Browsing by Subject "Epidemiology"
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Item A Look at Diabetes Mellitus and the Effects of a Study Drug on Diabetic Nephropathy(2002-08-01) Schlueter, Cynthia K.; Debbie Lewis; Clifton Cage; Rustin ReevesDuring my internship, I assisted with a twenty-four week, phase 2, double blinded, placebo controlled trial for a drug being developed to slow, if not prevent, the development of ESRD from overt neuropathy in patients with both type 1 and type 2 diabetes. This drug is a naturally occurring component of vitamin B6 and is an AGE-inhibitor. The AGE-inhibitory effect of the study drug was discovered by isolating Amadori products in the pathway to AGE formation. Once the intermediates were isolated, the sponsor’s scientists searched for compounds that could specifically block the conversion of these Amadori products into AGEs. The study drug was found to be a strong inhibitor of this pathway. In comparison, the common AGE inhibitor, aminoguanidine was found to be ineffective in blocking the post-Amadori foundation AGEs. Therefore, it must block AGE formation at one of the less clinically relevant pathways, and should be less effective in treating nephropathy according to the sponsor’s scientists. This study included type 1 and type 2 patients with clinically diagnosed diabetic retinopathy and a urinary albumin excretion rate (UAE) of greater than 300 mg/24h. Other inclusion and exclusion criteria were applied for the safety of the subjects and greater viability of the data.Item A Mixed Methods Approach to the Definition of Family Health Promotion Practices for Mexican Sonoran Mothers(2006-12-01) Montiel-Carbajal, Maria Martha; Sue LurieMontiel-Carbajal, Maria M., A Mixed Methods Approach to the Definition of Family Health Promotion Practices for Mexican Sonoran Mothers. Doctor of Public Health (Social and Behavioral Sciences), December 2006, 143 pp., 14 tables, 1 illustration, bibliography, 55 titles. The purpose of this research was to study the family health promotion practices of a sample of Mexican mothers living in the state of Sonora Mexico through a concurrent mixed method approach that included (1) a qualitative component with face to face and in-depth interviews, investigator observations, and analysis of content; (2) a quantitative component consisting of statistical analysis of data from selected selections of the National Survey for the Evaluation of Health Services 2002-2003. For the qualitative component 15 mothers, with mean age of 40 years, mean years of education of 10 years, living with their families were selected to form a purposive sample, and assigned to one of three groups: married working mothers, non-married working mothers, or married non-working mothers. The qualitative component was naturalistic and descriptive using semi-structured interviews with the mothers, and individual questionnaires to collect demographic and housing information. The quantitative component used the survey responses provided by the database of the National Survey for the Evaluation of Health Services 2002-2003, from 404 female adults age 18 and older, living in the urban zone of Sonora. The qualitative component showed that mothers conceptualize the health status of the family as a priority. The specific practices they use depend on the set of external resources and internal strengths of the family in order to overcome the physical, environmental, relational, or economic barriers they found to the promotion of health practices. The participants also reported being unsatisfied with the access and quality of the social health care system. The data from the quantitative component showed that Mexican Sonoran women living in the urban area reported having good health and felt satisfied with their health status; their satisfaction with the social health care system was fair. The group of non-married working mothers was detected to be more at risk for cardiovascular diseases due to a greater proportion of smokers and drinking paired with low amount of exercise. The results provided valuable information to formulate health promotion programs and future policies to be implemented with the target population.Item A Study of Hepatitis A Seropositivity in Dallas County, 1998-1999(2001-05-01) Fulda, Kimberly G.; Antonio Rene; John Licciardone; Sally BlakelyFulda, Kimberly G., A Study of Hepatitis A Seropositivity in Dallas County, 1998 – 1999. Master of Public Health (Epidemiology), May 2001, 39 pp., 4 tables, 9 figures, references, 28 titles. The purpose of this study was to determine incidence rates per 100,000 population of hepatits A (HAV) in Dallas County for 1998 and 1999. Individuals who tested seropositive for hepatitis A between January 1, 1998 and December 31, 1999 were included. The variables of interest were sex, race, age, Zone Improvement Plan (ZIP code), and date of occurrence. Rates for 1998 were 1.9 times higher in Dallas County than the United States. In 1999, the Dallas County rate increased over 1.6 times. Rates were significantly higher in males for both years, and rates were highest among Hispanics and lowest among Blacks. Differences in age distribution varied between years by increasing in ages 50 and older in 1999. Several ZIP codes exceeded rates of 20 per 100,000 for both 1998 and 1999. Dallas County met the Advisory Committee on Immunization Practices guidelines for routine vaccination of all children in 1999.Item A Sun Awareness Pilot Project(2002-05-01) Franklin, Gillian A.; Claudia Coggin; Kristine A. Lykens; Doug A. MainsFranklin, Gillian A., A Sun Awareness Pilot Project. Masters of Public Health (Health Management and Policy), May 2002, 53 pp., 7 tables, bibliography, 48 titles. The most common cancer in the United States today is skin cancer; it is also the most preventable. At least 90% of all skin cancers is caused by sun exposure. Americans have a one in six lifetime risk of developing skin cancer and in Texas the rate is one in three. The purpose of this pilot project was to increase the level of sun protection knowledge and awareness in parents who brought their children in for a six-month immunization visit. The project was modeled after the Australian Cancer Council’s “Slip! Slop! Slap!” campaign. Data was collected from five pediatric clinics in this pretest/posttest design study. Multiple variables regarding demographics, skin type, knowledge, beliefs, sun-protective practices, and attitudes were included. Overall, parental sun protective knowledge and awareness increased. The information obtained from this pilot project may influence future public health decisions regarding education and prevention of skin cancers.Item Adult Women and Coronary Heart Disease: Studies on Surgical Procedures and Perception(2010-12-01) Schlorke, Patricia; Bae, Sejong; Biswas, Swati; Chen, OliveSchlorke, Patricia J., Adult Women and Coronary Heart Disease: Studies on Surgical Procedures and Perception. Doctor of Public Health (Biostatistics), December 2010, 124 pp., 12 tables, 3 figures, bibliography, 95 titles. Coronary heart disease (CHD) was the number one cause of death in the United States. The main CHD symptom was a heart attack. The most common form of a heart attack was chest pain and shortness of breath, which occurred in men. However, women did not usually have chest pain, but other symptoms such as abdominal pain or indigestion. This could lead women to perceive or believe that they would not have heart disease or heart attacks. This thought could lead women to not obtaining health care, such as surgical procedures, for CHD. Health professionals knew the signs and symptoms of CHD in men, but they may be uncertain in their diagnosis in women. This could lead to women not asking their health care professional about heart attacks or other symptoms. The purpose of this dissertation analyzed CHD in two areas in all women 18 years and older. These two areas were: (a) comparing hospital length of stay between men and women who had either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA); and (b) women’s perceptions about CHD. Data for the surgical procedures study came from the 2006 National Hospital Discharge Survey (NHDS) and for the perception study came from the 2007 Behavioral Risk Factor Surveillance System (BRFSS). The results showed for the surgical procedures men and women had increased hospital days of care (DOC) for all surgical procedures. The results for the perception study showed women varied by age, race-ethnicity, education, income, and other factors in heart attack symptom knowledge. These two studies had the following conclusions. The results for increased hospital DOC had implications, such as increased health utilization, for present and future hospitalizations. The results for heart attack symptom knowledge showed a need for more awareness and communication of heart attack symptoms among all women across the United States.Item Allele-Specific Effects of Extracellular Superoxide Dismutase on Expression and Disease Susceptibility(2010-12-01) Jun, Sujung; Ladislav DoryOur lab previously reported a new allele for extracellular superoxide dismutase (ecSOD), expressed in 129P3/J mice (129), which differs from the wild-type, expressed in C57BL/6J and other strains. The newly discovered allele is associated with significantly increased circulating and heparin-releasable ecSOD activity and amount. To examine the properties of the two forms of ecSOD in an identical environment, I have generated congenic mice expressing either ecSOD allele on C57BL/6 genomic background. The congenic mice plasma ecSOD phenotypes show the same differences reported in the founder mice, indicating that the ecSOD genotype is largely responsible for the observed differences in the ecSOD phenotypes of the C57 and 129 strains. Tissue enzyme distribution of 129 allele is associated with higher levels of enzyme in most tissues; despite profoundly lower levels of the corresponding mRNA levels in the tissues. These results also suggest significant allele-specific differences in the regulation of ecSOD synthesis and intracellular processing/secretion of ecSOD. The increased rates of synthesis and secretion of 129 ecSOD relative to wt ecSOD is confirmed by using stably transfected CHO cells with either of ecSOD allele. The effects of the increased ecSOD levels in tissues on the susceptibility to asbestos-induced lung injury as well as bacterial infections were also investigated in congenic mice. Accordingly congenic mice with the 129 allele were significantly resistant to asbestos-induced fibrosis and injury. On the other hand, the expression of 129 allele significantly aggravated susceptibility to Listeria and Streptococcus infection compared to C57 allele and ecSOD KO mice, suggesting that ecSOD plays an important role in the modulation of immune responses triggered by bacterial infection. Overall this study confirmed the ecSOD allele-specific effects on the ecSOD phenotype and on the disease susceptibilities. In conclusion, the congenic mice offer an excellent model to examine the regulatory mechanisms of ecSOD expression and the role of ecSOD in various diseases involving oxidative stress.Item An Analysis of Osteoporosis-Related Hip Fractures, Using Hospital Discharge Data(2001-12-01) Rubin, Bernard; Antonio A. Rene; Douglas Mains; Muriel MarshallThe purpose of this study is to assess whether a current physician practice may inadequately diagnose osteoporosis in a high risk population of postmenopausal women who have sustained a hip fracture. A review of all patients discharged from Texas hospitals during calendar year 1999 was analyzed, using the Public Use Data File provided through the Texas Health Care Information Council. A total of 13,628 women over the age of 55 were admitted to hospital with a fractured hip. Only 2,233, or 16.3%, of women were also coded with the diagnosis of osteoporosis (P [less than] 0.001). Forty to fifty percent of postmenopausal women have osteoporosis. Therefore, women presenting with a fragility fracture form an even more at-risk subset of the population, such that one would expect a majority of these women to carry a diagnosis of osteoporosis. Percentages of Caucasian, non-Hispanic women in each group were comparable. The age distribution in each group was comparable, implying that the coded diagnosis of osteoporosis was not related to the age of the women when admitted to the hospital. In conclusion, physicians practicing in Texas during calendar year 1999 inadequately diagnosed osteoporosis in a high risk population of postmenopausal women who were admitted to hospital with fractured hip. Future analysis of subsequent analysis databases will be able to identify whether or not continuing medical education efforts will cause physicians to diagnose osteoporosis in this high risk population more frequently.Item An Epidemiological Profile of Poisoning Episodes Among Texans Utilizing Hospital Discharge Survery Data(2003-05-01) Ramisetty-Mikler, Suhasini; Rene, Antonio; Blakely, Sally; Mains, DouglasRamisetty-Mikler, Suhasini, An Epidemiological Profile of Poisoning Episodes Among Texans Utilizing Hospital Discharge Survey Data. Master of Public Health (Epidemiology), May, 2003, 68pp., 15 tables, references, 43 titles. This retrospective study of hospital discharge data provides an epidemiological profile of admissions, type of poisoning causing the hospitalization, and the intent of injury among Texans (N=12,541) during 1999. Overall, females are more frequently admitted, the rates increased with age through age 50 and declined thereafter among non-HIV patients. Psychotropic drugs and analgesics are the top two substances causing more than half of all admissions and one-third among children under age 14. Approximately 61% of all poisoning admissions are self-inflicted. The self-infliction risk is two times greater among non-HIV females and is highest (8 fold) among teenagers (age 15 to 17) compared to children 14 years or younger. The risk decreased with age (7 fold) through middle ages and dropped significantly after age 40 (4.5 times). Self-infliction is less likely after age 60. Whites are 1.5 times more likely than Blacks to self inflict among both HIV and non-HIV patients.Item An Evaluation of Acanthosis Nigricans School Screening Results in Richardson Independent School District to Determine the Association of Acanthosis Nigricans and Other Factors for Type 2 Diabetes Mellitus(2005-05-01) Gardner, Janet E.; Urrutia-Rojas, Ximena; McConathy, Walter J.; Cipher, Daisha J.Gardner, Janet E., An Evaluation of Acanthosis Nigricans School Screening Results in Richardson Independent School District to Determine the Association of Acanthosis Nigricans and Other Risk Factors for Type 2 Diabetes Mellitus. Master of Public Health (Community Health), May 2005, 65 pp., 11 tables, reference list, 47 titles. Cases of Type 2 diabetes mellitus (T2DM) have been increasing at alarming rates in Texas. Identifying underlying factors, such as acanthosis nigricans (AN), elevated body mass index and hypertension, which might contribute to the development for type 2 diabetes, is critical. This study analyzed the relationship of AN with these risk factors of T2DM. Richardson Independent School District screening results for 2003-2004 were analyzed. This study concluded that calculated BMI values yielded the highest association with grades of AN. BMI-for-age percentiles greater than or equal to the 95th percentile and elevated diastolic and/or systolic blood pressures were strongly associated with AN grades.Item Assessment of Obesity as a Cardiovascular Disease Risk Factor in a Geriatric Rural Texas Community - A Six Month Follow-Up(1999-12-01) Coustasse, Alberto; Antonio Rene; Doug A. Mains; Gilbert RamirezCoustasse, Alberto, Assessment of Obesity as a Cardiovascular Disease Risk Factor in a Geriatric Rural Texas Community – A Six Month Follow-up. Master of Public Health Track, Public Health Administration, December 1999, 22 pp., 9 tables, 9 illustrations, bibliography, 7 titles. The health fair approach was used as a method to establish individual and population health status baselines and to provide a mechanism to follow-up with an elderly population in a rural Texas community. A controlled trial sample of forty-four seniors was initially screened in a primary care clinic in August 1998. Patients were reevaluated at six months and results demonstrated a 46% increase in BMI [Body Mass Index]; 62% remained obese; 62% maintained elevated cholesterol or increased cholesterol values to abnormal values; 61% maintained or increased their BP [blood pressure] to abnormal values. A significant finding was that a change of one unit in the BMI correlated with a change of 19.88 mmHg [millimeter mercury] of SBP [systolic blood pressure] and 18.59 mmHg of DBP [diastolic blood pressure]. The societal economic impact of mortality and morbidity (without the benefit of target interventions) for the initial forty-four seniors was projected at & 74,949. Keywords: Health fairs; obesity; cardiovascular; cost; case management.Item Association Between Breastfeeding and Asthma: A Cross-Sectional Study(2003-08-01) Trombley, Ann M.; Manuel Bayona; Raghbir SandhuTrombley, Ann M., Association Between Breastfeeding and Asthma: A Cross-Sectional Study. Master of Public Health (Epidemiology), August 2003, 17 pp., 12 tables, bibliography, 54 titles. Controversy has surrounded the topic of breastfeeding and if it provides a protective effect against childhood asthma. The objective of this study was to assess whether a relationship exists between breastfeeding and childhood asthma. This study also examined several significant predictors of childhood asthma. A cross-sectional study was conducted using NHANES 1999-2000 data to identify and assess the crude and multivariate associations between the above mentioned variables and asthma and the effect that breastfeeding has on these relationships. Prevalence of asthma in this study was 12.5 per 100. Mexican Americans were found to have a protective association with the development of asthma. A strong protective association was found for those who were breastfed and the development of childhood asthma (OR=0.693, p-value=0.014).Item Associations Between Socioeconomic Statuses and Behavioral Risk Factors and Self-Reported Health Status(2005-05-01) Wu, Gang; Daisha Cipher; Shande Chen; Sejong BaeWu, Gang, Association Between Socioeconomic Statuses and Behavioral Risk Factors and Self-Reported Health Status. Master of Public Health (Biostatistics), May 2005, 70pp., 5 figures, 4 tables, references, 58 titles. Socioeconomic statuses (SES) and behavioral risk factors determine more than 70% of overall health outcome of American population. The effects of SES and behavioral risk factors on self-reported health status (SRHS) were studied using binary logistic regression models. Age group, education level, ethnicity, physical activities, cholesterol intake, smoking status, and drinking status were identified as significant predictors (p [less than] 0.05) to SRHS based on overall model. Significant predictors for each ethnic group varied based on the same model separated by ethnicity: White (insurance coverage, physical activities, smoking status, and drinking status), Black (gender, vegetable intake, and Hispanic (cholesterol intake). Ethnic disparities in SES and behavioral risk factors were discussed. The findings may have potential importance in public health intervention.Item Asthma Mortality and Toxic Release in Texas - An Ecological Study 1980-2001(2004-05-01) Maddipatla, Sreeram; Manuel BayonaMaddipatla, S., Asthma Mortality and Toxic Release in Texas - An Ecological Study 1980-2001. Master of Public Health (Environmental Health) April 2004, 97 pp., 4 tables, bibliography, 94 titles. There is a lack of literature examining how the spatiotemporal trend of asthma may have impacted different ethnic/racial compositions of Texans. The present study sought to evaluate the geographic-temporal variations in asthma mortality in Texans over a 22-year period, retrospectively, and examine whether the trend of environmental Toxic Release Inventory (TRI) concentrations and their spatiotemporal persistence might place an uneven burden on particular racial groups. The study concentrates on the time period between 1980-2001 and first evaluates geographic excess of asthma mortality in different racial groups at the county level and characterizes the excess burden by spatiotemporal variations. After this assessment, the impact of TRI on asthma mortality over this period of time is analyzed. Based on these two analyses, this would identify which racial/ethnic groups in which Texas regions might have been affected the most by regarding mortality over time, and suggested priority geographic areas for policy intervention. At the end of this study, it could be said that there might be an association between the TRI release and increased asthma mortality in the Black male population.Item Canonical Transient Receptor Potential 6 (TRPC6) Dysregulation in Mesangial Cells and Glomerular Hyperfiltration during the Early Stages of Diabetes(2010-12-01) Graham, Sarabeth M.; Rong MaGlomerular mesangial cells (MCs) regulate the glomerular filtration rate (GFR) by contracting and relaxing in response to agonists. The contractile function of MCs is controlled by intracellular Ca2+. Canonical Transient receptor potential 6 (TRPC6) contribute to Ca2+ signaling in a variety of cells. However, the physiological and pathological relevance of TRPC6 in MCs remains unknown. The present study was conducted to examine 1) if TRPC6 mediated an agonist-induced Ca2+ response in MCs and if this Ca2+ signaling mechanism was impaired in diabetes 2) the mechanism by which TRPC6 is dysregulated in diabetes. In the first study, angiotensin II (AngII)-stimulated membrane currents were significantly enhanced in TRPC6 overexpressing MCs, but significantly attenuated in cells with TRPC6 knockdown. AngII-induced calcium influx was suppressed in MCs with TRPC6 knockdown, as well as in MCs cultured in high glucose (HG). HG reduced both the mRNA and protein levels of TRPC6, but not other isoforms of TRPCs, in a time and dose dependent manner. Furthermore, in streptozotocin (STZ)-induced diabetic rat glomeruli, TRPC6 but not TRPC1 was downregulated. In the second study, we found that the diabetes-induced decrease in TRPC6 protein expression was specific for glomeruli and no change in TRPC6 expression was observed in the heart or aorta. In cultured MCs, hydrogen peroxide (H2O2) decreased TRPC6 protein expression in a dose and time dependent manner. Antioxidants prevented the inhibitory effect of HG on TRPC6 in MCs. Consistently, treatment of STZ-diabetic rats with tempol preserved TRPC6 in the glomeruli. Nox4 knockdown led to an increase in TRPC6 protein in MCs. Furthermore, PMA, but not its analog 4α-PDD, suppressed TRPC6 and this PMA effect was not altered by catalase. A PKC inhibitor, Gö6976, attenuated the downregulation of TRPC6 caused by both HG and H2O2. Taken together, these studies suggest that TRPC6 participates in Ca2+ signaling in MCs and hyperglycemia in diabetes downregulates TRPC6 protein expression through a Nox4-ROS-PKC pathway.Item Cardiovascular Fitness and Lung Function of Adult Men and Women in the United States: NHANES 1999-2002.(2008-12-01) Jackson, HannahThere is a distinct disparity between adult males and females in lung function and cardiovascular fitness in the United States. This study utilizes a nationally representative sample in order to determine predictors of lung function between men and women. Simple means analysis, logistic and linear regressions were utilized in order to determine predictors of lung function between genders. Continuous analyses of lung function reveal that sex and BMI are the most important predictors of VO2 max. However, analyses of clinical cut-points of cardiovascular fitness indicate that gender was not a significant predictor.Item Cell line authentication and contamination assessment for human cell cultures(2015-05-01) Ormos, Andrea; Arthur J. Eisenberg; Rhonda Roby; John V. PlanzCell line authentication is an essential step in ensuring the integrity and reproducibility of biomedical research. The major contaminants in cell cultures are fungi, viruses, bacteria and contamination from other cell lines of the same or different species. Contaminants alter the physiology and properties of cells, compromising the results of experiments. In this study, an improved multiplex assay was developed, detecting mycoplasma and mouse cell line contamination, while performing DNA typing. The assay was tested on cell cultures, the reproducibility of the assay was verified, sample collection and procedures were optimized and limit of detection for contaminants were determined. A survey was conducted to assess the interest in an in-house cell line authentication and contamination assessment service.Item Defining the Prostate Cancer Population in Texas Using Hospital Discharge Data(2004-05-01) Manuel, Christopher J.; Karan Singh; Antonio A. ReneManuel, Christopher J., Defining the prostate cancer population in Texas using hospital discharge data. Masters of Public Health (Biostatistics), May 2004, 25 pp., 6 tables, bibliography, 35 titles. The Texas Health Care Information Council (THCIC) was created by the 74th Texas Legislature in 1995. THCIC’s primary purpose is to provide data that will enable Texas consumers and health plan purchasers to make informed health care decisions. This data also serves the purpose of providing information about disease trends and hospital discharges. The purpose of this study was to describe the disease status of prostate cancer in the state of Texas. Prostate cancer is the most common non-cutaneous male malignancy and ranks as the second cause of cancer-related mortality among men in the United States. Epidemiologic data was extracted from the data set for analysis looking at disease trends based on a variety of factors such as age, race, and insurance.Item Differences in Risk of Injury Between Stimulant-Treated and Untreated ADHD Patients(2006-08-01) Segars, Larry W.; Raghbir Sandhu; Krisine LykensSegars, Larry W., Differences in Risk of Injury between Stimulant-Treated and Untreated ADHD Patients. Doctor of Public Health (Epidemiology), August 2006, 63 pp, 7 tables, 0 illustrations, references, 78 titles. ADHD is a common psychiatric disorder of childhood and adolescence that also occurs in adults and spans the life of the patient. ADHD is characterized by lack of focus, distractibility, and poor concentration. Limited data have been generated focusing on ADHD patients and the association with an increased risk of injury. Unfortunately, no study has been published evaluating the effect of stimulant treatment for ADHD on the risk of injury requiring ambulatory medical care. This research utilized four concatenated years, specifically 1998-2001, of the National Ambulatory Medical Care Survey (NAMCS). This dissertation is comprised of five chapters beginning with a description of ADHD, its characteristics, diagnosis, and treatment. This overview chapter is followed by a complete review of the literature describing the publication’s which assessed the association between ADHD and the risk of injury. The next chapter is a thorough review of the NAMCS and its methodology. The concatenated dataset captured 889 office visits associated with a diagnosis of ADHD, 666 of which were also related to the prescription of a stimulant for the management of ADHD. Using NAMCS’s weight variable these values produced a national estimate of 21,223,391 office visits associated with the ADHD diagnosis and 15,604,329 office visits associated with the prescription of a stimulant for ADHD. This research determined that there was a borderline statistically significant increased association with the prescription of a stimulant for the treatment of ADHD and the risk of injury requiring treatment in an ambulatory medical care setting. Interestingly, compared to patient’s who recorded their race as Caucasian, patients who recorded their race as “Other”; representing the races of Asian, Native Hawaiian/Other Pacific Islander, or American Indian/Alaska Native, and individuals indicating more than one race, had a statistically significant increased risk of injury necessitating treatment in an ambulatory medical care setting. Potential theories for this unique finding, along with the limitations of this research, are provided in the final discussion chapter.Item Diverse Immune Responses Mediated by Beta-Adrenergic and Corticotropin-Releasing Hormone Receptors in a Model of Pneumococcal sepsis(2010-08-01) Kim, Byung-Jin; Harlan JonesNeuroendocrine stimulation can impact disease states by regulating immune function. The purpose of our studies was to define the functional role of stress-induced neuroendocrine factors, catecholamines and corticotropin-releasing hormone (CRH) on immune responses involved in the pathogenesis of Streptococcus pneumoniae (S. pneumoniae) infection implementing both in vitro and in vivo methodology. Dendritic cells play a pivotal role in antigen presentation and cytokine production, influencing both innate and adaptive immunity. Initial studies examined the potential immunomodulatory effect of epinephrine and CRH on DC cytokine production in response to the bacterial pathogenic ligand, lipopolysaccharide (LPS). In addition, the ability of DC to dictate CD4+ T cell activation as a consequence of CRH or epinephrine pre-treatment was examined using an in vitro co-culture system. Epinephrine and CRH pre-treatment resulted in a preferential increase in IL-23 and IL-10 cytokine production. In contrast, IL-12p70 was significantly attenuated in response to epinephrine and CRH pre-treatment. Preferences in IL-23 and IL-10 cytokine production by DC pre-treated with epinephrine and CRH corresponded with an increase in IL-4 and IL-17A, but not IFN-y cytokine production by CD4+ T cells. These results suggest that exposure to stress-derived epinephrine/CRH dictates dendritic cells to generate a dominant Th2/Th17 phenotype in the context of subsequent exposure to a pathogen. Our second study examined the functional properties of IL-23 during pulmonary S. pneumoniae infection. IL-23 plays a crucial role in establishing host defenses against extracellular pathogens. Further investigation is still required to define the impact of IL-23 on acute pulmonary S. pneumoniae infection. Utilizing IL-23p19 genetic deficient mice, we determined bacterial load, cytokine production and the contribution of neutrophils against S. pneumoniae infection using monoclonal antibody-mediated systemic neutrophil depletion. The absence of IL-23 induced a higher bacterial load in lung and blood as compared to IL-23 competent counterparts. In the absence of IL-23, production of proinflammatory cytokines such as IL-6, IL-12p70 as well as IL-17A and IFN- were dampened as compared to wild type mice. In addition, neutrophil distribution was also altered in IL-23-deficient mice, suggesting impaired neutrophil recruitment into lung. Interestingly, neutrophil depletion did not impact bacterial load in lung and blood in both IL-23 competent and deficient mice. These findings, suggest a novel role of IL-23 in pulmonary S. pneumoniae infection, potentially independent of neutrophil function. We next examined the possible impact of CRH and catecholamines as regulators of immune function against acute bacterial infection in response to stress. Utilizing a murine model of acute pulmonary S. pneumoniae infection and restraint stress, we selectively blocked CRH receptors (CRHR1 and CRHR2) as well as the 2 adrenergic receptor prior to restraint stress followed by intranasal pulmonary S. pneumoniae infection. Antagonist administration did not impact restraint stress-induced physiological responses as compared to restraint stressed mice, which did not receive receptor antagonists. However, following S. pneumoniae infection, physiological changes including weight and temperature were altered in response to administration of selective CRH receptor and β2 adrenergic receptor antagonists. Survival rate, bacterial load and cytokine production corresponded with physiological differences observed in response to selective CRH receptor and 2 adrenergic receptor antagonists. Importantly, preferential differences in bacterial colonization and survival corresponded with distinct differences in inflammatory cytokine production and immune cell distribution along pulmonary airways. In particular, opposing effects in IL-17A and neutrophil accumulation was found among mice administered the CRHR1 versus the CRHR2 antagonists. Together, these findings indicate that activation of each receptor can influence immune responses against S. pneumoniae infection. Thus, our findings provide further understanding of how stress-derived neuroendocrine factors directly impact immune responses related to immunopathology and immunoprotection.Item Epidemiologic Assessment of a Targeted Tuberulosis Screening and Treatment Program Based on Geographic and Molecular Clustering(2005-08-01) Moonan, Patrick KevinMoonan, Patrick K., Epidemiologic Assessment of a Targeted Tuberculosis Screening and Treatment Program Based on Geographic and Molecular Clustering. Doctor of Public Health (Disease Prevention and Control), August 2005, 93 pp., 12 tables, 7 illustrations, bibliography, 148 tables. One of the primary goals of the tuberculosis elimination strategy is to interrupt the transmission of mycobacterium tuberculosis (TB). The most effective way to accomplish this goal is to identify and treat individuals who have active tuberculosis. However, even in highly effected tuberculosis control programs, M. tuberculosis continues to be transmitted to others, largely because most transmission occurs before diagnosis and initiation of therapy. Under the current recommendations, testing should be targeted at specific high-risk populations. While a strategy of targeted testing and treatment of persons most likely to develop tuberculosis is attractive, it is uncertain how best to accomplish this goal. This is the first study to assess the use of geographic and molecular surveillance in guiding a targeted tuberculosis screening and treatment of active tuberculosis and latent tuberculosis infection that monitors potential transmission in a defined high risk geographic area. The results of this geographically targeted program demonstrate significant yield for discovering active cases, latent tuberculosis infection, and recent transmission (TST converters). In this setting, geographically targeted screening identified as many as 19.8 tuberculosis cases per 1,000 persons screened and as many as 292.4 latent tuberculosis infections per 1,000 persons screened. Additionally, successful treatment of these individuals reduced the number of both cases and latent infection identified. Over a three-year period the case detection rate, latent infection detection rate, and TST conversion rate was reduced by 335%, 171% and 285% respectively.
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