tailieunhanh - Báo cáo y học: " Influence of genetic variations in TLR4 and TIRAP/Mal on the course of sepsis and pneumonia and cytokine release: an observational study in three cohorts"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Influence of genetic variations in TLR4 and TIRAP/Mal on the course of sepsis and pneumonia and cytokine release: an observational study in three cohorts. | Kumpf et al. Critical Care 2010 14 R103 http content 14 3 R103 RESEARCH Open Access Influence of genetic variations in TLR4 and TIRAP Mal on the course of sepsis and pneumonia and cytokine release an observational study in three cohorts Oliver Kumpf 21 Evangelos J Giamarellos-Bourboulis22 3 Alexander Koch24 Lutz Hamann5 Maria Mouktaroudi2 3 Djin-Ye Oh5 6 Eicke Latz7 8 Eva Lorenz9 David A Schwartz10 Bart Ferwerda2 Christina Routsi11 Chryssanthi Skalioti3 Bart-Jan Kullberg2 Jos WM van der Meer2 Peter M Schlag12 Mihai G Netea2 Kai Zacharowski4 and Ralf R Schumann5 Abstract Introduction It has been proposed that individual genetic variation contributes to the course of severe infections and sepsis. Recent studies of single nucleotide polymorphisms SNPs within the endotoxin receptor and its signaling system showed an association with the risk of disease development. This study aims to examine the response associated with genetic variations of TLR4 the receptor for bacterial LPS and a central intracellular signal transducer TIRAP Mal on cytokine release and for susceptibility and course of severe hospital acquired infections in distinct patient populations. Methods Three intensive care units in tertiary care university hospitals in Greece and Germany participated. 375 and 415 postoperative patients and 159 patients with ventilator associated pneumonia VAP were included. TLR4 and TIRAP Mal polymorphisms in 375 general surgical patients were associated with risk of infection clinical course and outcome. In two prospective studies 415 patients following cardiac surgery and 159 patients with newly diagnosed VAP predominantly caused by Gram-negative bacteria were studied for cytokine levels in-vivo and after ex-vivo monocyte stimulation and clinical course. Results Patients simultaneously carrying polymorphisms in TIRAP Mal and TLR4 and patients homozygous for the TIRAP Mal SNP had a significantly higher risk of severe infections after surgery odds ratio OR .

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