Development and validation of the Neuro Symptom Inventory in the primary brain tumor patient population

Symptoms has been shown to predict quality of life, treatment course and survival in solid tumor patients. Currently, no instrument exists that measures both cancer-related symptoms and the neurologic symptoms that are unique to persons with primary brain tumors (PBT). The aim of this study was to develop and validate an instrument to measure symptoms in patients who have PBT. A conceptual analysis of symptoms and symptom theories led to defining the symptoms experience as the perception of the frequency, intensity, distress, and meaning that occurs as symptoms are produced, perceived, and expressed. The M.D. Anderson Symptom Inventory (MDASI) measures both symptoms and how they interfere with daily functioning in patients with cancer, which is similar to the situational meaning defined in the analysis. A list of symptoms pertinent to the PBT population was added to the core MDASI and reviewed by a group of experts for validity. As a result, 18 items were added to the core MDASI (the MDASI-BT) for the next phase of instrument development, establishing validity and reliability through a descriptive, cross-sectional approach with PBT patients. Data were collected with a patient completed demographic data sheet, an investigator completed clinician checklist, and the MDASI-BT. Analysis evaluated the reliability and validity of the MDASI-BT in PBT patients. Data were obtained from 201 patients. The number of items was reduced to 22 by evaluation of symptom severity as well as cluster analysis. Regression analysis showed more than half (56%) of the variability in symptom severity was explained by the brain tumor module items. Factor analysis confirmed that the 22 item MDASI-BT measured six underlying constructs: (a) affective; (b) cognitive; (c) focal neurologic deficits; (d) constitutional symptoms; (e) treatment-related symptoms; and (f) gastrointestinal symptoms. The MDASI-BT was sensitive to disease severity and if the patient was hospitalized. The MDASI-BT is the first instrument to measure symptoms in PBT patients that has demonstrated reliability and validity. It is the first step in a program of research to evaluate the occurrence of symptoms and plan and evaluate interventions for PBT patients. ^

A conditional Mdm2 allele shows the importance of Mdm2 in heart development

Over 50% of sporadic tumors in humans have a p53 mutation highlighting its importance as a tumor suppressor. Considering additional mutations in other genes involved in p53 pathways, every tumor probably has mutant p53 or impaired p53-mediated functions. In response to a variety of cellular and genotoxic stresses, p53, mainly through its transcriptional activity, induces pathways involved in apoptosis and growth arrest. In these circumstances and under normal situations, p53 must be tightly regulated. Mdm2 is an important regulator of p53. Mdm2 inhibits p53 function by binding and blocking its transactivation domain. In addition, Mdm2 helps target p53 for degradation through its E3 ligase activity. Mdm2 null mice are embryonic lethal due to apoptosis in the blastocysts. However, a p53 null background rescues this lethality demonstrating the importance of the p53-Mdm2 interaction, particularly during development. The lethality of the Mdm2 null mouse prior to implantation limits the ability to investigate the role of Mdm2 in regulating p53 in a temporal and tissue specific manner. Does p53 need to be regulated in all tissues throughout the life of a mouse? Does Mdm2 always have to regulate it? To address these questions, we created a conditional Mdm2 allele. The conditional allele, Mdm2FM, in the presence of Cre recombinase results in the deletion of exons 5 and 6 of Mdm2 (most of the p53 binding domain) and represents a null allele. ^ The Mdm2FM allele was crossed with a heart muscle specific Cre expressing mouse (α-myosin heavy chain promoter driven Cre) to ask whether Mdm2 acts as a negative regulator of p53 in the heart. The heart is the most prominent organ early in embryogenesis and is shaped by cell death and proliferation. p53 does not appear to be active in the heart in response to some types of stress, so it remained to be determined if it has to be regulated in normal heart development. Loss of Mdm2 in the heart results in heart defects as early as E9.5. Loss of Mdm2 results in stabilized p53 and apoptosis. This apoptosis leads to a thinning of the myocardial wall particularly in the ventricles and abnormal ventricular structure. Eventually the abnormal heart fails resulting in lethality by E13.5. The embryonic lethality is rescued in a p53 null background. Thus, Mdm2 is important in regulating p53 in the development of the heart. ^

Generation of an hTERT-restricted, CMV-augmented oncolytic adenovirus capable of tumor-specific transgene expression: Development, characterization, and optimization

Current shortcomings in cancer therapy require the generation of new, broadly applicable, potent, targeted treatments. Here, an adenovirus is engineered to replicate specifically in cells with active human telomerase promotion using a modified hTERT promoter, fused to a CMV promoter element. The virus was also modified to contain a visible reporter transgene, GFP. The virus, Ad/hTC-GFP-E1 was characterized in vitro and demonstrated tumor specific activity both by dose and over time course experiments in a variety of cell lines. In vivo, Ad/hTC-GFP-E1 was affected at suppressing tumor growth and providing a survival benefit without causing any measurable toxicity. To increase the host range of the vector, the fiber region was modified to contain an RGD-motif. The vector, AdRGD/hTC-GFP-E1, was recharacterized in vitro, revealing heightened levels of infectivity and toxicity however maintaining a therapeutic window between cancer and normal cell toxicity. AdRGD/hTC-GFP-E1 was administered in vivo by limb perfusion and was observed to be tumor specific both in expression and replication. To further enhance the efficacy of viral vectors in lung delivery, asthma medications were investigated for their abilities to enhance transgene delivery and expression. A combination of bronchodilators, mast cell inhibitors, and mucolytic agents was devised which demonstrated fold increases in expression in immunocompetent mouse lungs as single agents and more homogenous, intense levels of expression when done in combination of all agents. To characterize the methods in which some cancers are resistant or may become resistant to oncolytic treatments, several small molecule inhibitors of metabolic pathways were applied in combination with oncolytic infection in vitro. SP600125 and PD 98059, respective JNK and ERK inhibitors, successfully suppressed oncolytic toxicity, however did not affect infectivity or transgene expression of Ad/hTC-GFP-E1. JNK and ERK inhibition did significantly suppress viral replication, however, as analyzed by lysate transfer and titration assays. In contrast, SB 203580, an inhibitor for p38, did not demonstrate any protective effects with infected cells. Flow cytometric analysis indicated a possible correlation with G1 arrest and suppressed viral production, however more compounds must be investigated to clarify this observation. ^

Identification and characterization of new genes involved in Drosophila heart development

Heart development is a crucial and conserved process that is related to the major type of human birth defects. Dorsal vessel, the Drosophila heart, has been regarded as an insightful system to identify new genes and study gene functions involved in heart development. Using heart-specific GFP transgenes, I did a genetic screen for cardiogenic genes on Drosophila chromosome II. Drosophila mutants that carry chromosome II deficiencies were tested for their phenotypes of heart development. Based on the screen results, chromosome regions containing genes required for heart development were identified. Fly strains with single gene mutations located within the defined deficiency regions were tested further. Seven genes have been identified to be involved in heart development. ^ The LIM homeodomain transcription factor gene tailup (tup) was further studied for its function in heart development. Based on this study, tup is expressed in cardioblasts and pericardial cells of the heart tube, as well as in associated lymph glands and alary muscles. In depth analysis of tup mutant phenotypes demonstrated tup is required for normal development of both heart and lymph glands. Tup was shown to bind to two DNA recognition sequences in the dorsal vessel enhancer of the Hand bHLH transcription factor gene, with one site proven essential for the expression of Hand in lymph glands, pericardial cells, and Svp/Doc cardioblasts. Together, these studies demonstrate that Tup is a critical new transcription factor in dorsal vessel morphogenesis and lymph gland formation, and strongly suggest Tup is a direct regulator of the expression of Hand in these developmental processes. ^

The medical malpractice insurance "crises" and federal medical malpractice tort reform: Collection and analysis of bills passed by the United States House of Representatives from 1995--2005

There have been three medical malpractice insurance "crises" in the United States over a time spanning roughly the past three decades (Poisson, 2004, p. 759-760). Each crisis is characterized by a number of common features, including rapidly increasing medical malpractice insurance premiums, cancellation of existing insurance policies, and a decreased willingness of insurers to offer or renew medical malpractice insurance policies (Poisson, 2004, p. 759-760). Given the recurrent "crises," many sources argue that medical malpractice insurance coverage has become too expensive a commodity—one that many physicians simply cannot afford (U.S. Department of Health and Human Services [HHS], 2002, p. 1-2; Physician Insurers Association of America [PIAA], 2003, p. 1; Jackiw, 2004, p. 506; Glassman, 2004, p. 417; Padget, 2003, p. 216). ^ The prohibitively high cost of medical liability insurance is said to limit the geographical areas and medical specializations in which physicians are willing to practice. As a result, the high costs of medical liability insurance are ultimately said to affect whether or not people have access to health care services. ^ In an effort to control the medical liability insurance crises—and to preserve or restore peoples' access to health care—every state in the United States has passed "at least some laws designed to reduce medical malpractice premium rates" (GAO, 2003, p.5-6). More recently, however, the United States has witnessed a push to implement federal reform of the medical malpractice tort system. Accordingly, this project focuses on federal medical malpractice tort reform. This project was designed to investigate the following specific question: Do the federal medical malpractice tort reform bills which passed in the House of Representatives between 1995 and 2005 differ in respect to their principle features? To answer this question, the text of the bills, law review articles, and reports from government and private agencies were analyzed. Further, a matrix was compiled to concisely summarize the principle features of the proposed federal medical malpractice tort reform bills. Insight gleaned from this investigation and matrix compilation informs discussion about the potential ramifications of enacting federal medical malpractice tort reform legislation. ^

Development and formative evaluation of an obesity prevention intervention for the pediatric primary care setting: Helping HAND (Healthy Activity and Nutrition Directions)

As the obesity epidemic continues to increase, the pediatric primary care office setting remains a relatively unexplored arena to offer obesity prevention interventions for children. The increased risk for adult obesity among 10 to 14 year-old children who are overweight, suggests obesity prevention programs should be introduced just before this age or early in this age period. Research is also accumulating on the importance of targeting parents along with children, since parents are in charge of the home environment for children. Therefore, the aim of this project was to develop an obesity prevention program called Helping HAND (Healthy Activity and Nutrition Directions) based on Social Cognitive Theory and authoritative parenting techniques for the pediatric primary care setting and conduct one-on-one interviews with parents as the initial formative evaluation of the intervention material for the obesity prevention intervention. A secondary aim of the project was to determine the feasibility of identifying appropriate subjects for the intervention, and conducting qualitative evaluations of the materials through recruitment through pediatric primary care settings. ^

The Skip To Breakfast project: Development, implementation, and feasibility evaluation of an intervention to increase healthful breakfast consumption among fifth grade students and their families

Children and adults frequently skip breakfast and rates are currently increasing. In addition, the food choices made for breakfast are not always healthy ones. Breakfast skipping, in conjunction with unhealthy breakfast choices, leads to impaired cognitive functioning, poor nutrient intake, and overweight. In response to these public health issues, Skip To Breakfast, a behaviorally based school and family program, was created to increase consistent and healthful breakfast consumption among ethnically diverse fifth grade students and their families, using Intervention Mapping™. Four classroom lessons and four parent newsletters were used to deliver the intervention. For this project, a healthy, "3 Star Breakfast" was promoted, and included a serving each of dairy product, whole grain, and fruit, each with an emphasis on being low in fat and sugar. The goal of this project was to evaluate the feasibility and acceptability of the intervention. A pilot-test of the intervention was conducted in one classroom, in a school in Houston, during the Fall 2007 semester. A qualitative evaluation of the intervention was conducted, which included focus groups with students, phone interviews of parents, process evaluation data from the classroom teacher, and direct observation. Sixteen students and six parents participated in the study. Data were recorded and themes were identified. Initial results showed there is a need for such programs. Based on the initial feedback, edits were made to the intervention and program. Results showed high acceptability among the teacher, students, and parents. It became apparent that students were not reliably getting the parent newsletters to their parents to read, so a change to the protocol was made, in which students will receive incentives for having parents read newsletters and return signed forms, to increase parent participation. Other changes included small modifications to the curriculum, such as, clarifying instructions, changing in-class assignments to homework assignments, and including background reading materials for the teacher. The main trial is planned to be carried out in Spring 2008, in two elementary schools, utilizing four, fifth grade classes from each, with one school acting as the control and one as the intervention school. Results from this study can be used as an adjunct to the Coordinated Approach To Child Health (CATCH) program. ^

Development and preliminary validation of the cancer family impact scale for colorectal cancer

This study aimed to develop and validate The Cancer Family Impact Scale (CFIS), an instrument for use in studies investigating relationships among family factors and colorectal cancer (CRC) screening when family history is a risk factor. We used existing data to develop the measure from 1,285 participants (637 families) across the United States who were in the Johns Hopkins Colon Cancer Genetic Testing study. Participants were 94% white with an average age of 50.1 years, and 60% were women. None had a personal CRC history, and eighty percent had 1 FDR with CRC and 20% had more than one FDR with CRC. The study had three aims: (1) to identify the latent factors underlying the CFIS via exploratory factor analysis (EFA); (2) to confirm the findings of the EFA via confirmatory factor analysis (CFA); and (3) to assess the reliability of the scale via Cronbach's alpha. Exploratory analyses were performed on a split half of the sample, and the final model was confirmed on the other half. The EFA suggested the CFIS was an 18-item measure with 5 latent constructs: (1) NEGATIVE: negative effects of cancer on the family; (2) POSITIVE: positive effects of cancer on the family; (3) COMMUNICATE: how families communicate about cancer; (4) FLOW: how information about cancer is conveyed in families; and (5) NORM: how individuals react to family norms about cancer. CFA on the holdout sample showed the CFIS to have a reasonably good fit (Chi-square = 389.977, df = 122, RMSEA= 0.058 (.052-.065), CFI=.902, TLI=.877, GF1=.939). The overall reliability of the scale was α=0.65. The reliability of the subscales was: (1) NEGATIVE α = 0.682; (2) POSITIVE α = 0.686; (3) COMMUNICATE α = 0.723; (4) FLOW α = 0.467; and (5) NORM α = 0.732. ^ We concluded the CFIS to be a good measure with most fit levels over 0.90. The CFIS could be used to compare theoretically driven hypotheses about the pathways through which family factors could influence health behavior among unaffected individuals at risk due to family history, and also aid in the development and evaluation of cancer prevention interventions including a family component. ^

Insulin-like growth factor binding protein 2 (IGFBP2) promotes glioma development and progression

Overexpression of insulin-like growth factor binding protein 2 (IGFBP2) is associated with progression and poor survival in many types of human cancer (such as prostate, ovarian, adrenocortical, breast, colorectal carcinomas, leukemia, and high-grade gliomas). We therefore hypothesize that IGFBP2 is a key regulator of tumor progression. We tested our hypothesis in gliomas using the somatic gene transfer RCAS-tva mouse model system, which permits the introduction of specific genes into specific, cell lineages, in this case glial cells (RCAS: Replication competent avian sarcomavirus, tv-a: avian RCAS virus receptor). Mice are transgenic and harbor the tv-a receptor under the control of a glial-specific promoter and study genes are cloned into the RCAS vector for post-natal intracranial delivery. For these experiments, the study genes were IGFBP2, platelet-derived growth factor B (PDGFB), K-Ras, Akt, and IIp45 (invasion inhibitory protein 45 kDa; known to bind and block IGFBP2 activity), which were delivered separately and in combination. Our results show that PDGFB signaling leads exclusively to the formation of low-grade (WHO grade II) oligodendrogliomas. PDGFB delivered in combination with IGFBP2 results in the formation of anaplastic oligodendrogliomas (WHO grade III), which are characterized by increased cellularity, vascular proliferation, small regions of necrosis, increased mitotic activity, and increased activation of the Akt pathway. IIp45 injected in combination with PDGFB and IGFBP2 ablates IGFBP2-induced tumor progression, which results in formation of low-grade oligodendrogliomas, and an overall reduction in tumor incidence. K-Ras expression was required to form astrocytomas with either IGFBP2 or Akt, indicating the activation of two separate pathways is necessary for gliomagenesis. In ex vivo experiments, blockade of Akt by an inhibitor led to decreased viability of cells co-expressing IGFBP2 versus PDGFB expression alone. This study provides definitive evidence, for the first time, that: (1) IGFBP2 plays a role in activation of the Akt pathway, (2) IGFBP2 collaborates with K-Ras or PDGFB in the development and progression of two major types of glioma, and (3) IGFBP2-induced tumor progression can be ablated by IIp45 or by specific inhibition of the Akt pathway. ^

Modeling survival and the development of second primary tumors among Hodgkin's disease patients

Hodgkin's disease (HD) is a cancer of the lymphatic system. Survivors of HD face varieties of consequent adverse effects, in which secondary primary tumors (SPT) is one of the most serious consequences. This dissertation is aimed to model time-to-SPT in the presence of death and HD relapses during follow-up.^ The model is designed to handle a mixture phenomenon of SPT and the influence of death. Relapses of HD are adjusted as a covariate. Proportional hazards framework is used to define SPT intensity function, which includes an exponential term to estimate explanatory variables. Death as a competing risk is considered according to different scenarios, depending on which terminal event comes first. Newton-Raphson method is used to estimate the parameter estimates in the end.^ The proposed method is applied to a real data set containing a group of HD patients. Several risk factors for the development of SPT are identified and the findings are noteworthy in the development of healthcare guidelines that may lead to the early detection or prevention of SPT.^

Role of IkappaB kinase beta in inflammation-mediated breast cancer development

Breast cancer is the second most common farm of cancers and the second leading cause of cancer death for American women. Clinical studies indicate inflammation is a risk factor for breast cancer development. Among the cytokines and chemokines secreted by the infiltrating inflammatory cells, tumor necrosis factor a (TNFα) is considered one of the most important inflammatory factors involved in inflammation-mediated tumorigenesis. ^ Here we found that TNFα/IKKβ signaling pathway is able to increase tumor angiogenesis through activation of mTOR pathway. While investigating which molecule in the mTOR pathway involved in TNFα/IKKβ-mediated mTOR activation, our results showed that IKKβ physically interacts with and phosphorylates TSC1 at Ser487 and Ser511 in vitro and in vivo. Phosphorylation of TSC1 by IKKβ inhibits its association with TSC2, alters TSC2 membrane localization, and thereby activates mTOR. In vitro angiogenesis assays and orthotopic breast cancer model reveals that phosphorylation of TSC1 by IKKβ enhances VEGF expression, angiogenesis and culminates in tumorigenesis. Furthermore, expression of activated IKKβ is associated with TSC1 Ser511 phosphorylation and VEGF production in multiple tumor types and correlates with poor clinical outcome of breast cancer patients. ^ Furthermore, dysregulation of tumor suppressor FOXO3a contributes to the development of breast cancer. We found that overexpression of IKKβ led to inhibition of FOXO3a-mediated transactivation activity. While investigating the underlying mechanisms of IKKβ-mediated dysregulation of FOXO3a, our results showed that IKKβ physically associated with FOXO3a and phosphorylated FOXO3a at Ser644 in vitro and in vivo. The phosphorylation of FOXO3a by IKKβ altered its subcellular localization from nucleus to cytoplasm and promoted its degradation through ubiquitin-proteasome pathway. Mutation of FOXO3a at Ser644 prevented IKKβ-induced ubiquitination and degradation. In vitro cell proliferation assay and orthotopic breast cancer model revealed that phosphorylation of FOXO3a by IKKβ overrode FOXO3a-mediated repression of tumor progression. ^ In conclusion, our findings identify IKKβ-mediated suppressions of both TSC1 and FOXO3a are critical for inflammation-mediated breast cancer development through increasing tumor angiogenesis and evading apoptosis, respectively. Understanding the role of IKKβ in both FOXO3a and TSC/mTOR signaling pathways provides a critical insight of inflammation-mediated diseases and may provide a target for clinical intervention in human breast cancer. ^

Use of cognitive interviewing in the development of a Spanish language genetic knowledge instrument

Study purpose. Genetic advances are significantly impacting healthcare, yet recent studies of ethnic group participation in genetic services demonstrate low utilization rates by Latinos. Limited genetic knowledge is a major barrier. The purpose of this study was to field test items in a Spanish-language instrument that will be used to measure genetic knowledge relevant to type 2 diabetes among members of the ethnically heterogeneous U.S. Latino community. Accurate genetic knowledge measurement can provide the foundation for interventions to enhance genetic service utilization. ^ Design. Three waves of cognitive interviews were conducted in Spanish to field test 44 instrument items Thirty-six Latinos, with 12 persons representative of Mexican, Central and South American, and Cuban heritage participated, including 7 males and 29 females between 22 and 60 years of age; 17 participants had 12 years or less of education. ^ Methods. Text narratives from transcriptions of audiotaped interviews were qualitatively analyzed using a coding strategy to indicate potential sources of response error. Through an iterative process of instrument refinement, codes that emerged from the data were used to guide item revisions at the conclusion of each phase; revised items were examined in subsequent interview waves. ^ Results. Inter-cultural and cross-cultural themes associated with difficulties in interpretation and grammatical structuring of items were identified; difficulties associated with comprehension reflected variations in educational level. Of the original 44 items, 32 were retained, 89% of which were revised. Six additional items reflective of cultural knowledge were constructed, resulting in a 38-item instrument. ^ Conclusions. Use of cognitive interviewing provided a valuable tool for detecting both potential sources of response error and cultural variations in these sources. Analysis of interview data guided successive instrument revisions leading to improved item interpretability and comprehension. Although testing in a larger sample will be essential to test validity and reliability, the outcome of field testing suggests initial content validity of a Spanish-language instrument to measure genetic knowledge relative to type 2 diabetes. ^ Keywords. Latinos, genetic knowledge, instrument development, cognitive interviewing ^

A project to improve the information seeking skills and increase the use of evidence-based research in public health practice

The ability of public health practitioners (PHPs) to work efficiently and effectively is negatively impacted by their lack of knowledge of the broad range of evidence-based practice information resources and tools that can be utilized to guide them in their development of health policies and programs. This project, a three-hour continuing education hands-on workshop with supporting resources, was designed to increase knowledge and skills of these resources. The workshop was presented as a pre-conference continuing education program for the Texas Public Health Association (TPHA) 2008 Annual Conference. Topics included: identification of evidence-based practice resources to aid in the development of policies and programs; identification of sources of publicly available data; utilization of data for community assessments; and accessing and searching the literature through a collection of databases available to all citizens of Texas. Supplemental resources included a blog that served as a gateway to the resources explored during the presentation, a community assessment workbook that incorporates both Healthy People 2010 objectives and links to reliable sources of data, and handouts providing additional instruction on the use of the resources covered during the workshop.^ Before- and after-workshop surveys based on Kirkpatrick's 4-level model of evaluation and the Theory of Planned Behavior were administered. Of the questions related to the trainer, the workshop, and the usefulness of the workshop, participants gave "Good" to "Excellent" responses to all one question. Confidence levels overall increased a statistically significant amount; measurements of attitude, social norms, and control showed no significant differences before and after the workshop. Lastly, participants indicated they were likely to use resources shown during the workshop within a one to three month time period on average. ^ The workshop and creation of supplemental resources served as a pilot for a funded project that will be continued with the development and delivery of four 4-week long webinar-based training sessions to be completed by December 2008. ^

Analysis of prognostic factors for the development of metastases and survival in renal cell carcinoma patients

Introduction and objective. A number of prognostic factors have been reported for predicting survival in patients with renal cell carcinoma. Yet few studies have analyzed the effects of those factors at different stages of the disease process. In this study, different stages of disease progression starting from nephrectomy to metastasis, from metastasis to death, and from evaluation to death were evaluated. ^ Methods. In this retrospective follow-up study, records of 97 deceased renal cell carcinoma (RCC) patients were reviewed between September 2006 to October 2006. Patients with TNM Stage IV disease before nephrectomy or with cancer diagnoses other than RCC were excluded leaving 64 records for analysis. Patient TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were analyzed in relation to time to metastases. Time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from metastases to death. Finally, analysis of laboratory values at time of evaluation, Eastern Cooperative Oncology Group performance status (ECOG), UCLA Integrated Staging System (UISS), time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from evaluation to death. Linear regression and Cox Proportional Hazard (univariate and multivariate) was used for testing significance. Kaplan-Meier Log-Rank test was used to detect any significance between groups at various endpoints. ^ Results. Compared to negative lymph nodes at time of nephrectomy, a single positive lymph node had significantly shorter time to metastasis (p<0.0001). Compared to other histological types, clear cell histology had significant metastasis free survival (p=0.003). Clear cell histology compared to other types (p=0.0002 univariate, p=0.038 multivariate) and time to metastasis with log conversion (p=0.028) significantly affected time from metastasis to death. A greater than one year and greater than two year metastasis free interval, compared to patients that had metastasis before one and two years, had statistically significant survival benefit (p=0.004 and p=0.0318). Time from evaluation to death was affected by greater than one year metastasis free interval (p=0.0459), alcohol consumption (p=0.044), LDH (p=0.006), ECOG performance status (p<0.001), and hemoglobin level (p=0.0092). The UISS risk stratified the patient population in a statistically significant manner for survival (p=0.001). No other factors were found to be significant. ^ Conclusion. Clear cell histology is predictive for both time to metastasis and metastasis to death. Nodal status at time of nephrectomy may predict risk of metastasis. The time interval to metastasis significantly predicts time from metastasis to death and time from evaluation to death. ECOG performance status, and hemoglobin levels predicts survival outcome at evaluation. Finally, UISS appropriately stratifies risk in our population. ^

The association between uterus shape and development of chronic conditions in a retrospective corhort of diethylstilbestrol-exposed women in Minnesota and Texas

Diethylstilbestrol (DES) exposed women are well known to be at increased risk of gynecologic cancers and infertility. Infertility may result from DES associated abnormalities in the shape of women's uteri, yet little research has addressed the effect of uterine abnormalities on risk of infertility and reproductive tract infection. Changes in uterine shape may also influence the risk of autoimmune disease and women's subsequent mental health. A sample of consenting women exposed in utero to hormone who were recruited into the DESAD project, underwent hysterosalpingogram (HSG) from 1978 to 1984. These women also completed a comprehensive health questionnaire in 1994 which included women's self-reports of chronic conditions. HSG data were used to categorize uterine shape abnormalities as arcuate shape, hypoplastic, wide lower segment, and constricted. Women were recruited from two of the four DESAD study sites in Houston (Baylor) and Minnesota (Mayo). All women were DES-exposed. Adjusted relative risk estimates were calculated comparing the range of abnormal uterine shaped to women with normal shaped uteri for each of the four outcomes: infertility, reproductive tract infection, autoimmune disease and depressive symptoms. Only the arcuate shape (n=80) was associated with a higher risk of infertility (relative risk [RR]= 1.53, 95% CI = 1.09, 2.15) as well as reproductive tract infection (RR= 1.74, 95% CI = 1.11, 2.73). In conclusion, DES-associated arcuate shaped uteri appeared to be associated with the higher risk of a reproductive tract infection and infertility while no other abnormal uterine shapes were associated with these two outcomes.^