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Biomedical subjects

R C Paton

Publications and source records attributed to R C Paton.

At least 19 recordsLinked to original sources
PubMed1993

Some computational models at the cellular level.

A number of viewpoints on how a cell can be modelled are discussed in this paper in light of the ability it has to process information. The paper begins with a very brief summary of four general types of computation: sequential, parallel, distributed, and emergent. These form the general framework from which a number of comparisons are made. Several metaphors are introduced to enable reflections to be made about cellular computational properties. The most important metaphor, namely the cell as a machine, is discussed, and then a number of other ideas are introduced that complement much current thinking in this area. The idea of networks or circuits in the cell is then developed, as this provides a means of describing the mechanisms within a machine. Following on from this, three further metaphors are applied in order to overcome certain limitations in current machine thinking, cell-as-society, cell-as-text, and cell-as-field.

Animals↗
PubMed1983

Platelets and diabetic vascular disease.

Tests of platelet behaviour in vitro, particularly aggregation and retention and in vivo tests such as measurement of platelet survival and plasma levels of beta-thromboglobulin are frequently abnormal in diabetic patients, particularly in those with vascular disease. The concept has therefore arisen that platelet hyper-reactivity is one factor responsible for diabetic microangiopathy. Whereas there is experimental and histological evidence for the mediation of platelets in the pathogenesis of atherosclerosis, direct evidence of platelet involvement in microangiopathy is scanty. Similar alterations in platelet behaviour have been observed in a variety of other conditions with vessel wall damage in common and evidence is presented which suggests that these platelet abnormalities may be secondary to vessel wall injury. In diabetic subjects, some changes in platelet behaviour are reversed by improved glycaemic control. Evidence that platelets are involved in the pathogenesis of diabetic microangiopathy therefore remains circumstantial, though current trials of anti-platelet agents may enable a more precise evaluation of their role.

Adenosine Diphosphate↗
PubMed1983

Fibrinogen, a modulator of erythrocyte adhesion to vascular endothelium.

The high incidence of thrombosis in inflammatory states and previous reports of increased adhesion of erythrocytes to endothelial cells in diabetes mellitus and sickle cell anemia prompted us to study the effect of fibrinogen and fibronectin on erythrocyte-endothelial interactions. Purified human fibrinogen enhanced erythrocyte adhesion in a concentration-dependent fashion. Erythrocytes from normal subjects, diabetics, and patients with sickle cell anemia were studied. The ratio between the adhesion of normal red cells in a 4 gm/L fibrinogen to adhesion in buffer without fibrinogen was 3.6 (p less than 0.001). Fibronectin also increased red cell adhesion but the effect was less than that of fibrinogen. The addition of fibronectin to fibrinogen limited the enhancing effect of fibrinogen, although the effect of the mixture was greater than that of fibronectin alone (p less than 0.05). Anti-von Willebrand factor and antifibronectin, which react with endothelial cells, also produced an increase in erythrocyte adhesion. The potentiation of adhesion by fibrinogen was also seen in experiments using red cells from patients with sickle cell anemia or diabetes mellitus. These observations provide possible mechanisms for the involvement of plasma proteins in vascular occlusive diseases.

Adult↗
PubMed1982

6-oxo-prostaglandin F1 alpha and thromboxane B2 in uterine vein blood--a possible role in menstrual bleeding.

The role of the haemostatic system in relation to menstrual bleeding is poorly understood. Platelet retention to glass beads and plasma concentrations of 6-oxo-PGF1 alpha and thromboxane B2 were measured in uterine and peripheral venous blood obtained from 18 women undergoing abdominal hysterectomy. Concentrations of 6-oxo-PGF1 alpha were significantly (p less than 0.01) higher in uterine (1.4 +/- 0.3 ng/ml, mean +/- SEM) than in peripheral vein blood (0.2 +/- 0.1 ng/ml) as was the level of thromboxane B2 (0.5 +/- 0.1 and 0.2 +/- 0.1 ng/ml, respectively). Platelet retention in uterine vein blood (11 +/- 4%) was significantly lower than in peripheral blood (42 +/- 4%; p less than 0.01) and the degree of platelet retention correlated inversely with the plasma concentration of 6-oxo-PGF1 alpha (r -0.43; p less than 0.01). There was a significant rank correlation between time since menstruation and concentrations of 6-oxo-PGF1 alpha in uterine (tau + 0.69; p less than 0.001) and peripheral (tau + 0.56; p less than 0.05) vein blood. The results indicate that an increased local production of prostacyclin (PGI2) relative to thromboxane A2 at the time of menstruation could contribute to the mechanism of uterine bleeding.

Adult↗
PubMed1982

Aspirin, dipyridamole and platelet survival in patients with diabetes mellitus.

1. Platelet survival in 27 insulin-dependent diabetic patients with severe retinopathy was studied in a double-blind cross-over trial using placebo, aspirin (990 mg/day) and a combination of dipyridamole (225 mg/day) with aspirin at two dosage levels (330 mg and 990 mg/day). 2. Twenty patients (group I) had 51Cr-labelled-platelet survival after treatment with placebo and the high-dose-aspirin/dipyridamole combination. The remaining seven patients (group II) had platelet-regeneration times measured after each of the four treatment periods. 3. Treatment of group I patients with the high-dose-aspirin/dipyridamole combination resulted in significant (P less than 0.001) prolongation of platelet survival from 7.3 +/- 0.2 (mean +/- SEM days to 8.4 +/- 0.1 days. 4. In group II patients, when compared with the mean placebo result of 7.2 +/- 0.2 days, the mean aspirin-labelled-platelet-regeneration time was significantly (P less than 0.01) longer only after high-dose-aspirin/dipyridamole (9.8 +/- 0.5 days) but not after low-dose-aspirin/dipyridamole (8.3 +/- 0.5 days) or aspirin alone (7.3 +/- 0.3 days). 5. These results suggest that it may be premature to consider reducing the dose of aspirin in aspirin/dipyridamole combinations below 1 g/day when used as antithrombotic therapy.

Adult↗
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↗