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Thilo Menges,
Inke R König,
Hamid Hossain,
Simon Little,
Svetlin Tchatalbachev,
Felix Thierer,
Holger Hackstein,
Isolda Franjkovic,
Thorsten Colaris,
Florian Martens,
Katja Weismüller,
Tanja Langefeld,
Jürgen Stricker,
Gunter Hempelmann,
Pieter E Vos,
Andreas Ziegler,
Bram Jacobs,
Trinad Chakraborty,
Gregor Bein
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ABSTRACT: Patients encountering severe trauma are at risk of developing sepsis syndrome and subsequent multiple organ failure. This is often associated with fatal outcome despite survival of the initial injury. We postulate that variation of the gene coding for tumor necrosis factor (TNF)-alpha is associated with increased occurrence of sepsis syndrome and mortality in trauma patients.
Prospective cohort study; validation in an external replication sample.
Tertiary academic medical center.
We included 159 severely traumatized patients from a single center. Serial blood samples were analyzed for serum concentrations of TNF-alpha and lymphotoxin-alpha (LTA). We genotyped nine polymorphisms in the TNF gene and tested for an association with sepsis syndrome and outcome. Genetic associations were validated in an external replication sample (n = 76). We examined the peripheral blood transcriptome in 28 patients by whole genome-based profiling and validated the results.
None.
Carriage of the TNF rs1800629 A allele was associated with higher TNF-alpha serum concentrations on the first day after trauma and during follow-up (two-sided p = 5.0 x 10(-5)), with development of sepsis syndrome (odds ratio 7.14, two-sided p = 1.2 x 10(-6); external validation sample [n = 76]: odds ratio 3.3, one-sided p = .03), and with fatal outcome (odds ratio 7.65, two-sided p = 1.9 x 10(-6)). Carriage of the TNF rs1800629 A allele was associated with differential expression of genes representing stronger proinflammatory and apoptotic responses compared with carriage of the wild-type allele.
Common TNF gene variants are associated with sepsis syndrome and death after severe injury. These findings are strongly supported by functional data and may be important for developing preemptive anti-inflammatory interventions in carriers of the risk-associated allele.
Critical care medicine 06/2008; 36(5):1456-62, e1-6. · 6.37 Impact Factor
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ABSTRACT: The development of medical research networks within the framework of translational research has fostered interest in the integration of clinical and biological research data in a common database. The building of one single database integrating clinical data and biological research data requires a concept which enables scientists to retrieve information and to connect known facts to new findings.Clinical parameters are collected by a Patient Data Management System and viewed in a database which also includes genomic data. This database is designed as an Entity Attribute Value model, which implicates the development of a data warehouse concept.For the realization of this project, various requirements have to be taken into account which has to be fulfilled sufficiently in order to align with international standards.Data security and protection of data privacy are most important parts of the data warehouse concept. It has to be clear how patient pseudonymization has to be carried out in order to be within the scope of data security law.To be able to evaluate the data stored in a database consisting of clinical data collected by a Patient Data Management System and genomic research data easily, a data warehouse concept based on an Entity Attribute Value datamodel has been developed.
Studies in health technology and informatics 02/2005; 116:9-14.
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Jörg Mühling,
Markus Fuchs,
Marie E Campos,
Jens Gonter,
Jörg M Engel,
Armin Sablotzki, Thilo Menges,
Stefan Weiss,
Marius G Dehne,
Matthias Krüll,
Gunter Hempelmann
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ABSTRACT: For the first time, a procedure is described for the quantitative analysis of free alpha-keto acid content in human neutrophils (PMNs) relative to single cell number by reversed-phase fluorescence high-performance liquid chromatography. The procedure is minimally invasive and is unsurpassed in the quality of PMN separation, ease of sample preparation as well as sample stability. This method can satisfy the rigorous demands for an ultra-sensitive, comprehensive and rapid intracellular alpha-keto acid analysis in particularly for the surveillance of severe diseases as well as cellular or organ dysfunction.
Journal of Chromatography B 07/2003; 789(2):383-92. · 2.89 Impact Factor
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ABSTRACT: Objective: Cardiovascular surgery with extracorporeal circulation causes a systemic inflammatory response, which can lead to organ failure and increased postoperative morbidity. Advances in knowledge about the interactions between markers of cellular and humoral immunity involved in the inflammatory response to cardiopulmonary bypass (CPB) may reduce the deleterious effects and improve the outcome for patients undergoing cardiac surgery. Methods: To determine the release of immunoinhibiting cytokines during CPB, we measured plasma levels of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in 30 patients undergoing elective coronary artery bypass grafting. Arterial blood samples were collected at eight time points before, during and after CPB, using a standardized ELISA-technique. Results: Plasma IL-10 and TGF-β increased significantly after weaning off CPB (P<0.05) and peaked respectively at time of skin closure (IL-10, 308±180 pg/ml; TGF-β, 1860±906 pg/ml; mean peak ±S.D.). Postoperatively, 6 h, IL-10 decreased to 19.8±9.8 pg/ml (P<0.05) and TGF-β decreased to 1133±547 pg/ml (P<0.05). Conclusions: Both cytokines are major immunoregulatory factors with negative influence on T cell-mediated immunologic response. The significantly elevated levels at the end of CPB indicate that IL-10 and TGF-β may be important factors of immunologic dysregulation following CPB.
European Journal of Cardio-Thoracic Surgery.
