Using fMRI to quantify the time dependence of remifentanil analgesia in the human brain.

To understand and exploit centrally acting drugs requires reliable measures of their time course of action in the human brain. Functional magnetic resonance imaging (fMRI) is able to measure noninvasively, drug-induced changes in task-related brain activity. Here, we have characterized, in a specific region of the brain, the time of onset of action and the half-life of action of a clinically relevant dose of a potent opioid analgesic agent, remifentanil. These times were established from the temporal variation of the amplitude of the blood oxygen level-dependent response in the insular cortex contralateral to a painfully hot thermal stimulus, in volunteers receiving a remifentanil infusion. The insular cortex has repeatedly been reported as activated by noxious thermal stimulation. The times of onset and offset of drug action were each characterized by a half-life for changes in fMRI signal from within the insula. These characteristic times agreed with the observed drug-induced analgesia and previous pharmacokinetic-pharmacodynamic measurements for remifentanil. We have successfully measured, for the first time using fMRI, temporal pharmacological parameters for a CNS-active drug based on its effect on task-related activity in a specific brain region. Comparison of the time course of regional brain activity with pain perception could reveal those regions engaged in drug-induced analgesia.     

Unexpected findings and misdiagnoses in coroner’s autopsies performed for trauma at the University of the West Indies,Kingston, Jamaica

There has been significant improvement in medical diagnostic technology, but discrepancy rates between clinical and postmortem diagnoses remain relatively high. This study aimed to identify misdiagnoses and missed (unexpected) findings documented during complete coroner’s autopsies performed for trauma at the University of the West Indies (UWI) and evaluate their influence on patient outcome. We retrospectively reviewed the reports of all coroner’s autopsies performed for trauma, between 2003 and 2012, at the UWI. For each case, we extracted age, gender, trauma type, mechanism and topography, clinical and postmortem diagnoses and hospitalization duration. The data were used to calculate frequencies, proportions and discrepancy rates. 955 coroner’s autopsies were performed during the 10-year period; reports were available for 933. 396 of these were performed for trauma; 365 met the inclusion criteria. 260 (71.2%) of the 365 autopsies had at least one discrepancy. There were 746 clinical and 1118 autopsy diagnoses; 382 were discrepant (372 missed [unexpected] diagnoses, 6 mis-diagnoses and 4 over-diagnoses). The discrepancy rate (misdiagnoses and missed diagnoses) was 33.8%, and the majority (55%) occurred in patients hospitalized for <1 day. Cardiopulmonary diseases were the most commonly missed diagnoses. The discrepancy rate was intermediate to those previously reported in the literature. The short hospitalization duration in most patients suggests that limited time for clinical investigation may be a contributor to discrepancy. However, increased awareness among clinicians of the common major missed diagnoses should enhance their early diagnosis, even when clinical signs are subtle, hopefully producing improved patient outcome.     

糖,是友还是敌？

对于糖尿病朋友来说,糖的问题一直是引发争议的焦点。尽管所有人都知道糖能为身体提供能量,但仍有不少人认为,糖尿病人的饮食中,糖的比重应该越少越好。