Further delineation of Weaver syndrome

Seven new cases of Weaver syndrome are described, including the first reported case in an adult. Overgrowth is usually but not always present. The combination of characteristic facies and developmental delay, with the peculiar radiographic findings of accelerated dysharmonic osseous maturation and splaying of the distal long bones, is diagnostic of Weaver syndrome.     

“Conventional” isthmus ablation without fluoroscopy

Recently, a new technology for nonfluoroscopic 4-D catheter tracking has been introduced (MediGuide). This system allows precise catheter visualization on prerecorded conventional fluoroscopy loops. We report about the first experience in atrial flutter ablation using a MediGuide-supported ablation catheter. For successful ablation besides the 6 s for loop acquisition, no further fluoroscopy was used.     

Neuropathische Schmerzen

Neuropathic pain is caused by lesions in the somatosensory system. Characteristic but not exclusive features are spontaneous burning pain, electrifying and shooting pain, hyperalgesia, and allodynia. The basic concept of the pathophysiology of neuropathic pain is the combination of peripheral and central sensitization. Knowledge on the molecular mechanisms has grown exponentially in recent years. The problem lies in identifying the individual mechanisms and in determining a comprehensive concept. Progress has also been made in assessment, e.g., methods for detecting dysfunction of nociceptors have significantly improved. In addition, there are many more therapeutic options available than 15 years ago. The drugs available include antidepressants, anticonvulsants, opioids, and topical medications. Data from controlled trials and recommendations from guidelines are available.     

Antiendomysial and antihuman recombinant tissue transglutaminase antibodies in the diagnosis of coeliac disease: a biopsy-proven European multicentre study

OBJECTIVE: To investigate the value of serum antitissue transglutaminase IgA antibodies (IgA-TTG) and IgA antiendomysial antibodies (IgA-EMA) in the diagnosis of coeliac disease in cohorts from different geographical areas in Europe. The setting allowed a further comparison between the antibody results and the conventional small-intestinal histology. METHODS: A total of 144 cases with coeliac disease [median age 19.5 years (range 0.9-81.4)], and 127 disease controls [median age 29.2 years (range 0.5-79.0)], were recruited, on the basis of biopsy, from 13 centres in nine countries. All biopsy specimens were re-evaluated and classified blindly a second time by two investigators. IgA-TTG were determined by ELISA with human recombinant antigen and IgA-EMA by an immunofluorescence test with human umbilical cord as antigen. RESULTS: The quality of the biopsy specimens was not acceptable in 29 (10.7%) of 271 cases and a reliable judgement could not be made, mainly due to poor orientation of the samples. The primary clinical diagnosis and the second classification of the biopsy specimens were divergent in nine cases, and one patient was initially enrolled in the wrong group. Thus, 126 coeliac patients and 106 controls, verified by biopsy, remained for final analysis. The sensitivity of IgA-TTG was 94% and IgA-EMA 89%, the specificity was 99% and 98%, respectively. CONCLUSIONS: Serum IgA-TTG measurement is effective and at least as good as IgA-EMA in the identification of coeliac disease. Due to a high percentage of poor histological specimens, the diagnosis of coeliac disease should not depend only on biopsy, but in addition the clinical picture and serology should be considered.     

Separating stimulus‐driven and response‐related LRP components with Residue Iteration Decomposition (RIDE)

When the lateralized readiness potential (LRP) is recorded in stimulus–response compatibility (SRC) tasks, two processes may overlap in the LRP, stimulus‐driven response priming and activation based on response selection rules. These overlapping processes are hard to disentangle with standard analytical tools. Here, we show that Residue Iteration Decomposition (RIDE), based on latency variability, separates the overlapping LRP components from a Simon task into stimulus‐driven and response‐related components. SRC affected LRP amplitudes only in the stimulus‐driven component, whereas LRP onsets were affected only in the response‐locked component. Importantly, the compatibility effect in reaction times was more similar to the effect in the onsets of the RIDE‐derived response‐locked LRP component than in the unseparated LRP. Thus, RIDE‐separated LRP components are devoid of distortions inherent to standard LRPs.     

Anterior vs Posterior Hippocampal Subfields in an Extended Psychosis Phenotype of Multidimensional Schizotypy in a Nonclinical Sample

Numerous studies have implicated involvement of the hippocampus in the etiology and expression of schizophrenia-spectrum psychopathology, and reduced hippocampal volume is one of the most robust brain abnormalities reported in schizophrenia. Recent studies indicate that early stages of schizophrenia are specifically characterized by reductions in anterior hippocampal volume; however, studies have not examined hippocampal volume reductions in subclinical schizotypy. The present study was the first to examine the associations of positive, negative, and disorganized schizotypy dimensions with hippocampal subfield volumes in a large sample (n = 195) of nonclinically ascertained young adults, phenotyped using the Multidimensional Schizotypy Scale (MSS). Hippocampal subfields were analyzed from high-resolution 3 Tesla structural magnetic resonance imaging scans testing anatomical models, including anterior vs posterior regions and the cornu ammonis (CA), dentate gyrus (DG), and subiculum subfields separately for the left and right hemispheres. We demonstrate differential spatial effects across anterior vs posterior hippocampus segments across different dimensions of the schizotypy risk phenotype. The interaction of negative and disorganized schizotypy robustly predicted left hemisphere volumetric reductions for the anterior and total hippocampus, and anterior CA and DG, and the largest reductions were seen in participants high in negative and disorganized schizotypy. These findings extend previous early psychosis studies and together with behavioral studies of hippocampal-related memory impairments provide the basis for a dimensional neurobiological hippocampal model of schizophrenia risk. Subtle hippocampal subfield volume reductions may be prevalent prior to the onset of detectable prodromal clinical symptoms of psychosis and play a role in the etiology and development of such conditions.     

Situating language in a minimal social context: how seeing a picture of the speaker’s face affects language comprehension

Natural use of language involves at least two individuals. Some studies have focused on the interaction between senders in communicative situations and how the knowledge about the speaker can bias language comprehension. However, the mere effect of a face as a social context on language processing remains unknown. In the present study, we used event-related potentials to investigate the semantic and morphosyntactic processing of speech in the presence of a photographic portrait of the speaker. In Experiment 1, we show that the N400, a component related to semantic comprehension, increased its amplitude when processed within this minimal social context compared to a scrambled face control condition. Hence, the semantic neural processing of speech is sensitive to the concomitant perception of a picture of the speaker’s face, even if irrelevant to the content of the sentences. Moreover, a late posterior negativity effect was found to the presentation of the speaker’s face compared to control stimuli. In contrast, in Experiment 2, we found that morphosyntactic processing, as reflected in left anterior negativity and P600 effects, is not notably affected by the presence of the speaker’s portrait. Overall, the present findings suggest that the mere presence of the speaker’s image seems to trigger a minimal communicative context, increasing processing resources for language comprehension at the semantic level.     

Secretory products from human adipocytes impair endothelial function via nuclear factor kappaB

Hyperplasia and hypertrophy of fat cells can be found in obesity, and increased adiposity is associated with endothelial dysfunction as an early event of atherosclerosis. However, it is unclear whether human adipocytes directly influence endothelial function. To study the crosstalk between fat and endothelial cells, human umbilical venous endothelial cells (HUVECs), and human coronary artery endothelial cells (HCAECs) were cultured in infranatants (Adipo) of primary differentiated human adipocytes. Interestingly, incubation of HUVECs and HCAECs with Adipo significantly increased monocyte adhesion 7.3 and 2.2-fold, respectively. VCAM-1, ICAM-1, and E-selectin in HUVECs were upregulated 3.9, 3.0, and 9.5-fold, respectively, under these conditions. Furthermore, Adipo significantly stimulated NFkappaB activity 1.9-fold. The NFkappaB inhibitor MG-132 and heat inactivation significantly reversed Adipo-stimulated monocyte adhesion. TNFalpha-neutralizing antibodies partly reversed Adipo-induced monocyte adhesion. In contrast, thiazolidinedione-pretreatment of human adipocytes did not alter the effects of Adipo. Adipo did not show cytotoxic effects. Taken together, we demonstrate that endothelial dysfunction is induced by adipocyte-secreted factors via NFkappaB partly dependent on TNFalpha.     

Opioide bei chronischem Arthroseschmerz

Background

The efficacy, tolerability and safety of opioid therapy in chronic osteoarthritis (OA) pain is under debate. We updated a Cochrane systematic review on the efficacy and safety of opioids in chronic OA pain published in 2009.

Methods

We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in chronic osteoarthritis (OA) pain. We included double-blind randomized placebo-controlled studies lasting ≥?4 weeks. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables.

Results

We included 20 RCTs with 33 treatment arms and 8545 participants. Median study duration was 12 (4–24) weeks. Oxycodone and tramadol were each tested in six studies; buprenorphine, hydromorphone, morphine and tapentadol each in two studies and codeine, fentanyl and oxymorphone in one study each. Results are reported with 95?% confidence intervals (CIs). Opioids were superior to placebo in reducing pain intensity (SMD ??0.22 [??0.28, ??0.17], p?<?0.00001; 16 studies with 6743 participants). Opioids were not superior to placebo in 50?% pain reduction (RD ??0.00 [??0.07, 0.07], p?=?0.96; two studies with 2684 participants). Opioids were superior to placebo in terms of reports of much or very much global improvement (RD 0.13 [0.05, 0.21], p?=?0.002; three studies with 2251 participants). Opioids were superior to placebo in improving physical functioning (SMD ??0.22 [??0.28, ??0.17], p?<?0.00001; 14 studies with 5887 participants). Patients dropped out more frequently with opioids than with placebo (RD 0.17 [0.14, 0.21], p?<?0.00001; 15 studies with 6834 participants; number needed to harm 5 [4–6]. There was no significant difference between opioids and placebo in the frequency of serious adverse events (SAE) or deaths over the respective observation periods.

Conclusion

Opioids were superior to placebo in terms of efficacy and inferior in terms of tolerability. The effect sizes of average reduction in pain intensity and physical disability were small. Opioids and placebo did not differ in terms of safety. The conclusion on the safety of opioids compared to placebo is limited by the low number of SAE and deaths. Short-term opioid therapy may be considered in selected chronic OA pain patients. No current evidence-based guideline recommends opioids as first-line treatment option for chronic OA pain. To provide superior evidence for future treatment guidelines, RCTs must directly compare existing pharmacological and nonpharmacological therapies and administer these in various combinations and sequences.The English full-text version of this article is freely available at SpringerLink (under “Supplemental”).