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Biomedical subjects

R C Paton

Publications and source records attributed to R C Paton.

31 records · Page 2Linked to original sources
PubMed1981

Effects of diet and gliclazide on the haemostatic system of non-insulin-dependent diabetics.

The effect of the sulphonylurea gliclazide on tests of haemostatic function was studied in 14 newly diagnosed non-insulin-dependent diabetics. After two months' treatment with diet alone 11 of the 14 were given gliclazide; the three others remained on dietary treatment. Compared with pretreatment values, significant reductions in platelets retention, factor VIII-related antigen, factor VIII coagulant activity, and plasma heparin neutralising activity accompanied a fall in the plasma glucose concentration due to either diet alone or diet and gliclazide. The beneficial effects of gliclazide on platelet abnormalities seem likely to be due to its hypoglycaemic action rather than to any direct effect on haemostatic function.

Adult↗
PubMed1981

Increased adhesion of erythrocytes to endothelial cells in diabetes mellitus and its relation to vascular complications.

We studied the adhesion of erythrocytes from 30 diabetic patients and 25 controls to human endothelial cells. Washed erythrocytes were labeled with 51Cr and added to confluent endothelial cells cultured from umbilical veins. After incubation at 37 degrees C, the nonadherent erythrocytes were removed by sequential washings. The percentage of erythrocytes adhering to cultured endothelium after each wash was significantly higher when erythrocytes were from diabetics than when they were from controls (P less than 0.005). After the fifth wash, the mean adhesion ratio (percentage of adhering diabetic red cells: percentage of adhering control red cells) was 2.33 (range, 0.8 to 5.2). Increased adhesion was related to the extent of vascular complications in the diabetics, as assessed by a vascular score. With the same technique, fewer erythrocytes adhered to plastic and to cultured human fibroblasts than to endothelial cells, although the adhesion of the diabetic red cells to these surfaces was higher than that of the controls. These results suggest that in diabetes there is an intrinsic erythrocyte abnormality that is related to vascular disease.

Adult↗
PubMed1981

Haemostatic changes in diabetic coma.

Diabetic coma is frequently associated with thromboembolic complications. A prospective study was undertaken of the haemostatic changes occurring in 15 patients (12 with ketoacidosis, three with the hyperosmolar syndrome) during diabetic coma. When compared with the results after stabilization of the diabetes, ketoacidosis was associated with significantly higher levels of factor VIII coagulant activity, factor VIII-related antigen and fibrin degradation products, a shorter partial thromboplastin time and reduced concentrations of antithrombin III. These results suggest that in uncomplicated ketoacidosis, haematological changes occur which may reflect vascular endothelial damage and intravascular fibrin deposition. Out of three deaths, two patients (both with the hyperosmolar syndrome) had evidence of disseminated intravascular coagulation. To reduce further the mortality and morbidity from diabetic coma, controlled clinical trials of anticoagulant and antiplatelet drugs may be indicated.

Adolescent↗
PubMed1981

Changes in thrombin-stimulated platelet malondialdehyde production during the menstrual cycle.

Forty normal women had thrombin-stimulated platelet malondialdehyde (MDA) production measured during their menstrual cycle. Twenty women in this group were taking the combined oral contraceptive pill (OCP). Platelet MDA production was found to fall by 30% during normal menstruation and the week when the subjects were not taking a combined OCP, but it remained constant throughout the remainder of the cycle. No significant change in initial platelet aggregation response to stimulation by thrombin, change in plasma thrombin clotting time, plasma heparin neutralising activity (HNA), or plasma antithrombin III (AT-III) activity was seen when the platelet MDA production was reduced. The bleeding time results showed some variation throughout the menstrual cycle but these did not appear to be related to the variation in platelet MDA production.

Adult↗
PubMed1981

The in vitro effect of ticlopidine on fibrinogen and factor VIII binding to human platelets.

The mode of action of the antiplatelet agent ticlopidine is not yet fully understood. Its multiple effects on platelet function include prolongation of the bleeding time, reduction in primary and secondary waves of ADP-induced aggregation and inhibition of collagen and thrombin-induced aggregation. We have studied the in vitro effects of ticlopidine on fibrinogen binding induced by ADP and adrenaline as well as factor VIII/vWF binding induced by ristocetin. 125I-fibrinogen binding was measured in suspensions of freshly-washed normal platelets stimulated by 10 microM ADP or 10 microM adrenaline. The binding of 125I-factor VIII/vWF in the presence of 1 mg/ml ristocetin was measured in both washed and paraformaldehyde-fixed platelets. Ticlopidine at final concentrations of 200, 100, 50 and 25 microM inhibited both ADP and adrenaline-induced fibrinogen binding in a dose-dependent manner. The mean % inhibition of ADP-induced fibrinogen binding was 82, 73, 42 and 32 respectively. The mean % inhibition of adrenaline-induced fibrinogen binding was 86, 82, 60 and 35 respectively. In contrast, the factor VIII/vWF binding was unaffected by ticlopidine at all concentrations except at 200 microM using fresh platelets where a slight inhibition (19%) was observed. These results suggest that ticlopidine either inhibits platelet activation and consequently fibrinogen binding, or inhibits the binding directly, presumably by having an effect on the specific configuration of the platelet membrane required for normal fibrinogen binding.

Anticoagulants↗
PubMed1981

Von Willebrand factor, diabetes mellitus and retinopathy.

Von Willebrand factor (VIII: vWf) is a glycoprotein which is essential for normal platelet adhesion to vascular subendothelium, particularly at the high shear rates encountered in small blood vessels. VIII: vWf is distributed in plasma, platelets and subendothelium, though the contributions of each pool to normal hemostasis is unknown. Raised plasma of VIII: vWf have been frequently described in association with diabetes, the highest concentrations being found in patients with retinopathy. In addition, concentrations of VIII: vWf appear to be influenced by the degree of metabolic control of the diabetics, particularly high levels being found during diabetic coma. Plasmatic concentrations of VIII: vWf greater than normal have not been shown to result in increased platelet adhesion or aggregation, so that is seems unlikely that the high levels of plasmatic VIII: vWf contribute directly to the pathogensis of retinopathy. On the other hand, increases in VIII: vWF during episodes of poor metabolic control could be evidence of reversible injury to the vascular endothelium, whereas stable, high concentrations may indicate the presence of microangiopathy.

Blood Coagulation Factors↗
PubMed1979

Platelet function in hairy-cell leukaemia.

A quantitative study of various aspects of platelet function was carried out in eight patients with typical hairy-cell leukaemia (HCL). In at least two patients platelet aggregation was convincingly reduced to more than one aggregating agent (ADP, adrenaline, collagen, thrombin, and ristocetin). Granular storage capacity for {(14)C} 5-HT was reduced in five of the six patients tested. The two patients with definitely abnormal aggregation had the greatest reduction in granular storage pool and the longest bleeding times of those tested but, like the other patients, they did not have a clinical haemostatic defect. It was concluded that a granular storage pool defect (SPD) was at least partly responsible for aggregation abnormalities in HCL since the platelet release reaction in response to thrombin appeared to be normal. All our patients ran a chronic course uncomplicated by any of the factors known to predispose to a platelet SPD acquired in the circulation. Although in the one patient tested before and after splenectomy there was some improvement in platelet aggregation after operation, there was no clear general relationship between defective platelet function and either previous splenectomy or platelet count. Since a direct involvement of the megakaryocytic series in the underlying cell proliferation of HCL seems unlikely, it is concluded that the platelet defect can most reasonably be attributed to the production of abnormal platelets as a result of marrow fibrosis and/or infiltration by hairy cells.

Bleeding Time↗
PubMedDate not supplied

Diagrammatic representations for modelling biological knowledge.

The contemporary research and development context in multidisciplinary biology has a serious requirement for integrating knowledge from disparate sources, and facilitating much-needed inter- and intra-disciplinary dialogue. A multiplicity of models arises when pluralistic approaches to modelling are followed, and also when there is not only a requirement to model systems and data, but also knowledge of systems and data. The challenges of addressing this multiplicity do not only include articulating the structure of complex systems, but also placing modelling within the framework of a process as well as a product. The graph representations presented here facilitate dialogue, modelling, clarification and specification of concepts, and the sharing of terms. This paper explores relationships between collections of graph representations. It is hoped that in future, when readers look at a node or a process in a graph, they will have a much deeper appreciation of relationships and context.

Data Display↗