Neurophysiological investigation of the central nervous action of the hypnotic agent etomidate in cats (author's transl)]

1. The action of etomidate (0.125-4.0 mg/kg) injected intravenously or into the right atrium (time of injection about 1 sec) was investigated in cats under different central nervous conditions. 2. In decerebrate unanaesthetized animals and in lightly anaesthetized (pentobarbitone) animals with an intact CNS etomidate (0.25-4 mg/kg i.v.) caused a decrease of the spontaneous lumbar fusimotor activity and a strong depression of the fusimotor pinnareflex. Partly a reversal of this reflex from excitation to inhibition was observed. The effects occurred within 20 sec after the injection and lasted for 5-70 min, showing a clear non-linear relationship with the injected dose. 3. In encephale isole preparations etomidate (0.125-1 mg/kg injected intra-right atrially) caused distinct changes of the spontaneous EEB (decrease of frequency, increase of amplitude, occurrence of steeper waves) and a depression of the arousal reactions in the EEB following different stimuli (acoustic stimuli and different stimuli in the area of the face and eyes). These effects occurred within 8 sec after the injection and lasted up to 40 min, dependent upon the injected dose. 4. The character and the principal similarity of the results observed in decerebrate animals and in animals with intact CNS suggest that a considerable part of the action of etomidate consists of a depression of the activity and reactivity of the brain stem reticular formation.     

CD34+ human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells

Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34+ cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34+ Kit-, CD34+ Kit(low), and CD34+ Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34+ Kit(low) cells showed signs of engraftment according to analysis of CD45+ cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34+ Kit(high) cells and two fetuses receiving CD34+ Kit- cells failed to show evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34+ Kit(low) cells exhibited signs of engraftment upon serial examination. Earlier in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population.     

Design and Implementation of a Controlled Clinical Trial to Evaluate the Effectiveness and Efficiency of Routine Opt-out Rapid Human Immunodeficiency Virus Screening in the Emergency Department

In 2006, the Centers for Disease Control and Prevention (CDC) released revised recommendations for performing human immunodeficiency virus (HIV) testing in health care settings, including implementing routine rapid HIV screening, the use of an integrated opt-out consent, and limited prevention counseling. Emergency departments (EDs) have been a primary focus of these efforts. These revised CDC recommendations were primarily based on feasibility studies and have not been evaluated through the application of rigorous research methods. This article describes the design and implementation of a large prospective controlled clinical trial to evaluate the CDC's recommendations in an ED setting. From April 15, 2007, through April 15, 2009, a prospective quasi-experimental equivalent time-samples clinical trial was performed to compare the clinical effectiveness and efficiency of routine (nontargeted) opt-out rapid HIV screening (intervention) to physician-directed diagnostic rapid HIV testing (control) in a high-volume urban ED. In addition, three nested observational studies were performed to evaluate the cost-effectiveness and patient and staff acceptance of the two rapid HIV testing methods. This article describes the rationale, methodologies, and study design features of this program evaluation clinical trial. It also provides details regarding the integration of the principal clinical trial and its nested observational studies. Such ED-based trials are rare, but serve to provide valid comparisons between testing approaches. Investigators should consider similar methodology when performing future ED-based health services research.