Tumors in the contralateral breast following radiation therapy for breast cancer

The proportional distribution of independent malignant tumors in the contralateral breast following treatment for breast cancer was investigated to assess the influence of scattered radiation as a cause of these tumors. In a population of 172 patients the proportion of contralateral tumors in each quadrant and the center (the nipple-areolar complex) was compared with the expected, or natural, distribution found in the general population, in the absence of radiation. The observed/expected ratio for contralateral tumors was 1.43 for the upper-inner quadrant; 0.97, lower-inner quadrant; 1.51, center; 0.76, upper-outer quadrant; and 0.64, lower-outer quadrant. In each quadrant, except the lower-inner, the observed/expected ratio differed from 1.00 with statistical significance at the 5% level (one-tail). The same analysis, stratified by age and menopausal status, showed a similar shift of tumors, with more than expected in the inner quadrants and center and less than expected in the outer quadrants, although the results did not show statistical significance at the 5% level for all strata. For each patient the mean absorbed radiation dose for each quadrant and center of the breast was estimated, based on measurements in a tissue-equivalent phantom. Among patients the doses ranged from 0.5 to 8 Gy; within individuals, doses to the inner quadrants typically were a factor of three times higher than doses to the outer quadrants. The results suggest that radiation may be a risk factor for contralateral breast tumors and warrants further investigation. ^

Case-control study of association of maternal recall of diarrhea or use of antimicrobials in the periconceptional period and neural tube defects

In June 1995 a case-control study was initiated by the Texas Department of Health among Mexican American women residing in the fourteen counties of the Texas-Mexico border. Case-women had carried infants with neural tube defect. Control-women had given birth to infants without neural tube defects. The case-control protocol included a general questionnaire which elicited information regarding illnesses experienced and antibiotics taken from three months prior to conception to three months after conception. An assessment of the associations between periconceptional diarrhea and the risk of neural tube defects indicated that the unadjusted association of diarrhea and risk of neural tube defect was significant (OR = 3.3, CI = 1.4–7.6). The unadjusted association of use of oral antimicrobials and risk of neural tube defect was also significant (OR = 3.4, CI = 1.6–7.3). These associations persisted among women who had no fever during the periconceptional period and were present irrespective of folate intake. Diarrhea was associated with an increased risk of NTD independent of use of antimicrobials. The converse was also true; antimicrobials were associated with an increased risk of NTD independent of diarrhea. Further research regarding these potentially modifiable risk factors is warranted. Replication of these findings could result in interventions in addition to folate supplementation. ^

Cervical cancer screening in Hispanic women as compared with other ethnic groups on an urban campus

Although Pap screening has decreased morbidity and mortality from cervical cancer, reported statistics indicate that among ethnic groups, Hispanic women are one of the least likely to follow screening guidelines. Human papillomavirus (HPV), a major risk factor for cervical cancer, as well as pre-cancerous lesions, may be detected by early Pap screening. With a reported 43% prevalence of HPV infection in college women, regular Pap screening is important. The purpose of this descriptive, cross-sectional survey was to examine self-reported cervical cancer screening rates in a target population of primarily Mexican-American college women, and to discover if recognized correlates for screening behavior explained differences in screening rates between this and two other predominant groups on the University of Houston Downtown campus, non-Hispanic white and African-American. The sample size consisted of 613 women recruited from summer 2003 classes. A survey, adapted from an earlier El Paso study, and based on constructs of the Health Belief Model (HBM), was administered to women ages 18 and older. It was found that although screening rates were similar across ethnic groups, overall, the Hispanic group obtained screening less frequently, though this did not reach statistical significance. However, a significant difference in lower screening rates was found in Mexican American women ages <25. Additionally, of the predicted correlates, the construct of perceived barriers from the HBM was most significant for the Mexican American group for non-screening. For all groups, knowledge about cervical cancer was negatively correlated with ever obtaining Pap screening and screening within the past year. This implies that if health counseling is given at the time of women's screening visits, both adherence to appropriate screening intervals and risk factor avoidance may be more likely. Studies such as these are needed to address both screening behaviors and likelihood of follow-up for abnormal results in populations of multicultural, urban college women. ^

Application of stellar photometry to the analysis of microarray images

Improvements in the analysis of microarray images are critical for accurately quantifying gene expression levels. The acquisition of accurate spot intensities directly influences the results and interpretation of statistical analyses. This dissertation discusses the implementation of a novel approach to the analysis of cDNA microarray images. We use a stellar photometric model, the Moffat function, to quantify microarray spots from nylon microarray images. The inherent flexibility of the Moffat shape model makes it ideal for quantifying microarray spots. We apply our novel approach to a Wilms' tumor microarray study and compare our results with a fixed-circle segmentation approach for spot quantification. Our results suggest that different spot feature extraction methods can have an impact on the ability of statistical methods to identify differentially expressed genes. We also used the Moffat function to simulate a series of microarray images under various experimental conditions. These simulations were used to validate the performance of various statistical methods for identifying differentially expressed genes. Our simulation results indicate that tests taking into account the dependency between mean spot intensity and variance estimation, such as the smoothened t-test, can better identify differentially expressed genes, especially when the number of replicates and mean fold change are low. The analysis of the simulations also showed that overall, a rank sum test (Mann-Whitney) performed well at identifying differentially expressed genes. Previous work has suggested the strengths of nonparametric approaches for identifying differentially expressed genes. We also show that multivariate approaches, such as hierarchical and k-means cluster analysis along with principal components analysis, are only effective at classifying samples when replicate numbers and mean fold change are high. Finally, we show how our stellar shape model approach can be extended to the analysis of 2D-gel images by adapting the Moffat function to take into account the elliptical nature of spots in such images. Our results indicate that stellar shape models offer a previously unexplored approach for the quantification of 2D-gel spots. ^

REGULATION OF CYTOSKELETAL ASSEMBLY: A STUDY OF THE INTERACTION OF FILAMIN AND F-ACTIN

Filamin is a high molecular weight (2 x 250,000) actin crosslinking protein found in a wide variety of cells and tissues. The most striking feature of filamin is its ability to crosslink F-actin filaments and cause ATP-independent gelation and contraction of F-actin solutions. The gelation of actin filaments by filamin involves binding to actin and crosslinking of the filaments by filamin self-association. In order to understand the role of filamin-actin interactions in the regulation of cytoskeletal assembly, two approaches were used. First, the structural relationship between self-association and actin-binding was examined using proteolytic fragments of filamin. Treatment of filamin with papain generated two major fragments, 90Kd and 180Kd. Upon incubation of the papain digest with F-actin and centrifugation at 100,000 x g, only the 180Kd fragment co-sedimented with F-actin. The binding of the 180Kd fragment, P180, was similar to native filamin in its sensitivity to ionic strength. Analytical gel filtration studies indicated that, unlike native filamin, P180 was monomeric and did not self-associate. Thermolysin treatment of P180 produced a 170Kd fragment, PT170, which no longer bound and co-sedimented with F-actin. These results suggested that filamin contained a discrete actin-binding domain. In order to locate the actin-binding domain, affinity purified antibodies to the papain and thermolysin sensitive regions of filamin were used in conjunction with filamin fragments generated by digestion with S. aureus V8 protease and elastase. The results indicated that the papain and thermolysin cleavage sites were close together, and, most likely, within 10Kd of one another. Taken together, these data suggest that filamin contains a discrete, internal actin-binding domain. The second approach was to use the non-crosslinking fragment P180 to develop a quantitative assay of filamin-actin binding. The binding of ('14)C-carboxyalkylated P180 was examined using the co-sedimentation assay. ('14)C-P180 binding to actin was equivalent to that of unlabelled P180 and exhibited comparable sensitivity of binding to changes in ionic strength. Within 5 min. of incubation the process had reached equilibrium. The specificity of binding was shown by the lack of binding of ('14)C-PT170. The binding of ('14)C-P180 was found to be a reversible and saturable process, with a K(,d) of 2 x 10('-7) M. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI ^

Understanding treatment-related symptoms, symptom management techniques, and symptom management self-efficacy in a sample of non-muscle invasive bladder cancer patients

The current literature available on bladder cancer symptom management from the perspective of the patients themselves is limited. There is also limited psychosocial research specific to bladder cancer patients and no previous studies have developed and validated measures for bladder cancer patients’ symptom management self-efficacy. The purpose of this study was to investigate non-muscle invasive bladder cancer patients’ health related quality of life through two main study objectives: (1) to describe the treatment related symptoms, reported effectiveness of symptom-management techniques, and the advice a sample of non-muscle invasive bladder cancer patients would convey to physicians and future patients; and (2) to evaluate Lepore’s symptom management self-efficacy measure on a sample of non-muscle invasive bladder cancer patients. Methods. A total of twelve (n=12) non-muscle invasive bladder cancer patients participated in an in-depth interview and a sample of 46 (n=4) non-muscle invasive bladder cancer patients participated in the symptom-management self-efficacy survey. Results. A total of five symptom categories emerged for the participants’ 59 reported symptoms. Four symptom management categories emerged out of the 71 reported techniques. A total of 62% of the participants’ treatment related symptom-management techniques were reported as effective in managing their treatment-related symptoms. Five advice categories emerged out of the in-depth interviews: service delivery; medical advice; physician-patient communication; encouragement; and no advice. An exploratory factor analysis indicated a single-factor structure for the total population and a multiple factor structure for three subgroups: all males, married males, and all married participants. Conclusion. These findings can inform physicians and patients of effective symptom-management techniques thus improving patients’ health-related quality of life. The advice these patients’ impart can improve service-delivery and patient education.^

Women physicians' specialty choices

Three hypotheses have been offered to explain the historical specialty selection by women physicians. They are: (1) women choose the specialty for which the training requirements and working conditions interfere least with their commitments to marriage and children; (2) women tend to select the more "feminine" specialties such as pediatrics and psychiatry, and to avoid the "masculine" fields such as surgery; and (3) women have been deliberately excluded from male-dominated fields such as surgery. While the above hypotheses may be true to a greater or lesser degree, none of them has been adequately tested.^ The major study hypotheses are as follows: (1) female physicians' choice of specialty is influenced by the following reasons: (a) family responsibilities; (b) sex role expectations; and (c) sex discrimination; (2) female physicians' choice of specialty is also influenced by their age and ethnicity; and (3) the primary reasons for choosing a given specialty vary by type of specialty.^ The reasons for specialty selection will be explored based on a survey of women graduates of one of the oldest medical schools in the United States, The University of Texas Medical Branch (UTMB) in Galveston, Texas (n = 930). The survey response rate was 75.3% (700 respondents).^ The results for the first study hypothesis showed that fewer than 14% of the respondents agreed that sex role expectations, sex discrimination and family responsibilities played a role in their choice of specialty. Fifty nine percent of the respondents disagreed with the idea that sex role expectations influenced specialty selection and 64% disagreed that family responsibilities had an effect on the selection of their specialty. Around half (49%) were uncertain of the influence of sex discrimination. It was concluded that sex discrimination, sex role expectations and family responsibilities did not have a major impact on specialty selection.^ With respect to the second hypothesis, age was significant in Internal Medicine, Obstetrics/Gynecology and Psychiatry. Women physicians in Internal Medicine and Obstetrics/Gynecology were significantly younger (less than 45 years old) while physicians in Psychiatry were significantly older (45 years or older) than other specialties studied.^ The third hypothesis was confirmed: the reasons for choosing a given specialty varied by specialty.^ Respondents' comments written on the survey provided insight into other possible reasons for specialty selection including exploration of the role of mentoring and job satisfaction.^ The retrospective cross-sectional study design used in this study does not adequately capture the fact that different reasons may be given for the choice of specialty at different points in time, e.g., as the time of choosing a residency program versus several years into the future.^ In conclusion, approaches that explore the range of reasons that women elect to enter and stay within a given specialty must be explored to gain richer understanding of the complex and dynamic nature of women physicians' professional lives. (Abstract shortened by UMI.) ^

The History of Pathology in Texas

The History of Pathology in Texas is the study of the changes of disease in Texas from the frontier days to the 1990s. Marilyn Miller Baker wrote the book for the Texas Society of Pathologists. The book was published in 1996 with a forward by Vernie A. Stembridge, MD, the Ashbel Smith Professor and Chairman Emeritus of Pathology at the University of Texas Southwestern Medical Center at Dallas. The book covers the story of pathology from the "performance of crude autopsies" on the frontier through the emergence of bacteriology and immunology and beyond.

Shifting the focus: Addressing breast cancer disparities at the health care organization level

The purpose of this study was to understand the scope of breast cancer disparities within the Texas Medical Center. The goal was to increase the awareness of breast cancer disparities at the health care organization level, and to foster the development of organizational interventions to reduce breast cancer disparities. The study seeks to answer the following questions: 1. Are hospitals in the Texas Medical Center implementing interventions to reduce breast cancer disparities? 2. What are their interventions for reducing the effects of non clinical factors on breast cancer treatment disparities? 3. What are their measures for monitoring, continuously improving, and evaluating the success of their interventions? ^ This research project was designed as a mixed methods case study. Quantitative breast cancer data for the years 2000-2009 was obtained from the Texas Cancer Registry (TCR). Qualitative data collection and analysis was done by conducting a total of 20 semi-structured interviews of administrators, physicians and nurses at five hospitals (A, B, C, D and E) in the Texas Medical Center (TMC). For quantitative analysis, the study was limited to early stage breast cancer patients: local and regional. The dependent variable was receipt of standard treatment: Surgery (Yes/No), BCS vs Mastectomy, Chemotherapy (Yes/No) and Radiation after BCS (Yes/No). The main independent variable was race: non-Hispanic White (NHW) , non-Hispanic Black (NHB), and Hispanic. Other covariates included age at diagnosis, diagnosis date, percent poverty, grade, stage, and regional nodes. Multivariate logistic regression was used to test the adjusted association between receipt of standard care and race. Qualitative data was analyzed with the Atlas.ti7 software (ATLAS.ti GmbH, Berlin). ^ Though there were significant differences by race for all dependent variables when the data was analyzed as a single group of all hospitals; at the level of the individual hospitals the results were not consistent by race/ethnicity across all dependent variables for hospitals A, B, and E. There were no racial differences in adjusted analysis for receipt of chemotherapy for the individual hospitals of interest in this study. For hospitals C and D, no racial disparities in treatment was observed in adjusted multivariable analysis. All organizations in this study were aware of the body of research which shows that there are disparities in breast cancer outcomes for patient population groups. However, qualitative data analysis found that there were differences in interest among hospitals in addressing breast cancer disparities in their patient population groups. Some organizations were actively implementing directed measures to reduce the breast cancer disparity gap in outcomes for patients, and others were not. Despite the differences in levels of interest, quantitative data analysis showed that organizations in the Texas Medical Center were making progress in reducing the burden of breast cancer disparities in the patient populations being served.^