[Neuromonitoring and neuroprotection in cardiac anaesthesia. Nationwide survey conducted by the Cardiac Anaesthesia Working Group of the German Society of Anaesthesiology and Intensive Care Medicine]

OBJECTIVE: The primary objective of this nationwide survey carried out in department of cardiac anesthesia in Germany was to identify current practice with regard to neuromonitoring und neuroprotection. METHODOLOGY: The data are based on a questionnaire sent out to all departments of cardiac anesthesia in Germany between October 2007 und January 2008. The anonymized questionnaire contained 26 questions about the practice of preoperative evaluation of cerebral vessels, intra-operative use of neuromonitoring, the nature und application of cerebral protective measures, perfusion management during cardiopulmonary bypass, postoperative evaluation of neurological status, and training in the field of cerebral monitoring. RESULTS: Of the 80 mailed questionnaires 55% were returned and 90% of department evaluated cerebral vessels preoperatively with duplex ultrasound. The methods used for intra-operative neuromonitoring are electroencephalography (EEG, 60%) for type A dissections (38.1%), for elective surgery on the thoracic and thoraco-abdominal aorta (34.1% and 31.6%, respectively) and in carotid surgery (43.2%) near infrared spectroscopy (40%), evoked potentials (30%) and transcranial Doppler sonography (17.5%), with some centers using combined methods. In most departments the central nervous system is not subjected to monitoring during bypass surgery, heart valve surgery, or minimally invasive surgery. Cerebral protective measures used comprise patient cooling on cardio-pulmonary bypass (CPB 100%), extracorporeal cooling of the head (65%) and the administration of corticosteroids (58%), barbiturates (50%) and antiepileptic drugs (10%). Neuroprotective anesthesia consists of administering inhalation anesthetics (32.5%; sevoflurane 76.5%) and intravenous anesthesia (20%; propofol and barbiturates each accounting for 46.2%). Of the departments 72.5% cool patients as a standard procedure for surgery involving cardiovascular arrest and 37.5% during all surgery using CPB. In 84.6% of department CPB flow equals calculated cardiac output (CO) under normothermia, while the desired mean arterial pressure (MAP) varies between 60 and 70 mmHg (43.9%) and between 50 and 60 mmHg (41.5%), respectively. At body temperatures less than 18 degrees C CPB flow is reduced below the calculated CO (70%) while 27% of departments use normothermic flow rates. The preferred MAP under hypothermia is between 50 and 60 mmHg (59%). The results of intra-operative neuromonitoring are documented on the anesthesia record (77%). In 42.5% of the departments postoperative neurological function is estimated by the anesthesiologist. Continuing education sessions pertaining to neuromonitoring are organized on a regular basis in 32.5% of the departments and in 37.5% individual physicians are responsible for their own neuromonitoring education. CONCLUSION: The present survey data indicate that neuromonitoring and neuroprotective therapy during CPB is not standardized in cardiac anesthesiology departments in Germany. The systemic use of available methods to implement multimodal neuromonitoring would be desirable.

The prognostic value of cytology and fluorescence in situ hybridization in the follow-up of nonmuscle-invasive bladder cancer after intravesical Bacillus Calmette-Guérin therapy

Molecular markers reliably predicting failure or success of Bacillus Calmette-Guérin (BCG) in the treatment of nonmuscle-invasive urothelial bladder cancer (NMIBC) are lacking. The aim of our study was to evaluate the value of cytology and chromosomal aberrations detected by fluorescence in situ hybridization (FISH) in predicting failure to BCG therapy. Sixty-eight patients with NMIBC were prospectively recruited. Bladder washings collected before and after BCG instillation were analyzed by conventional cytology and by multitarget FISH assay (UroVysion, Abbott/Vysis, Des Plaines, IL) for aberrations of chromosomes 3, 7, 17 and 9p21. Persistent and recurrent bladder cancers were defined as positive events during follow-up. Twenty-six of 68 (38%) NMIBC failed to BCG. Both positive post-BCG cytology and positive post-BCG FISH were significantly associated with failure of BCG (hazard ratio (HR)= 5.1 and HR= 5.6, respectively; p < 0.001 each) when compared to those with negative results. In the subgroup of nondefinitive cytology (all except those with unequivocally positive cytology), FISH was superior to cytology as a marker of relapse (HR= 6.2 and 1.4, respectively). Cytology and FISH in post-BCG bladder washings are highly interrelated and a positive result predicts failure to BCG therapy in patients with NMIBC equally well. FISH is most useful in the diagnostically less certain cytology categories but does not provide additional information in clearly malignant cytology.

Changes in bone mineral density over 18 months following kidney transplantation: the respective roles of prednisone and parathyroid hormone

Prednisone is a major factor of bone loss after kidney transplantation. The role of hyperparathyroidism and immunosuppressors is less clear.

Dual-energy X-ray absorptiometry for measuring total bone mineral content in the rat: study of accuracy and precision

Sequential studies of osteopenic bone disease in small animals require the availability of non-invasive, accurate and precise methods to assess bone mineral content (BMC) and bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA), which is currently used in humans for this purpose, can also be applied to small animals by means of adapted software. Precision and accuracy of DXA was evaluated in 10 rats weighing 50-265 g. The rats were anesthetized with a mixture of ketamine-xylazine administrated intraperitoneally. Each rat was scanned six times consecutively in the antero-posterior incidence after repositioning using the rat whole-body software for determination of whole-body BMC and BMD (Hologic QDR 1000, software version 5.52). Scan duration was 10-20 min depending on rat size. After the last measurement, rats were sacrificed and soft tissues were removed by dermestid beetles. Skeletons were then scanned in vitro (ultra high resolution software, version 4.47). Bones were subsequently ashed and dissolved in hydrochloric acid and total body calcium directly assayed by atomic absorption spectrophotometry (TBCa[chem]). Total body calcium was also calculated from the DXA whole-body in vivo measurement (TBCa[DXA]) and from the ultra high resolution measurement (TBCa[UH]) under the assumption that calcium accounts for 40.5% of the BMC expressed as hydroxyapatite. Precision error for whole-body BMC and BMD (mean +/- S.D.) was 1.3% and 1.5%, respectively. Simple regression analysis between TBCa[DXA] or TBCa[UH] and TBCa[chem] revealed tight correlations (n = 0.991 and 0.996, respectively), with slopes and intercepts which were significantly different from 1 and 0, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Consequences of the combined loss of BOK and BAK or BOK and BAX

The multi-BCL-2 homology domain pro-apoptotic BCL-2 family members BAK and BAX have critical roles in apoptosis. They are essential for mitochondrial outer-membrane permeabilization, leading to the release of apoptogenic factors such as cytochrome-c, which promote activation of the caspase cascade and cellular demolition. The BOK protein has extensive amino-acid sequence similarity to BAK and BAX and is expressed in diverse cell types, particularly those of the female reproductive tissues. The BOK-deficient mice have no readily discernible abnormalities, and its function therefore remains unresolved. We hypothesized that BOK may exert functions that overlap with those of BAK and/or BAX and examined this by generating Bok−/−Bak−/− and Bok−/−Bax−/− mice. Combined loss of BOK and BAK did not elicit any noticeable defects, although it remains possible that BOK and BAK have critical roles in developmental cell death that overlap with those of BAX. In most tissues examined, loss of BOK did not exacerbate the abnormalities caused by loss of BAX, such as defects in spermatogenesis or the increase in neuronal populations in the brain and retina. Notably, however, old Bok−/−Bax−/− females had abnormally increased numbers of oocytes from different stages of development, indicating that BOK may have a pro-apoptotic function overlapping with that of BAX in age-related follicular atresia.

A validated assay by liquid chromatography-tandem mass spectrometry for the simultaneous quantification of elvitegravir and rilpivirine in HIV positive patients

Because of the large variability in the pharmacokinetics of anti-HIV drugs, therapeutic drug monitoring in patients may contribute to optimize the overall efficacy and safety of antiretroviral therapy. An LC–MS/MS method for the simultaneous assay in plasma of the novel antiretroviral agents rilpivirine (RPV) and elvitegravir (EVG) has been developed to that endeavor. Plasma samples (100 μL) extraction is performed by protein precipitation with acetonitrile, and the supernatant is subsequently diluted 1:1 with 20-mM ammonium acetate/MeOH 50:50. After reverse-phase chromatography, quantification of RPV and EVG, using matrix-matched calibration samples, is performed by electrospray ionization–triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The stable isotopic-labeled compounds RPV-13C6 and EVG-D6 were used as internal standards. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<6.4%), as well as EVG and RPV short and long-term stability in plasma. Calibration curves were validated over the clinically relevant concentrations ranging from 5 to 2500 ng/ml for RPV and from 50 to 5000 ng/ml for EVG. The method is precise (inter-day CV%: 3–6.3%) and accurate (3.8–7.2%). Plasma samples were found to be stable (<15%) in all considered conditions (RT/48 h, +4°C/48 h, −20°C/3 months and 60°C/1 h). Selected metabolite profiles analysis in patients' samples revealed the presence of EVG glucuronide, that was well separated from parent EVG, allowing to exclude potential interferences through the in-source dissociation of glucuronide to parent drug. This new, rapid and robust LCMS/MS assay for the simultaneous quantification of plasma concentrations of these two major new anti-HIV drugs EVG and RPV offers an efficient analytical tool for clinical pharmacokinetics studies and routine therapeutic drug monitoring service.

The gender typicality of faces and its impact on visual processing and on hiring decisions

Past research has shown that the gender typicality of applicants’ faces affects leadership selection irrespective of a candidate’s gender: A masculine facial appearance is congruent with masculine-typed leadership roles, thus masculine-looking applicants are hired more certainly than feminine-looking ones. In the present study, we extended this line of research by investigating hiring decisions for both masculine- and feminine-typed professional roles. Furthermore, we used eye tracking to examine the visual exploration of applicants’ portraits. Our results indicate that masculine-looking applicants were favored for the masculine-typed role (leader) and feminine-looking applicants for the feminine-typed role (team member). Eye movement patterns showed that information about gender category and facial appearance was integrated during first fixations of the portraits. Hiring decisions, however, were not based on this initial analysis, but occurred at a second stage, when the portrait was viewed in the context of considering the applicant for a specific job.

The changing values of children and preferences regarding family size in south Africa

This study extends the ongoing studies on values of children and intergenerational relations into an African context with the following key questions: To what extent can the structure of values of children (VOC) identified in previous studies be found in South Africa and what are women's preferences regarding the size of small, large, and ideal families? The sample consisted of three cohorts of Black South African women from the Limpopo Province. Factor analyses showed that the dimensions of VOC found in South Africa are a conglomeration of different values. Identified dimensions were Social/Emotional and Traditional/Utilitarian with respect to reasons for wanting children. Regarding reasons for not wanting children, Child as Source of Constraints and Constraints to Have a Child were identified. Intergenerational comparisons showed variations in the importance of value of children dimensions and in preferences regarding family size. Values of children of younger mothers were related to the number of children these women had and to their preferences regarding family size. The findings are discussed within the changing socio-political context of South Africa.

Spontaneous peristaltic airway contractions propel lung liquid through the bronchial tree of intact and fetal lung explants

Spontaneous contractions of the fetal airways are a well recognized but poorly characterized phenomenon. In the present study spontaneous narrowing of the airways was analyzed in freshly isolated lungs from early to late gestation in fetal pigs and rabbits and in cultured fetal mouse lungs. Propagating waves of contraction traveling proximal to distal were observed in fresh lungs throughout gestation which displaced the lung liquid along the lumen. In the pseudoglandular and canalicular stages (fetal pigs) the frequency ranged from 2.3 to 3.3 contractions/min with a 39 to 46% maximum reduction of lumen diameter. In the saccular stage (rabbit) the frequency was 10 to 12/min with a narrowing of approximately 30%. In the organ cultures the waves of narrowing started at the trachea in whole lungs, or at the main bronchus in lobes (5.2 +/- 1.5 contractions/min, 22 +/- 8% reduction of lumen diameter), and as they proceeded distally along the epithelial tubes the luminal liquid was shifted toward the terminal tubules, which expanded the endbuds. As the tubules relaxed the flow of liquid was reversed. Thus the behavior of airway smooth muscle in the fetal lung is phasic in type (like gastrointestinal muscle) in contrast to that in postnatal lung, where it is tonic. An intraluminal positive pressure of 2.33 +/- 0.77 cm H(2)O was recorded in rabbit fetal trachea. It is proposed that the active tone of the smooth muscle maintains the positive intraluminal pressure and acts as a stimulus to lung growth via the force exerted across the airway wall and adjacent parenchyma. The expansion of the compliant endbuds by the fluid shifts at the airway tip may promote their growth into the surrounding mesenchyme.