TY - THES A1 - Lang, Thomas T1 - Vergleich der rheologischen Qualität von Erythrozytenkonzentraten, gewonnen durch herkömmliche Vollblutspende oder Multikomponentenspende und Einfluß der Entnahmeverfahren auf ausgewählte rheologische Laborparameter und in-vivo-Mikrozirkulation des Spenders T1 - Comparison of the rheological quality of red cell concentrates extracted from conventional whole blood donation or multicomponent apheresis and examination of the influence of the extraction method on selected rheological laboratory parameters and in-vivo microcirculation of the donor N2 - 20 Probanden nahmen im prospektiven Paarvergleich im Abstand von mindestens 8 Wochen im cross-over-Verfahren an je einer Vollblutspende (VBS) und einer maschinellen Multikomponentenspende (MKS) teil. Die erzeugten leukozyten-depletierten Erythrozytenkonzentrate beider Gruppen wurden mittels CPD-50 antikoaguliert und über einen Zeitraum von 63 Tagen in PAGGS-Mannitol gelagert. Beurteilt wurden zum einen rheologische in-vitro-Parameter bei Spendern und Blutkonserven in zweiwöchentlichen Abständen: oszillierende Kapillarviskosimetrie, Erythrozytenaggregometrie und Filtrometrie. Zudem kam bei den Maschinenspendern die neue Methode der Laser-Doppler-Anemometrie zur Ermittlung der kapillären in-vivo-Blutflußgeschwindigkeit in Einzelkapillaren zur Anwendung. Konkordant kam es in beiden Gruppen zum Ansteigen der viskösen Viskosität der Erythrozytenkonzentrate mit überproportionalem Anstieg nach 7 Wochen Lagerung. Die elastische Viskosität stieg ebenfalls in beiden Gruppen an, hier wurden in der Gruppe der Vollblutspender bereits zu Beginn deutlich höhere Werte gemessen, welche in der Vergleichsgruppe erst nach 49 Tagen erreicht wurden. Bei den Blutspendern konnten 24 Stunden nach Spende Veränderungen von visköser und elastischer Viskosität gezeigt werden, welche stark mit Erythrozytenanzahl, Hämoglobin und Hämatokrit korrelierten. Bei konstanten Werten der dynamischen Erythrozytenaggregation zeigte die statische Erythrozytenaggregation bei den Vollblutspenden nach drei Wochen eine Zunahme, in der MKS-Gruppe imponierte ein biphasisches Verhalten mit initialer Abnahme der Lichttransmission. Unabhängig vom Spendeverfahren, trat eine deutliche Abnahme der Filtrierbarkeit der Produkte in beiden Gruppen in den letzten beiden Lagerungswochen auf. Eindrucksvoll war die Reduktion der Filterokklusionsrate auf unter 40 % des Ausgangswertes durch Leukozytenfiltration vor der Lagerung. Bereits 1 Stunde nach der Spende konnten filtrometrische Veränderungen bei den Spendern gezeigt werden, das Signifikanzniveau wurde hier nur knapp verfehlt. Die Bestimmung der kapillären Blutflußgeschwindigkeit zeigte eine Stunde nach Spende eine deutliche Abnahme auf 81 % des Ausgangswertes (p=0,064) in der Gruppe der Maschinenspender. Dies wird als Ausdruck einer diskreten Kreislaufbelastung durch das Aphereseverfahren gewertet. N2 - 20 test persons took part in the prospective pair-comparison at intervals of at least eight weeks in the cross-over method, consisting of one whole blood donation and one automated cytapheresis. The produced leukocyte-depleted red blood cell concentrates of both groups were anticoagulated via CPD-50 and stored in PAGGS-Mannitol for a period of 63 days. Rheological in-vitro parameters of the donors and the products were evaluated at intervals of two weeks: oscillating capillary viscosimetry, erythrocyte aggregometry and filtrometry. Furthermore the new method of laser-Doppler anemometry was implemented with the cytapheresis group in order to determine the capillary in-vivo blood flow velocity in single-capillaries. In both groups the viscous viscosity of the red blood cell concentrates increased by a disproportionately rise after seven weeks in storage. The elastic viscosity also increased in both groups. Notably higher values were gauged in the cytapheresis group already at the beginning, which were reached by the comparison group only after 49 days. 24 hours after the donation alterations of viscous and elastic viscosity of the donors’ blood could be observed, highly correlating with number of erythrocytes, hemoglobin and hematocrit. With the values of the dynamic erythrocyte aggregation remaining constant the static erythrocyte aggregation of whole blood donors showed an increase after three weeks. Within the automated cytapheresis group a biphasic behaviour with initial decrease of light transmission was noticeable. Independent of the donation method a significant decrease of the products’ filterability could be noted in both groups during the last two weeks in storage. The reduction of the clogging rate to below 40 % of the initial value by means of leukocyte filtration before putting the samples into storage was quite impressive. Filtrometric alterations within the donor groups could be verified only one hour after the donation. The level of significance was not reached here. In the automated cytapheresis group the capillary blood flow velocity showed a significant decrease to 81 % of its initial value (p=0,064) one hour after the donation. This is seen as the expression of a discrete strain on the donor’s circulation caused by the apheresis. KW - Blut KW - Erythrozyten KW - Rheologie KW - Apherese KW - Qualität KW - blood KW - erythrocyte KW - rheology KW - cytapheresis KW - quality Y1 - 2002 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-6055 ER - TY - JOUR A1 - Weber, Heike A1 - Scholz, Claus Jürgen A1 - Domschke, Katharina A1 - Baumann, Christian A1 - Klauke, Benedikt A1 - Jacob, Christian P. A1 - Maier, Wolfgang A1 - Fritze, Jürgen A1 - Bandelow, Borwin A1 - Zwanzger, Peter Michael A1 - Lang, Thomas A1 - Fehm, Lydia A1 - Ströhle, Andreas A1 - Hamm, Alfons A1 - Gerlach, Alexander L. A1 - Alpers, Georg W. A1 - Kircher, Tilo A1 - Wittchen, Hans-Ulrich A1 - Arolt, Volker A1 - Pauli, Paul A1 - Deckert, Jürgen A1 - Reif, Andreas T1 - Gender Differences in Associations of Glutamate Decarboxylase 1 Gene (GAD1) Variants with Panic Disorder N2 - Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females. Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype6gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype6gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score. Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder. KW - Medizin Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75830 ER - TY - JOUR A1 - Rayner, Christopher A1 - Coleman, Jonathan R. I. A1 - Purves, Kirstin L. A1 - Hodsoll, John A1 - Goldsmith, Kimberley A1 - Alpers, Georg W. A1 - Andersson, Evelyn A1 - Arolt, Volker A1 - Boberg, Julia A1 - Bögels, Susan A1 - Creswell, Cathy A1 - Cooper, Peter A1 - Curtis, Charles A1 - Deckert, Jürgen A1 - Domschke, Katharina A1 - El Alaoui, Samir A1 - Fehm, Lydia A1 - Fydrich, Thomas A1 - Gerlach, Alexander L. A1 - Grocholewski, Anja A1 - Hahlweg, Kurt A1 - Hamm, Alfons A1 - Hedman, Erik A1 - Heiervang, Einar R. A1 - Hudson, Jennifer L. A1 - Jöhren, Peter A1 - Keers, Robert A1 - Kircher, Tilo A1 - Lang, Thomas A1 - Lavebratt, Catharina A1 - Lee, Sang-hyuck A1 - Lester, Kathryn J. A1 - Lindefors, Nils A1 - Margraf, Jürgen A1 - Nauta, Maaike A1 - Pané-Farré, Christiane A. A1 - Pauli, Paul A1 - Rapee, Ronald M. A1 - Reif, Andreas A1 - Rief, Winfried A1 - Roberts, Susanna A1 - Schalling, Martin A1 - Schneider, Silvia A1 - Silverman, Wendy K. A1 - Ströhle, Andreas A1 - Teismann, Tobias A1 - Thastum, Mikael A1 - Wannemüller, Andre A1 - Weber, Heike A1 - Wittchen, Hans-Ulrich A1 - Wolf, Christiane A1 - Rück, Christian A1 - Breen, Gerome A1 - Eley, Thalia C. T1 - A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders JF - Translational Psychiatry N2 - Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r(g) approximate to 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We (h(SNP)(2)) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and estimated the variance in therapy outcomes that could be explained by common genetic variants learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h(SNP)(2) could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits. KW - Human behaviour KW - Personalized medicine KW - Prognostic markers KW - Psychiatric disorders Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225048 VL - 9 IS - 150 ER -