XIPHOPHORUS ENZYME GENE EXPRESSION: TISSUE SPECIFICITY, GENETIC CONTROL, AND STABILITY IN CULTURED CELLS

Five permanent cell lines were developed from Xiphophorus maculatus, X. helleri, and their hybrids using three tissue sources, including adults and embryos of different stages. To evaluate cell line gene expression for retention of either tissue-of-origin-specific or ontogenetic stage-specific characters, the activity distribution of 44 enzyme loci was determined in 11 X. maculatus tissues, and the developmental genetics of 17 enzyme loci was charted in X. helleri and in helleri x maculatus hybrids using starch gel electrophoresis. In the process, eight new loci were discovered and characterized for Xiphophorus.^ No Xiphophorus cell line showed retention of tissue-of-origin-specific or ontogenetic stage-specific enzyme gene expressional traits. Instead, gene expression was similar among the cell lines. One enzyme, adenosine deaminase (ADA) was an exception. Two adult-origin cell lines expressed ADA, whereas, three cell lines derived independently from embryos did not. ADA('-) expression of Xiphophorus embryo-derived cell lines may represent retention of an embryonic gene expressional trait. In one cell line (T(,3)) derived from 13 pooled interspecific hybrid (F(,2)) embryos, shifts with time were observed at enzyme loci polymorphic between the two species. This suggested shifts in ratios of cells of different genotypes in the population rather than unstable gene expression in one dominant cell type.^ Verification of this hypothesis was attempted by cloning the culture--seeking clones having different genetic signatures. The large number of loci electrophoretically polymorphic between the two species and whose alleles segregated independently into the 13 progeny from which this culture originated almost guaranteed the presence of different genetic signatures (lineages) in T(,3).^ Seven lineages of cells were found within T(,3), each expressing genotypes at some loci not characteristic of the expression of the culture-as-a-whole, supporting the hypothesis tested. Quantitative studies of ADA expression in the whole culture (ADA('-)) and in clones of these seven lineages suggested the predominance in T(,3) of ADA deficient cell lineages, although moderate to high ADA output clones also occurred. Thus, T(,3) has the potential to shift phenotypes from ADA('-) to ADA('+) by simply changing proportions of its constituent cell types, demonstrating that such shifts can occur in any cell culture containing cells of mixed expressional characteristics.^

Time to renal disease and end-stage renal disease in PROFILE: a multiethnic lupus cohort.

BACKGROUND: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE). METHODS AND FINDINGS: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic-demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE.In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcgammaRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model. CONCLUSIONS: Fcgamma receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated.

Aboral ectoderm-specific expression and regulation of the LpS1 genes of {\it Lytechinus pictus\/}

The Spec genes serve as molecular markers for examining the ontogeny of the aboral ectoderm lineage of sea urchin embryos. These genes are activated at late-cleavage stage only in cells contributing to the aboral ectoderm of Strongylocentrotus purpuratus and encode 14,000-17,000 Da calcium-binding proteins. A comparative analysis was undertaken to better understand the mechanisms underlying the activation and function of the Spec genes by investigating Spec homologues from Lytechinus pictus, a distantly related sea urchin. Spec antibodies cross-reacted with 34,000 Da proteins in L. pictus embryos that displayed a similar ontogenetic pattern to that of Spec proteins. One cDNA clone, LpS1, was isolated by hybridization to a synthetic oligonucleotide corresponding to a calcium-binding domain or EF-hand. The LpS1 mRNA has developmental properties similar to those of the Spec mRNAs. LpS1 encodes a 34,000 Da protein containing eight EF-hand domains, which share structural homology with the Spec EF-hands; however, little else in the protein sequence is conserved, implying that calcium-binding is important for Spec protein function. Genomic DNA blot analysis showed two LpS1 genes, LpS1$\alpha$ and LpS1$\beta$, in L. pictus. Partial gene structures for both LpS1$\alpha$ and $\beta$ were constructed based on genomic clones isolated from an L. pictus genomic library. These revealed internal duplications of the LpS1 genes that accounted for the eight EF-hand domains in the LpS1 proteins. Sequencing analysis showed there was little in common among the 5$\sp\prime$-flanking regions of the LpS1 and Spec genes except for the presence of a binding site for the transcription factor USF.^ A sea urchin gene-transfer expression system showed that 762 base pairs (bp) of 5$\sp\prime$-flanking DNA from the LpS1$\beta$ gene were sufficient for correct temporal and spatial expression of reporter genes in sea urchin embryos. Deletions at the 5$\sp\prime$ end to 511, 368, or 108bp resulted in a 3-4 fold decrease in chloramphenicol acetyltransferase (CAT) activity and disrupted the restricted activation of the lac Z gene in aboral ectoderm cells.^ A full-length Spec1 protein and a truncated LpS1 protein were induced and partially purified from an in vitro expression system. (Abstract shortened with permission of author.) ^

An analysis of two methods for the classification of stage of readiness to obtain repeat mammography screening

Background and purpose: Breast cancer continues to be a health problem for women, representing 28 percent of all female cancers and remaining one of the leading causes of death for women. Breast cancer incidence rates become substantial before the age of 50. After menopause, breast cancer incidence rates continue to increase with age creating a long-lasting source of concern (Harris et al., 1992). Mammography, a technique for the detection of breast tumors in their nonpalpable stage when they are most curable, has taken on considerable importance as a public health measure. The lifetime risk of breast cancer is approximately 1 in 9 and occurs over many decades. Recommendations are that screening be periodic in order to detect cancer at early stages. These recommendations, largely, are not followed. Not only are most women not getting regular mammograms, but this circumstance is particularly the case among older women where regular mammography has been proven to reduce mortality by approximately 30 percent. The purpose of this project was to increase our understanding of factors that are associated with stage of readiness to obtain subsequent mammograms. A secondary purpose of this research was to suggest further conceptual considerations toward the extension of the Transtheoretical Model (TTM) of behavior change to repeat screening mammography. ^ Methods. A sample (n = 1,222) of women 50 years and older in a large multi-specialty clinic in Houston, Texas was surveyed by mail questionnaire regarding their previous screening experience and stage of readiness to obtain repeat screening. A computerized database, maintained on all women who undergo mammography at the clinic, was used to identify women who are eligible for the project. The major statistical technique employed to select the significant variables and to examine the man and interaction effects of independent variables on dependent variables was polychotomous stepwise, logistic regression. A prediction model for each stage of readiness definition was estimated. The expected probabilities for stage of readiness were calculated to assess the magnitude and direction of significant predictors. ^ Results. Analysis showed that both ways of defining stage of readiness for obtaining a screening mammogram were associated with specific constructs, including decisional balance and processes of the change. ^ Conclusions. The results of the present study demonstrate that the TTM appears to translate to repeat mammography screening. Findings in the current study also support finding of previous studies that suggest that stage of readiness is associated with respondent decisional balance and the processes of change. ^

Physiologic and psychosocial stage-based differences for dietary fat consumption in women with type 2 diabetes

Purpose. This cross-sectional, observational study explored differences among groups staged for intent to decrease dietary fat intake in women with type 2 diabetes in relation to demographic, weight concern, physiological, and psychosocial variables. ^ Methods. A sample of 100 community-dwelling, English-speaking women, who were over age 30 and had type 2 diabetes for at least a year, was accessed through a culturally diverse endocrinology clinic. Subjects completed 7 self-report instruments: demographic sheet, with 11-point weight satisfaction scale; staging algorithm; fat intake (MEDFICTS); depression (CES-D); diabetes-specific dietary knowledge (ADKnowl), social support and self-efficacy scales (SE-Type 2). Physiological variables were abstracted from the medical record (HbA 1c, blood pressure, serum cholesterol and triglycerides). ^ Results. The women's average age was 57.69 years ( SD = 3.07); 50% were married. Subjects were well-educated ( M = 14 years; SD = 3.33), with average diabetes duration of 10.57 years (SD = 9.11), high body mass index (M = 35.72; SD = 8.36), low diabetes-specific dietary knowledge, low weight satisfaction, but in good diabetes control. Racial/ethnic composition was 44% non-Hispanic-White-American, 18% Hispanic-White-American, 15% non-Hispanic-African-American, 16% Hispanic-African-American and 5% other. Fat intake was low and differed by racial/ethnic demographics. The highest fat intake scores were for non-Hispanic-African-Americans (M = 53), followed by Hispanic-White-Americans (M = 51), non-Hispanic-White-Americans (M = 45), and Hispanic-African-Americans (M = 32), who had the lowest fat intake scores. ^ MANOVA analyses revealed no significant differences between stages of behavior change in relation to psychosocial or weight concern variables, age, education, HbA1c, or cholesterol levels. Single women were more likely to be in the three preaction stages (precontemplation, contemplation, and preparation); married women were equally distributed across stages (the preaction stages plus action and maintenance). African-American women (Hispanic and non-Hispanic) were more likely in contemplation and preparation. Triglycerides were higher in women in the action stage than contemplation or preparation. Systolic blood pressure was higher in action than preparation; diastolic blood pressure was higher in action than preaction. ^ Conclusions. Healthcare professionals should consider race, ethnicity, and marital status in client interactions. Dietary intake can vary according to both race and ethnicity; collapsing racial/ethnic groups can alter means and distributions, generating faulty conclusions. Further research is warranted to explore relationships between dietary self-care and marital status, race, ethnicity, and physiological variables. ^

Bayesian dual threshold design with Dirichlet distribution: An alternative way to frequentist multi-stage phase II designs in oncology

Many phase II clinical studies in oncology use two-stage frequentist design such as Simon's optimal design. However, they have a common logistical problem regarding the patient accrual at the interim. Strictly speaking, patient accrual at the end of the first stage may have to be suspended until all patients have events, success or failure. For example, when the study endpoint is six-month progression free survival, patient accrual has to be stopped until all outcomes from stage I is observed. However, study investigators may have concern when accrual is suspended after the first stage due to the loss of accrual momentum during this hiatus. We propose a two-stage phase II design that resolves the patient accrual problem due to an interim analysis, and it can be used as an alternative way to frequentist two-stage phase II studies in oncology. ^

Evaluation of the causal pathways through which subjective norms influence mammography intention and stage of change in a national sample of women veterans

Few studies have investigated causal pathways linking psychosocial factors to each other and to screening mammography. Conflicting hypotheses exist in the theoretic literature regarding the role and importance of subjective norms, a person's perceived social pressure to perform the behavior and his/her motivation to comply. The Theory of Reasoned Action (TRA) hypothesizes that subjective norms directly affect intention; while the Transtheoretical Model (TTM) hypothesizes that attitudes mediate the influence of subjective norms on stage of change. No one has examined which hypothesis best predicts the effect of subjective norms on mammography intention and stage of change. Two statistical methods are available for testing mediation, sequential regression analysis (SRA) and latent variable structural equation modeling (LVSEM); however, software to apply LVSEM to dichotomous variables like intention has only recently become available. No one has compared the methods to determine whether or not they yield similar results for dichotomous variables. ^ Study objectives were to: (1) determine whether the effect of subjective norms on mammography intention and stage of change are mediated by pros and cons; and (2) compare mediation results from the SRA and LVSEM approaches when the outcome is dichotomous. We conducted a secondary analysis of data from a national sample of women veterans enrolled in Project H.O.M.E. (H&barbelow;ealthy O&barbelow;utlook on the M&barbelow;ammography E&barbelow;xperience), a behavioral intervention trial. ^ Results showed that the TTM model described the causal pathways better than the TRA one; however, we found support for only one of the TTM causal mechanisms. Cons was the sole mediator. The mediated effect of subjective norms on intention and stage of change by cons was very small. These findings suggest that interventionists focus their efforts on reducing negative attitudes toward mammography when resources are limited. ^ Both the SRA and LVSEM methods provided evidence for complete mediation, and the direction, magnitude, and standard errors of the parameter estimates were very similar. Because SRA parameter estimates were not biased toward the null, we can probably assume negligible measurement error in the independent and mediator variables. Simulation studies are needed to further our understanding of how these two methods perform under different data conditions. ^

The relationship between risk perception and ethnicity as an explanation for late stage skin cancer diagnosis in Black and Hispanic populations: An analysis using data from the 2005 Health Information and National Trends Survey

Objective. The purpose of this study was to determine the relationship between ethnicity and skin cancer risk perception while controlling for other risk factors: education, gender, age, access to healthcare, family history of skin cancer, fear, and worry. ^ Methods. This study utilized the Health Information National Trends Survey (HINTS) dataset, a nationally representative sample of 5,586 individuals 18 years of age or older. One third of the respondents were chosen at random and asked questions involving skin cancer. Analysis was based on questions that identified skin cancer risk perception, fear of finding skin cancer, and frequency of worry about skin cancer and a variety of sociodemographic factors. ^ Results. Ethnicity had a significant impact on risk perception scores while controlling for other risk factors. Other risk factors that also had a significant impact on risk perception scores included family history of skin cancer, age, and worry. ^

14-3-3 zeta overexpression in early stage breast disease and tumor progression

Recent progress in diagnostic tools allows many breast cancers to be detected at an early pre-invasive stage. Thus, a better understanding of the molecular basis of early breast cancer progression is essential. 14-3-3 is a family of highly conserved and ubiquitously expressed proteins that are expressed in all eukaryotic organisms. In mammals there are seven isoforms, which bind to phosphor-serine/threonine residues regulating essential cellular processes such as signal transduction, cell cycle progression, and apoptosis. Our laboratory has discovered that a particular 14-3-3 family member, Zeta, is overexpressed in over 40% of breast tumor tissues. Furthermore, I examined the stage of breast disease in which 14-3-3ζ overexpression occurs and found that increased expression of 14-3-3ζ begins at the stage of atypical ductal hyperplasia, a very early stage of breast disease that confers increased risk for progress toward breast cancer. To determine whether 14-3-3ζ overexpression is a decisive early event in breast cancer, I overexpressed 14-3-3ζ in MCF10A cells, a non-transformed mammary epithelial cell (MEC) line and examined its impact on acini formation in a three dimensional (3D) culture model which simulates a basic unit of structure in the mammary gland. I discovered that 14-3-3ζ overexpression severely disrupted the acini architecture resulting in the disruption of polarity and luminal filling. Both are critical morphological events in the pre-neoplastic breast disease. This thesis focuses on the molecular mechanism of luminal filling. Proper lumen formation is a result of anoikis, a specific type apoptosis of cells not attached to the basement membrane. I found that 14-3-3ζ overexpression conferred a resistance to anoikis. Additionally, 14-3-3ζ overexpression in MCF10A cells and in MECs from 14-3-3ζ transgenic mice reduced expression of p53, which is known to mediate anoikis. Mechanistically, 14-3-3ζ induced hyperactivation of the PI3K/Akt pathway which led to phosphorylation and translocation of the MDM2 to the nucleus resulting in increased p53 degradation. Ectopic expression of p53 restored luminal apoptosis in 14-3-3ζ overexpressing MCF10A acini in 3D cultures. These data suggest that 14-3-3ζ overexpression is a critical event in early breast disease and down-regulation of p53 is one of the mechanisms by which 14-3-3ζ alters MEC acini structure and may increase the risk of progression to breast cancer. ^

Cost-effectiveness analysis of a 2-stage community-based hepatocellular carcinoma screening program in Taiwan

Hepatocellular carcinoma (HCC) has been ranked as the top cause of death due to neoplasm malignancy in Taiwan for years. The high incidence of HCC in Taiwan is primarily attributed to high prevalence of hepatitis viral infection. Screening the subjects with liver cirrhosis for HCC was widely recommended by many previous studies. The latest practice guideline for management of HCC released by the American Association for the Study of Liver Disease (AASLD) in 2005 recommended that the high risk groups, including cirrhotic patients, chronic HBV/HCV carriers, and subjects with family history of HCC and etc., should undergo surveillance.^ This study aims to investigate (1) whether the HCC screening program can prolong survival period of the high risk group, (2) what is the incremental cost-effectiveness ratio of the HCC screening program in Taiwan, as compared with a non-screening strategy from the payer perspective, (3) which high risk group has the lowest ICER for the HCC screening program from the insurer's perspective, in comparison with no screening strategy of each group, and (4) the estimated total cost of providing the HCC screening program to all high risk groups.^ The high risk subjects in the study were identified from the communities with high prevalence of hepatitis viral infection and classified into three groups (cirrhosis group, early cirrhosis group, and no cirrhosis group) at different levels of risk to HCC by status of liver disease at the time of enrollment. The repeated ultrasound screenings at an interval of 3, 6, and 12 months were applied to cirrhosis group, early cirrhosis group, and no cirrhosis group, respectively. The Markov-based decision model was constructed to simulate progression of HCC and to estimate the ICER for each group of subjects.^ The screening group had longer survival in the statistical results and the model outcomes. Owing to the low HCC incidence rate in the community-based screening program, screening services only have limited effect on survival of the screening group. The incremental cost-effectiveness ratio of the HCC screening program was $3834 per year of life saved, in comparison with the non-screening strategy. The estimated total cost of each group from the screening model over 13.5 years approximately consumes 0.13%, 1.06%, and 0.71% of total amount of adjusted National Health Expenditure from Jan 1992 to Jun 2005. ^ The subjects at high risk of developing HCC to undergo repeated ultrasound screenings had longer survival than those without screening, but screening was not the only factor to cause longer survival in the screening group. The incremental cost-effectiveness ratio of the 2-stage community-based HCC screening program in Taiwan was small. The HCC screening program was worthy of investment in Taiwan. In comparison with early cirrhosis group and no cirrhosis group, cirrhosis group has the lowest ICER when the screening period is less than 19 years. The estimated total cost of providing the HCC screening program to all high risk groups consumes approximately 1.90% of total amount of adjusted 13.5-year NHE in Taiwan.^

Clinical relevance of polymorphic DNA copy number variation (CNV) in African American women with stage I-II breast cancer

Objectives. The chief goal of this study was to analyze copy number variation (CNV) in breast cancer tumors from 25 African American women with early stage breast cancer (BC) using molecular inversion probes (MIP) in order to: (1) compare the degree of CNV in tumors compared to normal lymph nodes, and (2) determine whether gains and/or losses of genes in specific chromosomes differ between pathologic subtypes of breast cancer defined by known prognostic markers, (3) determine whether gains/losses in CN are associated with known oncogenes or tumor suppressor genes, and (4) determine whether increased gains/losses in CN for specific chromosomes were associated with differences in breast cancer recurrence. ^ Methods. Twenty to 37 nanograms of DNA extracted from 25 formalin-fixed paraffin embedded (FFPE) tumor samples and matched normal lymph nodes were added to individual tubes. Oligonucleotide probes with recognition sequences at each terminus were hybridized with a genomic target sequence to form a circular structure. Probes are released from genomic DNA obtained from FFPE samples, and those which have been correctly "circularized" in the proper allele/nucleotide reaction combination are amplified using polymerase chain reaction (PCR) primers. Amplicons were fluorescently labeled and the tag sequences released from the genome homology regions by treatment with uracil-N-glycosylase to cleave the probe at the site where uracils are present, and detected using a complementary tag array developed by Affymetrix. ^ Results. Analysis of CN gains and losses from tumors and normal tissues showed marked differences in tumors with numerous chromosomes affected. Similar changes were not observed in normal lymph nodes. When tumors were stratified into four groups based on expression or lack of expression of the estrogen receptor and HER2/neu, distinct patterns of CNV for different chromosomes were observed. Gains or losses in CN for specific chromosomes correlated with amplifications/deletions of particular oncogenes or tumor suppressor genes (i.e. such as found on chromosome 17) known to be associated with aggressive tumor phenotype and poor prognosis. There was a trend for increases in CN observed for chromosome 17 to correlate inversely with time to recurrence of BC (p=0.14 for trend). CNV was also observed for chromosomes 5, 8, 10, 11, and 16, which are known sites for several breast cancer susceptibility alleles. ^ Conclusions. This study is the first to validate the MIP technique, to correlate differences in gene expression with known prognostic tumor markers, and to correlate significant increases/decreases in CN with known tumor markers associated with prognosis. The results of this study may have far reaching public health implications towards identifying new high-risk groups based on genomic differences in CNP, both with respect to prognosis and response to therapy, and to eventually identify new therapeutic targets for prevention and treatment of this disease. ^

Response to chemotherapy, recurrence and survival in advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish BRCA mutations, compared to those without

Objectives. Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish (AJ) BRCA founder mutations, compared to sporadic ovarian cancer patients. The purpose of this study was to determine if this association exists in ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations. In addition, we sought to account for possible "survival bias" by minimizing any lead time that may exist between diagnosis and genetic testing. ^ Methods. Patients with stage III/IV ovarian, fallopian tube, or primary peritoneal cancer and a non-Ashkenazi Jewish BRCA1 or 2 mutation, seen for genetic testing January 1996-July 2007, were identified from genetics and institutional databases. Medical records were reviewed for clinical factors, including response to initial chemotherapy. Patients with sporadic (non-hereditary) ovarian, fallopian tube, or primary peritoneal cancer, without family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, year of diagnosis, and vital status at time interval to BRCA testing. When possible, 2 sporadic patients were matched to each BRCA patient. An additional group of unmatched, sporadic ovarian, fallopian tube and primary peritoneal cancer patients was included for a separate analysis. Progression-free (PFS) & overall survival (OS) were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were calculated for variables of interest. Matched pairs were treated as clusters. Stratified log rank test was used to calculate survival data for matched pairs using paired event times. Fisher's exact test, chi-square, and univariate logistic regression were also used for analysis. ^ Results. Forty five advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations, 86 sporadic-matched and 414 sporadic-unmatched patients were analyzed. Compared to the sporadic-matched and sporadic-unmatched ovarian cancer patients, non-AJ BRCA mutation carriers had longer PFS (17.9 & 13.8 mos. vs. 32.0 mos., HR 1.76 [95% CI 1.13–2.75] & 2.61 [95% CI 1.70–4.00]). In relation to the sporadic- unmatched patients, non-AJ BRCA patients had greater odds of complete response to initial chemotherapy (OR 2.25 [95% CI 1.17–5.41]) and improved OS (37.6 mos. vs. 101.4 mos., HR 2.64 [95% CI 1.49–4.67]). ^ Conclusions. This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations, confirming the previous studies in the Jewish population. Our efforts to account for "survival bias," by matching, will continue with collaborative studies. ^

Association of left ventricular hypertrophy and stage of hypertension by ambulatory blood pressure monitor

Hypertension in adults is defined by risk for cardiovascular morbidity and mortality, but in children, hypertension is defined using population norms. The diagnosis of hypertension in children and adolescents requires only casual blood pressure measurements, but the use of ambulatory blood pressure monitoring to further evaluate patients with elevated blood pressure has been recommended in the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. The aim of this study is to assess the association between stage of hypertension (using both casual and 24 hour ambulatory blood pressure measurements) and target organ damage defined by left ventricular hypertrophy (LVH) in a sample of children and adolescents in Houston, TX. A retrospective analysis was performed on the primary de-identified data from the combination of participants in two, IRB approved, cross-sectional studies. The studies collected basic demographic data, height, weight, casual blood pressures, ambulatory blood pressures, and left ventricular measurements by echocardiography on children age 8 to 18 years old. Hypertension was defined and staged using the criteria for ambulatory blood pressure reported by Lurbe et al. [1] with some modification. Left ventricular hypertrophy was defined using left ventricular mass index (LVMI) criteria specific for children and adults. The pediatric criterion was LVMI2.7 > 95th percentile for gender and the adult criterion was LVMI2.7 > 51g/m2.7. Participants from the original studies were included in this analysis if they had complete demographic information, anthropometric measures, casual blood pressures, ambulatory blood pressures, and echocardiography data. There were 241 children and adolescents included: 19.1% were normotensive, 17.0% had white coat hypertension, 11.6% had masked hypertension, and 52.4% had confirmed hypertension. Of those with hypertension, 22.4% had stage 1 hypertension, 5.8% had stage 2 hypertension, and 24.1% had stage 3 hypertension. Participants with confirmed hypertension were more likely to have LVH by pediatric criterion than those who were normotensive [OR 2.19, 95% CI (1.04–4.63)]; LVH defined by adult criterion did not differ significantly in normotensives compared with hypertensives [OR 2.08, 95% CI (0.58–7.52)]. However, there was a significant trend in the increased prevalence of LVH across the six blood pressure categories for LVH defined by both pediatric and adult criteria (p < 0.001 and p = 0.02, respectively). Additionally, the mean LVM indexed by height 2.7 had a significantly increased trend across blood pressure stages from normal to stage 3 hypertension (p < 0.02). Pediatric hypertension is defined using population norms, and although children with mild hypertension are not at increased odds of having target organ damage defined by LVH, those with severe hypertension are more likely to have LVH. Staging hypertension by ambulatory blood pressure further describes an individual's risk for LVH target organ damage. ^

Occupational performance of Mexican Americans with end-stage-renal-disease living on dialysis in the lower Rio Grande Valley

The number of people with end-stage-renal-disease (ESRD) and living with dialysis is a growing public health concern. Most studies about the impact of ESRD on people’s lives have placed attention on the medical and clinical dimension of ESRD. Very few have given attention to the environmental and cultural context in which people with ESRD live, the adaptation that these individuals must make to adjust to living with ESRD and dialysis, or the occupations in which they engage. Additionally these studies have not focused on Mexican Americans who are disproportionately affected by this illness and condition. This qualitative study explores the needs, perceptions, and issues facing Mexican Americans with ESRD living with dialysis as well as their families. Participants were residents of the Lower Rio Grande Valley and included individuals with ESRD, family members, and the healthcare providers who give care to them. The Health Belief Model and Lifestyle Performance Model served as the theoretical frameworks. The study also explored the daily occupations of this population. ^ In-depth interviews were conducted on 15 Mexican Americans with ESRD living with dialysis, 15 family members, and six dialysis healthcare providers. A video documentary of the day-to-day life of three individuals with ESRD and their families was produced. Such data do not currently exist and will greatly enhance the understanding of the human experience of living with ESRD. The results suggest that a collective effort of the family unit is at work to deal with the demands of dialysis. An imbalance and disharmony exist among the occupational activities, which creates occupational deprivation and disruption for both the individuals and family members. Implications for practice and recommendations for further research are described. ^

Examination of the influence of behavioral, normative and control beliefs on the adherence to a prescribed renal diet among elderly populations with chronic to end-stage renal disease

The 1999-2004 prevalence of chronic kidney disease in adults 20 year or older (15.5 million) is an estimated 7.69%. The risk of developing CKD is exacerbated by diabetes, hypertension and/or a family history of kidney disease. African Americans, Hispanics, Pacific Islanders, Native Americans, and the elderly are more susceptible to higher incidence of CKD. The challenges of aging coupled with co-morbidities such as kidney disease raises the potential for malnutrition among elderly (for the purpose of this study 55 years or older) populations. Lack of adherence to prescribed nutrition guidelines specific to renal failure jeopardizes body homeostasis and increases the likelihood of future morbidity and resultant mortality. The relationship and synergy that exists between diet and disease is evident. Clinical experience with renal patients has indicated the importance of adherence to diet therapy specific to kidney disease. Extension investigation of diet adherence among endstage renal disease patients revealed a sizeable dearth in the current literature. This thesis study was undertaken to help reduce that void. The study design is qualitative and descriptive. Support, cooperation, and collaboration were provided by the University of Texas Nephrology Department, University of Texas Physicians, and DaVita Dialysis Centers. Approximately 105 male and female chronic to end-stage kidney disease patients were approached to participate in elicitation interviews in dialysis treatment facilities regarding their present diet beliefs and practices. Eighty-five were recruited and agreed to participate. Inclusion criteria required individuals to be between 35-90 years of age; capable of completing a 5-10 minute interview; and English speaking. Each kidney patient was asked seven (7) non-leading questions developed from the constructs of the Theory of Planned Behavior. The study presents a descriptive comparison of behavioral, normative, and control beliefs that influence adherence to renal diets by age, race, and gender. The study successfully concluded that behavioral, normative, and control beliefs of chronic to end-stage renal patients promoted execution and adherence to prescribed nutrition. This study provides valuable information for dietitians, technicians, nurses, and physicians to assess patient compliance toward prescribed nutrition and the means to support or improve that performance. ^