Twelve healthy male patients (mean age 41 years) completed a double-blind, placebo-controlled, within-subject crossover investigation of brain SERT occupancy by sibutramine 15 mg daily at steady state. Correlations were measured between occupancy and (i) plasma concentrations of sibutramine, M1 and M2; (ii) appetite selleck inhibitor suppression.
C-11-DASB PET scans were performed on the HRRT camera. Binding potentials (BPND) were calculated by the Logan reference tissue (cerebellum) method. SERT occupancy was modest (mean 30 +/- 10%), was similar across brain regions, but varied widely across subjects (15-46%). Occupancy was correlated positively (p = 0.09) with M2 concentration, but not with sibutramine or M1. No significant www.selleckchem.com/products/shp099-dihydrochloride.html appetite suppression was seen at < 25% occupancy and greatest suppression was associated with highest occupancy (25-46%). However, several subjects with occupancy (36-39%) in the higher range had no appetite suppression. SERT occupancy by clinical doses of sibutramine is of modest magnitude and may be mediated predominantly by M2 in humans. 5-HT reuptake inhibition may be necessary but is not sufficient for sibutramine’s efficacy in humans, supporting preclinical data suggesting that the hypophagic effect requires the co-inhibition of both SERT and NET. Neuropsychopharmacology
(2010) 35, 741-751; doi:10.1038/npp.2009.182; published online 4 November 2009″
“Background CT imaging of head-injured children has risks of radiation-induced malignancy. Our aim was to identify children at very low risk of clinically-important traumatic brain injuries (ciTBI) for whom CT might be unnecessary.
Methods We enrolled patients younger than 18 years presenting within 24 h of head trauma with Glasgow Coma Scale scores Calpain of 14-15 in 25 North American emergency departments. We derived and validated age-specific prediction rules for ciTBI (death from traumatic brain injury, neurosurgery, intubation >24 h, or hospital admission >= 2 nights).
Findings We enrolled and analysed 42412 children (derivation and validation populations:
8502 and 2216 younger than 2 years, and 25 283 and 6411 aged 2 years and older). We obtained CT scans on 14969 (35.3%); ciTBIs occurred in 376 (0.9%), and 60 (0.1%) underwent neurosurgery. In the validation population, the prediction rule for children younger than 2 years (normal mental status, no scalp haematoma except frontal, no loss of consciousness or loss of consciousness for less than 5 s, non-severe injury mechanism, no palpable skull fracture, and acting normally according to the parents) had a negative predictive value for ciTBI of 1176/1176 (100.0%, 95% CI 99.7-100.0) and sensitivity of 25/25 (100%, 86.3-100.0). 167 (24.1%) of 694 CT imaged patients younger than 2 years were in this low-risk group.