When Is a Bispectral Index of 60 Too Low?: Rational Processed Electroencephalographic Targets Are Dependent on the Sedative-Opioid Ratio

Background: Opioids are commonly used in conjunction with sedative drugs to provide anesthesia. Previous studies have shown that opioids reduce the clinical requirements of sedatives needed to provide adequate anesthesia. Processed electroencephalographic parameters, such as the Bispectral Index (BIS; Aspect Medical Systems, Newton, MA) and Auditory Evoked Potential Index (AAI; Alaris Medical Systems, San Diego, CA), can be used intraoperatively to assess the depth of sedation. The aim of this study was to characterize how the addition of opioids sufficient to change the clinical level of sedation influenced the BIS and AAI.

Methods: Twenty-four adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the modified Observer's Assessment of Alertness/Sedation score, BIS, and AAI were measured at each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for each pharmacodynamic endpoint.

Results: Response surface models adequately characterized all pharmacodynamic endpoints. Despite the fact that sevoflurane-remifentanil interactions were strongly synergistic for clinical sedation, BIS and AAI were minimally affected by the addition of remifentanil to sevoflurane anesthetics.     

3He MRI in mouse models of asthma.

In the study of asthma, a vital role is played by mouse models, because knockout or transgenic methods can be used to alter disease pathways and identify therapeutic targets that affect lung function. Assessment of lung function in rodents by available methods is insensitive because these techniques lack regional specificity. A more sensitive method for evaluating lung function in human asthma patients uses hyperpolarized (HP) (3)He MRI before and after bronchoconstriction induced by methacholine (MCh). We now report the ability to perform such (3)He imaging of MCh response in mice, where voxels must be approximately 3000 times smaller than in humans and (3)He diffusion becomes an impediment to resolving the airways. We show three-dimensional (3D) images that reveal airway structure down to the fifth branching and visualize ventilation at a resolution of 125 x 125 x 1000 microm(3). Images of ovalbumin (OVA)-sensitized mice acquired after MCh show both airway closure and ventilation loss. To also observe the MCh response in naive mice, we developed a non-slice-selective 2D protocol with 187 x 187 microm(2) resolution that was fast enough to record the MCh response and recovery with 12-s temporal resolution. The extension of (3)He MRI to mouse models should make it a valuable translational tool in asthma research.     

Alterations in cholinergic and non-cholinergic neurotransmitter receptor densities in transgenic Tg2576 mouse brain with beta-amyloid plaque pathology.

Cholinergic deficits in Alzheimer's disease are accompanied by a number of alterations in other transmitter systems including glutamate, noradrenaline and serotonin, suggesting the involvement also of other neurotransmitter systems in the pathogenesis of the disease. To address the question whether beta-amyloid may contribute to these deficits, brain tissue from transgenic Tg2576 mice with Alzheimer plaque pathology at ages of 5 (still no significant plaque load) and 17 months (moderate to high cortical beta-amyloid plaque load) were examined for a number of cholinergic and non-cholinergic markers. Transgenic mice with no significant plaque load demonstrated reduced hemicholinium-3 (HCh-3) binding to choline uptake sites in anterior brain regions as compared to non-transgenic littermates, while in aged transgenic mice with high number of plaque deposits decreased HCh-3 binding levels were accompanied by increased vesicular acetylcholine transporter binding in selected cortical brain regions. In aged transgenic mice GABA(A), NMDA, AMPA, kainate, and beta-adrenergic as well 5-HT(1A)- and 5-HT(2A)-receptor binding levels were hardly affected, whereas alpha(1)- and alpha(2)-adrenoceptor binding was increased in selected cerebral cortical regions as compared to non-transgenic littermates. The development of changes in both cholinergic and non-cholinergic markers in transgenic Tg2576 mouse brain already before the onset of progressive plaque deposition provides in vivo evidence of a modulatory role of soluble beta-amyloid on cortical neurotransmission and may be referred to the deficits in learning and memory observed in these mice also before significant plaque load.     

Predictive testing for Huntington's disease: I. Predictors of uptake in South Wales

In Wales, predictive testing for Huntington's disease (HD) has not been offered proactively to families and uptake of testing is low in comparison to other centres. Little is known of those not requesting testing, particularly those not in direct contact with the genetics service. This study examined differences between a cohort of 22 test applicants and a random group of 32 'non-requesters', drawn from the South Wales HD register. Respondents were interviewed by means of a semi-structured schedule in their own homes. The study groups differed significantly on a number of variables including: knowledge of the availability of testing; perceived attitudes of family members and significant others to testing; length of knowledge and perceived stressfulness of being at risk; and perceived ability to cope with an unfavourable result. Overall, knowledge of testing procedures was poor and at-risk individuals' understanding of genetic terminology was at odds with scientific distinctions. Discussion focuses on the organisational and psychological factors associated with lack of knowledge of the availability of testing and the interpretation of reported coping capacities.     

Prediction of global outcome with acute neuropsychological testing following closed-head injury.

Delaying assessment until emergence from post-traumatic amnesia increases completion rates, but this practice causes variable time delays from the date of injury to testing, which can complicate the interpretation of research findings. In the current study, the performance of 105 head injury survivors on simple tests of language comprehension and attention was used to predict global outcome. It was hypothesized that 1 month performance on these measures would aid in the prediction of Disability Rating Scale (DRS) and Glasgow Outcome Scale (GOS) scores collected at 6 months post injury. Only raw scores on the modified Test of Complex Ideational Material accounted for a significant amount of the variance in DRS scores (4.4%) above that accounted for by age, education, Glasgow Coma Scale score, and pupil response. However, testability at 1 month post injury on all four tests consistently accounted for a larger portion of the variance in DRS scores (10.1-13.2%) and significantly improved prediction of GOS scores. Galveston Orientation and Amnesia Test scores collected at 1 month post injury accounted for substantially less variance in DRS scores (7.7-8.4%). Neuropsychological data, including the testability of patients, collected uniformly at 1 month following injury can contribute to the prediction of global outcome.