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
David A. Schwartz
Jos WM Van der Meer
Peter M. Schlag
Mihai G. Netea
Ralf R. Schumann
- 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) 5.5; confidence interval (CI): 1.34 - 22.64; P = 0.02 and OR: 7.3; CI: 1.89 - 28.50; P < 0.01 respectively). Additionally we found significantly lower circulating cytokine levels in double-mutant individuals with ventilator associated pneumonia and reduced cytokine production in an ex-vivo monocyte stimulation assay, but this difference was not apparent in TIRAP/Mal-homozygous patients. In cardiac surgery patients without infection, the cytokine release profiles were not changed when comparing different genotypes. Conclusions: Carriers of mutations in sequential components of the TLR signaling system may have an increased risk for severe infections. Patients with this genotype showed a decrease in cytokine release when infected which was not apparent in patients with sterile inflammation following cardiac surgery.
Nähe der Antike : eine Ansprache
Rudolf G. Binding
- Frankfurter gelehrte Reden und Abhandlungen VIII. Heft : Zwei Ansprachen zur Eröffnung der Ortsgruppe Frankfurt am Main der Gesellschaft für antike Kultur am 9. Dezember 1925 Nähe der Antike / Rudolf G. Binding Zeit und Antike / W. F. Otto.
Fachspezifischer Anhang für den Bachelorstudiengang Theater-, Film- und
Medienwissenschaft im Hauptfach an der Johann Wolfgang Goethe-Universität
Frankfurt am Main vom 30. Mai 2012 : vorläufig genehmigt vom Präsidium in der Sitzung am 21. August 2012
AStA-Zeitung : Dezember 2010
AStA-Zeitung : April 2010
AStA-Zeitung : Wahlausgabe 2012
AStA-Zeitung Uni FFM : Ausgabe 2 - 2012
AStA-Zeitung Uni FFM: 01/2013
The magical cure for a never-ending story
- The key hypothesis is that the IT industry lure us into the IT world with a promise to solve our information problems. Do we sign the contract, we will recognise that the IT industry can´t keep the promise. One reason: they themselves lost sight over there own game. Therefore they have to invent new tools continiously. LIS professionals should not leave the field IT professionals. LIS professional should rather put stress on to reveal the difference in the value chain between data – information – knowledge. Information and knowledge is brainware and not produced by hard and software in the sense of IT philosophy. Against the background of the language game of Jean-François Lyotard, the author explains the information and knowledge society as language game invented by the IT industry. Furthermore his beliefs of postmodernen LIS professionals and the consequences involved for LIS traning will be presented.
Medical knowledge, computer, technology and doctors