ABSTRACT
This randomized, double-blind, placebo-controlled study evaluated the antipyretic effect and safety of intravenous (i.v.) acetaminophen using an endotoxin-induced fever model. Subjects exhibiting sufficient fever response following administration of reference standard endotoxin (RSE) were randomly assigned to receive i.v. acetaminophen 1,000 mg (n = 31) or matching placebo (n = 29). The primary efficacy end point was the weighted sum of temperature differences from baseline through 6 h. Relative to placebo, i.v. acetaminophen administration produced a rapid decrease in temperature that persisted throughout the 6-h study period. The primary end point favored i.v. acetaminophen over placebo (P < 0.001). Temperature differences from baseline reached statistical significance at T30 min after endotoxin administration (15 min after completing the study medication infusion). Acetaminophen administered i.v. was well tolerated, and the frequency of adverse events was comparable to that after administration of i.v. placebo. This study shows that i.v. acetaminophen in a single 1,000-mg dose is safe and effective in reducing fever.
Subject(s)
Acetaminophen/therapeutic use , Antipyretics/therapeutic use , Fever/drug therapy , Acetaminophen/administration & dosage , Acetaminophen/adverse effects , Adult , Alanine Transaminase/blood , Antipyretics/administration & dosage , Antipyretics/adverse effects , Aspartate Aminotransferases/blood , Body Temperature/drug effects , Double-Blind Method , Endotoxins , Endpoint Determination , Female , Fever/chemically induced , Humans , Injections, Intravenous , Male , Sample Size , Treatment OutcomeABSTRACT
An intrathecal opioid infusion using an implanted programmable pump is frequently used for controlling refractory pain. Morphine, which is the only opioid presently approved by the FDA for use in such pumps, occasionally fails to work or is not tolerated by the patient; therefore other opioids are considered for infusions. When switching from one drug to another, it is important to consider not only equianalgesic dose conversions, but also lipophilicity. We report on three cases that demonstrate the need to use only a fraction of the equianalgesic dose when shifting from lipophilic to nonlipophilic opioids in such infusions.
ABSTRACT
The sperm of Caenorhabditis elegans translocate in a fashion similar to sperm of Ascaris suum even though their pseudopods are longer, more plastic in shape, and form multiple expansions zones around their perimeter. Mutants in spe-11 form primary spermatocytes with a defective perinuclear region, but the resulting spermatozoa can still crawl and fertilize eggs. However, the resultant zygotes die due to the absence of sperm-supplied spe-11. Computer-assisted analysis of translocating spe-11 sperm reveals a novel defect in the dynamic morphology of their pseudopods. A similar analysis of the C. elegans mutant unc-54, which lacks the most abundant isoform of myosin II, reveals no defect in sperm motility, as expected, since C. elegans sperm have substituted the protein MSP for actin in the process of pseudopod expansion. These results reveal an unexpected defect in the dynamic morphology of pseudopods of spe-11 sperm. This defect, however, does not significantly affect crawling velocity, and it demonstrates how computer-assisted motion analysis systems can reveal subtle behavioral phenotypes in C. elegans mutant spermatozoa.