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Biomedical subjects

M Greaves

Publications and source records attributed to M Greaves.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1989

Antibody-dependent cellular cytotoxicity of vascular endothelium: characterization and pathogenic associations in systemic sclerosis.

Ten sera from 48 patients with systemic sclerosis were found to be capable of producing cytotoxicity of human umbilical venous and arterial endothelium when co-cultured with peripheral blood mononuclear cells. Fractionation of sera on Ultrogel and the preparation of monomeric IgG by ion exchange and affinity chromatography suggested that the cytotoxicity was mediated by anti-endothelial antibodies capable of pre-sensitizing target cells in a mechanism that resembled antibody-dependent cellular cytotoxicity. These anti-endothelial antibodies together with C1q-binding immune complexes and anti-cardiolipin antibodies were found in 18 of 28 patients so investigated, suggesting that multiple immunological mechanisms may be involved in the pathogenesis of the vascular lesion of systemic sclerosis.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1988

A method for the determination of activated factor VII using bovine and rabbit brain thromboplastins: demonstration of increased levels in disseminated intravascular coagulation.

Factor VII levels as measured in one stage clotting assays are dependent on the degree of activation of factor VII and on the type of thromboplastin used. Bovine thromboplastin (BT) is known to be more sensitive to factor VIIa than human brain thromboplastin and the different sensitivities of these reagents to VIIa have formed the basis of a method for determining VIIa in plasma (16). Since human thromboplastin is no longer widely available, we have re-evaluated this method using bovine and two rabbit thromboplastins (Manchester Reagent, RT MR and Diagen activated, RT Diagen). Activated factor VII was generated in normal plasma by cold activation for 24 hours. During this period, factor VII assays using bovine thromboplastin increased markedly with time whereas the assays using rabbit thromboplastins showed considerably less change. The ratio of factor VII (bovine thromboplastin)/factor VII (rabbit thromboplastin) is a sensitive index of activated factor VII in plasma. The mean ratio in normal plasmas (using BT and RT MR) was found to be 1.02 (+/- s.d., range 0.80-1.24). The ratio was measured in 29 samples from patients with disseminated intravascular coagulation (D.I.C.) and was found to be increased in 24 (mean 1.71, range 0.93-3.38).

Adult↗
PubMed1988

Elevated von Willebrand factor antigen in systemic sclerosis: relationship to visceral disease.

Plasma levels of the factor VIII complex (von Willebrand factor antigen, factor VIII coagulant and ristocetin co-factor) were measured in 28 patients with systemic sclerosis. Elevated von Willebrand factor antigen was found in 12 patients overall and in 10 of 16 patients characterized by severe extensive visceral disease, with a resulting positive correlation between the extent of visceral involvement and the plasma level of von Willebrand factor antigen (r = 0.60, p less than 0.001). Factor VIII coagulant and ristocetin co-factor levels, however, frequently failed to parallel the increases of von Willebrand factor antigen, supporting the view that these increases were due to in vivo endothelial damage. The findings suggest that vascular damage is an important aspect of the visceral lesions of systemic sclerosis.

Adult↗
PubMed1988

Thrombovascular disease and familial plasminogen deficiency: a report of three kindreds.

We report three kindreds in whom plasminogen deficiency was associated with thrombosis and in whom the ratio of functional and immunological values of plasminogen was consistent with type I deficiency. An additional subject with plasminogen deficiency is also described. The three propositi presented with venous thrombotic disease. The fourth subject presented with a thrombotic stroke. Investigation of family members in three of these four cases revealed other subjects who were found to have low levels of plasminogen and who were asymptomatic. The pattern of inheritance appears to be autosomal dominant. In one woman, plasminogen levels were shown to rise to within the normal range during pregnancy and returned to low levels after delivery. A total of eight pregnancies were reviewed in our series and no thrombotic events occurred.

Adult↗
PubMed1988

Fibrinolysis during normal human pregnancy: complex inter-relationships between plasma levels of tissue plasminogen activator and inhibitors and the euglobulin clot lysis time.

Although it has been previously considered that blood fibrinolytic capacity is reduced during pregnancy, this has been disputed. Also the mechanisms underlying any change in fibrinolysis in pregnancy require clarification. We have therefore measured the plasma activity of tissue plasminogen activator (t-PA) and inhibitors (t-PAi) and the concentration of the pregnancy specific inhibitor (PA12) antigen, as well as the euglobulin clot lysis time (ECLT) during normal pregnancy. Plasma concentrations of fibrinogen, plasminogen, fibrin(ogen) degradation products (FDP) and cross-linked products (D-dimer) were also monitored. We confirm a marked reduction of the fibrinolytic activity of the plasma euglobulin fraction from the second trimester, and a parallel reduction in t-PA and increase in t-PAi activities, with rapid return to non-pregnant levels post-partum. In contrast, PAI2, whilst undetectable in non-pregnant control plasma, was already measurable in the first trimester, increased through pregnancy, and remained at a high concentration up to at least 48 h post-partum. Fibrinogen and plasminogen concentrations rose progressively through pregnancy and FDP and D-dimer were frequently detectable in late pregnancy plasma. Changes in the ECLT and plasma t-PA and t-PAi activities in pregnancy cannot therefore be directly related to the concentration of PAI2 antigen. Also, despite the apparent marked reduction in fibrinolytic capacity fibrin(ogen) breakdown products are frequently present in increased plasma concentrations in late pregnancy.

Female↗
PubMed1988

Association between necropsy evidence of disseminated intravascular coagulation and coagulation variables before death in patients in intensive care units.

The necropsy findings in 21 patients on an intensive care unit, on whom coagulation studies had been performed immediately before death, were assessed. Eleven of the patients were retrospectively studied and 10 were reviewed consecutively in a prospective study. Fifteen patients (eight retrospective and seven prospective) had evidence of disseminated intravascular coagulation. Microthrombi were most often found in the lungs and kidneys. The most common abnormal coagulation tests in patients with necropsy evidence of disseminated intravascular coagulation were raised serum concentrations of fibrinogen and fibrin degradation products, prolonged prothrombin time, and reduced platelet counts. Reduced fibrinogen concentrations and a prolonged thrombin time were the least commonly observed abnormalities. There was no difference in either the prevalence or magnitude of abnormality of any particular coagulation variable test result between those patients with evidence of disseminated intravascular coagulation at necropsy and those without.

Adult↗
PubMed1988

Acquired dysfibrinogenaemia masquerading as disseminated intravascular coagulation in acute pancreatitis.

Acquired dysfibrinogenaemia as the cause of coagulation abnormalities occurred in a case of acute pancreatitis. Initial coagulation studies showed a prolonged thrombin time and increased concentrations of serum fibrinogen/fibrin degradation products and plasma D-dimer. Further studies on purified fibrinogen showed evidence of degradation of the C-terminal ends of the A-alpha chains, which, it is suggested, resulted from the action of circulating pancreatic proteases. Fibrin polymerisation was thus shown to be impaired, which explains the prolongation of the thrombin time. There was a temporal relation between increased amylase activities and the prolonged thrombin time, both of which returned to normal three weeks after admission. Acquired dysfibrinogenaemia may be an underrecognized phenomenon in acute pancreatitis and may lead to misinterpretation of coagulation test abnormalities.

Acute Disease↗