Surgery
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Patients sustaining major trauma are predisposed to the development of organ dysfunction. We have shown that oxidant stress generated by hemorrhagic shock/resuscitation (S/R) in rodents increases lipopolysaccharide (LPS)-induced lung injury and translocation of nuclear factor kappa B (NF-kappaB) in alveolar macrophages (AMs). In addition, using a cellular model, we have shown that priming with oxidants reprograms LPS signaling through an Src-dependent pathway. In the present studies, we hypothesize that oxidant priming by S/R in vivo involves Src family kinases. ⋯ Oxidant stress generated during S/R in vivo causes Src family kinase activation in AMs. Inhibition of Src activation by PP2 attenuates AM priming for increased LPS responsiveness after hemorrhagic shock and causes a modest reduction in lung injury. Inhibition of the Src family kinases may be a novel approach for the treatment of lung injury after trauma.
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Randomized Controlled Trial Clinical Trial
Effects of long-term oxandrolone administration in severely burned children.
Severe burns cause exaggerated catabolism of muscle protein and inhibit bone deposition. Weakness and bony growth arrest interfere with rehabilitation. The purpose of this study was to determine whether oxandrolone administration for 1 year after the burn reverses muscle and bone catabolism in hypermetabolic pediatric burn patients. ⋯ Long-term administration of oxandrolone safely improves LBM, BMC, and BMD in severely burned children.
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Randomized Controlled Trial Clinical Trial
Epidural analgesia improves outcome after multiple rib fractures.
Rib fractures are common and associated with significant pulmonary morbidity. We hypothesized that epidural analgesia would provide superior pain relief, and reduce the risk of subsequent pneumonia. ⋯ The use of epidural analgesia is limited in the trauma population due to numerous exclusion criteria. However, when feasible, epidural analgesia is associated with a decrease in the rate of nosocomial pneumonia and a shorter duration of mechanical ventilation after rib fractures.
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In a model of traumatic brain injury (TBI), 2 protocols compared changes in intracranial pressure (ICP), coagulation, and neurologic outcome after intravenous fluid (IVF) resuscitation with either Hextend (HEX, 6% hetastarch in lactated electrolyte injection) or standard of care, crystalloid plus mannitol (MAN). ⋯ Hextend as the sole resuscitation fluid after severe TBI reduces fluid requirement, obviates the need for mannitol, improves neurologic outcome, and has no adverse effect on the coagulation profile relative to the crystalloid plus mannitol standard of care.
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Ischemia/reperfusion injury (I/R injury) of the liver remains a significant problem during liver surgery and transplantation. I/R injury is associated with liver apoptosis, which is mediated by death receptors such as Fas and tumor necrosis factor alpha (TNF-alpha), and/or mitochondrial dysfunction induced by cellular stress. Caspase-8 is presumed to be the apex of the death-mediated apoptosis pathway, whereas caspase-3 belongs to the "effector" proteases in the apoptosis cascade. Synthetic small interfering RNAs (siRNAs) specifically suppress gene expression by RNA interference. Therefore, we evaluated the therapeutic efficacy of caspase-8 and caspase-3 siRNA in a murine model of liver I/R injury. ⋯ Small interfering RNA targeted to caspase-8 and caspase-3 provided significant protection against I/R injury to the liver. This approach could be therapeutic in liver transplantation and other conditions associated with I/R injury to the liver.