PubMed Health⌕ Search

Biomedical subjects

W S Etches

Publications and source records attributed to W S Etches.

14 recordsLinked to original sources
PubMed2000

Warfarin monitoring in patients with anticardiolipin antibodies, but without lupus anticoagulants.

Misleading international normalized ratios (INR) may be obtained from anticoagulated patients with lupus anticoagulants (LA). As a result, special precautions have been suggested for oral anticoagulant dosing. It is possible that plasma from subjects with an anticardiolipin antibody (ACA) without an LA could also affect the INR. We have studied nine such subjects who were anticoagulated and compared them with 11subjects who had neither antibody. The INR was performed, using local specific ISIs, with 11 different thromboplastins. No substantial difference was seen between the ACA-positive and ACA-negative patients, for either individual thromboplastins or patients. We similarly measured INRs in eight nonanticoagulated patients with ACAs. No effect on the INR results was observed. Thus, in these anticoagulated and nonanticoagulated patients we detected no evidence of any effect of an ACA on the INR.

Analysis of Variance↗
PubMed2000

Flow cytometric detection of CD79a expression in T-cell acute lymphoblastic leukemias.

We evaluated the lineage specificity of CD79a in acute leukemias using 3-color flow cytometry in 58 consecutive cases. A panel of cell-surface antigens, including myeloid-associated markers, B-cell-associated markers, and T-cell-associated markers, was used. All cases of acute myeloid leukemia were CD79a-, whereas all cases of B-lineage acute lymphoblastic leukemia (ALL) were CD79a+. Three of 8 cases of T-cell ALL showed variable CD79a expression, indicating the presence of a blast subset expressing a relatively high level of CD79a. We investigated the clinical and pathologic characteristics of these 3 cases. All 3 cases had L1 or L2 morphology and expressed surface CD3. None of the other B-cell-associated markers were positive, although 1 case expressed CD13 and CD33. Uncommon random karyotypic abnormalities were identified in all 3 cases. Molecular studies demonstrated monoclonal gene rearrangement of T-cell receptor gamma in 2 of 3 cases. All 3 patients were 18 years old or younger; 1 patient did not enter remission, and 1 had disease relapse in 8 months. Our findings provide further support for the existence of a subset of T-cell ALL coexpressing CD3 and CD79a. Further study of the clinical and biologic significance of this subset may be warranted.

Adolescent↗
PubMed1997

vWf inhibitor detection by competitive ELISA.

An inhibitor to von Willebrand factor (vWf) was detected in the plasma from two patients with histories of mild bleeding and one patient with a severe deficiency in the Factor VIII complex using a competitive enzyme-linked immunosorbent assay (ELISA) procedure. IgG antibodies from the patients' plasmas were shown to bind to vWf immobilised on polystyrene beads by flow cytometry. The inhibitor also potentiated a recently described platelet function assay based on stirring vWf immobilised on polystyrene beads with platelet rich plasma (PRP). Upon addition of mAb IV.3, potentiation of vWf bead-induced platelet activation was lost indicating that the enhancement of platelet activation was Fc receptor-dependent. Since the ELISA described can be used to quantitate vWf and to detect inhibitors to vWf in plasma samples, the method should prove useful in differentiating acquired vWd from congenital vWd.

Adenosine Triphosphate↗
PubMed1997

Platelet activation by a novel solid-phase agonist: effects of VWF immobilized on polystyrene beads.

The interaction between platelets stirred in suspension and VWF immobilized on polystyrene beads was studied. Platelets aggregated and released ATP in response to stirring with VWF beads. Closer examination of the interaction using transmission electron microscopy revealed that the platelets did not simply aggregate with one another but initially adhered to the beads and spread. Platelets in suspension then bound to the bead-adherent platelets forming layers of platelets associated with each bead. The VWF bead-induced platelet activation was completely inhibited by addition of monoclonal antibody (mAb) to GPIb or GPIIb/IIIa. In addition, the activation response was inhibited in the presence of aspirin, indomethacin or the thromboxane receptor antagonist BM13.177, demonstrating a dependence on an intact cyclo-oxygenase pathway. Platelet function studies were carried out on 30 patients with a history of mild bleeding using conventional optical aggregation and VWF bead-induced platelet activation. 12 patients were abnormal by conventional optical aggregometry, whereas 27 patients showed depressed ATP release in response to VWF beads. The results suggest that easily-bruised patients may have a platelet function defect rather than a vascular-based abnormality and that VWF bead-induced platelet activation is a more sensitive test for detecting platelet dysfunction.

Aspirin↗
PubMed1997

Antiphospholipid antibody-dependent C5b-9 formation.

The relationship between the presence of antiphospholipid antibodies (APA) and the production of the terminal membrane attack complex (MAC) of complement (C5b-9) was studied. Serum samples from known high positive APA patients induced platelet activation and destruction which was inhibited by heat-inactivation of the sera. The response was restored if the heat-inactivated APA-positive sera were supplemented with normal sera. Adsorption of the APA-positive sera with phospholipid (PL)-coated polystyrene beads inhibited platelet destruction. Addition of monoclonal antibody (mAb) to C5b-9 (aE11) also inhibited platelet destruction, suggesting that the APA-dependent platelet destruction might be complement-mediated. Purified APA, in the presence of normal serum, induced C5b-9 formation and binding to PL-coated beads in a dose-dependent manner as detected by flow cytometry. Prospective analysis of 200 serum samples for C5b-9 production showed that all sera testing negative for the presence of APA also tested negative for C5b-9 production. All sera with high levels of IgG binding to PL (GPL) showed evidence of C5b-9 production. Sera with low or moderate GPL values showed varying levels of C5b-9 production. These data suggest that complement may play a key role in APA-dependent platelet activation, in vivo.

Adenosine Triphosphate↗
PubMed1996

Bleeding in a patient taking Lorenzo's oil: evidence for a vascular defect.

We describe a man with adrenoleukodystrophy receiving Lorenzo's oil (glycerol trioleate and glycerol trierucate) who developed purpura, petechiae, and bleeding. Bleeding time was markedly increased (>20 min), although he had only borderline thrombocytopenia (120 x 10(9)/1) and conventional platelet aggregation studies were normal (except for a borderline response to low concentration collagen), as were results using a new technique employing immobilised von Willebrand factor. Together these results suggest that bleeding in this man resulted from a defect in vascular wall function or in the interaction of platelets with the endothelium.

Adrenoleukodystrophy↗
PubMed1995

Binding of cardiolipin to polystyrene beads: evidence for a lamellar phase orientation.

The association of cardiolipin with polystyrene beads was studied using 31P-NMR and electron microscopy. In the presence and absence of fetal calf serum, cardiolipin appeared to bind to the polystyrene beads in lamellar phase as assessed by 31P-NMR imaging. Electron microscopic analysis revealed an even coating of phospholipid about the beads with extensive micelle binding. Cardiolipin-coated beads challenged with ACA-positive sera followed by immunogold indicated antibody bound to micelles associated with the bead. Studies conducted with ACA IgG purified from patient sera indicated that some ACA bound to CL beads in the absence of a source of ACA cofactor (i.e. gelatin-blocked beads), some ACA required beta 2-GPI for binding (i.e. no binding in the presence of beta 2-GPI-depleted plasma), whereas other ACA which showed negligible binding with gelatin-blocked beads, showed enhanced binding in the presence of beta 2-GPI-depleted plasma. The data indicate that: (1) cardiolipin binds to polystyrene beads in lamellar phase, (2) ACA bind to phospholipid micelles bound directly to the polystyrene beads, and (3) ACA differ between individuals displaying varying phospholipid and phospholipid/cofactor substrate specificities.

Antibodies, Anticardiolipin↗
PubMed1995

Heparin-induced thrombocytopenia: an improved method of detection based on lumi-aggregometry.

Heparin-induced thrombocytopenia (HIT) is a recognized complication of heparin administration. Early detection of this syndrome is essential in the prevention of immune-mediated thromboembolic sequelae. The 14C-serotonin release assay (SRA) has been used in reference laboratories to identify sera from patients on heparin therapy capable of inducing platelet dense granule release. In an attempt to improve existing methodologies, we employed luminographic detection of platelet-dense granule ATP release as an endpoint of HIT antibody-mediated platelet activation. Sera tested included 10 SRA confirmed positive and five SRA confirmed negative samples (to establish the assay), five samples from patients with thrombocytopenia not on heparin therapy and 34 patients suspected of HIT syndrome. All SRA confirmed positive sera (n = 19) were positive by the luminographic procedure. 24/26 SRA confirmed negative sera and five sera from thrombocytopenic patients not on heparin therapy were negative using luminography. Two of four sera yielding equivocal SRA results were found to be positive by the luminographic technique. The data suggest that the use of a lumiaggregometer in the coagulation laboratory to detect HIT antibody-induced platelet activation is a reliable alternative to the SRA. The luminographic procedure is both rapid and sensitive, and does not require the use of biohazardous radio-isotopes.

Adenosine Triphosphate↗
PubMed1993

Detection of antiphospholipid antibodies by flow cytometry: rapid detection of antibody isotype and phospholipid specificity.

Laboratory diagnosis of antiphospholipid antibodies is important in patients with clinical features of the antiphospholipid syndrome, such as thrombosis and fetal loss. We have developed a novel method for the detection of antiphospholipid antibodies using flow cytometry. Anionic phospholipids cardiolipin, phosphatidylserine and phosphatidylinositol are coated onto polystyrene beads of different sizes, allowing detection and semiquantitation of their respective phospholipid antibody isotypes. The results of the flow cytometric method closely correlate those of the standardised anticardiolipin enzyme-linked immunosorbent assay (ELISA), but the method is quicker and is versatile in its ability to detect IgG, IgM and IgA antibody isotypes at the same time. The method promises to be useful in evaluating the significance of phospholipid specificity and antibody isotypes in patients with the antiphospholipid syndrome.

Antibodies, Antiphospholipid↗
PubMed1985

A double-blind controlled pilot study of plasma exchange versus sham apheresis in chronic progressive multiple sclerosis.

Twenty patients with chronically progressive multiple sclerosis (MS) were randomised in a double-blind controlled study to assess the efficacy of plasma exchange therapy. All patients were immunosuppressed with prednisone and azathioprine and underwent either plasma exchange or sham apheresis. The 10 patients in each group were similar in age, sex, duration of disease and degree of disability. Clinical and laboratory responses were assessed immediately following the course of exchange or sham therapy, and 3 to 6 months later, by individuals blinded to the type of therapy administered. Although modest improvement was suggested on clinical examination in 7 of 10 patients exchanged and 3 of the 10 sham treated group, this was transient and was not accompanied by any change in disability status scores. No differences in abnormal laboratory investigations were demonstrable between the two patient groups following therapy. We conclude that plasma exchange therapy using this protocol is unlikely to be of clinical benefit as an adjunct in the management of chronically progressive M.S.

Adult↗
PubMed1985

Variant congenital dyserythropoietic anaemia with ringed sideroblasts.

A family is described with mild anaemia characterized by marked dyserythropoiesis and by prominent ringed sideroblasts. Inheritance is autosomal recessive. Other features include marked microcytosis, poikilocytosis, mild haemolysis, slightly increased haemoglobin A2, bone marrow erythroid hyperplasia and non-specific structural abnormalities of erythroid precursors on electron microscopy. This appears to be a previously unreported type of hereditary anaemia with both dyserythropoiesis and ringed sideroblasts. We propose the designation 'variant congenital dyserythropoietic anaemia with ringed sideroblasts'.

Adult↗