J Trauma
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Nuclear factor-kappa B (NF-kappa B) plays a critical role in the cellular response to a variety of stimuli, and it regulates the production of various inflammatory cytokines, adhesion molecules, and enzymes. Polymorphonuclear leukocytes (PMNLs) play a central role in systemic inflammatory response after severe insult. The role of NF-kappa B in activation of PMNLs, however, has not been clear. We developed a simple flow cytometric method for quantifying expression of intranuclear NF-kappa B in PMNLs, and we used it to evaluate NF-kappa B activity in patients with systemic inflammatory response syndrome (SIRS). ⋯ Our new flow cytometric method proved useful for quantifying intranuclear NF-kappa B expression in PMNLs. In PMNLs from SIRS patients, intranuclear NF-kappa B expression and oxidative activity were significantly elevated with positive correlation, and enhanced expression of NF-kappa B may play an important role in PMNL activation in SIRS.
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With rising health care costs, methods to decrease length of hospital stay without compromising care are necessary. One area that extends length of stay in trauma patients is inpatient anticoagulation to a therapeutic international normalized ratio. The 1998 American College of Chest Physicians guidelines recommend thromboprophylaxis with low-molecular-weight heparin (LMWH) and oral warfarin in this population. The LMWH Expedited Anticoagulation Program (LEAP) was created with the following goals: to decrease the number of inpatient warfarin days and to reduce overall number of hospital days. ⋯ LEAP has successfully decreased the number of inpatient days on warfarin and total hospital days for trauma patients requiring deep venous thrombosis prophylaxis. These results have substantially decreased health care costs and increased available hospital beds in this era of high hospital occupancy.
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Splanchnic hypoperfusion is believed to be central in the pathogenesis of hemorrhagic shock-induced acute respiratory distress syndrome and multiple organ failure. Our previous work focused on the portal circulation as the conduit for gut-derived mediators of acute respiratory distress syndrome. Our current focus is the proinflammatory effects of postshock mesenteric lymph. We hypothesize that postshock lymph induces neutrophil (PMN)-mediated endothelial cell damage in an intercellular adhesion molecule-1 (ICAM-1)-dependent fashion, and devised a two-insult model to test this hypothesis. ⋯ Postshock mesenteric lymph activates endothelial cells for increased ICAM-1 expression and PMN adherence. Furthermore, postshock lymph acts as an inciting event in a two-event in vitro model of PMN-mediated endothelial cell injury. These findings further substantiate the key mechanistic role of mesenteric lymph in hemorrhagic shock-induced acute lung injury and suggest that ICAM-1 expression is pivotal in the two-event model of multiple organ failure.
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The past century has seen improvement in trauma care, with a resulting decrease in therapeutically preventable deaths. We hypothesize that further major reduction in injury mortality will be obtained through injury prevention, rather than improvements in therapy. ⋯ Dramatically improving therapy (no errors, cure for multiple organ failure, sepsis, and pulmonary embolus) in a modern trauma system would decrease trauma mortality by 13%. In contrast, more than half of all deaths are potentially preventable with preinjury behavioral changes. Injury prevention is critical to reducing deaths in the modern trauma system.
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Clinical Trial Controlled Clinical Trial
Alteration of the postinjury hyperinflammatory response by means of resuscitation with a red cell substitute.
Transfusion of stored packed red blood cells (PRBCs) has unintended effects beyond the desired results of increased oxygen delivery. A particular concern is the potential for lipid and cytokine mediators present in PRBCs to augment the postinjury inflammatory response that sometimes culminates in multiple organ failure. Through the use of a polymerized human hemoglobin (PolyHeme), we have been able to measure the inflammatory response in patients resuscitated with minimal exposure to banked components in the early postinjury period. ⋯ Consistent with concerns about the immunoinflammatory response to transfusion of PRBCs, we observed exaggerated levels of three markers associated with adverse outcome. The clinical significance of these findings with respect to the development of multiple organ failure awaits further study.