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Biomedical subjects

C D Forbes

Publications and source records attributed to C D Forbes.

At least 181 records · Page 10Linked to original sources

The novel effect of a new prostacyclin analogue ZK36374 on the aggregation of human platelets in whole blood.

Platelet aggregation was studied at 37 degrees C in citrated whole human blood, using the Ultra Flo 100 Whole Blood Platelet Counter. Aggregation was measured as a fall in the number of single platelets following addition of an aggregating agent. At peak aggregation, the fall in the number of platelets induced by ADP (10 microM), collagen (1 microgram/ml) or thrombin (0.2 U/ml) was about 90%. When blood was incubated with the prostacyclin-analogue ZK36374, the aggregation responses to ADP, collagen and thrombin were reduced with IC50's = 0.5, 1.5 and 3 nM respectively and the corresponding IC100's were: 1, 3 and 12 nM. When ZK36374 was added at peak aggregation, the number of single platelets increased significantly due to disaggregation of preformed platelet aggregates. It is concluded that the present technique represents a rapid, sensitive and more physiological approach for investigating the effects of pharmacological agents on platelet aggregation.

Adenosine Diphosphate↗

Immunological abnormalities in haemophilia: are they caused by American factor VIII concentrate?

Scottish patients with haemophilia, most of whom had received no American factor VIII concentrate for over two years, were found to have immunological abnormalities similar to those in their American counterparts--that is, a reduced proportion of T helper cells, an increased proportion of T suppressor cells, and a reduced response to concanavilin A. Factor VIII from both the United States and Scotland severely inhibited the in vitro lymphocyte response to mitogens in patients and controls. The American and Scottish concentrates could not be distinguished in terms of either patient usage or their effect in vitro. These results argue against a disease vector specific to American blood products.

Adult↗

Plasma fibrinopeptide A and beta-thromboglobulin in patients with chest pain.

Plasma levels of beta-thromboglobulin (BTG) and fibrinopeptide A (FPA), markers of platelet release and thrombin generation respectively, were measured in 48 patients within 3 days of admission to hospital for acute chest pain. Twenty-one patients had a confirmed myocardial infarction (MI); 15 had unstable angina without infarction; and 12 had chest pain due to noncardiac causes. FPA and BTG were also measured in 23 control hospital patients of similar age. Mean plasma BTG levels were not significantly different in the 4 groups. Mean plasma FPA levels were significantly higher in all 3 groups with acute chest pain when compared to the control subjects (p less than 0.01), but there were no significant differences between the 3 groups. Increased FPA levels in patients with acute chest pain are not specific for myocardial infarction, nor for ischaemic chest pain.

Adult↗

Prognostic value of beta-thromboglobulin in patients with transient cerebral ischaemia.

Plasma levels of beta-thromboglobulin (BTG) and fibrinopeptide A (FPA), markers of platelet alpha-granule release and thrombin generation respectively, were measured in 27 subjects with transient cerebral ischaemic attacks (TIA), 43 age-matched controls, and 32 young controls. BTG and FPA were both higher in elderly controls than in young controls. BTG was higher in TIA subjects than in age-matched controls and higher in the 12 TIA subjects who had further vascular events in the next year than in those who had no further events. FPA was not significantly associated with TIA or with further events. These results support a relationship between platelet activation and TIA and suggest that BTG levels indicate a group at higher risk of further vascular events.

Adult↗

Blood viscosity and haemostasis in the nephrotic syndrome.

Blood viscosity and its major determinants (haematocrit, plasma viscosity and fibrinogen) as well as several haemostatic variables were measured in 21 patients with the nephrotic syndrome, and 21 controls matched for age, sex, smoking habit and serum creatinine. Blood viscosity was significantly increased in the nephrotic group, measured at a low shear rate (mean increase 41%, p less than 0.01) and at a high shear rate (mean increase 25%, p less than 0.01). Haematocrit was not significantly increased, but plasma viscosity was significantly higher (p less than 0.01), associated with increased plasma macroglobulins especially fibrinogen, which was increased to double the plasma concentration of the control group (p less than 0.01). Nephrotic subjects also had increased plasma levels of alpha 2-macroglobulin, factor VIII activity, factor VIII antigen and beta-thromboglobulin; differences in antithrombin III, fibrin degradation products, plasminogen, and platelet count were not significant. We suggest that increased blood and plasma viscosity may play a role in the vascular complications of the nephrotic syndrome.

Adult↗

Platelet aggregation studies in whole human blood.

Since the development of the photometric aggregometer, platelet aggregation studies are routinely performed on platelet-rich plasma (PRP). We have studied platelet aggregation in fresh citrated whole human blood using the recently developed Ultra Flo 100 Whole Blood Platelet Counter. Aggregation of platelets in whole blood was induced with adenosine 5'-diphosphate (ADP; 0.25-10 microM), collagen (0.25-1.0 microgram/ml) and thrombin (0.05-0.2U/ml). Platelet aggregation induced by ADP and thrombin was maximum within 1 min, and that of collagen within 3 mins. Aggregation responses to low concentration of ADP and thrombin were rapidly reversible, whereas responses to collagen and high concentrations of ADP and thrombin were virtually irreversible. The aggregation of platelets was indicated by a fall in platelet count; confirmed by scanning electron micrographs which revealed the presence of large aggregates of platelets, and was prevented when blood was treated with EDTA as anticoagulant. The present technique appears to be rapid, sensitive and reliable; and allows direct measurement of platelet aggregation and disaggregation in whole blood in vitro and ex-vivo.

Adenosine Diphosphate↗

Relation of atrial fibrillation and high haematocrit to mortality in acute stroke.

Clinical and laboratory abnormalities and the presence of atrial fibrillation on admission were examined in relation to hospital mortality in a retrospective study of the 320 patients with acute stroke admitted to a medical unit in a 5-year period. Of clinical factors, only increasing age and the presence of coma were associated with mortality. Atrial fibrillation, present in 25% of all patients, was associated with an increased mortality in patients aged 60-79 years (67% vs 44%, p less than 0.01). In patients under 75 years the mortality associated with raised haematocrit (0.50 or more), present in 11% of all patients, was more than twice as high as it was in those with lower haematocrit (71% vs 31%, p less than 0.005). Other laboratory variables associated with a high mortality were increased levels of mean red cell volume, white cell count, erythrocyte sedimentation rate, globulin, and blood urea and creatinine; and decreased levels of albumin. The high prevalence of and increased mortality associated with atrial fibrillation and raised haematocrit in stroke patients indicate the need for further studies of stroke prevention and treatment in these patients.

Acute Disease↗

Intermittent epoprostenol (prostacyclin) infusion in patients with Raynaud's syndrome. A double-blind controlled trial.

Two groups of outpatients (7 in each group) with Raynaud's syndrome, matched for severity of illness, were randomly allocated to receive at weekly intervals for three weeks either a 5 h intravenous infusion of buffer or epoprostenol (prostacyclin, PGI2) in buffer (7.5 ng/kg/min after the first hour). PGI2 reduced the frequency and duration of ischaemic attacks (both p less than 0.01). Hand temperature measurements with a thermocouple were significantly improved at 1 week; 6 weeks after the last infusion hand temperatures had returned to baseline. There was a corresponding loss of clinical response 8-10 weeks after the last infusion.

Clinical Trials as Topic↗

Epoprostenol (prostacyclin) and severe arterial disease. A double-blind trial.

A 96 h infusion of epoprostenol (prostacyclin) or placebo was given as a treatment for rest pain to 28 patients with severe peripheral arterial disease. 24 h after the end of the infusion patients given epoprostenol had significantly less pain and took fewer analgesics tablets than did the controls. In some patients the epoprostenol effect lasted for over 1 month.

Arterial Occlusive Diseases↗

The haemophilic patient's self-perception of changes in health and life-style arising from self-treatment.

Twenty three adults and twenty children with haemophilia, all on self-treatment, participated in the present study. They were interviewed as to how they perceive the effects of self-treatment upon various aspects of their life. It was found that the ability to treat themselves was perceived by patients as a great improvement over their previous treatment regimes for which they had had to go to hospital. Twelve of the adult patients had participated in our previous studies concerned with the social an psychological aspects of haemophilia. The analysis of the responses of these twelve patients showed that self-treatment is perceived so positively that some of the patients' earlier perceptions were distorted to correspond with their present and more optimistic perceptions of their condition. However, the number and type of psychosomatic symptoms was found to be unchanged by self-treatment and the unemployment rate has not decreased.

Adolescent↗

Dazoxiben, a thromboxane synthetase inhibitor, in the treatment of Raynaud's syndrome: a double-blind trial.

1 UK-37248 (dazoxiben), an orally active thromboxane synthetase inhibitor, was evaluated in a double-blind trial of patients with severe Raynaud's syndrome. 2 Twenty patients were enrolled in the study. Eleven of these patients received dazoxiben 400 mg day and nine received matching placebo capsules. Treatment was given for 6 weeks and the patients reviewed at 2 weekly intervals during the study. 3 Assessment of response was judged by clinical symptoms and hand temperature measurements. Haematological and haemostatic studies were also carried out. 4 Results show a significant clinical improvement in patients receiving dazoxiben for six weeks. Hand temperature measurements, and haematological and haemostatic blood tests remained unchanged, however, apart from the expected lowering in plasma thromboxane B2 levels. 5 The mechanism of action of the drug would appear not to be mediated through increased prostacyclin production and further studies are under way to determine how improvement has been obtained in these patients.

Adult↗

Thromboembolic complications in Cushing's syndrome.

Thromboembolic events are thought to occur with increased frequency in Cushing's syndrome due to the predisposing factors, obesity, hypertension, a raised haematocrit and major surgery plus a 'hypercoagulable state'. To examine this postulate further we have studied 43 patients with Cushing's syndrome retrospectively and 10 patients prospectively to determine the incidence of arterial and venous thrombosis, both spontaneous and post-operative. Arterial events were noted in four cases (9%) and deep vein thrombosis or pulmonary thromboembolism (PTE) occurred in six cases (11%). Post-operative PTE occurred in 2.7% of all operations. These vascular complications tended to occur in the older patients with Cushing's syndrome. In our series, clinically significant thromboembolic episodes appear no more common than expected and the indications for prophylactic anticoagulation (the older and more obese patients) may not be different from other patients undergoing major surgery. An incidental finding was of a greater frequency of hypertension in Cushing's patients due to an adrenal adenoma.

Adrenalectomy↗

Abnormal blood viscosity and haemostasis in long-standing retinal vein occlusion.

Blood viscosity and several haemostatic factors were measured in 42 patients with long-standing retinal vein occlusion and 33 control subjects. Blood viscosity, haematocrit, plasma viscosity, fibrinogen, fibrinopeptide A, and beta-thromboglobulin were increased in the 20 subjects with capillary nonperfusion or new vessels, but not in the 22 subjects without these complications. Patients with nonperfusion or new vessels also had a lower platelet count than patients without complications. Increased levels of factor VIII antigen and decreased levels of antithrombin III were found in the retinal vein occlusion group as a whole. These findings suggest that blood viscosity, platelets, and coagulation may be involved in retinal vein occlusion and its vascular complications.

Aged↗

Coronary artery disease in severe haemophilia.

It has been suggested that the coagulation defect in haemophilia A protects these patients from coronary artery disease. We report two patients with severe haemophilia, who each had severe atheroma localised to the coronary arteries. Both patients had received only small amounts of factor VIII concentrates in their lifetime because of various social reasons. In one case death resulted from myocardial infarction secondary to an occlusive thrombus in a coronary artery. The implications of these findings to the pathogenesis of vascular disease are discussed.

Arteriosclerosis↗