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Biomedical subjects

S Lopaciuk

Publications and source records attributed to S Lopaciuk.

At least 37 records · Page 2Linked to original sources
PubMed1994

Secretory response of the vessel wall to DDAVP and venous occlusion in von Willebrand's disease.

The aim of this study was to compare the secretory response of the vascular wall in vivo to DDAVP (i.v. 0.3 microgram/kg, 30 min) and to venous occlusion (VO, 20 min) in control healthy subjects, patients with von Willebrand's disease type I (vWd I) and patients with von Willebrand's disease type III (vWd III). In controls (n = 10) and vWd I (n = 12), DDAVP induced a 2 to 3-fold rise in plasma von Willebrand factor antigen (vWf: Ag), factor VIII coagulant activity (VIII: C) and tissue--type plasminogen activator antigen (t-PA:Ag). VO was less effective in increasing vWf: Ag and VIII:C but produced a greater rise in t-PA:Ag. Large increments (over 10-fold) were observed in plasmin-alpha 2-antiplasmin complexes following both stimuli. In vWd III (n = 10), DDAVP and VO failed to increase vWf:Ag, VIII:C and t-PA:Ag. No significant changes in plasmin-alpha 2-antiplasmin complexes were observed in this group. Moreover, the baseline t-PA:Ag values were significantly lower in vWd III (2.17 +/- 1.13 ng/ml) than in controls (4.84 +/- 1.97 ng/ml, p < 0.001). A significant increase in urokinase--type plasminogen activator antigen (u-PA:Ag) was found only in controls after VO. Neither controls nor patients with vWd showed any changes in plasma fibronectin levels following DDAVP. The low t-PA:Ag results and the abnormal fibrinolytic response to DDAVP and VO in patients with severe (type III) vWd indicate that their endothelial cell abnormality is more extensive than the defect in the synthesis or release of vWf.

Adult↗
PubMed1994

[Inherited thrombophilia].

The prevalence of inherited thrombophilia in the general population (1 in 2,500) is higher than that of hemophilia and related bleeding disorders. Well established causes of thrombophilia include deficiencies of natural coagulation inhibitors: antithrombin III, protein C and protein S. It is likely that other inherited disorders, such as deficiency of the second cofactor for activated protein C, deficiency of heparin cofactor II, hypo- and dysplasminogenemias, dysfibrinogenemias and homocysteinemia, may predispose to thrombosis. This review discusses clinical and laboratory aspects of these disorders and summarizes the management of individuals with inherited thrombophilia.

Anticoagulants↗
PubMed1993

[Thrombocytopenia associated with HIV infection].

Thrombocytopenia is a common complication of human immunodeficiency virus (HIV) infection. Its pathogenesis has not yet been established. An increased platelet destruction either due to the nonspecific deposition of circulating immune complexes on platelets or to the presence of specific antiplatelet antibodies as well as direct infection of megakaryocytes by HIV with a resulting decrease in platelet production have been reported as possible mechanisms. About 30-50% of patients with moderate thrombocytopenia may show spontaneous remission. Patients with either severe thrombocytopenia (platelet count < 20 x 10(9)/l) or bleeding are usually first treated with corticosteroids or azidothymidine. If improvement does not occur, further therapeutic approaches are the same as for chronic idiopathic thrombocytopenic purpura. HIV-associated thrombocytopenia has no prognostic significance with regard to AIDS risk.

HIV Infections↗
PubMed1992

Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial.

In a prospective multicenter trial, 149 consecutive patients with phlebographically proven proximal and/or distal deep vein thrombosis of the leg were randomly allocated to receive subcutaneously for 10 days either low molecular weight heparin CY 216 (Fraxiparine) in a fixed dose or unfractionated heparin (UFH) in doses adjusted according to the activated partial thromboplastin time. Pre- and post-treatment phlebograms were assessed blindly using the Arnesen's score system in 134 patients available for analysis of the treatment efficacy. The mean phlebographic score after 10 days of treatment was significantly decreased in both groups (p less than 0.001) in comparison with the baseline score but the difference in score changes between the two groups was not statistically significant. There was an improvement in 45/68 patients (66%) in the Fraxiparine group and in 32/66 patients (48%) in the UFH group, and an increase in the thrombus size in 10/68 (15%) and 12/66 (18%), respectively. One symptomatic non-fatal pulmonary embolism and one major bleeding episode were observed in the UFH group. During a follow-up period of 3 months, two rethromboses had occurred in the UFH group and none in the Fraxiparine group. It is concluded that subcutaneous fixed dose Fraxiparine is safe and at least as effective as subcutaneous adjusted UFH in the treatment of deep vein thrombosis.

Adult↗
PubMed1991

[Preliminary experience with achieving immune tolerance in patients with hemophilia A and circulating factor VIII inhibitor].

The appearance of antibodies to factor VIII is a serious complication in the treatment of haemophilia A. A protocol is presented aiming at suppression of the anticoagulant using continued treatment with factor VIII (25 u/kg b.w. twice weekly). Ten patients with previous maximal factor VIII antibody titre from 7 to 2900 Bethesda units were treated. So far the inhibitor was eradicated in 3 cases treated continuously for from 5 to 20 months. In two of these three cases successful surgical procedures were performed without anamnestic response.

Adolescent↗
PubMed1990

Venostasis but not DDAVP infusion provokes the plasma fibronectin increase.

Plasma fibronectin (pFN), von Willebrand factor antigen (vWf:Ag), factor VIII procoagulant activity, fibrinogen, euglobulin lysis time (ELT) and hematocrit were determined in healthy blood donors before and after venostasis as well as after intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP). Both venostasis and DDAVP provoked an increase in vWf:Ag and shortening in the ELT. In contrast, venostasis only but not DDAVP induced an increase in pFN levels which was statistically significant with and without correction for a concomitant hematocrit increment. The results indicate that there is a distinct difference in the patterns of venostasis and DDAVP mediated release of proteins from the vessel wall.

Adult↗
PubMed1990

Different effects of human neutrophil elastase on platelet glycoproteins IIb and IIIa of resting and stimulated platelets.

The effect of human neutrophil elastase (HNE) on the structure and receptor activity of platelet glycoprotein IIb/IIIa complex was studied. Resting platelets, which bound only traces of 125I-fibrinogen in the absence of ADP, were found to be barely susceptible to HNE. As shown by immunoblotting experiments, treatment of such platelets with HNE (14 micrograms/ml) did not provoke a detectable cleavage of GPIIb but resulted in a partial digestion of GPIIIa and appearance of 110 kDa fragment. Such proteolytic modification of the GPIIb/IIIa complex was accompanied by a slight increase in the binding of fibrinogen to blood platelets in the absence of ADP. Treatment of partially activated platelets (spontaneous activation during washing procedure) with HNE caused a progressive loss of GPIIb and degradation of GPIIIa to 110 kDa and 60 kDa fragments. These spontaneously stimulated platelets had initially a high number of fibrinogen binding sites exposed, corresponding to approximately 50% of receptor capacity observed in platelets activated by the optimal concentration of ADP. Digestion of GPIIb/IIIa by HNE of such platelets markedly increased the exposure of fibrinogen receptors. Thus, the stimulation of platelets increases significantly the susceptibility of the GPIIb/IIIa complex to proteolysis by HNE. However, such modification of the GPIIb/IIIa does not destroy its function as a receptor for fibrinogen either on the resting or activated platelets.

Blood Platelets↗
PubMed1990

Nebulized heparin and anabolic steroid in the prevention of postoperative deep vein thrombosis following elective abdominal surgery.

One hundred eighty three patients, all over 40 years old, who underwent major abdominal surgery, were randomized into 3 groups: Group I received a single dose of nebulized heparin (800 IU per kg b.w.) administered by inhalation one day prior to surgery. Group II besides the above, also received a single injection of 50 mg of long acting anabolic steroid (nandrolone phenylpropionate) intramuscularly. Group III received 5000 IU heparin subcutaneously on hr prior to surgery as well as every 12 h for the next 5 postoperative days. Postoperatively the patients were evaluated for deep vein thrombosis (DVT) using the 125-I-fibrinogen test. The occurrence of DVT was determined as: in Group I--16%, in Group II--7.9%, in Group III--7.8%. Haemorrhagic complications (clinically important) were observed in 7.8% of patients from Group III, but only in 1.7% of patients in Group I and 1.6% in Group II. For DVT prophylaxis following abdominal surgery a single application of nebulized heparin and long acting anabolic steroid is as effective as conventional low-dose subcutaneous heparin administration, but gives less haemorrhagic complications. This method is also more advantagenous in term of acceptance by the patients and represents considerable saving of nursing time.

Abdomen↗
PubMed1990

Cryoprecipitate of intermediate purity produced in a closed thaw-siphon system from DDAVP stimulated blood donor plasma.

The effects of intravenous administration of DDAVP to blood donors and the use of DDAVP plasma for the production of cryoprecipitate in the closed thaw-siphon system were evaluated. DDAVP treatment produced on the average a 3.2-fold rise in plasma levels of factor VIII. Von Willebrand factor antigen increased to a lesser extent. Cryoprecipitate prepared from 220-280 ml aliquots of DDAVP stimulated donor plasma contained 472 +/- 210 units of factor VIII and 276 +/- 130 units of von Willebrand factor antigen. The average yield of factor VIII was 57% of that in the prefrozen plasma. The specific activity of factor VIII in cryoprecipitate was 0.77 +/- 0.44 U/mg protein, comparable to that for intermediate purity concentrates. Thus, by the use of DDAVP and the thaw-siphon technique it is possible to produce cryoprecipitate 4-7 times as potent as conventionally manufactured preparations.

Blood Donors↗
PubMed1988

Monocytes of patients congenitally deficient in plasma factor XIII lack factor XIII subunit a antigen and transglutaminase activity.

Monocytes isolated from patients with severe deficiency in plasma Factor XIII of blood coagulation (FXIII) were tested for FXIII antigen and transglutaminase activity. By immunoperoxidase method the patients' monocytes, in contrast to normal controls, showed no reaction with a monospecific antibody against FXIII subunit a. This result was confirmed by immunoblotting technique, as well. In addition, tissue macrophages tested in one of the patients were also exempt of FXIII subunit a antigen. The transglutaminase activity in FXIII deficient monocytes was below the limit of the detection of the dansylcadaverine incorporation assay. The results suggest that FXIII subunit a of monocytes/macrophages and its plasma and platelet counterparts are closely related or identical proteins and demonstrate that the transglutaminase activity in monocytes is of FXIII origin and tissue transglutaminase is present, if at all, only in insignificant amount.

Antigens↗
PubMed1987

HIV antibody status and immunological abnormalities in Polish haemophiliacs.

Sera of 520 multitransfused haemophiliacs were examined for antibody to HIV; 447 patients had haemophilia A and 73 had haemophilia B. In 382 patients with haemophilia A and in 62 with haemophilia B solely Polish-made blood products were used for replacement therapy. The remaining haemophiliacs had also received imported clotting factor concentrates prior to the investigation. Only 8 patients (haemophilia A - 7, haemophilia B - 1) developed anti-HIV and all of them had been exposed to commercial concentrates. The analysis of T-cell subsets demonstrated an inverted T4/T8 ratio (less than 1.0) in 7 (30%) of the 23 haemophiliacs treated solely with domestic cryoprecipitate and in 3 (37%) of the 8 seropositive recipients of commercial concentrates. The most frequent alteration in both subgroups was a reduced ratio with either normal absolute numbers or an increase in T8 cells. Increased serum IgG levels were found in 82% of the users of cryoprecipitate and in 75% of the seropositive patients. Serum beta-2-microglobulin level was elevated in 69 and 62% of each subgroup, respectively. The observed immunological abnormalities, at least in the cryoprecipitate treated subgroup, may be causally related to factors other than HIV infection.

Adolescent↗
PubMed1985

Anticoagulant properties of extracellular slime substance produced by Staphylococcus epidermidis.

Slime produced by S. epidermidis strain KH 11 was extracted with phenol-saline. The saline phase was fractionated on a DEAE-Sepharose CL-6B column. The crude slime solution and its phenol-saline fraction were found to possess anticoagulant properties. They inhibited the coagulation of human plasma by thrombin, prolonged the activated partial thromboplastin time, but did not change the rate of plasma coagulation by reptilase. The anticoagulant effect of slime could be neutralized by rather high concentrations of protamine sulphate. In the presence of plasma, the staphylococcal slime also inhibited in a concentration dependent fashion the amidolytic activity of thrombin and factor Xa against synthetic chromogenic substrates. Both antithrombin III (AT III) and other plasma component(s), presumably heparin cofactor II, were required for the full expression of the slime effect. The anticoagulant action of slime was markedly less AT III dependent than that of heparin. The activity was resistant to heating (100 degrees C, 30 min). Slime and its fractions were stronger inhibitors of thrombin than of factor Xa. Fraction IV separated by DEAE-Sepharose chromatography and particularly rich in galactose and glucuronic acid had the highest inhibitory potency. It is conceivable that slime component(s) similar to glycosaminoglycans from other sources can carry the anticoagulant activity.

Anticoagulants↗
PubMed1985

Effect of proteolysis on quantitation of plasma fibronectin concentration by two immunoassays (electroimmunoassay and immunoturbidimetric technique).

Quantitation of fibronectin (FN) concentration is strongly influenced by FN fragmentation with trypsin, kallikrein and plasmin. Digestion by trypsin and kallikrein leads to a progressive decline in FN detectability by the immunoturbidimetric technique to zero values but is associated with an increase in the height of rockets in the Laurell's electroimmunoassay. Plasmin mediated FN fragmentation induces a strong overestimation of the FN content by the electroimmunoassay and, at very high enzyme concentrations, provokes an underestimation of FN by the immunoturbidimetric technique. The decline in FN reactivity in the immunoturbidimetric assay coincides with the disappearance of heavy fractions migrating only slightly faster than native FN in SDS-PAGE. The increase in the height of rockets in the electroimmunoassay is the highest when fractions of intermediate rate of migration prevail in the SDS-PAGE pattern. Concomitant use of these two immunoassays can distinguish native FN from its degraded form and may possibly provide a partial explanation for discrepancies in published studies on the concentration of circulating FN in various pathological states.

Antibodies↗
PubMed1985

Alterations of blood platelet function induced by neutral proteases from human leukocytes.

Washed human platelets are damaged by two neutral proteases from human leukocytes (elastase-like protease, ELP and chymotrypsin-like protease, CLP). The damage is manifested as inhibited aggregation by ristocetin and collagen, and enhanced aggregation by ADP in the presence of fibrinogen. Similarly to alpha-chymotrypsin (alpha-CT), CLP also increases binding of 125I-fibrinogen to platelets and renders platelets aggregable by human fibrinogen. ELP is less effective in this respect possibly due to damage to platelet receptors for fibrinogen. In the plasma medium platelets are not sensitive to leukocytic proteases added at concentrations that provoke some prolongation of the time of plasma clotting by thrombin.

Adenosine Diphosphate↗
PubMed1985

Plasma fibronectin concentrations in healthy and septic infants.

The concentration of plasma fibronectin was determined by Laurell's electroimmunoassay in 75 preterm or term newborns within the first 2 days of life, in 97 healthy infants aged from 3 days to 12 months, in 40 septic infants and in 38 healthy adult subjects. The mean fibronectin concentration in citrated plasma of normal adults was 318 +/- 84 ml/l. Healthy eutrophic term newborns 1-2 days old had approximately one-third of the fibronectin concentration of adults. There was no significant difference in the values between healthy term and eutrophic preterm newborns or between eutrophic and hypotrophic newborns. The plasma fibronectin increased strongly over the 1st month of life. No significant difference was observed between fibronectin levels in infant boys and girls. The values in septic newborns and septic older infants were significantly lower when compared with those of age-matched healthy controls. It is speculated that this deficiency, because of linkage to fibrin in disseminated intravascular coagulation or due to increased utilisation as a nonspecific opsonin and sequestration at sites of tissue injury, may contribute to organ failure in septicaemia.

Adult↗