Effect of indomethacin on bile acid-phospholipid interactions: implication for small intestinal injury induced by nonsteroidal anti-inflammatory drugs.

The injurious effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the small intestine was not appreciated until the widespread use of capsule endoscopy. Animal studies found that NSAID-induced small intestinal injury depends on the ability of these drugs to be secreted into the bile. Because the individual toxicity of amphiphilic bile acids and NSAIDs directly correlates with their interactions with phospholipid membranes, we propose that the presence of both NSAIDs and bile acids alters their individual physicochemical properties and enhances the disruptive effect on cell membranes and overall cytotoxicity. We utilized in vitro gastric AGS and intestinal IEC-6 cells and found that combinations of bile acid, deoxycholic acid (DC), taurodeoxycholic acid, glycodeoxycholic acid, and the NSAID indomethacin (Indo) significantly increased cell plasma membrane permeability and became more cytotoxic than these agents alone. We confirmed this finding by measuring liposome permeability and intramembrane packing in synthetic model membranes exposed to DC, Indo, or combinations of both agents. By measuring physicochemical parameters, such as fluorescence resonance energy transfer and membrane surface charge, we found that Indo associated with phosphatidylcholine and promoted the molecular aggregation of DC and potential formation of larger and isolated bile acid complexes within either biomembranes or bile acid-lipid mixed micelles, which leads to membrane disruption. In this study, we demonstrated increased cytotoxicity of combinations of bile acid and NSAID and provided a molecular mechanism for the observed toxicity. This mechanism potentially contributes to the NSAID-induced injury in the small bowel.

Colorectal cancer screening: Racial/ethnic and gender disparities in a population-based cross-sectional analysis of the United States

Gender and racial/ethnic disparities in colorectal cancer screening (CRC) has been observed and associated with income status, education level, treatment and late diagnosis. According to the American Cancer Society, among both males and females, CRC is the third most frequently diagnosed type of cancer and accounts for 10% of cancer deaths in the United States. Differences in CRC test use have been documented and limited to access to health care, demographics and health behaviors, but few studies have examined the correlates of CRC screening test use by gender. This present study examined the prevalence of CRC screening test use and assessed whether disparities are explained by gender and racial/ethnic differences. To assess these associations, the study utilized a cross-sectional design and examined the distribution of the covariates for gender and racial/ethnic group differences using the chi square statistic. Logistic regression was used to estimate the prevalence odds ratio and to adjust for the confounding effects of the covariates. ^ Results indicated there are disparities in the use of CRC screening test use and there were statistically significant difference in the prevalence for both FOBT and endoscopy screening between gender, χ2, p≤0.003. Females had a lower prevalence of endoscopy colorectal cancer screening than males when adjusting for age and education (OR 0.88, 95% CI 0.82–0.95). However, no statistically significant difference was reported between racial/ethnic groups, χ 2 p≤0.179 after adjusting for age, education and gender. For both FOBT and endoscopy screening Non-Hispanic Blacks and Hispanics had a lower prevalence of screening compared with Non-Hispanic Whites. In the multivariable regression model, the gender disparities could largely be explained by age, income status, education level, and marital status. Overall, individuals between the age "70–79" years old, were married, with some college education and income greater than $20,000 were associated with a higher prevalence of colorectal cancer screening test use within gender and racial/ethnic groups. ^

The association of area socioeconomic status and cancer screening: A systematic review and multilevel study

Background. The gap between actual and ideal rates of routine cancer screening in the U.S., particularly for colorectal cancer screening (CRCS) (1;2), is responsible for an unnecessary burden of morbidity and mortality, particularly for disadvantaged groups. Knowledge about the effects of individual and area influences is being advanced by a growing body of research that has examined the association of area socioeconomic status (SES) and cancer screening after controlling for individual SES. The findings from this emerging and heterogeneous research in the cancer screening literature have been mixed. Moreover, multilevel studies in this area have not yet adequately explored the possibility of differential associations by population subgroup, despite some evidence suggesting gender-specific effects. ^ Objectives and methods. This dissertation reports on a systematic review of studies on the association of area SES and cancer screening and a multilevel study of the association between area SES and CRCS. The specific aims of the systematic review are to: (1) describe the study designs, constructs, methods, and measures; (2) describe the association of area SES and cancer screening; and (3) identify neglected areas of research. ^ The empiric study linked a pooled sample of respondents aged ≥50 years without a personal history of colorectal cancer from the 2003 and 2005 California Health Interview Surveys with a comprehensive set of census-tract level area SES measures from the 2000 U.S. Census. Two-level random intercept models were used to test 2 hypotheses: (1) area SES will be associated with adherence to two modalities of CRCS after controlling for individual SES; and (2) gender will moderate the relationship between area socioeconomic status and adherence to both modalities of CRCS. ^ Results. The systematic review identified 19 eligible studies that demonstrated variability in study designs, methods, constructs, and measures. The majority of tested associations were either not statistically significant or significant and in the positive direction, indicating that as area SES increased, the odds of CRCS increased. The multilevel study demonstrated that while multiple aspects of area SES were associated with CRCS after controlling for individual SES, associations differed by screening modality and in the case of endoscopy, they also differed by gender. ^ Conclusions. Conceptual and methodologic heterogeneity and weaknesses in the literature to date limit definitive conclusions about the underlying relationships between area SES and cancer screening. The multilevel study provided partial support for both hypotheses. Future research should continue to explore the role of gender as a moderating influence with the aim of identifying the mechanisms linking area SES and cancer prevention behaviors. ^

Prevalence and determinants of colonic polyps in children undergoing colonoscopy: A large hospital-based cross-sectional study

Background. Colorectal polyps are abnormal growths in the wall of the colon including the rectum. The study aims to estimate the prevalence and type of colonic polyps in children undergoing colonoscopic examination at Texas Children's Hospital (TCH) in Houston, Texas during 2000-2007. Also, to examine the factors associated with colonic polyps and the potential determinants of colonic polyps in children undergoing colonoscopy and compare those who had colonic polyps with those who did not on colonoscopy, and determine the significant risk factors of colonic polyps in these children. ^ Methods. We conducted a cross sectional study to analyze data collected at TCH. We obtained demographic, clinical, and histopathology information on consecutive patients who underwent colonoscopy during 2000-2007 from endoscopic records contained in the PEDS-CORI registry (Pediatric Endoscopy Database System-Clinical Outcomes Research Initiative), and abstracted data from the accompanying histopathology reports. ^ Results. We identified 2,693-unique patients, under 18 years of age, who underwent colonoscopy. Approximately 65.5% were white non-Hispanic, and 10.8% African-American. The mean age was 8.7 years and 51.8% were female patients. Polyps were present in 174 patients (6.5%). The most common two histological types were juvenile (60.6%), inflammatory (17.4%). We found that the prevalence of polyps was higher in younger aged children (12.9% in 0-5 years) than in older aged children (4% in 15-17 years), and slightly higher in males than in females (7.9% and 5.4% respectively). For males only, the odds of polyps were statistically significantly higher in Blacks and Hispanics compared to white non Hispanics (OR of 2.2 and 2.1, respectively, and 95% CI of 1.3, 3.9 and 1.3, 3.5 respectively). The indications for colonoscopy were different for children with polyps compared to those without polyps, i.e., 47.0% vs. 19.8% respectively for lower GI bleeding, 2.7% vs. 21.4% respectively for abdominal pain/bloating, and, or 0.9% vs. 9.6% respectively for diarrhea. ^ Conclusion. Colorectal polyps occur in about 1 in 15 children and adolescents undergoing first colonoscopy. The demographic variable of younger age is strongly associated with having polyps irrespective of ethnicity. Lower GI bleeding is strongly related to the presence of colorectal polyps in children and adolescents undergoing colonoscopy.^

Prevalence of gastro esophageal reflux disease following the Montreal Consensus and its association with Helicobacter pylori infection and obesity in a random sample of adults of Ciudad Juarez, Mexico, 2004.

Gastroesophageal reflux disease is a common condition affecting 25 to 40% of the population and causes significant morbidity in the U.S., accounting for at least 9 million office visits to physicians with estimated annual costs of $10 billion. Previous research has not clearly established whether infection with Helicobacter pylori, a known cause of peptic ulcer, atrophic gastritis and non cardia adenocarcinoma of the stomach, is associated with gastroesophageal reflux disease. This study is a secondary analysis of data collected in a cross-sectional study of a random sample of adult residents of Ciudad Juarez, Mexico, that was conducted in 2004 (Prevalence and Determinants of Chronic Atrophic Gastritis Study or CAG study, Dr. Victor M. Cardenas, Principal Investigator). In this study, the presence of gastroesophageal reflux disease was based on responses to the previously validated Spanish Language Dyspepsia Questionnaire. Responses to this questionnaire indicating the presence of gastroesophageal reflux symptoms and disease were compared with the presence of H. pylori infection as measured by culture, histology and rapid urease test, and with findings of upper endoscopy (i.e., hiatus hernia and erosive and atrophic esophagitis). The prevalence ratio was calculated using bivariate, stratified and multivariate negative binomial logistic regression analyses in order to assess the relation between active H. pylori infection and the prevalence of gastroesophageal reflux typical syndrome and disease, while controlling for known risk factors of gastroesophageal reflux disease such as obesity. In a random sample of 174 adults 48 (27.6%) of the study participants had typical reflux syndrome and only 5% (or 9/174) had gastroesophageal reflux disease per se according to the Montreal consensus, which defines reflux syndromes and disease based on whether the symptoms are perceived as troublesome by the subject. There was no association between H. pylori infection and typical reflux syndrome or gastroesophageal reflux disease. However, we found that in this Northern Mexican population, there was a moderate association (Prevalence Ratio=2.5; 95% CI=1.3, 4.7) between obesity (≥30 kg/m2) and typical reflux syndrome. Management and prevention of obesity will significantly curb the growing numbers of persons affected by gastroesophageal reflux symptoms and disease in Northern Mexico. ^