Search PubMed⌕ Search

Biomedical subjects

M E Rick

Publications and source records attributed to M E Rick.

At least 37 records · Page 2Linked to original sources
PubMed1995

Acquired von Willebrand's disease: a rare manifestation of postpartum thyroiditis.

This report describes the diagnosis of acquired type I von Willebrand disease in a 30-year-old woman (G5P5) who presented with complaints of excessive bleeding in the postpartum period. The patient's additional complaints of fatigue, depression, and inability to lose weight resulted in laboratory testing that indicated hypothyroidism due to thyroiditis. Clinical symptoms and laboratory tests for von Willebrand disease and hypothyroidism normalized with L-thyroxine replacement. Thyroiditis resulting in symptomatic hypothyroidism occurs in 2-4 per cent of postpartum women. The possibility of underlying hypothyroidism should be considered for those patients, especially if they are parous women, who appear to have an acquired bleeding disorder suggestive of von Willebrand disease.

Adolescent↗
PubMed1994

Diagnosis and management of von Willebrand's syndrome.

von Willebrand's disease is the most common of the inherited bleeding disorders. It is caused by quantitative and/or qualitative abnormalities of von Willebrand factor, and it usually presents with bleeding from mucosal surfaces. The diagnosis is confirmed by measuring von Willebrand factor activity and antigen levels, factor VIII activity, and performing a multimer analysis of von Willebrand factor. Treatment may require plasma-derived concentrates, but can often be accomplished with DDAVP, a vasopressin analogue that causes transient release of von Willebrand factor from body storage sites.

Deamino Arginine Vasopressin↗
PubMed1994

Laboratory diagnosis of von Willebrand's disease.

The diagnosis of von Willebrand's disease is becoming complex as more is understood about the disease. Clinical information and laboratory data are necessary for the diagnosis because of the overlap of normal and abnormal laboratory values. A complete evaluation including von Willebrand factor multimers, ristocetin-induced platelet aggregation, factor VIII activity level, and a template bleeding time is necessary to correctly classify the patient so that optimal treatment may be given.

Clinical Laboratory Techniques↗
PubMed1990

Factor IXa and von Willebrand factor modify the inactivation of factor VIII by activated protein C.

Activated protein C inactivates factor VIII by proteolytic cleavage of the heavy chain of factor VIII. Protein S and calcium ions are cofactors in this reaction. We have examined the effects of several potential modulators of this reaction, including phospholipids, von Willebrand factor, and factor IXa, all of which bind factor VIII. Our results indicate that neither resting nor stimulated platelets nor phospholipid vesicles protect factor VIII from inactivation by activated protein C in either the presence or the absence of protein S. However, the addition of von Willebrand factor decreases the inactivation of factor VIII by activated protein C by 20% to 30%, and factor IXa, which is known to protect factor VIII from inactivation by activated protein C, confers additional protection with von Willebrand factor. The active site of factor IXa is necessary for the protective effect, because native factor IX and active site-inhibited factor IXa do not protect factor VIII from inactivation. Thus there is an additive protective effect when von Willebrand factor and factor IXa are present with factor VIII, leading to a decrease in the inactivation by activated protein C. These factors may be particularly important in stabilizing factor VIII in the circulation and during the early stages of coagulation.

Amino Acid Chloromethyl Ketones↗
PubMed1989

Characterization of a monoclonal antibody, OVB1, which binds to a unique determinant in human ovarian carcinomas and myeloid cells.

A monoclonal antibody, OVB1, was generated against a human ovarian carcinoma cell line, OVCAR-3. The antigen reacting with this antibody was strongly expressed on the external surface of the plasma membrane of OVCAR-3 cells and cells of 4/4 other ovarian carcinoma lines. Variable density and homogeneity of expression was found on cells from 5/5 breast carcinoma lines. Various ovarian tumor specimens and normal human tissues were frozen, cryostat-sectioned, and examined for OVB1 reactivity using immunoperoxidase methods. A strong, uniform, homogeneous reaction on 10/10 ovarian carcinoma specimens and variable, non-homogeneous reactions on breast tumors were seen. Normal tissues reacting with the antibody include thyroid, pituitary pars intermedia, breast ductal epithelium, Auerbach's plexus and neuronal processes in the GI tract, colonic mucosal epithelium, and salivary gland ductal epithelium. Polymorphonuclear leukocytes, eosinophils, and approximately 13% of peripheral lymphocytes, as well as cells around germinal centers in lymph nodes and spleen, showed strong reactivity by immunofluorescence and/or immunoperoxidase. Expression of the OVB1 antigen in the myeloid cells of normal human bone marrow occurred from the promyelocyte stage through to more mature cells in a subpopulation of myeloblasts. Indirect immunofluorescence of live peripheral blood cells showed localization to the surface of PMNs, eosinophils, and certain lymphocytes. Double-immunofluorescence studies (with a direct fluorescein-anti-lactoferrin antibody conjugate) showed co-localization of OVB1 and OKM1 (anti-C3bi receptor) antibodies to specific granules of PMNs. Localization of OVB1 and OKM1 antibodies to granular structures in the PMN was confirmed by electron microscopy using the ferritin bridge technique. The antigen reacting with the OVB1 antibody was shown to be neuraminidase sensitive, but protease insensitive. The OVB1 monoclonal antibody may be useful in identification of ovarian tumors and subclassification of myeloid leukemias.

Antibodies, Monoclonal↗
PubMed1989

Bleeding disorders in pregnant patients with rheumatic diseases.

Although the bleeding disorders that occur in patients with rheumatic diseases are not different during pregnancy than at other times, their diagnosis and management are often different during pregnancy. In idiopathic thrombocytopenic purpura, for instance, antiplatelet antibodies may cross the placenta and cause life-threatening thrombocytopenia in the fetus while the mother is asymptomatic. Management of this disease has changed significantly in the past 5 years with the use of intravenous gammaglobulin which appears to lessen the degree of fetal as well as maternal thrombocytopenia when administered during the peripartum period. The utilization of plasmapheresis and plasma infusions for patients with thrombotic thrombocytopenic purpura has salvaged both the mother and the fetus in a disease which was fatal in more than 60 per cent of patients prior to their use. The outcome of pregnancy in this patient population has markedly improved with this treatment. The stimulus for the production of factor VIII inhibitors in the postpartum period is still not understood, but guidelines for management have changed, with the increased likelihood of decreasing the antibody and inducing tolerance with regimens including factor VIII, immunosuppressive agents and intravenous gammaglobulin in those patients who require treatment. The diagnosis of von Willebrand's disease during pregnancy is difficult because of the physiologic increase in von Willebrand factor during pregnancy; in this instance family studies may help in the diagnosis of this relatively common, autosomal dominant inherited disorder. Management now includes treatment with desmopressin as well as cryoprecipitate replacement therapy.

Female↗
PubMed1989

Subendothelial matrix of cultured endothelial cells contains fully processed high molecular weight von Willebrand factor.

Von Willebrand factor (vWf) is an adhesive glycoprotein composed of identical subunits linked by disulfide bonds to form multimers of varying sizes. VWf is found in platelets and plasma, where it functions in the adhesion of platelets to exposed subendothelium. Subendothelial matrix contains vWf, but the multimeric composition of matrix vWf, its binding site in matrix, and the mechanism by which it is delivered to matrix are unknown. Using human umbilical vein endothelial cell (HUVE) cultures, we have partially characterized subendothelial matrix vWf. Matrix from HUVE was solubilized in sodium dodecyl sulfate and electrophoresed on 1.25% agarose gels. The extracted vWf was composed of extremely high molecular weight (HMW) multimers of vWf not normally found in plasma. The vWf content of HUVE supernatant, extract, and matrix was quantitated and characterized by radioimmunoassay, agarose gel electrophoresis, and densitometry. The matrix-bound or -associated vWf represented 4% to 18% of total HUVE vWf. Western blot analysis of matrix vWf after reduction showed a subunit species of 220 kd. Long-term incubation of HUVE with phorbol 12-myristate 13-acetate (PMA), a compound that causes release of HMW vWf from Weibel-Palade bodies in HUVE, resulted in a marked decrease in matrix vWf (0.2% to 1% of the total vWf). The multimeric pattern of the remaining matrix vWf continued to show predominantly HMW multimers.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1988

Plasma fibrinopeptide A, beta-thromboglobulin, and platelet factor 4 in diabetic retinopathy.

We examined plasma levels of fibrinopeptide A, beta-thromboglobulin, and platelet factor 4 in diabetic patients. Among diabetic patients (n = 33) plasma levels of fibrinopeptide A, beta-thromboglobulin and platelet factor 4 were significantly higher than in controls (n = 41). In the subgroups of diabetic patients with (1) minimal (n = 13), and (2) moderate-severe (n = 14) retinopathy only plasma fibrinopeptide A levels were significantly higher than in controls. Among the total group of diabetic patients plasma levels of fibrinopeptide A increased significantly with increasing severity of retinopathy. These results suggest that diabetic retinopathy is associated with in vivo activation of blood coagulation factors and that this activation increases with advancing retinopathy.

Blood Platelets↗
PubMed1988

Phospholipase abolishes the effect of stimulated platelets on the thrombin activation of factor VIII.

Factor VIII functions as a cofactor in the intrinsic coagulation pathway and must first be activated to function optimally in this capacity. Low concentrations of thrombin activate factor VIII, and the presence of stimulated platelets is known to enhance the activation of factor VIII complexed to von Willebrand factor. The current studies show that platelets stimulated by thrombin, collagen, or calcium ionophore will increase the activation of isolated factor VIII by thrombin. Ongoing platelet release is not necessary for the enhanced factor VIII activation, nor is platelet von Willebrand factor or platelet membrane glycoproteins Ib or IIb/IIIa. Platelet membrane phospholipids, on the other hand, are important for the enhanced activation of factor VIII by thrombin because the effect of stimulated platelets is abolished by incubation of the stimulated platelets with phospholipases. These results suggest that the enhanced activation of factor VIII by thrombin in the presence of stimulated platelets may be mediated by factor VIII binding to platelet phospholipid or to a receptor whose functional integrity is dependent on surrounding membrane phospholipid.

Blood Platelets↗
PubMed1987

Interleukin 1 or endotoxin increases the release of von Willebrand factor from human endothelial cells.

von Willebrand factor (vWF), a large adhesive glycoprotein, is synthesized by vascular endothelial cells (EC). Plasma levels of vWF manifest a broad normal range, and are elevated during sepsis and in inflammatory states. Since the inflammatory mediator, interleukin 1 (IL1) and bacterial endotoxin (LPS) both initiate procoagulant changes in vascular endothelium, we investigated the effect of these substances on endothelial cell release and residual endothelial cell content of vWF-antigen (vWFAg). Cultured human EC exposed to either IL1 or LPS released greater amounts of vWFAg compared to control EC. The augmented release could be detected within 1-2 h after exposure to IL1 or LPS and was not inhibited by cycloheximide, suggesting that de novo protein synthesis was not required for release to occur. Residual cellular vWFAg was reciprocally lower in IL1- or LPS-treated EC at 24 and 48 h, indicating that compensatory increase in synthesis of vWFAg did not occur during this time interval. Released vWF contained the higher molecular weight multimers observed in normal endothelial cells, and it possessed ristocetin cofactor activity. We propose that release of functional vWF from EC exposed to inflammatory mediators may be at a mechanism for localization of platelets and enhanced thrombogenicity at inflammatory foci.

Cells, Cultured↗
PubMed1987

Thrombocytopenia associated with pregnancy in a patient with type IIB von Willebrand's disease.

Thrombocytopenia may accompany variant (type IIB) von Willebrand's disease (vWD) and is thought to result from binding of the abnormal von Willebrand factor (vWF) to the patient's platelets with subsequent platelet aggregate formation and clearance. We have studied a patient with type IIB vWD who became thrombocytopenic during two pregnancies. During the third trimester of pregnancy, her platelet counts dropped to 20,000 to 30,000/microL, and an increase in the intermediate-sized vWF multimers was seen on agarose gel electrophoresis. During this time her platelet-rich plasma showed spontaneous platelet aggregation, and her plasma caused spontaneous aggregation of normal washed platelets. Antibody to platelet glycoprotein Ib completely blocked the spontaneous platelet aggregation, while antibody to platelet glycoprotein IIb/IIIa did not block the response at the concentrations used. Inhibitors of platelet function that elevate platelet cyclic AMP also blocked the response, but aspirin had no effect on the spontaneous platelet aggregation. The patient illustrates that the platelet counts in one individual can vary greatly in type IIB vWD and that the thrombocytopenia that occurs can appear under physiologic conditions that stimulate the endogenous production of the patient's abnormal vWF. The mechanisms leading to spontaneous platelet aggregation and thrombocytopenia appear to be similar to those described for other patients with type IIB vWD.

Adult↗
PubMed1986

Retinal cotton-wool spots: an early finding in diabetic retinopathy?

Five insulin dependent diabetic patients are reported on who had a few small retinal cotton-wool spots or 'soft exudates' either totally isolated or associated with fewer than 10 microaneurysms. These observations suggest that cotton-wool spots may be an early finding in diabetic retinopathy. Significant biological abnormalities in these patients were high levels of glycosylated haemoglobin and mild increases in thrombin generation, indicating slight activation of the coagulation system. The possible significance of these clinical and biological findings is discussed.

Adult↗
PubMed1986

Platelets modulate the proteolysis of factor VIII:C protein by plasmin.

Factor VIII coagulant protein (VIII:C) functions as a critical cofactor with factor IXa, calcium ions, and phospholipid during the activation of factor X. In the course of this reaction, the activity of VIII:C is first increased and then is destroyed by one or more serine proteases that are part of the coagulation sequence. In this study, we have investigated the influence of platelets on the inactivation of VIII:C by plasmin. Platelets were separated from plasma proteins in the presence of granule release inhibitors and were incubated with plasmin and isolated VIII:C or the complex of purified VIII:C/von Willebrand factor (vWF); VIII:C activity and antigen levels were assessed over time. In the presence of platelets, the isolated VIII:C showed an initial increase in VIII:C activity that was not present when platelets were absent, and the VIII:C/vWF showed an increase in VIII:C activity over that seen when platelets were absent. In addition, platelets stabilized VIII:C activity over a one-hour time course when compared with buffer. The VIII:C antigen did not increase and decreased slowly whether platelets were present or absent. Preincubating the platelets with ristocetin, collagen, or plasmin did not alter the results, and experiments using platelets from a patient with severe von Willebrand's disease also showed a pattern similar to that seen with normal platelets. Experiments using fixed platelets or phospholipid vesicles showed that they did not support the activation reaction or delay the inactivation reaction. These studies demonstrate that platelets modulate the activation and inactivation of VIII:C by plasmin, apparently by a mechanism that is independent of the platelet release reaction.

Blood Platelets↗
PubMed1986

DDAVP in type IIa von Willebrand's disease.

1-D-Amino(8-D-arginine)-vasopressin (DDAVP) infusion in three patients with type IIa von Willebrand's disease (vWD) resulted in a normalization of the factor VIII coagulant, factor VIII-related antigen, and von Willebrand factor (vWF) (ristocetin cofactor) activities and the bleeding time. The normalization of these hemostatic parameters persisted for four hours. Over the same time period there was a marked increase in the quantity of the vWF multimers when blood was collected in the presence of protease inhibitors. The vWF multimers present were even larger than the normal. When blood was collected in the absence of protease inhibitors, a smaller increase in the plasma vWF multimers was observed and fewer of the intermediate and larger vWF multimers were seen; multimers larger than those present in normal plasma were not visualized. The platelet vWF multimers and activities did not change with or without inhibitors. These studies suggest that there is a subgroup of patients with type IIa vWD who respond to DDAVP with complete normalization of their hemostatic abnormalities and whose vWF is sensitive to proteolysis.

Antigens↗
PubMed1986

DDAVP infusion in five patients with type Ia glycogen storage disease and associated correction of prolonged bleeding times.

Five patients with glycogen storage disease type I (GSD-I) were evaluated for a bleeding diathesis and subsequently were given an infusion of 1-deamino-8-D-arginine vasopressin (DDAVP). Although platelet counts were normal or slightly elevated, the baseline template bleeding times were prolonged in four of the patients. Prothrombin times and activated partial thromboplastin times were normal, while ADP- and epinephrine-induced platelet aggregations were absent in the three patients tested. Ristocetin- and collagen-induced platelet aggregations were abnormal. Laurell and immunoradiometric determinations of the factor VIII-related antigen (vWf antigen) were decreased. Glyoxyl agarose gel electrophoresis of the patients' plasma revealed abnormal multimer patterns in four of the five patients. After the DDAVP infusion the platelet aggregation abnormalities persisted; however, the bleeding time and the von Willebrand antigen and activity corrected. We conclude that GSD-Ia patients may have a metabolically acquired form of von Willebrand's syndrome as well as an acquired intrinsic platelet defect, and that DDAVP may be useful in the management of bleeding in these patients.

Adult↗
PubMed1986

Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand's disease.

We studied 17 patients with moderate to mild type I von Willebrand's disease (vWd) and correlated the bleeding time with the plasma von Willebrand factor antigen (vWf Ag), the plasma vWf activity (ristocetin cofactor), the platelet vWf Ag, and the platelet vWf activity. We found an excellent correlation between the bleeding time and the platelet vWf activity and, to a lesser extent, between the bleeding time and the platelet vWf Ag. The length of the bleeding time was inversely proportional to the level of the platelet vWf (P less than .001) or, to a lesser extent, the platelet vWf Ag (P less than .05). The plasma vWf Ag and activity did not correlate significantly with the bleeding time. These studies indicate that the platelet vWf is one of the important bleeding time factors in type I vWd and that the platelet vWf plays an important role in the early steps of hemostasis.

Bleeding Time↗