TY  - JOUR
A1  - Gilbert, F.
A1  - Schneemann, C.
A1  - Scholz, C. J.
A1  - Kickuth, R.
A1  - Meffert, R. H.
A1  - Wildenauer, R.
A1  - Lorenz, U.
A1  - Kellersmann, R.
A1  - Busch, A.
T1  - Clinical implications of fracture-associated vascular damage in extremity and pelvic trauma
JF  - BMC Muscuskeletal Disorders
N2  - Background:
Vascular damage in polytrauma patients is associated with high mortality and morbidity. Therefore, specific clinical implications of vascular damage with fractures in major trauma patients are reassessed.

Methods:
This comprehensive nine-year retrospective single center cohort study analyzed demography, laboratory, treatment and outcome data from 3689 patients, 64 patients with fracture-associated vascular injuries were identified and were compared to a control group.

Results:
Vascular damage occurred in 7% of patients with upper and lower limb and pelvic fractures admitted to the trauma room. Overall survival was 80% in pelvic fracture and 97% in extremity fracture patients and comparable to non-vascular trauma patients. Additional arterial damage required substantial fluid administration and was visible as significantly anemia and disturbed coagulation tests upon admission. Open procedures were done in over 80% of peripheral extremity vascular damage. Endovascular procedures were predominant (87%) in pelvic injury.

Conclusion:
Vascular damage is associated with high mortality rates especially in combination with pelvic fractures. Initial anemia, disturbed coagulation tests and the need for extensive pre-clinical fluid substitution were observed in the cohort with vascular damage. Therefore, fast diagnosis and early interventional and surgical procedures are necessary to optimize patient-specific outcome.
KW  - endovascular repair
KW  - extremity trauma
KW  - fracture-associated vascular damage
KW  - level of evidence: IV
KW  - surgical trauma room
KW  - pelvic trauma
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176252
VL  - 19
IS  - 404
ER  - 
TY  - JOUR
A1  - Schraut, K. G.
A1  - Jakob, S. B.
A1  - Weidner, M. T.
A1  - Schmitt, A. G.
A1  - Scholz, C. J.
A1  - Strekalova, T.
A1  - El Hajj, N.
A1  - Eijssen, L. M. T.
A1  - Domschke, K.
A1  - Reif, A.
A1  - Haaf, T.
A1  - Ortega, G.
A1  - Steinbusch, H. W. M.
A1  - Lesch, K. P.
A1  - Van den Hove, D. L.
T1  - Prenatal stress-induced programming of genome-wide promoter DNA methylation in 5-HTT-deficient mice
JF  - Translational Psychiatry
N2  - The serotonin transporter gene (5-HTT/SLC6A4)-linked polymorphic region has been suggested to have a modulatory role in mediating effects of early-life stress exposure on psychopathology rendering carriers of the low-expression short (s)-variant more vulnerable to environmental adversity in later life. The underlying molecular mechanisms of this gene-by-environment interaction are not well understood, but epigenetic regulation including differential DNA methylation has been postulated to have a critical role. Recently, we used a maternal restraint stress paradigm of prenatal stress (PS) in 5-HTT-deficient mice and showed that the effects on behavior and gene expression were particularly marked in the hippocampus of female 5-Htt+/- offspring. Here, we examined to which extent these effects are mediated by differential methylation of DNA. For this purpose, we performed a genome-wide hippocampal DNA methylation screening using methylated-DNA immunoprecipitation (MeDIP) on Affymetrix GeneChip Mouse Promoter 1.0 R arrays. Using hippocampal DNA from the same mice as assessed before enabled us to correlate gene-specific DNA methylation, mRNA expression and behavior. We found that 5-Htt genotype, PS and their interaction differentially affected the DNA methylation signature of numerous genes, a subset of which showed overlap with the expression profiles of the corresponding transcripts. For example, a differentially methylated region in the gene encoding myelin basic protein (Mbp) was associated with its expression in a 5-Htt-, PS- and 5-Htt × PS-dependent manner. Subsequent fine-mapping of this Mbp locus linked the methylation status of two specific CpG sites to Mbp expression and anxiety-related behavior. In conclusion, hippocampal DNA methylation patterns and expression profiles of female prenatally stressed 5-Htt+/- mice suggest that distinct molecular mechanisms, some of which are promoter methylation-dependent, contribute to the behavioral effects of the 5-Htt genotype, PS exposure and their interaction.
KW  - mice
KW  - DNA
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119199
VL  - 4
ER  -