Citations

Background Different cerebrospinal fluid (CSF) amyloid-beta 1–42 (A β 1–42 ), total Tau (Tau) and Tau phosphorylated at threonine 181 (P-Tau) levels are reported, but currently there is a lack of quality control programmes. The aim of this study was to compare the measurements of these CSF biomarkers, between and within centres. Methods Three CSF-pool samples were distributed to 13 laboratories in 2004 and the same samples were again distributed to 18 laboratories in 2008. In 2004 six laboratories measured A β 1–42 , Tau and P-Tau and seven laboratories measured one or two of these marker(s) by enzyme-linked immunosorbent assays (ELISAs). In 2008, 12 laboratories measured all three markers, three laboratories measured one or two marker(s) by ELISAs and three laboratories measured the markers by Luminex. Results In 2004, the ELISA intercentre coefficients of variance (interCV) were 31%, 21% and 13% for A β 1–42 , Tau and P-Tau, respectively. These were 37%, 16% and 15%, respectively, in 2008. When we restricted the analysis to the Innotest ® ( N = 13) for A β 1–42 , lower interCV were calculated (22%). The centres that participated in both years ( N = 9) showed interCVs of 21%, 15% and 9% and intra-centre coefficients (intraCV) of variance of 25%,18% and 7% in 2008. Conclusions The highest variability was found for A β 1–42 . The variabilities for Tau and P-Tau were lower in both years. The centres that participated in both years showed a high intraCV comparable to their interCV, indicating that there is not only a high variation between but also within centres. Besides a uniform standardization of (pre)analytical procedures, the same assay should be used to decrease the inter/intracentre variation.

An instrumented wheel system for three-dimensional kinetic analysis of upper extremity during wheelchair propulsion has been designed and validated. This system allows the direct measurements of three-dimensional dynamic forces and moments on the handrim during wheelchair propulsion in a laboratory setting as well as in the field. Static loading tests showed a high linearity and little drift (coefficient of determination, r2 > 0.999). Under dynamic loading, the instrumented wheel provided the well-matched measurement forces and moments with the predicted values from the inverse dynamic method using video-based kinematic data (correlation coefficient, ρ > 0.97). The three-dimensional handrim forces and moments during wheelchair propulsion by a non-disabled subject were demonstrated.

Background— Patients with heart failure have high levels of central sympathetic outflow and also have a high prevalence of sleep-related breathing disorders, predominantly central sleep apnea. The options for treating central sleep apnea in heart failure are limited and include theophylline. Whether theophylline alters sympathetic activity in heart failure patients is not known. Methods and Results— Using a single-blinded, randomized, placebo-controlled study design, we investigated the sympathetic, hemodynamic, neurohumoral, and ventilatory effects of theophylline in patients with congestive heart failure compared with healthy control subjects closely matched for age, sex, and body mass index. Theophylline increased muscle sympathetic nerve activity and lowered transcutaneous CO 2 in the control subjects but only lowered transcutaneous CO 2 in the heart failure patients. Theophylline nearly doubled plasma renin concentration in both the healthy subjects ( P <0.01) and the heart failure patients ( P <0.02). Conclusions— Our study shows that in heart failure patients, there are differential effects of theophylline: in contrast to healthy subjects, theophylline does not increase sympathetic activity in heart failure, whereas increases in plasma renin and ventilation are still evident. These novel findings may have important implications for understanding the potential harmful and beneficial effects of theophylline and related substances in heart failure patients.

Acute injury to the intestinal mucosa is a major dose-limiting complication of abdominal radiation therapy. We studied the role of the transcription factor NF-κB in protection against radiation-induced apoptosis in the intestinal epithelium in vivo . We use mice in which NF-κB signaling through IκB-kinase (IKK)-β is selectively ablated in intestinal epithelial cells to show that failure to activate epithelial cell NF-κB in vivo results in a significant increase in radiation-induced epithelial cell apoptosis. Furthermore, bacterial lipopolysaccharide, which is normally a radioprotective agent, is radiosensitizing in IKKβ-deficient intestinal epithelial cells. Increased apoptosis in IKKβ-deficient intestinal epithelial cells was accompanied by increased expression and activation of the tumor suppressor p53 and decreased expression of antiapoptotic Bcl-2 family proteins. These results demonstrate the physiological importance of the NF-κB system in protection against radiation-induced death in the intestinal epithelium in vivo and identify IKKβ as a key molecular target for radioprotection in the intestine. Selective preactivation of NF-κB through IKKβ in intestinal epithelial cells could provide a therapeutic modality that allows higher doses of radiation to be tolerated during cancer radiotherapy.