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Biomedical subjects

F E Preston

Publications and source records attributed to F E Preston.

At least 145 records · Page 8Linked to original sources
PubMed1990

Platelet aggregation by oral streptococci.

One proposed mechanism in the pathogenesis of infective endocarditis is the direct aggregation of platelets by the bacteria causing the disease. Some, but not all, strains of Streptococcus sanguis have been reported to aggregate platelets but the taxonomy of this and related taxa has changed recently. The ability to aggregate platelets by 24 genetically grouped laboratory stock strains was studied along with 8 recent isolates from cases of endocarditis. Strains belonging to S. sanguis could aggregate platelets, but not S. gordonii, "S. parasanguis", S. mitis, S. oralis or related taxa. Also, preliminary data indicate that certain biotypes of S. sanguis lack the ability to aggregate platelets. Of the recent clinical isolates, only 4 aggregated platelets and each of these showed phenotypes typical of S. sanguis. These data suggest that the ability to aggregate platelets is not essential for an organism to be able to cause endocarditis, although it may be a significant virulence factor.

Humans↗
PubMed1990

A comparative evaluation of assays for markers of activated coagulation and/or fibrinolysis: thrombin-antithrombin complex, D-dimer and fibrinogen/fibrin fragment E antigen.

Measurements were made of levels of D-dimer in plasma and serum, thrombin-antithrombin complex (TAT) in plasma and fibrinogen/fibrin fragment E antigen (FgE) in serum in a normal healthy control group and in patients with a range of disorders associated with hypercoagulability. Levels were determined in 31 normal healthy controls, 30 patients with disseminated intravascular coagulation (DIC), 21 patients with deep venous thrombosis (DVT), 27 patients with myocardial infarction (MI), 26 patients with acute leukaemia and 56 patients with liver disease. Considering all subjects, significant correlations were established between the results of all assays. Notably high correlations (r greater than 0.9) were established between plasma and serum levels of D-dimer, between plasma levels of D-dimer and serum levels of FgE, and between serum levels of D-dimer and FgE. All assays showed very high discrimination (sensitivity) between the normal control group and patients with DIC (97-100%), but there were marked differences between the assays in sensitivity for DVT and MI. In general, the FgE assay was more sensitive than the D-dimer assay, whilst both the FgE and D-dimer assays were more sensitive than the TAT assay. The same trends were apparent in the capability of the assays to discriminate between the normal control group and patients with acute leukaemia and liver disease: disorders with an unknown prevalence of activation of coagulation/fibrinolysis. Our results indicated that measurements of fibrinogen/fibrin degradation products (FDPs) in serum were almost unaffected by artefacts. The data further suggested that the broad-spectrum FgE assay was better than the more specific D-dimer assay in detecting clinical hypercoagulability. Our study showed that, in the clinical conditions examined, FDPs were more effective markers of hypercoagulability than TAT.

Acute Disease↗
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

Rapid assessment of haemophilia A carrier state by non-invasive techniques using the polymerase chain reaction.

The polymerase chain reaction (PCR) was used to amplify two polymorphic regions in the factor VIII gene. In vitro synthesis of DNA was achieved using samples obtained from buccal cells, urine, and hair follicles in addition to purified genomic and crude DNA samples prepared from whole blood. Female members of two kindreds affected with haemophilia A were assessed for carrier state using direct restriction fragment length polymorphism analysis of amplified gene products in the Bc1I and XbaI regions. It is concluded that this is a non-invasive, rapid, and inexpensive technique for carrier detection.

Carrier State↗
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

Recurrent multiple-branch retinal arteriolar occlusions in a patient with protein C deficiency.

A 34-year-old woman is presented who has recurrent, multiple, retinal arteriolar occlusions associated with a deficiency in protein C, a vitamin K-dependent anticoagulant. Protein C is a naturally occurring anticoagulant and if there is a deficiency, it can lead to episodes of thrombosis; the deficiency can be acquired or congenital. This is the first documented case of retinal arteriolar occlusion associated with a congenital deficiency of this protein. The mechanism for arteriolar occlusion in this patient is discussed, and whilst the role of protein C deficiency remains presumptive, it is strongly implicated.

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↗
PubMed1988

Do extra-platelet sources contribute to the plasma level of thrombospondin?

Thrombospondin, a trimeric glycoprotein contained in the platelet alpha-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relationship between plasma thrombospondin levels and platelet count in samples from profoundly thrombocytopenic patients with marrow hypoplasia, using the platelet-specific alpha-granule protein beta-thromboglobulin as control. Serum concentrations of both proteins were highly correlated with platelet count, but while plasma beta-thromboglobulin levels and platelet count also correlated, there was no relationship between the number of platelets and thrombospondin concentrations in plasma. Serial sampling of patients recovering from bone marrow depression indicated that the plasma thrombospondin contributed by platelets is superimposed on a background concentration of at least 50 ng/ml probably derived from a non-platelet source, and plasma thrombospondin levels do not simply reflect platelet release.

Adolescent↗
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

The relationship between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity with warfarin.

1 The effect of low dose steady state warfarin (0.2 mg and 1 mg daily) on clotting factor activity and vitamin K1 metabolism was studied in seven healthy volunteers. 2 Steady state plasma warfarin concentrations were 41-99 ng ml-1 for the 0.2 mg dose and 157-292 ng ml-1 for the 1 mg dose. 3 There was a significant prolongation of the mean prothrombin time (0.9 s) after 1 mg warfarin daily, but no significant change in prothrombin time after 0.2 mg warfarin daily. There was no significant change in individual clotting factor activity (II, VII, IX or X) with either dose of warfarin. 4 Following the administration of a pharmacological dose of vitamin K1 (10 mg), all seven volunteers had detectable levels of vitamin K1 2,3-epoxide with both doses of warfarin (Cpmax 31-409 ng ml-1). 5 Both the Cpmax and the AUC for vitamin K1 2,3-epoxide were significantly greater on 1 mg of warfarin daily than 0.2 mg daily (P less than 0.01). 6 The apparent dissociation between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity, produced by warfarin, may reflect the insensitivity of functional clotting factor assays to a small reduction in clotting factor concentration.

Blood Coagulation Factors↗
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↗