Biomedical subjects

David A Sterling

Publications and source records attributed to David A Sterling.

7 recordsLinked to original sources

PubMed2006

Identification of a mesothelioma phenotype.

Despite the strong association of asbestos exposure to mesothelioma, only a fraction of persons exposed develop this neoplasm which is characterized by long latency and shortened survival. Familial clustering implicates both exposure and genetic predisposition as causative, but a biologically relevant mesothelioma phenotype essential to genetic analysis has not been defined. To identify a more extensive set of traits that would define a mesothelioma phenotype for the purpose of genetic analysis, we set to determine characteristics that distinguish mesothelioma patients from others exposed to asbestos and to identify factors that predict the presence of mesothelioma over other mesenchymal tumors of the peritoneum and carcinoma metastatic to the pleura. We compared demographics in four asbestos-exposed groups (controls n=347, bronchogenic cancer n=67, mesothelioma n=179 and benign asbestos-induced lung disease (BALD) n=3757). Within the mesothelioma group, we compared traits to identify characteristics associated with shortened survival. We found that compared to other asbestos-exposed groups, subjects with mesothelioma were younger at first asbestos exposure, had a greater risk of a second cancer diagnosis (odds ratio=3.29), had a longer disease latency, and had a greater risk of cancer among first-degree relatives (point estimate for risk 2.93; 95% CI 2.5-3.5). Thoracic tumor location, work exposure and male gender were consistently associated with shortened survival (1.9+/-1.3 years). We conclude that thoracic tumor location, work exposure, male gender, long latency, early age at first exposure, presence of a second cancer, and first-degree relative with cancer define a phenotype that sets mesothelioma patients with a short survival apart from other asbestos-exposed individuals. We propose that this phenotype be applied to candidate gene analysis.

Age Factors↗

PubMed2006

Asthma status and severity affects missed school days.

Excessive school absence disrupts learning and is a strong predictor of premature school dropout. School-aged children with asthma are absent more often compared to their healthy peers without asthma; yet, the causes are inadequately documented. We sought to determine the difference in mean absence days between children with and without asthma, the relationship between asthma severity and missed days from school, and if incident absences were due to asthma in a predominantly African American urban school district in the Midwestern United States. A cross-sectional analysis was conducted of 9014 students (grades K-12) followed for absenteeism over the 2002-2003 academic year. A subset of 543 students with asthma was assessed for asthma severity and cause of absence. Those with asthma (9.7% of students) were absent (mean = 9.2 days) approximately 1.5 more days compared to those without asthma (mean = 7.9 days) (p = .006). In the analysis comparing asthma severity and absenteeism, after adjusting for demographic variables and enrollment time, mean days absent increased with increasing asthma severity level: mild intermittent (mean = 8.5 days), mild persistent (mean = 11.3 days), moderate persistent (mean = 10.3 days), and severe persistent (mean = 11.6 days) (p = .001). Out of 1537 tracked absences that resulted from illness, 478 (31%) were due specifically to asthma-related symptoms. Children with asthma are absent from school more often compared to their healthy peers and this appears to be driven by the underlying severity of symptoms. (J Sch Health. 2006;76(1):18-24).

Absenteeism↗

PubMed2005

Occupational physician perceptions of bioterrorism.

The rationale for most preparedness training of healthcare professionals is based on the assumption that most persons infected following a biological incident will present first to emergency departments of acute care facilities or to ambulatory settings such as private physician offices, and such incidences would be recognized, appropriately treated, and reported to the local health departments. However, an alternative first point of contact is industry, a location where workers gather and disperse on a regular and documented basis, and require healthcare. In industry there are health professionals responsible for the health, safety and on-site well-being of the workforce and surrounding community; these professionals are in a position for early recognition, surveillance, and isolation. Targeted education must be provided to these health professionals. To address perceptions of risk and preferred educational delivery methods for bioterrorism and emerging infections-related materials, a survey of occupational physicians was performed during the spring of 2001. Within the 2 months following the September 11 terrorist attack and subsequent anthrax bioterrorism event, and before release of any results from the first survey, a follow-up mail survey was initiated in November 2001. Response rate to the pre- and post-September 11 survey were 58% (n = 56) and 33% (n = 33), respectively. No significant demographic differences were observed between the respondents of the pre- and post-surveys. Perceptions of likelihood of another bioterrorism event increased between surveys, as would be expected; however, a tendency to believe that it would not happen locally persisted. Even though over 90% of the physicians had received immediate training following September 11, additional training/education needs were demonstrated. Although training and education modules can be designed without information based on the population that can be on the receiving end, it rarely accomplishes its goal. Results from this survey can serve as a base for designing various levels of targeted training and educational material specific to the perceived need, method of obtaining information and the format considered to be most conducive for learning. Potential consequences from lack of bioterrorism preparedness due to low perception of need and threat awareness need to be addressed.

Adult↗

PubMed2004

Changing patterns in asbestos-induced lung disease.

STUDY OBJECTIVES: To determine patterns in asbestos-induced lung diseases found in older, less exposed workers. DESIGN: Review of a database evaluating lung function, smoking status, form of asbestos-induced lung disease, and radiograph abnormalities. SETTING: Outpatient clinic. PARTICIPANTS: A total of 3383 asbestos-exposed workers referred for independent medical evaluation, including control subjects who lacked asbestos-specific radiograph abnormalities (n = 243), subjects with low International Labor Organization (ILO) scores (n = 2,685), high ILO scores (n = 312), bronchogenic cancer (n = 63), and mesothelioma (n = 80). Of these, 3,327 workers have specific smoking status information and 3,312 workers have lung volume measures. INTERVENTIONS: Chest radiographs were interpreted by a certified B-reader, and abnormalities were quantified according to the ILO scoring system. Spirometry and lung volume measurement were performed. Subjects completed a self-administered questionnaire that was reviewed at the time of examination. Control subjects were screened on two separate occasions at least 10 years apart to exclude subclinical or slowly progressive asbestos-induced lung disease. MEASUREMENTS AND RESULTS: The mean age of the population was 65.1 +/- 9.9 years, and the latency was 41.4 +/- 10.1 years (+/- SD). Most subjects (41.8%) had normal pulmonary function. Obstruction was the most common pulmonary function abnormality (25.4%), followed by restriction (19.3%) and a mixed pattern (6.0%). Most subjects (79.4%) had low ILO scores. Benign pleural abnormalities were the only findings in 54% of subjects with low ILO score. Subjects with high ILO scores were older, smoked more, and had a longer latency than subjects with low ILO scores and control subjects. Smokers were younger, had a shorter latency, and had paradoxically greater ILO scores than nonsmokers. Subjects with bronchogenic cancer and mesothelioma had longer latencies than control subjects and subjects with benign asbestos-induced lung disease. CONCLUSIONS: Asbestos-induced lung disease today is characterized by low ILO scores, long latencies, greater disease magnitude in smokers, and a normal or obstructive pattern of pulmonary function abnormality. Spirometric evaluation in the absence of lung volume measurements caused misclassification that resulted in overestimation of the presence of a restrictive pattern of pulmonary function.

Adult↗

PubMed2004

Effectiveness of cleaning and health education in reducing childhood lead poisoning among children residing near superfund sites in Missouri.

In this study, the authors evaluated whether a combination of tailored education, lead dust removal by trained cleaning specialists, and family follow-up visits would be more effective than conventional health educational programs in reducing elevated blood lead levels in children living in or near lead mining hazardous waste sites. The authors randomized children between 6 and 72 mo of age with blood lead levels between 10 and 20 microg/dl into 3 groups: standard care, tailored newsletters, or tailored newsletters and specialized cleaning. The authors obtained questionnaires, blood lead levels, and environmental lead samples during initiation and compared them with the same items obtained at 3, 6, and 9 mo follow-up. They used a linear mixed effect model to evaluate the intervention effect. Blood lead levels decreased overall 1.54 microg/dl (12.1%) during the study. The authors found that tailored newsletters and specialized cleaning produced the greatest decline in blood lead levels, but no statistical differences were found among the methodologies. The small decline observed in blood lead levels reduced levels to below 10 microg/dl for 40% of the children.

Child↗

PubMed2003

Association between genetic polymorphisms in the prostate-specific antigen gene promoter and serum prostate-specific antigen levels.

BACKGROUND: Recent evidence suggests that genetic variation in the promoter of the prostate-specific antigen (PSA) gene may contribute to individual variation in serum PSA levels. However, polymorphisms associated with variations in PSA levels have not been identified. METHODS: We used the polymerase chain reaction to amplify the promoter region of the PSA genes (nucleotide positions -3873 to -5749 with respect to the start of transcription) of 409 healthy white men at risk for lung disease. Polymerase chain reaction products were sequenced to identify polymorphisms in the PSA gene promoter and to genotype the men for common single nucleotide polymorphisms (SNPs) and were cloned into luciferase reporter constructs to assay PSA promoter activity in human LNCaP prostate cancer cells. Analysis of variance was used to test the association of polymorphism frequencies with mean serum PSA levels. All statistical tests were two-sided. RESULTS: The -4643G/A SNP (G allele) had a 21.2% prevalence and was associated with increases in serum PSA levels (P =.017) and PSA promoter activity (P<.001). The -5412C/T SNP (C allele) had a 22.0% prevalence and was associated with an increase in serum PSA levels (P =.0015). The -5429T/G SNP (G allele) had a 23.0% prevalence, was associated with an increase in serum PSA levels (P =.021), and was in linkage disequilibrium with the -5412C/T SNP. The promoter activity of the -5412 C/-5429 G haplotype was higher than that of the -5412 T/-5429 T haplotype (P<.001). CONCLUSIONS: Genetic variations in the PSA promoter are associated with serum PSA levels in men without prostatic disease. PSA promoter genotype information may help to refine models of PSA cutoff values.

Aged↗

PubMed2002

Association studies of serum prostate-specific antigen levels and the genetic polymorphisms at the androgen receptor and prostate-specific antigen genes.

Testing for serum prostate-specific antigen (PSA) levels has been widely used to screen for prostate cancer. However, PSA testing has low specificity and sensitivity because PSA is not prostate cancer-specific. PSA is encoded by the APS gene, and the expression of this gene is regulated by androgens. W. Xue et al. Cancer Res., 60: 839-841, 2000 reported recently that serum PSA levels are associated with a G/A polymorphism at androgen responsive element 1 (ARE1) of APS and/or the CAG repeats in exon 1 of the androgen receptor (AR) gene. This result, if confirmed, may significantly increase the specificity and sensitivity of PSA testing by incorporating genotype-specific thresholds. In this study, we tested for the association between serum PSA levels and these single nucleotide polymorphisms (SNPs) in a large sample of 518 men. For the AR gene, we observed slightly (but not statistically significant) higher mean serum PSA levels in men with shorter CAG repeats (<or=21) or shorter GGC repeats (<or=16). For the ARE1 of the APS, we found slightly (but not statistically significant) lower PSA levels in men with the AA genotype. It is worth noting that this observation is opposite to the findings of W. Xue et al. Cancer Res., 60: 839-841, 2000. We hypothesize that the effects of ARE1 and AR genotypes on mean PSA levels may reflect the effect of other causal polymorphisms in these genes, which are in linkage disequilibrium with these polymorphisms. A systematic approach is required to identify sequence variants in these genes and other related genes, and to test for an association between these variants and PSA levels in large samples.

Adult↗