Specific, Reversible Cytostatic Protection of Normal Cells Against Negative Effects of Chemotherapy

Chemotherapy is a common and effective method to treat many forms of cancer. However, treatment of cancer with chemotherapy has severe side effects which often limit the doses of therapy administered. Because some cancer chemotherapeutics target proliferating cells and tissues, all dividing cells, whether normal or tumor, are affected. Cell culture studies have demonstrated that UCN-01 is able to reversibly and selectively arrest normal dividing cells; tumor cells lines do not undergo this temporary arrest. Following UCN-01 treatment, normal cells displayed a 50-fold increase in IC50 for camptothecin; tumor cells showed no such increased tolerance. We have examined the response of the proliferating tissues of the mouse to UCN- 01 treatment, using the small bowel epithelium as a model system. Our results indicate that UCN-01 treatment can cause a cell cycle arrest in the gut epithelium, beginning 24 hours following UCN-01 administration, with cell proliferation remaining suppressed for one week. Two weeks post-UCN-01 treatment the rate of proliferation returns to normal levels. 5-FU administered during this period demonstrates that UCN-01 is able to provide protection to normal cells of the mouse within a narrow window of efficacy, from three to five days post-UCN-01. UCN-01 pretreated mice displayed improved survival, weight status and blood markers following 5-FU compared to control mice, indicating that UCN-01 can protect normal dividing tissues. The mechanism by which UCN-01 arrests normal cells in vivo was also examined. We have demonstrated that UCN-01 treatment in mice causes an increase in the G1 phase cell cycle proteins cdk4 and cyclin D, as well as the inhibitor p27. Phosphorylated Rb was also elevated in the arrested cells. These results are a departure from cell culture studies, in which inhibition of G1 phase cyclin dependent kinases led to hyposphosphorylation of Rb. Future investigation will be required to understand the mechanism of UCN-01 action. This is important information, especially for identification of alternate compounds which could provide the protection afforded by UCN-01.

Atlas of cancer mortality in the United Arab Emirates aided by application of geographic information system methods

The aim of this study was to determine cancer mortality rates for the United Arab Emirates (UAE) and to create an atlas of cancer mortality for the UAE. This atlas is the first of its kind in the Gulf country and the Middle East. Death certificates were reviewed for a period from January 1, 1990 to December 31, 1999 and cancer deaths were identified. Cancer mortality cases were verified by comparing with medical records. Age-adjusted cancer mortality rates were calculated by gender, emirate/medical district and nationality (UAE nationals and overall UAE population). Individual rates for each emirate were compared to the overall rate of the corresponding population for the same cancer site and gender. Age-adjusted rates were mapped using MapInfo software. High rates for liver, lung and stomach cancer were observed in Abu Dhabi, Dubai and the northern emirates, respectively. Rates for UAE nationals were greater compared to the overall UAE population. Several factors were suggested that may account for high rates of specific cancers observed in certain emirates. It is hoped that this atlas will provide leads that will guide further epidemiologic and public health activities aimed at preventing cancer. ^

Trends in health information seeking among cancer and non-cancer adults between 2003 and 2005: A descriptive analysis of Health Information National Trends Survey (HINTS) data

Cancer is the second leading cause of death in the United States. With the advent of new technologies, changes in health care delivery, and multiplicity of provider types that patients must see, cancer care management has become increasingly complex. The availability of cancer health information has been shown to help cancer patients cope with the management and effects of their cancers. As a result, more cancer patients are using the internet to find resources that can aid in decision-making and recovery. ^ The Health Information National Trends Survey (HINTS) is a nationally representative survey designed to collect information about the experiences of cancer and non-cancer adults with health information sources. The HINTS survey focused on both conventional sources as well as newer technologies, particularly the internet. This study is a descriptive analysis of the HINTS 2003 and HINTS 2005 survey data. The purpose of the research is to explore the general trends in health information seeking and use by US adults, and especially by cancer patients. ^ From 2003 to 2005, internet use for various health-related activities appears to have increased among adults with and without cancer. Differences were found between the groups in the general trust in information media, particularly the internet. Non-cancer respondents tended to have greater trust in information media than cancer respondents. ^ The latter portion of this work examined characteristics of HINTS respondents that were thought to be relevant to how much trust individuals placed in the internet as a source of health information. Trust in health information from the internet was significantly greater among younger adults, higher-earning households, internet users, online seekers of health or cancer information, and those who found online cancer information useful. ^

Endemic tuberculosis, the homeless, and public transportation: A merging of geographical information systems surveillance and the Houston Tuberculosis Initiative Surveillance project

To reach the goals established by the Institute of Medicine (IOM) and the Centers for Disease Control's (CDC) STOP TB USA, measures must be taken to curtail a future peak in Tuberculosis (TB) incidence and speed the currently stagnant rate of TB elimination. Both efforts will require, at minimum, the consideration and understanding of the third dimension of TB transmission: the location-based spread of an airborne pathogen among persons known and unknown to each other. This consideration will require an elucidation of the areas within the U.S. that have endemic TB. The Houston Tuberculosis Initiative (HTI) was a population-based active surveillance of confirmed Houston/Harris County TB cases from 1995–2004. Strengths in this dataset include the molecular characterization of laboratory confirmed cases, the collection of geographic locations (including home addresses) frequented by cases, and the HTI time period that parallels a decline in TB incidence in the United States (U.S.). The HTI dataset was used in this secondary data analysis to implement a GIS analysis of TB cases, the locations frequented by cases, and their association with risk factors associated with TB transmission. ^ This study reports, for the first time, the incidence of TB among the homeless in Houston, Texas. The homeless are an at-risk population for TB disease, yet they are also a population whose TB incidence has been unknown and unreported due to their non-enumeration. The first section of this dissertation identifies local areas in Houston with endemic TB disease. Many Houston TB cases who reported living in these endemic areas also share the TB risk factor of current or recent homelessness. Merging the 2004–2005 Houston enumeration of the homeless with historical HTI surveillance data of TB cases in Houston enabled this first-time report of TB risk among the homeless in Houston. The homeless were more likely to be US-born, belong to a genotypic cluster, and belong to a cluster of a larger size. The calculated average incidence among homeless persons was 411/100,000, compared to 9.5/100,000 among housed. These alarming rates are not driven by a co-infection but by social determinants. The unsheltered persons were hospitalized more days and required more follow-up time by staff than those who reported a steady housing situation. The homeless are a specific example of the increased targeting of prevention dollars that could occur if TB rates were reported for specific areas with known health disparities rather than as a generalized rate normalized over a diverse population. ^ It has been estimated that 27% of Houstonians use public transportation. The city layout allows bus routes to run like veins connecting even the most diverse of populations within the metropolitan area. Secondary data analysis of frequent bus use (defined as riding a route weekly) among TB cases was assessed for its relationship with known TB risk factors. The spatial distribution of genotypic clusters associated with bus use was assessed, along with the reported routes and epidemiologic-links among cases belonging to the identified clusters. ^ TB cases who reported frequent bus use were more likely to have demographic and social risk factors associated with poverty, immune suppression and health disparities. An equal proportion of bus riders and non-bus riders were cultured for Mycobacterium tuberculosis, yet 75% of bus riders were genotypically clustered, indicating recent transmission, compared to 56% of non-bus riders (OR=2.4, 95%CI(2.0, 2.8), p<0.001). Bus riders had a mean cluster size of 50.14 vs. 28.9 (p<0.001). Second order spatial analysis of clustered fingerprint 2 (n=122), a Beijing family cluster, revealed geographic clustering among cases based on their report of bus use. Univariate and multivariate analysis of routes reported by cases belonging to these clusters found that 10 of the 14 clusters were associated with use. Individual Metro routes, including one route servicing the local hospitals, were found to be risk factors for belonging to a cluster shown to be endemic in Houston. The routes themselves geographically connect the census tracts previously identified as having endemic TB. 78% (15/23) of Houston Metro routes investigated had one or more print groups reporting frequent use for every HTI study year. We present data on three specific but clonally related print groups and show that bus-use is clustered in time by route and is the only known link between cases in one of the three prints: print 22. (Abstract shortened by UMI.)^

HPV knowledge, HPV vaccine awareness and initiation among Hispanics: The role of language, information seeking, and information scanning

Background. Among Hispanics, the HPV vaccine has the potential to eliminate disparities in cervical cancer incidence and mortality but only if optimal rates of vaccination are achieved. Media can be an important information source for increasing HPV knowledge and awareness of the vaccine. Very little is known about how media use among Hispanics affects their HPV knowledge and vaccine awareness. Even less is known about what differences exist in media use and information processing among English- and Spanish-speaking Hispanics.^ Aims. Examine the relationships between three health communication variables (media exposure, HPV-specific information scanning and seeking) and three HPV outcomes (knowledge, vaccine awareness and initiation) among English- and Spanish-speaking Hispanics.^ Methods. Cross-sectional data from a survey administered to Hispanic mothers in Dallas, Texas was used for univariate and multivariate logistic regression analyses. Sample used for analysis included 288 mothers of females aged 8-22 recruited from clinics and community events. Dependent variables of interest were HPV knowledge, HPV vaccine awareness and initiation. Independent variables were media exposure, HPV-specific information scanning and seeking. Language was tested as an effect modifier on the relationship between health communication variables and HPV outcomes.^ Results. English-speaking mothers reported more media exposure, HPV-specific information scanning and seeking than Spanish-speakers. Scanning for HPV information was associated with more HPV knowledge (OR = 4.26, 95% CI = 2.41 - 7.51), vaccine awareness (OR = 10.01, 95% CI = 5.43 - 18.47) and vaccine initiation (OR = 2.54, 95% CI = 1.09 - 5.91). Seeking HPV-specific information was associated with more knowledge (OR = 2.27, 95% CI = 1.23 - 4.16), awareness (OR = 6.60, 95% CI = 2.74 - 15.91) and initiation (OR = 4.93, 95% CI = 2.64 - 9.20). Language moderated the effect of information scanning and seeking on vaccine awareness.^ Discussion. Differences in information scanning and seeking behaviors among Hispanic subgroups have the potential to lead to disparities in vaccine awareness.^ Conclusion. Findings from this study underscore health communication differences among Hispanics and emphasize the need to target Spanish language media as well as English language media aimed at Hispanics to improve knowledge and awareness.^

Global practice experience: A useful lens for understanding patient and staff perceptions of successful integration of health information technology in primary care

Making healthcare comprehensive and more efficient remains a complex challenge. Health Information Technology (HIT) is recognized as an important component of this transformation but few studies describe HIT adoption and it's effect on the bedside experience by physicians, staff and patients. This study applied descriptive statistics and correlation analysis to data from the Patient-Centered Medical Home National Demonstration Project (NDP) of the American Academy of Family Physicians. Thirty-six clinics were followed for 26 months by clinician/staff questionnaires and patient surveys. This study characterizes those clinics as well as staff and patient perspectives on HIT usefulness, the doctor-patient relationship, electronic medical record (EMR) implementation, and computer connections in the practice throughout the study. The Global Practice Experience factor, a composite score related to key components of primary care, was then correlated to clinician and patient perspectives. This study found wide adoption of HIT among NDP practices. Patient perspectives on HIT helpfulness on the doctor-patient showed a suggestive trend that approached statistical significance (p = 0.172). Clinicians and staff noted successful integration of EMR into clinic workflow and their perception of helpfulness to the doctor-patient relationship show a suggestive increase also approaching statistical significance (p=0.06). GPE was correlated with clinician/staff assessment of a helpful doctor-patient relationship midway through the study (R 0.460, p = 0.021) with the remaining time points nearing statistical significance. GPE was also correlated to both patient perspectives of EMR helpfulness in the doctor-patient relationship (R 0.601, p = 0.001) and computer connections (R 0.618, p = 0.0001) at the start of the study. ^