Biomedical subjects

A Keréveur

Publications and source records attributed to A Keréveur.

5 recordsLinked to original sources

PubMed1999

Up-regulation of adhesion and MHC molecules on splenic monocyte/macrophages in adult haemophagocytic syndrome.

Haemophagocytic syndrome (HPS) has been associated with the abnormal activation of mono/macrophages and increased cytokine production. However, neither the phenotype of haemophagocytic monomacrophages nor the cellular origin of cytokine production have been described. We studied splenic monomacrophages and lymphocytes from five patients with HPS (two HIV- and three HIV+) and from controls without HPS (three normal HIV and two pathological HIV+). Using flow-cytometry, we observed a marked increase in the expression of MHC class I and II, M-CSF-receptor and adhesion molecules LFA-1, LFA-3, ICAM-1 (P<0.05) on HPS+ splenic monomacrophages compared to HPS-, which was independent of their HIV status. A high percentage of CD8+ lymphocytes from 4/5 HPS+ patients produced TNF alpha and IFNgamma, but no IL-6 upon in-vitro activation. In a fifth patient CD4+ but not CD8+ lymphocytes produced these cytokines. Although other cytokines might be involved in the pathophysiology of HPS as suggested by the high expression of M-CSF-receptor, these results suggest that TNF alpha and IFNgamma secretion by T cells might play a role in the up-regulation of adhesion and MHC molecules on monomacrophages from HPS.

Adolescent↗

PubMed1996

[Lipoprotein anomalies in HIV infections].

Alterations in lipid parameters occur during many acute infections. Different studies suggest that variations in lipid parameters can be used as markers of the progression of human immunodeficiency virus (HIV) infection. Hypocholesterolemia is observed in asymptomatic HIV+ subjects, then hypertriglyceridemia appears in patients with AIDS. Several hypotheses have been raised concerning the potential causes and consequences of these modifications. Cytokine effects on different enzymes of lipid metabolism, studied in vitro and in vivo, are thought to be partially responsible for the dyslipidemia. Hypertriglyceridemia could participate in cachexia and dementia could be facilitated by the changes in cholesterol metabolism. The use of the lipid parameters is proposed in HIV positive subjects, especially during anti-viral treatment.

Cholesterol↗

PubMed1995

[New antithrombotic agents].

The wide range of compounds currently being developed is the result of the continuing need for validated new antithrombotic agents. The prevention and treatment of venous thrombosis is predominated by anticoagulants: low molecular weight heparins, and potentially new antithrombin agents including hirudin. The effectiveness of new antiplatelet agents, and particularly c7E3 and integrelin, confirms the hypothesis concerning the role played by platelets in thrombogenesis in coronary arteries. But, due to the proaggregating effect of thrombin, anticoagulants could also have an important role in preventing arterial clots, either when given alone or in combination. Finally, the development of antithrombin and anti-platelet-glycoprotein IIb IIIa given orally is one of the major objectives of current research. Until the ideal antithrombotic agent is discovered, multiple-drug regimens combining anticoagulants and/or antiplatelet agents could be proposed in patients with a very high risk of thrombosis. Such regimens must taken into account the increased risk of bleeding and be adapted on the basis of careful laboratory surveillance.

Factor Xa Inhibitors↗

PubMed1995

[Hypersensitivity and resistance to antivitamins K].

During the initial phase or during treatment with oral anticoagulants, hypersensitivity or resistance may be observed, requiring significant changes in prescribed dosage. A thorough knowledge of the mode of action of vitamin K and its antagonists is useful to improve understanding of unexpected response to oral anticoagulant therapy. These abnormal responses may be due to poor compliance to treatment by the patient, insufficient or excessive vitamin K intake, interference with other drugs or abnormalities of the hepatic enzymes which are the target of oral anticoagulant drugs. The search for a cause is justified by the risks associated with these abnormal responses. It must be rigorously undertaken with an accurate interrogation, use of an anticoagulation monitoring leaflet and, if necessary, measurement of plasma concentrations and pharmacokinetics of the anticoagulant drug.

4-Hydroxycoumarins↗

PubMedDate not supplied

Vitamin K metabolism in a patient resistant to vitamin K antagonists.

We investigated various pharmacokinetic and pharmacodynamic parameters in a 63-year-old man, resistant to warfarin, fluindione, acenocoumarol and phenprocoumon. Daily doses of up to 30 mg of the long-acting phenprocoumon yielded a drug concentration of 85 mg/l (usual range 1-5 mg/l) but the international normalized ratio remained around 1. The plasma half-life of phenprocoumon was approximately 350 h (normal 120-150 h). Thus, the resistance was not due to malabsorption or to an accelerated metabolism of the drug. The level of vitamin K1 (1,202 ng/l) was insufficient to induce resistance. Decarboxyprothrombin concentrations were low, demonstrating that the gamma-carboxylation of the precursors of the vitamin K-dependent coagulation factors was not effectively reduced. The concentration of vitamin K epoxide, normally increased under oral anticoagulation, correlated to the vitamin K concentration (r2 = 0.77) but the quotient epoxide/vitamin K remained 4-fold lower than that of 22 warfarin-sensitive patients, suggesting an absence of blockade of the vitamin K reductase by phenprocoumon. This resistance to all the molecular forms of the vitamin K antagonists is most likely due to a reduced affinity of the drugs to a mutant vitamin K reductase.

Drug Resistance↗