IL-6 transsignalling modulates the early effector phase of EAE and targets the blood-brain barrier

Interleukin-6 (IL-6) plays a crucial role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). It exerts its cellular effects by a membrane-bound IL-6 receptor (IL-6R), or, alternatively, by forming a complex with the soluble IL-6R (sIL-6R), a process named IL-6 transsignalling. Here we investigate the role of IL-6 transsignalling in myelin basic protein (MBP)-induced EAE in the Lewis rat. In vivo blockade of IL-6 transsignalling by the injection of a specifically designed gp130-Fc fusion protein significantly delayed the onset of adoptively transferred EAE in comparison to control rats injected with PBS or isotype IgG. Histological evaluation on day 3 after immunization revealed reduced numbers of T cells and macrophages in the lumbar spinal cord of gp130-Fc treated rats. At the same time, blockade of IL-6 transsignalling resulted in a reduced expression of vascular cell adhesion molecule-1 on spinal cord microvessels while experiments in cell culture failed to show a direct effect on the regulation of endothelial adhesion molecules. In experiments including active EAE and T cell culture, inhibition of IL-6 transsignalling mildly increased T cell proliferation, but did not change severity of active MBP-EAE or regulate Th1/Th17 responses. We conclude that IL-6 transsignalling may play a role in autoimmune inflammation of the CNS mainly by regulating early expression of adhesion molecules, possibly via cellular networks at the blood-brain barrier.     

Autogenous bone grafting for chronic anteroinferior glenoid defects via a complete subscapularis tenotomy approach

Introduction  Open reconstruction of severe anteroinferior chronic glenoid defects via a complete subscapularis (SSC) tenotomy using a tricortical iliac crest bone grafting technique has been reported. The purpose of this study was to evaluate the clinical and radiological results in patients who underwent this procedure and to investigate the influence of the anterior approach on the structure and function of the SSC musculotendinous unit. Materials and methods  Ten patients (two women/eight men, mean age 28.7 years) underwent reconstruction of significant chronic glenoid defects in cases of recurrent shoulder instability with significant glenoid bone loss, using a tricortical autogenous iliac crest in combination with a capsulolabral repair. The patients were followed up clinically (clinical SSC tests and signs, Constant score, Rowe score, Walch-Duplay score, WOSI, MISS), by standard radiographs (true a/p, axillary and glenoid profile view), computed tomography (graft integration, inferior glenoid area) and bilateral magnetic resonance imaging [SSC tendon integrity, cross sectional area, defined muscle diameters and signal intensity analysis (ratio ISP/upper SSC and ISP/lower SSC)]. Results  After a mean follow-up of 37.9 months, the mean Constant score averaged 88.3 points, the Rowe score 89.5 points, the Walch-Duplay score 83.5 points, the MISS 80.6 points and the WOSI 82.6%. No recurrent subluxations or dislocations were observed. Clinical signs for SSC insufficiency were present in 80% of cases. Two patients had grade I and one patient grade II osteoarthritis according to Samilson and Prieto classification. CT imaging revealed a consolidated autograft in all cases with an 18.4% increase of the inferior glenoid area postoperatively (P < 0.05). No tendon ruptures were found. MR imaging revealed muscular atrophy (P < 0.05) and fatty infiltration of the SSC (P > 0.05) muscle compared to the contralateral side. Conclusion  Open reconstruction of anteroinferior chronic glenoid defects via a complete SSC tenotomy using an iliac crest bone grafting technique allows an anatomic reconstruction of the anteroinferior glenoid with good and excellent clinical results. The anterior approach may lead to atrophy and fatty infiltration of the SSC muscle despite an intact tendon. However, this did not affect the results in terms of stability.     

Criteria in Sentinel Lymph Nodes of Melanoma Patients that Predict Involvement of Nonsentinel Lymph Nodes

Background Previous studies described various criteria in sentinel lymph nodes (SLN) of melanoma patients that predict the involvement of further, nonsentinel lymph nodes (NSLN). Such criteria may facilitate the selection of patients who might benefit from a completion lymph node dissection (CLND). However, it is currently unclear which parameters are most important. Methods A total of 180 melanoma patients with positive SLNB and subsequent CLND were investigated. Histopathologic parameters in the SLN were systematically evaluated and compared with regard to NSLN positivity. Twenty-eight of these patients (16.0%) had positive NSLN. Results By univariate analysis several criteria with regard to tumor burden and location of melanoma cells in the SLN correlated with NSLN involvement, such as positivity by hematoxylin-eosin (H&E) staining (P < .001), largest diameter of clusters (P < .001), capsular involvement (P = .001), extranodal extension (P < .001), and tumor penetrative depth (P < .001). Multivariate analysis revealed three independent parameters: (1) positivity of the SLN by H&E staining (versus by immunohistochemistry alone), (2) relative tumor burden >10% of total lymph node tissue, and (3) perinodal intralymphatic tumor. In 23 of 28 patients with positive NSLN the SLN was positive by H&E staining, in 15 of 28 patients the relative tumor burden was >10%, and 13 of 28 showed perinodal intralymphatic tumor. In 5 of 28 patients with NSLN involvement, these three parameters were negative. Conclusions Histopathologic examination of the SLN can identify patients at risk for NSLN positivity.     

The hippocampus in families with schizophrenia in relation to obstetric complications

BACKGROUND: Hippocampal volume reduction is a well replicated finding in schizophrenia. Evidence indicates a contribution of genetic and environmental factors, especially the influence of obstetric complications to this volume reduction. The aim of this study was to compare hippocampal volume of schizophrenic patients as well as and their relatives with control subjects and to quantify the additional contribution of obstetric complications. METHODS: T1 weighted MRI brain scans of 50 schizophrenic patients, 88 first-degree relatives and 53 healthy control subjects were used to perform volumetric measurements on the left and right hippocampus. A set of clinical measures including obstetric complications were recorded for all family members. RESULTS: Numerically our measurements revealed a hippocampal volume reduction in schizophrenic patients (left: - 14%, right: - 15%) and, although less pronounced, in their unaffected relatives (left: - 6%, right: - 10%). Noted differences in hippocampal volume between schizophrenic patients and controls were only significant for the left side. Hippocampal volumes of patients and their relatives with obstetric complications were reduced bilaterally. CONCLUSIONS: Hippocampal volume reduction is present in schizophrenic patients and their first-degree relatives, suggesting an influence of genetic factors.. In addition, however, obstetric complications have also been shown to play a major role.     

The glutamate receptor 2 subunit controls post-synaptic density complexity and spine shape in the dentate gyrus

In adult brain the majority of AMPA glutamate receptor (GluR) subunits contain GluR2. In knock-out (KO) mice the absence of GluR2 results in consequences for synaptic plasticity including cognitive impairments. Here the morphology of dendritic spines and their synaptic contacts was analysed via three-dimensional reconstruction of serial electron micrographs from dentate gyrus (DG) of adult wild type (WT) and GluR2 KO mice. Pre-embedding immunocytochemical staining was used to examine the distribution and subcellular localization of AMPA receptor GluR1 and N -methyl- d -aspartate receptor NR1 subunits. There were no significant changes in synapse density in the DG of GluR2 KO compared with WT mice. However, in GluR2 KO mice there was a significant decrease in the percentage of synapses on mushroom spines but an increase in synapses on thin spines. There was also a large decrease in the proportion of synapses with complex perforated/segmented post-synaptic densities (PSDs) (25 vs. 78% in WT) but an increase in synapses with macular PSDs (75 vs. 22%). These data were coupled in GluR2 KO mice with significant decreases in volume and surface area of mushroom spines and their PSDs. In both GluR2 KO and WT mice, NR1 and GluR1 receptors were present in dendrites and spines but there was a significant reduction in NR1 labelling of spine membranes and cytoplasm in GluR2 KO mice, and a small decrease in GluR1 immunolabelling in membranes and cytoplasm of spines in GluR2 KO compared with WT mice. Our data demonstrate that the absence of GluR2 has a significant effect on both DG synapse and spine cytoarchitecture and the expression of NR1 receptors.     

Gender aspects of parents’ needs of schizophrenia patients

Background  Most studies about the problems and needs of schizophrenia carers included only one care-giving relative, usually the patients’ mothers. Methods  101 mothers and fathers of the same patients suffering from schizophrenia were included into this study. Their needs were assessed by means of the “Carers’ Needs Assessment for Schizophrenia”. Results  Mothers reported significantly more often problems than fathers concerning stress due to earlier life events and burn-out. Mothers needed interventions such as individual psychoeducation or family counselling more than twice as often as fathers. Overall, mothers reported higher numbers of problems and needs for intervention than fathers. The number of mothers’ problems was predicted by not living with a partner and by a shorter duration of the patients’ illness. The number of mothers’ needs was predicted by more psychiatric symptoms, not living with a partner and a shorter duration of the patients’ illness. Among fathers we could not identify any predictors, neither for the number of problems nor for the number of needs. Conclusions  Fathers and mothers often report problems and frequently need professional support. Overall, mothers exhibited more problems and needs for interventions than fathers. The differences between mothers and fathers indicate the importance of considering the carer’s gender in clinical work.     

Visual noise effects on emotion perception: brain potentials and stimulus identification

Event-related potential (ERP) studies revealed an early posterior negativity (EPN) for emotionally arousing pictures. Two studies explored how this effect relates to perceptual stimulus characteristics and stimulus identification. Adding various amounts of visual noise varied stimulus perceptibility of high and low arousing picture contents, which were presented as rapid and continuous stream. Measuring dense sensor event-related potentials, study I determined that noise level was linearly related to the P1 peak. Subsequently, enlarged EPNs to emotionally arousing contents were observed, however, only for pictures containing low amounts of noise, which also enabled stimulus identification as shown by study II. These data support the notion that the EPN may serve as a measure of affective stimulus evaluation at an early transitory processing period.     

Disease mechanisms in neuropathic itch

Itch, also known as pruritus, is an unpleasant cutaneous sensation that provokes the desire to scratch. Itch is a common symptom of inflammatory skin disorders, but it can also occur in neurological diseases associated with injury to nervous tissue, in the absence of any skin disease and without any notable physiological stimuli in the periphery. This 'neuropathic' type of itch occurs either in combination with neuropathic pain or independently and is thought to be underdiagnosed. In this Review, we describe the physiological characteristics of specific neuronal systems in the PNS and CNS that transmit and process pruriceptive information, and we consider pathological changes that occur in these systems after nerve lesions. We then introduce a classification system for itch and highlight the similarities and differences between neuropathic itch and neuropathic pain. A summary of neuropathic syndromes in the PNS and CNS that are associated with itch is presented. Finally, we propose appropriate treatment strategies for neuropathic itch, in view of the fact that this condition has different mechanisms of itch generation to other types of itch and consequently requires different therapies.     

Emotional well-being in children and adolescents treated with atomoxetine for attention-deficit/hyperactivity disorder: Findings from a patient,parent and physician perspective using items from the pediatric adverse event rating scale (PAERS)

Background  

The objective of this analysis was to measure changes in items on the Pediatric Adverse Event Rating Scale (PAERS) that relate to emotional well-being of children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) during treatment with atomoxetine for up to 24 weeks from the perspective of the patient, the parent, and the physician.