Publications by authors named "Nicolas Gambier"

31 Publications

Multiplex detection of 14 fentanyl analogues and U-47700 in biological samples: Application to a panel of French hospitalized patients.

Forensic Sci Int 2020 Dec 6;317:110437. Epub 2020 Sep 6.

Université de Lorraine, CHRU-Nancy, Department of Clinical Pharmacology and Toxicology, F-54000, Nancy, France; Université de Lorraine, CNRS, IMoPA, F-54000 Nancy, France. Electronic address:

Synthetic opioids (SO) associated with the recent alarming increase of deaths and intoxications in United States of America and Europe are not detected by the usual first-line opiates drug screening assays. We developed a liquid chromatography tandem mass spectrometry analytical method for the multiplex detection of 14 fentanyl analogues (2-furanylfentanyl, 4-ANPP, 4-methoxybutyrylfentanyl, acrylfentanyl, alfentanil, carfentanil, despropionyl-2-fluorofentanyl, fentanyl, methoxyacetylfentanyl, norfentanyl, ocfentanil, remifentanil, sufentanil and valerylfentanyl) and U-47700 in whole blood and urine samples. The method was validated according to the requirements of ISO 15189. A simple and fast liquid-liquid extraction (LLE) with De-Tox Tube-A was performed leading to better recovery of molecules in urine than in blood samples. Depending on the compound, the limits of detection (LODs) ranged from 0.01 to 0.10 ng/mL and from 0.02 to 0.05 ng/mL in whole blood and urine, respectively. Calibration curves were linear in the range 0.5-50.0 ng/mL and the limit of quantification (LOQ) ranged from 0.10 to 0.40 ng/mL in blood. Internal quality controls at 1 and 40 ng/mL showed intra-day and between-day precision and accuracy bias below 10% in urine and 15% in blood. The method was applied to the screening of 211 urine samples from patients admitted in emergency or addiction departments. The presence of legal fentanyl analogues in 5 urine samples was justified by their therapeutic use as analgesics. Only one patient was concerned by fentanyl misuse and addiction whereas no illegal SO was detected. This study is not in favor of a huge misuse of SO in the Lorraine region.
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http://dx.doi.org/10.1016/j.forsciint.2020.110437DOI Listing
December 2020

Temocillin dosage adjustment in a preterm infant with severe renal disease: a case report.

J Antimicrob Chemother 2020 12;75(12):3652-3655

Université de Lorraine, CHRU-Nancy, Department of Clinical Pharmacology and Toxicology, F-54000 Nancy, France.

Background: Temocillin is a carboxypenicillin antibiotic indicated in complicated urinary tract infections due to susceptible ESBL-producing Enterobacteriaceae. While temocillin therapeutic schemes for adult patients with normal or impaired renal function are evidence based, little is known in paediatric populations.

Objectives: We report herein the management of temocillin treatment in a preterm infant with end-stage renal disease.

Patients And Methods: The patient was a 7-month-old preterm infant born at 35 weeks gestation and treated by temocillin for 10 days for a bacteraemic urinary tract infection due to a susceptible ESBL-producing Enterobacter cloacae complex strain. Temocillin was administered by continuous infusion using a loading dose of 25 mg followed by a maintenance dose of 70 mg daily. Determination of MIC and temocillin plasma and urinary concentration was performed.

Results: Clinical improvement was observed 24 h after the initiation of temocillin treatment. Temocillin concentrations ranged between 21.6 and 35.5 mg/L in urine between the first and the sixth day of treatment and between 47.0 and 61.8 mg/L in plasma after 6 and 10 days of treatment, respectively. Temocillin concentrations were found to be above the determined MIC of 6 mg/L. From the measured concentrations, we can postulate that 100%fT>MIC was achieved in urine and at least equal to 40% in plasma.

Conclusions: Temocillin dosing adjustment performed in the present reported case allowed safe and effective treatment. The strategy described herein could be used as a basis for further clinical studies relative to temocillin use in a paediatric population with renal impairment.
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http://dx.doi.org/10.1093/jac/dkaa356DOI Listing
December 2020

Evaluation of KRAS, NRAS and BRAF mutations detection in plasma using an automated system for patients with metastatic colorectal cancer.

PLoS One 2020 15;15(1):e0227294. Epub 2020 Jan 15.

Université de Lorraine, CNRS UMR 7039 CRAN, Institut de Cancérologie de Lorraine, Service de Biopathologie, Nancy, France.

Background: Cell-free DNA detection is becoming a surrogate assay for tumor genotyping. Biological fluids often content a very low amount of cell-free tumor DNA and assays able to detect very low allele frequency mutant with a few quantities of DNA are required. We evaluated the ability of the fully-automated molecular diagnostics platform Idylla for the detection of KRAS, NRAS and BRAF hotspot mutations in plasma from patients with metastatic colorectal cancer (mCRC).

Materials And Methods: First, we evaluated the limit of detection of the system using two set of laboratory made samples that mimic mCRC patient plasma, then plasma samples from patients with mCRC were assessed using Idylla system and BEAMing digital PCR technology.

Results: Limits of detection of 0.1%, 0.4% and 0.01% for KRAS, NRAS and BRAF respectively have been reached. With our laboratory made samples, sensitivity up to 0.008% has been reached. Among 15 patients' samples tested for KRAS mutation, 2 discrepant results were found between Idylla and BEAMing dPCR. A 100% concordance between the two assays has been found for the detection of NRAS and BRAF mutations in plasma samples.

Conclusions: The Idylla system does not reach as high sensitivity as assays like ddPCR but has an equivalent sensitivity to modified NGS technics with a lower cost and a lower time to results. These data allowed to consider the Idylla system in a routine laboratory workflow for KRAS, NRAS and BRAF mutations detection in plasma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227294PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961936PMC
May 2020

Antibiotic prophylaxis with high-dose cefoxitin in bariatric surgery: an observational prospective single center study.

Antimicrob Agents Chemother 2019 Oct 7. Epub 2019 Oct 7.

Department of Anesthesiology and Intensive Care Medicine, University Hospital of Nancy, Vandoeuvre-Lès-Nancy F-54511, France

Background: The optimal dose of cefoxitin for antibiotic prophylaxis in obese patients remains uncertain. We evaluated the adequacy of a 4-gram dosing regimen of cefoxitin against the most frequent pathogens that infect patients undergoing bariatric surgery.

Methods: This observational prospective study included obese patients who required bariatric surgery and a 4-gram dose of cefoxitin as an antibiotic prophylaxis. Serum concentrations were measured during surgery (incision, wound closure and in case of reinjection). The pharmacokinetic/pharmacodynamic (PK/PD) target was to obtain free cefoxitin concentrations above 4× MIC, from incision to wound closure (100% ƒT). The targeted MIC was based on the worst-case scenario (the highest ECOFF value of , Enterobacteriaceae and anaerobic bacteria). The secondary outcomes were the factors related to underdosage.

Results: Two hundred patients were included. The mean age of the patients was 46 (±12) years-old, and the mean BMI was 45.8 (±6.9) kg/m Bypass surgery was the preferred technique (84%). The percentages of patients who met the PK/PD target (100% T) of cefoxitin were 37.3%, 1.1% and 0% for , Enterobacteriaceae and anaerobic bacteria, respectively. BMIs below 50 kg/m (OR 0.29, 95% CI [0.11-0.75], P = ) and a shorter duration of surgery (OR 0.97, 95% CI [0.95-0.99], P = ) were associated with reaching the target concentrations.

Conclusions: In obese patients undergoing bariatric surgery, a regimen of 4 grams of cefoxitin led to an inadequate coverage for most common pathogens. A longer surgery duration and BMI over 50 kg/m increase the risk of underdosage.
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http://dx.doi.org/10.1128/AAC.01613-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879239PMC
October 2019

AEME production in cocaine positive hair after thermal hair treatment.

Forensic Sci Int 2019 Sep 26;302:109894. Epub 2019 Jul 26.

Service de Toxicologie Médico-légale, Laboratoire National de Santé, Dudelange, Luxembourg.

Introduction: Currently, hair straightening has become a regular hair treatment for women but likewise for men. Several studies have shown that thermal straightening has an influence on the concentration of ethyl glucuronide and of drugs of abuse content in hair. Heat treatment of hair may decrease concentrations of cocaine (COC) and of cocaethylene (CE) in hair and increase concentrations of benzoylecgonine (BZE). The goal of this study was to evaluate the influence of thermal straightening on anhydroecgonine methyl ester (AEME), a known cocaine smoking marker, in hair.

Method: 42 positive COC hair samples were treated in vitro with iron plates heated to 200°C. During this treatment one lock of hair was put sequentially 30 times in contact with a hair straightener during 2s, the other lock was not treated. The hair samples were analyzed by a validated GC/MS method for AEME, COC and its metabolites BZE, norcocaine (NC), ecgonine methyl ester (EME) and CE.

Results: After treatment, a median increase of concentrations was observed for AEME (110.3%) and BZE (27.6%) whereas a median decrease was found for COC (56.9%), NC (46.7%), EME (33.3%) and CE (41.7%). The median BZE/COC ratio of 0.6 in not treated hair increased to 1.5 in treated hair.

Conclusion: Regarding our in vitro results, AEME may be produced by thermal hair straightening. Therefore, the presence of AEME in hair should not be used as an irrefutable prove of cocaine smoking. Our study shows that for the interpretation of AEME results in hair, potential heat treatment of hair should be considered. A ratio BZE/COC higher 1 appears to be a good marker to identify thermal treatment of hair before collection. Finally, thermal straightening should be documented during hair collection and should also be considered for the interpretation of COC results in hair.
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http://dx.doi.org/10.1016/j.forsciint.2019.109894DOI Listing
September 2019

Paracetamol Misuse and Dental Pain: Results from the French Observational DAntaLor Study.

J Oral Facial Pain Headache 2019 Winter;33(1):123-129

Aims: To evaluate the risk of hepatotoxicity due to unintentional paracetamol misuse in patients with acute dental pain.

Methods: A prospective multicenter observational survey was performed in patients consulting, without appointment, the odontology departments of three main French hospitals in the Lorraine region over a 3-month period. Patients were asked to fill out a medical questionnaire while seated in the waiting room. Those who completed the questionnaire, had dental pain, and took paracetamol were included in the DAntaLor study. Misuse was defined as a daily dose of more than 4 g of paracetamol per day. The risk of hepatotoxicity was considered high if the supposed ingested dose was above the threshold of 150 mg.kg.24h, 125 mg.kg.24h, or 100 mg.kg.24h over periods of 24, 48, and 72 hours, respectively. Hepatotoxicity was suspected in the presence of clinical symptoms.

Results: Of the 1,810 patients consulting the odontology departments, 741 were included in the study. Painkillers were used in 74.4% of the cases, and paracetamol was taken by 81.7%. Paracetamol was self-medicated in 85.5% of the patients and misused by 6.0%. Clinical symptoms were observed in 1.6% of the patients with no paracetamol misuse. For patients consuming more than 4 g per day and experiencing mild unspecific clinical symptoms of hepatotoxicity, the suspected ingested dose category was below one of the three previously defined thresholds for 11.8% and was above for 40.0%.

Conclusion: Patients with dental pain are at risk of paracetamol overdose and hepatotoxicity.
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http://dx.doi.org/10.11607/ofph.1861DOI Listing
November 2019

Intravenous single administration of amiodarone and breastfeeding.

Fundam Clin Pharmacol 2019 Jun 4;33(3):367-372. Epub 2019 Jan 4.

Centre Hospitalier Régional Universitaire de Nancy, Centre Régional de Pharmacovigilance de Nancy, Hôpital Central, 29, avenue du Maréchal de Lattre de Tassigny, CO, 60 034, 54 035, Nancy cedex, France.

Amiodarone treatment is contraindicated during breastfeeding. As the regional pharmacovigilance centre, we were contacted for information relative to the possibility of breastfeeding after single intravenous administration of 450 mg amiodarone to a breastfeeding woman. A monitoring of amiodarone concentration in plasma and milk was performed in the mother. At day 4, milk concentration of amiodarone reached a peak (233 μg/L) and milk to plasma ratio was determined to 3.5. Milk concentration was still detectable at day 10 (132 μg/L). The maximal relative infant dose was estimated to be 0.6% of the maternal weight-adjusted dosage, corresponding to 0.18% of the usual posology used in children by parenteral route. The review of the literature retrieved one publication suggesting that a single intravenous administration of 150 mg of amiodarone to a mother represents a negligible infant risk based on low breast milk concentration. The French National Pharmacovigilance database query did not disclose any case of side effects during breastfeeding after a single dose of amiodarone. A very limited exposition of breastfed newborns to amiodarone, as well as a low risk of side effects, is expected after a single administration of amiodarone to their mothers.
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http://dx.doi.org/10.1111/fcp.12439DOI Listing
June 2019

Postmortem Hyperthermia: Two Case Reports and a Review of the Literature.

Am J Forensic Med Pathol 2018 12;39(4):364-366

Institut de médecine légale de Strasbourg, Université de Strasbourg, Strasbourg, France.

In this daily practice, the forensic pathologist is rarely confronted with postmortem hyperthermia associated with the rapid onset of rigor mortis. We report 2 similar cases where the rectal temperature value taken during the on-scene investigations by the forensic pathologist was greater than 40°C (104°F) in both cases, and rigor mortis was complete within less than 6 hours postmortem. The first case was due to a deadly intoxication by ecstasy and the second one to the deadly association of methadone and a possible neuroleptic malignant syndrome. Infection-related deaths were eliminated. Thus, the association of postmortem hyperthermia and rapid-onset rigor mortis would suggest in the first hypothesis a toxic death, particularly 3,4-methylenedioxymethamphetamine. However, an autopsy and toxicological analysis are necessary to confirm the cause of death.
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http://dx.doi.org/10.1097/PAF.0000000000000431DOI Listing
December 2018

Substance use and misuse in a mountain ultramarathon: new insight into ultrarunners population?

Res Sports Med 2017 Apr-Jun;25(2):244-251. Epub 2017 Jan 23.

c Department of Pulmonary Function Testing and Exercise Physiology , CHRU Nancy , Nancy , France.

Endurance and ultra-endurance events have become increasingly popular. The aim of our study was to explore the use of medication among endurance runners participating in the 2014 Infernal Trail des Vosges. Among the 389 runners engaged, 297 (76.3%) completed a specific questionnaire dealing with substance use/misuse. Our results show a 27% (before the race) and 18% (during the race) prevalence of substance use. The two major classes of substances used were non-steroidal anti-inflammatory drugs (NSAIDs; 9.8%) and painkillers (6.7%), principally because of osteo-articular pain (29.6%) or to prevent pain (28.2%). A positive correlation was found between substance consumption before (past month) and during the race (overall medication: p < 0.0001; NSAIDs: p = 0.008). Our results could be explained by the specific characteristics of ultrarunners predominantly motivated by personal achievement and general health (recreational approach). However, education interventions should further be delivered regarding the risks of substance use in ultra-endurance events.
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http://dx.doi.org/10.1080/15438627.2017.1282356DOI Listing
October 2017

Management of Tacrolimus-Telaprevir Drug-Drug Interaction in a Liver Transplant Patient With Hepatitis C Virus: Practical Considerations.

Transplantation 2015 Sep;99(9):e163-4

1 Department of Clinical Pharmacology and Toxicology, CHU Nancy, Nancy, France. 2 Université de Lorraine, UMR 7365 CNRS-UL, IMoPA, Vandœuvre-lès-Nancy, France. 3 Pharmacovigilance Center of Lorraine, CHU Nancy, Nancy, France. 4 Department of Biochemistry, CHU Strasbourg, Strasbourg, France. 5 Department of Hepatology and Gastroenterology, CHU Nancy, Vandoeuvre-lès-Nancy, France.

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http://dx.doi.org/10.1097/TP.0000000000000859DOI Listing
September 2015

[Counterfeit and Falsified Drugs: an Overview].

Therapie 2015 Sep-Oct;70(5):455-64. Epub 2015 Jun 12.

CHU Nancy, Laboratoire de Pharmacologie Clinique et Toxicologie, Nancy, France - CHU Nancy, Centre Régional de Pharmacovigilance de Lorraine, Nancy, France - Université de Lorraine, UMR CNRS 7365 IMoPA, Vandoeuvre-lès-Nancy, France.

If the traffic of fake medicines may represent an economic threat for the pharmaceutical industry, it can also be responsible of safety concerns for patients. Despite fake drugs represent a real threat for public health, the intended punishments are until now only based on intellectual property rights. Estimated to generate more than 55 billion euros per year, the traffic of falsified drugs varies from a country to another one. Indeed, the proportion of falsified drugs ranges from 1% in industrialized countries with a regulated and controlled distribution system to 60% of medicines in some developing countries. Currently, the measures developed to limit this traffic concern five main areas: legislation / regulation, cooperation, enforcement, technology and communication. Communication actions should be performed to inform health professionals as the populations about the risks of using drugs purchased outside the legal drug market.
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http://dx.doi.org/10.2515/therapie/2015031DOI Listing
December 2015

Early withdrawal effects in a heavy cannabis smoker during hemodialysis.

Biol Psychiatry 2015 Mar 23;77(5):e25-6. Epub 2014 Aug 23.

Centre Hospitalier Universitaire de Nancy, Maison des Addictions, Nancy; Université Lorraine, Faculté de Médecine, Nancy; Centre Psychothérapique de Nancy, Nancy, France.

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http://dx.doi.org/10.1016/j.biopsych.2014.07.032DOI Listing
March 2015

Death of an alcohol-dependent patient following intentional drug intoxication: implication of baclofen?

Eur Addict Res 2014 4;20(6):300-4. Epub 2014 Oct 4.

Department of Clinical Pharmacology and Toxicology, CHU Nancy, Nancy, France.

Used in the treatment of spasticity at low doses, baclofen is also prescribed off-label at high doses for the treatment of alcohol dependence. Several cases of baclofen intoxication have been reported, but only 1 case deals with the treatment of alcohol dependence. Thus, we report the first death in the context of baclofen off-label use of an alcohol-dependent patient with a high blood baclofen concentration after intentional drug intoxication. The safety profile of baclofen in the treatment of alcohol dependence is reviewed and discussed, underlining the obligatory caution that may support any prescription of high doses of baclofen in this off-label indication and especially in patients with concomitant psychiatric disorders.
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http://dx.doi.org/10.1159/000362409DOI Listing
June 2015

[Methandienone misuse: interest of medical anti-doping units].

Therapie 2014 May-Jun;69(3):249-50. Epub 2014 Jun 18.

Service des Examens de la Fonction respiratoire et de l'Aptitude à l'Exercice, CHU de Nancy, Vandœuvre-lès-Nancy, France - Antenne médicale de Prévention du Dopage de Lorraine, CHU de Nancy, Vandœuvre-lès-Nancy, France.

We report a case of methandienone misuse leading to a preventive action of the Lorraine medicale anti-doping unit.
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http://dx.doi.org/10.2515/therapie/2014023DOI Listing
September 2014

Dose-response of superparamagnetic iron oxide labeling on mesenchymal stem cells chondrogenic differentiation: a multi-scale in vitro study.

PLoS One 2014 30;9(5):e98451. Epub 2014 May 30.

Ingénierie Moléculaire et Physiopathologie Articulaire - Unité Mixte de Recherches 7365 Centre National de la Recherche Scientifique - Université de Lorraine, Vandoeuvre Lès Nancy, France.

Aim: The aim of this work was the development of successful cell therapy techniques for cartilage engineering. This will depend on the ability to monitor non-invasively transplanted cells, especially mesenchymal stem cells (MSCs) that are promising candidates to regenerate damaged tissues.

Methods: MSCs were labeled with superparamagnetic iron oxide particles (SPIO). We examined the effects of long-term labeling, possible toxicological consequences and the possible influence of progressive concentrations of SPIO on chondrogenic differentiation capacity.

Results: No influence of various SPIO concentrations was noted on human bone marrow MSC viability or proliferation. We demonstrated long-term (4 weeks) in vitro retention of SPIO by human bone marrow MSCs seeded in collagenic sponges under TGF-β1 chondrogenic conditions, detectable by Magnetic Resonance Imaging (MRI) and histology. Chondrogenic differentiation was demonstrated by molecular and histological analysis of labeled and unlabeled cells. Chondrogenic gene expression (COL2A2, ACAN, SOX9, COL10, COMP) was significantly altered in a dose-dependent manner in labeled cells, as were GAG and type II collagen staining. As expected, SPIO induced a dramatic decrease of MRI T2 values of sponges at 7T and 3T, even at low concentrations.

Conclusions: This study clearly demonstrates (1) long-term in vitro MSC traceability using SPIO and MRI and (2) a deleterious dose-dependence of SPIO on TGF-β1 driven chondrogenesis in collagen sponges. Low concentrations (12.5-25 µg Fe/mL) seem the best compromise to optimize both chondrogenesis and MRI labeling.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098451PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039474PMC
January 2015

[Adherence to medication and epilepsy: a current issue].

Therapie 2013 Sep-Oct;68(5):297-301. Epub 2013 Nov 14.

CHU Nancy, Pôle NTC, Service de Neurologie, Nancy, France.

As in other chronic diseases, adherence to medication in epilepsy is critical for seizure control. Its assessment remains challenging in research as in clinical practice. Recent evidences showed another face of nonadherence: the overconsumption of antiepileptic drugs. Some educational interventions with easy implementation were found to be effective in improving adherence and should be therefore more used in everyday practice.
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http://dx.doi.org/10.2515/therapie/2013051DOI Listing
January 2014

Nicorandil and ulceration: how to dig the furrow.

Eur J Dermatol 2013 Jul-Aug;23(4):528-9

Department of Clinical Pharmacology, University Hospital, Nancy, 54035, France.

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http://dx.doi.org/10.1684/ejd.2013.2071DOI Listing
June 2014

[Acute kidney injury following naproxene use in an ultraendurance female athlete].

Presse Med 2013 Sep 27;42(9 Pt 1):1274-6. Epub 2013 Feb 27.

CHU de Nancy, service des examens de la Fonction respiratoire et de l'aptitude à l'exercice, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France. Electronic address:

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http://dx.doi.org/10.1016/j.lpm.2012.09.030DOI Listing
September 2013

Effect of dynamic loading on MSCs chondrogenic differentiation in 3-D alginate culture.

Biomed Mater Eng 2012 ;22(4):209-18

UMR CNRS - Université de Lorraine, Vandoeuvre-lès-Nancy, France.

Mesenchymal stem cells (MSCs) are regarded as a potential autologous source for cartilage repair, because they can differentiate into chondrocytes by transforming growth factor-beta (TGF-β) treatment under the 3-dimensional (3-D) culture condition. In addition to these molecular and biochemical methods, the mechanical regulation of differentiation and matrix formation by MSCs is only starting to be considered. Recently, mechanical loading has been shown to induce chondrogenesis of MSCs in vitro. In this study, we investigated the effects of a calibrated agitation on the chondrogenesis of human bone MSCs (MSCs) in a 3-D alginate culture (day 28) and on the maintenance of chondrogenic phenotypes. Biomechanical stimulation of MSCs increased: (i) types 1 and 2 collagen formation; (ii) the expression of chondrogenic markers such as COMP and SOX9; and (iii) the capacity to maintain the chondrogenic phenotypes. Notably, these effects were shown without TGF-β treatment. These results suggest that a mechanical stimulation could be an efficient method to induce chondrogenic differentiation of MSCs in vitro for cartilage tissue engineering in a 3-D environment. Additionally, it appears that MSCs and chondrocyte responses to mechanical stimulation are not identical.
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http://dx.doi.org/10.3233/BME-2012-0710DOI Listing
November 2012

Efficacy of early clinical evaluation in predicting direct home discharge of elderly patients after hospitalization in internal medicine.

South Med J 2012 Feb;105(2):63-7

Assistance Publique-Hôpitaux de Paris, Université Paris XIII, Service de Médecine Interne, Hôpital Avicenne, Bobigny, France.

Objectives: Early evaluation of direct home discharge (DHD) after hospitalization of elderly patients is important to organize discharge planning quickly. Many scores, scales, and indices have been developed to improve discharge planning. Is clinical judgment better than functional status, comorbidity, or cognitive function scales in predicting DHD of elderly patients after hospitalization?

Methods: Ninety-seven patients, aged 75 years or older, admitted from the emergency department to an internal medicine department in a French teaching hospital between December 1, 2006 and May 1, 2007, were enrolled prospectively in the study. Demographic, clinical, and laboratory characteristics and functional status, comorbidity, and cognitive function scales were determined. The primary outcome was the percentage of correct discharge prediction made by junior and senior doctors within the first 48 hours upon admission. Univariate analysis and logistic regression were assessed to determine predictive variables of patients' discharge.

Results: Junior and senior doctors obtained correct prediction in 74.2% and 73.2% of cases, respectively (P > 0.99). Activities of daily living, instrumental activities of daily living, and duration of hospitalization were predictive of DHD (95% confidence interval [CI] -6.1 to 0.2, P = 0.037; 95% CI -2.1 to 9.9, P = 0.003; 95% CI -3 to 9.1, P = 0.0001, respectively) in the univariate analysis. Instrumental activities of daily living was an independent predictive variable of patients' discharge in a logistic regression. No difference between clinical evaluation and the use of an independent predictive variable regarding the prediction of DHD was found.

Conclusions: Early clinical evaluation is as effective as the use of functional status scales to predict DHD of hospitalized elderly patients.
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http://dx.doi.org/10.1097/SMJ.0b013e318242d74dDOI Listing
February 2012

Misuse of acetaminophen in the management of dental pain.

Pharmacoepidemiol Drug Saf 2011 Sep 1;20(9):996-1000. Epub 2011 Jul 1.

Emergency Dental Service, CHU of Nancy, Nancy, France.

Purpose: We highlight the risk associated with acetaminophen misuse in patients having dental pain in France based on a series of cases of unintentional acetaminophen overdose reported by the Emergency Dental Service of Nancy over a 9-month period.

Methods: Data were collected by querying the French Pharmacovigilance database. Each retrieved clinical data were reviewed by a clinician.

Results: Thirteen cases of acetaminophen overdose were reported to the Regional Pharmacovigilance Center of Lorraine, Nancy, France. Most cases (10/13) concerned men aged 20-40 years old. Mild, unspecific clinical symptoms were observed in seven of 13 patients. The median value of the supposed ingested dose was 137 mg/kg/24 h. Liver enzyme activity was tested in 10 patients and was abnormal in four patients. N-acetylcysteine treatment was administered to four patients.

Conclusions: We propose that even patients with mild clinical symptoms with a supposed ingested dose of acetaminophen greater than 150 mg/kg/24 h should be referred to an emergency department and that liver enzyme activity should be analyzed. No case of liver failure was observed during our short survey. However, hepatotoxicity of repeated supratherapeutic ingestion of acetaminophen was suspected in four patients. Patients and practitioners should thus be better informed about the risk of unintentional acetaminophen overdose following supratherapeutic acetaminophen ingestion.
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http://dx.doi.org/10.1002/pds.2171DOI Listing
September 2011

Transient elastography as a screening tool for liver fibrosis and cirrhosis in a community-based population aged over 45 years.

Gut 2011 Jul 10;60(7):977-84. Epub 2010 Nov 10.

Unité d' Hépatologie, Hopital Avicenne, France.

Background: Liver stiffness measurement (LSM) has been used to measure fibrosis in patients with various types of chronic liver diseases. However, its usefulness as a screening procedure in apparently healthy people had not been evaluated to date.

Methods: 1358 subjects >45 years old from a general population attending for a medical check-up were consecutively enrolled in the study. All subjects were submitted to medical examination and laboratory tests in addition to LSM, performed on the same day by a single operator. Subjects with LSM values >8 kPa were referred to a liver unit for further investigations.

Results: 168 subjects were not considered for analysis due to missing data (n=23), LSM failure (n=51) or unreliable LSM values (n=94). Among the 1190 remaining subjects, 89 (7.5%) had LSM >8 kPa including nine patients with LSM >13 kPa. Despite the fact that normal liver tests were observed in 43% of them (38 out of 89), a specific cause of chronic liver disease was found in all cases. Non-alcoholic fatty liver disease (NAFLD) was the likely cause of chronic liver disease in 52 patients, alcoholic liver disease (ALD) in 20, and both causes were associated in seven additional patients. Hepatitis C virus and hepatitis B virus chronic hepatitis was documented in five and four cases, respectively, and primary biliary cirrhosis in one. Liver biopsy was obtained for 27 patients, including the nine patients with LSM >13 kPa, who were diagnosed with liver cirrhosis due to ALD (n=5), chronic hepatitis C (n=3) or chronic hepatitis B (n=1). The 18 remaining biopsies showed liver fibrosis in all cases except one (isolated steatosis), with ALD and NAFLD being present in six and eight cases, respectively.

Conclusion: LSM proved to be a useful and specific procedure to screen for cirrhosis in the general population and to detect undiagnosed chronic liver disease in apparently healthy subjects.
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http://dx.doi.org/10.1136/gut.2010.221382DOI Listing
July 2011

Arterial and venous thromboembolic events during anti-TNF therapy: a study of 85 spontaneous reports in the period 2000-2006.

Biomed Mater Eng 2009 ;19(4-5):355-64

Regional Pharmacovigilance Center of Lorraine, Nancy, France.

Background: Systemic inflammation such as rheumatoid arthritis (RA) and Crohn's disease (CD) may be responsible for vascular comorbidity. TNF-alpha blockade was expected to lower these comorbidities but several cases of arterial and venous thromboembolic events (TE) have been reported.

Objectives: The aim of this work was to study retrospectively the main characteristics of spontaneously notified TNF-alpha blockers related TE over a 7-year period.

Methods: TE related to infliximab, etanercept and adalimumab spontaneously notified to the French adverse drug reporting system database between January 2000 and December 2006 were analyzed. Separate analysis of arterial TE and venous TE was performed. Risk factors for each category of TE were assessed with consensual criteria.

Results: 85 TE were analyzed, representing 4.5% of all the spontaneously notified adverse reactions of the 3 TNF-alpha blockers in the database. 42 were arterial events and 43 were venous events. The incidence was not significantly different between the 3 TNF-alpha blockers. Mean delay of TE onset after treatment initiation was 10.6 months. It was significantly shorter for etanercept (6.1 months, p=0.001) especially for venous TE (2.4 months). 16 among the 42 patients with arterial TE had 2 or more risk factors whereas 39 among the 43 patients with venous TE had no RF or only one. Most of patients (79/85) received concomitant systemic corticosteroids and/or methotrexate and/or COX-2 selective inhibitors. 23 patients had been investigated for autoimmunity, 13 had antinuclear and/or antiphospholipid antibodies. Main limitations of this study were underreporting and heterogeneous report contents.

Conclusion: Despite its limitations, this study suggests that venous TE could be favoured by TNF-alpha blockers therapy since they occurred in patients with no or few risk factors for venous thrombosis. However, this needs to be more evaluated by controlled studies.
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http://dx.doi.org/10.3233/BME-2009-0600DOI Listing
March 2010

Pharmacogenomics and antihypertensive drugs: a path toward personalized medicine.

Per Med 2007 Nov;4(4):393-412

Équipe Inserm, Génétique Cardiovasculaire, du CIC 9501, Faculté de Pharmacie, Université Henri Poincaré, Nancy I, 30 rue Lionnois, 54000 Nancy, France.

Pharmacogenomics focuses on genes and the transcriptome and proteome. It has the potential to enhance healthcare management by improving disease diagnosis and implementing treatments adapted to each patient. Previously, pharmacogenetics of candidate genes focused on clinical research. It is now extended by using genome-wide approaches to elucidate the inherited basis of differences between individuals in their response to drugs. We summarize relevant polymorphisms of genes involved in the pharmacokinetics and pharmacodynamics of antihypertensive drugs and we give an overview of the state of pharmacogenomic research in hypertension medicine. Even if things are getting better, current pharmacogenetic studies still lack power, adequate selection of candidate genes and knowledge of their functions at the physiological level. Finally, some specific end point phenotypes (i.e., peptides or proteins related to the metabolic cycle targeted by the drug) should be integrated to propose data that are easily applicable to personalized medicine.
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http://dx.doi.org/10.2217/17410541.4.4.393DOI Listing
November 2007

Interaction between CYP1A1 T3801C and AHR G1661A polymorphisms according to smoking status on blood pressure in the Stanislas cohort.

J Hypertens 2006 Nov;24(11):2199-205

INSERM U525, Faculté de Pharmacie, Université Henri Poincaré Nancy 1, Nancy, France.

Background: CYP1A1, one of the key enzymes in detoxifying toxic components produced during cigarette smoking, is regulated by aromatic hydrocarbon receptor (AHR). A CYP1A1 T3801C polymorphism, associated with a higher CYP1A1 inducibility and enhanced catalytic activity, has been linked to stroke, triple vessel disease and may, therefore, be associated with blood pressure (BP). The relation of the widely studied G1661A polymorphism of the human AHR gene with BP is unknown.

Objectives: To investigate the genetic influence of CYP1A1 T3801C and AHR G1661A polymorphisms on BP in relation to tobacco consumption.

Design And Participants: Study participants were selected from a French longitudinal cohort of volunteers for a free health check-up. These individuals (302 men and 311 women) were not taking medication that can affect blood pressure. Information about active smoking status was obtained by a self-administered questionnaire.

Results: After multiple regression analysis, systolic blood pressure (SBP) and diastolic blood pressure (DBP) did not differ significantly according to their tobacco status excepted for DBP in men. In addition, neither CYP1A1 T3801C nor AHR G1661A polymorphism was linked to blood pressure. However, systolic and diastolic blood pressures differed significantly according to CYP1A1 T3801C genotype between ex-smokers and smokers. Finally, the interaction between CYP1A1 T3801C and AHR G1661A polymorphisms explained a significant difference of SBP and DBP between carriers of both CYP1A1-C3801 and AHR-A1661 alleles.

Conclusion: This study is the first to show an interaction between the CYP1A1 T3801C and AHR G1661A polymorphisms. This interaction could explain the difference in blood pressure level between smokers and non-smokers/ex-smokers but needs to be confirmed in a large sample.
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http://dx.doi.org/10.1097/01.hjh.0000249697.26983.aaDOI Listing
November 2006