High resolution ultrasound in posterior interosseous nerve syndrome

Introduction: Posterior interosseous nerve (PIN) syndrome is a rare compression neuropathy of the PIN in the region of the supinator muscle, most common by the arcade of Frohse. We aimed to specify ultrasonographic findings in patients with PIN syndrome in comparison to healthy volunteers. Methods: Ultrasound images and clinical data of 13 patients with PIN syndrome confirmed by neurological examination and electrophysiological testing were evaluated retrospectively. Anteroposterior nerve diameters measured at the arcade of Frohse were compared with those of 20 healthy volunteers. The echotexture and the presence of a caliber change of the PIN were additionally assessed. Results: Enlargement of the PIN was seen in all patients with PIN syndrome, but not in volunteers (statistically significant difference in mean diameter P < 0.05). Furthermore, edema and caliber change of the PIN were present in all patients. Conclusions: High‐resolution ultrasound allows for differentiation between patients with PIN syndrome and healthy volunteers. Muscle Nerve 49 : 35–39, 2014     

Effects of serum and plasma matrices on multiplex immunoassays

Multiplexed fluorescence or electrochemiluminescence immunoassays of soluble cytokines are commonly performed in the context of human serum or plasma, to look for disease biomarkers and to monitor the immune system in a simple and minimally invasive way. These assays provide challenges due to the complexities of the matrix (serum or plasma) and the presence of many cytokines near the limit of detection of the assay. Here, we compare the readout of matched serum and plasma samples, which are generally correlated. However, a subset of cytokines usually have higher levels in serum, and the non-specific background is significantly increased in serum versus plasma. Presumably as a result of this non-specific background, disease-related decreases in low-abundance cytokines can sometimes be detected in plasma but not in serum. We further show, through spike recovery experiments, that both serum and plasma inhibit the readout of many cytokines, with some variability between donors, but with serum causing greater inhibition than plasma in many cases. Standard diluents from different vendors can partially reverse this inhibition to varying degrees. Dilution of samples can also partly overcome the inhibitory effect of the matrix. We also show that dilution is nonlinear and differentially affects various cytokines. Together, these data argue that (1) plasma is a more sensitive matrix for detecting changes in certain low-abundance cytokines; (2) calculation of concentrations in serum or plasma matrices is inherently inaccurate; and (3) dilution of samples should not be assumed to be linear, i.e., all comparisons need to be made among similarly diluted samples.     

In vitro exposure of isolated cells to native gaseous compounds Development and validation of an optimized system for human lung cells

An exposure system for adherent growing cells to native gaseous compounds was developed using air/liquid culture techniques on the basis of the Cultex system'. In contrast to other exposure systems the reproducible testing of native environmentally relevant gases without changing their physical or chemical properties including heating, CO2- content and humidity is possible. Specially designed systems for medium flow and gas support guarantee the nutrification and humidification as well as the direct gas contact of the exposed cells which are cultivated on microporous membranes (0.4 microm pore size). The system works independently of a cell culture incubator offering the possibility to analyze any relevant gas mixture directly under indoor or outdoor conditions. Several experimental approaches were carried out to characterize the properties of the system. In exploratory experiments without cells, the reproducibility and quality of the gas/membrane contact could be demonstrated. Exposures of human lung fibroblasts (Lk004 cells) and human lung epithelial cells (HFBE-21 cells) to synthetic air, ozone (202 ppb, 510 ppb) and nitrogen dioxide (75 ppb to 1,200 ppb) established that cells could be treated for 120 minutes without significant loss of cellular viability. At the same time, the experiments confirmed that such exposure times are long enough to detect biological effects of environmentally relevant gas mixtures. The analysis of viability (viable cell number, tetrazoliumsalt cleavage) and intracellular end-points (oxidized/reduced glutathione, ATP/ADP) showed that both gases induced relevant cellular changes. In summary, the efficiency and practicability of this newly developed exposure system for adherent human lung cells could be clearly demonstrated.     

Pharmacokinetics (PK) of S/D treated anti-D immunoglobulin after intramuscular injection in healthy volunteers: gender differences in PK.

The aim of this study was to investigate the pharmacokinetic profile of the new solvent/detergent (S/D) formulation of an anti-D IgG preparation, and to evaluate gender differences. RhD-negative subjects (m/f=10/8) received a single i.m. injection of 250 microg anti-D (Partobulin SDF). There was a rapid increase in median anti-D titers over the first 2 days, followed by a plateau from days 2-7. Interestingly, women had a higher maximum concentration (Cmax) of anti-D and a lower volume of distribution at steady state (Vss) than men. The half-life calculated in this study was 23 days. Thus, results are comparable to published data of the non-S/D treated predecessor product. Because of the observed gender differences in the pharmacokinetics we recommend to pursue the evaluation of sex differences in the pharmacokinetics of other antibodies during early phase drug development.