Introduction Urokinase receptor (uPAR, CD87), a glycosylphosphatidylinositol-anchored protein, is considered to play an important role in inflammation and fibrinolysis. The Gram-negative bacterium Burkholderia pseudomallei is able to survive and replicate within leukocytes and causes melioidosis, an important cause of pneumonia-derived community-acquired sepsis in Southeast Asia. We here investigated the expression and function of uPAR both in patients with septic melioidosis and in a murine model of experimental melioidosis. Methods Using a translational approach we conducted a patient study in patients with culture-confirmed sepsis caused by B. pseudomallei, in vitro experiments using wild-type (WT) and uPAR knockout (KO) cells, and mouse studies using WT and uPAR KO mice inoculated with B. pseudomallei. Results uPAR mRNA and surface expression was increased in patients with septic melioidosis in/on both peripheral blood monocytes and granulocytes as well as in the pulmonary compartment during experimental pneumonia-derived melioidosis in mice. uPAR-deficient mice intranasally infected with B. pseudomallei showed an enhanced growth and dissemination of B. pseudomallei when compared with WT mice, corresponding with increased pulmonary and hepatic inflammation. uPAR KO mice demonstrated significantly reduced neutrophil migration towards the pulmonary compartment after inoculation with B. pseudomallei. Further in vitro experiments showed that uPARdeficient macrophages and granulocytes display a markedly impaired phagocytosis of B. pseudomallei. Additional studies showed that uPAR deficiency did not influence hemostatic and fibrinolytic responses during severe melioidosis. Conclusions These data suggest that uPAR is crucially involved in the host defense against sepsis caused by B. pseudomallei by facilitating the migration of neutrophils towards the primary site of infection and subsequently facilitating the phagocytosis of B. pseudomallei. P2 A comparison of acute lung inflammation in Klebsiella pneumoniae B5055-induced pneumonia and sepsis in BALB/c mice
AbstractsBackground and Aims PTBI is the leading cause of death and long-term morbidity. Current recommendations for the management of severe PTBI (Glasgow Coma [GCS] score ≤8) indicate that ICP monitoring is appropriate in infants and children (Option). The most reliable methods of ICP monitoring are ventricular catheters and intra parenchymal systems. The aim of this study is to evaluate the management of PTBI based on continues monitoring of intraparenchymal ICP in a PICU in Algeria. Methods Between January 2005 and December 2009 we collected 308 PTBI, 57 patients had intraparenchymal ICP monitoring. The consensus is to treat ICP exceeding the 20 mmHg threshold, and to optimize cerebral perfusion pressure (CPP). Results The mean age was 8 years, hypoxia and hypotension were frequent at admission, median GCS after resuscitation = 6, ICP monitoring was set up by the intensivist in the PICU after un average time of 13 hours after trauma. Intracranial hypertension was detected and treated (mannitol, hyerventilation and thiopental) in more than 90% of cases. the average time of ICP monitoring was 5 days. No complications (infection, hemorrhage) with this technique was detected. Conclusion The etiology and the pathophysiology of raised ICP in PTBI is a complex challenge for the intensivist. CPP and ICP were the first brain-specific targets for goal-directed therapies enacted in PTBI. In this study, ICP monitoring allows to detect intracranial hypertension and guide treatment better than when this technique is absent even if it is not a standard of the recommendations. Background and Aims Echocardiography-derived low superior vena cava flow (SVCF) associates intraventricular haemorrhage, neurodisability and death. The weaknesses of the method relate to its variability. We aim to explore the relationship between two SVCF cut-off values to define PPS in LBWI and the patients' shortterm neonatal co-morbidities. Methods One hundred LBWI [27.4 (2) wks; 1014 (316) g] who reached illness score below threshold, underwent early (< 12h) and serial echocardiography for the first 96hs after birth. The primary outcome was low SVCF prevalence according to two thresholds: < 41 ml/k/min and [< 41 ml/k/min + SVCF repeatability index (RI)] (RI is twice the standard deviation of the differences divided by the mean of all the measures). Secondary outcomes were short-term neonatal clinical outcomes in relation to SVCF status. Results SVCF< 41 ml/k/min prevalence was 30% and was associated with immaturity (p=0.02), corioamnionitis (0.007), advanced resuscitation at birth (0.004), lower Apgar scores (p<0.01) and postnatal ischemic events (bowel perforation or arterial vasospasm) (p=0.002). At SVCF < 51 ml/k/min (41 ml/k/min + repeatability index) cut-off value, the PPS prevalence was 50%; in addition to the above-mentioned co-morbidities trends showed an association between PPS and combined adverse outcome (death or intracranial haemorrhage). Conclusions Low SVCF is highly prevalent in the sick LBWI during the early postnatal period.
S...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.