The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.

Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.

Teacher stress and health; examination of a model.

Stress in teaching derives from a variety of sources, and evidence exists linking such stress to physical and mental health concerns. Detailed examination of the linkages among personal factors, job stress, job satisfaction and symptomatology have not been done in this occupation, however, and the present study examines a model interrelating these variables. A survey of 245 predominantly female elementary school teachers in southeast Texas suggested that demographic factors and teaching background do not influence stress, satisfaction or health concerns. However, while job stress was the strongest predictor of job satisfaction, this stress had no direct relationship with health problems, an unexpected finding. Write-in responses by teachers indicated additional sources of stress, many of which were environmental or policy-based in nature. The implications of these findings for future research and stress management interventions for teachers are discussed.

A pilot study on cholesterol screening in the school environment.

A newly-developed analyzer measures total cholesterol from a single drop of blood and gives results within minutes. This procedure has made mass cholesterol screening inexpensive and less invasive than methods requiring a venipuncture blood sample, and it offers the opportunity for on-the-spot counseling and referral. In a pilot study, 610 high school students in the Victoria (Tex.) School District were screened for elevated cholesterol. Eighteen percent were found to have cholesterol levels above 180 mg/dl. Mean cholesterol values were higher for females than males, and higher for blacks and Hispanics than whites. Follow-up questionnaires indicated students and their parents understood the basic relationship between cholesterol and cardiovascular disease and how to modify their diet to reduce cholesterol intake. Telephone contact with parents of students with elevated cholesterol showed only about 27% of students with elevated cholesterol had visited a physician subsequent to the cholesterol testing.

Developing indicators for emergency medical services (EMS) system evaluation and quality improvement: a statewide demonstration and planning project.

BACKGROUND: The state of California, like every other state, has no system for assessing the quality of prehospital emergency medical services (EMS) care. As part of a statewide project, a process was designed for the evaluation and quality improvement (QI) of EMS in California. Local EMS agency (LEMSA) representatives made a commitment to submit data from both the providers and the hospitals they work with. INDICATOR SELECTION AND DEVELOPMENT: For conditions such as cardiac chest complaints, standardized indicators had already been developed, but for many other areas of interest there was either little literature or little consensus in the literature. Definitional differences were often linked to local-practice protocol differences. A related comparison challenge lay in the fact that care protocols may differ across systems. Some aspects of care may not be offered at all, which may reflect resource shortages or variable medical direction. DATA COLLECTION PROCEDURES: Each indicator was precisely defined, and definition sheets and data troubleshooting report forms were provided to participants in three data-collection rounds. Participants were given 1 month to collect the data, which consisted of summary-level elements (for example, average time to defibrillation for all patients 15 years or older who received defibrillation in 1998). Data were then aggregated, analyzed, and prepared for display in graphs and tables. ACCESS AND MEASUREMENT ISSUES: Numerous data collection problems were encountered. For example, not all participants could actually access data that they thought would be available. Linking data on patients as they travel through the continuum of EMS care (dispatch, field, hospital) and linking EMS data to hospital outcomes was also difficult. Yet even when data were easily available, challenges arose. The need for specificity, the potential misfit between definitions and the available data, and the challenges of data retrieval remained salient for the duration of the project and made cross-LEMSA and cross-provider comparison problematic. RECOMMENDATIONS AND LESSONS LEARNED: The project led to formal policy recommendations regarding development of a state-defined minimum data set of structure, process, and outcome indicators and their associated data elements; provision in the minimum data set for both local-level and statewide indicators; and provision of technical assistance at the local-provider level. EPILOGUE: Since the project's conclusion in June 2000, many regional and local EMS groups have begun to collect data on indicators. Many of the project's recommendations have been incorporated into the work plan of the state's System Review and Data Committee.

The human body burden of mirex in the southeastern United States.

Mirex is an organochlorine chemical with pesticidal and other industrial usages. Biologically, mirex was used as an insecticide for the control of imported fire ants in large areas of the southeastern United States. Evidence of mirex exposure in a national survey of chemicals in adipose tissue led to a more intensive survey of the general population in treated counties of the southeastern United States. Forty sites were selected randomly from 8 southeastern states where mirex was used widescale to combat fire ants; a total of 624 adipose tissue specimens were collected from these 40 sites. Tissue specimens were prepared by a modified Mills-Onley-Gather procedure and analyzed for mirex and selected other organochlorine compounds by electron-capture gas chromatography. Positive residue findings were confirmed by combined gas chromatography and mass spectrometry. Weighted statistical analysis of the data was conducted to estimate the level of mirex in the study area. It was estimated that 10.2% of the population of southern United States had quantifiable levels of mirex in adipose tissue. The estimated geometric mean of the quantifiable residue amounts was 0.286 ppm (lipid basis). Statistical tests of association and regression were used to investigate possible relationships between the presence and levels of mirex, and the Census Division or state of tissue-specimen collection, by age, race, and sex. These analyses indicated that region or location of tissue specimen collection (assumed to be area of residence) strongly related to both the presence of mirex residue and the amount of mirex residue detected. This may be correlated with the amount of mirex applied for fire ant control or with some other exposure patterns in different regions.