Plombières-lès-Dijon, France
Plombières-lès-Dijon, France

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Chapelle C.,French Institute of Health and Medical Research | Quenet S.,Jean Monnet University | Delavenne X.,Jean Monnet University | Delavenne X.,Laboratoire Of Pharmacologie Et Toxicologie | And 6 more authors.
Pharmacopsychiatry | Year: 2013

In a meta-analysis of case-control studies, Zhang et al. (2011) found an increased risk of venous thromboembolic events (VTE) in patients exposed to antipsychotics (OR=2.39 [1.71-3.35]). Our updated meta-analysis including the 2 available cohort studies, recognized as a more relevant type of observational study, showed a weaker, but still strong association (OR=1.84 [1.39; 2.44]). In view of the lack of data on the confirmed risk factors for VTE in existing studies, prospective studies including adjustment for these risk factors are warranted to confirm this association and to assess the benefit/risk ratio of antipsychotics in high-risk patients. © Georg Thieme Verlag KGStuttgart . New York.


Mekontso Dessap A.,AP HP | Mekontso Dessap A.,French Institute of Health and Medical Research | Mekontso Dessap A.,University Paris Est Creteil | Ouanes I.,AP HP | And 9 more authors.
Critical Care | Year: 2011

Introduction: Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question.Methods: We retrospectively compared patients with severe sepsis and septic shock in whom statin therapy had been discontinued or continued. The primary endpoint was the number of organ failure-free days at day 14. Secondary end-points included hospital mortality and safety. The association of statin continuation with outcome was evaluated for crude analysis and after propensity score matching and adjustment. We also measured plasma atorvastatin concentrations in a separate set of ICU septic patients continuing the drug.Results: Patients in whom statin therapy had been continued in the ICU (n = 44) had significantly more organ failure-free days (11 67891011121314 vs. 6 [0-12], mean difference of 2.34, 95%CI from 0.47 to 5.21, P = 0.03) as compared to others (n = 32). However, there were important imbalances between groups, with more hospital-acquired infections, more need for surgery before ICU admission, and a trend towards more septic shock at ICU admission in the discontinuation group. The significant association of statin continuation with organ failure free days found in the crude analysis did not persist after propensity-matching or multivariable adjustment: beta coefficients [95% CI] of 2.37 [-0.96 to 5.70] (P = 0.20) and 2.24 [-0.43 to 4.91] (P = 0.11) respectively. We found particularly high pre-dose and post-dose atorvastatin concentrations in ICU septic patients continuing the drug.Conclusions: Continuing statin therapy in ICU septic patients was not associated with reduction in the severity of organ failure after matching and adjustment. In addition, the very high plasma concentrations achieved during continuation of statin treatment advocates some caution. © 2011 Mekontso Dessap et al.; licensee BioMed Central Ltd.


Bousliman Y.,Laboratoire Of Pharmaco Toxicologie | Eljaoudi R.,Laboratoire Of Pharmacologie Et Toxicologie | Elcadi M.A.,Laboratoire Of Pharmacologie Et Toxicologie | Basset T.,Laboratoire Of Pharmaco Toxicologie | And 5 more authors.
Annales de Biologie Clinique | Year: 2012

Paraphenylenediamine is an aromatic amine used as a hair dye; it is responsible for poisoning characterized by respiratory distress involving life-threatening. The objective of this work is the development and validation of an assay of para-phenylenediamine in the whole blood. The method is based on the determination of paraphenylene diamine in whole blood by gas chromatography-mass spectrometry after liquid-liquid extraction and derivatization. The validation protocol has included the study of the recovery factor of extraction, the measurement range, accurency, repetability and intermediate precision. The calibration curve was linear between 98 and 1350 μg/L (r = 0.999), the limit of detection and quantification were 37 μg/L and 63μg/L respectively. The accuracy were 94.7%. Coefficients of variation were (2.3/6.8/9.7%) for repeatability and (4.4/8.7/9.8%) for intermediate precision. The method is suitable for quantification of PPD in acute poisoning situations. A method for the determination of the paraphenylene diamine in the whole blood by gas chromatography coupled to mass spectrometry was developed. The validation of the method showed good linearity, good accuracy and low limit of quantification.


Goirand F.,Laboratoire Of Pharmacologie Et Toxicologie | Royer B.,Laboratoire Of Pharmacologie Et Toxicologie | Hulin A.,Laboratoire Of Pharmacologie Et Toxicologie | Saint-Marcoux F.,Limoges University Hospital Center
Therapie | Year: 2011

Everolimus has proven efficacy for prevention of rejection in adult de novo renal and cardiac transplant recipient in combination with ciclosporine and corticosteroids. Therapeutic drug monitoring (TDM) with target trough concentration (C0) value from 3 to 8 μg/L has been proposed. Through a systematic review of the literature, this work explored a level of recommendation for this TDM. Everolimus exhibits both wide interindividual pharmacokinetic variability and poor relationship between dose and exposure. A good relationship has been reported between C0 values and global exposure to the drug (i.e. AUC). Although C0 > 3 μg/L has been associated with a decreased incidence of rejection, the upper limit of 8 μg/L has never been formally validated. No clinical trial testing other exposure indices or comparing efficacy and/or toxicity of everolimus therapy with and without TDM has been published so far. Consequently the level of recommendation for everolimus monitoring is "recommended. © Société Française de Pharmacologie et de Thérapeutique.


El Cadi M.A.,Laboratoire Of Pharmacologie Et Toxicologie | El Jaoudi R.,Laboratoire Of Pharmacologie Et Toxicologie | Bouslimane Y.,Laboratoire Of Pharmacologie Et Toxicologie | Bouklouze A.,Laboratoire Of Pharmacologie Et Toxicologie | Cherrah Y.,Laboratoire Of Pharmacologie Et Toxicologie
Medecine Therapeutique Medecine de la Reproduction, Gynecologie et Endocrinologie | Year: 2011

During the last 20years, exposure to products of endocrine disruptors has increased, which has increased concerns about the risks incurred to human health. Through food or through the air, these disruptors may cause adverse effects on population. The mechanism of toxicity is related primarily to the action of endogenous hormones by interfering with their synthesis, their transport, their connection, their action or elimination. The effects of endocrine disruptors are found mainly on the hypothalamic-pituitary-gonad axis and the hypothalamic-pituitary-thyroid axis. Several substances are classified as endocrine disruptors, the most studied are the organochlorine pesticides, dioxins, phthalates and bisphenol A and the list is not exhaustive. The aim of this work is to review the knowledge in the field of endocrine disruption, substances involved, their mechanisms and effects on health.


Castaing N.,Laboratoire Of Pharmacologie Et Toxicologie | Castaing N.,University of Bordeaux 1 | Benali L.,University of Bordeaux 1 | Ducint D.,Laboratoire Of Pharmacologie Et Toxicologie | And 6 more authors.
Journal of Analytical Toxicology | Year: 2011

The suicide of a 43-year-old male by intravenous injection of cisatracurium, a non-depolarizing neuromuscular blocking agent, and thiopental, an ultra-short-acting barbiturate, is presented. Systematic toxicological screening by gas chromatography-mass spectrometry (GC-MS), liquid chromatography (LC)-diode-array detection, and LC-MS-MS confirmed the presence of thiopental. A large peak in the GC-MS chromatogram was matched by the Pfleger-Maurer library as corlumine, but neither atracurium neither its metabolite, laudanosine, were detected. To confirm the absence or the presence of laudanosine in the blood sample, an ultra-performance liquid chromatography-MS-MS method for cisatracurium and laudanosine quantification was developed. The calibration range was 2.5-500 ng/mL for laudanosine and 10-500 ng/mL for cisatracurium. The biases were lower than 12.3%. Intraday and interday precisions, expressed as coefficient of variation, were lower than 13.3%. This method allowed to confirm the presence of laudanosine and measurement of laudanosine in all samples. The femoral blood concentration was therapeutic (0.46 μg/mL). This case report documents a possible analytical pitfall and describes a simple and fast method for cisatracurium determination. Moreover, the purpose of this case report was to document the postmortem redistribution of cisatracurium and laudanosine, which could help make it possible to interpret tissue or cardiac blood concentrations in forensic cases where femoral blood is not available.


Regnaut O.,Unite medico judiciaire | Manaouil C.,Unite medico judiciaire | Manaouil C.,University of Picardie Jules Verne | Defouilloy C.,Unite medico judiciaire | And 3 more authors.
Revue de Medecine Legale | Year: 2015

Clozapine (Leponex®), an atypical antipsychotic, is considered one of the most effective antipsychotics but can induce many side effects including constipation. We present a young woman, with banal gastrointestinal history, hospitalized in psychiatric and treated with clozapine. Death seemed related to occlusion of constipation with Ogilvie's syndrome or toxic megacolon. This is an acute dilatation of previously healthy colon, in the absence of mechanical obstruction. Iatrogenic cause may be mentioned. The mortality rate can go up to 40% in case of ischemia or perforation. There is usually previous to gastrointestinal symptoms and simple additional tests may regain colonic dilatation. Clozapine induced gastrointestinal hypomotility because of its anticholinergic properties. Constipation is a factor favoring toxic megacolon often overlooked because of underlying pathological land on which it grows. Increased monitoring of constipation associated with early treatment should be the rule in the treated schizophrenic patients. © 2015 Elsevier Masson SAS.


PubMed | Laboratoire Of Pharmacologie Et Toxicologie
Type: Case Reports | Journal: Journal of analytical toxicology | Year: 2011

The suicide of a 43-year-old male by intravenous injection of cisatracurium, a non-depolarizing neuromuscular blocking agent, and thiopental, an ultra-short-acting barbiturate, is presented. Systematic toxicological screening by gas chromatography-mass spectrometry (GC-MS), liquid chromatography (LC)-diode-array detection, and LC-MS-MS confirmed the presence of thiopental. A large peak in the GC-MS chromatogram was matched by the Pfleger-Maurer library as corlumine, but neither atracurium neither its metabolite, laudanosine, were detected. To confirm the absence or the presence of laudanosine in the blood sample, an ultra-performance liquid chromatography-MS-MS method for cisatracurium and laudanosine quantification was developed. The calibration range was 2.5-500 ng/mL for laudanosine and 10-500 ng/mL for cisatracurium. The biases were lower than 12.3%. Intraday and interday precisions, expressed as coefficient of variation, were lower than 13.3%. This method allowed to confirm the presence of laudanosine and measurement of laudanosine in all samples. The femoral blood concentration was therapeutic (0.46 g/mL). This case report documents a possible analytical pitfall and describes a simple and fast method for cisatracurium determination. Moreover, the purpose of this case report was to document the postmortem redistribution of cisatracurium and laudanosine, which could help make it possible to interpret tissue or cardiac blood concentrations in forensic cases where femoral blood is not available.

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