/st> The most reliable independent predictors of PONV were female gender, history of PONV or motion sickness, non-smoker, younger age, duration of anaesthesia with volatile anaesthetics, and postoperative opioids. There is no or insufficient evidence for a number of commonly held factors, such as preoperative fasting, menstrual cycle, and surgery type, and using these factors may be counterproductive in assessing a patient's risk for PONV.

Paclitaxel (Taxol) is a well established chemotherapeutic agent for the treatment of solid tumors, but it is limited in its usefulness by the frequent induction of peripheral neuropathy. We found that prolonged exposure of a neuroblastoma cell line and primary rat dorsal root ganglia with therapeutic concentrations of Taxol leads to a reduction in inositol trisphosphate (InsP 3)-mediated Ca 2؉ signaling. We also observed a Taxol-specific reduction in neuronal calcium sensor 1 (NCS-1) protein levels, a known modulator of InsP 3 receptor (InsP3R) activity. This reduction was also found in peripheral neuronal tissue from Taxol treated animals. We further observed that short hairpin RNA-mediated NCS-1 knockdown had a similar effect on phosphoinositide-mediated Ca 2؉ signaling. When NCS-1 protein levels recovered, so did InsP 3-mediated Ca 2؉ signaling. Inhibition of the Ca 2؉ -activated protease -calpain prevented alterations in phosphoinositide-mediated Ca 2؉ signaling and NCS-1 protein levels. We also found that NCS-1 is readily degraded by -calpain in vitro and that -calpain activity is increased in Taxol but not vehicle-treated cells. From these results, we conclude that prolonged exposure to Taxol activates -calpain, which leads to the degradation of NCS-1, which, in turn, attenuates InsP 3-mediated Ca 2؉ signaling. These findings provide a previously undescribed approach to understanding and treating Taxolinduced peripheral neuropathy.calcium imaging ͉ dorsal root ganglia ͉ endoplasmic reticulum ͉ polyneuropathy ͉ inositol 1,4,5-trisphosphate receptor

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