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Biomedical subjects

F E Preston

Publications and source records attributed to F E Preston.

At least 181 records · Page 10Linked to original sources

Acute encephalopathy coincident with seroconversion for anti-HTLV-III.

Acute encephalopathy was associated with the appearance of antibodies to human T-lymphotropic virus (HTLV-III) in two patients. A third patient showed seroconversion for anti-HTLV-III, but the temporal association was not established so precisely. The illness was characterised by a prodromal period of up to 2 weeks, characterised by pyrexia, general malaise, and changes of mood. The encephalopathy culminated in epileptiform seizures in two of the patients. Electroencephalographic changes were compatible with viral encephalitis, and cerebrospinal-fluid pleocytosis was minimal. Neurological signs and symptoms resolved quickly in all patients, and no residual central-nervous-system sequelae were apparent.

Acquired Immunodeficiency Syndrome↗

Progressive liver disease in haemophilia: an understated problem?

In an 8-year study of 79 unselected patients with haemophilia who had received clotting factor concentrates, there was evidence of chronic progressive liver disease in at least 17 (21%). 8 patients had chronic active hepatitis and 9 had cirrhosis (5 with oesophageal varices). Histological evidence suggested that non-A non-B hepatitis was mainly responsible, although the influence of other viruses could not be excluded. Serial liver biopsies showed progression from chronic persistent hepatitis to chronic active hepatitis and cirrhosis within 6 years, suggesting that chronic persistent hepatitis in haemophiliacs is not as benign as hitherto supposed. Symptoms and abnormal physical signs were uncommon in these patients. There was no relation between degree of abnormality of serum aminotransferase levels and severity of the underlying liver disease. It is anticipated that liver disease in haemophiliacs will become an increasing clinical problem in the future.

Adolescent↗

Effect of stanozolol on factors VIII and IX and serum aminotransferases in haemophilia.

The treatment of haemophilia has been dramatically improved since the introduction of factor VIII and IX concentrates, however these concentrates have brought new problems such as hepatitis and A.I.D.S. An oral agent which could raise endogenous levels of factor VIII and IX would be of great benefit. Danazol, an anabolic steroid, has recently been shown to increase levels of factors VIII and IX in haemophilia. We therefore studied the effect of stanozolol, a closely related anabolic steroid, in 15 patients with haemophilia A or Christmas disease over a 2-4 week period. There was no consistent change in factor VIIIc or factor IX, and fibrinolysis was significantly enhanced. No effect was apparent on the incidence of spontaneous bleeds. However serum aminotransferases which were abnormal in 11 of the 15 patients at the start of the study fell significantly with stanozolol therapy. This raises the interesting possibility that anabolic steroids may be beneficial in patients with chronic liver diseases.

Blood Viscosity↗

The effects of dietary omega-3 polyunsaturated fatty acids on erythrocyte membrane phospholipids, erythrocyte deformability and blood viscosity in healthy volunteers.

We have examined, in normal subjects, the effects of a daily dietary supplement of fish oil concentrate ('maxEPA'), providing 3 g of omega-3 fatty acids, on erythrocyte membrane phospholipids, erythrocyte deformability and blood viscosity. After 3 weeks, incorporation of C20:5 omega 3 into erythrocyte phosphatidyl choline (PC) was greater compared to phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS). After 6 weeks, there was no further increase in total erythrocyte C20:5 omega 3, but its distribution amongst phospholipid subclasses had changed. C20:5 omega 3 had increased further in PE and PS, but decreased in PC. Incorporation of C20:5 omega 3 also occurred into PC, PE and PS. omega-3 Fatty acids were incorporated almost entirely at the expense of C18:2 omega 6, but total unsaturation of phospholipids was increased. This is consistent with increased lipid fluidity, which may be an important determinant of erythrocyte deformability. The same dosage of maxEPA also resulted in a significant increase in erythrocyte deformability and a concomitant reduction in whole blood viscosity. Since plasma viscosity and haematocrit were unchanged it seems likely that the effects on blood rheology were mediated by changes in erythrocyte lipid fluidity. Modification of blood rheology by dietary omega-3 fatty acids is of potential value in the treatment of vascular disease.

Blood Viscosity↗

Effects of dietary fish oil supplementation on the fatty acid composition of the human platelet membrane: demonstration of selectivity in the incorporation of eicosapentaenoic acid into membrane phospholipid pools.

The fatty acid composition of membrane phospholipids of stimulated and unstimulated platelets was studied in six normal volunteers given a daily dietary supplement of a fish oil rich in eicosapentaenoic acid (EPA) for 4 weeks. The supplement was equivalent to 1.8 g of EPA daily. Thromboxane synthesis and platelet aggregation responses to sodium arachidonate, thrombin and the ionophore A23187 were also investigated. A marked increase in the relative EPA content of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was noted after 2 and 4 weeks fish oil supplementation. However, there was no incorporation into phosphatidylinositol (PI) or phosphatidylserine (PS). The relative arachidonic acid (AA) content of PC and PE was significantly reduced at 2 and 4 weeks but that of PI and PS remained unchanged. Significant reductions in the relative linoleic acid content of total phospholipids, PC and PE were also noted. Stimulation of platelets obtained after 4 weeks fish oil supplementation by thrombin and A23187 was associated with a marked reduction in the AA content of PI and a minor reduction in that of PE. There was no change in the relative proportions of EPA in PI, PS, PC or PE after stimulation. Throughout the study there were no significant changes in platelet aggregation responses or in platelet thromboxane production. Our results indicate that the incorporation of EPA into the platelet membrane phospholipids is selective and that if PI is the major source of AA for platelet prostaglandin biosynthesis then the reported beneficial effects of EPA on haemostasis cannot be explained on the basis of its incorporation into and mobilization from the platelet membrane phospholipid pool.

Adult↗

The routine measurement of platelet volume: a comparison of aperture-impedance and flow cytometric systems.

The effect of dipotassium ethylenediaminetetraaceticacid (EDTA) on the platelet count and mean volume (MPV) was evaluated using two routine measurement systems, a Coulter S Plus Phase 1 (S+) and a Technicon H6000 (H6000). In normal subjects (n = 29) MPV increased by 17% during 39 h storage in EDTA when measured by the S+. In contrast MPV decreased by 22% when measured by the H6000. MPV differences of up to 40% were observed between the two systems. Concomitant platelet counts, in both systems, changed by less than 4%. Using the anticoagulant sodium citrate and prostaglandin E1 (Na-citrate/PGE1 there were no significant changes in MPV measured by the S+ during 7 h storage, although a linear decrease in platelet count was observed. A decrease in H6000 MPV was observed whether the blood was stored in EDTA or Na-citrate/PGE1. Methodology, anticoagulation and storage time all influence MPV. Until these determinants are standardized the clinical value of MPV cannot be assessed.

Alprostadil↗

The postoperative fibrinolytic shutdown: a rapidly reverting acute phase pattern for the fast-acting inhibitor of tissue-type plasminogen activator after trauma.

The plasma activity level of the recently discovered fast-acting inhibitor of tissue-type plasminogen activator (t-PA) was found to be temporarily increased after surgery, myocardial infarction and severe trauma. Detailed analysis of the postoperative period revealed simultaneously increased t-PA antigen and inhibition and decreased t-PA activity only on the first postoperative day. These changes were more rapid than those in fibrinogen and C-reactive protein. It is concluded that t-PA inhibition shows the most rapidly changing pattern observed so far in response to trauma. The postoperative fibrinolytic shutdown in blood fibrinolytic activity can be ascribed to a primary increase in t-PA inhibitor levels.

Antigens↗

Hemolytic-uremic syndrome: demonstration of abnormalities of platelet reactivity and insensitivity to prostaglandin I2.

Platelet aggregation and thromboxane synthesis and platelet sensitivity to the antiaggregatory action of prostaglandin I2 were studied serially in a subject suffering from adult hemolytic-uremic syndrome. Platelet aggregation in vitro was defective during the acute phase of the disease and recovered during the convalescent phase. Defective aggregation was not associated with a failure of thromboxane synthesis although it was related to an intrinsic platelet defect rather than an inhibitor in the plasma. The platelets were insensitive to prostaglandin I2, even in the recovery phase of the disease. Furthermore, plasma from the patient rendered normal platelets insensitive to prostaglandin I2 and more sensitive to aggregating agents. It is concluded that the platelet abnormality in hemolytic-uremic syndrome is complex and it combines both an intrinsic platelet abnormality and a plasma component.

Acute Disease↗

Thrombotic vascular disease.

Thrombovascular disease represents one of the most important causes of morbidity and mortality. Although coronary artery disease attracts most attention, other types of vascular disease also make a substantial contribution to the overall statistics. These include microangiopathy, particularly in relation to diabetes mellitus, and deep vein thrombosis and its associated complications of pulmonary embolus and postphlebitic syndrome.

Arteries↗

Modulation of rapid plasminogen activator inhibitor in plasma by stanozolol.

Fibrinolytic activity in plasma euglobulin fractions can be increased by oral administration of stanozolol. This increase is not caused by increased synthesis or release of tissue-type plasminogen activator. A decreased level of fast acting t-PA inhibition is very probably the cause of the higher activity. These results suggest that this inhibition has a regulatory role on fibrinolysis in vivo.

Adult↗

Stanozolol-induced changes in fibrinolysis and coagulation in healthy adults.

The effect of orally-administered stanozolol, 5 mg b.d. on fibrinolysis, coagulation and on various haematological and biochemical parameters have been studied in 16 healthy adults, 8 males and 8 females. Statistically significant enhancement of extrinsic (tissue-type) plasminogen activator activity was detected in all subjects studied. This was associated with significant increases in plasma plasminogen and a concomitant reduction in histidine-rich glycoprotein. There were no changes in plasma urokinase activity. Changes in the coagulation system included significant reduction in plasma fibrinogen and elevation of protein C and antithrombin III. Changes in plasma lipids included significant reduction of HDL cholesterol associated with an increase in LDL triglycerides. No change occurred in total cholesterol. There were no major differences between the sexes, nor were there serious side effects. The effects of stanozolol on extrinsic (tissue-type) plasminogen activator activity, "free" plasminogen, protein C and antithrombin III, argue strongly in favour of its therapeutic potential.

Adult↗

Beneficial effect of fish oil on blood viscosity in peripheral vascular disease.

Reports suggest that the low incidence of ischaemic heart disease in Greenlandic Eskimos is related to the effect of a diet rich in eicosapentaenoic acid on platelet reactivity and plasma lipid concentrations. A double blind randomised investigation was therefore conducted of the effects on blood viscosity of dietary supplementation with an oil rich in this fatty acid (1.8 g/day, given as fish oil) and an eicosapentaenoic acid poor oil (as corn/olive oil) in patients with peripheral arterial disease. A statistically significant reduction in whole blood viscosity was observed at seven weeks in those patients receiving the eicosapentaenoic acid rich oil. No changes in plasma viscosity, haemoglobin concentration, packed cell volume, or platelet count were seen. A significant fall in plasma triglyceride concentration was also noted only in the patients receiving oil rich in eicosapentaenoic acid; plasma concentrations of cholesterol and high density lipoprotein cholesterol were unchanged. It is concluded that rheological changes that result from a diet rich in eicosapentaenoic acid may contribute to the suggested protective effects of such a diet against arterial disease and that such changes are of potential therapeutic importance in established arterial disease.

Aged↗