Accuracy and interrater reliability for the diagnosis of Barrett's neoplasia among users of a novel, portable high-resolution microendoscope.

The high-resolution microendoscope (HRME) is a novel imaging modality that may be useful in the surveillance of Barrett's esophagus in low-resource or community-based settings. In order to assess accuracy and interrater reliability of microendoscopists in identifying Barrett's-associated neoplasia using HRME images, we recruited 20 gastroenterologists with no microendoscopic experience and three expert microendoscopists in a large academic hospital in New York City to interpret HRME images. They prospectively reviewed 40 HRME images from 28 consecutive patients undergoing surveillance for metaplasia and low-grade dysplasia and/or evaluation for high-grade dysplasia or cancer. Images were reviewed in a blinded fashion, after a 4-minute training with 11 representative images. All imaged sites were biopsied and interpreted by an expert pathologist. Sensitivity of all endoscopists for identification of high-grade dysplasia or cancer was 0.90 (95% confidence interval [CI]: 0.88-0.92) and specificity was 0.82 (95% CI: 0.79-0.85). Positive and negative predictive values were 0.72 (95% CI: 0.68-0.77) and 0.94 (95% CI: 0.92-0.96), respectively. No significant differences in accuracy were observed between experts and novices (0.90 vs. 0.84). The kappa statistic for all raters was 0.56 (95% CI: 0.54-0.58), and the difference between groups was not significant (0.64 vs. 0.55). These data suggest that gastroenterologists can diagnose Barrett's-related neoplasia on HRME images with high sensitivity and specificity, without the aid of prior microendoscopy experience.

Patella lead x-ray fluorescence measurements are independent of sample orientation.

In vivo x-ray fluorescence bone lead measurements assess long-term lead exposure. Tibia, calcaneus, and patella are the most commonly sampled bones. Patella measurements also include lead signals from the distal femur, proximal tibia, and synovium. It is therefore important to know whether the orientation of the patella relative to the measurement system substantially affects the measured patella lead concentrations and their measurement uncertainties. This study examined whether these parameters exhibited a dependence on the orientation of the patella with respect to the measurement system, a dependence that could arise from varying nonpatella contributions. There was no effect of orientation on measured patella lead concentration, but there was a highly significant effect of orientation on the measurement uncertainty. These data do not conclusively show that there are no nonpatella contributions to a patella lead measurement; rather, that any such contributions are not a function of measurement orientation over the range of orientations considered. Further study is required if the contribution of nonpatella tissues to a patella lead XRF-measured concentration is to be fully addressed. This study also filled a gap in the literature by quantifying the within-patella (29%) and between-patella (71%) variability of measured patella lead concentrations from replicate measures of nine patellae.

Seasonal distribution of antiphospholipid antibodies.

BACKGROUND AND PURPOSE: The purpose of this study was to determine if there was a seasonal variation in antiphospholipid antibody (aPL) titers and whether this variation differed between stroke cases and control subjects. METHODS: IgG and IgM anticardiolipin and antiphosphatidyl serine antibody titers were obtained on serum samples from 884 stroke patients and 1024 control subjects over a 7-year period. Temporal distributions by month of blood draw were evaluated. RESULTS: Marked seasonal differences in the proportion of positive titers were found for control subjects, but no seasonal variability among patients was noted. In control subjects, positive titers occurred less frequently in the summer months, mirroring the seasonal trends seen in respiratory track infections and rheumatic fever. CONCLUSIONS: Our data suggest some aPL antibodies arise from different origins in patients and control subjects. The seasonality observed in the apparently normal population may be related to antibodies of infectious origin and is consistent with the reported lack of association with thrombosis of infection-related antibodies.

The effect of measurement location on tibia lead XRF measurement results and uncertainty.

The aims of this study were to determine whether the location on the tibia measured by 109Cd-based K-shell x-ray fluorescence (XRF) affected the measurement result and its uncertainty, and whether higher tibia lead levels at the extremities of the tibia and/or inhomogeneity in the distribution of lead in the tibia could be inferred therefrom. Replicate XRF measurements were performed at multiple locations on ten adult cadaver intact legs and on nine bare tibiae dissected from them. Mean lead levels in the bare tibiae ranged from 16 to 48 microg Pb per g of bone mineral. Bare tibia measurements showed that both the XRF result and its uncertainty increased towards the proximal and distal ends of the tibia. The XRF result decreased away from the medial-lateral mid-point of the tibia, but XRF uncertainty was not significantly affected. Intact leg measurements showed no effect of proximal distal location on XRF result but did show an effect on XRF uncertainty. We conclude that the XRF method used can determine the differences in bone lead level resulting from the more trabecular composition at the ends of the tibia, and we present limited evidence for localized regions of low tibia lead level.

Variability in XRF-measured tibia lead levels.

A few studies have examined the variability in 109Cd-based K-shell x-ray fluorescence (KXRF) bone lead measurements from replicate measurements made either at the same time or over a period of time, and one of these studies has shown that the uncertainty in an individual measurement is an underestimate of the standard deviation of replicate measurements. Variability in KXRF tibia lead measurements was assessed from ten cadaver intact legs, from the bare tibiae dissected from nine of these legs, and from four in vivo volunteers. Cadaver legs underwent replicate measurements on multiple occasions. In vivo volunteers underwent single measurements of the left tibia monthly for one year. Average tibia lead levels in the cadaver legs and in vivo volunteers ranged from 6 to 50 and from 6 to 13 microg Pb per g of bone mineral respectively. The factors influencing the standard deviation of replicate measurements were investigated. Both cadaver and in vivo measurements confirmed that the uncertainty in an individual measurement is an underestimate of the standard deviation of replicate measurements, suggesting a methodological deficiency probably shared by most current 109Cd-based K-shell XRF lead measurement systems.

The association of blunted nocturnal blood pressure dip and stroke in a multiethnic population.

Nondipping has been defined as a reduction in the mean systolic and diastolic blood pressure (BP) of <10% from awake to sleep. We hypothesized that nondipping might be associated with stroke in minority populations. We monitored BP over a 24 h period with an ambulatory device in 166 cases from a multiethnic population of stroke survivors (63 blacks, 61 non-Hispanic whites, and 42 Caribbean Hispanics, aged 69.5 +/- 11 years) and 217 community control subjects (73 blacks, 107 non-Hispanic whites, and 67 Caribbean Hispanics, aged 69 +/- 9 years). Prevalence of nondipping was significantly greater among cases than among control subjects (64% v. 37%, P < .001). In a multiple logistic regression model adjusted for traditional risk factors for stroke, nondipping conferred an increased risk for stroke. Probability of stroke associated with nondipping (odds ratio (OR) 2.5, confidence interval (CI) 1.6 to 4.0) was equal to that of traditional risk factors. Nondipping increased the chance of having a stroke in both non-Hispanic whites (OR 4.2, P < .001) and blacks/Caribbean Hispanics (OR 1.9, P = .03). The strength of the contribution of nondipping to stroke risk was similar in all ethnic groups. Nondipping was associated with stroke in both men and women. Given the previous reports that nondipping contributes to stroke risk in European and Asian populations, these data suggest that nondipping may be universally associated with risk for stroke.

Antiphosphatidyl serine antibodies are independently associated with ischemic stroke.

OBJECTIVE: To determine whether elevated titers of antiphosphatidyl serine antibodies (aPS) are associated with an increased risk of ischemic stroke in a general stroke population. BACKGROUND: aPS are members of the family of antiphospholipid antibodies that has been associated with increased stroke risk. Although aPS have been demonstrated to occur in 18% of a group of young patients with cerebrovascular symptoms, their prevalence in the general stroke population is unknown, and no controlled study to assess the strength of their association with ischemic stroke has been undertaken previously. METHODS: A case-control study comparing 267 acute ischemic stroke patients and 653 community controls. Sera were obtained immediately after acute stroke in patients. Titers of IgG aPS >16 IgG phospholipid units or IgM aPS >22 IgM phospholipid units were considered positive. Odds ratios (ORs) were obtained by logistic regression, adjusting for age, gender, race/ethnicity, history of hypertension, diabetes mellitus, cardiovascular disease, and cigarette smoking. RESULTS: The adjusted OR was 5.6 (95% confidence interval [CI] 1.8, 18.0) for IgG aPS and 2.9 (95% CI 1.6, 5.3) for IgM aPS. The adjusted OR for either an elevated IgG or IgM aPS was 3.2 (95% CI 1.8, 5.5). CONCLUSIONS: This study demonstrates that elevated IgG and IgM antiphosphatidyl serine antibodies titers are associated with increased risk of ischemic stroke. The prevalence of these antibodies is lower, but the associated stroke risk is comparable with that of anticardiolipin antibodies.

Elevated anticardiolipin antibody titer is a stroke risk factor in a multiethnic population independent of isotype or degree of positivity.

BACKGROUND AND PURPOSE: Previous studies have produced conflicting results regarding the putative association between anticardiolipin antibodies (aCL) and infarction in the general stroke population. These inconsistencies may be a function of sample size and methodological differences among the studies. The purpose of the present study, the largest case-control study of this issue to date, was to assess aCL status as an independent risk factor for ischemic stroke in a multiethnic, urban population. METHODS: We obtained aCL titers in 524 hospitalized acute stroke patients and 1020 community controls enrolled in the Minorities Risk Factors and Stroke Study. The results were interpreted as negative (30.0 GPL or 15.0 MPL units). Odds ratios (ORs) were adjusted for age, sex, race/ethnicity, history of diabetes, hypertension, atrial fibrillation, coronary artery disease, and current cigarette smoking. RESULTS: A positive aCL titer was present in 11% (111/1020) of controls and 34% (180/524) of cases. The adjusted OR for any positive aCL titer was 4.0 (95% CI, 3.0 to 5.5). For any positive IgG aCL titer this value was 3.9 (95% CI, 2.8 to 5.5), and for any positive IgM aCL titer it was 3.4 (95% CI, 2.1 to 5.5). There were no significant differences in ORs associated with high- or low-positive IgG or IgM aCL titers. CONCLUSIONS: In the largest study of its kind to date, aCL antibodies were demonstrated to be independent stroke risk factors across the 3 ethnic groups studied, conferring a 4-fold increased risk of ischemic stroke. IgG and for the first time IgM aCL were each shown to be associated with increased stroke risk. The prevalence of these antibodies and the stroke risk associated appear greater than previously reported.

Pesticides and inner-city children: exposures, risks, and prevention.

Six million children live in poverty in America's inner cities. These children are at high risk of exposure to pesticides that are used extensively in urban schools, homes, and day-care centers for control of roaches, rats, and other vermin. The organophosphate insecticide chlorpyrifos and certain pyrethroids are the registered pesticides most heavily applied in cities. Illegal street pesticides are also in use, including tres pasitos (a carbamate), tiza china, and methyl parathion. In New York State in 1997, the heaviest use of pesticides in all counties statewide was in the urban boroughs of Manhattan and Brooklyn. Children are highly vulnerable to pesticides. Because of their play close to the ground, their hand-to-mouth behavior, and their unique dietary patterns, children absorb more pesticides from their environment than adults. The long persistence of semivolatile pesticides such as chlorpyrifos on rugs, furniture, stuffed toys, and other absorbent surfaces within closed apartments further enhances urban children's exposures. Compounding these risks of heavy exposures are children's decreased ability to detoxify and excrete pesticides and the rapid growth, development, and differentiation of their vital organ systems. These developmental immaturities create early windows of great vulnerability. Recent experimental data suggest, for example, that chlorpyrifos may be a developmental neurotoxicant and that exposure in utero may cause biochemical and functional aberrations in fetal neurons as well as deficits in the number of neurons. Certain pyrethroids exert hormonal activity that may alter early neurologic and reproductive development. Assays currently used for assessment of the toxicity of pesticides are insensitive and cannot accurately predict effects to children exposed in utero or in early postnatal life. Protection of American children, and particularly of inner-city children, against the developmental hazards of pesticides requires a comprehensive strategy that monitors patterns of pesticide use on a continuing basis, assesses children's actual exposures to pesticides, uses state-of-the-art developmental toxicity testing, and establishes societal targets for reduction of pesticide use.

Volume of ventricular blood is an important determinant of outcome in supratentorial intracerebral hemorrhage.

OBJECTIVE: To determine the prognostic significance and pathophysiologic implication of intraventricular extension of supratentorial intracerebral hemorrhage. DESIGN: Prospective study. SETTING: Acute stroke and neurointensive care units of a tertiary care hospital. PATIENTS: One hundred twenty-nine patients with supratentorial intracerebral hemorrhage, managed medically. INTERVENTIONS: Two patients had intraventricular catheters placed for external drainage. No patient received thrombolytics or surgical evacuation of clot. MEASUREMENTS AND MAIN RESULTS: Of the 129 patients, 47 had intraventricular extension of their hemorrhages. These patients had larger intraparenchymal hemorrhages (36.6 cm3 vs. 15.0 cm3) and lower initial Glasgow Coma Scale scores (mean, 9.6 vs. 13.7). Their 30-day mortality rate was 43% compared with only 9% among those without ventricular extension. Univariate and multivariate logistic regression modeling was used to assess the prognostic significance of various measures of intraventricular hemorrhage. The presence of intraventricular hemorrhage, the number of ventricles containing blood, fourth ventricular blood, and intraventricular hemorrhage volume were each related to 30-day mortality in a univariate analysis, but only intraventricular hemorrhage volume contributed significantly to outcome prediction in the presence of Glasgow Coma Scale score. CONCLUSIONS: Volume of intraventricular hemorrhage is an important determinant of outcome in supratentorial intracerebral hemorrhage.

Lead exposure among young urban women.

OBJECTIVE: Blood lead levels have declined among every age group in the United States, but urban minority residents remain at disproportionate risk for elevated lead levels. Our objective was to measure lead burden in young women of childbearing age in New York City. We also describe successful means of recruiting this population into a cohort study. MATERIAL AND METHODS: Healthy women aged 18-25 attending a New York City health care center in 1995-1998 were eligible for participation. Participants were recruited by health care providers, the study coordinator and the participants themselves. Venous blood samples were obtained for whole blood lead, ferritin and hematocrit measurements, and detailed questionnaires were administered. RESULTS: 239 women have been recruited to date. The population is predominately minority: 62% African-American, 33% Hispanic and 5% Caucasian/Asian. The average age of participants is 19.3 years. Recruitment of participants into the study is predominantly (55%) through "word of mouth" from previously enrolled participants. Few participants learned of the study through their health care providers. The mean blood lead level among study participants is 2.1 +/- 1.7 micrograms/dl, which is consistent with the most recent United States national survey. CONCLUSIONS: Blood lead levels are low in young, urban minority women of childbearing age in New York City. In this population, recruitment efforts were substantially enhanced with the help of enrolled participants and the health care community.

Stroke recurrence is more frequent in Blacks and Hispanics.

This study was designed to measure recurrent stroke rates and identify their determinants in a mixed ethnic population. A cohort of 299 patients (110 black, 57 Hispanic and 132 white) admitted to a large urban hospital with an acute stroke between November 1, 1991, and July 1, 1993, was followed for a mean of 17.8 months. Demographic and historical data and stroke subtype and severity were recorded at the time of the index stroke. The main outcome measure was stroke recurrence. The unadjusted relative risk of stroke recurrence for blacks, relative to white, was 2.0 (95% CI: 0.9-4.4) and for Hispanics, relative to whites, it was 2.6 (95% CI: 1.08-60). Ethnicity appeared to be associated with recurrence risk only among first-ever strokes: the risk for blacks, relative to whites, was 2.4 (95% CI: 1.02-5.5) and for Hispanics it was 2.9 (95% CI: 1.2-7.4). None of the other putative risk factors for stroke recurrence identified at the time of initial hospitalization were associated with risk of recurrence.

Polymorphisms of H-ras-1 and p53 in breast cancer and lung cancer: a meta-analysis.

Certain polymorphic variants of H-ras-1 and p53 have been investigated for an association between inheritance and cancer risk. The results of a metaanalysis, which reviews studies of H-ras-1 rare alleles and p53 codon 72 allelic variants in breast and lung cancer, are presented. The data constituted evidence for elevated risk of both breast and lung cancer with inheritance of rare H-ras-1 alleles. Calculated population attributable risks are 0.092 and 0.037 for breast and lung cancer, respectively. The frequency of the rare H-ras-1 alleles was observed to be greater in African Americans than in Caucasians, and a specific allele (A3.5) that is common in African Americans was found only at low frequency in Caucasians. For p53 a consensus has yet to be reached. Lung cancer studies conducted in Caucasian and African-American populations have found no evidence of risk associated with the proline variant of codon 72. Two similar studies conducted in Japanese populations suggested an association between p53 genotype distribution and lung cancer risk. However, one implicates the proline allele but the other implicates the arginine allele. The frequency of the proline variant is significantly dependent on race. Frequencies have been reported for control populations of Japanese (0.347 and 0.401), Caucasian (0.295, 0.284, and 0.214), African American (0.628 and 0.527), and Mexican American (0.263).

The Minorities Risk Factors and Stroke Study (MRFASS). Design, methods and baseline characteristics.

African-Americans and probably Latinos are at increased risk of stroke compared with white, non-Latino Americans. This study seeks to determine if the known risk factors for stroke can account for this increased risk. In this case-control study controls (neighborhood volunteers) were group-matched to acute stroke cases by ethnicity in a ratio of approximately 2:1 for African-Americans and Latinos and 1:1 for whites. Extensive historical, clinical and laboratory data were collected on each subject. For each ethnic group cases were somewhat older and less well-educated than the volunteer controls. Patients in each ethnic group were similar with regard to time from stroke onset to hospital admission, stroke severity, length of stay, discharge disposition and mortality rate. With minor exceptions the distributions of stroke subtypes within each ethnic group appeared similar to those previously reported. Subject recruitment for this case-control study was completed in the manner and time frame planned. Analysis of risk factor information from this sample should provide valuable information regarding the relative risk associated with the major modifiable risk factors for stroke in the minority groups studied.

Chrysotile asbestos fibers mediate homologous recombination in Rat2 lambda fibroblasts: implications for carcinogenesis.

Asbestos fibers are widespread environmental carcinogens whose mutagenicity is now established. Nonetheless, the molecular nature of these mutations and the mechanisms by which they accelerate carcinogenesis remain poorly understood. We have assessed the ability of asbestos fibers to promote homologous recombination, a potent mechanism for generating intrachromosomal rearrangements, such as deletions, and mitotic recombination. For this, we have developed a new assay which determines the extent to which a marker gene present in DNA introduced by asbestos can recombine with homologous genes residing in a transfected cell. We have demonstrated that Calidria chrysotile fibers are mutagenic and are able to mediate transfection of molecularly marked mutant lacI genes in a manner that results in their preferential recombination with homologous wild-type genes in the transfected cell. Asbestos induced recombination events may play a significant role in asbestos mutagenesis and carcinogenesis, and promotion of recombination may underlie the well-recognized synergy of asbestos with other carcinogens.

Unraveling the chronic toxicity of lead: an essential priority for environmental health.

Although population exposure to lead has declined, chronic lead toxicity remains a major public health problem in the United States affecting millions of children and adults. Important gaps exist in knowledge of the pathophysiology of chronic lead intoxication. These gaps have impeded development of control strategies. To close current gaps in knowledge of chronic lead toxicity, we propose an integrated, multidisciplinary, marker-based research program. This program combines a) direct measurement of individual lead burden by 109Cd X-ray fluorescence analysis of lead in bone, b) determination of ALA-D phenotype, an index of individual susceptibility to lead, and c) assessments of subclinical injury produced by lead in the kidneys, nervous system and, reproductive organs. Data from this research will provide answers to questions of great public health importance: a) Are current environmental and occupational standards adequate to prevent chronic lead intoxication? b) is lead mobilized from the skeleton during pregnancy or lactation to cause fetal toxicity? c) Is lead mobilized from bone during menopause to cause neurotoxicity? d) What is the significance of genetic variation in determining susceptibility to lead? e) What is the contribution of lead to hypertension, renal disease, chronic neurodegenerative disease or declining sperm counts? f) Is chelation therapy effective in reducing body lead burden in persons with chronic overexposure to lead?