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Biomedical subjects

M Greaves

Publications and source records attributed to M Greaves.

At least 37 records · Page 2Linked to original sources
PubMed1990

Elevated platelet-free calcium in uraemia.

Bleeding complications in uraemia are not uncommon. The pathogenesis of haemorrhage in uraemia is still a matter of controversy and the pattern of bleeding suggests a defect of primary haemostasis. Platelet aggregation and biochemistry, including calcium levels, have been studied; however, the results are controversial. We have examined platelet aggregation, platelet-free calcium and calmodulin in platelet-rich plasma because of the significant role of calcium and calmodulin in regulating platelet and other cells' functions. Platelet aggregation in uraemic subjects was similar to that of controls. Platelet basal free cytosolic calcium and platelet calcium in response to 10 microM Ca++ ionophore A23187 in eight subjects with uraemia were 117 +/- 33 nM and 2025 +/- 398 nM (mean +/- SEM) respectively. By contrast in seven matched healthy controls basal calcium and ionophore-stimulated calcium values were 47 +/- 14 nM and 1354 +/- 414 nM, significantly less than in the patients with uraemia (P less than 0.05). The sensitivity of uraemic platelets to A23187 was similar to that of controls. Calmodulin activity in platelet-rich plasma of 12 subjects with uraemia showed no significant difference from that of controls [1.86 +/- 0.29 micrograms/ml (mean +/- SEM) and 2.0 +/- 0.37 micrograms/ml (mean +/- SEM) respectively]. We conclude that despite elevation of platelet calcium in uraemia, which may be due to a plasma factor such as parathyroid hormone, platelet aggregation is normal and bleeding in uraemia is more likely to be due to other factors, including the effect of reduced haematocrit on platelet endothelial interaction. Disturbances in platelet calcium cannot explain the bleeding manifestations in uraemia but warrant further investigation in order to identify the pathogenic mechanisms responsible.

Adolescent↗
PubMed1990

Inhibition of activated protein C and its cofactor protein S by antiphospholipid antibodies.

We have investigated the effects of purified IgG fractions from plasma containing the lupus anticoagulant (LAC) and/or IgG anticardiolipin antibody (ACA) on the degradation of factor Va by an activated protein C-protein S complex. Plasma samples from 10 patients were studied. LAC was detected by a Russell's Viper venom technique. ACA was determined by ELISA. IgG fractions were obtained from each plasma sample by protein A-Sepharose fractionation. This fraction was shown to exhibit ACA/LAC activity. Using purified activated protein C (APC), protein S and phosphatidylserine/phosphatidylcholine, factor Va degradation was assessed in the presence and absence of IgG fractions from LAC/ACA containing plasmas. After 2 min incubation the mean factor Va degradation by APC and protein S in the presence of IgG LAC/ACA fractions was 14% compared with 52% with normal IgG. A similar effect was seen when phospholipid was substituted by washed freeze-thawed platelets. Experiments employing varying concentrations of protein S and phospholipid revealed marked differences in respect of the inhibitory specificity of the different antiphospholipid antibodies. These results indicate that antiphospholipid antibodies have an inhibitory effect on the activated protein C/protein S complex and provide some explanation for a relationship between antiphospholipid antibodies and thrombosis.

Autoantibodies↗
PubMed1990

Megakaryocyte ploidy in thrombocytosis: improved microdensitometric measurements with a new image analysis system.

Megakaryocyte (MK) nuclear deoxyribonucleic acid (DNA) content was measured on a new image analysis system. Feulgen-stained bone marrow aspirate smears were analysed from 9 patients with thrombocytosis. Average optical density (OD) of stained nuclei was evaluated by pixel discrimination over 128 grey levels. Projected nuclear area was delineated manually. The product of these two parameters gave an index of nuclear DNA content. Neutrophils were used as 2N reference cells. Reproducibility of OD, nuclear area and their product was excellent for individual cells (CV less than 2.0% for MKs, less than 4.0% for neutrophils). The average CV for DNA content of 18 groups of 10 neutrophils was 5.5% (range 3.0-9.7%). A significant linear regression existed between MK nuclear area and DNA content (p much less than 0.001) for 627 MKs in essential thrombocythaemia (ET) and 346 MKs in reactive thrombocytosis (RT). Compared with RT, more 8N and 64N MKs were seen in ET (p less than 0.05). 128N MKs were unique to ET. Image analysis of MK ploidy may assist the clinical discrimination between primary and secondary thrombocytosis.

DNA↗
PubMed1990

A placebo-controlled, double-blind study of eicosapentaenoic acid-rich fish oil in patients with stable angina pectoris.

A study was carried out to evaluate the clinical and haematological effects of dietary supplementation with eicosapentaenoic acid (EPA)-rich fish oil (MaxEPA', 2.8 g EPA daily) compared to placebo (olive oil) in 10 patients with stable angina pectoris. After 3 months, there was a significant increase in red cell deformability (p less than 0.001), reduced whole blood viscosity (p less than 0.02), and prolonged skin bleeding time (p less than 0.001) in the fish oil group compared to the placebo group. Haematocrit, plasma viscosity, fibrinogen concentration, platelet count, and in vitro platelet aggregation were unaltered. No significant symptomatic or objective improvement was noted in angina pectoris in either group despite the significant rheological changes produced in the patients receiving fish oil.

Adult↗
PubMed1989

DN 9693: a phosphodiesterase inhibitor with a platelet membrane effect.

We have examined the in vitro effects of DN 9693 (piperidinylimidazo-quinazolinone) on various aspects of platelet reactivity. Our results are consistent with its known function as a phosphodiesterase inhibitor in that it increased platelet cyclic AMP, particularly in conjunction with an adenylate cyclase stimulator, and exerted a profound inhibitory effect on platelet aggregation responses to a variety of agonists. DN 9693 also inhibited ristocetin-induced platelet agglutination (RIPA). We therefore examined its effect on ristocetin co-factor assays and on the binding of a monoclonal antibody (McAb) to platelet membrane glycoprotein Ib (GPIb). The drug inhibited the binding of the monoclonal antibody in a dose-dependent manner. This suggests an effect of the drug on the platelet surface membrane with reduced expression of GPIb. Our results indicate that in addition to its anticipated inhibitory effect on platelet aggregation, DN 9693 may also inhibit platelet adhesion.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Prostacyclin production by human umbilical vein endothelium in response to serum from patients with systemic sclerosis.

Sera from 29 patients with systemic sclerosis and 30 normal controls were examined for their effect on prostacyclin release by human umbilical vein endothelial cells during periods of response of 15 min and 72 h and for their effect on endothelial growth and 3H-thymidine uptake during a 72-h culture period. In contrast to previous reports, no significant differences were detected between patient and control sera in their effect on endothelial cell prostacyclin release, growth or 3H-thymidine uptake.

Adult↗
PubMed1989

Arachidonic acid transformation is not stimulated in delayed pressure urticaria.

Little is known about the molecular mechanisms or inflammatory mediators involved in delayed pressure urticaria (DPU). Pressure sufficient to provoke lesions was applied to the back of six patients with DPU. The levels of products of arachidonic acid transformation in skin exudate from the pressure challenged skin were estimated immediately after pressure was removed and 6 h later when lesions were present. These were compared to levels estimated in a similar way from unchallenged skin in these patients. Levels of leukotriene C4/D4/E4, prostaglandin E2, 12-hydroxyeicosatetraenoic acid and leukotriene B4 were not raised in lesional skin. Our results suggest that arachidonic acid metabolism is not stimulated in DPU.

Adult↗
PubMed1989

Vitamin D metabolism in myeloma.

We measured serum concentrations of vitamin D metabolites in 27 patients with myeloma, 16 of whom were hypercalcaemic. Serum values were compared with values from normal controls. Serum concentrations of calcitriol (1.25-dihydroxyvitamin D; 1.25(OH)2D3) were decreased in both hyper- and normocalcaemic patients, but more markedly so in hypercalcaemia. These findings were not solely due to impaired renal function nor due to an inadequate supply of 25-hydroxyvitamin D, and in hypercalcaemic patients were reversed by diphosphonate treatment. We conclude that hypercalcaemia in myeloma is not mediated by abnormalities in vitamin D metabolism. Decreased serum concentrations of 1.25(OH)2D3 may adversely affect both skeletal and tumour metabolism.

Adult↗
PubMed1989

Plasma D-dimer levels and their relationship to serum fibrinogen/fibrin degradation products in hypercoagulable states.

Plasma D-dimer was measured and compared with serum fibrinogen/fibrin degradation product levels (FDPs) in patients with disseminated intravascular coagulation (DIC) and other conditions associated with a hypercoagulable state. D-dimer (N less than 200 ng/ml) was elevated in all 43 patients with DIC, in 48 of 59 patients with liver disease, in 22 of 27 patients with acute leukaemia at presentation, in 17 of 23 patients with malignant disease, in 29 of 39 women in the third trimester of a complicated pregnancy, in 17 of 18 patients with deep venous thrombosis and in only four of 27 patients with acute myocardial infarction. There was a significant correlation between plasma D-dimer and serum FDP levels (P less than 0.01) as follows; DIC: r = 0.58, liver disease: r = 0.57, acute leukaemia: r = 0.84, malignancy: r = 0.87. The frequent elevation of D-dimer observed in liver disease, acute leukaemia, malignancy and complicated pregnancy indicates that a hypercoagulable state is a common occurrence in these conditions although in liver disease elevated levels resulting from a failure of normal clearance mechanisms cannot be excluded. The close relationship between D-dimer and FDP levels suggests that serum FDPs predominantly arise from the interaction of plasmin with crosslinked fibrin rather than with fibrinogen in the conditions in which these were compared.

Blood Coagulation Disorders↗
PubMed1989

Antithrombin Sheffield: amino acid substitution at the reactive site (Arg393 to His) causing thrombosis.

A Sheffield family with a predisposition towards thrombosis has been shown to have a functional abnormality of antithrombin. The abnormality was detected as reduced heparin cofactor activity, with normal antigenic levels of antithrombin. Crossed immunoelectrophoresis performed in the absence and presence of heparin was normal. The antithrombin was isolated by heparin Sepharose affinity chromatography. It had normal mobility on SDS polyacrylamide gel electrophoresis. However, the second order rate constant of inhibition of thrombin was about half that of normal, and this was compatible with a heterozygous abnormality involving the reactive site. The antithrombin was further purified by chromatography on thrombin-Sepharose (to remove the normal component), reduced, S-carboxymethylated and fragmented with cyanogen bromide. A pool containing the reactive site region was digested with trypsin and the molecular size of peptides generated determined by fast atom bombardment mass spectrometry. The two peptides adjacent to the Arg393-Ser394 bond of mass 2290 and 700 were almost absent from the mass spectrum, but an additional peptide of mass 2952 was present. Subdigestion with V8 protease reduced the mass of this peptide to 1748. These peptides generated by trypsin and V8 protease were almost identical to those obtained when another variant, antithrombin Glasgow, was treated in the same way (Erdjument et al, 1988). It is concluded that the molecular abnormality of antithrombin Sheffield is identical to that of antithrombin Glasgow, Arg393 to His.

Adult↗
PubMed1989

Blood usage for elective surgery. A reappraisal of the need for autologous transfusion.

To assess the need for a pre-operative autologous transfusion programme in a large teaching hospital, a review of blood cross-matching and transfusion practice for three elective surgical procedures was undertaken. For hysterectomy, the cross-match rate was 28%, and the transfusion rate only 8%. For transurethral resection of prostate and hemicolectomy, all patients were cross-matched, but only 19% and 36%, respectively, transfused. Given these figures, an autologous transfusion programme was not felt to be cost-effective. Local audit is necessary before this can be ascertained for a given district, as is consideration of the likelihood of infectious hazards in the regional blood supply.

Blood Grouping and Crossmatching↗
PubMed1989

Permanent transvenous pacing after a Mustard procedure.

We report the case of a 20-year-old man born with transposition of the great vessels who underwent emergency balloon septostomy and subsequently a Mustard procedure. When aged 20 years, he had several syncopal attacks due to sinoatrial disease for which he was simply and successfully paced transvenously in VVI mode.

Adult↗