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Background: Bundle checklists are increasingly utilized in patient care, but data are inconsistent regarding their efficacy in reducing nosocomial complication rates. We examined whether checklist usage was associated with nosocomial complications; when documented, elements were verified by provider bedside rounds. Methods: We performed a retrospective cohort study of trauma patients admitted to our hospital during a three-phase implementation of a quality improvement project. For this analysis, patients were categorized under predocumentation (PD), documentation only (DO), or documentation with provider review (PR) cohort based on temporal designations. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between documentation cohorts and nosocomial complications. Results: No difference was observed in mean hospital stay, intensive care unit (ICU) days, or ventilator days. The DO cohort showed no significant differences in the risk of complications. Among ICU patients, when compared with the PD cohort, the PR cohort demonstrated a decreased risk of all complications OR 0.72 (95% CI 0.55-0.93), pulmonary embolus OR 0.29 (95% CI 0.11-0.73), pneumonia OR 0.66 (95% CI 0.50-0.88), and death OR 0.50 (95% CI 0.31-0.79). Conclusions: Bedside confirmation of bundle checklists during physician extender rounds reduces the risk of pulmonary embolus, pneumonia, and death when compared to chart documentation alone. This study underscores the importance of the team approach to the bundle checklist and it's ability to reduce morbidity and mortality. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of the Florida visual acuity licensing standard for drivers 80 years and older on fatal motor vehicle collision (MVC) involvement. Methods: Motor vehicle collision fatality rates for all Florida residents and for drivers 80 years and older were compared before and after the visual acuity licensing standard was implemented in January 2004. Results: From 2001 to 2006, there was a nonsignificant (P=.06) increase in MVC fatality rates in Florida; in contrast, fatality rates among drivers 80 years and older demonstrated a significant downward linear trend (P=.01).When comparing prelaw (2001-2003) and post-law (2004-2006) periods, the fatality rate among all-aged occupants increased by 6% (rate ratio, 1.06; 95% confidence interval, 0.99-1.14); conversely, fatalities among drivers 80 years and older decreased significantly by 17% (rate ratio, 0.83; 95% confidence interval, 0.72-0.98). Conclusions: Despite little evidence for an association between visual acuity and MVC involvement, the results of this study suggest that a vision screening law targeting Floridians 80 years and older resulted in a reduction in the MVC fatality rate among such drivers. The exact mechanism responsible for this association is unclear and future research should attempt to identify what might explain this relationship. [ABSTRACT FROM AUTHOR]

Studies have shown salutary effects of 17β-estradiol following trauma- hemorrhage on different cell types. 17β-Estradiol also induces improved circulation via relaxation of the aorta and has an anti-apoptotic effect on endothelial cells. Because mitochondria play a pivotal role in apoptosis, we hypothesized that 17β-estradiol will maintain mitochondrial function and will have protective effects against H2O2-induced apoptosis in endothelial cells. Endothelial cells were isolated from rats' aorta and cultured in the presence or absence of H2O2, a potent inducer of apoptosis. In additional studies, endothelial cells were pretreated with 17β-estradiol. Flow cytometry analysis revealed H2O2-induced apoptosis in 80.9% of endothelial cells; however, prior treatment of endothelial cells with 17β-estradiol resulted in an ~40% reduction in apoptosis. This protective effect of 17β-estradiol was abrogated when endothelial cells were cultured in the presence ICI-182780, indicating the involvement of estrogen receptor (ER). Fluorescence microscopy revealed a 17β-estradiol-mediated attenuation of H2O2-induced mitochondrial condensation. Western blot analysis demonstrated that H2O2-induced cytochrome c release from mitochondrion to cytosol and the activation of caspase-9 and -3 were decreased by 17β-estradiol. These findings suggest that 17β-estradiol attenuated H2O2-induced apoptosis via ER-dependent activation of caspase-9 and -3 in rat endothelial cells through mitochondria. [ABSTRACT FROM AUTHOR]

Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether 17β-estradiol (E2) treatment following trauma-hemorrhage alters these ET-1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor (ER) subtypes (ER-α and ER-β) and the endothelium-localized downstream mechanisms of actions of E2 remain unclear. We hypothesized that E2 attenuates increased ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-S-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma-hemorrhage with or without E2 treatment, and alterations in tension were determined in vitro. Dose-response curves to ET-1 were determined, and the vasoactive properties of E2, propylpyrazole triol (PPT, ER-α agonist), and diarylpropionitrile (DPN, ER-β agonist) were determined. The results showed that trauma-hemorrhage significantly increased ET-1-induced vasoconstriction; however, administration of E2 normalized ET-1-induced vasoconstriction in trauma-hemorrhage vessels to the sham-operated control level. The ER-~3 agonist DPN counteracted ET-1-induced vasoconstriction, whereas the ER-α agonist PPT was ineffective. Moreover, the vasorelaxing effects of E2 were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide (NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E2. Thus, E2 administration attenuates ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway that is dependent on endothelium-derived NO synthesis. [ABSTRACT FROM AUTHOR]

Since cardiac function is depressed in males but not in proestrus (PE) females following trauma-hemorrhage (T-H), we examined whether different estrus cycles influence cardiac function in female rats under those conditions. We hypothesized that females in the PE cycle only will have normal cardiac function following T-H and resuscitation. Sham operation or T-H was performed in five groups of rats (250-275 g) including PE, estrus (E), metestrus (ME), diestrus (DE), and ovariectomized (OVX) females (n = 6-7 per group). Cardiac function was determined 2 h after T-H, following which cardiomyocytes were isolated and nuclei extracted. Cardiomyocyte IL-6 and NF-κB expressions were measured using Western blotting. Moreover, plasma IL-6, estradiol, and progesterone levels were measured using ELISA or ETA kits. Results (1-way ANOVA) indicated that following T-H, 1) cardiac function was depressed in DE, E, ME, and OVX groups but maintained in the PE group; 2) the PE group had the highest plasma estrogen level; 3) plasma IL-6 levels increased significantly in DE, E, ME, and OVX groups, but the increase was attenuated in the PE group; 4) cardiomyocyte IL-6 protein level increased significantly in DE, E, ME and OVX groups after TH, but the increase was attenuated in the PE group; and 5) cardiomyocyte NF-κB expression increased significantly but was attenuated in the PE group. These data collectively suggest that the estrus cycle plays an important role in cardiac function following TH. The salutary effect seen in PE following TH is likely due to a decrease in NF-κB-dependent cardiac lL-6 pathway. [ABSTRACT FROM AUTHOR]

Although studies indicate that 17β-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats (∼300 g) underwent laparotomy and hemorrhagic shock (35–40 mmHg for ∼90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17β-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-α, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-α, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17β-estradiol on organ functions after T-H. [ABSTRACT FROM AUTHOR]

Flutamide, an androgen receptor antagonist, is thought to improve cardiovascular function by blocking the androgen receptor after trauma-hemorrhage (T-H). Although 17β- estradiol (E2) and flutamide improve cardiac function after T-H, whether E2 and flutamide produce their salutary effect via the same or a different mechanism is unknown. We hypothesized that E2 and flutamide mediate their effects via estrogen receptor (ER)-mediated upregulation of peroxisome proliferator-activated receptor coactivator 1 (PGC-1). PGC-1, a key regulator of cardiac mitochondrial function, induces mitochondrial genes by activating transcription factors such as nuclear respiratory factor 2 (NRF-2), which regulates mitochondrial proteins [i.e., mitochondrial transcription factor A (Tfam), cytochrome-c oxidase subunit IV, and β-ATP synthase]. Adult male rats underwent T-H [5-cm midline incision and hemorrhage (blood pressure = 40 mmHg for ∼90 mm)] and resuscitation. At the onset of resuscitation, rats received vehicle, flutamide (25 mg/kg), or E2 (50 µg/kg). Another group received the ER antagonist ICI-182780 (3 mg/kg) with or without flutamide. Flutamide or E2 administration after T-H restored depressed cardiac function. Moreover, E2 and flutamide normalized expression of cardiac PGC-1, NRF-2, Tfam, cytochrome-c oxidase subunit LV, and the mitochondrial DNA-encoded gene cytochrome-c oxidase subunit I and β-ATP synthase, mitochondrial ATP, and cytochrome-c oxidase activity. However, if the ER antagonist ICI-182780 was administered with flutamide, flutamide-mediated PGC-1 upregulation was totally abolished. These results indicate that E2 and flutamide upregulate PGC-1 via the ER. Thus PGC-1 upregulation appears to be the common mechanism by which E2 and flutamide mediate their salutary effects on cardiac function after T-H. [ABSTRACT FROM AUTHOR]

A growing body of evidence indicates that heme degradation products may counteract the deleterious consequences of hypoxia and/or ischemia-reperfusion injury. Because heme oxygenase (HO)-1 induction after adverse circulatory conditions is known to be protective, and because females in the proestrus cycle (with high estrogen) have better hepatic function and less hepatic damage than males after trauma-hemorrhage, we hypothesized that estrogen administration in males after trauma-hemorrhage will upregulate HO activity and protect the organs against dysfunction and injury. To test this hypothesis, male Sprague-Dawley rats under went 5-cm laparotomy and hemorrhagic shock (35–40 mmHg for 93 ± 2 rain), followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17Β-Estradiol and/or the specific HO enzyme inhibitor chromium mesoporphyrin (CrMP) were administered at the end of resuscitation, and the animals were killed 24 h thereafter. Trauma-hemorrhage reduced cardiac output, myocardial contractility, and serum albumin levels. Portal pressure and serum alanine aminotransferase levels were markedly increased under those conditions. These parameters were significantly improved in the 17Β-estradiol-treated rats. Estradiol treatment also induced increased HO-1 mRNA expression, HO-1 protein levels, and HO enzymatic activity in cardiac and hepatic tissue compared with vehicle treated trauma-hemorrhage rats. Administration of the HO inhibitor CrMP prevented the estradiol-induced attenuation of shock-induced organ dysfunction and damage. Thus the salutary effects of estradiol administration on organ function after trauma-hemorrhage are mediated in part via upregulation of HO-1 expression and activity. [ABSTRACT FROM AUTHOR]

Prolactin (PRL) is involved in the regulation of immune functions under normal and pathological conditions. Trauma-hemorrhage (T-H) produces profound immunosuppression in male mice but not in proestrus female mice. Administration of PRL in males after T-H, however, restores immune functions. In this study, PRL+/+ and transgenic (PRL-/-) male and female mice were used to assess immune suppression after T-H and to determine the reasons for the hormone's beneficial effect. In vitro lymphoproliferation assay with Nb2 cells showed complete absence of PRL in the circulation of the transgenic PRL-/- mice of both sexes, whereas very high levels of the hormone were detected in the wild-type PRL+/+ mice of both sexes. Moreover, T-H resulted in the appearance of significant levels of the hormone in circulation, but only in PRL+/+ mice. Splenocyte proliferation in male PRL-/- mice was significantly lower than in PRL+/+ mice after T-H. Marginal differences between PRL+/+ and PRL-/- mice were observed in the release of IL-2 and IFN-γ by splenocytes, while the release of IL-10 was significantly higher in PRL-/- than in PRL+/+ mice. A significant observation of our study is the release of a ∼25-kDa protein in the concanavalin A-stimulated splenocytes of male PRL+/+ and PRL-/- mice that was active in the in vitro lymphoproliferation assay with Nb2 cells. It is unlikely that this protein is PRL because it is also present in the splenocyte extracts of PRL-/- transgenic mice. Nonetheless, because control of lymphoid cell proliferation is considered one of the characteristics of the immune system, the local release of this protein may be significant in the differences observed in splenocyte cytokine release after T-H in wild-type as well as transgenic mice. [ABSTRACT FROM AUTHOR]

Recent studies have shown that administration of dehydroepiandrosterone (DHEA) after trauma-hemorrhage (T-H) improves cardiovascular and hepatic function in male animals. Although androstenediol, one of the DHEA metabolites, has been recently reported to produce salutary effects on cardiac function and splanchnic perfusion after T-H, it remains unknown whether androstenediol per se has any salutary effects on hepatic function under those conditions. To study this, male Sprague-Dawley rats underwent laparotomy and ∼90 min of hemorrhagic shock (35-40 mmHg), followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. Androstenediol (1 mg/kg body wt iv) was administered at the end of resuscitation, and the animals were killed 24 h later. T-H significantly reduced portal blood flow, bile production, and serum albumin levels. Portal pressure, serum alanine aminotransferase, hepatic nitrate/nitrite, inducible nitric oxide synthase (iNOS), and endothelin-1 markedly increased after T-H. The alterations in these parameters induced by T-H were significantly attenuated in rats treated with androstenediol. Endothelial NOS (eNOS) expression, which was not different between T-H and sham, was found to be significantly elevated in T-H androstenediol-treated rats. These data suggest that improvement in hepatic perfusion by androstenediol after T-H is likely due to a decrease in endothelin-1 and induction of eNOS. Moreover, the decrease in hepatic damage after androstenediol administration is likely related to liver iNOS downregulation. Thus androstenediol appears to be a novel and useful adjunct for restoring hepatic function in male animals after adverse circulatory conditions. [ABSTRACT FROM AUTHOR]

Although systemic interleukin-6 (IL-6) level is elevated, hepatocellular function is impaired and liver injury occurs after trauma-hemorrhage (T-H), it remains unknown whether a causal relationship exists between elevated IL-6 levels and liver injury after T-H. We hypothesized that IL-6 is causative in the development of hepatic dysfunction and injury after T-H. To examine this, adult male Sprague-Dawley rats underwent a 5-cm midline laparotomy and were subjected to hemorrhagic shock (blood pressure = 35 mmHg for ∼90 min), followed by resuscitation (Ringer lactate, 4 times the shed blood volume). At 2, 5, and 24 h thereafter, blood samples were collected and the liver isolated and perfused for 60 min. Portal inflow pressure was measured, and perfusate samples were collected to measure IL-6, alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels. A significant positive correlation between plasma levels of IL-6 and ALT and perfusate levels of IL-6 and LDH levels was observed. In a second series of experiments, rats were treated with immunoglobulin G (IgG) or antibodies against rat IL-6 (anti-IL-6) at the onset of resuscitation. At 5 h after resuscitation, anti-IL-6 treatment attenuated the T-H induced increases in plasma ALT and thromboxane B2 (a thromboxane A2 metabolite) levels, and bile flow was normalized to sham levels. Perfusion of livers from normal rats with IL-6 did not alter portal pressure; however, perfusion of a stable thromboxane A2 analog dose dependently increased portal pressure. Thus IL-6 plays a significant role in the induction of hepatic dysfunction and liver injury after T-H that appears to be in part mediated by increased thromboxane A2 levels. [ABSTRACT FROM AUTHOR]

A prolonged depression of cardiovascular function occurs in males after trauma-hemorrhagic shock (T-H). Although a correlation between increased circulatory IL-6 levels and poor outcome has been reported after T-H, it remains unknown whether T-H increases IL-6 levels locally in cardiomyocytes and whether there is a correlation between altered cardiac function and local IL-6 production after T-H. T-H was induced in normal, castrated (2 wk before T-H), and 17β-estradiol (E2)-treated (0.5 mg sc, 1 wk before T-H) adult male rats. At 2 h after T-H or sham operation, cardiac output, heart rate, mean arterial pressure, positive and negative first derivative of pressure (± dP/dt), stroke volume, and total peripheral resistance were determined. Cardiomyocytes were isolated and divided into two parts: one was used for measurements of intracellular IL-6 levels using fluorescein-activated cell sorting, and the other was used to isolate RNA to determine IL-6 gene expression by quantitative real-time PCR. In addition, cardiac IL-6 protein levels were measured in freshly isolated hearts by Western blotting. Cardiac output, stroke volume, +dP/dt, -dP/dt, and total peripheral resistance were markedly altered after T-H. These parameters, except -dP/dt, improved significantly in the castrated group; however, all these parameters were restored in E2-treated males. Cardiomyocyte IL-6 mRNA expression and intra- cellular IL-6 production increased after T-H. Cardiac IL-6 protein levels increased after T-H in freshly isolated heart. Castration and E2 treatment attenuated cardiomyocyte intracellular IL-6 levels and car- diac IL-6 protein levels after T-H; however, only E2 treatment attenuated cardiomyocyte IL-6 gene expression. Thus there is an inverse correlation between cardiomyocyte IL-6 levels and cardiac function after T-H. The salutary effects of E2 on cardiac function after T-H may be due in part to decreased IL-6 synthesis in cardiomyocytes. [ABSTRACT FROM AUTHOR]

Recent studies have shown that dehydroepiandrosterone (DHEA) administration after trauma-hemorrhage (T-H) improves cardiovascular function and decreases cytokine production in male animals. Although androstenediol, one of the metabolites of DHEA, is reported to have estrogen-like activity, it remains unknown whether androstenediol per se has any salutary effects on cytokines and cardiovascular function after T-H. To examine this effect, male Sprague-Dawley rats underwent laparotomy and were bled to and maintained at a mean arterial blood pressure of 35-40 mmHg for ∼90 min. The animals were resuscitated with four times the volume of maximal bleedout volume in the form of Ringer lactate. Androstenediol (1 mg/kg body wt iv) or vehicle was administered at the end of resuscitation. Twenty-four hours after resuscitation, cardiac function and organ blood flow were measured by using 85Sr-microspheres. Circulating levels of nitrate/nitrite and IL-6 were also determined. Cardiovascular function and organ blood flow were significantly depressed after T-H. However, these parameters were restored by androstenediol treatment. The elevated plasma ILo6 levels after T-H were also lowered by androstenediol treatment. In contrast, plasma levels of nitrate/nitrite were the highest in the androstenedioltreated T-H animals. Because androstenediol administration after T-H decreases cytokine production and improves cardiovascular function, this agent appears to be a novel and useful adjunct for restoring the depressed cardiovascular function and for cytokine production in males after adverse circulatory conditions. [ABSTRACT FROM AUTHOR]

IL-6 and TNF-α production by Kupffer cells is markedly stimulated following traumahemorrhage (T-H). Because IL-10 is an anti-inflammatory cytokine, the aim of this study was to determine whether IL-10 regulates Kupffer cell proinflammatory cytokine release following T-H. To study this, we subjected adult male Sprague-Dawley rats to sham operation or T-H. The procedure involved a 5-cm midline laparotomy and ∼90 min of hemorrhagic shock (35 mmHg), followed by resuscitation with four times the shed blood volume in the form of Ringer's lactate. At 2 h after the end of resuscitation, livers were perfused in vitro and perfusate was collected. In separate studies, Kupffer cells were isolated and incubated with different concentrations of anti-IL-10 MAb. IgG was used as control. After 16 h of incubation, IL-6 and TNFα levels were measured by ELISA. Plasma IL-10 levels increased significantly following T-H. IL-10 levels in the perfusate and IL-10 production by cultured Kupffer cells were also significantly higher in the T-H group. When Kupffer cells were incubated with 10 μg/ml of anti-IL-10 MAb, IL-6 and TNF-α production were significantly increased in both sham and T-H groups compared with those not treated with anti-IL-10 MAb. However, these changes were not observed when the cells were incubated with irrelevant (control) IgG. These results indicate that IL-10 production by Kupffer cells early after T-H may play a pivotal role in attenuating the proinflammatory cytokine environment, possibly in an autocrine/paracrine manner. [ABSTRACT FROM AUTHOR]

Although gender differences exist in cardiovascular endothelial function, it remains unclear whether such differences are also seen in small intestinal endothelial function. To determine this, untreated male, age-matched proestrus female, castrated male, and 17β-estradiol (E2)treated noncastrated male rats were studied. Dose response curves to ACh and nitroglycerin (NTG) were determined by measuring changes in perfusion pressure by using an isolated small intestinal perfusion model. Endothelium-derived nitric oxide (NO) production/release was indirectly determined by the ability of intact endothelium to suppress serotonin (10-5 M)-induced perfusion pressure changes. Intestinal tissue levels of NO were also measured. Moreover, plasma levels of androgen and E2 were determined and correlated with ACh (10-8 M)-induced perfusion pressure reductions. ACh-induced intestinal perfusion pressure reductions in proestrus females, castrated males, and E2-treated noncastrated males were significantly higher than in untreated males. NTG-induced perfusion pressure reductions were not significantly different among groups. Perfusion pressures after administration of serotonin (10-5 M) and intestinal tissue levels of NO in proestrus females, castrated males, and E2-treated noncastrated males were also significantly higher than in untreated males. Plasma androgen levels in proestrus females, castrated males, and in E2-treated noncastrated males were significantly lower compared with untreated males. There was a positive correlation between plasma androgen and ACh-reduced perfusion pressure; however, E2 levels did not show a similar relationship. Thus androgens appear to play an inhibitory role in small intestinal endothelial function. These properties in male vessels can be modulated by decreasing the level of circulating androgens or by E2 treatment. [ABSTRACT FROM AUTHOR]

Hypothesis: Sex differentially influences heme oxygenase (HO) expression following trauma and hemorrhagic shock. Design: Prospective controlled animal study. Setting: A university laboratory. Interventions: Female Sprague-Dawley rats in the proestrus stage of their estrus cycle and male rats underwent a 5-cm midline laparotomy (ie, induction of soft tissue trauma) and were bled to a mean arterial blood pressure of 35 mm Hg for approximately 90 minutes, after which they were resuscitated with Ringer lactate solution (4 × the shed blood volume). In another group of animals, tin protoporphyrin IX was used to block HO activity. Main Outcome Measures: Liver samples were collected for analysis of HO expression and activity, plasma samples were collected, and alanine transaminase levels were determined 5 hours after resuscitation. Portal pressure and bile production were measured in vivo 5 hours after resuscitation. Results: Trauma and hemorrhage induced a 2-fold increase in hepatic HO1 expression (the inducible form of HO) in proestrus females compared with males. Hepatic expression of HO2 (a constitutive isoform of HO) was unaffected by sex or trauma and hemorrhage. Blockade of HO in vivo with tin protoporphyrin IX abolished the sex differences caused by diverse HO1 expression. Treatment with tin protoporphyrin IX also elevated the portal pressure, decreased bile production, and increased alanine transaminase to similar levels in proestrus females and males following trauma and hemorrhage. Conclusions: Sex influences the hepatic expression of HO1 following trauma and hemorrhage. The enhanced induction of HO1 expression and activity in females after trauma and hemorrhage may attenuate hepatocellular dysfunction and injury by maintaining microcirculation via the increased production of carbon monoxide. [ABSTRACT FROM AUTHOR]

Hypothesis: Administration of a single dose of progesterone following trauma and hemorrhage in progesterone-deficient rats would ameliorate the inflammatory response and hepatocellular damage. Setting: A university laboratory. Interventions: Ovariectomized female Sprague-Dawley rats (250-350 g; Charles River Laboratories, Wilmington, Mass) underwent a 5-cm midline laparotomy (ie, induction of soft tissue trauma), were bled to a mean arterial blood pressure of 35 mm Hg for about 90 minutes, and then were resuscitated using Ringer lactate solution. Progesterone (25 mg/kg of body weight) or vehicle was administered subcutaneously at the end of resuscitation. In additional animals, Kupffer cells were isolated following trauma, hemorrhage, and resuscitation and treated in vitro with progesterone, lipopolysaccharide, or both. Main Outcome Measures: Six hours following resuscitation, plasma tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) levels and liver myeloperoxidase activity were determined. Hepatocellular function (maximum velocity of indocyanine green clearance [V[sub max]] and the efficiency of the active transport or Michaelis-Menten constant [K[sub m]]) and plasma levels of transaminases were measured 20 hours after resuscitation. Kupffer cell IL-6 and TNF-α production were assessed. Results: Plasma levels of TNF-α, IL-6, aspartate aminotransferase, and alanine aminotransferase, as well as hepatic myeloperoxidase activity were increased, whereas indocyanine green clearance was depressed in vehicle-treated rats following trauma-hemorrhage. Animals treated with progesterone showed significantly reduced levels of the TNF-α, IL-6, and transaminases as well as reduced myeloperoxidase activity in the liver. Progesterone-treated animals showed increased V[sub max] and K[sub max] values for indocyanine green. In vitro treatment of Kupffer cells with progesterone decreased TNF-α production but did not affect the production... [ABSTRACT FROM AUTHOR]

Trauma-hemorrhage and resuscitation (TH) produces profound immunodepression and enhances susceptibility to sepsis in males but not in proestrus females, suggesting gender dimorphism in the immune responses. However, the mechanism responsible for the maintenance of immune functions in proestrus females after TH is unclear. Splenic T lymphocytes express receptors for estrogen (ER), contain enzymes involved in estrogen metabolism, and are the major source of cytokine production; the metabolism of 17β-estradiol was assessed in the splenic T lymphocytes of proestrus and ovariectomized mice by using appropriate substrates after TH. Analysis for aromatase and 17β-hydroxysteroid dehydrogenases indicated increased 17β-estradiol synthesis and low conversion into estrone in T lymphocytes of proestrus but not of ovariectomized mice. The effect of 17βestradiol on T lymphocyte cytokine release was reliant on ER expressions. This was apparent in the differences of ER expression, especially that of ER-β, and an association between increased 17β-estradiol synthesis and sustained release of IL-2 and IL-6 in T lymphocytes of proestrus females after TH. Because 17β-estradiol is able to regulate cytokine genes, and the splenic T lymphocyte cytokine releases is altered after TH, continued synthesis of 17β-estradiol in proestrus females appears to be responsible for the maintenance of T lymphocyte cytokine release associated with the protection of immune functions after TH. [ABSTRACT FROM AUTHOR]

Proestrous female rodents are protected from the deleterious effects of trauma-hemorrhage that are observed in males. We hypothesized that the gender dimorphic outcome after trauma-hemorrhage might be related to gender differences in endothelial function and organ perfusion under such conditions. Male and cycle-matched proestrous female Sprague-Daw]ey rats underwent a midline laparotomy, hemorrhagic shock (40 mmHg for ∼90 min), and resuscitation (Ringer lactate, 4× shed blood volume over 60 min). Various parameters were measured 2 h after completion of resuscitation. In the first set of animals, the ]eft ventricle was cannulated and heart performance (maximal rate of left ventricular pressure increase) as well as cardiac output and organ perfusion rates were determined with [sup 85]Sr microspheres. In the second set of animals, aortic vessel rings were harvested and relaxation in response to acetylcholine and nitroglycerin was measured. In the third set of animals, in situ isolated small intestine was perfused to measure the response of the splanchnic vessel bed to acetylcholine and nitroglycerin. After trauma-hemorrhage and resuscitation, females maintained cardiac output and demonstrated increased splanchnic and cardiac perfusion compared with ma]es. Moreover, female intestines did not manifest the endothelial dysfunction that was observed in male intestines after hemorrhagic shock. We conclude that proestrous females show improved endothelial function and tissue perfusion patterns after hemorrhagic shock and that this genderspecific response might be a potential mechanism contributing to the beneficial effects of the proestrus stage under such conditions. [ABSTRACT FROM AUTHOR]

Hypothesis: Flutamide, a testosterone receptor antagonist, produces various beneficial effects in male rats following hemorrhagic shock, possibly as a result of a direct vasodilating effect on large and small vessels in the rat. Design, Interventions, and Main Outcome Measures: The aorta and the small intestine were isolated from normal male and female Sprague-Dawley rats. Isolated aortic rings were placed in the organ bath and constricted by 2 × 10[sup -7]M norepinephrine bitartrate (Sigma, St Louis, Mo). Flutamide-induced and testosterone-induced vascular relaxation dose-response curves were then determined. The dose-response curves of flutamide were also determined in the small blood vessels of the isolated small intestine under conditions of constant flow following preconstriction induced by 5 × 10[sup -6]M norepinephrine bitartrate. The effects of prior incubation with testosterone (8 × 10[sup -5]M) and sex differences on flutamide-induced vascular relaxation were also examined in aortic rings and in the small intestine. Moreover, flutamide-induced relaxation in endothelium-denuded aortic rings and in aortic rings from animals subjected to trauma and hemorrhagic shock was examined. Results: Flutamide induced significant relaxation in aortic rings and small intestinal blood vessels in healthy males. The flutamide-induced relaxation in vessels from normal males was partially attenuated by prior incubation with the male sex steroid testosterone, and was significantly lower in females. Flutamide-induced vascular relaxation in the aorta was partially attenuated by endothelium removal, but it was not significantly affected by trauma and hemorrhagic shock in male rats. Conclusions: Flutamide has a direct vasodilating effect on large and small vessels in rats, which involves sex-dependent mechanisms. Thus, the beneficial effects of flutamide on cardiovascular responses in males following trauma and hemorrhagic shock may be due to the direct vascular... [ABSTRACT FROM AUTHOR]

Examines the acute respiratory distress syndrome after injury. Regulation of alveolar macrophage chemokine and cytokine after hemorrhage and sepsis; Induction of sepsis by cecal ligation and puncture; Development of lung edema and leukocyte activation.

Examines the influence of decreased 5αdihydrotestosterone catabolism in suppressing T lymphocyte functions after trauma-hemorrhage in males. Result of prior castration; Presence of steroidogenic enzymes; Reference to th release of interleukin-2 and -6.

Background. Recent studies have shown that the intestinal barrier function is altered and macromolecules can translocate after trauma and hemorrhagic shock. The translocated molecules are absorbed from the lymphatic tissue or directly enter the circulation in the gut. However, it remains unknown to what degree these compartments contribute to the clearance of the macromolecules.Methods. Male Sprague-Dawley rats (350–400 g) underwent a 5-cm midline laparotomy (i.e., soft tissue injury), were bled to a mean arterial pressure of 35 mmHg and maintained for approximately 90 min, and then resuscitated with Ringer’s lactate (4× the shed blood volume) over 60 min. At 2 h after resuscitation, a solution containing 51Cr-EDTA, FITC-dextran-4 kDa, and rhodamine B-dextran-40 kDa was instilled into a jejunal blind loop and their concentrations were determined in mesenteric lymph and blood samples harvested between 2 h and 4 h after resuscitation.Results. Trauma-hemorrhage and crystalloid resuscitation significantly increased mesenteric lymph flow and the mucosal permeability for the three marker molecules. There was no difference in the concentrations of 51Cr-EDTA between the blood and lymph compartment after trauma-hemorrhage. However, the high molecular weight marker (rhodamine-B-dextran-40 kDa) accumulated in significantly higher concentrations in the mesenteric lymph than in the plasma under such conditions.Conclusions. The accumulation of macromolecules in the mesenteric lymph suggests that this compartment plays an important role in the altered gut barrier function after trauma-hemorrhage. [Copyright &y& Elsevier]

Both traumatic forequarter amputation and scapulothoracic dissociation are rare and life-threatening injuries. We present the case of a 31-year old woman who was ejected from a car after a motor vehicle accident and sustained an apparent partial forequarter amputation. Upon examination her injury was found to share many characteristics with a scapulothoracic dissociation injury. With both injuries mortality is high and prompt diagnosis and treatment imperative. By viewing scapulothoracic dissociation and forequarter amputation as a continuum faster recognition and appropriate treatment may be implemented for these devastating injuries. [ABSTRACT FROM AUTHOR]

Discusses two cases of delayed blunt cardiac rupture in which the diagnosis was delayed by the presence of an associated pericardial tear with decompression into the mediastinum and pleural space. Factors that obscured the diagnosis; Recommendations for diagnostic algorithms.

Most retrospective studies evaluating fresh-frozen plasma:packed red blood cell ratios in trauma patients requiring massive transfusion (MT) are limited by survival bias. As prospective resource-intensive studies are being designed to better evaluate resuscitation strategies, it is imperative that patients with a high likelihood of MT are identified early. The objective of this study was to develop a predictive model for MT in civilian trauma patients. Patients admitted to the University of Alabama at Birmingham Trauma Center from January 2005 to December 2007 were selected. Admission clinical measurements, including blood lactate 5 mMol/L or greater, heart rate greater than 105 beats/min, international normalized ratio greater than 1.5, hemoglobin 11g/dL or less, and systolic blood pressure less than 110 mmHg, were used to create a predictive model. Sensitivity (Sens), specificity (Spec), positive predictive value (PPV), and negative predictive value (NPV) were calculated for all possible combinations of clinical measurements as well as each measure individually. A total of 6638 patients were identified, of whom 158 (2.4%) received MT. The best-fit predictive model included three or more positive clinical measures (Sens: 53%, Spec: 98%, PPV: 33%, NPV: 99%). There was increased PPV when all clinical measurements were positive (Sens: 9%, Spec: 100%, PPV: 86%, NPV: 98%). All combinations or clinical measures alone yielded lower predictive probability. Using these emergency department clinical measures, a predictive model to successfully identify civilian trauma patients at risk for MT was not able to be constructed. Given prospective identification of patients at risk for MT remains an imprecise undertaking, appropriate resources to support these efforts will need to be allocated for the completion of these studies. [ABSTRACT FROM AUTHOR]

The purpose of the study was to compare tubing-related injuries to wakeboarding- and water skiing-related injuries. Data was collected from the 2000-2007 National Electronic Injury Surveillance Survey for 1,761 individuals seeking care at an emergency department due to a tubing-, wakeboarding, or water skiing-related injury. Data included patient age and sex, as well as injury characteristics including body region injured (i.e., head and neck, trunk, shoulder and upper extremity, and hip and lower extremity) and diagnosis of injury (e.g., contusion, laceration, or fracture). Case narratives were reviewed to ensure that a tubing-, wakeboarding-, or water skiing-related injury occurred while the individual was being towed behind a boat. Severe injury (defined as an injury resulting in the individual being hospitalized, transferred, held for observation) was compared among the groups using logistic regression. Wakeboard- and tubing-related injuries more commonly involved the head and neck, while water skiing-related injuries were likely to involve the hip and lower extremity. Tubing-related injuries, compared to water skiing-related injuries, were more likely to be severe (OR 2.31, 95% CI 1.23-4.33). Like wakeboarding and water skiing, tubing has inherent risks that must be understood by the participant. While tubing is generally considered a safer alternative to wakeboarding and water skiing, the results of the current study suggest otherwise. Both the number and severity of tubing- related injuries could be prevented through means such as advocating the use of protective wear such as helmets while riding a tube or having recommended safe towing speeds prominently placed on inner tubes. [ABSTRACT FROM AUTHOR]

Recognition of the adverse effects of allogeneic blood resulted in the decreased use of red blood cell (RBC) transfusion in surgical practice in the 1990s. Our objective was to evaluate patterns of RBC transfusion utilization among trauma patients during the current decade. Blunt trauma patients admitted to a regional trauma center between 2000 and 2007 were identified (n = 16,011). Annual trends in RBC utilization were estimated (negative binomial regression for continuous dependent variables and logistic regression for dichotomous variables). Models were stratified by Injury Severity Score to adjust for injury severity. Although the proportion of patients receiving a blood transfusion within 48 hours of hospitalization significantly increased (P < 0.0001), there was no significant change in the rate of units transfused (P = 0.5152) among transfused patients. After stratification by Injury Severity Score, a significantly decreasing trend in the proportion of severely injured patients transfused was observed (P = 0.0243). Annual variation in the relatively less injured groups was not significant. In the current decade, transfusion utilization at a Level I trauma center has demonstrated minimal variation on a year-to-year basis. Among the severely injured, the temporal decrease in relatively early utilization of RBC transfusion may reflect increasing inclination to accept a greater degree of anemia in higher acuity patients. [ABSTRACT FROM AUTHOR]

Studies suggesting that increased trauma center (TC) patient votume leads to improved patient outcomes have produced inconsistent results. It is possible that the combination of TC patient volume and TC resources has a greater influence over outcomes than TC volume atone. Patients admitted to 131 TCs from 1994 to 2002 were included. TC density was calculated as the ratio of TC adult beds to patient volume and categorized into quartiles. Adjusted risk ratios (RRs) and 95 per cent confidence intervals (CIs) compared mortality of groups (Ql [low density]-Q4 [high density]). Relative to Q4 TCs, for penetrating injuries with ISS <15, elevated mortality was seen for Q2 (low-moderate density) TCs (RR 1.47, CI 1.09-1.99) and Q3 (high-moderate density) TCs (RR 1.81, CI 1.36-2.41); but for ISS >15, mortality was lowest for Ql (RR 0.78, CI 0.68-0.89). For blunt injury, mortality was similar for low- and high-density TCs but elevated for low-moderate- and high-moderate-density TCs. Mortality at low-density TCs was decreased overall and for penetrating injuries specifically but similar for blunt injuries when compared with high-density TCs. Enhanced resources measurements will clarify the relationship between patient volume, resources, and mortality. [ABSTRACT FROM AUTHOR]

Background: The fine balance between vasoconstrictors and vasodilators maintains portal circulation. Studies have shown that portal response to endothelin-1 (ET-1), a potent vasoconstrictor, is enhanced following hemorrhagic-shock, which subsequently leads to the impaired hepatic circulation and hepatic damage. Although protective effects of 17β-estradiol (E2) against hepatic damage following trauma-hemorrhage have been observed, it remains unknown whether E2 directly improves hepatic circulation. We hypothesized that the salutary effects of E2 are mediated, at least in part, by the attenuation of portal response to ET-1 following trauma-hemorrhage.Materials and methods: Male adult Sprague-Dawley rats were randomly assigned to sham operation or trauma-hemorrhage with or without in vivo E2 treatment. Trauma-hemorrhage included midline laparotomy and ∼90 min of hemorrhagic shock (35 mmHg), then resuscitation with four times the shed blood volume with Ringer’s lactate solution over 60 min. For the E2 treatment group, 1 mg/kg of E2 was added to the Ringer’s lactate solution. At 5 h after the end of resuscitation, the liver was isolated and perfused in vitro to measure portal pressure responses to exogenous ET-1 (60 pmol in 150 ml perfusate, bolus) with or without E2 (1,500 pg/ml).Results: Peak portal pressure after the administration of ET-1 was significantly higher in vehicle-treated trauma-hemorrhage group compared with the sham group. This effect was significantly attenuated in the E2 treatment group. Furthermore, E2 treatment restored bile production and prevented hepatic damage following trauma-hemorrhage.Conclusions: The beneficial effects of estradiol observed following trauma-hemorrhage, at least partly, are caused by the attenuation of portal pressure response to increased ET-1. [Copyright &y& Elsevier]

: BackgroundRecent studies have shown that the acute phase protein α1-acid-glycoprotein (AAG) directly modifies endothelial cell responsiveness and is a crucial factor for maintaining endothelial barrier function. We hypothesized that the addition of AAG to the resuscitation fluid will prevent edema formation, increases circulating blood volume, and reduces tissue inflammation following soft tissue trauma and hemorrhagic shock.: Materials and methodsMale Sprague-Dawley rats (338 ± 28 g) underwent a 5-cm midline laparotomy (i.e., induction of soft tissue trauma) and were bled to and maintained at a mean arterial pressure of 35 mm Hg for 90 min. The rats were then resuscitated with four times the shed blood volume with Ringer’s lactate containing 200 mg/kg AAG or the same amount of albumin. At 6 h after resuscitation, organ wet-to-dry weight ratios and circulating blood volume (Evans blue dilution) were determined. Neutrophil accumulation (myeloperoxidase activity, MPO) and tissue lipid peroxidation (thiobarbituric acid reactive substances) were also measured in the lungs, liver, and intestine.: ResultsAdministration of AAG during the resuscitation significantly increased circulating blood volume and reduced edema formation, neutrophil accumulation, and lipid peroxidation. Interestingly, concomitant plasma IL-6 levels increased while TNF-α levels were not significantly affected.: ConclusionsSince addition of AAG to the resuscitation fluid increased circulating blood volume, reduced edema formation, and neutrophil accumulation following trauma and hemorrhagic shock, supplementation of this acute phase protein appears to be a potential adjunct to prevent capillary leakage in patients undergoing major traumatic injury. [Copyright &y& Elsevier]

Studies have shown that 17β-estradiol has salutary effects on immune functions after trauma–hemorrhage (TH). It remains unknown, however, whether 17β-estradiol has a similar effect in a double-hit model of TH and subsequent sepsis. It is also unknown if under those conditions the circulating immune cells accurately represent immunological responses occurring in fixed tissues, such as the spleen. To study this, pre-castrated mice were hormonally treated and then subjected to soft-tissue trauma (i.e. midline laporatomy), hemorrhagic shock (MAP 35±5 mmHg for 90 min followed by resuscitation) and 24 h later sepsis was induced by cecal ligation and puncture (CLP). Splenic macrophages (SMφ) and peripheral blood mononuclear cells (PBMC) were isolated and cultured with LPS. 5α-Dihydrotestosterone-treated mice showed a depressed pro-inflammatory cytokine production after TH-sepsis in both SMφ and PBMC. In contrast, the 17β-estradiol treated groups showed suppressed pro-inflammatory cytokine production in the PBMC population under those conditions. In summary, 17β-estradiol was able to prevent immune dysfunction after TH and subsequent sepsis. However, the beneficial effects of 17β-estradiol were limited to tissue-fixed Mφ, suggesting compartmentalization of the response. Thus, events occurring in the tissue-fixed cells are not necessarily reflected in the circulating PBMC population. [Copyright &y& Elsevier]

This retrospective study reports, outcomes, after early and delayed surgical stabilization of fractures of the pelvic ring, in terms of pulmonary complications, length of hospital stay, and cost of hospitalization. The hospital course of 151 patients admitted to an academic teaching hospital who sustained acute fractures of the pelvic ring between June 1996 and December 2000 was reviewed. Patient demographics, Injury Severity Score (ISS), timing of operative fixation, and the incidence of pulmonary complications were analyzed. Radiographs were reviewed and fractures classified according to the modified Tile system. Tile fracture types B and C patients who underwent fixation within 1 week of injury (n = 71) were compared to those in whom surgery was delayed (n = 28). Adjusting for the ISS, early-repair patients had a lower risk of pulmonary complications (RR = 0.49, 95% CI = 0.25-0.96), a reduced length of hospital stay (12.2 vs. 20.5 days; P = 0.0005), and overall reduced cost of care ($57,084 vs. $158,625; P = 0.0317). Pelvic ring fixation within the first week of injury results in significantly reduced incidence of pulmonary complication, hospital stay, and cost of care regardless of injury severity. The coordinated team approach to insure prompt resuscitation, stabilization, and operative fixation results in more optimal patient outcomes. [ABSTRACT FROM AUTHOR]