Anesthesiology
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Randomized Controlled Trial
Mechanism-based pharmacokinetic-pharmacodynamic modeling of the antinociceptive effect of buprenorphine in healthy volunteers.
The objective of this investigation was to characterize the pharmacokinetic-pharmacodynamic relation of buprenorphine's antinociceptive effect in healthy volunteers. ⋯ This is consistent with observations in rats, suggesting that the rate-limiting step in the onset and offset of the antinociceptive effect is biophase distribution rather than slow receptor association-dissociation. In the dose range studied, no saturation of receptor occupancy occurred explaining the lack of a ceiling effect for antinociception.
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Randomized Controlled Trial
Short thyromental distance: a predictor of difficult intubation or an indicator for small blade selection?
Short thyromental distance (TMD; < 5 cm) has been correlated with difficult direct laryngoscopic intubation in adult patients. The authors hypothesized that a smaller Macintosh curved blade (No. 2 MCB) would improve the predicted difficult laryngoscopy in short-TMD patients over that with a standard Macintosh curved blade (No. 3 MCB). ⋯ The predicted difficult laryngoscopy and intubation with the use of the adult No. 3 MCB in standard adult patients with a TMD < or = 5 cm is significantly easier with use of the smaller No. 2 MCB.
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Neuropathic pain and radicular low back pain both have a major impact on human health worldwide. Microarray gene analysis on central nervous system tissues holds great promise for discovering novel targets for persistent pain modulation. ⋯ These two models of persistent pain produce similar allodynic outcomes but produce differential gene expression. These results suggest that diverging mechanisms lead to a common behavioral outcome in these pain models. Furthermore, these distinct pathophysiologic mechanisms in neuropathic versus radicular pain may implicate unique drug therapies for these types of chronic pain syndromes.
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Mutations in the ryanodine type 1 receptor (RyR1) are causative for malignant hyperthermia. Studies in human B lymphocytes have shown that measurement of RyR1-mediated intracellular Ca(2+) (Ca(2+)(i)) release can differentiate between normal and malignant hyperthermia-susceptible individuals. The authors have further developed the B-cell assay by pharmacologically characterizing RyR1-mediated Ca release in two normal human B-cell lines and demonstrating increased sensitivity of lymphocytes to the RyR1 agonist 4-chloro-m-cresol (4-CmC) in the porcine model of MH. ⋯ RyR1-mediated Ca(2+) signals can be pharmacologically distinguished from other intracellular sources in human B cells, and alterations of RyR1 function can be successfully detected using Ca(2+) release from intracellular stores as an end point.