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BACKGROUND Mechanical ventilation causes ventilator-induced lung injury in animals and humans. Mitogen-activated protein kinases have been implicated in ventilator-induced lung injury though their functional significance remains incomplete. We characterize the role of p38 mitogen-activated protein kinase/mitogen activated protein kinase kinase-3 and(More)
INTRODUCTION Promising preclinical results have been obtained with blood purification therapies as adjuvant treatment for sepsis. However, the mechanisms by which these therapies exert beneficial effects remain unclear. Some investigators have suggested that removal of activated leukocytes from the circulation might help ameliorate remote organ injury. We(More)
BACKGROUND Intracranial pressure (ICP) monitoring is considered the standard of care for severe traumatic brain injury (TBI) and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed. METHODS OBJECTIVE The objective was to compare efficacy of guideline-based management in which a(More)
Mechanical ventilation, often required to maintain normal gas exchange in critically ill patients, may itself cause lung injury. Lung-protective ventilatory strategies with low tidal volume have been a major success in the management of acute respiratory distress syndrome (ARDS). Volutrauma causes mechanical injury and induces an acute inflammatory(More)
BACKGROUND Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing(More)
INTRODUCTION Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis. METHODS We performed prospective, randomized animal studies at a university research(More)
BACKGROUND The role of the receptor for advanced glycation end-products (RAGE) has been shown to differ in two different mouse models of asbestos and bleomycin induced pulmonary fibrosis. RAGE knockout (KO) mice get worse fibrosis when challenged with asbestos, whereas in the bleomycin model they are largely protected against fibrosis. In the current study(More)
INTRODUCTION Prior work suggests that leukocyte trafficking is determined by local chemokine gradients between the nidus of infection and the plasma. We recently demonstrated that therapeutic apheresis can alter immune mediator concentrations in the plasma, protect against organ injury, and improve survival. Here we aimed to determine whether the removal of(More)
CITATION Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, McGuinness S, Rajbhandari D, Taylor CB, Webb SA; CHEST Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group: Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012, 367:1901-1911.(More)
After iron, zinc is the most abundant essential trace metal. Intracellular zinc ([Zn](i)) is maintained across a wide range of cells and species in a tight quota (100 to 500 μM) by a dynamic process of transport, intracellular vesicular storage, and binding to a large number of proteins (estimated at 3-10% of human proteome). As such, zinc is an integral(More)