No evidence for preferential transmission of common valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor gene (BDNF) in ADHD

Summary Attention deficit/hyperactivity disorder (ADHD) is a highly heritable common neurodevelopmental disorder with onset in childhood. A coding SNP (rs6265, Val66Met) of the brain-derived neurotrophic factor gene (BDNF) has recently been associated with ADHD. More specifically, paternal over-transmission of the common Val66 allele to affected children had been observed. We aimed to confirm these findings in a large, sufficiently powered, and well characterized German ADHD family sample. The Val66Met polymorphism of BDNF was genotyped in 294 families comprising one or more affected sibs (468 children). Contrary to previous reports, we did not observe over-transmission of the common Val66 allele, from either parent to affected children. We did not find support for an involvement of the Val66 allele of the Val66Met polymorphism of BDNF in the pathogenesis of ADHD in our sample. First two authors contributed equally.     

Family-based association study of serotonergic candidate genes and attention-deficit/hyperactivity disorder in a German sample

Summary Alterations in the serotonergic pathway have been implicated in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to investigate seven genetic variants in three genes (serotonin transporter (5-HTT), serotonin receptor 1B (5-HTR1B) and serotonin receptor 2A (5-HTR2A)), which have previously been shown to be associated with ADHD. The polymorphisms under investigation were the 5-HTTLPR, the VNTR in intron 2 and the 3′UTR SNP in 5-HTT, the 5-HTR1B variations 861G>C and 102T>C, and the 5-HTR2A variations His452Tyr and 1438G>A. We genotyped these variants in a sample of 102 families with 229 children with ADHD according to DSM-IV criteria. Among the affected children, 69% fulfilled criteria for the combined type, 27% for the predominantly inattentive type, and 4% for the predominantly hyperactive-impulsive type. Associations were tested by the pedigree transmission disequilibrium test (PDT). All investigated polymorphisms in serotonergic candidate genes showed no association to ADHD in our sample. Earlier studies of these polymorphisms had also shown inconsistent results, with some studies reporting significant associations and others demonstrating no association. This discordance between studies may reflect variation in patient ascertainment criteria, genetic heterogeneity, too low statistical power for the expected effects or false positive results in the initial reports. We cannot rule out the possibility that other variations in the investigated genes contribute to the etiology of ADHD.     

Children and adolescents with obsessive-compulsive disorder and comorbid attention-deficit/hyperactivity disorder: preliminary results of a prospective follow-up study

Summary. In the present study, we have investigated the influence of comorbid attention deficit hyperactivity disorder (ADHD) on early onset obsessive compulsive disorder (OCD). For that purpose, we compared 20 patients with “OCD with ADHD” and 20 randomly selected patients with “OCD without ADHD”. “OCD with ADHD” patients tended to show an earlier age of OCD onset, a higher severity of symptoms and a higher persistence rate than OCD patients without ADHD. Both groups appear to develop different patterns of comorbid disorders. The first two authors have equally contributed to the study. Correspondence: Susanne Walitza, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany     

Improving Osteoporosis Assessment in the Fracture Clinic

INTRODUCTION

The aim of this study was to compare the effectiveness of different ways of referring patients to an osteoporosis assessment service at an orthopaedic fracture clinic of a hospital in the UK.

PATIENTS AND METHODS

Three methods of identifying and referring to an osteoporosis assessment service were evaluated.

RESULTS

Relying on doctors for such a referral gave a catchment rate of only 1.6%. Involving patients themselves, asking them to self-refer, increased the catchment rate to 63% (P < 0.0001). Having a specialist osteoporosis and fracture liaison nurse present in clinic and reviewing the notes of patients checking in, to see if they match criteria for osteoporosis assessment, further increased catchment to 77% (P = 0.036).

CONCLUSIONS

Simply having an osteoporosis assessment service and strict criteria to identify which patients should be referred to such a service will not necessarily increase catchment rate for osteoporosis patients. A nurse physically present in the clinic provided the best result, and supports the need of investing in an osteoporosis and fracture liaison nurse.     

Endoscopic anatomy of the thecal sac using a flexible steerable endoscope

In this study the ability for upward-orientated endoscopic visualization of thecal subarachnoid space using a flexible steerable endoscope was evaluated in order to compare endoscopic anatomical findings with the already known macroscopic ones of the incontained structures and to test the approach for clinical employment. For this purpose, four adult phenol-formalin embalmed cadavers were used and the approach selected was through a laminectomy window at the S1-S2 level. The dura mater was opened and a flexible steerable endoscope (Storz, of 2.8 mm external diameter with one working channel) was inserted subarachnoidally for upward-orientated observation of the content of thecal sac. By using this approach filum terminale, lower lumbar, sacral and coccygeal nerve rootlets were identified and observed in detail. By moving the endoscope even more upwards, inspection of the upper part of the thecal subarachnoid space and conus medullaris was also possible. The findings collected from the study indicate that this approach for upward-orientated intradural subarachnoid endoscopy gives an appropriate working and inspecting window to the lower, as well as to the upper part of the thecal subarachnoid space and even of the conus medullaris. Furthermore, inspection and identification of lower lumbar, sacral and coccygeal nerve rootlets is possible and efficient and the endoscopic anatomical observations coincide with the already known gross-anatomical ones.     

Epstein-Barr virus negative clonal plasma cell proliferations and lymphomas in peripheral T-cell lymphomas: a phenomenon with distinctive clinicopathologic features

Clonal B-cell populations have been described in peripheral T-cell lymphomas (PTCL) as secondary Epstein-Barr virus (EBV) driven B-cell expansions that may evolve to an overt B-cell lymphoma. EBV-negative B-cell proliferations associated with T-cell lymphomas are uncommon and not well characterized. We studied 15 patients who developed an EBV-negative B-cell proliferation or malignant lymphoma associated with PTCL. The T-cell tumors were 8 PTCL, not otherwise specified, 4 angioimmunoblastic T-cell lymphomas, and 3 cutaneous PTCL. The B-cell component was intermingled with the PTCL in all patients and it was classified as clonal/monotypic plasma cell proliferation in 8 lesions, clonal/monotypic large B-cell proliferation in 4 patients, and B-cell lymphoma with plasmacytic/plasmablastic differentiation in 3 patients. Two patients had 2 clonally unrelated plasma cell proliferations associated with the same PTCL. All cases showed cytoplasmic Ig light chain restriction. Clonal IgH and T-cell receptor rearrangements were detected in 11/12 and 11/13 cases examined, respectively. EBV, cytomegalovirus, and HHV-8 were not observed in any of the examined cases. Sequential samples in 7 patients showed persistence of the PTCL and the B-cell component in 4, the PTCL without the B-cell lymphoma in 2, and progression of the B-cell neoplasm in 1. Patients followed an aggressive clinical course similar to conventional PTCL. In conclusion, EBV-negative clonal or mononotypic B-cell proliferations in patients with PTCL present with a spectrum of lesions ranging from plasma cell proliferations to overt lymphomas with plasmacytic/plasmablastic features. The distinctive features of these patients suggest that these lesions represent a specific phenomenon in PTCL.