next 2 h shock was characterized by a reduced cardiac output, tachycardia, reduced arterial pH and an increased level of lactate. The survival rate at the end of the 8 h experimental period was only 10%. The protease inhibitor aprotinin (Trasylol), given as a continuous intravenous infusion 1000 kallikrein inhibitor units (k.i.u.) kg-1h-1 together with a bolus of 40,000 k.i.u. kg-1, significantly inhibited the severity and incidence of the initial endotoxin response (increase in right atrial pressure and systemic hypotension), perhaps suggesting the direct or indirect involvement of kinins. Aprotinin did not reduce the delayed effects of endotoxin (sustained reduction in cardiac output, lacticacidosis), nor did it improve survival at 8 h. Indeed, there was some evidence that aprotinin exaggerated the delayed effects of endotoxin in this model.

Animals↗

Rapid radiometric assay used to assess lactoferrin in granulocytes.

We describe a rapid, precise, and sensitive radiometric assay for human lactoferrin. In this typical "sandwich"-type assay, anti-human lactoferrin is adsorbed onto a polystyrene sphere and bound lactoferrin is detected by the subsequent binding of 125I-labeled anti-human lactoferrin. The assay is accurate for lactoferrin concentrations of 5 to 1500 micrograms/L and takes about 2.5 h to complete. The within-assay and interassay variations (CV) are 5% and 13%, respectively. Neither lysozyme nor heparin, substances that form complexes with lactoferrin, interfered with lactoferrin measurement by this method. The assay has been applied to the measurement of lactoferrin in polymorphonuclear leukocytes of both healthy adults and neonates. We found significantly (p less than 0.001) less lactoferrin in the latter, an abnormality that may be related to known functional deficits of polymorphonuclear leukocytes during the newborn period.

Adult↗

Appetite and weight change in patients presenting with depressive illness.

Appetite and weight in 193 moderately depressed outpatients who satisfied Feighner's criteria for a primary depressive episode were found to be strongly associated with previous appetite and weight history. There was no overall association between weight change and severity of depression, nor with the classical features of endogenous depression, such as early morning waking and morning worsening of mood. Appetite change in either direction was, however, associated with a more severe degree of depression on the Hamilton and Beck scales. Normal appetite changes in response to stress occur in an exaggerated way in this depressive illness.

Adult↗

Aspects of the cardiovascular pharmacology of exaprolol.

This study confirms that exaprolol is a potent beta-adrenoceptor antagonist, having a pA2 value of 9.8 for the inhibition of the inotropic and chronotropic responses of guinea-pig isolated atrial preparations to isoprenaline. In the anaesthetized cat, exaprolol blocks both the myocardial stimulatory and vasodilating effects of isoprenaline, suggesting that it is a non-selective antagonist at beta-adrenoceptors. Exaprolol also has direct electrophysiological effects on cardiac (Purkinje) tissue, reducing the rate of rise of phase 0 of the action potential. This direct action together with its marked blockade of beta-adrenoceptors may explain the drug's ability to markedly suppress the ischaemic ventricular arrhythmias that follow coronary artery occlusion in anaesthetized rats.

Action Potentials↗

Changes occurring in appetite and weight during short-term antidepressant treatment.

Changes in appetite and weight were recorded in mild to moderately depressed out-patients during the course of clinical trials of various antidepressant drugs. After six weeks, differences due to treatment regimes were minimal. Patients who on becoming depressed experienced severe changes in appetite and weight in either direction, tended to return to normal. The significant associations of appetite and weight change during treatment were with weight, appetite, and carbohydrate preference at presentation, and also with the 'appetite history' and 'weight history'. The associations with the degree of depression were relatively minor.

Antidepressive Agents↗

The release of prostanoids during the acute pulmonary response to E. coli endotoxin in anaesthetized cats.

1 The administration of E. coli endotoxin (2 mg/kg i.v.) to anaesthetized cats results in a characteristic acute pulmonary response. This consists of increases in pulmonary artery pressure and airways resistance and a reduction in lung compliance. 2 Plasma concentrations of prostaglandin E2 (PGE2), PGF2 alpha, thromboxane B2 and 6-keto PGF1 alpha were measured by radioimmunoassay in aortic and pulmonary arterial blood samples before, during and after the acute pulmonary response to endotoxin. 3 Endotoxin administration resulted in the rapid release of PGF2 alpha and thromboxane B2 from the lungs. The time course of this release was parallel to that of the pulmonary hypertensive and airways responses to endotoxin. PGE2 and 6-keto PGF1 alpha were released more gradually and with greater variations between individual animals. 4 During the delayed shock phase (2 h after endotoxin) the concentrations of PGE2, PGF2 alpha and 6-keto PGF1 alpha were once again elevated in both the aorta and pulmonary artery. Thromboxane B2 concentrations were not increased at this time. 5 These results suggest that PGF2 alpha and thromboxane A2 may be mediators of the acute pulmonary responses to endotoxin.

Anesthesia↗

The implications of managing confused and disabled people in non-specialist residential homes for the elderly.

Local Authority residential homes for the elderly are caring for substantial proportions of physically disabled and mentally confused residents in non-specialist settings. The results of an intensive study of six homes caring for varying proportions of disabled and confused residents are summarized. The homes are compared in terms of staff training and attitudes, physical care of residents, social environment, and attitudes of residents. The authors suggest that a "mix" of residents can have advantages over segregation and that most homes can manage around 30% confused residents. If this is to be successful, attention should be given to staffing levels, staff training and the role of health service staff in residential homes.

Aged↗

Polymyxin B sulphate protects cats against the haemodynamic and metabolic effects of E. coli endotoxin.

1 The intravenous administration of E. coli endotoxin (2 mg/kg) in cats anaesthetized with pentobarbitone resulted in an initial acute increase in right atrial pressure and a transient systemic hypotension. Later (from 1 h onwards) there was a progressive decrease in cardiac output, a reduced right atrial filling pressure, systemic hypotension and a profound metabolic acidosis (lactate of 30 +/- 1 mg/100 ml at 5 h compared with 5.1 +/- 0.5 mg/100 ml pre-endotoxin). Only one of eight animals so treated survived 8 h. 2 Polymyxin B sulphate, given intravenously (1 min before endotoxin) as a bolus injection (5 mg/kg) followed by a continuous intravenous infusion (additional 5 mg/kg given over a 30 min period) prevented the endotoxin-induced pulmonary (right atrial) hypertension but not the acute systemic hypotension. 3 Polymyxin B sulphate reduced the delayed haemodynamic effects of endotoxin (systemic hypotension, decrease in cardiac output); all the eight animals so treated survived 8 h compared with only 1/8 of the controls. 4 Polymyxin B did not prevent the initial (1-3 h) and marked metabolic acidosis following endotoxin; however, after 3 h, arterial lactate levels returned towards control whereas in the endotoxin-alone group they continued to increase until death. 5 The mechanism of this marked protective effect of the antibiotic and the possible clinical repercussions are discussed; the most likely explanation for the protection is in chemical combination with the lipid A moiety of the endotoxin.

Animals↗

Staff monitoring: a better way to get ahead?

William Burrell, area administrator, Jim Haig, area management services officer and Brian Hughes, area personnel officer discuss the thorny subject of staff monitoring and its development in Northamptonshire AHA. They seek to answer questions raised in Andrew Wall's article, 'Bonus schemes--have they a future', published in the November issue of 'Health Service and Manpower Review'.

Efficiency↗

A comparison of two different services treating schizophrenia: a cost-benefit approach.

This study compares the clinical and social outcome for 2 cohorts of patients who had a first admission for schizophrenia 4 years earlier. One cohort was treated in a psychiatric unit attached to a teaching district general hospital (DGH)(T)), while the other was treated at an area mental hospital (AMH) with modern rehabilitation facilities. The clinical outcome for the 2 cohorts was broadly similar, but the DGH(T) imposed less of a strain on relatives, and was associated with less unmet need. The DGH unit tended to have significantly shorter durations of stay for its patients, so that its total hospital costs were less than those for the AMH despite higher unit costs. The cost-benefit analysis shows that, where these particular patients are concerned, the DGH(T) unit is economically superior to the AMH despite the fact that it supports a large teaching staff, and that these economic advantages are accompanied by various non-monetary advantages.

Cost-Benefit Analysis↗

Gliomatous transformation and demyelinating diseases.

The clinical and pathological details are described of three patients with demyelinating diseases associated with a glioma, the effects of which proved fatal. The findings suggest that the tumours developed from neoplastic transformation of glia in areas of established demyelination.

Brain↗