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T-Lymphozyten spielen eine entscheidende Rolle in der Pathophysiologie der Rheumatoiden Arthritis. Sie fördern einerseits die perpetuierende Entzündung innerhalb der Membran und besitzen andererseits die Fähigkeit auf die Inflammationen regulativ bzw. suppressiv zu wirken. In der hier vorliegenden Arbeit wurde untersucht, ob entzündungsfördernde T-Zellprodukte und regulatorische T-Zellpopulationen innerhalb der Synovialmembran nachweisbar sind, und wie unstimulierte periphere TZellen auf Synovialmembranzellen "in vitro" reagieren. Innerhalb der Synovialmembran konnte eine Population von CD4(+)CD25(+) regulatorischen T-Zellen (Tregs) durchflusszytometrisch nachgewiesen werden. Immunhistochemische Analysen des Gewebes konnten eine Akkumulation dieser Zellen innerhalb von Sekundärfollikeln des Synovialmembrans nachweisen. Die ELISPOT-Analyse ausgewählter Zytokine resultierte in der Detektion immunsuppressiver (IL-10) und immunstimulatorischer Zytokine in Synovialmembranzellkultur. Hier konnte erstmalig eine autologe IFN-gamma Produktion auf Proteinebene nachgewiesen werden. Klinische Betrachtungen der IFN-gamma Produktion zeigten eine starke Assoziation mit dem Rheumafaktor. Zusätzlich findet sich eine tendenzielle Abnahme der immunstimulatorischen Kapazität mit der Dauer der Erkrankung. Eine Betrachtung der intrasynovialen IL-10 Produktion unter Berücksichtigung des klinischen Entzündungsparameter CRP, zeigt einen starken Zusammenhang zwischen den beiden Parametern. ELISPOT Analysen einer Co-Kultur zwischen autologen CD4(+) und CD8(+) PBMCs und Synovialmembranzellen ergaben eine Abnahme der autologen IFN-gamma Produktion ohne Zunahme der Interleukin- 10 Produktion. Eine Aktivierung der Zellkultur lässt diesen Effekt verschwinden. Durch Aufreinigung der PBMCs konnte der stärkste suppressive Effekt innerhalb der CD4(+)CD25(+) T-Zellfraktion nachgewiesen werden, welcher marginal durch Aktivierung der Zellkultur unterbrochen werden konnte. Regulatorische Effekte konnten auch innerhalb der CD8(+) T-Zellfraktion dokumentiert werden, welche sich aber durch spezifische anti-CD3 Ab und anti-CD28 Ab Aktivierung verliert. Die Beeinflussung der suppressiven Eigenschaften von T-Zellen bzw. ihrer spezialisierten T-Zellpopulationen könnte in Zukunft zu einer besseren Therapie der Rheumatoiden Arthritis führen.
(1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced.
(2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored.
(3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%.
(4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.
Objectives: Within a randomized controlled trial contrasting the outcome of manualized cognitive-behavioral (CBT) and short term psychodynamic therapy (PDT) compared to a waiting list condition (the SOPHO-Net trial), we set out to test whether self-reported attachment characteristics change during the treatments and if these changes differ between treatments.
Research design and methods: 495 patients from the SOPHO-Net trial (54.5% female, mean age 35.2 years) who were randomized to either CBT, PDT or waiting list (WL) completed the partner-related revised Experiences in Close Relationships Questionnaire (ECR-R) before and after treatment and at 6 and 12 months follow-up. The Liebowitz Social Anxiety Scale (LSAS) was administered at pre-treatment, post-treatment, and at 6-month and 1-year follow-up. ECR-R scores were first compared to a representative healthy sample (n = 2508) in order to demonstrate that the clinical sample differed significantly from the non-clinical sample with respect to attachment anxiety and avoidance.
Results: LSAS scores correlated significantly with both ECR-R subscales. Post-therapy, patients treated with CBT revealed significant changes in attachment anxiety and avoidance whereas patients treated with PDT showed no significant changes. Changes between post-treatment and the two follow-ups were significant in both conditions, with minimal (insignificant) differences between treatments at the 12- month follow-up.
Conclusions: The current study supports recent reviews of mostly naturalistic studies indicating changes in attachment as a result of psychotherapy. Although there were differences between conditions at the end of treatment, these largely disappeared during the follow-up period which is line with the other results of the SOPHO-NET trial.
Trial registration: Controlled-trials.com ISRCTN53517394
Objective: The aim of the study was to analyse the psychometric properties of the EQ-5D in patients with social phobia.
Methods: We used a sample of 445 patients with social phobia with five measurement points over a 30 month period. The discriminative ability of the EQ-5D was analysed by comparing the patients' responses with the general population and between different disease severity levels. For test-retest reliability we assessed the level of agreement in patients' responses over time, when there was no change in the Liebowitz Social Anxiety Scale (LSAS). Construct validity was analysed by identifying correlations of the EQ-5D with more specific instruments. For responsiveness we compared the means of EQ VAS/EQ-5D index anchored on improved (deteriorated) health status and computed effect sizes as well as a receiver operating characteristic (ROC) curve.
Results: Compared to the general population, patients with social phobia reported more problems in the dimensions "usual activities", "pain/discomfort", and "anxiety/depression" and less problems in "mobility" and "self-care". The EQ-5D was able to distinguish between different disease severity levels. The test-retest reliability was moderate (intraclass correlation coefficient > 0.6). Correlations between the EQ-5D and other instruments were mostly small except for correlations with Beck Depression Inventory. The EQ-5D index seemed to be more responsive than the EQ VAS, but with only medium effect sizes (0.5 < effect size < 0.8) in the British EQ-5D index and only significant in patients with improved health status. The ROC analysis revealed no significant results.
Conclusions: The EQ-5D was moderately reliable and responsive in patients with improved health status. Construct validity was limited.
Trial registration: Current controlled trials ISRCTN53517394.