• A Randomized Control Trial of Benefits of Intrahopsital Exercise on Post-Transplantation Deconditioning in the Pediatric Hematopoietic Stem Cell Transplant Population

      Smith, Charles; The University of Arizona College of Medicine – Phoenix; Ngwube, Alexander (The University of Arizona., 2019)
      Deconditioning is a common adverse effect of short and long-term immobilization. For months pediatric hematopoietic stem cell transplant patients can be quarantined while hospitalized, much of which time is spent immobilized putting these patients at a higher risk for loss of muscle strength, functionality, endurance, and quality of life. Studies have shown that exercise as an effective countermeasure to deconditioning in stem cell transplant patients. However, research is lacking in pediatric HSCT due to the complications associated with treatment. This study was conducted to determine if there is a correlation between intrahopsital exercise and improved functionality, endurance, strength, and quality of life. In addition, this randomized control study looked at the merit and feasibility of adding an exercise routine into treatment plans. We have currently recruited 23 of our target 40 patients, 12 in the control arm and 11 in the intervention arm, ages 8-17 at Phoenix Children’s Hospital. Each participant received baseline measured by an OT or a PT for functionality using (WeeFIM), muscle strength using manual muscle testing (MMT), endurance using the 6-minute walk test, and quality of life using the NIH PROMIS measures. Measurements were taken again at discharge and 6-weeks post-discharge. During hospital admittance the intervention group performed exercise routines 3-times weekly while the control group were encouraged to spend time out of bed. Patients recruited were receiving their first HSCT and did not have any post-HSCT complications such as severe infection or GVHD. Data and results are limited due to the timepoint of the study and the limited number of recruited patients affecting the power of the study. No statistically significant difference is noted between the two arms in functional status, muscle strength, or endurance. There appears to be an increase in quality of life patients in the interventional arm compared to the control arm. Simple analysis has shown that compliance with time out of bed decreases across both groups the further away from transplant. Currently the study is midway, and data is limited to make any conclusions but shows promise.
    • A Systematic Review of Physician-Patient Interactions and the Effect of Health Care Provider Bias and Knowledge on Adolescent Contraception Counseling in Developing Countries and Comprehensive Review: Contraceptive Use and Impact of Physician Counseling for Adolescent Patients of Method Choices and Side Effects in Developing Countries

      Cooke, Alexandra; The University of Arizona College of Medicine – Phoenix; Beyda, David (The University of Arizona., 2019)
      Unmet need for contraceptives in developing countries remains a social and health problem and adolescents are more likely to struggle in starting long-acting contraceptive methods, often due to side effect or other concerns. This study aimed to analyze the biases in the provider-patient relationship and counselling practices for adolescent patients in developing countries. Attention was placed on patient’s preferred method, cultural and moral biases, knowledge gaps of patient and providers, side effect knowledge, and attitudes impacting the relationship upon counseling quality and likelihood of contraceptive use. Systematic review of articles with MeSH terms “developing countries,” “contraception,” “adolescents,” and other search terms yielded 6745 articles; 14 articles were chosen for further review. Findings highlight negative impacts of providers’ ethical concerns and knowledge gaps when addressing method use and side effects. Low knowledge base by providers of varying skill level also highlight a need for improved training on family planning methods.
    • A Systematic Review of the Effectiveness of HIV Intervention Programs on HIV Rates, Condom Use, and Abstinence in Adolescents in Low Resource Countries and The Pathophysiology, Role, Prevention, and Treatment of HIV in Low Resource Countries

      Keerthi, Svadharma; The University of Arizona College of Medicine – Phoenix; Yoblonski, Lara (The University of Arizona., 2019)
      There are high rates of HIV in adolescent girls in low resource countries due to the high incidence and prevalence of sexual violence. The purpose of this project is to collect the data of educational programs that aim to decrease rates of HIV and describe their characteristics, specifically, the rates of HIV, the rate of sexual violence, condom use, and sexual practices before and after intervention by education programs. The data shows that none of the studied measures changed after educational programs.
    • A Systematic Review on the Effect of Misoprostol in the Prevention of Postpartum Hemorrhage in Sub-Saharan African Women of Reproductive Age

      Kassi, Luce Auriane; The University of Arizona College of Medicine – Phoenix; Brady, Michael (The University of Arizona., 2019)
      Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide. Oxytocin is the uterotonic drug of choice to prevent PPH. This systematic review was performed to evaluate the use of misoprostol as a possible alternative in resource-poor settings. Articles were selected on PubMed and the International Journal of Obstetrics and Gynecology based on their primary outcomes (estimated blood loss (EBL) in mL), region (Sub-Saharan Africa) and purpose (comparing (1) misoprostol with oxytocin or with a controlled placebo (2) and different doses of misoprostol). All meta-analyses used a Cohen’s D scale. There was no difference between the use of oxytocin over misoprostol and meta-analysis shows that when used separately, both medications decreased total EBL. Misoprostol at 400 and 600 mcg did not show any difference on EBL compared to oxytocin. In combination with oxytocin, there was no difference on EBL compared to misoprostol alone. When oxytocin was not added to misoprostol, there also was no difference on EBL compared to misoprostol alone. This study suggests that misoprostol may be a sustainable alternative to prevent PPH in resource-poor areas where oxytocin is unavailable.
    • Abnormal Face‐hand Testing is Associated with Anosognosia in Patients with Neuropathologically‐confirmed Alzheimer’s Disease

      Derksen, Brenna; The University of Arizona College of Medicine - Phoenix; Jacobson, Sandra (The University of Arizona., 2014-04)
      Objective To investigate whether specific elements of the neurological and neuropsychological evaluation are associated with anosognosia for memory impairment in subjects with neuropathologically-confirmed Alzheimer’s disease. Methods Included were subjects from the Arizona Study of Aging and Neurodegenerative Disease with clinically documented dementia and neuropathological confirmation of AD for whom anosognosia could be confirmed based on antemortem data. Anosognosia was defined by a discrepancy between 1) the patient’s self-report and results of testing, and/or 2) the patient’s self-report and the caregiver’s report regarding memory impairment. The anosognosic and non-anosognosic groups were compared on targeted clinical, cognitive, and neuropathological findings. Results Of 61 subjects included, 34 were diagnosed as anosognosic, and 27 non-anosognosic. The anosognosic group performed worse on two tests of frontal systems function - letter fluency (COWAT) (p=0.010) and a score derived from the Trailmaking test (Trailmaking B time – Trailmaking A time) (p=0.015). In addition, significantly more anosognosic subjects (92%) had abnormal results on face-hand testing (double simultaneous stimulation) compared to non-anosognosic subjects (62% abnormal; p=0.018). Significance In this study of patients with moderate Alzheimer’s disease (mean CDR=2), the anosognosic group showed significantly greater impairment on tests of frontal/executive function. In addition, this group had a significantly higher rate of abnormal face-hand testing, consistent with right parietal pathology. The FHT, which takes about 30 seconds to administer, may prove useful as a marker for anosognosia risk in AD.
    • Acute Exercise Alters Promoter Methylation in Human Skeletal Muscle

      DeMenna, Jacob; The University of Arizona College of Medicine - Phoenix; Coletta, Dawn (The University of Arizona., 2016-04)
      Background And Significance: Insulin resistance is an underlying disease of obesity and type 2 diabetes, which is a metabolic health crisis in the United States. Insulin resistance is caused by a combination of environmental and genetic factors. Understanding the epigenetic factors, specifically DNA methylation and how it influences the expression of genes linked to insulin resistance is of critical importance. Research Question: In this project, we set out to identify patterns of changes in DNA methylation in response to an acute exercise in healthy control subjects. Methods: Five lean (BMI = 23.6 ± 3.3 kg/m2) volunteers underwent a euglycemic hyperinsulinemic clamp with a baseline muscle biopsy and a single bout of aerobic exercise on a stationary bicycle for 48 minutes, rotating between 70 and 90% of VO2max, with a muscle biopsy taken 24 hours after completing the exercise. DNA was isolated from the baseline and 24 hours muscle biopsy, and next‐generation reduced representation bisulfite sequencing (RRBS) was performed, with analysis of the data using methylSig, and KEGG pathway analysis. Results: RRBS analysis captured 676,937 methylation sites, and of these 47,459 were differently methylated following acute exercise (P<0.05) with 4,574 sites occurring in promoter and untranslated (5’ and 3’) regions. The site with the greatest increase in methylation was within the gene NADP(+) ‐dependent malic enzyme cytosolic form (ME1) that demonstrated a significant methylation difference of +63.3%. A site in the gene for adenomatosis polyposis coli down‐regulated 1‐like (APCDD1L) was observed to have the most significant decrease in methylation by ‐65.3%. The gene with the highest incidence of differentially methylated sites was the gene for cardiomyopathy associated 5 (CMYA5) with 11 sites demonstrating a mean increase in methylation of 30.47%. The gene family with sequence similarity 176, member B protein (FAM176B) had the highest frequency of methylated sites (n=7) that were decreased in methylation with a mean decrease of ‐24.28%. KEGG pathway analysis was performed, which revealed significant (P<0.05) increases in methylation in the pathways of Wnt signaling, Heterotrimeric G‐protein signaling ‐Gi alpha and Gs alpha mediated, Cadherin signaling, Melanogenesis, Axon Guidance, and Neuroactive ligand‐receptor interaction. Significantly 4 enriched pathways with decreased methylation post exercise demonstrated one pathway, the Calcium signaling pathway. Conclusion: Our data demonstrates that a single bout of exercise can alter the DNA methylation pattern in skeletal muscle. Changes were observed in genes related to metabolic pathways, supporting previously published findings of changes in mRNA and proteins involved in metabolism following exercise. Future work is warranted with obese and type 2 diabetic participants to explore the differences in response to exercise between these groups.
    • Additional Hearing Screenings in Pediatrics: Does Earlier, More Consistent Screening Make a Difference?

      Loeb, Sophie; The University of Arizona College of Medicine – Phoenix; Samaddar, Kristen (The University of Arizona., 2019)
      Phoenix Children’s Hospital has implemented a program, following the guidelines set by the Ear Foundation, to do annual hearing screenings from birth to school age. This is in contrast to the recommendations by Bright Futures, which state that screening should be done at birth and then annually after the child has begun kindergarten. This study may help determine the incidence of failed hearing screenings and frequency with which failed screenings translate to an intervention, as well as drive clinical decisions on the frequency/number of screenings at well-child checks.
    • Adductor Canal Nerve Block to Improve Total Knee Arthroplasty Recovery

      Kozinn, Rachel; The University of Arizona College of Medicine - Phoenix; Sachdev, Harkanwal; Kozinn, Stuart (The University of Arizona., 2018-02-26)
      Pre-operative peripheral nerve block (PNB) is an adjunct anesthesia technique used in patients undergoing total knee arthroplasty to improve post-operative pain and speed overall recovery. Effective pain management and ability to ambulate post-operatively directly affects the patient’s pace of rehabilitation and recovery. Two types of peripheral nerve blocks, the standard femoral nerve block, and a more specific adductor canal block, have relative advantages and disadvantages. Research on the effectiveness of the adductor canal block for analgesia in patients who have received a total knee arthroplasty is limited. The purpose of this scholarly project is to study the efficacy of the adductor canal block (ACB) as compared with the femoral nerve block (FNB) for post-operative pain management in total knee arthroplasty. We have retrospectively reviewed 40 patients who each received a total knee arthroplasty by a single orthopedic surgeon during the study period from January 2014 to June 2015.
    • After receiving language concordant, individual health education interventions, do Spanish speaking, diabetic inpatients at a safety net hospital demonstrate acquired diabetes self-management competency as measured by pre-training and post training evaluation of key, diabetes self-management knowledge?

      Cagle, Jonathan; The University of Arizona College of Medicine - Phoenix; Abdollahi, Shagyegh (The University of Arizona., 2018-03-28)
      The purpose of this research was to assess the quality of the inpatient, health education diabetes program as it relates to primary Spanish speaking patients. Complications from diabetes account for huge personal and financial costs. There is substantial evidence supporting the use of targeted diabetes education to reduce complications but we need to know if our education interventions are valid. In order to accomplish this by auditing the knowledge of a sample of inpatient diabetics before and after receiving the standard MMC Spanish language diabetes education interventions via Spanish language pre and post surveys (standardized by the previously validated SKILLD survey). Demographic and clinical data were analyzed and all significant data (p value <0.05) were considered for their importance. The data demonstrated that in all 10 items on the survey, overall patients were able to demonstrate significant improvement in survey scores. Additionally, comparisons of demographic data demonstrated that being less than 50 years old was associated with improved survey scores. This indicates overall benefit of the training program as well as possible insight into need for more aggressive training for patients greater than 50 years in age.
    • Alcohol Withdrawal: Does Sex Matter?

      Canales, Francisco; The University of Arizona College of Medicine - Phoenix; Carlson, Richard (The University of Arizona., 2018-03-28)
      Alcohol Withdrawal Syndrome (AWS) occurs after an individual significantly reduces or completely stops consuming alcohol after a period of constant consumption. Existing literature plentifully describes social factors that contribute to lower likelihood of development of alcohol dependence among women. Physiological differences make alcohol dependent women more likely to develop alcoholrelated hepatic complications. Animal studies suggest that ovarian hormones are neuroprotective and lead to lower incidence of seizures and allow for quicker recovery from AWS.
    • An Analysis of Mortality, Morbidity, and Primary Care Providers in Arizona's 126 Primary Care Areas

      Wassermann, Michael; The University of Arizona College of Medicine – Phoenix; Cartsonis, Jonathan (The University of Arizona., 2019)
      The United States is currently facing a primary care provider shortage. Medical schools nationwide have increased enrollment in order offset the effects of the shortage. In order to justify the effects of increasing total quantity of future physicians, there should be a demonstrated relationship between total quantity of providers and a reduction in morbidity / mortality at a population health level. This study investigates if there is any association between the total number of primary care providers and mortality per 100,000 persons (all deaths, heart disease, all cancer, chronic lower respiratory disease, and all accidents), or morbidity per 100,000 persons (chronic diseases, congestive heart failure, hypertension, uncontrolled diabetes, and stroke)? Is there any difference in total number of primary care providers, mortality per 100,000 persons, or morbidity per 100,000 persons in rural vs urban primary care areas? Data was gathered from the Arizona Department of Health Services community profiles dashboard. 2013 morbidity / mortality data for all 126 of Arizona’s Primary Care Areas was analyzed utilizing linear regression and Wilcoxon rank sum. Linear regression demonstrated a statistically significant reduction in a number of mortality / morbidity categories as total number of primary care providers increased. Correlation data demonstrated a statistically significant relationship between number of primary care providers and increase in chronic lower respiratory diseases (p value = 0.027). Additionally, rural primary care areas showed higher incidence of congestive heart failure (p < 0.001) and chronic diseases (p = 0.02) and lower total numbers of primary care providers (p < 0.001) compared with urban primary care areas. Our findings demonstrate distinct differences between urban and rural primary care areas. There may be some association between total number of primary care providers and their potential effect on mortality/morbidity incidence. Further research needs to be completed in order to elucidate a greater understanding of these potential relationships.
    • An Analysis of the “Angelina Jolie Effect”: Does the Media Influence Patients’ Contralateral Prophylactic Mastectomy Decisions?

      Gosney, Jayme; The University of Arizona College of Medicine – Phoenix; Bernard, Robert (The University of Arizona., 2019)
      Following genetic testing and counseling, many women elect to undergo prophylactic surgery to reduce their risk of developing breast and ovarian cancer. Bilateral prophylactic mastectomy (BPM) can decrease a woman’s risk of developing breast cancer by more than 90%.4 However, contralateral prophylactic mastectomy (CPM) does not increase survival for the majority of women with breast cancer, which is contrary to the increasing incidence of CPM.5,7 Angelina Jolie published an op-ed in The New York Times in May 2013 regarding her decision to undergo BPM. She pursued preventative surgery due to her strong family history of breast cancer and positive test for a BRCA mutation. While Jolie’s situation is not analogous to that of women undergoing CPM, it is possible that in many women’s minds, the situations are similar. This study is a retrospective review that examines the relationship between popular magazine articles written about prophylactic mastectomy and the number of CPM surgeries performed.
    • Analysis of Field Delivered Therapy for Chlamydia and Gonorrhea in Maricopa County

      Ebbing, Brittany; The University of Arizona College of Medicine - Phoenix; Taylor, Melanie (The University of Arizona, 2017-05-08)
      Chlamydia and gonorrhea are among the most frequently reported infectious diseases in the United States. These two diseases are easily treated with antibiotics; however, challenges exist in providing treatment to cases and their sexual partners. Maricopa County implemented a Field Delivered Therapy (FDT) protocol to treat chlamydia and gonorrhea cases and contacts in 2009. Ultimately, this project sought to inform other public health departments across the United States regarding the benefits of FDT program to treat gonorrhea and chlamydia and provide better insight on how to treat the two most commonly reported infectious diseases. Existing data was analyzed from April 1, 2011 to October 31, 2014 (42 months) for all patients that received FDT in Maricopa County utilizing pharmacy records and electronic health records (PRISM and eClinicalWorks). The following pieces of information were collected from these data sources: gender, age, race/ethnicity, diagnosis, number of partners, and time to treatment. The data were then divided into four FDT groups (FDT, expedited partner therapy via FDT, FDT attempted and FDT planned). There were 172 patients in this analysis; 140 diagnosed or in contact with chlamydia and 16 diagnosed or in contact with gonorrhea. There were 79 patients (45.9%) in the FDT group, 28 (16.3%) in the FDT EPT group, 28 (16.3%) in the FDT attempted and 37 (21.5%) in the FDT planned group. The median age of these patients was 23.8 (range 16.6‐31); 111 (64.5%) were female. The median time to treatment for these patients was 24.6 days (range 0‐64.5 days). Most patients (79.6%) lived outside of central Phoenix. The median number of sexual partners reported by these patients was 6.6 (range 1‐19.7 partners). A majority of the patients were <25 years old, except for in the FDT EPT group where 100% of patients were >25 years old. And the group with the largest <19‐year‐old population (32%) was in the FDT group. All the groups had a female majority, except in the FDT EPT group where 75% of the patients were male. Most patients in the FDT only group received testing at an outside hospital or outpatient clinic, while the FDT attempted and planned were more often tested at the STD clinic. Future Direction/Conclusion Many of the patients that received FDT are young women, some pregnant, that lived outside of Central Phoenix. However, a majority of the overall clients that received expedited partner therapy via FDT were male, a typically hard to reach population for treatment of potentially asymptomatic infections. This study demonstrates an effective method of delivering partner treatment to men. This study can be used to inform other public health departments about this novel practice and to help Maricopa County grow their FDT program to reach even more untreated patients.
    • Analysis of Risk Factors Associated with Fatal Motor Vehicle Collisions in Arizona

      Liu, Margaret; The University of Arizona College of Medicine – Phoenix; Fischione, Mark; Skinner, Ruby (The University of Arizona., 2019)
      In 2014, Arizona had 109,554 motor vehicle collisions (MVCs), 708 of which were fatal. The objective of this study was to analyze behavioral patterns in drivers which resulted in fatal MVCs. This was a retrospective chart review of MVCs in 13 Arizona counties from 2007 to 2015. Results showed a high incidence of high-risk behaviors due to substance use and lack of safe driving practices, including 26% of subjects with an ethanol content above the legal limit, 10% with THC in their system at the time of the collision, 9% with amphetamines or cocaine, 8.5% with benzodiazepines, and 5% with opiates. More than 50% had a combination of substances. Other notable characteristics were the lack of seatbelt use in 30% of subjects, and lack of motorcycle helmet use in 69% of motorcycle drivers. More data is needed on distracted driving behaviors, particularly related to cellular phone use, in order to optimally target future legislation and prevention.
    • Analysis of the Proposed Implementation of a Public Health District in Maricopa County

      Hoffman, Laura; The University of Arizona College of Medicine - Phoenix; England, Bob; Barraza, Leila (The University of Arizona., 2016-03-25)
      Background: Since the number and variety of services that a public health department is able to provide is related to its financial resources, it is important that each department have secure funding. The Public Health District model, in which the public health department is mostly funded by a dedicated public tax, rather than as a dependent on the county’s overall budget, has been proposed as an option for the Maricopa County Department of Public Health (MCDPH). This model was implemented in neighboring Pinal County in 2007 and is funded by a 0.1% sales tax. Specific aims: Our study aims are: (1) analyze the current MCDPH funding structure in comparison to other similarly sized county-managed public health departments, as well as review the development and structure of the Pinal County Public Health Services District as a local reference; (2) project the likely financial effects of the implementation of a tax-based Public Health District in Maricopa County; and (3) assess the potential effects on MCDPH management and public health outcomes in Maricopa County. We hypothesize that the implementation of a Public Health District in Maricopa County will secure a source of stable and increased funding and allow for improved public health services. Methods: Specific Aim 1: Budget data for FY 2011-2012 was analyzed for revenue types and percent contribution for each county department in the comparison. Budget data for FY 2003- 2014 for Pinal and Maricopa counties was analyzed in a similar manner. Phone interview with Pinal County Director, Mr. Thomas Schryer, was completed regarding the development of the Public Health District model in Pinal County; Specific Aim 2: Revenue data from the Maricopa County Jail Excise Tax was reviewed and utilized as a proxy to estimate potential income generated by a 0.1% sales tax; Specific Aim 3: The 2012 Maricopa County Community Health Assessment was evaluated to identify areas of need. Results: Specific Aim 1: Funding structures varied greatly between county public health departments, though heavy reliance on government funds was a common theme. Pinal County demonstrated increased funding stability with an increase in overall revenue budget upon implementation of Public Health District model. Specific Aim 2: Estimated revenue from a 0.1% sales tax was calculated to be $70 million in FY 2014-2015, with potential average revenue of $92 million over the next ten years. Specific Aim 3: Top areas for health improvement in Maricopa County include obesity, diabetes, lung cancer, cardiovascular disease and access to care. Conclusion: The current funding structure of the MCDPH follows the trend of other similarly sized county-managed public health departments with a heavy reliance on government funds. The potential revenue generated from a 0.1% sales tax in Maricopa County would be sufficient to significantly decrease the department’s dependence on general county funds and government grants. The result is increased overall funding and financial stability, thus helping the department to better target area needs and improve public health outcomes.
    • Analyzing Unspecified Chest Pain Diagnoses and the Impact of Physician Staffing at the PVAHCS ED

      Lodgek, Erica; The University of Arizona College of Medicine - Phoenix; Abbaszadegan, Hamed (The University of Arizona., 2018-04-05)
      Emergency department overcrowding is a reality that exists within the healthcare system. To standardize monitoring performance, the VHA Directive establishes ED performance metric goals (targets) and minimum standards (thresholds) on a fiscal year basis. In line with these pre-determined metrics, the outcomes examined within this study include the number of patients diagnosed with unspecified chest pain and the respective Door to Doc, Admission Decision, Admission Delay, ED LOS, and Inpatient LOS times. The reasoning behind specifically examining patients with unspecified chest pain was because it was one of the top 10 diagnoses made at the PVAHCS ED for the year of 2016 and is an acuity level only assigned to physician providers. The reason for this study is to determine the impact increased physician staffing has on the flow of the Phoenix VA ED with regard to the described outcome measures. Therefore, examining if unspecified chest pain patients solely seen by physicians have improved flow within the ED.
    • Anatomic Patterns of Relapse and Progression Following Treatment with 131I-MIBG in Metastatic Neuroblastoma

      Fishel Ben-Kenan, Rotem; The University of Arizona College of Medicine - Phoenix; Polishchuk, Alexei (The University of Arizona., 2018-03-30)
      Purpose and Background: Neuroblastomais the most common pediatric extracranialsolid tumor •50% of patients present with metastatic disease typically involving bone and bone marrow •Despite intensive multimodality therapy, 40% of patients with high-risk neuroblastomawill experience relapse •131I-MIBG is an active salvage agent for relapsed and refractory MIBG-avid disease •It is unknown whether disease progression following 131I-MIBG treatment occurs in previously involved vs. new sites of disease •A better understanding of this pattern may inform the use of consolidative focal therapies following 131I-MIBG administration
    • Androgen Receptor Expression in Human Coronary Vascular Smooth Muscle During Cytokine, Angiotensin II or Hypoxic Exposure

      Prather, Zachary; The University of Arizona College of Medicine - Phoenix; Gonzales, Rayna (The University of Arizona., 2012-05-01)
      An increasing body of evidence suggests that androgens may exert beneficial effects against the development and progression of vascular inflammation during pathological conditions. Our previous data have shown that the potent androgen receptor (AR) agonist, dihydrotestosterone (DHT), attenuates inflammation-induced vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2) in human primary vascular smooth muscle (VSM) cells. Although this response was not blocked by the AR antagonist bicalutamide, it is not known if AR expression is altered during an inflammatory insult in VSM. The goal of this study was to investigate the effects of a variety of inflammatory stimuli: Angiotensin II (more recently recognized as a mediator of inflammation in the blood vessel wall (Ruiz-Ortega, et al. 2000) (Alvarez, et al. 2004)), hypoxia, and interleukin-1 beta (IL-1β; cytokine) on AR expression in human VSM cells. Since DHT’s effect in the presence of an inflammatory stimulus is AR independent, we hypothesized levels of AR are decreased favoring less of an androgenic contribution during pro-inflammatory conditions. We initially confirmed that human VSM expresses AR and levels of the receptor are increased following androgen treatment in the absence of an 5 inflammatory stimulus. We further demonstrated that in addition to the full-length AR 110 kDa band detected via anti-AR-N20, we also detected a band migrating near 45 kDa in human VSM that is not present in rat testis lysate. Recent studies describe a variant form of the AR called AR45 expressed in human heart but not in rat (Ahrens-Fath, et al. 2005) (Weiss, Faus and Haendler 2007). Although we did not determine whether the bands migrating near 45 kDa were AR45 or possibly an endogenous break down product of the full-length AR (110 kDa) we did however observe expression of the lower migrating band during conditions of inflammation that may be cardioprotective. In the presence of an inflammatory stimulus we demonstrated that there was a consistent trend for IL-1β and angiotensin II (ang II) to decrease AR expression in human coronary artery VSM. Using an in vivo global ischemic model of inflammation, AR was robustly decreased following a 20- and 30-minute occlusion and 21 hr reperfusion in rat pial arteries. However, unlike ang II, cytokine, or ischemia, in vitro hypoxic exposure in human VSM cells increased the lower migrating band density (45 kDa) and had no effect on band density at 110 kDa. In summary, our results confirm that levels of the classic AR (and possibly the novel AR45 variant form) are present in human VSM. 6 Additionally levels of AR may be altered under conditions of inflammation in human VSM cells and following ischemia/reperfusion in rodent cerebral arteries. We conclude that the AR independent attenuation of COX-2 and VCAM-1 by DHT following an inflammatory insult may be due in part to a decrease of AR levels in the blood vessel wall.
    • Antipsychotic Rechallenge After Neuroleptic Malignant Syndrome with Catatonic Features

      Bond, Alicia Giuffrida; The University of Arizona College of Medicine - Phoenix; Cornelius, Christian (The University of Arizona., 2011-03)
      Neuroleptic malignant syndrome (NMS) is a life-threatening condition that can occur in patients who require long-term antipsychotic therapy, and who therefore must be rechallenged with antipsychotics after their NMS episode. Current guidelines are based on limited data and recommend that rechallenge be undertaken by titrating from low doses of low-potency antipsychotics, after a period of two weeks following resolution of symptoms. We present the case of a patient with an NMS course complicated by residual catatonia course and a literature review with analysis to determine whether time to rechallenge, potency of rechallenge drug, and dose of rechallenge drug are independent predictors of NMS recurrence in patients. One hundred thirteen instances of neuroleptic rechallenge in non-catatonic NMS cases and 29 cases of rechallenge in NMS with catatonic features were identified through broad Medline and PsycInfo database searches and were analyzed by a single reviewer for rechallenge data. Fifty-five cases involved female patients, and 87 male patients; patients ranged in age from 12 to 86, with a mean of 37. There was no statistically significant relationship found between rate of NMS recurrence and time elapsed before rechallenge, either for all cases or by subgroup. Although the recurrence rate for patients rechallenged with highest-potency antipsychotics was found to be higher than those rechallenged with lowest-potency drugs,the relationship was not significant. The maximum antipsychotic dose reached during rechallenge was significantly lower among patients with recurrence of NMS than those who did not recur, likely due to recurrences early in dose titration. There was no statistically significant relationship between starting dose and recurrence. Based on our analysis, time between resolution of symptoms and rechallenge may have no bearing on risk of recurrence, in contrast to current recommendations. Dose of rechallenge drug is also unlikely to be an independent predictor of recurrence. Several studies, including ours, have shown a statistically insignificant but consistent positive relationship between potency of rechallenge drug and risk of recurrence.
    • Arizona Alzheimer’s Registry: Strategy and Outcomes

      Saunders, Kelley; The University of Arizona College of Medicine - Phoenix; Tariot, Pierre (The University of Arizona., 2014-04)
      Background: The Arizona Alzheimer’s Consortium (AAC) is a statewide Alzheimer’s disease (AD) research consortium. In 2006 the AAC created the Arizona Alzheimer’s Registry (Registry), a screening and referral process for people interested in participating in AD-related research. The Registry goals were to increase awareness of AD research and accelerate enrollment into AAC studies. Registrants were matched to AAC studies according to interest, location, and eligibility. Methods: Anyone age 18 and older was eligible. Registrants were recruited by community outreach, mass mailings, earned and paid media, and the Internet. Those interested received a welcome packet, consent, and questionnaire, which were reviewed by staff via telephone prior to brief cognitive screening. Evaluation of medical history, cognitive status, and interests resulted in a referral to existing AAC studies or being held for future referral. Results: 2263 people contacted the Registry. 1257 consented and 1182 underwent an initial cognitive screening. Earned media was the most effective recruitment strategy. Registrants had a mean age of 68.1 (SD 10.6), 97% were Caucasian, had 15.2 (SD 2.7) mean years of education, and 60% were female. 30% reported a family history of dementia, 20% reported a diagnosis of cognitive impairment or dementia, and 70% subjectively reported normal cognition. Initial telephone assessments revealed 681 with no impairment, 269 with possible cognitive impairment, and 234 with possible dementia. 301 were referred to AAC sites for potential enrollment into a study. Conclusion: The Registry created an infrastructure and process to screen and refer a high volume of eager Registrants. These methods were found to be effective at prescreening individuals for studies, which facilitated AAC research recruitment. The established infrastructure and experiences gained from the Registry have served as the prototype for the web-based Alzheimer’s Prevention Registry, a national registry focusing on AD prevention research.