THE ROLE OF PLATELETS IN OVARIAN CARCINOMA

Platelets represent one of the largest storage pools of angiogenic and oncogenic growth factors in the human body. The observation that thrombocytosis (platelet count >450,000/uL) occurs in patients with solid malignancies was made over 100 years ago. However, the clinical and biological implications as well as the underlying mechanism of paraneoplastic thrombocytosis associated with ovarian carcinoma remains unknown and were the focus of the current study. Following IRB approval, patient data were collected on 619 patients from 4 U.S. centers and used to test associations between platelet count at initial diagnosis, clinicopathologic factors, and outcome. In vitro effects of plasma-purified platelets on ovarian cancer cell proliferation, docetaxel-induced apoptosis, and migration were evaluated using BrdU-PI flow cytometric and two-chamber chemotaxis assays. In vivo effects of platelet depletion on tumor growth, proliferation, apoptosis, and angiogenesis were examined using an anti-platelet antibody (anti-mouse glycoprotein 1ba, Emfret) to reduce platelets by 50%. Complete blood counts and number of mature megakaryocytes in the spleen and bone marrow were compared between control mice and ovarian cancer-bearing mice. Plasma levels of key megakaryo- and thrombopoietic factors including thrombopoietin (TPO), IL-1a, IL-3, IL-4, IL-6, IL-11, G-CSF, GM-CSF, stem cell factor, and FLT-3 ligand were assayed in a subset of 150 patients at the time of initial diagnosis with advanced stage, high grade epithelial ovarian cancer using immunobead-based cytokine profiling coupled with the Luminex® xMAP platform. Plasma cytokines significantly associated with thrombocytosis in ovarian cancer patients were subsequently evaluated in mouse models of ovarian cancer using ELISA immunoassays. The results of human and mouse plasma cytokine profiling were used to inform subsequent in vivo studies evaluating the effect of siRNA-induced silencing of select megakaryo- and thrombopoietic cytokines on paraneoplastic thrombocytosis. Thirty-one percent of patients had thrombocytosis at initial diagnosis. Compared to patients with normal platelet counts, women with thrombocytosis were significantly more likely to have advanced stage disease (p<0.001) and poor median progression-free (0.94 vs 1.35 years, p<0.001) and overall survival (2.62 vs 4.65 years, p<0.001). On multivariate analysis, thrombocytosis remained an independent predictor of decreased overall survival. Our analysis revealed that thrombocytosis significantly increases the risk of VTE in ovarian cancer patients and that thrombocytosis is an independent predictor of increased mortality in women who do develop a blood clot. Platelets increased ovarian cancer cell proliferation and migration by 4.1- and 2.8-fold (p<0.01), respectively. Platelets reduced docetaxel-induced apoptosis in ovarian cancer cells by 2-fold (p<0.001). In vivo, platelet depletion reduced tumor growth by 50%. Staining of in vivo specimens revealed decreased tumor cell proliferation (p<0.001) and increased tumor and endothelial cell apoptosis (p<0.01). Platelet depletion also significantly decreased microvessel density and pericyte coverage (p<0.001). Platelet counts increase by 31-130% in mice with invasive ovarian cancer compared to controls (p<0.01) and strongly correlate with mean megakaryocyte counts in the spleen and bone marrow (r=0.95, p<0.05). Plasma levels of TPO, IL-6, and G-CSF were significantly increased in ovarian cancer patients with thrombocytosis. Plasma levels of the same cytokines were found to be significantly elevated in orthotopic mouse models of ovarian cancer, which consistently develop paraneoplastic thromocytosis. Silencing TPO, IL-6, and G-CSF significantly abrogated paraneoplastic thrombocytosis in vivo. This study provides new understanding of the clinical and biological significance of paraneoplastic thrombocytosis in ovarian cancer and uncovers key humoral factors driving this process. Blocking the development of paraneoplastic thrombocytosis and interfering with platelet-cancer cell interactions could represent novel therapeutic strategies.

Childhood sexual victimization: Risk factor for drug use and sexual risk behaviors

The purpose of this dissertation was to survey men in the Harris County Jail (HCJ) to establish a more valid estimate of childhood sexual abuse (CSA) prevalence in a jailed-based population; to assess whether inmates with a history of CSA were at greater risk for use of drugs and alcohol and engaging in high-risk sexual behaviors than those without histories of childhood sexual abuse. ^ The first study determined the prevalence of childhood sexual abuse among incarcerated males in a county jail. In this study, sixty-three percent of the subjects reported having been sexually abused. Sixty-one percent reported abuse pre-puberty and 10% reported abuse post puberty. In pre-puberty abuse the initiation of first abuse occurred at a mean age of 5.6 years (SD 5.096, range: 2–13 years). ^ The second study explored the association between inmates with histories of CSA as a risk factor for sexual risk behaviors. A history of sexual abuse did not appear to be associated with an elevated risk of sexual risk behaviors. ^ The third study explored a history of drug use and a history of CSA among the inmates. A chi-square test showed that the inmates who reported a history of CSA, was significantly greater for the following drugs: Marijuana (02), Crack (03), Heroin/Morphine (.03), Amphetamines/Speed (01), Downers/Barbiturates (.001), Methamphetamine/Crystal Meth (.001), Valium .02), LSD/Acid (.001), and Inhalants (.001), p < .05). Significance was not found in alcohol, tobacco, cocaine, Quaaludes and methadone. ^ The research from this study provides empirical data supporting previous research. The current data shows that incarcerated inmates have a high prevalence of childhood sexual abuse and drug use. Sexual victimization as a child does not appear to be associated with an elevated risk of unsafe sexual behaviors. However, men who used drugs were twice as likely to have engaged in unprotected sex with casual and regular partners, and rarely used condoms with paid sex. Although our study methods do not permit a causal explanation for this association, we believe it is of concern. Finally, data in this study shows that sexually abused children are likely candidates for adult criminal behavior. ^

The effects of antipsychotic medications on eye movements in schizophrenia

Schizophrenia is the most prevalent mental disorder in the world, affecting approximately one percent of the population. Antipsychotic medications have successfully treated schizophrenic psychotic symptoms for years, however their positive effects on cognitive dysfunction, a core feature of schizophrenia, are inconclusive. Recent studies have shown that improved cognitive functioning is most often associated with the best long-term prognosis. Thus, clarifying the cognitive effects of commonly prescribed antipsychotic medications is pivotal to improving quality of life and long-term care of schizophrenic patients.^ Previous studies on cognitive dysfunction in schizophrenia utilized complex neuropsychological tasks requiring many intact areas of the brain for proper completion. These complexities make interpretation of acquired data difficult. Recently, eye movements have been identified as a more effective surrogate for investigating cognitive functioning. Eye movements are easily measured, require known discrete areas of the brain for processing, and are ubiquitous. They influence what we attend to and process in the brain; thus they are a pivotal aspect of cognitive functioning. This study sought to examine the effects of antipsychotic medications on eye movements in forty-two schizophrenic patients. These patients were divided equally into the three tested medication groups: haloperidol, olanzapine, and aripiprazole. To the extent possible, these groups were further separated into task-impaired and task-nonimpaired subgroups, and again analyzed. Clinical and neuropsychological scales were administered to assess clinical and eye movement changes.^ The results of this study found the olanzapine-treated group exhibited superior cognitive effects to the aripiprazole-treated group, who was superior to the haloperidol-treated group. Furthermore, upon subdivision into cognitively impaired and nonimpaired subgroups, both olanzapine-treated subgroups continued to show improvement, while only the aripiprazole-treated impaired subgroup showed cognitive benefit. The haloperidol-treated nonimpaired subgroup actually demonstrated worsening effects. Interestingly, despite the cognitive decline of some subgroups, the clinical assessment results indicated virtually all subgroups exhibited significant clinical improvement. Hence, careful selection of an antipsychotic medication is crucial, as this study shows some treatments may help whereas others may hinder cognitive functioning in schizophrenia. ^ The results of this study are extremely important given the relationship between cognitive improvement and long-term prognosis in schizophrenia. Finally, and perhaps most importantly, these results indicate that clinical improvement is not necessarily indicative of cognitive improvement. ^

Suspected outbreak of dengue fever in Houston: Clinical characteristics and determination of autochthonous transmission between 2003 and 2005

Houston, Texas maintains the appropriate climate and mosquito populations to support the circulation of dengue viruses. The city is susceptible to the introduction and subsequent local transmission of dengue virus with its proximity to dengue-endemic Mexico and the high degree of international travel routed through its airports. In 2008, a study at the University of Texas School of Public Health identified 58 suspected dengue fever cases that presented at hospitals and clinics in the Houston area. Serum or CSF samples of the 58 samples tested positive or equivocal for the presence of anti-dengue IgM antibodies (Rodriguez, 2008). Here, we present the results of an investigation aimed to describe the clinical characteristics of the 58 suspected dengue fever cases and to determine if local transmission had occurred. Data from medical record abstractions and personal telephone interviews were used to describe clinical characteristics and travel history of the suspected cases. Our analysis classified six probable dengue fever cases based on the case definition from the World Health Organization. Three of the probable cases for which we were able to obtain travel history had not recently traveled to an endemic area prior to onset of symptoms suggesting the illnesses were locally acquired in Houston. Further analysis led us to hypothesize that additional cases of dengue fever are present in our study population. Fifty-one percent of the study population was diagnosed with meningitis and/or encephalitis. Sixty percent of the individuals who received a lumbar puncture had abnormal CSF. Together these findings indicate viral infection with neurological involvement, which has been reported to occur with dengue fever. Among the individuals who received liver enzyme analysis, 54% had evidence of abnormal liver enzyme levels, a clinical sign commonly observed with dengue. Our results indicate that a suspected outbreak of dengue fever with autochthonous transmission occurred in the Houston area between 2003 and 2005. ^

Psychosocial predictors of HIV testing behaviors among high risk heterosexuals

Though a lot of progress has been made in the treatment, prevention, and in increasing the knowledge and awareness of HIV/AIDS, the CDC reports that over 21% of the people infected with HIV are unaware of their HIV serostatus. Thirty-one percent of people infected with HIV are diagnosed late in the disease progression, often too late to prevent the transmission or the progression of HIV to AIDS. CDC has set a goal to increase by the year 2010, the number of people aware of the HIV serostatus by 5%. ^ This study examined the association between decision-making and risk-taking (assessed using the decision-making confidence and risk-taking scales of the Texas Christian University Self Rating Form) and HIV testing behaviors within a population of heterosexuals at risk for HIV infections living in Harris County, Texas (N=923). Data used in the study was obtained during the first cycle of the National HIV Behavioral Surveillance among heterosexuals at risk for HIV infection (NHBS-HET1), conducted from October, 2006 to June, 2007. Eighty percent of the study population reported testing for HIV at some point in their lives. The results showed that individuals who scored high (>3.3) on the decision-making confidence scale of the TCU/SRF were more likely to be tested for HIV when compared to those who scored low on the scale (OR= 2.02, 95% CI= 1.44–2.84), and that individuals who score low on the risk-taking scale of the TCU/SRF were more likely to have been tested for HIV when compared to those who scored high on the scale (OR= 1.65, 95% CI= 1.2–2.31). Several demographic factors were also assessed for their association with HIV testing behaviors. Only sex was found to be associated with HIV testing. ^ The findings suggest that risk-taking and decision-making are predictors of HIV testing behaviors such as prior HIV testing within heterosexuals living in high-risk areas of Houston, Texas, and that intervention designed to improve the risk-taking and decision-making attributes of this population might improve HIV testing within this population.^

HIV prevalence and contextual risk-factors among injection drug users in Harris County, Texas

Injection drug use is the third most frequent risk factor for new HIV infections in the United States. A dual mode of exposure: unsafe drug using practices and risky sexual behaviors underlies injection drug users' (IDUs) risk for HIV infection. This research study aims to characterize patterns of drug use and sexual behaviors and to examine the social contexts associated with risk behaviors among a sample of injection drug users. ^ This cross-sectional study includes 523 eligible injection drug users from Houston, Texas, recruited into the 2009 National HIV Behavioral Surveillance project. Three separate set of analyses were carried out. First, using latent class analysis (LCA) and maximum likelihood we identified classes of behavior describing levels of HIV risk, from nine drug and sexual behaviors. Second, eight separate multivariable regression models were built to examine the odds of reporting a given risk behavior. We constructed the most parsimonious multivariable model using a manual backward stepwise process. Third, we examined whether HIV serostatus knowledge (self-reported positive, negative, or unknown serostatus) is associated with drug use and sexual HIV risk behaviors. ^ Participants were mostly male, older, and non-Hispanic Black. Forty-two percent of our sample had behaviors putting them at high risk, 25% at moderate risk, and 33% at low risk for HIV infection. Individuals in the High-risk group had the highest probability of risky behaviors, categorized as almost always sharing needles (0.93), seldom using condoms (0.10), reporting recent exchange sex partners (0.90), and practicing anal sex (0.34). We observed that unsafe injecting practices were associated with high risk sexual behaviors. IDUs who shared needles had higher odds of having anal sex (OR=2.89, 95%CI: 1.69-4.92) and unprotected sex (OR=2.66, 95%CI: 1.38-5.10) at last sex. Additionally, homelessness was associated with needle sharing (OR=2.24, 95% CI: 1.34-3.76) and cocaine use was associated with multiple sex partners (OR=1.82, 95% CI: 1.07-3.11). Furthermore, twenty-one percent of the sample was unaware of their HIV serostatus. The three groups were not different from each other in terms of drug-use behaviors: always using a new sterile needle, or in sharing needles or drug preparation equipment. However, IDUs unaware of their HIV serostatus were 33% more likely to report having more than three sexual partners in the past 12 months; 45% more likely to report to have unprotected sex and 85% more likely to use drug and or alcohol during or before at last sex compared to HIV-positive IDUs. ^ This analysis underscores the merit of LCA approach to empirically categorize injection drug users into distinct classes and identify their risk pattern using multiple indicators and our results show considerable overlap of high risk sexual and drug use behaviors among the high-risk class members. The observed clustering pattern of drug and sexual risk behavior among this population confirms that injection drug users do not represent a homogeneous population in terms of HIV risk. These findings will help develop tailored prevention programs.^

An overview of China's one child policy and health consequences on society

In 1979, China implemented the one child policy to stifle the burden of the massive demographic growth cast on the future economic development and quality of living conditions. At the time, a quarter of the world's population resided in China and occupied only 7 percent of the world's arable land (The World Factbook, 2006). The government set the target total population to about 1.4 billion for the year 2010 and to significantly reduce the natural increase rate. First this overview paper will describe population demographics and economy of China's society. This paper will also investigate what the one child policy entails and how it is implemented. Furthermore, the consequences of the policy in regard to population growth, sex ratio, marital discrepancies, adverse health of mother and child, aging population, and pension coverage will be examined. Finally, future recommendations and an alternative policy will be postulated to increase the effectiveness of the policy and improve its effects on health. ^

When Policy Opportunity is not Enough: College Access and Enrollment Patterns among Texas Percent Plan Eligible Students

In 1998, Texas initiated a bold new statewide university admission policy aimed at increasing college access for traditionally underserved students in the state. House Bill 588 (known as the Texas Top 10 Percent Plan (TTPP)) guaranteed automatic admission to the college or university of their choice for all top performing students in Texas public high schools. Fourteen years after the plan’s implementation, we see great strides and complexities in understanding student outcomes as a result of the percent plan. However, the legal controversy over the percent plan both in Texas and other states incorporating similar yet distinctly motivated alternative admissions plans continues to play out from institutional decision boards to the highest court in the nation. This study seeks to add to that discussion by exploring two questions. Descriptively, what are the admission and enrollment patterns within racial/ethnic groups of percent plan eligible students, over time, for Texas elite, emergent elite, and remaining public institutions? Given that all eligible percent plan students may enter the institution of choice in Texas, does which type of institution a TTPP student chooses relate to their race/ethnicity? The descriptive story told by the admission and enrollment distributions of equally eligible TTPP students is a complex but compelling one. Fundamentally, it identifies that statistically different application and enrollment patterns exist for Hispanic and especially African American TTPP beneficiaries relative to their White and Asian American counterparts.