Women awaken faster than men after electroencephalogram-monitored propofol sedation for colonoscopy: A prospective observational study.

BACKGROUND: Sedation for colonoscopy using intravenous propofol has become standard in many Western countries. OBJECTIVE: Gender-specific differences have been shown for general anaesthesia in dentistry, but no such data existed for gastrointestinal endoscopy. DESIGN: A prospective observational study. SETTING: An academic teaching hospital of Hannover Medical School. PATIENTS: A total of 219 patients (108 women and 111 men) scheduled for colonoscopy. INTERVENTION: Propofol sedation using electroencephalogram monitoring during a constant level of sedation depth (D0 to D2) performed by trained nurses or physicians after a body-weight-adjusted loading dose. MAIN OUTCOME MEASURES: The primary end-point was the presence of gender-specific differences in awakening time (time from end of sedation to eye-opening and complete orientation); secondary outcome parameters analysed were total dose of propofol, sedation-associated complications (bradycardia, hypotension, hypoxaemia and apnoea), patient cooperation and patient satisfaction. Multivariate analysis was performed to correct confounding factors such as age and BMI. RESULTS: Women awakened significantly faster than men, with a time to eye-opening of 7.3 ±â€Š3.7 versus 8.4 ±â€Š3.4 min (P = 0.005) and time until complete orientation of 9.1 ±â€Š3.9 versus 10.4 ±â€Š13.7 min (P = 0.008). The propofol dosage was not significantly different, with some trend towards more propofol per kg body weight in women (3.98 ±â€Š1.81 mg versus 3.72 ±â€Š1.75 mg, P = 0.232). CONCLUSION: The effect of gender aspects should be considered when propofol is used as sedation for gastrointestinal endoscopy. That includes adequate dosing for women as well as caution regarding potential overdosing of male patients. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02687568).

Mutated RAS and constitutively activated Akt delineate distinct oncogenic pathways, which independently contribute to multiple myeloma cell survival.

We have recently shown that approximately half of primary multiple myeloma (MM) samples display constitutive Akt activity, which disposes them for sensitivity to Akt inhibition. The Akt pathway counts among the signaling conduits for oncogenic RAS and activating mutations of K- and N-RAS frequently occur in MM. We therefore analyzed the relation between RAS mutation and Akt dependency in biopsies and CD138-purified cells from MM patients (n = 65) and the function of oncogenic RAS for MM cell survival in a range of MM cell lines with differing RAS status. Whereas RAS mutations do not predict Akt dependency, oncogenic RAS retains an important role for MM cell survival. Knockdown of either K- or N-RAS strongly decreased the viability of MM cells that harbored the respective oncogenic isoform, whereas ablation of wild-type RAS isoforms had little or no effect. Silencing of oncogenic RAS did not affect the Akt pathway, again indicating lack of a direct link. Combined inhibition of RAS and Akt strongly enhanced MM cell death. These data suggest that oncogenic RAS and Akt may independently contribute to MM cell survival. Targeting of both pathways could provide an attractive therapeutic strategy for patients with oncogenic RAS and dysregulated Akt signaling.

Life-threatening infection caused by daptomycin-resistant Corynebacterium jeikeium in a neutropenic patient.

Daptomycin is a novel lipopeptide antibiotic agent approved for the treatment of gram-positive life-threatening infections. Here we report, for the first time, the isolation of a highly daptomycin-resistant strain of Corynebacterium jeikeium causing a life-threatening infection in a neutropenic patient undergoing cord blood transplantation for secondary acute myeloid leukemia.

Hippocampal cannabinoid-1 receptor upregulation upon endothelin-B receptor deficiency: a neuroprotective substitution effect?

Endothelin (ETB)-receptors mediate anti-apoptotic actions. Lack of functional ETB-receptors leads to increased neuronal apoptosis in the hippocampus. The increased apoptosis must be compensated by other mechanisms, however, as ETB-deficient rats display normal overall brain morphology. To illuminate on brain plasticity in ETB-receptor deficiency, we studied the expression and function of another neuroprotective system, the cannabinoid CB1-receptors, in ETB-deficient hippocampus. We show that CB1 expression in hippocampus increases postnatally in all rats but that the increase in CB1-receptor expression is significantly higher in ETB-deficient compared to wildtype littermates. Neuronal apoptosis decreases during brain maturation but remains on a significantly higher level in the ETB-deficient compared to wildtype dentate. When investigating survival of hippocampal neurons in culture, we found significant protection against hypoxia-induced cell death with CB1-analogs (noladin, (9-tetrahydrocannabinol) only in ETB-deficient neurons. We suggest that CB1-receptor upregulation in the ETB-mutant hippocampus reflects an attempt to compensate for the lack of ETB-receptors.