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Biomedical subjects

M Zuzel

Publications and source records attributed to M Zuzel.

44 records · Page 3Linked to original sources

In vivo interactions of autoantibodies to factor VIII with the factor VIII complex.

Two non-haemophilic elderly patients who had developed autoantibodies to factor VIII were studied over a period of 9 months to 5 years. Sequential measurements of antibody to factor VIII (anti-VII:C), factor VIII coagulant activity (VIII:C), factor VIII coagulant antigen (VIII:CAg), factor VIII-related antigen (VIIIR:Ag), and factor VIII ristocetin cofactor (VIII:WF) were performed. Before treatment, low VIII:C, normal or increased VIII:CAg and high VIIIR:Ag levels were found and were indicative of the presence of circulating immune complexes. Immunosuppressive therapy induced progressive correction of VIII:C and VIIIR:Ag values. High levels of VIII:CAg subsided in the patient who relapsed. It is suggested that antibodies to factor VIII bind and remove VIII:C from the circulation thereby inducing an increased synthesis of VIII:CAg which may be associated with an augmented release or production of VIIIR:Ag.

Aged↗

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↗

Platelet function in hairy-cell leukaemia.

A quantitative study of various aspects of platelet function was carried out in eight patients with typical hairy-cell leukaemia (HCL). In at least two patients platelet aggregation was convincingly reduced to more than one aggregating agent (ADP, adrenaline, collagen, thrombin, and ristocetin). Granular storage capacity for {(14)C} 5-HT was reduced in five of the six patients tested. The two patients with definitely abnormal aggregation had the greatest reduction in granular storage pool and the longest bleeding times of those tested but, like the other patients, they did not have a clinical haemostatic defect. It was concluded that a granular storage pool defect (SPD) was at least partly responsible for aggregation abnormalities in HCL since the platelet release reaction in response to thrombin appeared to be normal. All our patients ran a chronic course uncomplicated by any of the factors known to predispose to a platelet SPD acquired in the circulation. Although in the one patient tested before and after splenectomy there was some improvement in platelet aggregation after operation, there was no clear general relationship between defective platelet function and either previous splenectomy or platelet count. Since a direct involvement of the megakaryocytic series in the underlying cell proliferation of HCL seems unlikely, it is concluded that the platelet defect can most reasonably be attributed to the production of abnormal platelets as a result of marrow fibrosis and/or infiltration by hairy cells.

Bleeding Time↗

Heparin-like activity in uterine fluid.

Uterine fluid was collected from a group of normal patients and a group of patients with menorrhagia. Heparin-like activity was detected in 34 out of 38 samples using an anti-Xa heparin assay. The heparin-like activity in uterine fluid was inhibited by adding the heparin antagonist hexadimethrine bromide to the assay. Concentrations of fibrinogen-fibrin degradation products (FDPs) were measured in five samples of uterine fluid. FDPs in the concentration detected had no effect on the anti-Xa assay. Heparin-like activity was higher in the group with menorrhagia, although the differences were not significant. Heparin-like activity increased throughout the menstrual cycle and decreased during menstruation, suggesting a possible cyclical variation in activity. There was no correlation between mast cell numbers in the endometrium and myometrium and heparin-like activity in uterine fluid and no correlation between the numbers and the stage in the menstrual cycle. In a few patients with intrauterine contraceptive devices (IUCDs) heparin-like activity was increased.

Body Fluids↗

Changes in the concentration of leucocytes and platelets in the peripheral blood during sterile inflammation in rabbits.

Glycogen in isotonic saline was infused into the peritoneal cavities of rabbits to produce sterile inflammation. This caused a small increase in the haematocrit value and larger decreases in the concentrations of circulation leucocytes and platelets. Circulating granulocytes decreased by about 40% in 2 h and increased in the next 2 h to about 4 times their initial concentration. Acetyl salicyclic acid (ASA) (10 mg/kg) infused with the glycogen did not affect the decrease significantly but accelerated the subsequent increase. Circulating mononuclear leucocytes, mostly lymphocytes, decreased progressively by about 75% after 4-5 h. This decrease was not affected by ASA. Circulating platelets decreased by about 30% in the first hour; this decrease was accelerated and augmented by ASA. Subsequently the platelet concentrations remained constant for at least 4-5 h. Glycogen so infused is known to activate complement, and ASA to inhibit prostaglandin synthetase. Therefore the results suggest that (i) the initial decrease in circulating granulocytes is mediated by activated complement; (ii) the emigration of granulocytes from blood into the inflammatory exudate is increased by prostaglandins; (iii) the initial decrease in circulating platelets is mediated by activated complement and antagonized by prostaglandins; and (iv) the decrease in circulating lymphocytes is mediated by activated complement and uninfluenced by prostaglandins.

Animals↗