• Imaging Evaluation of the Solitary Pulmonary Nodule

      Van Tassel, Lora; The University of Arizona College of Medicine - Phoenix; Korn, Ronald (The University of Arizona., 2012-05-01)
      An estimated 150,000 solitary pulmonary nodules (SPNs) are identified at chest radiography each year, making it important for physicians to understand how to characterize them and evaluate patients for potential malignancy. We performed an extensive literature search to identify risk factors, characteristics of SPNs, and available technologies used to identify and evaluate these nodules through a comprehensive literature search. Additionally, we present evidence-based management schemes for incidentally identified nodules. CONCLUSIONS: A number of features visible at thoracic CT are useful for determining whether an SPN is benign or malignant. FDG PET/CT plays an important role in the diagnosis and management of lung cancer and is an increasingly valuable tool for the characterization and management of SPNs. Unlike CT and MRI imaging, PET provides metabolic activity of a nodule. The information provided by PET/CT imaging allows for both morphological and anatomical characteristics as well as physiological data in the form of metabolism within the nodule itself. The information gained from PET is extremely useful for directing patient management and may obviate the need for invasive diagnostic procedures.
    • Incidence Estimates and Demographics of Scaphoid Fracture in the United States Population

      Van Tassel, Dane Carlisle; The University of Arizona College of Medicine - Phoenix; Wolf, Jennifer (The University of Arizona., 2012-05-01)
      Purpose: The epidemiology of scaphoid fracture occurrence is based mostly on retrospective analyses of small population centers. Analysis of a large injury database was performed with the hypothesis that previous studies have underestimated the incidence of scaphoid fracture. Methods: The National Electronic Injury Surveillance System (NEISS) is a probability sample of injuries in the United States presenting to emergency rooms. The NEISS model was queried for injuries classified as wrist fractures, and narrative data evaluated specifically for scaphoid fracture, over the 5-year period 2002-2006. Descriptive characteristics were analyzed with respect to patient demographics, location, mechanism, and sports/recreation participation. Results: A total of 507 injuries coded as fractures of the scaphoid comprised the dataset from 2002-2006, with weighted sampling estimating 21,481 scaphoid fractures nationwide during this time period. This results in an incidence rate for the US population of 1.47 fractures per 100,000 person-years (95% confidence intervals (CI), 1.31 to 1.63). 4 Conclusions: The NEISS dataset utilized in this study represents the largest single sample population for scaphoid fracture epidemiology in the medical literature. The estimated incidence of scaphoid fracture is higher in the U.S. than those reported for other countries.
    • The Incidence of Dysesthesia When Droperidol is Used for Prophylaxis of Post Operative Nausea and Vomiting

      Kassel, Kareem; The University of Arizona College of Medicine - Phoenix; Murray, Michael (The University of Arizona., 2012-04-30)
      Background: Multiple therapeutic regimens are used in an effort to attenuate the incidence of postoperative nausea and vomiting (PONV). Some drugs (e.g. dexamethasone, droperidol and scopolamine) are given preoperatively for prophylaxis in patients who are at increased risk of developing PONV. The use of droperidol has been associated with a relatively high incidence of dysesthesias (30% to 70%) in the outpatient setting, but we have not observed dysesthesias in most patients who receive it perioperatively. HYPOTHESIS: The incidence of dysesthesias in the perioperative period is less than that reported in the outpatient environment. Purpose: The primary goal was to determine the incidence of dysesthesia in patients treated with droperidol perioperatively for PONV. Secondary goals were to determine efficacy of droperidol for preventing PONV and the effect of droperidol on anxiety Methods: 30 patients who were at moderate to severe risk of developing PONV and met no exclusion criteria were asked to participate in the study. The consented patients completed a survey just prior to the intravenous administration of 0.625 mg of droperidol. 6 The survey was repeated 1 hour after the patient was admitted to the PACU Results: None of the patients reported dysesthesia (0%, p<.001). Patients also reported an average 2.2 point reduction on their 1-10 anxiety level after surgery and no patients complained of PONV. Conclusion: Dysesthesia from droperidol is much less common in the perioperative setting than has been reported in the outpatient setting. Based on result, low dose droperidol is expected to prove less likely to cause dysesthesias when used in the intraoperative setting for prophylaxis of PONV than reported in emergency departments and oncology clinics.
    • Investigating Molecular Mechanisms Driving Breast Cancer Metastasis into the CNS

      Holz, David R.; The University of Arizona College of Medicine - Phoenix; Tran, Nhan (The University of Arizona., 2012-04-30)
      This research project aims to identify unique candidate genes involved in breast cancer metastatic invasion into the central nervous system (CNS). The goal of this study focuses on studying and comparing the genomes of two distinct breast cancer cell lines that model a primary breast cancer and a CNS metastatic variant. These cell lines were established by Yoneda et al. by employing six serial rounds of tumor injection into mice followed by CNS isolation to select a unique clonal cell line that consistently metastasizes to the CNS. Denoted MDA MB-23-BR and MDA MB-231-P by their predilection for CNS metastasis and primary breast tumor growth patterns, respectively, this cell line pair represents a unique functional model for comparing a primary breast cancer and a CNS metastatic clone. Hypothesis: We hypothesized that the BR clone's predilection for CNS metastasis is likely due to unique genetic alterations either at a chromosomal or gene expression level that differ from the primary breast tumor line. The goals of this study aimed to probe the genomes of the MDA MB-23-BR and MDA MB-231-P using array CGH and microarray gene expression profiling to identify these potential 5 differential chromosomal patterns and distinct gene expression profiles between the Br and P cell lines. Results: Initial studies to assess the invasive properties of the BR and P lines showed an approximate five-fold increase in invasion of the BR line compared to the P line by employment of a modified Boyden chamber invasion assay. Results of the array CGH analysis did reveal small regions of relative chromosome loss of the BR line on chromosome 1 and chromosome 10. Results of the gene expression array analysis revealed 138 genes with either 2-fold overexpression or underexpression between the BR and P lines. Canonical Pathway analysis revealed two genes, ADAM19 and GAB1, that may play a role in cell survival and metastasis. Significance: This study successfully identified unique chromosomal and gene expression differences between the MDA MB-231 P and, BR cell lines. These differences, though preliminary, may represent unique genetic regions and genes that facilitate breast cancer metastasis to the CNS and could serve as novel candidates for both biomarker development and chemotherapeutic intervention.
    • Investigating the Role of IGF-1 Receptor in Glioma Cell Survival, Migration and Proliferation

      Sen, Lilia F; The University of Arizona College of Medicine - Phoenix; Berens, Michael (The University of Arizona., 2012-05-01)
      Glioblastoma (GB) is the most common primary brain tumor, distinctive by its aggressive, highly invasive, angiogenic and necrotic presentation. The Insulin-like growth factor (IGF) pathway plays an important role in cancer cell proliferation, survival and migration. This study was initiated to investigate the role of the IGF-1 receptor in glioma cell survival, migration and proliferation. We tested glioma cells’ response to IGF1 receptor inhibition and whether the response is dependent on the endogenous levels of pIGF1R β (phosphorylated IGF receptor). We used a small molecule inhibitor of IGF1R, Tyrphostin AG1024, to test for dose-dependent apoptosis and for sensitization to the combination treatment with temozolomide, an oral alkylating agent used for the treatment of Grade IV astrocytoma. We also observed that glioma cell migration and proliferation may depend on the endogenous level of pIGF1R β. Because IGF1R is widely expressed in healthy and malignant cells, development of therapeutic uses for IGF1R-inhibitors will require defining additional genomic or proteomic characteristics. This would confer differential vulnerability between tumor and normal cells. Further investigation is needed to determine the molecular predictors of a glioma cell’s response to IGF1R inhibition.
    • Investigation of Cytarabine Resistance: Targeting the Cell Cycle Checkpoints and Strategies for Overcoming Resistance of Acute Myeloid Leukemia to Cytarabine

      Buechel, Megan; The University of Arizona College of Medicine - Phoenix; Tibes, Raoul (The University of Arizona., 2012-04-30)
      Patients diagnosed with Acute myeloid leukemia (AML) often become resistant to standard chemotherapeutic regimens. Cytarabine, a nucleoside analog, is the standard of care therapy for AML treatment. We hypothesized that by using an siRNA platform to inhibit 572 kinases in combination with Ara-C (cytarabine) in two AML cell lines (THP-1 and TF-1) we would be able to identify potential therapeutic targets to improve sensitivity to Ara-C (cytarabine). Our siRNA screen identified CHK1 as the most potent sensitizer to Ara-C. However, other kinases involved in DNA repair and checkpoint activation also improved sensitivity of cells to Ara-C. Checkpoints are present at the G1/S transition, within S phase and at the G2/M transition. Within the G2/M checkpoint, CHK1 functions to halt the transition to mitosis when DNA damage is detected. Additional siRNA screening of proteins that function in the G2/M checkpoint identified WEE1 as a potent sensitizer as well. It is hypothesized that abrogation of the G2/M checkpoint prevents repair pathways from repairing genotoxic damage caused by chemotherapeutics. Therefore, a literature review of the checkpoint targeting and rational therapeutic targets for future treatments was conducted. Both WEE1 and CHK1 are currently 4 being targeted in order to enhance activity of various genotoxic chemotherapeutics in many different cancers and present rational targets for further investigated in combination with Ara-C in AML.
    • Modulation of Alzheimer’s Disease related APP Trafficking via Protein Kinase C

      Vithana, Rukmalee; The University of Arizona College of Medicine - Phoenix; Valla, Jon (The University of Arizona., 2012-05-01)
      Chronic phorbol ester treatment treatment of a neuroblastoma cell line, SH-SY5Y, was hypothesized to induce alterations in APP expression and trafficking such that the holoprotein will increasingly localize to mitochondria. Fluorescent immunocytochemistry and confocal microscopy was used primarily to visualize co-localization of Amyloid precursor protein (APP) to Translocase complex of the outer mitochondrial membrane (TOMM machinery) on the mitochondria. Co-localization experiments were inconclusive in showing that chronic phorbol 12-myristate 13- acetate (PMA) treatment affects APP trafficking to mitochondria. Due to those results, mitochondrial gradient fractionation experiments and subsequent western blots were started to determine if there was increased APP expression at the mitochondrial membrane and if protein kinase C (PKC) was activated by chronic PMA treatment.
    • The Montreal Cognitive Assessment and the Mini-Mental State Examination as Screening Instruments for Cognitive Impairment: Item Analyses and Threshold Scores

      Damian, Anne Mariam; The University of Arizona College of Medicine - Phoenix; Jacobson, Sandra (The University of Arizona., 2012-04-30)
      Objective: This study was performed to provide a detailed analysis of the MoCA versus the MMSE, including an item analysis and an examination of threshold scores appropriate for use in different clinical settings. Methods: 135 subjects enrolled in a longitudinal clinicopathologic study were administered the MoCA and MMSE. Subjects were classified as cognitively impaired or cognitively normal based on neuropsychological testing and consensus conference diagnosis. Results: 89 subjects were cognitively normal, 46 cognitively impaired (20 dementia, 26 MCI). ROC analysis showed that, for any threshold value selected for the MMSE to identify cognitive impairment, a MoCA value with better sensitivity and specificity could be identified. Recall performed best among individual items on the MMSE, and Orientation performed best on the MoCA. Overall, the best discrimination was obtained using a weighted combination of four items (2*MoCA-Orientation + MMSE-Recall + MoCA-Language + 0.5* MoCA-Visuospatial/Executive; AUC 0.94). A MoCA threshold score of 26 had a sensitivity of 98% and specificity of 52% for identifying cognitive 5 impairment. A MoCA threshold score of 21 had a sensitivity of 57% and specificity of 96%. Conclusions: The MoCA was superior to the MMSE in detecting cognitive impairment. Individual domains on the MoCA and MMSE made substantially different contributions to each instrument’s sensitivity, and a weighted subset of items from both instruments performed best in detecting cognitive impairment. A lower MoCA threshold score may be appropriate in a population with a higher prevalence of cognitive impairment such as a memory clinic.
    • MRI Findings Common to Infantile Hemangiomas

      Patel, Nirav; The University of Arizona College of Medicine - Phoenix; O'Haver, Judith; Price, Harper; Towbin, Richard (The University of Arizona., 2012-05-02)
      Background: Infantile hemangiomas (IH) are the most common vascular tumors of infancy. Children may have Magnetic Resonance Imaging (MRI) to establish or confirm the diagnosis or to further evaluate lesions that do not improve with treatment. Objective: Describe specific MRI findings common to infantile hemangiomas. Compare the imaging diagnosis with the clinical diagnosis of IH to determine diagnostic accuracy. Methods: A descriptive retrospective chart review on a convenience sample. Twenty-six patients had a total of 31 MR studies in the group. From these 31 studies, 16 also had magnetic resonance angiography (MRA). Results: Clinical diagnosis matched imaging diagnosis 96.8% of the time. Findings from imaging of the infantile hemangiomas included increased signal intensity on T2-weighted sequences (96.8%), isointense or decreased signal with T1-weighted sequences (83.9%) and moderate to marked contrast enhancement (78.5%). Lesions appeared to be high flow (64.5%), demonstrated lobulation (58.1%), and displayed central, low signal intensity dots on T2-weighted sequences (54.8%). In contrast, cystic spaces, intralesional DIC, phleboliths, focal intralesional inhomogenities, septation, edema, fat stranding, aneurysms, venous ectasia, and shunts were not features regularly seen in imaging of IHs in this study. Limitations: Small sample size on a convenience sample based at one institution. Conclusion: There are specific features to infantile hemangiomas on MR imaging that can be used for aid in diagnosis.
    • Non-emergency Use of Emergency Medicine Services According to Insurance Status in an Urban Population

      Morris, Gary; The University of Arizona College of Medicine - Phoenix; Petitti, Diana (The University of Arizona., 2012-05-01)
      Non-emergent use of Emergency Department (ED) resources has been targeted in political discourse as a potential for cost savings. The general consensus anecdotally is that there is a considerable amount of non-emergent ED use locally. The purpose of this study is to describe non-emergent use of the ED at Maricopa Medical Center and the association of non-emergent use with insurance and demographic variables. Computer-stored data about ED visits during the years 2008-2009 were provided by ASU’s Center for Health Information and visits were classified using an algorithm developed initially by Billings et al at the NYU Center for Health and Public Policy Research that uses International Classification of Diseases-9th edition Clinical Modification (ICD-9-CM) codes. The ICD-9-codes for each visit to the ED are obtained and the Billings algorithm is used to determine a percentage of likelihood that the visit was emergent or not after identifying visits that cannot be classified clearly as either emergent or non-emergent. After classifying ED visits, a statistical analysis was done to evaluate the association of demographic and insurance status variables with non-emergent use of the ED for all visits and for visits that were not due to injury, psychiatric conditions, alcohol or drugs. 4 We find that 47% of the visits were classified as non-emergent. Furthermore, of these non-emergent visits the rate of non-emergent use by insured patients is 34% compared to 54% rate for self-pay/charity patients and 50% rate for AHCCCS/Medicaid patients. Clearly there is a large volume of non-emergent use at MMC and a correlation exists between not having insurance and using the ED non-emergently at a higher rate compared to the insured population. All patient populations however did have a large number of non-emergent visits. Non-emergent ED use is then thought to be a valid target for health care policy discussion and a need exists for evaluating what the economic impact of these visits may be.
    • Non-Invasive Regional Oxygen Saturation Measurement in the Preterm Neonate

      Marrs, Laura; The University of Arizona College of Medicine - Phoenix; Martin, Gregory (The University of Arizona., 2012-04-30)
      There are several, predictable complications of prematurity that are faced by premature infants. Patent ductus arteriosus is among them. This study is an evaluation of a near infrared spectroscopy device to see if the premature infants can be monitored in order to detect significant ductal steal secondary to symptomatic PDA. We hypothesize that in these cases, there would be a difference between renal and cerebral regional oxygenation. To evaluate a difference, it is essential to first establish baseline regional oxygenation values, which are scarce in current literature. There are many pathophysiologic states experienced by premature infants, such as hypoxic spells and intraventricular hemorrhage, which may affect the data. Therefore, the effects of abnormal brain activity on cerebral monitoring are also evaluated. Our preliminary data shows a mean cerebral reading of 77.5189 and a mean renal reading of 70.9105, both without any linear trends. Now that normative data for regional oxygen saturation in the preterm neonate has been established, this opens up a pathway for the study of additional states, such as the left to right shunt of sPDA, since there is now a standard for comparison.
    • Pediatricians’ Attitudes and Practices Regarding Patient Immunization in Arizona

      Khan, Soofia; The University of Arizona College of Medicine - Phoenix; Sunenshine, Rebecca (The University of Arizona., 2012-04-30)
      Background: Despite the widespread availability of vaccines, including to the uninsured, significant numbers of both children and adults, remain unvaccinated or undervaccinated. Many reasons, including an increasing financial burden on primary care practices, availability of access to healthcare, and beliefs regarding vaccine safety, have been implicated; however, increasing concern has arisen regarding insurance payments for vaccines to providers [2, 5, 8]. Due to these concerns, we conducted a survey to understand the attitudes, perceptions and practices of Arizona pediatricians regarding vaccines and their reimbursement by insurance companies. Methods: In February 2011, 1407 standardized surveys were emailed, 87 surveys were faxed, and 216 surveys were mailed to AZ pediatricians who were listed in the Arizona Chapter of the American Academy of Pediatrics membership database. Results: From the 138 (9.0% response rate) responses, we identified that about half of all provider respondents refer insured and uninsured 5 patients to public health or other outside clinics for vaccines. The most common reason for outside patient referral for vaccine is inadequate reimbursement by insurance companies, and approximately one-third of providers did not vaccinate a patient due to inadequate reimbursement. Additionally, the vast majority of providers were interested in participating in a buying group run by TAPI. Conclusions: Based on our survey, inadequate reimbursement for vaccines by insurance companies negatively affects Arizona pediatricians’ provision of immunizations. A provider buying group coordinated by a not for profit immunization coalition is one possible solution for this problem.
    • Phase Two Study Examining Magnesium Dependent Tinnitus

      Patel, Alpen; The University of Arizona College of Medicine - Phoenix (The University of Arizona., 2012-05-01)
      Background: Recent studies in noise-induced and idiopathic sensorineural hearing loss have suggested that magnesium supplementation may lessen both hearing loss and the severity of tinnitus in patients. Further epidemiological evidence indicates that all age groups of Americans fall short of the recommended daily allowance for magnesium by 100 mg daily. Purpose: The purpose of this study was to examine any potential benefit in lessening the severity of tinnitus in patients taking supplemental magnesium. Research Design: The study was a single-arm, open-label, before-and-after study of oral magnesium (532 mg per day) in 26 patients for 3 months. Tinnitus severity was evaluated and recorded daily by the patient using the Tinnitus Distress Rating (TDR) scale of 0 (no tinnitus) to 10 (worst possible tinnitus). The Tinnitus Handicap Inventory (THI) was administered before and at the end of the study, and scores were converted to the grades of the 5-item Tinnitus Severity Scale (TSS).As a phase 2 study, the current design could not distinguish the effect of treatment from a placebo effect or regression to the mean. All data were collected at Mayo Clinic in Scottsdale, Arizona. 3 Study Sample: Patients with moderate to very severe tinnitus (TDR score of 3 through 8). Intervention: Daily magnesium supplementation, 532 mg; patient completion of the THI; and daily self-report of TDR. Data Collection and Analysis: The main outcome measures were mean TDR scale scores and THI scores as converted to TSS grades. The primary analysis was done on the basis of intention to treat. Results: Twenty-six patients were enrolled; 19 completed the study. The extent of handicap, as measured by THI/TSS, for subjects with slight or greater impairment was significantly decreased (P=.03). Patients who ranked slight or greater on the THI/TSS before intervention showed a significant decrease in the severity of their tinnitus at post-testing (P=.008). Conclusion: The results suggest that magnesium may have a beneficial effect on perception of tinnitus-related handicap when scored with the THI. Keywords: Magnesium; Tinnitus; Tinnitus Distress Rating; Tinnitus Handicap Inventory; Tinnitus Severity Scale
    • Preference of Health-related Learning Modalities Among Asian Americans in Maricopa County

      Chan, Nam; The University of Arizona College of Medicine - Phoenix; Hirano, Doug (The University of Arizona., 2012-04-30)
      Asian Americans are the fastest growing racial/ethnic group in the United States, with more than 60% of its members being foreign born, and 30% of limited English proficiency. Often perceived as the healthy and wealthy “Model Minority,” Asian Americans in fact suffer disproportionately in a number of areas of health, such as liver cancer and diabetes. There is a paucity of evidence-based interventions specifically adapted for and tested among Asian American to address these health disparities. We therefore aimed to investigate the preferred learning modalities in this population. We utilized a brief questionnaire to investigate how Asian Americans residing in Maricopa County prefer to learn and build skills related to health improvement. The results suggest that there is no dominant preference for learning modalities among Asian Americans; therefore, modalities in both individual and group learning should be offered. The only group that shows a statistically significant preference for individual learning is the respondents with postsecondary education. Consequently, in addition to group interventions such as the Diabetes Prevention Program, researchers should consider developing self-guided training on-line and through printed materials. This initial 4 research will help guide future efforts to educate the Asian American populations on diabetes prevention and other health conditions.
    • Prophylactic Dosing of Myofascial Release in a Human Fibroblast Model of Wound Closure

      Powell, Travis Joseph; The University of Arizona College of Medicine - Phoenix; Standley, Paul (The University of Arizona., 2012-05-01)
      Myofascial release (MFR) allows clinicians to directly stretch and palpate soft tissue restrictions, improving tissue elasticity, and maximizing range of motion. Research has focused on MFR following repetitive motion strain (RMS), however there is no known application of prophylactic MFR. Utilizing in vitro strain models we will investigate the role of prophylactic MFR in regulating fibroblast wound healing. We hypothesize that MFR treatments will have greater efficacy when used prior to the repetitive motion strain, increasing the rate of wound healing. Human fibroblasts were seeded onto 6-well collagen-I bioflex plates, strained with the Flexcell vacuum compression system. Sub-confluent cell constructs were wounded using sterile 1ml pipette tips to create an area devoid of cells. Spatial wound edge changes were monitored to determine closure rate at 0, 12, 24, 36 and 48 hours. Pooled data for 36 hours demonstrated that RMS closed 32% faster than the combined RMS+MFR and 30.5% faster than the non-strain control, p<0.05. This meant the data did not support the hypothesis, but prophylactic stretching has been shown to prevent and reduce injury in 5 other models. Prophylactic MFR requires additional studies to expand our model to include multiple dosed treatments with a stronger emphasis on prevention vs. healing.
    • Relationship Between Maternal Expectations of Perinatal Care and Postpartum Depression

      Williams, Danielle; The University of Arizona College of Medicine - Phoenix; Mattox, John (The University of Arizona., 2012-05-01)
      The incidence of postpartum depression (PPD) is estimated at 13-19%, with effects reaching far beyond the affected mother. However, its precise cause is still unknown. In this double-blinded study, a 30-question Maternal Expectations Survey (MES) was developed to explore the notion that unmet maternal expectations for labor, delivery, and the immediate postpartum period impose risk factors for PPD. The MES was administered to postpartum women at Banner Good Samaritan Medical Center; and scores were compared to those on the Edinburgh Postnatal Depression Scale (EPDS), administered 6 weeks postpartum to the same women in the outpatient setting of the clinic of their attending physician. Results of this interim analysis, using Poisson regression models, indicated that there is no significant correlation between total MES score and EPDS score. Two MES queries (relating to spontaneous onset of labor and coping mechanisms during labor) are independently predictive of an increased EPDS score. With attainment of adequate power, other components of the MES may emerge as genuine risk factors for PPD and help identify women who would benefit from earlier-than-usual, pre-emptive postpartum counseling. This study also served to buttress the validity of 5 considering the presence of neonatal health complications as a risk factor for PPD; and, conversely, it identified obstetric complications, neonatal health complications and a recent stressful life event as significant predictors of an increased MES score. Additionally, the presence of a written birth plan is also a significant predictor of increased
    • Renal Cell Carcinoma in Arizona American Indians/Alaska Natives

      Winegard, Billie; The University of Arizona College of Medicine - Phoenix; Flood, Timothy (The University of Arizona., 2012-05-02)
      OBJECTIVE – This study assesses trends in the incidence of cancers of the kidney and renal pelvis (K&RP) with focus on renal cell carcinoma (RCC) from 1995-2009 among American Indian/Alaska Natives (AI/AN) residing in Arizona. RESEARCH DESIGN AND METHODS – Using the Arizona Cancer Registry (ACR), we obtained the total number of new cases of cancers of the K&RP from 1995 through 2009. The incidence rates of these cancers, as well as the sub-group of RCC, were age-adjusted to the 2000 U.S. population for comparison between populations. Comparisons between demographic and tumor characteristics were also completed between AI/AN and non-Hispanic white cases. RESULTS – Between 1995 and 2009, 502 cases of K&RP were diagnosed in AI/AN in Arizona, with a majority of these cases (463, 92.23% of cases) being RCC of the kidney parenchyma. Over the study period, the age-adjusted incidence per 100,000 population was 19.18 for all tumors of the K&RP and 17.65 for RCC. Comparing the average age-adjusted rate over the first third (1995-1999) of the study period versus the last third (2005-2009), the rate of RCC among AI/AN increased 12.30% from 16.55 to 18.58 per 100,000 population. When this rate was stratified by sex, AI/AN males showed the most striking increase - 54.56% (19.22 to 29.70 cases of RCC per 100,000 population). While AI/AN females showed a decrease in the rate of 28.24% (14.20 to 10.19 cases per 100,000 population). CONCLUSIONS – The incidence rate of RCC has increased dramatically in Arizona AI/AN males. Research looking at this disease in this group is needed to determine which risk factors may be associated and to determine if any steps can be taken toward prevention or if there is a need for screening in this population.
    • A Role for Estrogen Receptor β in the Inhibition of Prostate Cancer Cell Growth

      Ibragimov, Angela; The University of Arizona College of Medicine - Phoenix; Handa, Robert (The University of Arizona., 2012-04-30)
      Prostate cancer (PC) and benign prostatic hypertrophy (BPH) are highly prevalent neoplasms. Studies have demonstrated the androgen-dependent nature of benign and pathologic growth of prostate cells. Although Androgen Receptors (AR) have strong proliferative activity in the prostate, recent studies have implicated an anti-proliferative role for Estrogen Receptor Beta (ERβ). This study investigates the effects of ERβ stimulation on normal prostate growth in vivo as well as on PC cell growth in vitro to better elucidate a mechanism for the proposed anti-proliferative actions of ERβ. We also study the interplay between concurrent androgen and ERβ stimulation on PC cell proliferation in vitro. Our hypothesis is that ERβ activation will decrease cell growth and increase cell death in PC cells. Three different ERβ-simulating compounds were analyzed; the selective ERβ agonist diarylpropionitrile (DPN), the dihydrotestosterone (DHT) metabolite 5 alpha androstane-3 β 17b diol (3β-diol), and the isoflavone metabolite, equol, a daidzein-derived compound with phytoestrogen properties. DPN (2mg/Kg) treatment of adult male EZC3 mice for 21 days caused a significant decrease in dorsolateral lobe weight as 4 compared to control (P=.0002). Equol has the same effect on the dorsolateral lobe weight of Sprague-Dawley rats. Furthermore, DPN treatment of human Lymph Node Carcinoma of the Prostate cells (LNCaP) decreased cell proliferation, an effect that was overcome by concurrent treatment with DHT. Interestingly, equol also showed an anti-proliferative effect in cells when used alone as well as in the presence of DHT. 3β-diol, however, did not alter cell growth. Prostate specific antigen (PSA) levels measured from treated LNCaP cells as a measure of androgen stimulation demonstrated that DPN does not interfere with the ability of DHT to stimulate the AR. Furthermore, in vitro data strongly suggest an antagonistic action of equol on the effects of DHT not seen by DPN or 3β-diol. Our data suggest an anti-proliferative role of some ERβ agonists, notably DPN and equol. Although these agonists are ligands of the same receptor, it appears that they activate different molecular pathways and have varying effects on androgen stimulation by DHT. The effects of ERβ agonists are of paramount importance in modulating hormone-induced PC cell proliferation and may have future clinical implication in this widely-prevalent disease condition.
    • The Role of Access: Acute Asthma Care Utilization in a 2008 Arizona Medicaid Population

      Ortiz, Zachary; The University of Arizona College of Medicine - Phoenix; Petitti, Diana (The University of Arizona., 2012-05-01)
      Prior research shows racial disparities in patient (IP) and emergency department (ED) use for children with asthma. It has been difficult to disentangle the effects of race/ethnicity from the effect of socioeconomic status on IP and ED use. To better understand the relationship between race/ethnicity and care in these settings, data from a cohort of 3490 school-age children with asthma enrolled in the AHCCCS (Medicaid) program in Maricopa County, Arizona in 2008 were analyzed. For children with asthma, odds ratios were estimated by comparing ‘any visit’ (ED or IP) to ‘no visits’ according to race/ethnicity. Among children with asthma, junior high and high school individuals were more likely to experience a visit compared to elementary school age individuals. African-Americans were about twice as likely to have at least one ED or IP visit compared with White, non-Hispanics. Odds ratios for having any ED or IP visit were also increased in Hispanics and Native-Americans compared with White, non-Hispanics but the increases were not statistically significant. Although the generalizability of the study is limited, the data suggest that differences in socioeconomic status do not fully explain racial disparities in use of the ED and IP settings for asthma care. Attempts 5 to further understand any causal relationship between race/ethnicity and asthma should be coupled with targeted interventions to minimize known disparities.
    • Segmental Glomerulosclerosis in Pima Indians with Type 2 Diabetes

      Seidel, Ruthanna; The University of Arizona College of Medicine - Phoenix; Weil, E. Jennifer (The University of Arizona., 2012-05-01)
      Diabetes mellitus is widespread in the United States, and diabetic kidney disease is one of the most common complications. There is increasing evidence that podocyte injury is the initial pathologic change in diabetic nephropathy, and podocytopathy often manifests on renal biopsy as segmental sclerosis in other kidney diseases. The purpose of this study was to determine if segmental sclerosis is widespread in diabetic kidney disease. This study examined 1142 glomeruli from 61 Pima Indians who had diabetes for at least ten years. 24 patients were normoalbuminuric, 20 were microalbuminuric, and 17 were macroalbuminuric. The presence of segmental sclerosis was noted, as was global sclerosis. Segmental sclerosis was present in less than 2% of glomeruli. All glomeruli showed evidence of diabetic nephropathy including mesangial hypercellularity and invasion of mesangium into capillary loops. These data suggest that segmental sclerosis is not present in significant amounts in diabetic kidney disease. Rather, pathologic changes in the glomeruli of diabetic patients occur in a more diffuse pattern.