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Find video protocols related to scientific articles indexed in Pubmed.
Study of blood and brain lithium pharmacokinetics in the rat according to three different modalities of poisoning.
Toxicol. Sci.
PUBLISHED: 10-31-2014
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Lithium-induced neurotoxicity may be life-threatening. Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns. We developed acute (intraperitoneal administration of 185 mg/kg-Li2CO3 in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg-Li2CO3 in rats receiving 800 mg/l-Li2CO3 in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg-Li2CO3 during 5 days in rats with 15 mg/kg-K2Cr2O7-induced renal failure). Delayed absorption (4.03 vs. 0.31 h), increased plasma elimination (0.65 vs. 0.37 l/kg/h) and shorter half-life (1.75 vs. 2.68 h) were observed in acute-on-chronically compared to acutely poisoned rats. Erythrocyte and cerebrospinal fluid kinetics paralleled plasma kinetics in both models. Brain lithium distribution was rapid (as early as 15 min), inhomogeneous and with delayed elimination (over 78h). However, brain lithium accumulation was more marked in acute-on-chronically than acutely poisoned rats [area-under-the-curve of brain concentrations (379±41 vs. 295±26, P<0.05) and brain-to-plasma ratio (45±10 vs. 8±2, P<0.0001) at 54h]. Moreover, brain lithium distribution was increased in chronically compared to acute-on-chronically poisoned rats (brain-to-plasma ratio: 9±1 vs. 3±0, P<0.01). In conclusion, prolonged rat exposure results in brain lithium accumulation, which is more marked in the presence of renal failure. Our data suggest that differences in plasma and brain kinetics may at least partially explain the observed variability between human intoxication patterns.
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Do Serotonin Reuptake Inhibitors Worsen Outcome of Patients Referred to the Emergency Department for Deliberate Multi-drug Exposure?
Basic Clin. Pharmacol. Toxicol.
PUBLISHED: 08-22-2014
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Incidence of poisonings with serotonin reuptake inhibitors (SRIs) is growing. SRI toxicity is considered low, but its actual impact in multi-drug poisonings remains unclear. Our objective was to evaluate the consequences of SRI exposure in patients referred to the emergency department (ED) for deliberate multi-drug exposure. Patients admitted for multi-drug exposure involving at least one SRI were matched with patients who did not ingest any SRI, according to age, gender, type of drug and ingested doses. Features of serotonin syndrome according to Sternbach's criteria and Hunter's serotonin toxicity criteria were evaluated from records. In 4 years, 148 SRI-exposed patients were included and compared to 296 matched controls. The SRIs mainly involved were escitalopram (22%), venlafaxine (20%), fluoxetine (19%), citalopram (15%) and paroxetine (11%). Serotonin syndrome was diagnosed in one patient, but actually occurred in five SRI-exposed patients based on the retrospective evaluation of records. Twenty patients (14%) exhibited one or more serotonin syndrome criteria. At least two of 11 of Sternbach's criteria and two of nine of Hunter's serotonin toxicity criteria were missing in each chart. Using a conditional logistic regression analysis, seizures (p = 0.04) and serotonin syndrome (p = 0.01 based on Sternbach's criteria and p = 0.004 based on Hunter's serotonin toxicity criteria) more frequently occurred in SRI-exposed patients. Requirement for mechanical ventilation was significantly increased (p = 0.03), although admission to the intensive care unit was not. In multi-drug-poisoned patients admitted to the ED, exposure to SRIs significantly increases the risk of seizures and requirement for mechanically ventilation. Diagnosis of serotonin syndrome remains insufficient justifying improved training.
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Development, validation and clinical application of a LC-MS/MS method for the simultaneous quantification of hydroxychloroquine and its active metabolites in human whole blood.
J Pharm Biomed Anal
PUBLISHED: 07-29-2014
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A rapid, sensitive and specific method using liquid chromatography coupled to tandem mass spectrometry was developed for the simultaneous quantification of hydroxychloroquine (HCQ) and its three major metabolites in human whole blood. The assay, using a sample volume of 100?L, was linear in a dynamic 25-2000ng/mL range (R(2)>0.99) for all four compounds and suitable for the determination of elevated HCQ concentrations up to 20,000ng/mL, after appropriate sample dilution. Inter- and intra-assay precisions were <18.2% and accuracies were between 84% and 113% for any analyte. No matrix effects were observed. The assay was successfully applied to a blood sample obtained from one poisoned patient following a massive HCQ self-ingestion resulting in an estimated concentration of 19,500ng/mL on hospital admission. In this patient, HCQ metabolites were identified and quantified at 1123, 465 and 91ng/mL for monodesethylhydroxychloroquine, desethylchloroquine and bisdesethylchloroquine, respectively. Further investigations are still required to assess the usefulness of the simultaneous measurement of blood concentrations of HCQ and its three active metabolites for monitoring HCQ treatment and managing HCQ poisoning.
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Quasi-experimental study of sodium citrate locks and the risk of acute hemodialysis catheter infection among critically ill patients.
Antimicrob. Agents Chemother.
PUBLISHED: 06-30-2014
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Critically ill patients who require renal replacement therapy (RRT) are vulnerable to catheter-related bloodstream infections (CRBSI). This study compared the risks of dialysis catheter infection according to the choice of locking solution in the intensive care unit (ICU). A prospective quasi-experimental study with marginal structural models (MSM) and 2:1 greedy propensity-score matching (PSM) was conducted at nine university-affiliated hospitals and three general hospitals. A total of 596 critically ill patients received either saline solution or heparin lock solution (the standard of care [SOC]) from 2004 to 2007 in the Cathedia cohort (n = 464 for MSM; n = 124 for PSM) or 46.7% citrate lock from 2011 to 2012 in the citrate (CLock) cohort (n = 132 for MSM; n = 62 for PSM) to perform RRT using intermittent hemodialysis. Catheter-tip colonization and CRBSI were analyzed. The mean duration (standard deviation [SD]) of catheterization was 7.1 days (6.1) in the SOC group and 7.0 days (5.9) in the CLock group (P = 0.84). The risk of dialysis catheter-tip colonization was lower in the CLock group (20.5 versus 38.7 per 1,000 catheter-days in the SOC group; hazard ratio [HR] from MSM, 0.73; 95% confidence interval [CI], 0.57 to 0.93; P < 0.02). Consistent findings were found from PSM (HR, 0.46; 95% CI, 0.22 to 0.95; P < 0.04). The risk of CRBSI was nonsignificantly different in the CLock group (1.1 versus 1.8 per 1,000 catheter-days in the SOC group; HR from MSM, 0.48; 95% CI, 0.12 to 1.87; P = 0.29). By reducing the risk of catheter-tip colonization, citrate lock has the potential to improve hemodialysis safety in the ICU. Additional studies are warranted before the routine use of citrate locks can be recommended in the ICU.
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Guidelines for reporting case studies on extracorporeal treatments in poisonings: methodology.
Semin Dial
PUBLISHED: 05-29-2014
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A literature review performed by the EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup highlighted deficiencies in the existing literature, especially the reporting of case studies. Although general reporting guidelines exist for case studies, there are none in the specific field of extracorporeal treatments in toxicology. Our goal was to construct and propose a checklist that systematically outlines the minimum essential items to be reported in a case study of poisoned patients undergoing extracorporeal treatments. Through a modified two-round Delphi technique, panelists (mostly chosen from the EXTRIP workgroup) were asked to vote on the pertinence of a set of items to identify those considered minimally essential for reporting complete and accurate case reports. Furthermore, independent raters validated the clarity of each selected items between each round of voting. All case reports containing data on extracorporeal treatments in poisoning published in Medline in 2011 were reviewed during the external validation rounds. Twenty-one panelists (20 from the EXTRIP workgroup and an invited expert on pharmacology reporting guidelines) participated in the modified Delphi technique. This group included journal editors and experts in nephrology, clinical toxicology, critical care medicine, emergency medicine, and clinical pharmacology. Three independent raters participated in the validation rounds. Panelists voted on a total of 144 items in the first round and 137 items in the second round, with response rates of 96.3% and 98.3%, respectively. Twenty case reports were evaluated at each validation round and the independent raters' response rate was 99.6% and 98.8% per validation round. The final checklist consists of 114 items considered essential for case study reporting. This methodology of alternate voting and external validation rounds was useful in developing the first reporting guideline for case studies in the field of extracorporeal treatments in poisoning. We believe that this guideline will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports may provide early signals of effectiveness and/or harm, thereby improving healthcare decision-making.
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Influence of ?-stat and pH-stat blood gas management strategies on cerebral blood flow and oxygenation in patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest: a crossover study.
Crit. Care Med.
PUBLISHED: 04-11-2014
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In patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest, two blood gas management strategies are used regarding the PaCO2 target: ?-stat or pH-stat. We aimed to compare the effects of these strategies on cerebral blood flow and oxygenation.
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High versus low blood-pressure target in patients with septic shock.
N. Engl. J. Med.
PUBLISHED: 03-18-2014
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The Surviving Sepsis Campaign recommends targeting a mean arterial pressure of at least 65 mm Hg during initial resuscitation of patients with septic shock. However, whether this blood-pressure target is more or less effective than a higher target is unknown.
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Favourable 5-year postdischarge survival of comatose patients resuscitated from out-of-hospital cardiac arrest, managed with immediate coronary angiogram on admission.
Eur Heart J Acute Cardiovasc Care
PUBLISHED: 02-25-2014
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On-admission coronary angiogram (CA) with angioplasty (percutaneous coronary intervention, PCI) may improve survival in patients resuscitated from out-of-hospital cardiac arrest (OHCA), but long-term survival data are scarce. We assessed long-term survival in OHCA patients managed with on-admission CA and PCI if indicated and compared survival rates in patients with/without acute coronary syndrome (ACS).
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CHADS2 and CHA2DS2-VASc scores can predict thromboembolic events after supraventricular arrhythmia in the critically ill patients.
J Crit Care
PUBLISHED: 01-05-2014
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Prediction of arterial thromboembolic events (ATEs) in relation to supraventricular arrhythmia (SVA) has been poorly investigated in the intensive care unit (ICU). We aimed at evaluating CHADS2 and CHA2DS2-VASc scores to predict SVA-related ATE in the ICU.
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Respiratory effects of buprenorphine/naloxone alone and in combination with diazepam in naive and tolerant rats.
Toxicol. Lett.
PUBLISHED: 01-03-2014
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Respiratory depression has been attributed to buprenorphine (BUP) misuse or combination with benzodiazepines. BUP/naloxone (NLX) has been marketed as maintenance treatment, aiming at preventing opiate addicts from self-injecting crushed pills. However, to date, BUP/NLX benefits in comparison to BUP alone remain debated. We investigated the plethysmography effects of BUP/NLX in comparison to BUP/solvent administered by intravenous route in naive and BUP-tolerant Sprague-Dawley rats, and in combination with diazepam (DZP) or its solvent. In naive rats, BUP/NLX in comparison to BUP significantly increased respiratory frequency (f, P<0.05) without altering minute volume (VE). In combination to DZP, BUP/NLX significantly increased expiratory time (P<0.01) and decreased f (P<0.01), tidal volume (VT, P<0.001), and VE (P<0.001) while BUP only decreased VT (P<0.5). In BUP-tolerant rats, no significant differences in respiratory effects were observed between BUP/NLX and BUP. In contrast, in combination to DZP, BUP/NLX did not significantly alter the plethysmography parameters, while BUP increased inspiratory time (P<0.001) and decreased f (P<0.01) and VE (P<0.001). In conclusion, differences in respiratory effects between BUP/NLX and BUP are only significant in combination with DZP, with increased depression in naive rats but reduced depression in BUP-tolerant rats. However, BUP/NLX benefits in humans remain to be determined.
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Emerging technologies and challenges for better and safer drugs.
Biotechnol. Lett.
PUBLISHED: 09-08-2013
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Regardless of stringent safety regulations and increased compound selectivity by pharmaceutical companies, prediction of toxicity in humans is still far from perfect and adverse drug reactions are still detected after drug marketing. High costs of failures due to toxicity has led pharmaceutical companies to search for screening methods that would allow detection of toxicity issues at an early stage and improve their preclinical and clinical toxicology. Thanks to the last decades biotechnology revolution, new technologies like toxicogenomics have demonstrated the capacity to improve toxicity assessment. However, our understanding of toxicological mechanisms is still incomplete and a wide range of approaches must be used to gain insight into toxicity issues. Consequently, an array of in silico, in vitro and in vivo methods is utilized to predict toxicity and its causative mechanisms, improving drug development processes and minimizing costs of failure.
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The large spectrum of pulmonary complications following illicit drug use: Features and mechanisms.
Chem. Biol. Interact.
PUBLISHED: 07-31-2013
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Damage to lungs may occur from systemic as well as inhalational exposure to various illegal drugs of abuse. Aspiration pneumonia probably represents the most common pulmonary complication in relation to consciousness impairment. Some pulmonary consequences may be specifically related to one given drug. Prolonged smoking of marijuana may result in respiratory symptoms suggestive of obstructive lung disease. Non-cardiogenic pulmonary edema has been attributed to heroin, despite debated mechanisms including attempted inspiration against a closed glottis, hypoxic damage to alveolar integrity, neurogenic vasoactive response to stress, and opiate-induced anaphylactoid reaction. Naloxone-related precipitated withdrawal resulting in massive sympathetic response with heart stunning has been mistakenly implicated. In crack users, acute respiratory syndromes called "crack-lung" with fever, hemoptysis, dyspnea, and pulmonary infiltration on chest X-rays have been reported up-to 48h after free-base cocaine inhalation, with features of pulmonary edema, interstitial pneumonia, diffuse alveolar hemorrhage, and eosinophil infiltration. The high-temperature of volatilized cocaine and the presence of impurities, as well as cocaine-induced local vasoconstriction have been suggested to explain alveolar damage. Some other drug-related pulmonary insults result from the route of drug self-administration. In intravenous drug users, granulomatous pneumonia with multinodular patterns on thoracic imaging is due to drug contaminants like talcum. Septic embolism from right-sided endocarditis represents an alternative diagnosis in case of sepsis from pulmonary origin. Following inhalation, pneumothorax, and pneumomediastinum have been attributed to increased intrathoracic pressure in relation to vigorous coughing or repeated Valsalva maneuvers, in an attempt to absorb the maximal possible drug amount. In conclusion, pulmonary consequences of illicit drugs are various, resulting in both acute life-threatening conditions and long-term functional respiratory sequelae. A better understanding of their spectrum and the implicated mechanisms of injury should help to improve patient management.
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Longitudinal study assessing the return of chloroquine susceptibility of Plasmodium falciparum in isolates from travellers returning from West and Central Africa, 2000-2011.
Myriam Gharbi, Jennifer A Flegg, Véronique Hubert, Eric Kendjo, Jessica E Metcalf, Lionel Bertaux, Philippe J Guerin, Jacques Le Bras, , Ahmed Aboubaca, Patrice Agnamey, Adela Angoulvant, Patricia Barbut, Didier Basset, Ghania Belkadi, Anne Pauline Bellanger, Dieudonné Bemba, Françoise Benoit-Vica, Antoine Berry, Marie-Laure Bigel, Julie Bonhomme, Françoise Botterel, Olivier Bouchaud, Marie-Elisabeth Bougnoux, Patrice Bourée, Nathalie Bourgeois, Catherine Branger, Laurent Bret, Bernadette Buret, Enrique Casalino, Sylviane Chevrier, Frédérique Conquere de Monbrison, Bernadette Cuisenier, Martin Danis, Marie-Laure Dardé, Ludovic de Gentile, Jean-Marie Delarbre, Pascal Delaunay, Anne Delaval, Guillaume Desoubeaux, Michel Develoux, Jean Dunand, Remy Durand, Odile Eloy, Nathalie Fauchet, Bernard Faugère, Alber Faye, Odile Fenneteau, Pierre Flori, Madeleine Fontrouge, Chantal Garabedian, Françoise Gayandrieu, Nadine Godineau, Pascal Houzé, Sandrine Houzé, Jean-Pierre Hurst, Houria Ichou, Laurence Lachaud, Agathe Lebuisson, Magalie Lefevre, Anne-Sophie Leguern, Gwenae Le Moal, Daniel Lusina, Marie-Claude Machouart, Denis Malvy, Sophie Matheron, Daniéle Maubon, Denis Mechali, Bruno Mégarbane, Guillaume Ménard, Laurence Millon, Muriel Mimoun Aiach, Philippe Minodier, Christelle Morelle, Gilles Nevez, Philippe Parola, Daniel Parzy, Olivier Patey, Pierre Patoz, Pascale Penn, Alice Pérignon, Stephane Picot, Jean-Etienne Pilo, Isabelle Poilane, Denis Pons, Marie Poupart, Bruno Pradines, Didier Raffenot, Christophe Rapp, Marie-Catherine Receveur, Claudine Sarfati, Yaye Senghor, Fabrice Simon, Jean-Yves Siriez, Nicolas Taudon, Marc Thellier, Maxime Thouvenin, Dominique Toubas.
Malar. J.
PUBLISHED: 01-19-2013
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Chloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system.
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Respiratory effects of diazepam/methadone combination in rats: a study based on concentration/effect relationships.
Drug Alcohol Depend
PUBLISHED: 01-15-2013
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Methadone may cause respiratory depression and fatalities. Concomitant use of benzodiazepines in methadone-treated patients for chronic pain or as maintenance therapy for opiate abuse is common. However, the exact contribution of benzodiazepines to methadone-induced respiratory toxicity remains debatable.
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Gender and strain contributions to the variability of buprenorphine-related respiratory toxicity in mice.
Toxicology
PUBLISHED: 01-14-2013
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While most deaths from asphyxia related to buprenorphine (BUP) overdose have been reported in males, higher plasma concentrations of BUP and its toxic metabolite norbuprenorphine (NBUP) have been observed in females. We previously demonstrated that P-glycoprotein (P-gp) modulation at the blood-brain barrier (BBB) contributes highly to BUP-related respiratory toxicity, by limiting NBUP entrance into the brain. In this work, we sought to investigate the role of P-gp-mediated transport at the BBB in gender and strain-related variability of BUP and NBUP-induced respiratory effects in mice. Ventilation was studied using plethysmography, P-gp expression using western blot, and transport at the BBB using in situ cerebral perfusion. In male Fvb and Swiss mice, BUP was responsible for ceiling respiratory effects. NBUP-related reduction in minute volume was dose-dependent but more marked in Fvb (p<0.01 at 1mg/kg NBUP and p<0.001 at 3 and 9mg/kg NBUP) than in Swiss mice (p<0.001 at 9mg/kg NBUP). Female Fvb mice were more susceptible to BUP than males with significantly increased inspiratory time (p<0.05) and to NBUP with significantly increased expiratory time (p<0.01). Following BUP administration, plasma BUP concentrations were significantly higher (p<0.01) and plasma NBUP concentrations significantly lower (p<0.001) in Fvb mice compared to Swiss mice. Plasma BUP concentrations were significantly higher (p<0.05) and plasma NBUP concentrations significantly lower (p<0.01) in male compared to female Fvb mice. In contrast, following NBUP administration, comparable plasma NBUP concentrations were observed in both genders and strains. No differences in P-gp expression or BUP and NBUP transport across the BBB were observed between male and female Fvb mice as well as between Swiss and Fvb mice. Our results suggest that P-gp-mediated transport across the BBB does not play a key-role in gender and strain-related variability in BUP and NBUP-induced respiratory toxicity in mice. Both gender- and strain-related differences in respiratory effects of BUP could be attributed to BUP itself rather than to its metabolite, NBUP.
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Comparison of tolerance to morphine-induced respiratory and analgesic effects in mice.
Toxicol. Lett.
PUBLISHED: 01-04-2013
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Morphine is responsible for severe poisonings in chronically treated patients. We hypothesize that toxicity could be related to the development of weaker tolerance for morphine-induced deleterious respiratory effects in comparison to analgesic effects. Our objectives were to compare tolerance to both effects in mice and investigate possible mechanisms for such possible differences. Tolerance to morphine-induced analgesia and respiratory effects was assessed using hot plate response latencies and plethysmography, respectively. Mechanisms of tolerance were investigated using binding studies to mu-opioid receptors (MOR) and adenylate cyclase (AC) activity measurement in homogenates of cell membranes from the periaqueductal gray region (PAG) and brainstem. Morphine (2.5 mg/kg) was responsible for analgesia with significant increase in inspiratory time. Acute tolerance to analgesia (p<0.01) and effects on respiratory frequency (p<0.05) was observed in mice pre-treated with 100 mg/kg morphine in comparison to saline. Following repetitive administration (2.5 mg/kg/day during 10 days), we observed a 13-fold increase in the effective dose-50% (ED??) of morphine-induced analgesia in comparison to a 2- or 4-fold increase in the ED?? of its related increase in inspiratory time determined in air and 4% CO?, respectively. No significant alteration in MOR expression was observed in either PAG or brainstem following repeated morphine administration. However, in PAG, in contrast to brainstem, superactivation of AC was observed in morphine-treated mice in comparison to controls (p<0.05). In conclusion, tolerance to morphine-induced respiratory effects is much more limited than tolerance to its analgesic effects in repeatedly morphine-treated mice. The difference in morphine-induced AC activation between the brainstem and the PAG contributes to the observed difference in tolerance between both morphine effects.
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Vascular access sites for acute renal replacement in intensive care units.
Clin J Am Soc Nephrol
PUBLISHED: 11-10-2011
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Several temporary venous catheterizations are sometimes required for acute renal replacement therapy (RRT) in the intensive care unit (ICU). This study compares first and second catheterizations in the femoral and jugular veins in terms of patient safety.
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Role of cardiac troponin in the diagnosis of acute myocardial infarction in comatose patients resuscitated from out-of-hospital cardiac arrest.
Resuscitation
PUBLISHED: 07-31-2011
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Troponin is a major diagnostic criterion of acute myocardial infarction (AMI) but in out-of-hospital cardiac arrest (OHCA) patients, its diagnostic value may be altered by cardiopulmonary resuscitation.
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Severe and prolonged neurologic toxicity following subcutaneous chlorpyrifos self-administration: a case report.
Clin Toxicol (Phila)
PUBLISHED: 03-05-2011
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Organophosphate poisoning by oral or inhalation routes is characterized by a typical time-course of clinical features.
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Important questions asked by family members of intensive care unit patients.
Crit. Care Med.
PUBLISHED: 03-02-2011
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Relatives often lack important information about intensive care unit patients. High-quality information is crucial to help relatives overcome the often considerable situational stress and to acquire the ability to participate in the decision-making process, most notably regarding the appropriate level of care. We aimed to develop a list of questions important for relatives of patients in the intensive care unit.
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Postintensive care unit psychological burden in patients with chronic obstructive pulmonary disease and informal caregivers: A multicenter study.
Crit. Care Med.
PUBLISHED: 02-08-2011
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To determine the prevalence and risk factors of symptoms of anxiety, depression, and posttraumatic stress disorder-related symptoms in patients with chronic obstructive pulmonary disease and their relatives after an intensive care unit stay.
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Serum sodium abnormalities during nonexertional heatstroke: incidence and prognostic values.
Am J Emerg Med
PUBLISHED: 02-03-2011
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Although heatstroke is often associated with dehydration, the clinical significance of serum sodium abnormalities in patients with heat-related illness during heat wave has been poorly documented.
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Predictors of mortality in verapamil overdose: usefulness of serum verapamil concentrations.
Basic Clin. Pharmacol. Toxicol.
PUBLISHED: 01-26-2011
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Verapamil poisoning may result in life-threatening cardiovascular morbidities and fatalities. To date, prognosticators of mortality have been poorly investigated and the use of serum verapamil concentration for prognosis remains unclear. We aimed to evaluate the ability of usual clinical and laboratory parameters including serum verapamil concentrations measured on admission to predict outcome (survival versus death) in verapamil poisoning. We reviewed the medical records of all intentional and symptomatic verapamil poisonings admitted over 8 years to two medical intensive care units. Clinical and laboratory parameters were measured in 65 patients, and final outcomes of survival or death recorded. A multivariable analysis was conducted to evaluate the prognostic values of recorded parameters. Life-threatening complications of verapamil poisonings included shock (62%), atrioventricular blocks (24%), sinoatrial blocks (20%), acute respiratory distress syndrome (19%) and cardiac arrest (11%) resulting in death (8%). Verapamil concentration measured on intensive care unit admission was the only independent factor associated with mortality (p = 0.01). The optimal verapamil cut-off point was 5.0 ?M (100% sensitivity, 91% specificity), which conferred a 2.76-times increase in odds of fatality. In conclusion, cardiovascular monitoring and assessment of organ failure are vital in symptomatic verapamil poisonings. The serum verapamil concentration has excellent prognostic ability for predicting fatality in verapamil overdose.
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Usefulness of routine laboratory parameters in the decision to treat refractory cardiac arrest with extracorporeal life support.
Resuscitation
PUBLISHED: 01-24-2011
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To evaluate the usefulness of routine laboratory parameters in the decision to treat refractory cardiac arrest patients with extracorporeal life support (ECLS).
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Value of post-resuscitation electrocardiogram in the diagnosis of acute myocardial infarction in out-of-hospital cardiac arrest patients.
Resuscitation
PUBLISHED: 01-18-2011
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Diagnosis of acute myocardial infarction (AMI) in out-of-hospital cardiac arrest (OHCA) patients is important because immediate coronary angiography with coronary angioplasty could improve outcome in this setting. However, the value of acute post-resuscitation electrocardiographic (ECG) data for the detection of AMI is debatable.
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Usefulness of the serum lactate concentration for predicting mortality in acute beta-blocker poisoning.
Clin Toxicol (Phila)
PUBLISHED: 12-30-2010
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Serum lactate measured in the emergency department was recently assessed as an excellent prognosticator of drug-overdose fatality, with the optimal lactate cutoff point being 3.0 mmol/L. However, lactates role has never been specifically studied in beta-blocker poisonings.
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Blood concentrations are better predictors of chioroquine poisoning severity than plasma concentrations: a prospective study with modeling of the concentration/effect relationships.
Clin Toxicol (Phila)
PUBLISHED: 11-17-2010
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Chloroquine causes rare but life-threatening toxicity. The prognostic value of plasma chloroquine concentrations in acute poisonings remains poorly investigated. We investigated the hypothesis that blood chloroquine concentrations better predicted chloroquine poisoning severity than plasma concentrations.
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Functional outcome after convulsive status epilepticus.
Crit. Care Med.
PUBLISHED: 10-05-2010
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Few outcome data are available about convulsive status epilepticus managed in the intensive care unit. We studied 90-day functional outcomes and their determinants in patients with convulsive status epilepticus.
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Dichlorvos, chlorpyrifos oxon and Aldicarb adducts of butyrylcholinesterase, detected by mass spectrometry in human plasma following deliberate overdose.
J Appl Toxicol
PUBLISHED: 09-03-2010
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The goal of this study was to develop a method to detect pesticide adducts in tryptic digests of butyrylcholinesterase in human plasma from patients poisoned by pesticides. Adducts to butyrylcholinesterase in human serum may serve as biomarkers of pesticide exposure because organophosphorus and carbamate pesticides make a covalent bond with the active site serine of butyrylcholinesterase. Serum samples from five attempted suicides (with dichlorvos, Aldicarb, Baygon and an unknown pesticide) and from one patient who accidentally inhaled dichlorvos were analyzed. Butyrylcholinesterase was purified from 2 ml serum by ion exchange chromatography at pH 4, followed by procainamide affinity chromatography at pH 7. The purified butyrylcholinesterase was denatured, digested with trypsin and the modified peptide isolated by HPLC. The purified peptide was analyzed by multiple reaction monitoring in a QTRAP 4000 mass spectrometer. This method successfully identified the pesticide-adducted butyrylcholinesterase peptide in four patients whose butyrylcholinesterase was inhibited 60-84%, but not in two patients whose inhibition levels were 8 and 22%. It is expected that low inhibition levels will require analysis of larger serum plasma volumes. In conclusion, a mass spectrometry method for identification of exposure to live toxic pesticides has been developed, based on identification of pesticide adducts on the active site serine of human butyrylcholinesterase.
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Continuous renal replacement therapy may increase the risk of catheter infection.
Clin J Am Soc Nephrol
PUBLISHED: 06-17-2010
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Little is known about the risks of catheter-related infections in patients undergoing intermittent hemodialysis (IHD) as compared with continuous renal replacement therapy (CRRT) techniques. We compared the two modalities among critically ill adults requiring acute renal replacement therapy (RRT).
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Early laryngeal injury and complications because of endotracheal intubation in acutely poisoned patients: a prospective observational study.
Clin Toxicol (Phila)
PUBLISHED: 05-29-2010
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Tracheal intubation may represent a life-saving supportive measure in many acutely poisoned patients. Although considered as a safe procedure, intubation may rapidly damage laryngeal mucosa. The incidence and nature of short-duration intubation-associated laryngeal injuries are unknown in the population of poisoned patients.
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Severe imported falciparum malaria: a cohort study in 400 critically ill adults.
PLoS ONE
PUBLISHED: 05-19-2010
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Large studies on severe imported malaria in non-endemic industrialized countries are lacking. We sought to describe the clinical spectrum of severe imported malaria in French adults and to identify risk factors for mortality at admission to the intensive care unit.
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Detection of adduct on tyrosine 411 of albumin in humans poisoned by dichlorvos.
Toxicol. Sci.
PUBLISHED: 04-15-2010
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Studies in mice and guinea pigs have shown that albumin is a new biomarker of organophosphorus toxicant (OP) and nerve agent exposure. Our goal was to determine whether OP-labeled albumin could be detected in the blood of humans exposed to OP. Blood from four OP-exposed patients was prepared for mass spectrometry analysis by digesting 0.010 ml of serum with pepsin and purifying the labeled albumin peptide by offline high performance liquid chromatography. Dimethoxyphosphate-labeled tyrosine 411 was identified in albumin peptides VRY(411)TKKVPQVSTPTL and LVRY(411)TKKVPQVSTPTL from two patients who had attempted suicide with dichlorvos. The butyrylcholinesterase activity in these serum samples was inhibited 80%. A third patient whose serum BChE activity was inhibited 8% by accidental inhalation of dichlorvos had undetectable levels of adduct on albumin. A fourth patient whose BChE activity was inhibited 60% by exposure to chlorpyrifos had no detectable adduct on albumin. This is the first report to demonstrate the presence of OP-labeled albumin in human patients. It is concluded that tyrosine 411 of human albumin is covalently modified in the serum of humans poisoned by dichlorvos and that the modification is detectable by mass spectrometry. The special reactivity of tyrosine 411 with OP suggests that other proteins may also be modified on tyrosine. Identification of other OP-modified proteins may lead to an understanding of neurotoxic symptoms that appear long after the initial OP exposure.
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Elevation of cardiac troponin I during non-exertional heat-related illnesses in the context of a heatwave.
Crit Care
PUBLISHED: 03-31-2010
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The prognostic value of cardiac troponin I (cTnI) in patients having a heat-related illness during a heat wave has been poorly documented.
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Prospective comparative assessment of buprenorphine overdose with heroin and methadone: clinical characteristics and response to antidotal treatment.
J Subst Abuse Treat
PUBLISHED: 01-06-2010
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Buprenorphine is a partial opioid agonist with a "ceiling effect" for respiratory depression. Despite this, it has been associated with severe overdoses. Conflicting data exist regarding its response in overdose to naloxone. We compared clinical overdose characteristics of buprenorphine with heroin and methadone and assessed responses to naloxone and flumazenil. Patients admitted to two intensive care units with severe opioid overdoses were enrolled into this 4-year prospective study. Urine and blood toxicological screening were performed to identify overdoses involving predominantly buprenorphine, heroin, or methadone. Eighty-four patients with heroin (n = 26), buprenorphine (n = 39), or methadone (n = 19) overdoses were analyzed. In the buprenorphine group, sedative drug coingestions were frequent (95%), whereas in the methadone group, suicide attempts were significantly more often reported (p = .0007). Buprenorphine overdose induced an opioid syndrome not differing significantly from heroin and methadone in mental status (as measured by Glasgow Coma Score) or arterial blood gases. Mental status depression was not reversed in buprenorphine overdoses with naloxone (0.4-0.8 mg) but did improve with flumazenil (0.2-1 mg) if benzodiazepines were coingested. In conclusion, buprenorphine overdose causes an opioid syndrome clinically indistinguishable from heroin and methadone. Although mental status and respiratory depression are often unresponsive to low-dose naloxone, flumazenil may be effective in buprenorphine overdoses involving benzodiazepines.
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Extracorporeal life support in a case of fatal flecainide and betaxolol poisoning allowing successful cardiac allograft.
Ann Emerg Med
PUBLISHED: 01-04-2010
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Use of cardiac allograft for transplantation from donors after acute poisoning is a matter of debate because of potential toxic organ injuries, especially if death results from massive ingestion of cardiotoxic drugs. We report successful allograft cardiac transplantation from a brain-dead patient after severe flecainide and betaxolol self-poisoning requiring extracorporeal life support. Extracorporeal life support was initiated in the emergency department because of a refractory cardiac arrest caused by the cardiotoxicants ingestion and continued after the onset of brain death to facilitate organ donation of the heart, liver, and kidneys. Forty-five months later, each organ recipient was alive, with normal graft function.
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Blood cocaine and metabolite pharmacokinetics after cardiac arrest in a body-packer case.
Hum Exp Toxicol
PUBLISHED: 11-19-2009
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Cocaine body packing, the internal concealment of cocaine for transportation between countries, may expose to life-threatening intoxications. No data is currently available on the pharmacokinetics of cocaine and its metabolites when a packet rupture occurs in a body packer.
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Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2).
Int. J. Neuropsychopharmacol.
PUBLISHED: 11-04-2009
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Drug interaction with P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may influence its tissue disposition including blood-brain barrier transport and result in potent drug-drug interactions. The limited data obtained using in-vitro models indicate that methadone, buprenorphine, and cannabinoids may interact with human P-gp; but almost nothing is known about drugs of abuse and BCRP. We used in vitro P-gp and BCRP inhibition flow cytometric assays with hMDR1- and hBCRP-transfected HEK293 cells to test 14 compounds or metabolites frequently involved in addiction, including buprenorphine, norbuprenorphine, methadone, ibogaine, cocaine, cocaethylene, amphetamine, N-methyl-3,4-methylenedioxyamphetamine, 3,4-methylenedioxyamphetamine, nicotine, ketamine, Delta9-tetrahydrocannabinol (THC), naloxone, and morphine. Drugs that in vitro inhibited P-gp or BCRP were tested in hMDR1- and hBCRP-MDCKII bidirectional transport studies. Human P-gp was significantly inhibited in a concentration-dependent manner by norbuprenorphine>buprenorphine>methadone>ibogaine and THC. Similarly, BCRP was inhibited by buprenorphine>norbuprenorphine>ibogaine and THC. None of the other tested compounds inhibited either transporter, even at high concentration (100 microm). Norbuprenorphine (transport efflux ratio approoximately 11) and methadone (transport efflux ratio approoximately 1.9) transport was P-gp-mediated; however, with no significant stereo-selectivity regarding methadone enantiomers. BCRP did not transport any of the tested compounds. However, the clinical significance of the interaction of norbuprenorphine with P-gp remains to be evaluated.
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Characteristics and comparative severity of respiratory response to toxic doses of fentanyl, methadone, morphine, and buprenorphine in rats.
Toxicol. Lett.
PUBLISHED: 08-26-2009
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Opioids are known to induce respiratory depression. We aimed to characterize in rats the effects of four opioids on arterial blood gases and plethysmography after intraperitoneal administration at 80% of their LD(50) in order to identify opioid molecule-specific patterns and classify response severity. Opioid-receptor (OR) antagonists, including intravenous 10 mg kg(-1)-naloxonazine at 5 min [mu-OR antagonist], subcutaneous 30 mg kg(-1)-naloxonazine at 24 h [mu1-OR antagonist], subcutaneous 3 mg kg(-1)-naltrindole at 45 min [delta-OR antagonist], and subcutaneous 5 mg kg(-1)-Nor-binaltorphimine at 6 h [kappa-OR antagonist] were pre-administered to test the role of each OR. Methadone, morphine, and fentanyl significantly decreased PaO(2) (P<0.001) and increased PaCO(2) (P<0.05), while buprenorphine only decreased PaO(2) (P<0.05). While all opioids significantly increased inspiratory time (T(I), P<0.001), methadone and fentanyl also increased expiratory time (T(E), P<0.05). Intravenous 10 mg kg(-1)-naloxonazine at 5 min completely reversed opioid-related effects on PaO(2) (P<0.05), PaCO(2) (P<0.001), T(I) (P<0.05), and T(E) (P<0.01) except in buprenorphine. Subcutaneous 30 mg kg(-1)-naloxonazine at 24 h completely reversed effects on PaCO(2) (P<0.01) and T(E) (P<0.001), partially reversed effects on T(I) (P<0.001), and did not reverse effects on PaO(2). Naltrindole reversed methadone-induced T(E) increases (P<0.01) but worsened fentanyls effect on PaCO(2) (P<0.05) and T(I) (P<0.05). Nor-binaltorphimine reversed morphine- and buprenorphine-induced T(I) increases (P<0.001) but worsened methadones effect on PaO(2) (P<0.05) and morphine (P<0.001) and buprenorphines (P<0.01) effects on pH. In conclusion, opioid-related respiratory patterns are not uniform. Opioid-induced hypoxemia as well as increases in T(I) and T(E) are caused by mu-OR, while delta and kappa-OR roles appear limited, depending on the specific opioid. Regarding severity of opioid-induced respiratory effects at 80% of their LD(50), all drugs increased T(I). Methadone and fentanyl induced hypoxemia, hypercapnia, and T(E) increases, morphine caused both hypoxemia and hypercapnia while buprenorphine caused only hypoxemia.
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Carbofuran poisoning detected by mass spectrometry of butyrylcholinesterase adduct in human serum.
J Appl Toxicol
PUBLISHED: 07-29-2009
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Carbofuran is a pesticide whose acute toxicity is due to inhibition of acetylcholinesterase. Butyrylcholinesterase (BChE) in plasma is inhibited by carbofuran and serves as a biomarker of poisoning by carbofuran. The goal was to develop a method to positively identify poisoning by carbofuran. Sera from an attempted murder and an attempted suicide were analyzed for the presence of carbofuran adducts on BChE. The BChE from 1 ml of serum was rapidly purified on a 0.2 ml procainamide-Sepharose column. Speed was essential because the carbofuran-BChE adduct decarbamylates with a half-life of about 2 h. The partially purified BChE was boiled to denature the protein, thus stopping decarbamylation and making the protein vulnerable to digestion with trypsin. The labeled peptide was partially purified by HPLC before analysis by LC/MS/MS in the multiple reaction monitoring mode on the QTRAP 2000 mass spectrometer. Carbofuran was found to be covalently bound to Ser 198 of human BChE in serum samples from two poisoning cases. Multiple reaction monitoring triggered MS/MS spectra positively identified the carbofuran-BChE adduct. In conclusion a mass spectrometry method to identify carbofuran poisoning in humans has been developed. The method uses 1 ml of serum and detects low-level exposure associated with as little as 20% inhibition of plasma butyrylcholinesterase.
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Prognostic factors in non-exertional heatstroke.
Intensive Care Med
PUBLISHED: 07-03-2009
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To identify the prognostic factors associated with mortality in heat-related illness.
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Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial.
Lancet
PUBLISHED: 07-01-2009
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Critically ill patients often require emergency intubation. The use of etomidate as the sedative agent in this context has been challenged because it might cause a reversible adrenal insufficiency, potentially associated with increased in-hospital morbidity. We compared early and 28-day morbidity after a single dose of etomidate or ketamine used for emergency endotracheal intubation of critically ill patients.
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Poisoning-related bowel infarction: characteristics and outcomes.
Clin Toxicol (Phila)
PUBLISHED: 06-05-2009
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Bowel infarction (BI) is a rare complication of poisoning. We aimed to describe the characteristics of BI in poisoned patients compared to nonpoisoned patients.
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Delayed immunosuppressive treatment in life-threatening paraquat ingestion: a case report.
J Med Toxicol
PUBLISHED: 05-06-2009
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Combined glucocorticoids and cyclophosphamide pulse therapy showed promising results in moderate-to-severe paraquat poisonings to reduce life-threatening respiratory complications. Its benefit has been observed when given early in the course of poisoning; however, whether its delayed administration remains beneficial is unknown.
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[Gamma-hydroxybutyric acid (GHB): more than a date rape drug, a potentially addictive drug].
Presse Med
PUBLISHED: 03-25-2009
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According to available information, GHB and its precursors--gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD)--are used especially in a nightlife scene characterized by the search for amplified sensations through the combination of electronic music, marathon dancing, and substance abuse. Evidence indicates that GHB/GHL is used particularly in some subpopulations and in places, such as in gay nightclubs. Commonly known as Gorliquid ecstasy, it was misused in the 1980s for its bodybuilding effects and in the 1990s as a recreational drug at music venues. In the same period, media coverage of the use of GHB in sexual assault (often referred to as date rape) brought the drug into the spotlight. GHB/GHL addiction is a recognized clinical entity evidenced by severe withdrawal symptoms when the drug is abruptly discontinued after regular or chronic use. There is evidence that negative health and social consequences may occur in recreational and chronic users. Nonfatal overdoses and deaths related to GHB have been reported. These undesirable effects and especially the deaths appear to have prompted campaigns to limit the use of GHB. Clinicians must also be aware of GBL, which is being sold and used as a substitute for GHB.
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Lithium poisoning: is determination of the red blood cell lithium concentration useful?
Clin Toxicol (Phila)
PUBLISHED: 02-10-2009
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Despite a narrow therapeutic index, lithium remains a cornerstone for the treatment of bipolar disease. As lithium poisoning may result in life-threatening neurotoxicity, measurement of the lithium concentration is mandatory in drug monitoring as well as for the diagnosis and prognostic evaluation of lithium poisoning. However, toxic symptoms do not always correlate with plasma concentrations. Therefore, more reliable indicators have been proposed, including measurement of the red blood cell (RBC) lithium concentration and the RBC-to-plasma lithium ratio.
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Respiratory toxicity of buprenorphine results from the blockage of P-glycoprotein-mediated efflux of norbuprenorphine at the blood-brain barrier in mice.
Crit. Care Med.
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Deaths due to asphyxia as well as following acute poisoning with severe respiratory depression have been attributed to buprenorphine in opioid abusers. However, in human and animal studies, buprenorphine exhibited ceiling respiratory effects, whereas its metabolite, norbuprenorphine, was assessed as being a potent respiratory depressor in rodents. Recently, norbuprenorphine, in contrast to buprenorphine, was shown in vitro to be a substrate of human P-glycoprotein, a drug-transporter involved in all steps of pharmacokinetics including transport at the blood-brain barrier. Our objectives were to assess P-glycoprotein involvement in norbuprenorphine transport in vivo and study its role in the modulation of buprenorphine-related respiratory effects in mice.
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Mechanisms of high-dose citalopram-induced death in a rat model.
Toxicology
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Citalopram, a selective serotonin reuptake inhibitor, is generally considered to be of low toxicity. However, serotonin syndrome, seizures, electrocardiographic abnormalities as well as respiratory failure and death have been described in patients with citalopram overdose. The mechanisms of severe toxicity remain unclear. Our objective was to study the mechanisms of death following high-dose citalopram administration in Sprague Dawley rats. The median lethal dose (MLD) of intraperitoneal (i.p.) citalopram was measured using Dixon & Bruces up-and-down method at 102 mg/kg. Dose-effect relationships of citalopram-induced clinical features, alterations in arterial blood gas and plethysmography, and disturbances in blood lactate, plasma and platelet serotonin concentrations were studied. Seizures were significantly increased in rats receiving 80% and 120% of citalopram MLD versus controls (p<0.05 and p<0.01, respectively). A significant decrease in body temperature was observed after 90 min in rats treated with doses >60% MLD in comparison to controls (p<0.05). The occurrence of serotonin behavioural syndrome was comparable in all groups. Citalopram administration did not result in significant hypoxemia, hypercapnia and lactate elevation. However, a significant moderate increase in the inspiratory time (p<0.05) accompanied with an expiratory braking was observed. A significant dose-related linear decrease in platelet serotonin and increase in plasma serotonin concentrations were measured (p<0.05). Pre-treatments of rats receiving 120% of citalopram MLD with diazepam (1.77 mg/kg) and cyproheptadine (17.1mg/kg) prevented seizures and death, but propranolol pre-treatment was ineffective. Neuroprotection with diazepam and cyproheptadine was not associated with decreased serotonin plasma concentrations. In conclusion, citalopram-induced deaths resulted from seizures in relation to serotonin release, whilst respiratory and metabolic toxicity was mild. Our observations support the role of serotonin-induced neurotoxicity in citalopram overdose and suggest that cyproheptadine and benzodiazepines, but not beta-blockers, may have a role in the management of citalopram toxicity.
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Extracorporeal treatment for thallium poisoning: recommendations from the EXTRIP Workgroup.
Clin J Am Soc Nephrol
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The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning. To test and validate its methods, the workgroup reviewed data for thallium (Tl).
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Drug Fever: a descriptive cohort study from the French national pharmacovigilance database.
Drug Saf
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Although known as a rare adverse drug reaction (ADR), drug fever (DF) remains an important issue in medicine, with the risk of leading to inappropriate and potentially harmful diagnostic and therapeutic interventions. Only sparse data regarding DF have been published.
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[Recommendations for the prescription, implementation and interpretation of medical examinations in biology in the context of severe poisoning].
Ann. Biol. Clin. (Paris)
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A multidisciplinary working group named "Toxicology and clinical biology" and whose members belong to the French Society of Clinical Biology (SFBC), Critical Care Medicine Society of French Language (SRLF), the French Society of Medical Emergency (SFMU), the French Society of Analytical Toxicology (SFTA), the Society of Clinical Toxicology (STC), and the National College of Biochemistry (CNBH) updated the professional practice recommendations published in 2003. These recommendations aimed the biologists who are not specialized in toxicology and more largely all the health professionals involved the management of severely poisoned patients. Among the data published in the initial edition, only the major table dealing with severe poisonings was updated, as all other supplements remained valid. The current revised table details poisonings due to fifty-five different xenobiotics and presents their main clinical features, useful biomarkers of toxicity, methods of identification or assays available in the emergent setting with their respective relevance and recommended delays to obtain their result. Assessments with a good agreement among the working group members regarding all laboratory issues for poisoning management are presented. A table updates the list of the main currently useful antidotes. A section on the value and place of toxicology screening was added.
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The clinical toxicology of ?-hydroxybutyrate, ?-butyrolactone and 1,4-butanediol.
Clin Toxicol (Phila)
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Gamma-hydroxybutyrate (GHB) and its precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), are drugs of abuse which act primarily as central nervous system (CNS) depressants. In recent years, the rising recreational use of these drugs has led to an increasing burden upon health care providers. Understanding their toxicity is therefore essential for the successful management of intoxicated patients. We review the epidemiology, mechanisms of toxicity, toxicokinetics, clinical features, diagnosis, and management of poisoning due to GHB and its analogs and discuss the features and management of GHB withdrawal.
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A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.
PLoS ONE
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To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis.
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The EXTRIP (EXtracorporeal TReatments In Poisoning) workgroup: guideline methodology.
Clin Toxicol (Phila)
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Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.
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