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Biomedical subjects

J R O'Brien

Publications and source records attributed to J R O'Brien.

At least 73 records · Page 4Linked to original sources

A pilot study of the effect of Gemfibrozil on some haematological parameters.

In a double-blind 13 week study the effects of Gemfibrozil were compared with placebo. Gemfibrozil was given to 10 patients with evidence of severe atherosclerosis; four similar patients acted as controls. As expected, in the treated group, total cholesterol and triglycerides decreased significantly and HDL cholesterol increased. The Fibrinogen did not change although the ESR increased markedly and the heparin neutralizing activity (HNA) of the plasma decreased (p = 0.01). The antithrombic activity increased. The change in the HNA correlated weakly to the total cholesterol both before and during treatment. These findings show that some of the effects of Gemfibrozil on atherosclerotic humans are similar to those of Clofibrate but others are different.

Aged↗

Platelets in the prediction of thrombotic risk.

A study is reported which tries to identify those members of the general population who may be at increased risk of vascular disease. It is probable that patients who have had previous thrombotic episodes are inherently more at risk of further episodes and that a thrombus many months ago will not affect current tests. Accordingly we carried out a number of tests involving platelets on 'controls', and on patients with a past history of either myocardial infarction or deep vein thrombosis (DVT) and patients suffering from intermittent claudication who also are assumed to be at higher risk than the controls. Differences were demonstrated between controls and patient groups and these differences were utilized to develop statistical functions with the ability to discriminate between the groups. The functions were then tested using a second set of data from similar groups. Those designed to discriminate between myocardial infarction patients and controls and between patients with claudication and controls were validated. The heparin thrombin clotting time was found to be the prime predictor variable; the platelet count, platelet volume, platelet factor 3 clotting time and the bleeding time have some predictive value. The antithrombin clotting time, platelet aggregation and platelet adhesiveness tests as measured were not found to have discriminating potential. It is suggested that these appropriate risk functions could be of practical value in identifying members of the general population who may be at greater risk than average. The discriminate functions for DVT patients and controls could not be validated, suggesting differences in platelet involvement in arterial and venous thrombosis.

Analysis of Variance↗

Haemostatic factors associated with ischaemic heart disease in men aged 45 to 64 years. The Speedwell study.

In the Speedwell study set up to examine primarily the relation of plasma lipids and ischaemic heart disease in men aged 45 to 64 years drawn randomly from the practices of 16 general practitioners, various haemostatic factors which may contribute both to thrombogenesis and atherogenesis were measured. Fibrinogen measured nephelometrically and plasma viscosity were positively associated with the prevalence of ischaemic heart disease. Antithrombin III was negatively associated with the prevalence of ischaemic heart disease. These associations were statistically significant at the 1% level of probability. Fibrinogen measured by a clotting method and the heparin neutralising activity of platelet poor plasma had negative and positive associations with ischaemic heart disease, respectively, but neither association achieved statistical significance. Because of the interrelation of these variables and also age, a multiple logistic regression analysis was undertaken separately for the two measures of fibrinogen. The negative association of "clottable' fibrinogen and the positive association of plasma viscosity with the prevalence of ischaemic heart disease were confirmed and both were statistically significant at the 5% level of probability. Apart from age the independent association of the other variables with ischaemic heart disease did not achieve statistical significance. Fibrinogen measured by both methods had positive and statistically significant associations with serum total cholesterol, but no associations with serum total triglycerides, smoking, or alcohol consumption. "Clottable' fibrinogen had an inverse and statistically insignificant association with serum high density lipoprotein cholesterol. The observed associations support the concept of the involvement of some haemostatic factors in the aetiology of ischaemic heart disease, and these associations are now being examined more critically in a longitudinal study.

Blood Coagulation Tests↗

Platelet functions in relation to diet and serum lipids in British farmers.

Coagulation and platelet aggregation induced by thrombin, ADP, adrenaline, and collagen were studied in three contrasted groups, each of 20 to 22 middle-aged male farmers. Serum lipids were similar in the three groups. In the west of Scotland group, however, platelet reactivity was significantly greater than in the east of Scotland. This was associated with a dietary intake, evaluated by three different techniques, higher in saturated fat but also lower in polyunsaturated fat and alcohol. Platelet function in the southern England group also correlated with dietary fats and in addition inversely with calcium intake. On an individual basis in the 63 farmers, all the platelet function tests were significantly correlated with the intake of saturated fat regulated by that of calcium and alcohol. The dietary effects on platelets appear to be mediated by the fatty acid composition of plasma lipids and of platelet phospholipids. In that fraction, the fatty acids 20:3 omega 9, 22:3 omega 9 and 20:4 were the most closely related to the platelet function tests. the trienoic acid 20:3 omega 9, identified with essential fatty acid deficiency, was also correlated with the intake of saturated fat and calcium. In this study, platelet functions were more dependent upon the dietary factors associated with coronary heart disease such as saturated fats, calcium, and alcohol than upon serum lipids.

Blood Coagulation↗

Intraplatelet serotonin and plasma 5-hydroxyindoles in health and disease.

Using a fluorometric test sensitive to serotonin (5-HT) and to other 5-hydroxyindoles (5-HIs) it was shown that platelets take up 5-HT and that the added 5-HT and the inherent test-positive material in platelet lysate can be directly measured. However, platelets do not take up 5-hydroxyindole acetic acid or the 5-HIs from the plasma. Thus, 5-HT and the other 5-HIs can be distinguished. Various methods of liberating intraplatelets 5-HT were investigated. Several anticoagulants, temperatures, and speeds of centrifugation were employed, with no effect on the results. It was found that in healthy donors, with increasing age, there was a decrease in intraplatelet 5-HT and an increase in plasma 5-HIs. The quantities of these substances were inversely related. In acute myocardial infarction, the 5-HT was normal taking age into account, but the plasma 5-HIs were increased. In postoperative patients, the platelet 5-HT was low and the plasma 5-HIs were normal. In patients with chest pain but no myocardial infarction, both platelet 5-HT and plasma 5-HIs were normal. The relevance of these findings to 5-HT metabolism and the evidence for in vivo activation of platelets is discussed.

Adolescent↗

Platelet function in acute myocardial infarction patients compared with controls.

A considerable number of tests were carried out comparing 33 patients with acute myocardial infarction (MI), 13 patients with chest pain (CP) and 47 controls. There was some evidence that the plasma platelet factor 4 (PF4) was different in the three groups. The heparin neutralizing activity (HNA) of platelet poor plasma was increased in the MI patients relative to the controls and the intra-platelet HNA was decreased. Malondialdehyde (MDA) formation by platelets maximally stimulated by thrombin was decreased in MI whilst the plasma 5-hydroxyindoles (5HIs) in MI was greatly increased. The acute phase proteins alpha 1 acid glycoprotein and fibrinogen were significantly raised in MI. The results in the CP group were intermediate between the MI and the controls. These findings define more precisely the changes in acute MI and are relevant to the concept of exhausted platelets.

Adult↗

Changes in the heparin neutralising activity of platelet poor plasma after immunisation.

Acute myocardial disease, which may be associated with abnormal platelet activity, has been reported after routine immunisation. Thirty-two army apprentices undergoing immunisation were studied for changes in the heparin neutralising activity (HNA) of platelet poor plasma. HNA increased after immunisation. This increase in HNA may represent an increase in platelet activation but may also relate to changes in acute phase proteins. These changes were not observed in elderly subjects undergoing immunisation with influenza vaccine.

Adolescent↗

The effect of ICI 55,897 and clofibrate on platelet function and other tests abnormal in atherosclerosis.

There is considerable evidence that the quantity or quality of plasma lipids influences platelet function tests, and clofibrate reduces high plasma lipids and alters some platelet tests. Clofibrate was accordingly given to patients with vascular disease who were at risk of thrombosis. The heparin thrombin clotting time (HTCT), initially short and thus possibly reflecting increased activation, was regularly returned to normal after about a month's delay. The fibrinogen was also normalized but the initially abnormal anti-thrombic activity became more abnormal. ICI 55,897, an analogue of clofibrate, also normalized the HTCT and the fibrinogen and had no adverse effect on the anti-thrombin levels. This compound has no effect on plasma lipids. If it can be shown that the correction of abnormal tests conveys clinical benefit these findings suggest that ICI 55,897 might clinically be more beneficial than clofibrate. However, direct comparison of clofibrate and ICI 55,897 suggests that clofibrate is more effective in normalizing the HTCT. The mechanism underlying these drug-induced changes are unknown but they cannot be directly related to lipid changes.

Aged↗