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In der vorliegenden Arbeit wurden 140 Bandscheiben vor und nach Nukleoplastie im 7-Tesla-Kleintier-MRT untersucht. Ziel war es, eine Volumenänderung durch Nukleoplastie im Nucleus der Bandscheibe am Schweinemodell nachzuweisen. Nachdem aus benachbarten Bandscheiben Pärchen gebildet wurden, folgte jeweils eine zufällige Zuordnung zur Versuchs- oder Kontrollgruppe. Beide Gruppen umfassten 70 Bandscheiben. In der Versuchsgruppe (n=70) wurde die Nukleoplastie, wie vom Hersteller empfohlen, in 6 Arbeitskanälen durchgeführt. In der Kontrollgruppe (n=70) ist das Verfahren der Nukleoplastie analog der Versuchsgruppe durchgeführt worden. Es wurde jedoch in Schein-Nukleoplastie ohne Applikation der Coblations- Energie durchgeführt. Die Durchführung der Nukleoplastie erfolgte in den Gruppen für den Operateur geblindet. Es wurden von allen Bandscheiben prä- und postoperative MRT-Bilddatensätze erhoben. Zum Vergleich der Volumenänderung zwischen der Versuchs- und der Kontrollgruppe erfolgte die Volumetrie des Bandscheibenkerns durch eine geblindete Auswertung der Bilder mit dem für wissenschaftliche Zwecke zugelassenen Programm OsiriX R . Die statistische Auswertung der Daten erfolgte mit dem Wilcoxon-Rangsummen-Test mittels SAS. Es wurde die zentrale Tendenz der Volumenänderung zwischen beiden Gruppen untersucht. Die Daten wurden zusätzlich in drei Untergruppen aufgeteilt (BWS, thorako-lumbaler Übergang, LWS). Es zeigt sich in allen Gruppen ein hochsignifikanter (p<0.0001) Unterschied zwischen der Versuchs- und der Kontrollgruppe. Die Volumenreduktion durch Nukleoplastie beträgt 0,127 ml oder 14,23% (n=140). Bei Betrachtung der Gruppen getrennt voneinander ergibt sich eine Volumenreduktion zum Ausgangsvolumen von 0,073 ml oder 7,12% (n=70, p<0,001) in der Versuchsgruppe und eine Volumenzunahme von 0,055 ml oder 7,12% (n=70, p<0,001) in der Kontrollgruppe. Die Arbeit ist somit die erste, die in dem gewählten Tiermodell in vitro zeigen konnte, dass es neben den bisher nachgewiesenen klinischen und druckreduzierenden Effekten auch zu einer Volumenreduktion durch Nukleoplastie kommt. 46

Abstract Background Duchenne muscular dystrophy (DMD) is a progressive muscle‐wasting disease caused by mutations in the dystrophin gene, which leads to structural instability of the dystrophin–glycoprotein‐complex with subsequent muscle degeneration. In addition, muscle inflammation has been implicated in disease progression and therapeutically addressed with glucocorticosteroids. These have numerous adverse effects. Treatment with human immunoglobulin G (IgG) improved clinical and para‐clinical parameters in the early disease phase in the well‐established mdx mouse model. The aim of the present study was to confirm the efficacy of IgG in a long‐term pre‐clinical study in mdx mice. Methods IgG (2 g/kg body weight) or NaCl solution as control was administered monthly over 18 months by intraperitoneal injection in mdx mice beginning at 3 weeks of age. Several clinical outcome measures including endurance, muscle strength, and echocardiography were assessed. After 18 months, the animals were sacrificed, blood was collected for analysis, and muscle samples were obtained for ex vivo muscle contraction tests, quantitative PCR, and histology. Results IgG significantly improved the daily voluntary running performance (1.9 m more total daily running distance, P < 0.0001) and slowed the decrease in grip strength by 0.1 mN, (P = 0.018). IgG reduced fatigability of the diaphragm (improved ratio to maximum force by 0.09 ± 0.04, P = 0.044), but specific tetanic force remained unchanged in the ex vivo muscle contraction test. Cardiac function was significantly better after IgG, especially fractional area shortening (P = 0.012). These results were accompanied by a reduction in cardiac fibrosis and the infiltration of T cells (P = 0.0002) and macrophages (P = 0.0027). In addition, treatment with IgG resulted in a significant reduction of the infiltration of T cells (P ≤ 0.036) in the diaphragm, gastrocnemius, quadriceps, and a similar trend in tibialis anterior and macrophages (P ≤ 0.045) in gastrocnemius, quadriceps, tibialis anterior, and a similar trend in the diaphragm, as well as a decrease in myopathic changes as reflected by a reduced central nuclear index in the diaphragm, tibialis anterior, and quadriceps (P ≤ 0.002 in all). Conclusions The present study underscores the importance of an inflammatory contribution to the disease progression of DMD. The data demonstrate the long‐term efficacy of IgG in the mdx mouse. IgG is well tolerated by humans and could preferentially complement gene therapy in DMD. The data call for a clinical trial with IgG in DMD.

Background: The association of polyomaviruses BK and JC with other opportunistic infections and graft-versus-host disease (GvHD) in allogeneic stem cell transplantation is controversially discussed. Methods: We conducted a retrospective study of 64 adult patients who received their first allogeneic stem cell transplantation between March 2010 and December 2014; the follow-up time was 2 years. Results: Acute leukemia was the most frequent underlying disease (45.3%), and conditioning included myeloablative (67.2%) and nonmyeloablative protocols (32.8%). All patients received 10 mg of alemtuzumab on day -2 (20 mg in case of mismatch) as GvHD prophylaxis. Twenty-seven patients (41.5%) developed cytomegalovirus (CMV) reactivation. BKPyV-associated hemorrhagic cystitis was diagnosed in 10 patients (15.6%). Other opportunistic infections caused by viruses or protozoa occurred rarely (<10%). There was no association of BKPyV or JCPyV with CMV reactivation, Epstein-Barr virus reactivation, human herpes virus 6, or parvovirus B19 infection requiring treatment. There was a significant correlation of BKPyV-associated hemorrhagic cystitis with toxoplasmosis (p = 0.013). Additionally, there was a significant link of simultaneous BKPyV and JCPyV viruria with toxoplasmosis (p = 0.047). BKPyV and JCPyV were not associated with GvHD, relapse, or death. Conclusion: We found no association of BKPyV or JCPyV with viral infections or GvHD. Only the correlation of both polyomaviruses with toxoplasmosis was significant. This is a novel and interesting finding.