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Biomedical subjects

B Polack

Publications and source records attributed to B Polack.

At least 73 records · Page 4Linked to original sources

[The use of enoxaparine for anticoagulation in extracorporeal circulation in hemodialysis at high risk for hemorrhage].

After evaluation of efficacy of a low molecular weight heparin (LMWH), enoxaparine (Lovenox), in patients on continuous hemodialysis without a particular known hemorrhagic risk, this same LMWH was administered during 493 dialysis sessions to 46 patients presenting various degrees of risk of hemorrhage. Lower doses of 0.5 mg/kg or 0.75 mg/kg as bolus injections were administered at the start of the 4 or 5 hourly session. Clotting in the extracorporeal circulation (ECC) was noted in 0.6% treatments, the product being effective in all other sessions. Only one case of bleeding can be imputed to the LMWH injected during hemodialysis (0.2% of sessions). Although an open trial, the superiority of enoxaparine both for antithrombotic activity in ECC, and its simple management, as well as the small number of hemorrhages noted, has led to the routine use of this method in all patients at hemorrhagic risk.

Adult↗

[Biological activity of enoxaprine (PK 10169) in hemodialysis. A dose study].

Anti-Xa and anti-IIa activity were evaluated in 42 patients with chronic renal insufficiency, in an open randomized trial, to determine optimal dose of PK 10169 for prevention of coagulation in extracorporeal circuit during hemodialysis sessions. PK 10169 was given as single doses of 0.75, 1 and 1.25 mg/kg at start of dialysis, into the arterial line. All dialysis sessions were continued over the 4 hours provided for without the need for further injections. A linear relation existed between anti-Xa and anti-IIa activity measured at end of dialysis and the dose injected (p less than 0.001). Efficacy and tolerance were assessed clinically and biologically and were rated excellent at the 3 dose levels, the best tolerance/efficacy ratio being at the 1 mg/kg dosage.

Adult↗

Protein C level at birth.

The protein C level was determined, on cord blood, for 30 healthy newborns by electro-immuno assay using a monospecific antiserum. For the newborns the mean level of protein C related antigen is about one third of normal adults' mean level. There is a good correlation between Protein C related antigen and prothrombin related antigen. The low level of these vitamin-K-dependent proteins is probably a consequence of partial liver immaturity at birth. Using two-dimensional immuno-electrophoresis we were unable to detect subcarboxylated forms of protein C. However these abnormal forms could be seen in vitamin-K deficiencies of neonates.

Administration, Oral↗

Molecular characterization of an abnormal fibrinogen by two-dimensional electrophoresis.

We examined normal and abnormal fibrinogen (fibrinogen "Grenoble") by two-dimensional gel electrophoresis to obtain data on possible defects at the molecular level. Fibrinogen Grenoble is characterized by an abnormal rate of fibrin monomer aggregation. The electrophoretic analysis revealed the presence of abnormal gamma chains. Two kinds of gamma chains can be detected in fibrinogen Grenoble: (a) normal gamma chains and (b) gamma chains Grenoble (gamma G) with a greater molecular mass but no modification in isoelectric point. The latter chain can be detected in whole plasma by two-dimensional gel electrophoresis. Metrological analysis was performed in an attempt to quantify observed differences between normal fibrinogen and fibrinogen Grenoble. On use of gels stained either with Coomassie Brilliant Blue or with silver, the partly qualified evaluation gives about 60% normal gamma chain and 40% gamma chain Grenoble.

Blood Coagulation Disorders↗

[Enoxaparin in the prevention of thrombosis of extracorporeal circulation during dialysis of patients with chronic renal failure].

Chronic renal failure patients under haemodialysis are exposed to two dangers: haemorrhage and clotting of the extracorporeal circulation circuit. This problem can be solved by using low molecular weight heparins. Two studies were conducted to evaluate the effectiveness and safety of a low molecular weight heparin: enoxaparin. The first study, which involved 42 chronic renal failure patients under haemodialysis without any particular risk, enabled the optimum dosage (1 mg/kg bodyweight) to be determined. The second study, which concerned 46 patients at high risk of haemorrhage who received enoxaparin 0.5 mg/kg or 0.75 mg/kg depending on the vascular approach, confirmed that enoxaparin was highly effective (clotting of the extracorporeal circuit in only 0.6 p. 100 of the cases) and well tolerated (bleeding in only 0.2 p. 100 of the cases).

Adult↗

Cultivation of rabbit Pneumocystis carinii on cells derived from rabbit (Oryctolagus cuniculus).

Cultivation of Pneumocystis carinii from rabbit onto cell monolayers was intended. Three cell types were used: rat lung derived cell line L2 and canine kidney derived cell line MDCK, and primary epithelial rabbit lung cells derived from 20 days old foetuses. These primary cells were also immortalized by transfection of the coding sequences for the large and small T antigens of the SV40 virus. P. carinii were extracted from lungs of corticoid treated young rabbits and were purified on Ficoll. In vitro development of P. carinii was assessed by counting the number of attached parasites on cells after staining. No development was observed on L2 nd MDCK cell lines. On the contrary, a development was observed on rabbit derived cells with a threefold increase of attached parasites on the third day of culture. Immortalized cells allowed also multiplication of attached P. carinii. These results are similar to those obtained with culture of rodent P. carinii onto cell monolayers.

Animals↗

Role of oxygen radicals in tissue factor induction by endotoxin in blood monocytes.

In response to bacterial endotoxin (lipopolysaccharide, LPS) monocytes synthesize and express on their surface tissue factor (TF) which triggers the blood coagulation cascade. Since LPS stimulates active oxygen species production by these cells, we investigated the roles of superoxide anion and nitric oxide in the induction of TF in human blood monocytes. Scavengers of reactive oxygen intermediates such as N-acetyl cysteine or pyrrolidine dithiocarbamate were able to block TF induction. In addition, inhibition of NADPH oxidase and/or NO synthase which are major sources of active oxygen species in phagocytes also blocked TF induction. The restoration of TF expression, in monocytes treated with inhibitors of reactive oxygen production, by N,N'-dimethyl-gamma, gamma'-dipyridylium dichloride and/or sodium nitrosylpentacyanoferrate (III), which generate respectively O2- and NO, suggests that these two radicals participate in the induction of TF at the surface of blood monocytes stimulated by LPS.

Drug Synergism↗

Protective role of platelets in chronic (Balb/C) and acute (CBA/J) Plasmodium berghei murine malaria.

The role of blood platelets in the pathogenesis of malaria remains unclear. In this study we investigated the role of experimentally caused thrombocytopaenia in chronic (Balb/C) and acute (CBA/J) Plasmodium-berghei-induced murine malaria. A group of 30 Balb/C mice were rendered thrombocytopaenic by injection of anti-mouse platelet serum given every 2 days from day 2 to day 8 after malaria infection. Compared with the control group, thrombocytopaenic mice showed a greater mortality. The Kaplan-Meier estimate of the risk of death was 4.37-fold higher in the thrombocytopaenic group. Parasitaemia and weight loss was in agreement with the protective effect of platelets. In the acute malaria model, the survival rate was less significant but the estimated risk of death was 1.7-fold higher in the treated group. These results suggesting a protective role of platelets in murine malaria are not in line with previous reports of the literature. Taken together our data suggest, however, that platelets, similarly to some inflammatory cytokines like TNF, play a dual role in the pathogenesis of malaria. Depending on experimental conditions, e.g. the time of onset of thrombocytopaenia, the beneficial role of platelets may outweigh the deleterious one.

Acute Disease↗

Animal pneumocystosis: a model for man.

Pneumocystis carinii is an important pulmonary pathogen responsible for morbidity and mortality in patients with AIDS. Apart from AIDS, cases of pneumocystosis have been reported in patients receiving immunosuppressive therapy associated with organ transplantation without chemoprophylaxis and in malignant blood diseases. In vitro models are only of limited interest because there is no continuous in vitro culture. The in vivo models have contributed a great deal to the understanding of human Pneumocystis carinii pneumonia. Indeed, animal models remain of prime interest for many purposes, principally comparative medicine, pathogenesis, epidemiology and immunology. Among animal models, the rabbit is a very susceptible host to P. carinii infection, and does not need glucocorticoid treatment. Moreover, antigenic and genomic data suggest that rabbit-derived Pneumocystis strains are more closely related to human Pneumocystis than those of mice or rats. We have therefore shown that the rabbit model permits the study of the pulmonary surfactant modification due to P. carinii infection. This model should be a very interesting model for pathogenesis or immune response studies in immunocompetent animals. The rabbit model could also be used for epidemiological studies. P. carinii transmission appears to be very rapid via contact of Pneumocystis-free rabbits with infected rabbits. These Pneumocystis-free animals could be helpful for characterizing the source and the reservoir and studying parasite transmission.

AIDS-Related Opportunistic Infections↗