Plasma riboflavin fluorescence as a diagnostic marker of mesenteric ischemia-reperfusion injury in rats.

Due to the delayed and vague symptoms, it is difficult to early diagnose mesenteric ischemia injuries in the dynamics of acute illness, leading to a 60-80 % mortality rate. Here, we found plasma fluorescence spectra can rapidly assess the severity of mesenteric ischemia injury in animal models. Ischemia-reperfusion damage of the intestine leads to multiple times increase in NADH, flavins, and porphyrin auto-fluorescence of blood. The fluorescence intensity ratio between blue-fluorophores and flavins can reflect the occurrence of shock. Using liquid chromatography and mass spectroscopy, we confirm that riboflavin is primarily responsible for the increased flavin fluorescence. Since humans absorb riboflavin from the intestine, its increase in plasma may indicate intestinal mucosa injury. Our work suggests a self-calibrated and reagent-free approach to identifying the emergence of fatal mesenteric ischemia in emergency departments or intensive care units.

Color vision deficiency in preschool children: the multi-ethnic pediatric eye disease study.

PURPOSE: To determine the sex- and ethnicity-specific prevalence of color vision deficiency (CVD) in black, Asian, Hispanic, and non-Hispanic white preschool children. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: The Multi-Ethnic Pediatric Eye Disease Study is a population-based evaluation of the prevalence of vision disorders in children in Southern California. A total of 5960 subjects 30 to 72 months of age were recruited for the study, of whom 4177 were able to complete color vision testing (1265 black, 812 Asian, 1280 Hispanic, and 820 non-Hispanic white). METHODS: Color vision testing was performed using Color Vision Testing Made Easy color plates (Home Vision Care, Gulf Breeze, FL), and diagnostic confirmatory testing was performed using the Waggoner HRR Diagnostic Test color plates (Home Vision Care). MAIN OUTCOME MEASURES: Testability of color vision in preschool children between 30 and 72 months of age and prevalence of CVD stratified by age, sex, and ethnicity. RESULTS: Testability was 17% in children younger than 37 months of age, increasing to 57% in children 37 to 48 months of age, 89% in children 49 to 60 months of age, and 98% in children 61 to 72 months of age. The prevalence of CVD among boys was 1.4% for black, 3.1% for Asian, 2.6% for Hispanic, and 5.6% for non-Hispanic white children; the prevalence in girls was 0.0% to 0.5% for all ethnicities. The ethnic difference in CVD was statistically significant between black and non-Hispanic white children (P = 0.0003) and between Hispanic and non-Hispanic white children (P = 0.02). In boys, most CVD cases were either deutan (51%) or protan (34%); 32% were classified as mild, 15% as moderate, and 41% as severe. CONCLUSIONS: Testability for CVD in preschool children is high by 4 years of age. The prevalence of CVD in preschool boys varies by ethnicity, with the highest prevalence in non-Hispanic white and lowest in black children.

Is continuation of antiplatelets until coronary artery bypass safe in Asians?

BACKGROUND: Controversies have arisen about the risks of discontinuing antiplatelets prior to coronary artery bypass grafting. METHODS: We retrospectively studied the effects of different strategies of antiplatelet discontinuation prior to coronary artery bypass on perioperative bleeding and major adverse cardiovascular events in Asian patients in a single center in Singapore. RESULTS: 402 patients were divided into 4 groups: group A had no antiplatelets before surgery; antiplatelets were stopped for 5-7 days in group B; 2-4 days in group C; and 0-1 day in group D. Compared to group B, group D had longer intensive care unit stays and more intraoperative transfusions of blood (p = 0.006) and blood products (p < 0.05). The 1-year major adverse cardiovascular event rate was higher in groups A and D (p = 0.027). Stopping antiplatelets within 24 h of surgery was one of multiple independent predictors of intraoperative transfusion but not the 1-year major adverse cardiovascular event rate. Patients on aspirin alone had less intraoperative transfusion of platelets and postoperative minor bleeding than those on combined therapy. CONCLUSION: Continuation of antiplatelets until 2 days before coronary artery bypass in Asian patients in our institution is unlikely to increase the risks of bleeding and perioperative transfusion. Taking antiplatelets within 24 h of surgery seems to be associated with a higher rate of 1-year major adverse cardiovascular events and bleeding, and an increased risk of blood product transfusion. Thirty-day and 1-year major adverse cardiovascular event rates were higher in patients without antiplatelet treatment.

Determining lower limits of detection of digital PCR assays for cancer-related gene mutations.

Digital PCR offers very high sensitivity compared to many other technologies for processing molecular detection assays. Herein, a process is outlined for determining the lower limit of detection (LoD) of two droplet-based digital PCR assays for point mutations of the epidermal growth factor receptor (EGFR) gene. Hydrolysis probe mutation-detection assays for EGFR p.L858R and p.T790M mutations were characterized in detail. Furthermore, sixteen additional cancer-related mutation assays were explored by the same approach. For the EGFR L8585R assay, the assay sensitivity is extremely good, and thus, the LoD is limited by the amount of amplifiable DNA that is analyzed. With 95% confidence limits, the LoD is one mutant in 180,000 wild-type molecules for the evaluation of 3.3 µg of genomic DNA, and detection of one mutant molecule in over 4 million wild-type molecules was achieved when 70 million copies of DNA were processed. The measured false-positive rate for the EGFR L8585R assay is one in 14 million, which indicates the theoretical LoD if an unlimited amount of DNA is evaluated. For the EFGR T790M assay, the LoD is one mutant in 13,000 for analysis of a 3.3 µg sample of genomic DNA, and the dPCR assay limit sensitivity approaches one mutant in 22,000 wild-type molecules.

Prevalence of myopia, hyperopia, and astigmatism in non-Hispanic white and Asian children: multi-ethnic pediatric eye disease study.

PURPOSE: To determine the age-, gender-, and ethnicity-specific prevalence of myopia, hyperopia, and astigmatism in non-Hispanic white (NHW) and Asian preschool children. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A population-based sample of 1501 NHW children and 1507 Asian children aged 6-72 months from Los Angeles County and Riverside County, California. METHODS: Eligible children underwent an in-home and in-clinic interview and a comprehensive eye examination including cycloplegic autorefraction from 100 census tracts. MAIN OUTCOME MEASURES: The proportion of children with myopia (spherical equivalent [SE] ≤-1.00 diopter [D]), hyperopia (SE ≥ +2.00 D) and cylindrical refractive error ≥1.50 D in the worse eye. The astigmatism type was defined as with-the-rule (WTR; +cylinder axis 90°±15°) and against-the-rule (ATR; + cylinder axis 180°±15°); all other orientations were considered oblique (OBL). RESULTS: The prevalence of myopia, hyperopia, and astigmatism in NHW children was 1.20% (95% confidence interval [CI], 0.76%-1.89%), 25.65% (95% CI, 23.5%-27.9%), and 6.33% (95% CI, 5.21%-7.68%), respectively. The prevalence of WTR, ATR, and OBL astigmatism in NHW children was 4.33%, 1.00%, and 1.00%, respectively. Prevalence was lower with older age groups for astigmatism (P = 0.0002), but not for myopia (P = 0.82) or hyperopia (P = 0.31). In Asian children, the prevalence of myopia, hyperopia, and astigmatism was 3.98% (95% CI, 3.11%-5.09%), 13.47% (95% CI, 11.8%-15.3%), and 8.29% (95% CI, 7.01%-9.80%), respectively. The prevalence of WTR, ATR, and OBL astigmatism was 6.50%, 0.80%, and 1.00% respectively. The prevalence of hyperopia was higher in girls than boys (P = 0.0002), but no differences were found for myopia and astigmatism. CONCLUSIONS: Hyperopia was the most common refractive error in both Asian and NHW children. However, compared with NHW children, myopia was relatively more prevalent, and hyperopia less prevalent, among Asian children. The prevalence of astigmatism was greatest in infants, and WTR astigmatism predominated at all ages. Myopia showed relatively stable prevalence across age groups, whereas hyperopia prevalence decreased after infancy and then increased again in older age groups; however, longitudinal studies are needed to evaluate refractive changes over time in individual children. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Quality assurance and training procedures for computer-aided detection and diagnosis systems in clinical use.

Computer-aided detection/diagnosis (CAD) is increasingly used for decision support by clinicians for detection and interpretation of diseases. However, there are no quality assurance (QA) requirements for CAD in clinical use at present. QA of CAD is important so that end users can be made aware of changes in CAD performance both due to intentional or unintentional causes. In addition, end-user training is critical to prevent improper use of CAD, which could potentially result in lower overall clinical performance. Research on QA of CAD and user training are limited to date. The purpose of this paper is to bring attention to these issues, inform the readers of the opinions of the members of the American Association of Physicists in Medicine (AAPM) CAD subcommittee, and thus stimulate further discussion in the CAD community on these topics. The recommendations in this paper are intended to be work items for AAPM task groups that will be formed to address QA and user training issues on CAD in the future. The work items may serve as a framework for the discussion and eventual design of detailed QA and training procedures for physicists and users of CAD. Some of the recommendations are considered by the subcommittee to be reasonably easy and practical and can be implemented immediately by the end users; others are considered to be "best practice" approaches, which may require significant effort, additional tools, and proper training to implement. The eventual standardization of the requirements of QA procedures for CAD will have to be determined through consensus from members of the CAD community, and user training may require support of professional societies. It is expected that high-quality CAD and proper use of CAD could allow these systems to achieve their true potential, thus benefiting both the patients and the clinicians, and may bring about more widespread clinical use of CAD for many other diseases and applications. It is hoped that the awareness of the need for appropriate CAD QA and user training will stimulate new ideas and approaches for implementing such procedures efficiently and effectively as well as funding opportunities to fulfill such critical efforts.

Prevalence and causes of visual impairment in Asian and non-Hispanic white preschool children: Multi-ethnic Pediatric Eye Disease Study.

PURPOSE: To determine the prevalence and causes of decreased visual acuity (VA). DESIGN: Population-based cross-sectional study. PARTICIPANTS: Multi-ethnic sample of children 30 to 72 months of age identified in Los Angeles. METHODS: All eligible children underwent a comprehensive ophthalmic evaluation including monocular VA testing, cover testing, cycloplegic autorefraction, fundus evaluation, and VA retesting with refractive correction. Decreased VA was defined as presenting or best-measured VA worse than 20/50 in children 30 to 47 months of age and worse than 20/40 for children 48 months of age and older. The prevalence and causes of decreased VA were determined, for both presenting and best-measured VA, in the better-seeing and the worse-seeing eyes. MAIN OUTCOME MEASURES: Prevalence and causes of decreased vision. RESULTS: Presenting VA was assessed in 1840 children and best-measured VA was assessed in 1886 children. Presenting VA was decreased in the worse eye of 4.2% of Asian children and of 3.6% of non-Hispanic white (NHW) children. Close to one-fourth of these cases had no identifiable cause, and 81% of these resolved on retesting. Decreased presenting VA in the worse eye with an identifiable ophthalmic cause was present in 3.4% of Asian children and in 2.6% of NHW children. Decreased presenting VA attributable to simple refractive error (myopia ≥ 0.5 diopters [D]; hyperopia ≥ 3.0 D; astigmatism ≥ 2.0 D or ≥ 1.5 D for children older than 36 months) was present in the worse eye of 2.3% of Asian children and of 1.4% of NHW children and in the better eye of 0.5% of Asian children and of 0.3% of NHW children. Decreased best-measured VA attributable to a cause was present in the worse eye of 1.2% of both Asian children and NHW children and in the better eye of 0.2% of Asian and of 0.3% of NHW children. Amblyopia related to refractive error was the most common cause, and was 10 times as common as ocular disease. Severe visual impairment was rare. CONCLUSIONS: Seventy percent of all decreased VA in Asian and NHW preschool children and more than 90% of decreased VA with an identifiable cause is related to refractive error--either uncorrected refractive error or amblyopia resulting from refractive error. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Aspirin protects against Barrett's esophagus in a multivariate logistic regression analysis.

BACKGROUND & AIMS: Better criteria are needed to identify patients who should be screened for Barrett's esophagus (BE) to reduce overtesting and improve the cost effectiveness. There is evidence that chemopreventive agents such as nonsteroidal anti-inflammatory drugs, particularly aspirin, reduce the risk of esophageal adenocarcinoma (EAC), but little is known about their effects on BE. We analyzed characteristics of patients with BE for factors that might be used in screening and management. METHODS: In this case-controlled study, we identified 434 patients with BE diagnosed at the first endoscopy (incident cases) at a single institution (1997-2010). BE cases were matched with controls on the basis of indication for endoscopy, year of endoscopy, and endoscopist. Risk factors analyzed included age, sex, body mass index, medical and social history, and medications. We performed a multivariate logistic regression analysis to identify clinical risk factors for BE. RESULTS: In a multivariate regression model, men had a greater risk for developing BE (odds ratio, 3.2; 95% confidence interval, 2.3-4.4), whereas current aspirin users had a lower risk than nonusers (odds ratio, 0.56; 95% confidence interval, 0.39-0.80). A subset analysis, limited to patients who had endoscopies for symptoms of gastroesophageal reflux disease, yielded similar findings. No interactions were found between aspirin use and smoking or use of acid-suppressive medications. CONCLUSIONS: In a case-controlled study of 434 patients with BE, current aspirin use appeared to reduce the risk of BE; previous studies associated aspirin use with a reduced risk of EAC. Although efforts were made to minimize biases in our analysis, the possibility of residual confounding remains.

Risk factors for astigmatism in preschool children: the multi-ethnic pediatric eye disease and Baltimore pediatric eye disease studies.

OBJECTIVE: To evaluate risk factors for astigmatism in a population-based sample of preschool children. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Population-based samples of 9970 children ages 6 to 72 months from Los Angeles County, California, and Baltimore, Maryland. METHODS: A cross-sectional study of children participating in the Multiethnic Pediatric Eye Disease Study and the Baltimore Eye Disease Study was completed. Data were obtained by clinical examination or by in-person interview. Odds ratios and 95% confidence intervals (CI) were calculated to evaluate potential associations between clinical, behavioral, or demographic factors and astigmatism. MAIN OUTCOME MEASURES: Odds ratios (ORs) for various risk factors associated with astigmatism. RESULTS: Participants with myopia (≤-1.0 diopters) were 4.6 times as likely to have astigmatism (95% CI, 3.56-5.96) than those without refractive error, whereas participants with hyperopia (≥+2.00 diopters) were 1.6 times as likely (95% CI, 1.39-1.94). Children 6 to <12 months of age were approximately 3 times as likely to have astigmatism than children 5 to 6 years of age (95% CI, 2.28-3.73). Both Hispanic (OR, 2.38) and African-American (OR, 1.47) children were as likely to have astigmatism than non-Hispanic white children. Furthermore, children whose mothers smoked during pregnancy were 1.46 times (95% CI, 1.14-1.87) as likely to have astigmatism than children whose mothers did not smoke. CONCLUSIONS: In addition to infancy, Hispanic and African-American race/ethnicity and correctable/modifiable risk factors such as myopia, hyperopia, and maternal smoking during pregnancy are associated with a higher risk of having astigmatism. Although the prevalence of smoking during pregnancy is typically low, this association may suggest etiologic pathways for future investigation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Risk factors associated with childhood strabismus: the multi-ethnic pediatric eye disease and Baltimore pediatric eye disease studies.

OBJECTIVE: To investigate risk factors associated with esotropia or exotropia in infants and young children. DESIGN: Population-based cross-sectional prevalence study. PARTICIPANTS: Population-based samples of 9970 children 6 to 72 months of age from California and Maryland. METHODS: Participants were preschool African-American, Hispanic, and non-Hispanic white children participating in the Multi-Ethnic Pediatric Eye Disease Study and the Baltimore Eye Disease Study. Data were obtained by parental interview and ocular examination. Odd ratios and 95% confidence intervals were calculated to evaluate the association of demographic, behavioral, and clinical risk factors with esotropia and exotropia. MAIN OUTCOME MEASURES: Odds ratios (ORs) for various risk factors associated with esotropia or exotropia diagnosis based on cover testing. RESULTS: In multivariate logistic regression analysis, esotropia was associated independently with prematurity, maternal smoking during pregnancy, older preschool age (48-72 months), anisometropia, and hyperopia. There was a severity-dependent association of hyperopia with the prevalence of esotropia, with ORs increasing from 6.4 for 2.00 diopters (D) to less than 3.00 D of hyperopia, to 122.0 for 5.00 D or more of hyperopia. Exotropia was associated with prematurity, maternal smoking during pregnancy, family history of strabismus, female sex, astigmatism (OR, 2.5 for 1.50 to <2.50 D of astigmatism, and 5.9 for ≥2.5 D of astigmatism), and anisoastigmatism in the J0 component (OR, ≥2 for J0 anisoastigmatism of ≥0.25 D). CONCLUSIONS: Prematurity and maternal smoking during pregnancy are associated with a higher risk of having esotropia and exotropia. Refractive error is associated in a severity-dependent manner to the prevalence of esotropia and exotropia. Because refractive error is correctable, these risk associations should be considered when developing guidelines for the screening and management of refractive error in infants and young children. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Risk factors for decreased visual acuity in preschool children: the multi-ethnic pediatric eye disease and Baltimore pediatric eye disease studies.

OBJECTIVE: To investigate risk factors associated with unilateral or bilateral decreased visual acuity (VA) in preschool children. DESIGN: Population-based, cross-sectional prevalence study. PARTICIPANTS: Population-based samples of 6504 children ages 30 to 72 months from California and Maryland. METHODS: Participants were preschool African-American, Hispanic, and non-Hispanic white children from Los Angeles, California, and Baltimore, Maryland. Data were obtained by a parental interview and a detailed ocular examination. Logistic regression models were used to evaluate the independent associations between demographic, behavioral, and clinical risk factors with unilateral and bilateral decreased VA. MAIN OUTCOME MEASURES: Odds ratios (ORs) for various risk factors associated with interocular difference (IOD) in VA of ≥2 lines with ≤20/32 in the worse eye, or bilateral decreased VA <20/40 or <20/50 if <48 months of age. RESULTS: In multivariate logistic regression analysis, 2-line IOD with a VA of ≤20/32 was independently associated with Hispanic ethnicity (OR, 2.05), esotropia (OR, 8.98), spherical equivalent (SE) anisometropia (ORs ranging between 1.5 and 39.7 for SE anisometropia ranging between 0.50 to <1.00 diopters [D] and ≥2.00 D), and aniso-astigmatism in J0 or J45 (ORs ranging between 1.4 and ≥5.3 for J0 or J45 differences ranging between 0.25 to <0.50 D and ≥1.00 D). Bilateral decreased VA was independently associated with lack of health insurance (OR, 2.9), lower primary caregiver education (OR, 1.7), astigmatism (OR, 2.3 and 17.6 for astigmatism 1.00 to <2.00 D and ≥2.00 D), and SE hyperopia ≥4.00 D (OR, 10.8). CONCLUSIONS: Anisometropia and esotropia are risk factors for IOD in VA. Astigmatism and high hyperopia are risk factors for bilateral decreased VA. Guidelines for the screening and management of decreased VA in preschool children should be considered in light of these risk associations. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Risk factors for hyperopia and myopia in preschool children the multi-ethnic pediatric eye disease and Baltimore pediatric eye disease studies.

PURPOSE: To describe the risk factors associated with hyperopia and myopia among children 6 to 72 months of age. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Population-based samples of 9970 children 6 to 72 months of age from Los Angeles County, California, and Baltimore, Maryland. METHODS: Participants were preschool African-American, Hispanic, and non-Hispanic white children (n = 9770) from Los Angeles, California, and Baltimore, Maryland. Parental questionnaires and a comprehensive eye examination were administered. Demographic, behavioral, and clinical risk factors associated with hyperopia (≥2.00 diopters [D]) and myopia (≤-1.00 D) were determined. MAIN OUTCOME MEASURES: Odds ratios (ORs) for risk factors associated with myopia and hyperopia. RESULTS: Compared with non-Hispanic whites, African-American (OR, 6.0) and Hispanic (OR, 3.2) children were more likely to be myopic. Children 6 to 35 months of age were more likely to be myopic compared with those 60 to 72 months of age (OR, ≥1.7). Compared with African-American children, non-Hispanic white (OR, 1.63) and Hispanic (OR, 1.49) children were more likely to be hyperopic. Children whose parents had health insurance (OR, 1.5) and those with a history of maternal smoking during pregnancy (OR, 1.4) were more likely to have hyperopia. Astigmatism of 1.5 D or more at any axis was associated with myopia (OR, 4.37) and hyperopia (OR, 1.43). CONCLUSIONS: Children in specific racial or ethnic groups and age groups are at higher risk of having myopia and hyperopia. Cessation of maternal smoking during pregnancy may reduce the risk of hyperopia in these children. Given that both myopia and hyperopia are risk factors for the development of amblyopia and strabismus, these risk factors should be considered when developing guidelines for screening and intervention in preschool children. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prevalence of astigmatism in 6- to 72-month-old African American and Hispanic children: the Multi-ethnic Pediatric Eye Disease Study.

PURPOSE: To determine the age-, gender-, and ethnicity-specific prevalence of astigmatism in African American and Hispanic children aged 6 to 72 months. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: The Multi-Ethnic Pediatric Eye Disease Study is a population-based evaluation of the prevalence of vision disorders in children ages 6 to 72 months in Los Angeles County, California. Seventy-seven percent of eligible children completed a comprehensive eye examination. This report provides the results from 2994 African American and 3030 Hispanic children. METHODS: Eligible children in 44 census tracts were identified during an in-home interview and scheduled for a comprehensive eye examination and in-clinic interview. Cycloplegic autorefraction was used to determine refractive error. MAIN OUTCOME MEASURES: The proportion of children with astigmatism defined as cylindrical refractive error ≥ 1.50 diopters (D) in the worse eye. The astigmatism type was defined as with-the-rule (WTR) (+ cylinder axis 90 ± 15 degrees) and against-the-rule (ATR) (+ cylinder axis 180 ± 15 degrees); all other orientations were considered oblique (OBL). The prevalence of astigmatism and its types were also determined for worse eye cylindrical refractive error ≥ 3.00 D. RESULTS: Prevalence of astigmatism ≥ 1.50 D was higher in Hispanic children compared with African American children (16.8% vs. 12.7%, respectively; P<0.0001). Hispanic children also showed a higher prevalence of astigmatism ≥ 3.00 D than African American children (2.9% vs. 1.0% respectively; P<0.0001). The prevalence of astigmatism ≥ 1.50 D showed a significant decreasing trend with age (P<0.0001). The prevalence of WTR, ATR, and OBL astigmatism ≥ 1.50 D was 13.9%, 0.6%, and 2.2%, respectively, in Hispanic children, and 7.8%, 2.2%, and 2.7%, respectively, in African American children. CONCLUSIONS: We observed ethnicity-related differences in astigmatism prevalence in preschool children. The age-related decrease in astigmatism prevalence in preschool children likely reflects emmetropization.

Fixation preference and visual acuity testing in a population-based cohort of preschool children with amblyopia risk factors.

PURPOSE: To compare the clinical assessment of fixation preference (FP) to visual acuity (VA) in a population-based sample of preschool children with amblyopia risk factors. DESIGN: Evaluation of diagnostic test in a population-based study. PARTICIPANTS: 243 children with anisometropia and/or strabismus, aged 30 to 72 months, living in Los Angeles County, CA [corrected] METHODS: Before measuring VA, FP testing was performed at near and usually without correction, using the binocular fixation pattern in children with strabismus >10 prism diopters (Delta), or the induced tropia test for children with strabismus

Stereoacuity testability in African-American and Hispanic pre-school children.

PURPOSE: To determine testability using the Randot Pre-school Stereoacuity Test in black and Hispanic children 30 to 72 months of age. METHODS: A population-based cohort of children 30 to 72 months of age was administered the Randot Pre-school Stereoacuity Test, with presenting refractive correction, and before cover testing, visual acuity testing, or refraction. Children who could not point to specified two-dimensional demonstration pictures, and children who would not try to name or match random dot figures to the corresponding two-dimensional pictures, were classified as unable to perform the test. Children who were able to perform the task but could not correctly identify at least two 800-arcsecond random dot figures were classified as having no stereopsis, and were retested by another examiner. RESULTS: Stereoacuity testing was attempted in 1662 Hispanic and 1470 black children. Overall, 80% of children were able to be tested; 33% of children 30 to 36 months of age, 73% of children 37 to 48 months of age, 96% of children 49 to 60 months of age, and 98% of children 61 to 72 months of age were testable. Older children were significantly more likely to complete testing successfully than younger children (p < 0.0001). After adjusting for age, there was no significant ethnicity-related difference in testability (p = 0.19); however, there was a small but significant gender-related difference (p = 0.0002) with more girls (82%) than boys (77%) able to complete testing. CONCLUSIONS: Eighty percent of children aged 30 to 72 months can be tested using the Randot Pre-school Stereoacuity test. Testability increases steadily with age, and 97% of children over 48 months of age can complete the test. Testability does not differ between children of Hispanic and black ethnicity.

A molecular/epidemiologic analysis of expression of cyclooxygenases 1 and 2, use of nonsteroidal antiinflammatory drugs, and risk of colorectal adenoma.

Nonsteroidal antiinflammatory drugs (NSAIDs) are postulated to protect against colorectal cancer and adenomas at least in part by a cyclooxygenase (COX-mediated mechanism. The results reported herein address the questions of what factors are associated with expression (relative messenger RNA levels) of COX-1 and COX-2 in colorectal adenomas and whether there is heterogeneity in the protective effect of NSAIDs by levels of COX expression. Paraffin-embedded tissue samples and data describing selected risk factors were obtained from cases enrolled in a case-control study of colorectal adenomatous polyps. RNA was isolated from paraffin-embedded specimens. Samples of complementary DNA were quantified using a fluorescence-based real-time detection method. We tested for differences in levels of COX expression among selected subgroups of cases using a standard Student t test. Odds ratios for the effects of NSAID variables were calculated using unconditional logistic regression in order to make use of all available data on COX expression. Results suggest that use of NSAIDs is associated with lower levels of COX-2 expression and that the protective effect of NSAIDs on polyp occurrence is stronger in the subgroup of cases with higher expression of COX-2 and a higher COX-2/COX-1 ratio. The results suggest that at least part of the protective effect of NSAIDs on the risk of colorectal adenoma involves a COX-mediated pathway.

Prostaglandin H synthase 2 variant (Val511Ala) in African Americans may reduce the risk for colorectal neoplasia.

Prostaglandin H synthase 2 (also known as cyclooxygenase-2) is thought to play a role in the prevention of colon cancer by aspirin, an inhibitor of the enzyme. We used DNA heteroduplex analysis to screen the prostaglandin H synthase 2 gene, to search for naturally occurring enzyme variants that may simulate the effects of aspirin. We found among African-Americans a single-nucleotide polymorphism that changes valine to alanine at residue 511 (V511A; GTT>GCT; g.5939T>C; allele frequency 0.045). The polymorphism was also seen among Asian-Indians (allele frequency, 0.03) but not among Chinese, Filipinos, Hispanics, Japanese, Koreans, Samoans, and Caucasians. The amino acid change is predicted to open a 53 cubic angstrom cavity near the active site of the enzyme, but no change in V(max), K(m), or thermal stability was observed for the variant enzyme in COS-1 cell transfection assays. Case-control analysis of African-Americans from two different study populations showed a 0.56 odds ratio for colorectal adenomas among polymorphism carriers (95% confidence interval, 0.25-1.27; 161 cases and 219 controls). A similar analysis of African-Americans nested in the Multiethnic Cohort Study showed a 0.67 odds ratio for colorectal cancer (95% confidence interval, 0.28-1.56; 138 cases and 258 controls). Consistency of the results across all three of the studies is potentially compatible with a protective effect of the polymorphism, mimicking aspirin.