ORCID Profile
0000-0003-0639-5536
Current Organisation
Centre Hospitalier Universitaire Vaudois
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Publisher: Public Library of Science (PLoS)
Date: 08-04-2011
Publisher: Springer Science and Business Media LLC
Date: 14-11-2008
Abstract: In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N-methyl-D-aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2 g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex- and age- matched healthy controls (p=0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo (p=0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia.
Publisher: BMJ
Date: 17-05-2011
Abstract: There are no evidence syntheses available to guide clinicians on when to titrate antihypertensive medication after initiation. To model the blood pressure (BP) response after initiating antihypertensive medication. Data sources electronic databases including Medline, Embase, Cochrane Register and reference lists up to December 2009. Trials that initiated antihypertensive medication as single therapy in hypertensive patients who were either drug naive or had a placebo washout from previous drugs. Office BP measurements at a minimum of two weekly intervals for a minimum of 4 weeks. An asymptotic approach model of BP response was assumed and non-linear mixed effects modelling used to calculate model parameters. Eighteen trials that recruited 4168 patients met inclusion criteria. The time to reach 50% of the maximum estimated BP lowering effect was 1 week (systolic 0.91 weeks, 95% CI 0.74 to 1.10 diastolic 0.95, 0.75 to 1.15). Models incorporating drug class as a source of variability did not improve fit of the data. Incorporating the presence of a titration schedule improved model fit for both systolic and diastolic pressure. Titration increased both the predicted maximum effect and the time taken to reach 50% of the maximum (systolic 1.2 vs. 0.7 weeks diastolic 1.4 vs. 0.7 weeks). Estimates of the maximum efficacy of antihypertensive agents can be made early after starting therapy. This knowledge will guide clinicians in deciding when a newly started antihypertensive agent is likely to be effective or not at controlling BP.
Publisher: SAGE Publications
Date: 28-02-2019
Abstract: Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infections are rare but associated with very high mortality rates. We report the case of a 14-year-old patient with Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infection and Influenza B pneumonia requiring veno-arterial extra-corporeal membrane oxygenator for refractory shock. In the absence of response to conventional therapy, we have inserted a Cytosorb® cartridge within the extra-corporeal membrane oxygenator circuit. A spectacular decrease in vasopressor requirements followed. Since clindamycin, a key component of Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus treatment, might be removed by Cytosorb® hemoadsorption, we have performed serial plasma concentrations measurements of the drug. Based on these measurements, we were able to develop a pharmacokinetic model incorporating variable plasma clearance. Patient’s exposure was estimated before, during and after Cytosorb® hemoadsorption. According to this model, Cytosorb® hemoadsorption did not seem to result in significant clindamycin removal. Cytosorb® hemoadsorption during Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infection appears safe and feasible and no adaptation of clindamycin dosage seems necessary
No related grants have been discovered for Thierry Buclin.