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Biomedical subjects

J R O'Brien

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

At least 55 records · Page 3Linked to original sources
PubMed1987

Effects of a fish oil supplement on serum lipids, blood pressure, bleeding time, haemostatic and rheological variables. A double blind randomised controlled trial in healthy volunteers.

Sixty male volunteers were randomised to take 10-16 ml of a fish oil supplement (MaxEPA) or 10-16 ml of olive oil for a period of 3-6 weeks. A fall in serum triglyceride of 54% (P less than 0.01) and a fall in diastolic blood pressure of 7% (P less than 0.05) was attributable to taking fish oil supplements. The bleeding time was prolonged by 12%, but this did not reach conventional levels of statistical significance. A global test of heparin-neutralising activity, the heparin thrombin clotting time, increased by 14% (P = 0.05) but there was no demonstrable effect on thrombin time, fibrinogen or (intraplatelet) platelet factor 4. A fall in red cell pore transit time of 23% was attributable to fish oil, but was not statistically significant. There was no convincing evidence of an effect of fish oil supplementation on total serum cholesterol, HDL-cholesterol, blood counts or platelet aggregation. A beneficial effect of fish oil on the cardiovascular risk profile was confirmed in this study. However, with this regime changes in total cholesterol, HDL-cholesterol and platelet aggregation are of unlikely clinical importance.

Adult↗
PubMed1987

Some long term effects of smoking on the haemostatic system: a report from the Caerphilly and Speedwell Collaborative Surveys.

Data from two community studies on men from South Wales and the west of England suggest that the effects of smoking on the haemostatic system remain for many years after giving up. Long term correlations between several variables, including plasma fibrinogen and white cell count, and the length of time after giving up were seen in ex-smokers. Dose response relations were apparent in current smokers in terms of the white cell count and two haematological variables, the packed and mean cell volumes. These long term correlations probably reflect the toxicity of other agents in tobacco smoke besides nicotine and carbon monoxide, which act only in the short term. Identification of these agents may further our understanding of the mechanism by which cigarette smoking is associated with atherosclerotic disease.

Blood Viscosity↗
PubMed1987

Shear stress activation of platelet glycoprotein IIb/IIIa plus von Willebrand factor causes aggregation: filter blockage and the long bleeding time in von Willebrand's disease.

The article explores the finding that high shear alone applied to normal, native blood results in platelet aggregation. A filter with tortuous capillary-sized channels permits a study of the effect of shearing forces at different pressures. Native, heparinized, citrated and EDTA blood and platelet-rich plasma (PRP) were forced through the filter. Normal and von Willebrand's blood were studied, as were the effects of antibodies to platelet glycoproteins (GPr) and to von Willebrand's factor (vWf) and of "membrane-active" drugs. Normally, the filter blocked at 40 mmHg but not at 5 mmHg. Transmission electronmicroscopy of the filter at 40 mmHg showed blockage by platelet aggregates. Initially, the mean transit time through the filter was 8 milliseconds. Platelet retention in the filter occurred in two phases. From 0 to 3 seconds, only high-shear, vWf, and GPrIIb/IIIa were required. From 10 to 20 seconds, retention presumably involved these three attributes, but divalent cations were also essential. Only this phase was inhibited by some membrane-active drugs. ADP- and thrombin-induced aggregation requires GPrIIb/IIIaand fibrinogen. Shear-induced blocking of the filter by blood with a normal concentration of fibrinogen requires GPrIIb/IIIa and vWf. This indicates a different type of exposure of GPrIIb/IIIa. The long bleeding time in vW disease highlights the absolute requirement for vWf and emphasizes the difference in exposure of GPrIIb/IIIa induced by shear stress. Evidently, a process similar to that occurring in the filter is required in normal capillary hemostasis.

Antibodies↗
PubMed1985

The heparin-mobilisable pool of platelet factor 4: a comparison of intravenous and subcutaneous heparin and Kabi heparin fragment 2165.

Some clinical advantages are claimed for low molecular weight heparin so the mobilisation of platelet factor 4 (PF 4) from the endothelial pool by the heparins may be relevant. Unfractionated (UF) heparin has been compared with Kabi heparin fragment 2165. A single intravenous (i.v.) injection of 60 iu/kg heparin was compared with 5000 anti-Xa units of Kabi-2165. Less PF 4 was mobilised by Kabi-2165 and some apparently remained in the pool and was released when the pool was subsequently challenged by giving i.v. heparin. Subcutaneous (s.c.) injections of 5000 iu heparin twice daily were compared with 5000 anti-Xa units of Kabi-2165 once daily, each given for a week. The plasma PF 4 was never raised yet when finally challenged with i.v. heparin the pool was "empty" or refractory after the s.c. heparin but some PF 4 remained after the s.c. Kabi-2165. The two glycosaminoglycans (GAGs) had widely differing half-lives but the t/2 of the PF 4 mobilised by the two GAGs was similar even though the PF 4 is apparently bound to the GAG.

Adult↗
PubMed1985

Haemostatic factors and ischaemic heart disease. The Caerphilly study.

In a preliminary report from the Caerphilly study four haemostatic factors showed univariate associations with prevalent ischaemic heart disease after adjusting for age. These factors were fibrinogen concentration, plasma viscosity, white cell count, and the heparin-thrombin clotting time. Age and these haemostatic variables were entered into a stepwise multiple logistic regression analysis; after age the white cell count and heparin-thrombin clotting time remained significantly associated with ischaemic heart disease. Further regression analyses indicated that diastolic blood pressure contributed additionally to this association with ischaemic heart disease but that smoking habit did not.

Adult↗
PubMed1984

Intra-platelet platelet factor 4 (IP.PF4) and the heparin-mobilisable pool of PF4 in health and atherosclerosis.

Some patients with clinical evidence of atherosclerosis and others with diabetes were compared with appropriate controls. The intraplatelet level of platelet factor 4 (PF4) was significantly decreased in the arteriopaths and was lower in the diabetics when compared with controls. Patients with transient ischaemic attacks and stroke have even lower values. Intravenous heparin liberates large amounts of PF4 from an unknown reservoir, perhaps the endothelium, into the plasma. Arteriopaths liberated significantly more PF4 than the controls and the diabetics most. If a second heparin injection is given 24 hr after the first, the resultant plasma PF4 level was on average half that achieved after the first injection and again the patients had higher levels than the controls. Thus the reservoir originally "emptied" of PF4 by the heparin had been partially refilled in 24 hr and the reservoir in the atherosclerotic patients then contained more than the controls. Patients with atherosclerosis and especially diabetics differ from controls in the PF4 content of their platelets and in their response to heparin and in the rate of refill of the "heparin-mobilisable pool of PF4".

Adult↗
PubMed1984

Platelet and other tests followed sequentially for 14 days after operation.

Nineteen patients were studied twice before and sequentially from 1 h to 14 days after operations lasting about 1 h. Eighteen tests were carried out, ideally on all the nine occasions blood collections were planned. Only significant changes are summarized. Immediately after the operation the plasma PF4 and beta TG were raised in parallel suggesting some platelet 'release' had occurred. At this time platelet aggregation to ADP and collagen had decreased by 57% to 64% and the plasma cyclic AMP had doubled. Next day these abnormalities had returned towards normal. By day 2 the fibrinogen and the heparin neutralizing activity were maximal; they returned towards normal by day 14. On day 14, when presumably all platelets present at operation had been removed the new platelets were 53% more numerous and 9.5% smaller; they contained 23% less PF4 and 42% less serotonin and 5-HT uptake was decreased, but the total amount of 5-HT and PF4 in the circulation probably remained constant. In summary these operations transitorily upset platelet function for a few hours and the platelets formed postoperatively were abnormal.

Adult↗