Psychische und familiäre Risiken für Kinder von Frauen mit Epilepsie?: Ergebnisse einer Längsschnittstudie

Abstract : This study investigates teratogenic effects of antiepileptic drugs (AED) by tracing from birth to adolescence 67 children born to epileptic women and a matched control sample of 49 children. We assessed the intellectual performance (Wechsler-Intelligence Tests) at adolescence as well as the prevalence of psycho-behavioral problems and the relationship to their parents. Adolescents who had been exposed to only one kind of drug during gestation (monotherapy), achieved moderately lower IQ's than those of the control group (-6 IQ scores). However, the effect was salient in polydrug-exposed offspring (-12 IQ scores). Generalized (major) maternal seizures during pregnancy did not add to this effect. The families' psychosocial ecology affected risk and control participants differentially: The intellectual development of adolescents with prenatal risks was significantly more vulnerable to adverse environmental circumstances than was that of controls. With regard to psychological stress the affected children unexpectedly reported significantly less psychological stress than the controls even though they had to assist their mothers more frequently and although they reported receiving little support from the

Strain and Strain Rate Imaging by Echocardiography – Basic Concepts and Clinical Applicability

Echocardiographic strain and strain-rate imaging (deformation imaging) is a new non-invasive method for assessment of myocardial function. Due to its ability to differentiate between active and passive movement of myocardial segments, to quantify intraventricular dyssynchrony and to evaluate components of myocardial function, such as longitudinal myocardial shortening, that are not visually assessable, it allows comprehensive assessment of myocardial function and the spectrum of potential clinical applications is very wide. The high sensitivity of both tissue Doppler imaging (TDI) derived and two dimensional (2D) speckle tracking derived myocardial deformation (strain and strain rate) data for the early detection of myocardial dysfunction recommend these new non-invasive diagnostic methods for extensive clinical use. In addition to early detection and quantification of myocardial dysfunction of different etiologies, assessment of myocardial viability, detection of acute allograft rejection and early detection of allograft vasculopathy after heart transplantation, strain and strain rate data are helpful for therapeutic decisions and also useful for follow-up evaluations of therapeutic results in cardiology and cardiac surgery. Strain and strain rate data also provide valuable prognostic information, especially prediction of future reverse remodelling after left ventricular restoration surgery or after cardiac resynchronization therapy and prediction of short and median-term outcome without transplantation or ventricular assist device implantation of patients referred for heart transplantation

Protection from cytomegalovirus after transplantation is correlated with immediate early 1–specific CD8 T cells

T cells are crucial for the control of cytomegalovirus (CMV) in infected individuals. Although CMV-specific T cells can be quantified by various methods, clear correlates of protection from CMV disease have not been defined. However, responses to the pp65 protein are believed to play an important role. Here, the proportions of interferon γ–producing T cells following ex vivo activation with pools of overlapping peptides representing the pp65 and immediate early (IE)-1 proteins were determined at multiple time points and related to the development of CMV disease in 27 heart and lung transplant recipients. Frequencies of IE-1–specific CD8 T cells above 0.2 and 0.4% at day 0 and 2 wk, respectively, or 0.4% at any time during the first months discriminated patients who did not develop CMV disease from patients at risk, 50–60% of whom developed CMV disease. No similar distinction between risk groups was possible based on pp65-specific CD8 or CD4 T cell responses. Remarkably, CMV disease developed exclusively in patients with a dominant pp65-specific CD8 T cell response. In conclusion, high frequencies of IE-1 but not pp65-specific CD8 T cells correlate with protection from CMV disease. These results have important implications for monitoring T cell responses, adoptive cell therapy, and vaccine design

α2C-Adrenoceptor polymorphism is associated with improved event-free survival in patients with dilated cardiomyopathy

Aims The sympathetic nervous system plays a central role in cardiac growth but its overstimulation is associated with increased mortality in patients with chronic heart failure. Pre-synaptic α2-adrenoceptors are essential feedback regulators to control the release of norepinephrine from sympathetic nerves. In this study we tested whether a deletion polymorphism in the human α2C-adrenoceptor gene (α2CDel322-325) affects progression of heart failure in patients with dilated cardiomyopathy (DCM). Methods and results We genotyped and phenotyped 345 patients presenting with DCM in the heart transplant unit of the German Heart Institute, starting in 1994. Patients were treated according to guidelines (99% ACEI, 76% β-blockers) and were followed until December 2002 or until a first event [death, heart transplantation, or implantation of a left ventricular assist device (LVAD) for a life-threatening condition] occurred. Mean follow-up time was 249 weeks (4.9 years) in event-free patients and 104 weeks (2 years) in patients with events. During follow-up, 51% of the patients exhibited an event: death (18%), implantation of LVAD as bridging for transplantation (7%), or heart transplantation (25%). By Kaplan-Meier analysis, DCM patients with the deletion variant Del322-325 in the α2C-adrenoceptor showed significantly decreased event rates (P=0.0043). Cox regression analysis revealed that the presence of the deletion was associated with reduced death rate (relative risk: 0.129, 95% CI: 0.18-0.9441, P=0.044) and event rates (relative risk: 0.167, 95% CI: 0.041-0.685, P=0.012). Conclusion α2C-Adrenoceptor deletion may be a novel, strong, and independent predictor of reduced event rates in DCM patients treated according to guideline

Author’s response

We are grateful to Demirkol et al. for their appreciativeletter regarding our paper ”Clinical, haemodynamic and echocardiographicfeatures of early cardiac graft dysfunction” [

Preamplification techniques for real-time RT-PCR analyses of endomyocardial biopsies

<p>Abstract</p> <p>Background</p> <p>Due to the limited RNA amounts from endomyocardial biopsies (EMBs) and low expression levels of certain genes, gene expression analyses by conventional real-time RT-PCR are restrained in EMBs. We applied two preamplification techniques, the TaqMan^®PreAmp Master Mix (T-PreAmp) and a multiplex preamplification following a sequence specific reverse transcription (SSRT-PreAmp).</p> <p>Results</p> <p>T-PreAmp encompassing 92 gene assays with 14 cycles resulted in a mean improvement of 7.24 ± 0.33 Ct values. The coefficients for inter- (1.89 ± 0.48%) and intra-assay variation (0.85 ± 0.45%) were low for all gene assays tested (<4%). The PreAmp uniformity values related to the reference gene CDKN1B for 91 of the investigated gene assays (except for CD56) were -0.38 ± 0.33, without significant differences between self-designed and ABI inventoried Taqman^®gene assays. Only two of the tested Taqman^®ABI inventoried gene assays (HPRT-ABI and CD56) did not maintain PreAmp uniformity levels between -1.5 and +1.5. In comparison, the SSRT-PreAmp tested on 8 self-designed gene assays yielded higher Ct improvement (9.76 ± 2.45), however was not as robust regarding the maintenance of PreAmp uniformity related to HPRT-CCM (-3.29 ± 2.40; p < 0.0001), and demonstrated comparable intra-assay CVs (1.47 ± 0.74), albeit higher inter-assay CVs (5.38 ± 2.06; p = 0.01). Comparing EMBs from each 10 patients with dilated cardiomyopathy (DCM) and inflammatory cardiomyopathy (DCMi), T-PreAmp real-time RT-PCR analyses revealed differential regulation regarding 27 (30%) of the investigated 90 genes related to both HPRT-CCM and CDKN1B. Ct values of HPRT and CDKN1B did not differ in equal RNA amounts from explanted DCM and donor hearts.</p> <p>Conclusion</p> <p>In comparison to the SSRT-PreAmp, T-PreAmp enables a relatively simple workflow, and results in a robust PreAmp of multiple target genes (at least 92 gene assays as tested here) by a mean Ct improvement around 7 cycles, and in a lower inter-assay variance in RNA derived from EMBs. Preliminary analyses comparing EMBs from DCM and DCMi patients, revealing differential regulation regarding 30% of the investigated genes, confirm that T-PreAmp is a suitable tool to perform gene expression analyses in EMBs, expanding gene expression investigations with the limited RNA/cDNA amounts derived from EMBs. CDKN1B, in addition to its function as a reference gene for the calculation of PreAmp uniformity, might serve as a suitable housekeeping gene for real-time RT-PCR analyses of myocardial tissues.</p

A genetic investigation of sex bias in the prevalence of attention-deficit/hyperactivity disorder

Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish populationregister data (N=77,905 cases, N=1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that females with ADHD may be at especially high risk of certain comorbid developmental conditions (i.e. autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score (PRS) analysis did not support a higher burden of ADHD common risk variants in female cases (OR=1.02 [0.98-1.06], p=0.28). In contrast, epidemiological sibling analyses revealed that the siblings of females with ADHD are at higher familial risk of ADHD than siblings of affected males (OR=1.14, [95% CI: 1.11-1.18], p=1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence

efficacy in prevention of rejection and impact on kidney function

Ziele der vorliegenden Arbeit sind die Bestimmung des klinischen Stellenwertes von als Standard eingesetzten MMF sowie die Analyse der Wertigkeit von EC-MPS und die Bestimmung der Effektivität und Sicherheit des von Everolimus in Kombination mit Cyclosporin im Vergleich zu MMF bei Herztransplantierten. In der Langzeitanwendung zeigt sich unter MMF im Vergleich zu Azathioprin ein signifikant verbessertes Langzeitüberleben nach 5 Jahren (94% versus 81%) sowie nach 10 Jahren (82% versus 61%). Die Gesamtsterblichkeit lag für die MMF-Patientengruppe signifikant niedriger (18,3% versus 47,9%). Unter MMF bestand eine signifikant geringere Rate an notwendigen Rejektionsbehandlungen pro Patient (0,96 versus 1,27). Wechselten Patienten im ersten Jahr nach HTx von Azathioprin auf MMF, so erzielten sie gleichgute Ergebnisse wie primär auf MMF eingestellte Empfänger. Bei MMF im Vergleich zu EC-MPS zeigt sich kein signifikanter Unterschied bezüglich zu behandelnder Rejektionen nach 12 Monaten (56,6% versus 57,7%). Unter MMF traten nicht-signifkant mehr Todesfälle (9,2% versus 5,1%) nach 12 Monaten auf. Eine Niereninsuffizienz entwickelten 38,2% der MMF- und 33,3% der EC-MPS-Patienten bis zu 12 Monate nach HTx. Unter Immunsuppression mit Everolimus im Vergleich zu MMF in Kombination mit Cyclosporin und Steroiden wurde der mittlere Cyclosporintalblutspiegel gegenüber dem Ausgangsblutspiegel im ersten Monat bis zum 12. Monat signifikant höher in der Everolimusgruppe (240±57ng/ml auf 101±26ng/ml; Δ57,9%) im Vergleich zu MMF (246±54ng/ml auf 160±41ng/ml; Δ35,0%) absenkt und lag im Monat 12 relativ um 36,9% niedriger war als unter MMF. Die Rejektionsrate war nach 12 Monaten unter Everolimus (23,6%) im Vergleich zu MMF (28,5%) niedriger, aber nicht signifikant unterschiedlich. Eine zunehmende aber nach dem 3. Monat stabilisierte Niereninsuffizienz bestand im Mittel in beiden Kollektiven. Die glomeruläre Filtrationsrate fiel über 12 Monate nach HTx in der Everolimusgruppe von 71±29ml/min/1.73m2 auf 57±27ml/min/1.73m2 im Vergleich zu 73±22 ml/min/1.73m2 auf 44±24 ml/min/1.73m2 unter MMF. Unter Immunsuppression mit Everolimus im Vergleich zu MMF und in Kombination mit Cyclosporin und Steroiden wurde der mittlere Cyclosporintalblutspiegel gegenüber dem Ausgangsblutspiegel im ersten Monat bis zum 12. Monat signifikant höher in der Everolimusgruppe (245±99ng/ml auf 110±50ng/ml; Δ55%) im Vergleich zu MMF (308±96ng/ml auf 180±55 ng/ml; Δ41,6%) absenkt und lag im Monat 12 relativ um 38,9% niedriger war als unter MMF. Es zeigten sich nicht- signifikant weniger bedeutsame Rejektionen nach 12 Monaten unter Everolimus (22,8%) im Vergleich zu MMF (29,8%). Die Einjahresüberlebensrate unterschied sich in beiden Behandlungs-gruppen nicht (89,1% versus 88,1%). Eine zunehmende, aber nach dem 3. Monat stabilisierte Niereninsuffizienz bestand im Mittel in beiden Kollektiven. Die glomeruläre Filtrationsrate fiel über 12 Monate nach HTx in der Everolimusgruppe von 72,5±27,9ml/min/1.73m2 auf 68,7±27,7ml/min/1.73m2 im Vergleich zu 76,8±32,1ml/min/1.73m2 auf 71,8±29,8ml/min/1.73m2 unter MMF und unterschied sich nicht signifikant.The aim of the study was to determine the clinical value of MMF and the value of EC-MPA, furthermore, the evaluation of efficacy and safety of Everolimus in combination with Cyclosporine compared with MMF in heart transplant recipients. Long-term use of MMF compared to Azathioprine shows a significantly improved survival after 5 years (94% versus 81%) and after 10 years (82% versus 61%). Overall mortality for MMF was lower (18,3% versus 47,9%). MMF demonstrated a significantly reduced rate of needed rejection treatments per patient (0,96 versus 1,27). MMF compared with EC-MPA demonstrated no significant difference with regard to treated rejections at 12 months (56,6% versus 57,7%). Under MMF, non-significantly more deaths occurrerd at 12 months (9,2% versus 5,1%). Impairment of kidney function occurred in 38,2% of MMF patients and in 33,3% of EC-MPA patients at month 12. Under immunosuppression with Everolimus compared to MMF in combination with Cyclosporine and steroids, baseline Cyclosporine trough levels compared with 12 month measurements were significantly lower for Everolimus (240±57ng/ml to 101±26ng/ml; Δ57,9%) compared with MMF (246±54ng/ml to 160±41ng/ml; Δ35,0%). Rejection rate at 12 months was lower for Everolimus (23,6%) compared to MMF (28,5%). Impairment of kidney function increased during the first 3 months and stabilized beyond. The glomerular filtration rate (GFR) dropped for Everolimus from 71 ± 29 ml/min/1.73m2 to 57 ± 27 ml/min/1.73m2 compared to 73 ± 22 ml/min/1.73m2 to 44 ± 24 ml/min/1.73m2 for MMF. Under immunosuppression with Everolimus compared to MMF in combination with Cyclosporine and steroids, baseline Cyclosporine trough levels compared with 12 month measurements were significantly lower for Everolimus (245±99ng/ml to 110±50ng/ml; Δ55%) compared with MMF (308±96ng/ml auf 180±55 ng/ml; Δ41,6%). Rejection rate at 12 months was lower for Everolimus (22,8%) compared with MMF (29,8%). There was no significant difference with reagard to survival in Everolimus compared with MMF (89,1% versus 88,1%). Impairment of kidney function increased during the first 3 months and stabilized beyond. GFR at 12 months dropped in Everolimus from 72,5 ± 27,9 ml/min/1.73m2 to 68,7 ± 27,7 ml/min/1.73m2 compared with 76,8 ± 32,1 ml/min/1.73m2 to 71,8 ± 29,8 ml/min/1.73m2 in MMF

Teacher training in the management of children with Attention Deficit Hyperactivity Disorder

Die Hyperkinetische Störung/Aufmerksamkeits-Defizit Hyperaktivitätsstörung stellt eine häufige Störung des Kindes- und Jugendalters dar, die sich aufgrund ihrer Symptomkonstellation sowie der begleitenden Komorbiditäten in hohem Ausmaß auf die Schul- und Berufslaufbahn der Betroffenen auswirken kann. Dem gegenüber steht bislang nur ein geringer Kenntnis- und Aus- bzw. Fortbildungsstand der unterrichtenden Lehrer an Regelschulen über einen angemessenen didaktischen und pädagogischen Umgang mit den Kindern. Des weiteren ist die Zusammenarbeit zwischen Schule, Elternhaus und therapeutischen Institutionen zumeist lückenhaft, so daß die in den klinischen Behandlungsleitlinien der psychiatrischen Fachgesellschaften postulierte sog. multimodale Behandlung keine zureichende Anwendung findet. Dieser Beitrag, der sich auf die Ergebnisse einer an einer Kölner Grundschule durchgeführten Intervention zum Umgang mit hyperkinetischen und oppositionellen Problemverhaltensweisen im Unterricht stützt, soll praktische Anhaltspunkte geben für eine erfolgversprechende pädagogische Arbeit. Diese beinhaltet erstens die umfassende Information von Lehrern über das Störungsbild, zweitens die verstärkte Einbindung des Lehrers in den psychotherapeutischen und medikamentösen Behandlungsprozeß und drittens die Durchführung geeigneter didaktischer und einfacher pädagogischtherapeutischer Maßnahmen im Umgang mit hyperkinetischen Kindern.(DIPF/Orig.)Attention Deficit/Hyperactivity Disorder is one of the most common behavior disorders in child and adolescent psychiatry. The problems resulting from the core symptoms of the disorder often endure into adolescence and adulthood placing these children at significant long-term risk for academic psychological and social morbidity. Despite the importance of the school in this process relatively few teachers of regular schools have sufficient knowlegde about the foundations and principles of treatment concerning ADHD nor do they receive adequate training how to deal with ADHD related problems in the classroom. Moreover there is a significant lack of cooperation between schools, parents and therapeutic institutions inhibiting a multimodal treatment. This article resumes the experiences of a 3 months ADHD intervention program for teachers in a Cologne elementary school. It gives informations and advices for appropriate measurements in the classroom setting that include: 1. intensive information of teachers about the disorder, 2. intensified involvement of teachers in the treatment process and 3. the implementation of distinct didactic elements and well structured principles of behaviour therapy in the school lessons.(DIPF/Orig.