Increased creatinine clearance in polytrauma patients with normal serum creatinine: a retrospective observational study

International audienceINTRODUCTION: The aim of this study, performed in an intensive care unit (ICU) population with a normal serum creatinine, was to estimate urinary creatinine clearance (CLCR) in a population of polytrauma patients (PT) through a comparison with a population of non trauma patients (NPT). METHODS: This was a retrospective, observational study in a medical and surgical ICU in a university hospital. A total of 284 patients were consecutively included. Two different groups were studied: PT (n = 144) and NPT (n = 140). Within the second week after admission to the ICU, renal function was assessed using serum creatinine, 24 h urinary CLCR . RESULTS: Among the 106 patients with a CLCR above 120 mL minute(-1) 1.73 m(-2), 79 were PT and 27 NPT (P < 0.0001). Only 63 patients had a CLCR below 60 mL minute(-1) 1.73 m(-2) with 15 PT and 48 NPT (P < 0.0001). Patients with CLCR greater than 120 mL minute(-1). 1.73 m(-2) were younger, had a lower SAPS II score and a higher male ratio as compared to those having CLCR lower than 120 mL minute(-1). 1.73 m(-2). Through a logistic regression analysis, age and trauma were the only factors independently correlated to CLCR. CONCLUSIONS: In ICU patients with normal serum creatinine, CLCR, is higher in PT than in NPT. The measure of CLCR should be proposed as routine for PT patients in order to adjust dose regimen, especially for drugs with renal elimination

Neonatal overfeeding by small-litter rearing sensitises hippocampal microglial responses to immune challenge:Reversal with neonatal repeated injections of saline or minocycline

The early-life period is extremely vulnerable to programming effects from the environment, many of which persist into adulthood. We have previously demonstrated that adult rats overfed as neonates have hypothalamic microglia that are hyper-responsive to an immune challenge, as well as hippocampal microglia that respond less efficiently to learning. We therefore hypothesised that neonatal overfeeding would alter the ability of hippocampal microglia to respond to an immune challenge with lipopolysaccharide (LPS) and that concomitant minocycline, a tetracycline antibiotic that suppresses microglial activity, could restore these responses. We induced neonatal overfeeding by manipulating the litter sizes in which Wistar rat pups were raised, so the pups were suckled in litters of four (neonatally overfed) or 12 (control-fed). We then examined the hippocampal microglial profiles 24 hour after an immune challenge with LPS and found that the neonatally overfed rats had dramatically increased microglial numbers in the hippocampus after immune challenge compared to control-fed rats. Attempts to reverse these effects with minocycline revealed repeated that neonatal injections, whether with minocycline or with saline, markedly suppressed microglial number and density throughout the hippocampus and abolished the difference between the groups in their responses to LPS. These data suggest that neonatal overfeeding not only can have lasting effects on hippocampal immune responses, but also that neonatal exposure to a protocol of repeated injections, irrespective of treatment, has a pronounced long-term impact, highlighting the importance of considering these effects when interpreting experimental data

Pharmacotherapy for Alcohol Dependence: Anticraving Medications for Relapse Prevention

Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence. These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence

Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS

Background: Minocycline is a tetracycline antibiotic that has been proposed as a potential conjunctive therapy for HIV-1 associated cognitive disorders. Precise mechanism(s) of minocycline’s functions are not well defined. Methods: Fourteen rhesus macaques were SIV infected and neuronal metabolites measured by proton magnetic resonance spectroscopy (1H MRS). Seven received minocycline (4 mg/kg) daily starting at day 28 post-infection (pi). Monocyte expansion and activation were assessed by flow cytometry, cell traffic to lymph nodes, CD16 regulation, viral replication, and cytokine production were studied. Results: Minocycline treatment decreased plasma virus and pro-inflammatory CD14+CD16+ and CD14loCD16+ monocytes, and reduced their expression of CD11b, CD163, CD64, CCR2 and HLA-DR. There was reduced recruitment of monocyte/ macrophages and productively infected cells in axillary lymph nodes. There was an inverse correlation between brain NAA/ Cr (neuronal injury) and circulating CD14+CD16+ and CD14loCD16+ monocytes. Minocycline treatment in vitro reduced SIV replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS stimulation. Conclusion: Neuroprotective effects of minocycline are due in part to reduction of activated monocytes, monocyte traffic. Mechanisms for these effects include CD16 regulation, reduced viral replication, and inhibited immune activation. Citation: Campbell JH, Burdo TH, Autissier P, Bombardier JP, Westmoreland SV, et al. (2011) Minocycline Inhibition of Monocyte Activation Correlate

Etude des cas de surdosage en paracétamol au cours de deux années ( 2001-2002) au Centre hospitalier universitaire de Toulouse

Le paracétamol est devenu progressivement l'antalgique-antipyrétique le plus utilisé dans le monde. Parallèlement, on observe une croissance du nombre de surdosages. Le risque majeur est une cytolyse hépatique centrolobulaire aiguë provoquée par la N-Acétyl-p-benzo-quinone-imine (NAPQI).Ce travail rétrospectif reprend toutes les observations (178 cas) du CHU de Toulouse du mois de janvier 2001 au mois d'octobre 2002 incluant tous les patients âgés de plus de 15 ans et ayant présenté un surdosage en paracétamol supérieur à 30 mg/L. Les éléments suivants ont été recherchés : données démographiques, type d'intoxication, facteurs de risque, dose de paracétamol ingérée, éléments cliniques et biologiques témoins d'une atteinte hépatique. Le risque d'atteinte hépatique a été évalué à l'aide de la paracétamolémie rapportée au nomogramme de Prescott. Enfin, la prise en charge thérapeutique a été étudiée.L'échantillon de population était jeune et féminin. Les surdosages en paracétamol représentent 4% des intoxications médicamenteuses de l'adulte, ils ont été le plus souvent réalisés avec une intention suicidaire. Le facteur de risque le plus fréquemment retrouvé a été l'alcoolisme chronique. Moins de 4% des patients ont présenté une paracétamolémie toxique. Cette étude montre l'intérêt d'évaluer le risque toxique par deux dosages sanguins en paracétamol espacés de 4 heures, ainsi que deux bilans hépatiques...TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocSudocFranceF

Influence de la microgravité simulée sur la pharmacocinétique du paracétamol (étude chez le rat)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocPARIS12-CRETEIL BU Eco. Gestion (940282103) / SudocSudocFranceF

Influence de la microgravité simulée sur la pharmacocinétique du paracétamol utilisé comme marqueur de la vidange gastrique (étude chez le rat et chez le volontaire sain)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Les intoxications médicamenteuses volontaires au méprobamate, étude de janvier 2001 à janvier 2003 inclus au CHU Rangueil-Larrey de Toulouse (aspects clinico-biologiques)

Le méprobamate est un tranquillisant largement prescrit. Sa consommation entraîne une forte dépendance physique et psychique ; de plus il est utilisé dans les tentatives d'autolyse..Notre étude rétrospective a été réalisée sur deux ans (janvier 2001 à janvier 2003 inclus) au CHU Rangueil-Larrey de Toulouse et porte sur 180 cas d'intoxications médicamenteuses volontaires au méprobamate chez 153 patients. Les critères de sélection étaient : un age supérieure ou égale à 18 ans et une méprobamatémie supérieure ou égale à 40 mg/L. La population étudiée était essentiellement féminine (65%) et quadragénaire. Les patients intoxiqués avaient comme points communs : un passé douloureux et traumatisant, un échec personnel (sentimental et/ou professionnel), une dépendance à un toxique (alcool, tabac ou autres) et enfin un évènement déclenchant. L'intoxication était dans un but d'autolyse dans tous les cas sauf un et le pourcentage de récidive était de 37.9 %. Nous déplorons un décès.TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocSudocFranceF