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Biomedical subjects

A J Palmer

Publications and source records attributed to A J Palmer.

12 recordsLinked to original sources
PubMed1992

Methohexitone antagonises kainate and epileptiform activity in rat neocortical slices.

Using a grease-seal technique on cortical slices, methohexitone (10-316 microM) dose dependently and reversibly reduced depolarising responses to kainate more than those to alpha-amino-3-hydroxy-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA). The respective pA2 values were 4.9 +/- 0.07, 3.6 +/- 0.03 and 4.0 +/- 0.05 whereas, for 6-nitro,7-sulphamoylbenz[F]quinoxalinedione (NBQX), they were 5.8 +/- 0.06, 6.7 +/- 0.05 and < 4.0. Methohexitone was also more effective than NBQX in reducing the spontaneous epileptiform activity occurring in these cortical slices. Thus 10 and 20 microM of this short-acting barbiturate reduced afterpotentials and burst frequencies respectively by about 50% whereas NBQX 10 microM only reduced burst frequency by some 15%. The results are discussed with respect to a putative methohexitone- and kainate-sensitive autoreceptor which facilitates presynaptic glutamate release.

Action Potentials↗
PubMed1992

Relation between treated blood pressure and death from ischaemic heart disease at different ages: a report from the Department of Health Hypertension Care Computing Project.

OBJECTIVE: To determine the relation between mortality from ischaemic heart disease (IHD) and treated blood pressure at different ages. DESIGN: Prospectively, 6216 patients were studied for a mean of 107 months. SETTING: Of the total patients, 95% were followed in five hospital-based hypertension clinics and the remainder in four group general practices. PATIENTS: Respectively, 2250 and 2126 hypertensive men and women aged < 60 years and 822 and 1018 aged > or = 60 years. MAIN OUTCOME MEASURES: Mortality (any mention on the death certificate) from IHD. RESULTS: Four hundred and sixty-seven patients died with IHD mentioned on the death certificate. The relation between both diastolic blood pressure (DBP) and systolic blood pressure (SBP) during the first 3-12 months of treatment and subsequent IHD mortality was examined. Under the age of 60 years the relative hazard rate (RHR) for death from IHD tended to increase with DBP in both men and women. Above the age of 60 years there was no important or significant relation between IHD mortality and treated DBP. For SBP there was no reduction in the positive relation between IHD mortality and blood pressure in the older age groups. The RHR for SBP ranged between 1.008 and 1.021 in men and women over and under the age of 60 years. CONCLUSIONS: The positive relation between DBP and IHD mortality decreased with increasing age and, in women aged > or = 60 years, even inverted, partly explaining the negative relation reported between DBP and total mortality in the very old.

Adolescent↗
PubMed1992

Quality of life in hypertensives treated with atenolol or captopril: a double-blind crossover trial.

AIM: To compare the effects of captopril and atenolol on quality of life of hypertensive patients. METHODS: In a randomly allocated double-blind crossover trial with two 6-week treatment periods captopril at 25 mg twice a day or atenolol at 50 mg once a day were administered to 265 hypertensive patients (mean age 56 years; 55% men). Of these, 65% were newly treated hypertensives and 35% were previously uncontrolled on a diuretic alone. A seated diastolic blood pressure of 95-115 mmHg was required after a 3-week placebo run-in period. Any previous diuretic therapy was changed to hydrochlorothiazide (25 mg once a day) and the dose was kept constant throughout the trial. Newly diagnosed patients did not take a diuretic at any time. Quality of life was assessed from self-completed questionnaires measuring psychological well-being, symptomatic side effects of treatment, and activity and perceived well-being (a health index). A relative's perception of the patients' mood was also obtained where possible. RESULTS: Twelve patients withdrew on atenolol and 10 on captopril. No differences between the drugs were observed in quality of life measures, and 95% confidence intervals suggested that important differences were excluded. CONCLUSION: We conclude that at the doses used in this trial there were no important differences between captopril and atenolol in their effects on quality of life.

Adult↗
PubMed1992

Relation between blood pressure and stroke mortality.

The relation between stroke mortality and blood pressure was investigated in 10,186 hypertensive patients followed up in the Department of Health Hypertension Care Computing Project for an average of 9 years. An untreated blood pressure measurement was available in 3,472 men and 3,405 women. The age-adjusted risk of stroke death increased by 1% for every 1 mm Hg increase in untreated systolic blood pressure. The relative hazard rate was 1.014 (95% confidence interval [CI], 1.007, 1.021) in men and 1.009 (1.003, 1.016) in women. The corresponding increases for 1 mm Hg for untreated diastolic blood pressure were almost 3% in men and again 1% in women (relative hazard rate 1.026 [95% CI, 1.014, 1.038] in men and 1.010 [1.000, 1.021] in women). Treated blood pressure measurements were available in 3,073 men and 3,148 women. Stroke mortality increased by 2% for a 1 mm Hg increase in treated systolic pressure and 3% for the corresponding increase in diastolic blood pressure. The relation between stroke mortality and blood pressure was similar over and under the age of 65, although the increase in mortality with pressure was greater for treated diastolic blood pressure in women under the age of 65 than over this age. There was no evidence for a J-shaped relation between stroke mortality and either systolic or diastolic pressure in men. In women there was a suggestion of such a relation, but since this relation was also observed for untreated pressures, any increase in risk at lower pressures is unlikely to be a result of treatment.

Blood Pressure↗
PubMed1991

Excitatory amino acids: new tools for old stories or pharmacological subtypes of glutamate receptors: electrophysiological studies.

Although the N-methyl-D-aspartate (NMDA) subtype of L-glutamate receptor is well characterized, the significance of non-NMDA glutamate-sensitive binding sites is not well documented. In this study, a new tricyclic quinoxalinedione (NBQX) and an arthropod toxin (philanthotoxin) were shown to block responses of spinal neurones in vivo to kainate, quisqualate, and AMPA in parallel but had little effect on responses to NMDA. Philanthotoxin appeared to be a use-dependent antagonist consistent with a channel-blocking mode of action. On cortical wedges in vitro, however, NBQX proved to be a more potent antagonist of AMPA and quisqualate than of kainate (pA2 values of 7.1, 7.0, and 5.6, respectively) with no effect at 10 microM on responses to NMDA. These studies provide evidence that on cortical neurones, but not on spinal neurones. AMPA and kainate depolarize by pharmacologically different mechanisms.

Amino Acids↗
PubMed1979

The synergistic effect of weight loss and changes in dietary lipids on the serum cholesterol of obese men with hypercholesterolaemia: implications for prevention of coronary heart disease.

The hypolipidaemic effect of a low-fat, low-cholesterol diet, alone and in combination with weight reduction, has been evaluated in two groups of obese men with hypercholesterolaemia. In 41 men who lost 10.3 kg over 11 months and maintained their lower weight for 23.5 months serum cholesterol fell by 1.68 mmol/l and remained steady at lower weight. In 20 similar men, the controls, whose weight fell by 0.8 kg over 39.5 months, serum cholesterol fell by 0.80 mmol/l. There was a significant linear correlation between change in weight and change in serum cholesterol. The change in serum cholesterol in the weight losers was greater than could be accounted for by change in dietary lipids. Weight reduction and low-fat, low-cholesterol diets appear to have a synergistic effect in reducing serum cholesterol.

Adult↗
PubMed1975

Type-IV hyperlipidaemia and weight-gain after maturity.

Twenty men with mild to moderate type-IV hypertriglyceridaemia were compared with normal men of the same age in the Busselton population survey. The type-IV men were not heavier but they were 3-2 cm. shorter and relatively hyperuricaemic. When gives a reducing diet, mean weight declined from 76-8 kg. to 68-7 kg. over 4-4 months and was kept steady over the next 10 months at 67-6 kg. Before, immediately after, and in the 10 months after weight reduction serum-triglycerides were 273, 112, and 126 mg. per 100 ml. and serum-cholesterol was 245, 227, and 226 mg. per 100 ml., respectively. On entry the mean daily calorie intake was 3165 and the contribution of the various nutrients were characteristic of the Australian diet. At lower weight, daily caloric intake was 2335. Protein intake was unchanged, but intake of fat and especially carbohydrate declined significantly. The findings support the view that type-IV hyperlipidaemia is the expression of a metabolic defect brought to light by weight-gain after maturity. In susceptible subjects "normal" weight-gain may be sufficient to induce hyperlipidaemia. Since type-IV and type-IIb hypertriglyceridaemias appear to increase the risk of coronary heart-disease, it is concluded that ideally no weight should be gained after reaching maturity. Avoidance of weight-gain should materially reduce the incidence of coronary disease in affluent western communities. Reduction to truly ideal weight gives much more impressive therapeutic results than drug therapy.

Body Weight↗
PubMed1975

Diet and atherosclerosis.

Diet and atherosclerosis are closely linked, both aetiologically and therapeutically. The aetiological association can be demonstrated most satisfactorily in animal experiments. In human beings the evidence must necessarily be more indirect and is largely based on dietary trials and epidemiological surveys linking the intake of cholesterol and saturated fat with morbidity and mortality from coronary disease. A modifying influence which has gained increasing recognition over recent years is the individual response to a given diet. This variability appears to be largely genetically determined, certainly in the defined primary hyperlipidaemic states, and possibly within the normal ranges of serum cholesterol levels. A change in food habits should be fully utilized therapeutically in any form of hyperlipidaemia, whether as a primary preventive measure before clinical diseases of atherosclerotic origin become manifest or in secondary prevention to delay further morbidity and mortality. With good dietary adherence, lipid levels may return to normal and there may be additional favourable effects on intravascular thrombosis. Many problems remain to be solved on the public health issue of advising changes in the national diet. A number of countries in which an atherogenic diet is habitually eaten have decided in favour of such a recommendation. Public education, identification of persons at risk and provision of readily available skilled medical and dietary counselling should constitute a national health project with rewarding long-term results.

Adult↗