Anesthesiology
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The authors describe the preclinical pharmacological properties of GAL-021, a novel peripheral chemoreceptor modulator. ⋯ GAL-021 behaved as a breathing control modulator in rodents and nonhuman primates and diminished opioid-induced respiratory depression without compromising opioid analgesia. It acted predominantly at the carotid body, in part by inhibiting KCa1.1 channels. Its preclinical profile qualified the compound to enter clinical trials to assess effects on breathing control disorders such as drug (opioid)-induced respiratory depression and sleep apnea.
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Observational Study
Visuospatial Ability as a Predictor of Novice Performance in Ultrasound-guided Regional Anesthesia.
Visuospatial ability correlates positively with novice performance of simple laparoscopic tasks. The aims of this study were to identify whether visuospatial ability could predict technical performance of an ultrasound-guided needle task by novice operators and to describe how emotional state, intelligence, and fear of failure impact on this. ⋯ An MRT predicts novice performance of an ultrasound-guided needling task on a turkey model and as a trait measure could be used as a tool to focus training resources on less-able individuals. Anxiety adversely affects performance. Therefore, both may prove useful in directing targeted training in ultrasound-guided regional anesthesia.
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Clinical Trial
Methadone Pharmacogenetics: CYP2B6 Polymorphisms Determine Plasma Concentrations, Clearance, and Metabolism.
Interindividual variability in methadone disposition remains unexplained, and methadone accidental overdose in pain therapy is a significant public health problem. Cytochrome P4502B6 (CYP2B6) is the principle determinant of clinical methadone elimination. The CYP2B6 gene is highly polymorphic, with several variant alleles. CYP2B6.6, the protein encoded by the CYP2B6*6 polymorphism, deficiently catalyzes methadone metabolism in vitro. This investigation determined the influence of CYP2B6*6, and other allelic variants encountered, on methadone concentrations, clearance, and metabolism. ⋯ CYP2B6 polymorphisms influence methadone plasma concentrations, because of altered methadone metabolism and thus clearance. Genetic influence is greater for oral than IV methadone and S- than R-methadone. CYP2B6 pharmacogenetics explains, in part, interindividual variability in methadone elimination. CYP2B6 genetic effects on methadone metabolism and clearance may identify subjects at risk for methadone toxicity and drug interactions.