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Stewart C Wang

Publications and source records attributed to Stewart C Wang.

13 recordsLinked to original sources
PubMed2004

Impaired hepatocyte regeneration in toll-like receptor 4 mutant mice.

Multiple lines of evidence suggest a role for endogenous lipopolysaccharides in toxin-induced liver injury. Toll-like receptor 4 has recently been implicated as a cell surface receptor important for lipopolysaccharide responsiveness. In these experiments, we sought to determine the role of toll-like receptor 4 in acute liver injury by carbon tetrachloride by utilizing the naturally occurring toll-like receptor 4 mutant and wild-type mice strains. Mice were injected with either carbon tetrachloride or the carrier. Serum transaminase levels peaked at 24 hr after carbon tetrachloride administration for both wild-type and mutant mice, with no significant histological difference in initial liver injury between the two groups. However, an overall decrease in hepatocyte proliferation was found in the mutant mice. Examination of the liver tissue revealed significant decreases in intrahepatic expressions of proinflammatory mediators. In conclusion, our results suggest that toll-like receptor 4 is important in the hepatic regenerative response to CCl4 liver injury via its role in modulating the inflammatory response to hepatic injury.

Animals↗
PubMed2004

Delayed repair for blunt thoracic aortic injury: is it really equivalent to early repair?

BACKGROUND: Blunt thoracic aortic injury (BTAI) is a severe injury that traditionally has mandated immediate surgical repair. Delaying operative intervention for BTAI can allow other life-threatening injuries to be managed first, but potentially increases the risk of aortic rupture and death. The objective of this study was to evaluate the outcome of delayed repair (DR) compared with early repair (ER) for BTAI and to assess the effectiveness of a protocol for medical control of systolic blood pressure and heart rate in those patients whose repairs were delayed. METHODS: This study is a retrospective review of University of Michigan Health System (UMHS) data from January 1, 1992, through March 1, 2003. ER was defined as operative repair within 16 hours from the time of injury. A similar analysis was conducted for patients with BTAI selected from the National Trauma Data Bank. RESULTS: For the UMHS data, there were 45 patients in the DR group and 33 patients in the ER group. Mortality in the ER group versus the DR group was 9% versus 20%. Multivariate analysis adjusting for age, Injury Severity Score, abdominal Abbreviated Injury Scale score, Glasgow Coma Scale score, and intubation status demonstrated an odds ratio for death from ER compared with DR of 1.72 (p = 0.57). Patients undergoing DR had an absolute increase in hospital length of stay (33.1 vs. 20.9 days) and complication rate (2.1 vs. 1.5 incidents per patient). A similar result was obtained for multivariate analysis of the National Trauma Data Bank data, with an odds ratio of 1.40 (p = 0.51) for death from ER versus DR. UMHS patients whose repairs were delayed achieved target systolic blood pressure and heart rate for 76% and 74% of the hourly measurements recorded, respectively. CONCLUSION: Patients with BTAI can safely undergo delayed aortic repair if other injuries warrant a higher treatment priority without increasing their overall risk of mortality. Delayed repair is, however, associated with a higher complication rate.

Adult↗
PubMed2004

Beta-blocker use is associated with improved outcomes in adult burn patients.

BACKGROUND: There is no direct evidence that beta-blockers improve mortality in burn victims. Beta-blockers attenuate hypermetabolic states in burned children, and perioperative use in elective adult cases has beneficial effects, which suggests that beta-blockers may also improve burn outcomes. However, beta-blockers decrease cardiac output and may decrease oxygen delivery, and theoretically may increase mortality. What is the effect of beta-blockers on healing time and mortality in burn patients? METHODS: This was a retrospective cohort study. We identified three cohorts of adult burn patients between 1996 and 2001: all who were on beta-blockers (BB) before their injury (PMH BB); all who were initiated on BB during their hospitalization for management of hypertension or tachyarrhythmia (HOSP BB); and control, who were never treated with beta-blockers. For each patient in the PMH BB and HOSP BB groups, two patients were placed in the control cohort by matching age and total body surface area burn. Premorbid conditions such as diabetes, hypertension, cardiac disease, renal insufficiency, and diuretic and calcium channel blocker use were analyzed. Multivariate regression models were used to identify independent modifiers. RESULTS: There were 21 PMH BB, 22 HOSP BB, and 86 control patients. All PMH BB patients remained on their BB regimen in the hospital. HOSP BB patients were initiated on beta-blockers at a mean of 8.8 days postinjury. There were no differences in age (mean, 58 +/- 17 years), total body surface area burned (mean, 14 +/- 12%), or mechanism of injury among the cohorts. The mortality rate was 5% for the PMH BB cohort, 27% for the HOSP BB cohort, and 13% for controls. The mean healing times were 51 +/- 29 days for PMH BB patients, 79 +/- 54 days for HOSP BB patients, and 60 +/- 39 for controls. In multivariate analyses, PMH BB was associated with a significant decrease in fatal outcome and healing time (p < or = 0.05 compared with control). CONCLUSION: Beta-blockers have the potential to improve adult burn outcomes. Postinjury treatment should be studied in a randomized, clinical trial.

Adrenergic beta-Antagonists↗
PubMed2004

Computed tomographic scanning reduces cost and time of complete spine evaluation.

BACKGROUND: We hypothesize that data collected from computed tomographic (CT) scans obtained for workup of chest or abdominal injuries provide data that are sufficient to screen for spinal fractures and will decrease the cost and time of spine evaluation after trauma. METHODS: We reviewed plain radiographs from 55 selected trauma patients who also underwent CT scanning of the chest, abdomen, and pelvis. We also timed the radiologic workup of 50 consecutive trauma patients to determine the time required to complete radiographic spine evaluation. RESULTS: Forty-seven patients had thoracolumbar fractures. Thirteen patients were found to have 33 thoracolumbar spine fractures identified by CT scan but not plain radiography. Fractures were found on initial trauma CT scans of the chest, abdomen, and pelvis obtained to evaluate for visceral injuries. No injuries seen on plain film were missed on CT scan. CONCLUSION: We recommend using the data acquired from CT scans to evaluate the spine, supplementing them with additional studies only when needed for further clarification.

Accidental Falls↗
PubMed2004

Gender differences in hip anatomy: possible implications for injury tolerance in frontal collisions.

Male occupants in frontal motor vehicle collisions have reduced tolerance for hip fractures than females in similar crashes. We studied 92 adult pelvic CT scans and found significant gender differences in bony pelvic geometry, including acetabular socket depth and femoral head width. Significant differences were also noted in the presentation angle of the acetabular socket to frontal loading. The observed differences provide biomechanical insight into why hip injury tolerance may differ with gender. These findings have implications for the future design of vehicle countermeasures as well as finite element models capable of more accurately predicting body tolerances to injury.

Accidents, Traffic↗
PubMed2003

The cushion effect.

BACKGROUND: The pattern and severity of crash injury depends on a complex interaction of biomechanical factors such as deceleration velocity at impact (delta-V), seat-belt and airbag use, and type of impact. Human body characteristics such as height and weight may play an important role. We hypothesized that body mass index (BMI) will influence crash injury patterns. METHODS: The University of Michigan Program for Injury Research and Education database was queried. Three cohorts were analyzed, lean (BMI </= 25 kg/m2), overweight (BMI 25-30 kg/m2), and obese (BMI > 30 kg/m2) RESULTS: There were 189 detailed crash cases, with 22 fatalities. There was an increased risk of fatal outcome associated with the obese cohort (adjusted odds ratio, 4.2 compared with lean; p = 0.04). Age, delta-V, seat-belt use, and type of impact were independent predictors of Injury Severity Score (ISS). After adjusting for other modifiers, being overweight was associated with decreased ISS (p = 0.03) and abdominal maximal Abbreviated Injury Scale (mAIS) score (p = 0.008) when compared with the lean cohort. However, the lower extremity mAIS score increased when overweight (p = 0.03) and obese cohorts (p = 0.001) were compared with the lean cohort. CONCLUSION: Although no difference in ISS was identified between the lean and obese cohorts, there was an increase in mortality with the obese cohort. The severity of lower extremity injuries increased with increasing BMI. The overweight cohort was associated with lower ISS and abdominal mAIS score compared with the lean cohort. This protection may be attributable to an increase in insulating tissue, or a "cushion effect," without a significant increase in mass and momentum.

Accidents, Traffic↗
PubMed2003

Increased depth of subcutaneous fat is protective against abdominal injuries in motor vehicle collisions.

The objective of this study was to determine the effect of differences in subcutaneous fat depth on adult injury patterns in motor vehicle collisions. Sixty-seven consecutive adult crash subjects aged 19-65 who received computed tomography of their chest, abdomen and pelvis as part of their medical evaluation and who consented to inclusion in the Crash Injury Research Engineering Network (CIREN) study were included. Subcutaneous fat was measured just lateral to the rectus abdominus muscle in a transverse section taken through the subject at the level of L4. Women had significantly greater subcutaneous fat depth than men. Increased subcutaneous fat depth was associated with significantly decreased injury severity to the abdominal region of females. A similar trend was noted in males although it did not reach statistical significance. Our findings suggest that increased subcutaneous fat may be protective against injuries by cushioning the abdominal region against injurious forces in motor vehicle collisions.

Abbreviated Injury Scale↗
PubMed2002

Thermal injury induces expression of CD14 in human skin.

BACKGROUND: Skin is equipped with an array of immune mediators aimed at fighting invading microbes. CD14 has been shown to play a key role in modulating the activation of cells by LPS. Since LPS levels within burn wounds are often found to be elevated, we sought to examine the expression of CD14 within human skin following thermal injury. METHODS: Patients who sustained partial thickness burns, were recruited into the study (n=57). Total RNA was isolated from both burn and normal (control) skin. Northern blot analysis and TaqMan RT-PCR were used to determine skin CD14 mRNA levels. Immunohistochemistry was used to localize CD14 expression in burned and normal skin. RESULTS: Quantitative PCR showed significantly increased CD14 expression levels in the immediate post-burn period (P<0.05 burn versus non-burn). Immunohistochemistry revealed more pronounced CD14 staining 24 h after the injury, reaching normal levels approximately 5-7 days post-burn. CONCLUSION: CD14 expression peaks within the first week post-burn before declining, reaching normal levels after 14 days. This loss of supranormal CD14 expression locally within the wound may contribute to a weakened host defense response 5-6 days after injury, when patients become especially vulnerable to infection.

Adolescent↗
PubMed2002

Prevalence of domestic violence and associated factors among women on a trauma service.

BACKGROUND: Despite the increasing recognition of the problem of domestic violence (DV), it has not been studied in surgical populations. METHODS: Eligible patients underwent screening for a recent history of DV and alcohol abuse (AA). Other demographic, health, and injury-related data were also collected. RESULTS: Of 127 subjects entered into the study, 18% screened positive for DV and 21% screened positive for AA. Of those screening positive for DV, 65% screened positive for AA compared with 12% of those screening negative for DV (p < 0.001.) Screening for DV was recommended by a vast majority of subjects, with only 6% of subjects responding that it was not appropriate. CONCLUSION: Both DV and AA have a high prevalence among female trauma patients admitted to trauma centers. Nearly all subjects recommended screening for DV. Screening for DV should be incorporated into the routine care of female trauma patients.

Adult↗
PubMed2002

An essential role for lipopolysaccharide-binding protein in pulmonary innate immune responses.

Lipopolysaccharide (LPS)-binding protein (LBP) greatly facilitates LPS activation of monocytic cells through the CD14 receptor, triggering activation of innate immune responses. An acute phase protein, LBP is produced predominantly by the liver; however, we and others have shown that LBP is produced extrahepatically in multiple locations, including the lung. The importance of LBP in the lung has remained unclear. LBP may make the host more acutely sensitive to LPS and development of septic complications; alternatively, it may be protective, aiding in detection, opsonization, and killing of bacteria. Our objective was to determine the role LBP plays in local pulmonary immune defenses to bacterial challenge. LBP knockout mice and age-matched C57BL/6 wild-type controls were challenged with direct intratracheal inoculation of Klebsiella pneumoniae. We observed a significant increase in mortality, earlier onset of bacteremia, and greater pulmonary bacterial loads in LBP knockout mice compared with controls. Total lung myeloperoxidase (MPO) activity, neutrophil recruitment to the alveolar space, and levels of KC--a chemokine involved in neutrophil recruitment--in bronchoalveolar lavage (BAL) fluid and lung homogenates were found to be significantly diminished in knockout mice compared with controls. Together, our findings suggest that LBP is essential in local pulmonary innate immune responses against bacteria.

Acute-Phase Proteins↗
PubMed2002

Activity of novispirin G10 against Pseudomonas aeruginosa in vitro and in infected burns.

The emergence of multidrug-resistant microbes has serious implications for managing infection and sepsis and has stimulated efforts to develop alternative treatments, such as antimicrobial peptides. The objective of this study was to test a designer peptide, novispirin G10, against multidrug-resistant microorganisms. By two-stage radial diffusion assays, its activity against such organisms compared favorably with that of standard antibiotics and other antimicrobial peptides. It killed bacteria very rapidly, was nonhemolytic, and was relatively noncytotoxic. The peptide induced an immediate, massive efflux of potassium from Pseudomonas aeruginosa, suggesting that it altered the permeability of its inner membrane. The presence of human serum reduced but did not eliminate its activity. We tested the in vivo activity of novispirin G10 in rats with an infected, partial-thickness burn that covered 20% of their total body surface area. The burned area was seeded with 10(6) CFU of a Silvadene-resistant P. aeruginosa strain, and 24 h later a single treatment with 0, 1, 3, or 6 mg of synthetic novispirin G10 (n = 16 at each concentration) per kg was given intradermally. Significant bacterial killing (P < 0.0001) was evident within 4 h in each peptide group compared to controls receiving vehicle. Antimicrobial peptides such as novispirin G10 may provide a useful alternative or adjunct to standard antibiotic agents in treating burns or other wound infections.

Amino Acid Sequence↗
PubMed2002

Activation of human and mouse Kupffer cells by lipopolysaccharide is mediated by CD14.

Upregulation of CD14 in Kupffer cells has been implicated in the pathogenesis of several forms of liver injury, including alcoholic liver disease. However, it remains unclear whether CD14 mediates lipopolysaccharide (LPS) signaling in this specialized liver macrophage population. In this series of experiments, we determined the role of CD14 in LPS activation of Kupffer cells by using several complementary approaches. First, we isolated Kupffer cells from human livers and studied the effects of anti-CD14 antibodies on LPS activation of these cells. Kupffer cells were incubated with increasing concentrations of LPS in the presence and absence of recombinant human LPS binding protein (LBP). With increasing concentrations of LPS, human Kupffer cell tumor necrosis factor-alpha (TNF-alpha) production (a marker for Kupffer cell activation) increased in a dose-dependent manner in the presence and absence of LBP. In the presence of anti-human CD14 antibodies, the production of TNF-alpha was significantly diminished. Second, we compared LPS activation of Kupffer cells isolated from wild-type and CD14 knockout mice. Kupffer cells from CD14 knockout mice produced significantly less TNF-alpha in response to the same amount of LPS. Together, these data strongly support a critical role for CD14 in Kupffer cell responses to LPS.

Acute-Phase Proteins↗