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Hôpital-Camfrout, France

Manceau S.,University of Paris Descartes | Giraud C.,University of Paris Descartes | Decleves X.,University of Paris Descartes | Batteux F.,University of Paris Descartes | And 8 more authors.
International Journal of Pharmaceutics | Year: 2010

The efficacy of drugs acting within lymphocytes depends on their intracellular concentrations, which could be modulated by membrane efflux transporters including P-glycoprotein (P-gp), encoded by the MDR1 gene. In particular, P-gp induction may compromise the efficacy of its substrates. Rifampicin and phenobarbital have been shown to induce P-gp in hepatic and intestinal cells through the activation of the nuclear receptors PXR and CAR. However, controversial data exist in human lymphocytes. We investigated the effect of these drugs on P-gp activity and expression in lymphocytes in vitro and ex vivo. CCRF-CEM cells and peripheral blood mononuclear cells (PBMCs) from healthy volunteers were incubated in the presence of rifampicin, phenobarbital, or without any drug. P-gp activity was measured by flow cytometry using DiOC6 efflux. MDR1, PXR and CAR mRNA expression were measured by quantitative RT-PCR. Neither P-gp activity nor MDR1 mRNA expression were modified by rifampicin or phenobarbital both in CCRF-CEM cells and PBMCs. Moreover, P-gp protein expression at the membrane was neither detectable nor induced. The very weak PXR and CAR mRNA expression levels in these cells could partly explain these results. Therefore, P-gp induction by rifampicin and phenobarbital may play a negligible role in drug interactions occurring within lymphocytes. © 2010 Elsevier B.V.

Ngo S.,CHU Rouen | Benhamou Y.,CHU Rouen | Armengol G.,CHU Rouen | Sauvetre G.,CHU Rouen | And 4 more authors.
Revue de Medecine Interne | Year: 2016

Introduction: While in most countries warfarin is the preferred anti-vitamin K, fluindione, a molecule with a prolonged half-life remains largely prescribed in France. Some of its side effects, including immuno-allergic complications, remain poorly understood. Case report: A 77-year-old woman presented with a febrile severe neutropenia of immunoallergic mechanism with a favourable outcome associated with fluindione, introduced 25 days earlier for the treatment of atrial fibrillation. Conclusion: This rare side effect is a reminder of the importance of biological monitoring in the first weeks following the introduction of fluindione and key diagnostic elements and therapeutic aspects of iatrogenic agranulocytosis. © 2015 Société nationale française de médecine interne (SNFMI).

Ciesla M.,Jagiellonian University | Wypasek E.,Jagiellonian University | Corral J.,University of Murcia | Alhenc-Gelas M.,Hematologie biologique | Undas A.,Jagiellonian University
Blood Coagulation and Fibrinolysis | Year: 2015

Type I antithrombin deficiency is an autosomal dominant disorder associated with thromboembolic complications mainly related to single-point mutations in SERPINC1, the gene encoding antithrombin. Chromosomal rearrangements have been found in up to 10% of cases with type I antithrombin deficiency. We report here the first heterozygous deletion of SERPINC1 exon 1 identified in a 44-year-old man with type I deficiency who developed deep vein thrombosis of the left leg complicated by pulmonary embolism. This study demonstrates that the search for large gene rearrangements in SERPINC1 can be a useful diagnostic approach, particularly in patients with type I antithrombin deficiency without mutations in SERPINC1. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Put N.,Catholic University of Leuven | Van Roosbroeck K.,Catholic University of Leuven | Konings P.,Catholic University of Leuven | Meeus P.,Catholic University of Leuven | And 25 more authors.
Annals of Hematology | Year: 2012

Translocations involving MYC are rare in chronic lymphocytic leukemia (CLL), and up to now, their prognostic significance remains unclear. We report the characteristics of 21 patients with CLL and nine patients with prolymphocytic leukemia (PLL), diagnosed in multiple centers (n=13), which showed an MYC translocation demonstrated by fluorescence in situ hybridization. The prevalence was estimated to be <1%. Advanced age and male predominance were observed. Morphological analysis frequently revealed the presence of prolymphocytes. A typical "CLL-immunophenotype" was found in four of nine cases with PLL. Moreover, CD5 and CD23 were frequently expressed in PLL. The latter findings are atypical for PLL and may suggest transformation or progression of an underlying CLL. MYC translocations were frequently observed with concomitant adverse cytogenetic markers, such as del(11q) (n=8/30) and/or del (17p)/monosomy 17 (n=7/30). In addition, the presence of unbalanced translocations (n=24 in 13/30 cases) and complex karyotype (n=16/30) were frequent in cases with MYC translocations. Altogether, del(17p)/monosomy 17, del(11q), and/or complex karyotype were observed in 22 of 30 patients. Survival outcome was poor: the median time to treatment was only 5 months, and overall survival (OS) from clinical diagnosis and from genetic detection was 71 and 19 months, respectively. In conclusion, CLL/PLL with MYC translocations is a rare entity, which seems to be associated with adverse prognostic features and unfavorable outcome. © Springer-Verlag 2012.

Wypasek E.,Jagiellonian University | Potaczek D.P.,Jagiellonian University | Alhenc-Gelas M.,Hematologie biologique | Undas A.,Jagiellonian University
Blood Coagulation and Fibrinolysis | Year: 2014

Protein S is one of the major natural anticoagulants. A missense serine 501 to proline (S501P) Heerlen polymorphism is associated with reduced levels of free protein S. Heerlen polymorphism, especially when combined with other thrombophilia risk factors, can lead to thromboembolic complications. To our knowledge, we report here the first Polish case associated with heterozygous Heerlen polymorphism resulting in type III protein S deficiency, detected in a 50-year-old man with several thrombotic episodes of deep and superficial veins and a highly positive thrombotic family history. The patient also had factor V Leiden mutation and persistently elevated anticardiolipin antibodies. It seems that increased risk of thrombotic complications could be explained in the patient by a synergy between the effects of Heerlen polymorphism, factor V Leiden heterozygous status and antiphospholipid syndrome. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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