Search PubMed⌕ Search

Biomedical subjects

Steven C Stain

Publications and source records attributed to Steven C Stain.

17 recordsLinked to original sources

The STAT4 and STAT6 pathways in pancreatitis-associated lung injury.

BACKGROUND: The STAT pathways are integral to the inflammatory response and these proteins provide a direct link between the cytokine receptors and cytokine-induced gene transcription. We examined the roles of STAT4 and STAT6 in lung injury after caerulein-induced severe acute pancreatitis. We hypothesized that a modified organ expression of cytokines and chemokines that occurs in transgenic mice may affect the systemic response to severe acute pancreatitis. METHODS: Acute pancreatitis [13-hourly intraperitoneal injections of caerulein (50 microg/kg body weight, 0.2 mL) or the same volume of saline] was induced in wild-type (BALB/c) and transgenic (STAT4 or STAT6) mice of the same background, 7 to 8 weeks old. The pancreatic and lung tissues were collected at 1, 6, 12, and 24 h after the completion of caerulein administration. Tissue leukocyte sequestration was assessed by myeloperoxidase (MPO) activity. Standard histological staining hematoxylin and eosin was performed and blindly scored by a pathologist for evidence of lung injury (pulmonary edema, accumulations of neutrophils and mononuclear cells, thickness of alveolar-capillary membrane, perivascular infiltrate, and hemorrhage). RESULTS: Caerulein-treated wild-type mice exhibited increased lung injury score at 1 through 12 h, as compared to saline controls. As compared to wild-type, STAT6-deficient mice had increased lung injury from 1 to 6 h, with full recovery by 12 h. An opposite pattern was observed in STAT4-deficient mice with mild injury seen at 1 and 6 h, and maximal injury at 12 h. MPO activity was significantly increased at 6 h in caerulein-treated wild-type mice compared to saline-treated controls. Caerulein-treated STAT6 and STAT4 mice had markedly increased MPO activity as compared with their saline controls during the first 6 h. Both caerulein-treated STAT4- and STAT6-deficient mice had significantly increased MPO activity in comparison with wild-type mice with pancreatitis at 6 h. CONCLUSION: We found the maximal lung injury after caerulein-induced pancreatitis occurred at different time-points in STAT4 and STAT6-deficient mice. These temporal differences may suggest alternative roles in the systemic inflammatory response associated with pancreatitis.

Acute Disease↗

Colorectal cancer prevention: adherence patterns and correlates of tests done for screening purposes within United States populations.

BACKGROUND: Studies exploring CRC testing prevalence and correlates within US populations have provided limited and sometimes conflicting information. The most recent national-level reports have described US usage of CRC tests but none have considered only those tests done specifically for screening reasons as an outcome variable. METHODS: Using the NHIS 2000 sample of >or=50 year-old, we assessed screening behavior using an outcome variable accounting for (1) any combination of recommended tests (2) done within their respective time guidelines, and (3) specifically for screening purposes. RESULTS: Only 25.8% (95% CI: 24.9-26.7%) of the population reported getting a test done for screening purposes within the recommended time. Most (>85%) of the FOBTs and only about 60% of endoscopies were done for screening. Among those who had an endoscopy within the recommended time, Blacks were more likely than Whites to report screening as the purpose of the test. Hispanics had the lowest test usage irrespective of test time, reason or type. Hispanics were 50% (p<0.001) less likely to be adherent, and Blacks approximately 22% (p<0.01) less likely to be adherent, than Whites. After multivariate adjustment, differences between Whites and Blacks disappeared; Hispanics remained less likely. Increasing education predicted higher adherence among Whites but only undergraduate completion did so among Blacks. Male gender predicted adherence only among Blacks and insurance only among Hispanics. CONCLUSIONS: Preventive screening for CRC is lower than estimates from previous studies. Future studies should consider accounting for test purpose. Our findings need confirmation through studies based on objective data.

Black or African American↗

Activation of nuclear factor kappa B and severe hepatic necrosis may mediate systemic inflammation in choline-deficient/ethionine-supplemented diet-induced pancreatitis.

OBJECTIVES: We hypothesized that hepatic injury is associated with severe acute pancreatitis (SAP) and may result in lung injury through nuclear factor kappa B (NF-kappaB)-dependent inflammatory mediators. The study characterizes the timing and determines the involvement of selected cytokines and chemokines in the pathogenesis of hepatocellular injury associated with SAP. METHODS: The SAP was induced in C57BL/6 mice by feeding a choline-deficient/ethionine-supplemented diet. The mice were killed at 12-hour intervals for 96 hours. Terminal deoxynucleotidyl transferase-mediated nick-end labeling staining was used to determine the extent of hepatic apoptosis. The NF-kappaB activation in nuclear protein extracts from liver tissue was measured using a sensitive RelA enzyme-linked immunoadsorbent assay. Tumor necrosis factor alpha, interleukin 6, macrophage inflammatory protein (MIP) 2, and keratinocyte-derived chemokine (KC) levels in homogenates of liver and lung tissues were measured by enzyme-linked immunoadsorbent assay. The SAP-associated neutrophil lung inflammation was measured as tissue myeloperoxidase activity. RESULTS: The SAP and subsequent liver injury were confirmed by histological analysis and rises in plasma amylase and transaminase levels. Severe hepatocellular apoptosis was detected at 36 and 48 hours after the diet initiation by terminal deoxynucleotidyl transferase-mediated nick-end labeling staining (P < 0.05) and subsequently progressed to hepatic necrosis. Liver NF-kappaB activation was detected at 36 hours (P < 0.05) and followed by a sharp increase in hepatocellular levels of interleukin 6, MIP-2, and KC at 72 hours and thereafter (P < 0.05). Levels of MIP-2 and KC in lung tissue were also elevated at 72 hours (P < 0.05) and closely correlated with increased myeloperoxidase activity and increased inflammatory cell infiltrate in the lung. CONCLUSIONS: Choline-deficient/ethionine-supplemented diet-induced SAP is accompanied with hepatocellular apoptosis and eventual necrosis. This injury is associated with the hepatic NF-kappaB activation leading to the production of NF-kappaB-dependent cytokines and chemokines in the liver, which may mediate the lung injury.

Animals↗

Do adverse histopathologic findings in colorectal cancer patients explain disparate outcomes?

We have previously reported reduced overall and disease-free survival in black patients from a 10-year retrospective review of 668 patients from tumor registry data. This study of 213 patients reports the analysis of available archived tissue from a city hospital (n=44 patients, 53% black) and from a university medical center (n=169, 10.6% black). Two senior pathologists independently reviewed slides for predetermined histologic criteria reported to correlate with survival: tumor type, stage at diagnosis, character of invasion, vascular or perineural invasion, the presence of residual adenoma, the presence of a Crohn's-like reaction and number of nodes resected. Differences in discrete variables were compared using the Chi-squared test. Differences in continuous variables were analyzed using independent t tests. No statistically significant differences were identified in tumor stage or type by institution or race. In patients treated at the city hospital, there was a higher incidence of infiltrating tumors (85% vs. 61%, p<0.001), vascular invasion (70% vs. 36%, p<0.05) and residual adenoma (84% vs. 39%, p<0.05); however, no differences by race were identified. Blacks at both hospitals had significantly more perineural invasion (81% vs. 30%, p<0.05) and Crohn's-like reaction (64% vs. 30%, p<0.05) when compared to white patients, although there was no difference between hospitals. The total number of lymph nodes resected was higher at the university hospital (17.0 vs. 8.9, p<0.001). There were no differences in number of nodes resected at either institution by race. Histopathologic findings did not explain the apparent disparity in survival. The differences in number of nodes harvested may suggest inadequate resection or insufficient recovery of nodes by the pathologist.

Black People↗

Objective assessment of videoconferenced lectures in a surgical clerkship.

BACKGROUND: A challenge to the practice of third-year clerkship rotations at remote locations is the maintenance of equivalent didactic lectures, especially in subspecialty components. There has been little objective assessment of the results of videoconference lectures on medical student clerkship education. METHODS: Third-year surgical clerkship students, randomly assigned to a 4-week rotation 75 miles from the medical school, received subspecialty lectures by interactive teleconference via an ISDN line at 128 kb/s. Weekly quiz results (% correct) of students who received videoconference lectures were compared with students receiving conventional lectures, and were analyzed by 2-tailed t tests for equality of means. RESULTS: A mean of 12 students were tested per quiz (range, 5-21 students) after videoconference lectures, and 98 students were tested after conventional lectures (range, 41-146 students). The mean quiz score of students receiving video lectures was 70.5% (range, 65.4% to 73.6%); and after conventional lectures the mean quiz score was 71.4% (range, 69.5% to 76.8%). There were no significant differences in the mean scores of the individual quizzes (P = .16-.92) or between the totals (P = .65). CONCLUSIONS: Telemedicine, using interactive videoconferencing, is an effective method for didactic lectures in a surgical clerkship. This technology allows students to receive interactive lectures at distant clinical sites and limit their travel.

Adult↗

Racial/ethnic disparity and predictors of leisure-time physical activity among U.S. men.

OBJECTIVES: To examine racial/ethnic disparity in and predictors of leisure-time physical activity (LTPA) among men. METHODS: We used the National Health Interview Surveys (NHIS) 1999-2000 data, a multistage probability sampling design producing a U.S. representative sample of 23,459 adult males. Data were analyzed using multinomial logistic regression. RESULTS: The likelihood of engaging in irregular or regular LTPA was associated with younger age, being unmarried, lower household sizes, higher levels of education and income, home ownership, U.S. citizenship, perceived better health status, contact with a health professional within a year, being a non-smoker, living in the West, and residing in a midsize metropolitan statistical area. Hispanics were significantly less likely to engage in regular LTPA than Whites and higher percentages of Hispanics were physically inactive in almost all age and education groups when compared to other races. Disparity between Whites and Blacks was less pronounced. Non-citizen Hispanics were twice as likely to be inactive than citizens and White non-citizens were 40% more likely to be inactive than citizens. Conversely, Black citizens were 20% more likely to be inactive than non-citizens. CONCLUSIONS: Racial/ethnic disparities exist after accounting for socio-demographic characteristics. Not being a citizen exacerbates the disparity between Hispanic and White men. While disparity did exist between Black and White men, this gap was not as large as between Hispanic and White men. Health-seeking behaviors, such as contact with a health professional and non-smoking status are modifiable and influence men of all racial and ethnic backgrounds to engage in LTPA.

Adolescent↗

Effect of race on long-term survival of breast cancer patients: transinstitutional analysis from an inner city hospital and university medical center.

Black women have the highest mortality for breast cancer. Our hypothesis is that racial disparities in breast cancer survival persist after controlling for stage of disease and treatment at both a city hospital as well as at a university hospital. Data from tumor registries of breast cancer patients at a city hospital and a university center were analyzed for overall and disease-specific survival, controlling for stage and treatment. Black patients presented with more advanced stages and had significantly worse survival compared with whites. After controlling for stage of disease and treatment, a difference in survival persisted for stage II patients, with blacks doing worse than whites at both institutions. Although there were socioeconomic differences, race was an independent prognostic factor, with black patients having the worse prognosis. The lower survival of black women with breast cancer is only partially explained by their advanced stage at diagnosis. Black women with potentially curable stage II cancer had a lower survival that is not explained by the variables measured.

Academic Medical Centers↗

Pulmonary MnSOD is nitrated following hepatic ischemia-reperfusion.

BACKGROUND: Ischemia-reperfusion (I/R) of remote organs is a common cause of lung injury. We observed that lung injury after partial hepatic I/R in mice coincides with the appearance of 3-nitrotyrosine (NT) in the lung tissue, a marker of peroxynitrite involvement and oxidant stress. Peroxynitrite can cause mitochondrial dysfunction by inactivation of manganese superoxide dismutase (MnSOD), the major antioxidant enzyme in mitochondria. Our aims were to examine whether pulmonary MnSOD is a target of nitration following hepatic I/R and whether nitrated MnSOD (N-MnSOD) correlates with acute lung injury. METHODS: Five 20-25-g male C57BL/6 mice underwent laparotomy, and atraumatic occlusion of the portal and arterial blood supply to the upper three lobes of the liver for 90 min. This warm ischemic period was followed by 4 h of reperfusion, and the animals were then euthanized. Lung injury was assessed by LDH and protein levels in bronchoalveolar lavage (BAL) fluid. Pulmonary MnSOD activity in pulmonary homogenates was measured by the cytochrome c reduction method. The presence of N-MnSOD was determined by immunoprecipitation (IP) and Western Blot analysis. Controls (N = 5) underwent sham operation. RESULTS: Elevated plasma transaminases confirmed hepatic injury. Lung injury was demonstrated by elevation in BAL protein and LDH levels (495.7 (48.4) versus 644.9 (37.3) [p < 0.05] and 56.5 (11.8) versus 345.2 (80) [p < 0.01], respectively). Immunoprecipitation and Western blot demonstrated N-MnSOD in the lung tissue of I/R animals but not controls. MnSOD activity decreased following I/R (8.1 (0.7) versus 10.8 (0.3) [p < 0.05]). CONCLUSIONS: Pulmonary MnSOD is both nitrated and inactivated following hepatic I/R and is associated with acute lung injury. These findings suggest that MnSOD incapacitance may contribute to I/R-induced lung injury and provide a therapeutic target in attenuating multisystem injury following hepatic I/R.

Animals↗

Endotoxin potentiates lung injury in cerulein-induced pancreatitis.

BACKGROUND: In this study we examine the effect of endotoxin (lipopolysaccharide) on lung injury in the setting of acute pancreatitis (AP). METHODS: Twelve hourly injections of cerulein (50 microg/kg/h) were used to induce pancreatitis in mice. Intraperitoneal lipopolysaccharide (LPS [6 mg/kg]) was administered 24 hours after the initial cerulein injection. Twenty-four hours after LPS injection, myeloperoxidase (MPO) activity, nuclear factor (NF)-kappaB activation, and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and chemokines MIP-2 and KC levels were measured in pancreas, liver, and lung tissues. Four groups of mice were studied: cerulein-LPS, cerulein-saline, saline-LPS, and saline-saline treated mice. RESULTS: Elevated serum lipase confirmed pancreatitis in cerulein treated mice. Lung MPO activity was significantly increased in the cerulein-LPS group. NF-kappaB was activated in the liver but not in pancreas and lung tissue. Chemokines MIP-2 and KC were elevated in pancreatic tissue only. CONCLUSIONS: These findings suggest that gram-negative infections may be an important predisposition for the development of adult respiratory distress syndrome in the setting of AP and that hepatic NF-kappaB may mediate multisystem injury.

Animals↗

Systemic nf-kappaB activation in a transgenic mouse model of acute pancreatitis.

BACKGROUND: Transcription factor NF-kappaB has been implicated in numerous human inflammatory diseases. Acute pancreatitis can result in remote tissue injury, but the involved mechanisms are unknown. This study evaluates the role of systemic NF-kappaB activation in the pathogenesis of lung inflammation in a transgenic pancreatitis model. MATERIALS AND METHODS: Using transgenic mice expressing photinus luciferase controlled by an NF-kappaB-dependent promoter, luciferase activity was measured in pancreas, liver, and lung tissues as a surrogate marker of NF-kappaB activity. Luciferase activity was measured by in vivo bioluminescence and correlated to an in vitro luciferase assay of organ homogenates. Following measurement of luciferase activity in uninjured animals, these animals were fed a choline-deficient, ethionine supplemented diet for 48 h to induce pancreatitis, and luciferase activity was then measured at 48, 60, 72, and 96 h. Lung inflammation was determined by total nucleated cell counts in bronchoalveolar lavage (BAL) fluid. RESULTS: Bioluminescence detected increased luciferase activity over the upper abdominal region at 48 and 60 h (P < 0.05), and over the thorax at 60 and 72 h (P < 0.05). Luciferase assays showed significantly increased luciferase activity in both liver and lung tissue at 48 (liver = P < 0.005, lung = P < 0.05) and 60 h (liver = P < 0.05, lung = P < 0.05) compared to activity in uninjured controls. Total nucleated cell counts in BAL fluid were significantly increased at 72 h (P < 0.05) compared with controls. CONCLUSION: In this model, NF-kappaB binding activity is increased in the liver and lung. These data suggest that the liver modulates pancreatitis-induced systemic inflammatory response syndrome (SIRS) and suggest strategies to reduce multisystem injury.

Acute Disease↗

Disparate outcomes in patients with colorectal cancer: effect of race on long-term survival.

BACKGROUND: Increasing evidence suggests significant disparity in colorectal cancer outcomes between black and white patients. Contributing factors may include advanced tumor stage at diagnosis, differences in treatment, more aggressive tumor biology, access to care, and patient comorbidity. HYPOTHESIS: Disparities in colorectal cancer outcomes exist despite similar objective measures of treatment. DESIGN AND SETTING: Ten-year retrospective review of all patients with colorectal cancer using tumor registries at a city hospital (n = 83) and a university medical center (n = 585) in the same city. We assessed stage at diagnosis; curative surgical resection; use of adjuvant treatment; overall, disease-free, and stage-specific survival; and socioeconomic status. Patients with nonwhite, nonblack ethnicity (4% overall) were excluded. Differences in stage and treatments were compared using the chi(2) test, and median survival rates were compared using log-rank tests. RESULTS: Significantly more black patients were treated at the city hospital (53.0%) vs the university medical center (10.6%) (P<.001). No differences were identified in stage distribution or treatments received between hospitals or between black and white patients. Significantly worse survival was noted among patients treated at the city hospital (2.1 vs 5.3 years; P<.001) and among black patients treated at both institutions (city hospital: 1.4 vs 2.1 years, and university hospital: 3.2 vs 5.7 years; P<.001 for both). Disease-free survival rates showed similar significant reductions for black patients at both institutions. There was no association between survival and socioeconomic status at either institution. CONCLUSION: The marked reductions in overall and disease-free survival for black patients with colorectal cancer do not seem to be related to variation in treatment but may be due to biologic factors or non-cancer-related health conditions.

Black or African American↗

Diagnosis and management of laryngotracheal trauma.

Laryngotracheal trauma is life-threatening. We identified 23 patients between 1992 and 1998 with laryngeal (12), tracheal (8), and combined injuries (3). Nineteen patients had penetrating trauma (gunshot wound, 12; stab wound, 7), and four patients had blunt injury. Flexible laryngoscopy identified the injury in 8 of 12 patients (75%), and computer tomography scan was positive in 9 of 9 patients (100%). Twelve of the 19 patients with penetrating wounds were managed by primary repair, 4 had endotracheal intubation without surgical repair, and 3 were observed. No patient with a blunt tracheal injury required repair. Two had endotracheal intubation, and two were observed. A high index of suspicion is essential to identifying laryngotracheal injury. Computer tomography scan is a sensitive diagnostic test for laryngotracheal injury, and may be indicated despite normal flexible laryngoscopy. The decision to repair injuries or observe injuries is primarily based on respiratory distress and associated injuries.

Adolescent↗

Electrosurgery.

Explore the source record for details and available documents.

Electrosurgery↗