2篇
您的检索式：作者名="Norman Junge"
|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Transition after pediatric liver transplantation-Perceptions of adults, adolescents and parents显示文摘AIM To develop a locally adapted, patient-focused transitionprogram, we evaluated the perceptions of adult and adolescent patients and parents regarding transitionprograms and transfer.METHODS We evaluated these perceptions by analyzing the responses of pre-transfer adolescents(n = 57), their parents(n = 57) and post-transfer adults(n = 138) from a cohort of pediatric-liver-transplant-patients using a self-designed questionnaire. Furthermore, we compared a responder group with a non-responder group as well as the provided answers with baseline characteristics and clinical outcomes to exclude selection bias, characterize high-risk patients for nonadherence and test for gender differences. Included in our study were all pre-transfer liver transplant and combined liver-kidney transplant recipients aged 11-19 currently under our care and their parents, as well as all post-transfer liver transplant and combined liverkidney transplant recipients aged ≥ 17 years who had received a liver transplant and were treated at our center during childhood.RESULTS Fifty-seven(24 female) pre-transfer patients who received a transplant in the previous 8-186 mo(mean 93.9 mo, median 92 mo, SD 53.8 mo) and 138(57 female) post-transfer patients who received a transplant in the preceding 2-29 years(mean 15.6 years, median 17, SD 6.90) met the inclusion criteria. A total of 67% of pre-transfer patients(71% of female; 64% of male; P = 0.78) and their parents replied. Additionally, 54% of post-transfer patients(26% of female; 48% of male; P = 0.01) replied. No differences in clinical outcomes were observed between the responder and non-responder groups, and responses did not differ significantly based on clinical complication rates, although they did differ based on gender and the location of medical follow-up after transfer. Adolescents were generally ambivalent toward transition programs. However, adults strongly supported transition programs. CONCLUSION Transition programs need to be developed in close collaboration with adolescents. The best clinical practices regarding transition should respect local circumstances, gender and the location of post-transfer medical follow-up. | Norman Junge Katarina Migal Imeke Goldschmidt Ulrich Baumann | 2017 | World Journal of Gastroenterology2017，23，13： | 2 |
| 2 | Homologous recombination mediates stable Fah gene integration and phenotypic correction in tyrosinaemia mouse-model显示文摘AIM To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout(Fah-/-) mice by homologous-recombination-mediated targeted addition of the Fah gene.METHODS C57 BL/6 Fah?exon5 mice served as an animal model for human tyrosinaemia type 1 in our study. The vector was created by amplifying human Fah c DNA including the TTR promoter from a lentivirus plasmid as described. The Fah expression cassette was flanked by homologous arms(620 bp and 749 bp long) of the Rosa26 gene locus. Mice were injected with 2.1 × 108 VP of this vector(r AAV8-ROSA26.HAL-TTR.FahROSA26.HAR) via the tail vein. Mice in the control group were injected with 2.1 × 108 VP of a similar vector but missing the homologous arms(r AAV8-TTR.Fah). Primary hepatocytes from Fah-/-recipient mice, treated with our vectors, were isolated and 1 × 106 hepatocytes were transplanted into secondary Fah-/-recipient mice by injection into the spleen. Upon either vector application or hepatocyte transplantation NTBC treatment was stopped in recipient mice. RESULTS Here, we report successful HR-mediated genome editing by integration of a Fah gene expression cassette into the 'safe harbour locus' Rosa26 by recombinant AAV8. Both groups of mice showed long-term survival, weight gain and FAH positive clusters as determined by immunohistochemistry analysis of liver sections in the absence of NTBC treatment. In the group of C57 BL/6 Fah?exon5 mice, which have been transplanted with hepatocytes from a mouse injected with r AAV8-ROSA26.HAL-TTR.Fah-ROSA26.HAR 156 d before, 6 out of 6 mice showed long-term survival, weight gain and FAH positive clusters without need for NTBC treatment. In contrast only 1 out 5 mice, who received hepatocytes from r AAV8-TTR.Fah treated mice, survived and showed few and smaller FAH positive clusters. These results demonstrate that homologous recombinationmediated Fah gene transfer corrects the phenotype in a mouse model of human tyrosinaemia type 1(Fah-/-mice) and is long lasting in a proliferating state of the liver as shown by withdrawal of NTBC treatment and serial transplantation of isolated hepatocytes from primary Fah-/-recipient mice into secondary Fah-/-recipient mice. This long term therapeutic efficacy is clearly superior to our control mice treated with episomal r AAV8 gene therapy approach.CONCLUSION HR-mediated r AAV8 gene therapy provides targeted transgene integration and phenotypic correction in Fah-/-mice with superior long-term efficacy compared to episomal r AAV8 therapy in proliferating livers. | Norman Junge Qinggong Yuan Thu Huong Vu Simon Krooss Christien Bednarski Asha Balakrishnan Toni Cathomen Michael P Manns Ulrich Baumann Amar Deep Sharma Michael Ott | 2018 | World Journal of Hepatology2018，10，2： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员