Antioxidants increase lipopolysaccharide-stimulated TNF alpha release in murine macrophages: role for altered TNF alpha mRNA stability.

Through their effects on gene activation, antioxidants have been reported to modulate cellular expression of several proinflammatory cytokines and adhesion molecules, an effect mediated by preventing translocation of the transcription factor nuclear factor-kappa B (NF-kappa B) into the nucleus. In addition, modulation of the intracellular redox state may have profound effects on cell activation and subsequent gene expression distinct from effects on NF-kappa B; these effects may account for the divergent effects of antioxidants on cytokine gene expression in various reports. In the present studies, we evaluated the effect of the antioxidant, pyrrolidine dithiocarbamate (PDTC), on murine and human myeloid cell tumor necrosis factor alpha (TNF alpha) gene and protein expression.

The relationship between trauma center volume and outcome.

In spite of the limited direct evidence available, increasing data support a positive volume-outcome association in trauma care. When coupled with the extensive indirect data suggesting that regions with organized systems of trauma care are associated with lower trauma-related mortality rates than regions where the number of centers and their level of commitment are unlimited and untested, there is little doubt that experience improves outcome and that volume plays a critical role in the accrual of experience. Although regionalization of trauma care has the inevitable consequence of increased prehospital transport times, particularly in rural areas remote from large trauma centers, some states have designed inclusive systems where a large number of smaller centers have been verified and designated as lower level trauma centers (i.

Payer status: the unspoken triage criterion.

Background: The cost of uncompensated trauma care is a significant barrier to trauma system development. Trauma center designation may burden an institution with an unprofitable mix of underinsured, severely injured patients. Concerns about inadequate reimbursement may motivate interhospital transfers on the basis of insurance status rather than medical necessity, potentially undermining the effectiveness of the system.

Timing of urgent thoracotomy for hemorrhage after trauma: a multicenter study.

Hypothesis: It is possible to quantify an amount of thoracic hemorrhage, after blunt and penetrating injury, at which delay of thoracotomy is associated with increased mortality.

Design: A retrospective case series.

Setting: Five urban trauma centers.

Relationship between trauma center volume and outcomes.

Context: The premise underlying regionalization of trauma care is that larger volumes of trauma patients cared for in fewer institutions will lead to improved outcomes. However, whether a relationship exists between institutional volume and trauma outcomes remains unknown.

Objective: To evaluate the association between trauma center volume and outcomes of trauma patients.

Impact of presenting physiology and associated injuries on outcome following traumatic rupture of the thoracic aorta.

We hypothesized that the predominant factor influencing outcome of traumatic rupture of the thoracic aorta (TRA) was the degree of shock on presentation and associated injuries. We reviewed our experience with TRA over a 15-year period. Patients were classified as "unstable" if presenting systolic blood pressure was <90 mm Hg or if it decreased to <90 mm Hg after admission.

Analysis of hypertrophic and normal scar gene expression with cDNA microarrays.

Hypertrophic scar is one form of abnormal wound healing. Previous studies have suggested that hypertrophic scar formation results from altered gene expression of extracellular matrix molecules. A broadscale evaluation of gene expression in hypertrophic scars has not been reported.

Effect of an older sibling and birth interval on the risk of childhood injury.

Objective: Certain family structures have been identified as putting children at high risk for injury. To further define children at highest risk, we set out to explore the effect of an older sibling and birth interval on the risk of injury related hospital admission or death.

Methods: Data were analyzed using a case-control design.

The effect of organized systems of trauma care on motor vehicle crash mortality.

Context: Despite calls for wider national implementation of an integrated approach to trauma care, the effectiveness of this approach at a regional or state level remains unproven.

Objective: To determine whether implementation of an organized system of trauma care reduces mortality due to motor vehicle crashes.

Design: Cross-sectional time-series analysis of crash mortality data collected for 1979 through 1995 from the Fatality Analysis Reporting System.

Communicating with the family: the risks of medical radiation to conceptuses in victims of major blunt-force torso trauma.

Background: Trauma surgeons must balance the risk and benefits of diagnostic radiographic procedures on potentially pregnant patients and should know the range and likelihood of effects that radiation might have on pregnancy.

Methods: We present guidelines for assessing such radiation risks. Knowledge of a patient's pregnancy status and an estimate of radiation dose to the conceptus (low, < 10 mGy [milligray]; intermediate, 10-250 mGy; high, > 250 mGy) allow provisional assessment of radiation-induced risks.

Effectiveness of state trauma systems in reducing injury-related mortality: a national evaluation.

Background: Regional trauma systems were proposed 2 decades ago to reduce injury mortality rates. Because of the difficulties in evaluating their effectiveness and the methodologic limitations of previously published studies, the relative benefits of establishing an organized system of trauma care remains controversial.

Methods: Data on trauma systems were obtained from a survey of state emergency medical service directors, review of state statutes and a previously published trauma system inventory.

Redox manipulation using the thiol-oxidizing agent diethyl maleate prevents hepatocellular necrosis and apoptosis in a rodent endotoxemia model.

Manipulation of the intracellular redox state has been shown to alter cell activation pathways with resultant changes in cellular function. Previous studies have suggested that thiol oxidation, using the glutathione-depleting agent diethyl maleate (DEM), was able to inhibit endothelial cell activation. We hypothesized that this agent might exert beneficial effects following endotoxemia in the rat, a model in which transendothelial migration of neutrophils is central to the development of hepatocellular injury.

Selective decontamination of the digestive tract in surgical patients: a systematic review of the evidence.

Objective: To determine the comparative efficacy of selective decontamination of the digestive tract in critically ill surgical and medical patients, and in selected subgroups of surgical patients with pancreatitis, major burn injury, and those undergoing major elective surgery and transplantation.

Data Sources: The MEDLINE database was searched from January 1966 to December 1996 using the terms "decontamination or prophylaxis," "intensive care units," and "antibiotics." The search was limited to English-language studies evaluating the efficacy of selective decontamination of the digestive tract in human subjects.

The glutathione depleting agent diethylmaleate prolongs renal allograft survival.

Introduction: Intercellular adhesion molecule 1 (ICAM-1) plays an important role in mediating allograft rejection through its role in cellular trafficking and as an important costimulatory signal mediating T cell activation. We have previously reported that systemic administration of the glutathione (GSH) depleting agent diethylmaleate (DEM) prevents upregulation of ICAM-1 in various inflammatory models, suggesting that this agent may offer benefit in preventing allograft rejection. Thus we evaluated the effects of DEM in a murine model of renal transplantation.

The indeterminate abdominal sonogram in multisystem blunt trauma.

Background: North American trauma centers are beginning to note the limitations of emergent torso sonography. The purpose of this prospective study was to evaluate the frequency, causes, associations, and sequelae of indeterminate (IND) sonograms in blunt trauma.

Methods: Among adult blunt trauma patients assessed with screening torso sonography, clinician sonographers recorded the abdominal sonogram as positive, negative, or IND for free fluid.

Thiol-mediated regulation of ICAM-1 expression in endotoxin-induced acute lung injury.

The intracellular redox state regulates several aspects of cell function, suggesting that strategies directed toward altering the cellular redox state may modulate cell activation in inflammatory states. As the most abundant intracellular thiol, glutathione plays a critical role as an intracellular redox buffer. Using diethylmaleate (DEM) as a glutathione-depleting agent, we evaluated the effects of GSH depletion in a rodent model of polymorphonuclear neutrophil (PMN)-dependent acute lung injury.

Tertiary peritonitis: clinical features of a complex nosocomial infection.

The objective of this study was to define risk factors for and the clinical course of recurrent or tertiary peritonitis. Intensive supportive care of patients with life-threatening intraabdominal infections has led to the emergence of a new clinical syndrome, tertiary peritonitis, defined as the persistence or recurrence of intraabdominal infection following apparently adequate therapy of primary or secondary peritonitis. We undertook a retrospective study of 59 patients admitted with intraabdominal infection to a surgical intensive care unit (ICU).

N-acetyl cysteine attenuates acute lung injury in the rat.

The development of the adult respiratory distress syndrome (ARDS) in the critically ill patient is associated with a significant morbidity and mortality. The pulmonary dysfunction in ARDS is largely secondary to neutrophil-mediated oxidant injury. The purpose of these studies is to examine the effect of the antioxidant N-acetyl cysteine (NAC) on a rodent model of lung injury.

Pyrrolidine dithiocarbamate attenuates endotoxin-induced acute lung injury.

Lung injury in the acute respiratory distress syndrome (ARDS) is in part due to polymorphonuclear leukocyte (PMN)-mediated oxidative tissue damage. By means of nuclear factor-kappaB (NF-kappaB) activation, oxidants may also induce several genes implicated in the inflammatory response. The dithiocarbamates are antioxidants with potent inhibitory effects on NF-kappaB.

Glutathione depletion prevents lipopolysaccharide-induced local skin inflammation.

Background: We have previously shown that the thiol-oxidizing agent diethyl maleate prevents lipopolysaccharide (LPS)-induced up-regulation of endothelial cell intercellular adhesion molecule-1 (ICAM-1) in vitro.

Objective: To determine the effect of glutathione depletion on the development of local skin inflammation in vivo, a model known to be dependent on ICAM-1.

Design: Swiss Webster mice were injected with intradermal LPS (30 micrograms) or isotonic saline solution.

The abdominal compartment syndrome.

The abdominal compartment syndrome refers to the alterations in respiratory mechanics, hemodynamic parameters and renal function that occur as a result of a sustained increase in intra-abdominal pressure. The syndrome may follow a diverse series of insults, including laparotomy for severe abdominal trauma, ruptured abdominal aortic aneurysm and intra-abdominal infection. Diagnosis depends on recognizing the clinical picture in patients at risk, followed by an objective measurement of intra-abdominal pressure.

The role of tyrosine phosphorylation in lipopolysaccharide- and zymosan-induced procoagulant activity and tissue factor expression in macrophages.

The expression of surface procoagulants by exudative macrophages represents an important mechanism underlying local fibrin deposition at sites of extravascular inflammation. The present studies investigated the contribution of tyrosine phosphorylation to the generation of macrophage procoagulant activity (PCA) and tissue factor expression in response to proinflammatory stimuli. Both lipopolysaccharide (LPS) and zymosan rapidly stimulated tyrosine phosphorylation in elicited murine peritoneal macrophages.