[Show abstract][Hide abstract] ABSTRACT: Sepsis is a leading cause of death in the United States and worldwide. Early recognition and effective management are essential for improved outcome. However, early recognition is impeded by lack of clinically utilized biomarkers. Complement factors play important roles in the mechanisms leading to sepsis and can potentially serve as early markers of sepsis and of sepsis severity and outcome. This review provides a synopsis of recent animal and clinical studies of the role of complement factors in sepsis development, together with their potential as disease markers. In addition, new results from our laboratory are presented regarding the involvement of the complement factor, mannose-binding lectin, in septic shock patients. Future clinical studies are needed to obtain the complete profiles of complement factors/their activated products during the course of sepsis development. We anticipate that the results of these studies will lead to a multipanel set of sepsis biomarkers which, along with currently used laboratory tests, will facilitate earlier diagnosis, timely treatment, and improved outcome.
[Show abstract][Hide abstract] ABSTRACT: Loss of plasma membrane integrity (LPMI) is a hallmark of necrotic cell death. The involvement of complement and ROS in the development of LPMI during the early stages of murine myocardial ischemia-reperfusion injury was investigated. LPMI developed within 1h of reperfusion to a level that was sustained through 24h. C3 deposition became significant at 3-h reperfusion and thus contributed little to LPMI prior to this time. SOD1 transgenic mice had significantly less LPMI compared with WT mice at 1h of reperfusion but not at later time points. Catalase transgenic mice were not protected from LPMI at 1-h reperfusion compared with WT mice, but had 69% less LPMI at 3-h reperfusion. This protection was transient. At 24-h reperfusion the LPMI of catalase transgenic mice was identical to that of WT mice. The delayed benefits of over-expressed catalase compared with SOD1 are consistent with its antioxidant action downstream of SOD1. The onset of LPMI occurs within 1h of reperfusion at a level that is maintained through 24h. ROS contribute significantly to LPMI during the first 3h of reperfusion, while complement deposition, which becomes significant after 3-h reperfusion, may contribute thereafter.
[Show abstract][Hide abstract] ABSTRACT: Cocaethylene (CE) is a toxic metabolite that is formed after simultaneous consumption of cocaine and ethanol. This potent stimulant is more toxic than cocaine and has a longer half-life. The deleterious hemodynamic and cardiovascular effects of CE have been proven in animal models. The aim of this study is to assess the impact of CE on clinical outcomes after trauma. We prospectively enrolled adult (≥13 years) trauma patients requiring admission. Predictor variables were age, sex, mechanism of injury, Injury Severity Score, base deficit, and toxicology groups (ethanol alone, cocaine alone, CE, and none). The outcomes examined were mortality, intensive care unit (ICU) admission, and length of hospital stay (LOS). We used nonparametric tests to compare continuous variables and χ² test to compare categorical data. We constructed a logistic regression to identify variables that could predict mortality and ICU admission. We enrolled 417 patients (74% male; 70% blunt injury; median age, 40 [range, 13-95]; overall mortality, 2.2%). Urine toxicology and serum ethanol level screens classified patients into the following groups: 13.4% ethanol only, 4.1% cocaine only, 8.9% CE, and 46% none. Mortality and LOS were not statistically different among the groups. In logistic regression analysis, none of the variables were statistically significant in predicting mortality. However, the presence of CE significantly increased the likelihood of ICU admission (odds ratio, 5.9; 95% confidence interval, 1.6-22). The presence of detectable CE in the urine does not increase the mortality or LOS in trauma patients requiring admission but does increase the likelihood of ICU admission.
No preview · Article · Nov 2010 · The American journal of emergency medicine