Host factors in metastasis: Direct lysis of bloodborne metastatic tumor cells by murine vascular endothelial cells

During the process of cancer metastasis, the majority of circulating tumor cells arrest in microcapillary beds and then rapidly die. To study whether vascular endothelial cells can directly lyse tumor cells, we isolated vascular endothelial cells by perfusion of lungs from immunocompetent or nude mice. The cells were grown in culture, and then cloned and characterized. Cloned endothelial cells were incubated with several lymphokines and cytokines. Cells incubated with IFN-$\gamma$ and TNF lysed a variety of tumor cells with different metastatic potential. Mouse skin and lung fibroblasts treated with the same cytokines did not. Endothelial cell mediated tumor cell lysis was not due to different binding ability of tumor cells to cytokine treated and untreated endothelial monolayers. Kinetic studies demonstrated that the continuous presence of cytokines in the tumor-endothelial cocultures was necessary to produce maximal lysis of tumor cells. Target cell lysis was not due to the direct effects of IFN-$\gamma$ or TNF, since vascular endothelial cells isolated from the lung of nude mice lysed human melanoma cells that are sensitive or resistant to TNF. Cytokine treated endothelial cells produced a high level of nitric oxide, which is known to be cytotoxic to a variety of target cells. The level of nitric oxide production was directly correlated with the degree of tumor cell lysis. A specific inhibitor of nitric oxide synthesis(N$\sp{\rm G}$-monomethyl-L-arginine), completely inhibited production of nitric oxide and tumor cell lysis. Treatment of cytokine activated endothelial cells with dexamethasone also inhibited tumor cell lysis. This inhibition was independent of tumor-endothelial adhesion but correlated with inhibition of nitric oxide production. Collectively, these results suggest that vascular endothelial cells can directly destory tumor emboli and thus play an active role in the pathogenesis of cancer metastasis. ^

Non-sexual household transmission of HCV infection: A cohort study

Objective. This study was designed to determine the prevalence and incidence of HCV infection among non-sexual household contacts of HCV-infected women and to describe the association between HCV infection and potential household risk factors in order to examine whether non-sexual household contact is a route of transmission for HCV infection. ^ Methods. A baseline prevalence survey included 409 non-sexual household contacts of 241 HCV-infected index women in the Houston area from 1994 to 1997. A total of 470 non-sexual household contacts with no evidence of HCV infection at baseline investigation were re-assessed approximately three years after baseline enrollment. Information on potential risk factors was collected through face to face interviews and blood samples were tested for anti-HCV with ELISA-2 and Matrix/RIBA-2. The relationships between HCV infection and potential risk factors were examined by using univariate and multivariate logistic regression analyses. ^ Results. The overall prevalence of anti-HCV positivity among 409 non-sexual household contacts was 4.4%. The highest prevalence of anti-HCV was found in parents (19.5%), followed by siblings (8.1%) and other relatives (5.6%); the children had the lowest prevalence of anti-HCV (1.2%). The univariate analysis showed that IDU, blood transfusion, tattoos, sexual contact with injecting drug users, more than 3 sexual partners in a lifetime, history of a STD, incarceration, previous hepatitis, and contact with hepatitis patients were significantly associated with HCV infection, however, sharing razors, nail clippers, toothbrushes, gum, food or beds with HCV-infected women, and history of dialysis, health care job, body piercing, and homosexual activities were not. Multivariate analysis found that IDU (OR = 221.7 with 95% CI of 22.8 to 2155.7) and history of a STD (OR = 11.7 with 95% CI of 1.2 to 113.1) were the only variables significantly associated with HCV infection. No such associations remained for other risk factors. The three-year cumulative incidence of anti-HCV among 352 non-sexual household contacts of HCV-infected women was zero. ^ Conclusion. This study has provided no evidence that non-sexual household contact is a likely route of transmission for HCV infection. The risk of sharing razors, nail clippers, toothbrushes, gum, food and/or beds with HCV-infected women is not evident and has not been shown to be the likely mode for HCV spread among family members. This study does suggest that IDU is the likely route of transmission for most HCV infection. Association also has been shown independently with a history of STD. The prevalence of anti-HCV among non-sexual household contacts was low. Exposure to common parenteral risk factors and sexual transmission between sexual partners may account for HCV spread among household members of HCV-infected persons. ^

Second, do less harm: The state of states' medical error reporting programs

Statement of the problem and public health significance. Hospitals were designed to be a safe haven and respite from disease and illness. However, a large body of evidence points to preventable errors in hospitals as the eighth leading cause of death among Americans. Twelve percent of Americans, or over 33.8 million people, are hospitalized each year. This population represents a significant portion of at risk citizens exposed to hospital medical errors. Since the number of annual deaths due to hospital medical errors is estimated to exceed 44,000, the magnitude of this tragedy makes it a significant public health problem. ^ Specific aims. The specific aims of this study were threefold. First, this study aimed to analyze the state of the states' mandatory hospital medical error reporting six years after the release of the influential IOM report, "To Err is Human." The second aim was to identify barriers to reporting of medical errors by hospital personnel. The third aim was to identify hospital safety measures implemented to reduce medical errors and enhance patient safety. ^ Methods. A descriptive, longitudinal, retrospective design was used to address the first stated objective. The study data came from the twenty-one states with mandatory hospital reporting programs which report aggregate hospital error data that is accessible to the public by way of states' websites. The data analysis included calculations of expected number of medical errors for each state according to IOM rates. Where possible, a comparison was made between state reported data and the calculated IOM expected number of errors. A literature review was performed to achieve the second study aim, identifying barriers to reporting medical errors. The final aim was accomplished by telephone interviews of principal patient safety/quality officers from five Texas hospitals with more than 700 beds. ^ Results. The state medical error data suggests vast underreporting of hospital medical errors to the states. The telephone interviews suggest that hospitals are working at reducing medical errors and creating safer environments for patients. The literature review suggests the underreporting of medical errors at the state level stems from underreporting of errors at the delivery level. ^

Examination of the engraftment of exogenous mesenchymal stem cells in ovarian tumors and their potential use as delivery vehicles for therapeutic genes

Interactions between neoplastic cells and the host stroma play a role in both tumor cell migration and proliferation. Stromal cells provide structural support for malignant cells, modulate the tumor microenvironment, and influence phenotypic behavior as well as the aggressiveness of the malignancy. In response, the tumor provides growth factors, cytokines, and cellular signals that continually initiate new stromal reactions and recruit new cells into the microenvironment to further support tumor growth. Since growing tumors recruit local cells, as well as supplemental cells from the circulation, such as fibroblasts and endothelial precursors, the question arises if it would be possible to access circulating stromal cells to modify the tumor microenvironment for therapeutic benefits. One such cell type, mesenchymal stem cells (MSC), could theoretically be engrafted into stroma. MSC are pluripotent cells that have been shown to form stromal elements such as myofibroblasts, perivascular tissues and connective tissues. Several reports have demonstrated that MSC can incorporate into sites of wound healing and tissue repair, due to active tissue remodeling and local paracrine factors, and given the similarity between wound healing and the carcinoma induced stromal response one can hypothesize that MSC have the potential to be recruited to sites of tumor development. In addition, gene-modified MSC could be used as cellular vehicles to deliver gene products into tumors. My results indicate that MSC home to and participate in tumor stroma formation in ovarian tumor xenografts in mice. Additionally, once homed to tumor beds, MSC proliferate rapidly and integrate. My studies aim at understanding the fate of MSC in the tumor microenvironment, as well as utilizing them for cellular delivery of therapeutic genes into the stroma of ovarian carcinomas. ^

Determining the feasibility and acceptability of a garden-based nutrition curriculum for preschoolers

Obesity rates around the nation have risen to epidemic proportions. Rates of childhood obesity are at very high levels with 24.4% of preschool-aged children in the U.S. currently considered as overweight or obese. The percentage of childhood obesity is much higher in the southern part of the United States as compared to the rest of the nation. Minority populations, especially African American and Hispanic, are affected more than other ethnic groups. Obesity prevention programs are needed targeting young children <6 years of age from minority populations. Currently, there are few obesity prevention programs that have been implemented and evaluated in children <6 years of age. Gardening programs have been successful in improving the health status of elementary school children by increasing fruit and vegetable intake and increasing preferences for healthier food choices. However, there is no evidence of the feasibility and acceptability of a garden-based obesity prevention program among preschoolers. This pretest study, a classroom-based gardening curriculum program with 16 lesson plans and coordinating activities for preschool age children (3-5 years old) enrolled in Head Start, provides the opportunity to address this need. The study included 103 preschoolers from two centers and 9 teachers or teachers' aides. Qualitative data on feasibility and acceptability was collected from process evaluation forms of individual lesson plans and focus groups with teachers. Teacher questionnaires assessed individual teacher characteristics and provided feedback regarding the curriculum. Quantitative measures of teachers' self-efficacy, attitudes, and knowledge pertaining to nutrition were analyzed from pre and post-test surveys. Results revealed this preschool garden-based nutrition curriculum was both feasible and acceptable. The program improved teacher's self-efficacy, knowledge, and attitudes about nutrition, with teacher's confidence in ability to teach a gardening curriculum increasing from a mean score of 2.14 to 3.00 from pre to post test (P value = 0.0046). These results indicate implementing garden-based nutrition lessons within preschools is achievable. Employing garden-based nutrition lessons in the classroom is the first step in teaching children about nutrition and gardening concepts. Constructing gardening beds for more hands-on learning is the next proposed step in the larger parent study of this program.^

An epidemiologic evaluation of a worksite based intervention

The healthcare industry spends billions on worker injury and employee turnover. Hospitals and healthcare settings have one of the highest rates of lost days due to injuries. The occupational hazards for healthcare workers can be classified into biological, chemical, ergonomic, physical, organizational, and psychosocial. Therefore, interventions addressing a range of occupational health risks are needed to prevent injuries and reduce turnover and reduce costs. ^ The Sacred Vocation Program (SVP) seeks to change the content of work, i.e., the meaningfulness of work, to improve work environments. The SVP intervenes at both the individual and organizational level. First the SVP attempts to connect healthcare workers with meaning from their work through a series of 5 self-discovery group sessions. In a sixth session the graduates take an oath recommitting them to do their work as a vocation. Once motivated to connect with meaning in their work, a representative employee group meets in a second set of five meetings. This representative group suggests organizational changes to create a culture that supports employees in their calling. The employees present their plan in the twelfth session to management beginning a new phase in the existing dialogue between employees and management. ^ The SVP was implemented in a large Dallas hospital (almost 1000 licensed beds). The Baylor University Medical Center (BUMC) Pastoral Care department invited front-line caregivers (primarily Patient Care Assistants, PCAs, or Patient Care Technicians, PCTs) to participate in the SVP. Participants completed SVP questionnaires at the beginning and following SVP implementation. Following implementation, employer records were collected on injury, absence and turnover to further evaluate the program's effectiveness on metrics that are meaningful to managers in assessing organizational performance. This provided an opportunity to perform an epidemiological evaluation of the intervention using the two sources of information: employee self-reports and employer administrative data. ^ The ability to evaluate the effectiveness of the SVP on program outcomes could be limited by the strength of the measures used. An ordinal CFA performed on baseline SVP questionnaire measurements examined the construct validity and reliability of the SVP scales. Scales whose item-factor structure was confirmed in ordinal CFA were evaluated for their psychometric properties (i.e., reliability, mean, ceiling and floor effects). CFA supported the construct validity of six of the proposed scales: blocks to spirituality, meaning at work, work satisfaction, affective commitment, collaborative communication, and MHI-5. Five of the six scales confirmed had acceptable measures of reliability (all but MHI-5 had α>0.7). All six scales had a high percentage (>30%) of the scores at the ceiling. These findings supported the use of these items in the evaluation of change although strong ceiling effects may hinder discerning change. ^ Next, the confirmed SVP scales were used to evaluate whether the intervention improved program constructs. To evaluate the SVP a one group pretest-posttest design compared participants’ self-reports before and after the intervention. It was hypothesized that measurements of reduced blocks to spirituality (α = 0.76), meaning at work (α = 0.86), collaborative communication (α = 0.67) and SVP job tasks (α = 0.97) would improve following SVP implementation. The SVP job tasks scale was included even though it was not included in the ordinal CFA analysis due to a limited sample and high inter-item correlation. Changes in scaled measurements were assessed using multilevel linear regression methods. All post-intervention measurements increased (increases <0.28 points) but only reduced blocks to spirituality was statistically significant (0.22 points on a scale from 1 to 7, p < 0.05) after adjustment for covariates. Intensity of the intervention (stratifying on high participation units) strengthened effects; but were not statistically significant. The findings provide preliminary support for the hypothesis that meaning in work can be improved and, importantly, lend greater credence to any observed improvements in the outcomes. (Abstract shortened by UMI.)^