• The CLASE Study: Endovascular Management of the Superficial Femoral Artery

      Shieh, Hester F.; The University of Arizona College of Medicine - Phoenix; Rodriguez, Julio (The University of Arizona., 2012-05-01)
      Objectives – The purpose of this study was to compare endovascular treatment modalities for peripheral vascular disease in the femoropopliteal arteries with respect to technical success, efficacy, and patency at mid-term follow up. Methods – A retrospective review of patients that underwent endovascular management of the femoropopliteal segment was conducted to evaluate patency. The CLASE study included five treatment arms: cryoplasty, laser, angioplasty/stent, Silverhawk atherectomy, and Viabahn endoluminal graft. Results – Between November 2004 and May 2009, 306 patients met inclusion criteria. There was a statistically significant difference in patencies among treatment groups (p=0.016), driven by laser having a significantly lower patency than the angioplasty/stent, Silverhawk atherectomy, and Viabahn endoluminal graft groups. Conclusions – Many of the expensive endovascular devices have poor patencies lasting less than six months. Angioplasty/stent is not inferior to these new devices, and may remain the standard of care.
    • Focusing on the Patient Encounter to Improve Adult Immunization Rates

      Moore, David A.; The University of Arizona College of Medicine - Phoenix; Birkholz, Karla (The University of Arizona., 2012-05-01)
      Objective: Healthy People 2010 established target goals for the percentage of adults immunized against Pneumococcus and seasonal influenza. Our objective was to create a vaccine program to allow our family practice clinic to reach these goals. Methods: Initial chart review (n=50) determined our clinic’s baseline percentages for Pneumococcus and billing records identified the number of influenza vaccines administered the previous year. We developed a vaccine program focused on direct intervention and executed it in two six-month phases; the first focused on seasonal influenza, and the second targeted Pneumococcus. We determined program efficacy of phase one (influenza) via shot volume and phase two by measuring post-program vaccine percentages thru a second chart review (n=104). Results: Pneumococcal coverage for adults age ≥65 dropped from 47 to 39% [95% CI: 23-71% & 22-56%], well short of the Healthy 4 People 2010 target of 90%. We measured a 16% volume increase in the administration of the seasonal influenza vaccine. Significance: Vaccines have tangible and positive effects on patient health. Direct intervention is an effective method for physicians to improve vaccine percentages, but is costly and time consuming.
    • 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
    • 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.
    • Establishing the Demographics and Rationale for Use of Preimplantation Genetic Diagnosis and Screening in Arizona and Outlying Locations

      Sprunger, Victoria; The University of Arizona College of Medicine - Phoenix; Hunt, Katherine (The University of Arizona., 2012-05-01)
      Background: Pre-implantation genetic diagnosis (PGD) and pre-implantation genetic screening (PGS) test for genetic diseases prior to implantation in cases utilizing in-vitro fertilization. While PGD/PGS use is expanding, ramifications for patients and society are unclear. Study Question: What is the current utilization and patient demographics of Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS) in Arizona Infertility clinics? Significance: Though PGD/PGS usage has grown, gaps remain in the understanding of current U.S. clinic experience. This study addresses these, focusing on the diverse Arizona patient population, by surveying all Arizona in-vitro fertilization clinics. Methods: Using capture-recapture method, all IVF-providing clinics within Arizona (n=11) were identified and sent an anonymous survey. Surveys were then analyzed. Results: Nine of eleven clinics responded. While patient demographics were similar, patient numbers per clinic differed and were not correlated with length of operation. Genetic tests differed amongst 5 clinics. Most favored self-regulatory models, recognized the Internet as the primary source of patient education, and valued increased PGD/PGS education. Conclusion: Patient demographics revealed that minority populations were not proportionally represented when compared to census data. Clinics offered differing sets of genetic tests and criteria for seeking these tests, indicating varying opinions amongst clinics about the ethicality of PGD/PGS.
    • Suppression of Lipopolysaccharide-induced Inflammatory Responses in RAW 264.7 Macrophages by Aqueous Extract of Clinopodium vulgare L. (Lamiaceae)

      Burk, David; The University of Arizona College of Medicine - Phoenix; Daskalova, Sasha (The University of Arizona., 2012-04-30)
      ETHNOPHARMACOLOGICAL RELEVANCE: The wild basil Clinopodium vulgare L. is commonly used in Bulgarian folk medicine for treatment of irritated skin, mastitis- and prostatitis-related swelling, as well as for some disorders accompanied with significant degree of inflammation (e.g. gastric ulcers, diabetes, and cancer). AIM OF STUDY: To determine the effect of aqueous extract of Clinopodium vulgare L. on LPS-induced inflammatory responses of murine RAW 264.7 macrophages. MATERIALS AND METHODS: Cell cytotoxicity was evaluated by MTT assay. Protein expression levels were monitored by Western blot analysis. Production of NO and PGE(2) was measured by the Griess colorimetric method and enzyme immunoassay, respectively. Activation of MMP-9 was visualized by gelatin zymography. Cytokine levels were determined by BioPlex assay. Intracellular ROS and free radical scavenging potential were measured by DCFH-DA and DPPH method, respectively. Xanthine oxidase activity was evaluated spectrophotometrically.
    • Sustainability of a Culturally Informed Community-Based Diabetes Prevention Program for Obese Latino Youth

      Greenwood-Ericksen, Margaret; The University of Arizona College of Medicine - Phoenix; Shaibi, Gabriel (The University of Arizona., 2012-04-30)
      Latino youth are disproportionately impacted by obesity and type 2 diabetes; however, few lifestyle interventions have targeted this population. Therefore, the purpose of this study was to assess the impact of a culturally informed lifestyle education pilot program on nutrition and physical activity behaviors among obese Latino youth. A retrospective chart review of 67 youths was conducted with self-reported nutrition and physical activity assessed both immediately following the program and after long-term follow-up. Body mass index (BMI) was evaluated to determine the impact of behavior changes on adiposity. Healthy nutrition and physical activity changes were reported by 20%-59% of youths immediately following the program. However, most of these changes were attenuated over the 261 ± 49 day follow-up with reported walking (25.4%) and sports participation (34.3%) sustained to a greater extent than dietary changes (3.4–14.9%). Nonetheless, children who continued walking at follow-up exhibited significantly larger reductions in BMI compared with those who did not (-1.63 ± 0.56 vs. 0.44 ± 0.30 kg/m2, P < .05). Based on our pilot study, we conclude that community-based lifestyle education programs can support behavior modification and weight management 5 in obese Latino youth. Ongoing support may be necessary to encourage
    • Design Requirements of Educational EHR for use in Case Based Instruction of First and Second Year Medical Students

      Germain, Michael; The University of Arizona College of Medicine - Phoenix; Silverman, Howard (The University of Arizona., 2012-04-30)
      Case based instruction (CBI) in medical education is a well established alternative to lecture format in the training of first and second year medical students. There have been previous documented attempts to include technology in CBI that have received positive feedback from students. Electronic health records are now being mandated by 2014 and historically there have been many barriers to adoption including lack of EHR technical skills by physicians. As a result, biomedical informatics education is being integrated into medical school curriculum with hope that better understanding of medical applications will prepare future physicians to utilize them. There has been no documented evidence of successful utilization of a commercial grade EHR within CBI despite many potential benefits in doing so. Previous attempts at accomplishing this task have been discovered but multiple challenges were encountered in developing a suitable educational EHR and as a result the attempt was unsuccessful. The following is a design project with the aim of highlighting specific design requirements, as well as, a theoretical usage scenario of a commercial grade EHR in CBI. Outlined as well is experimental design for future evaluation of such a system. There will be many 4 technological challenges that will need to be overcome and numerous resource requirements to get such a project functional. Despite this, all aspects of such a system are technologically feasible. Completion of such a system could result in potential commercial benefit and provide a platform for further investigation of early EHR training effect on physician-EHR acclimation.
    • Doctoring and Disabilities: Analyzing the Implementation of a Disabilities-focused Clinical Skills Program for Second-year Medical Students

      Churgin, Daniel; The University of Arizona College of Medicine - Phoenix; Campagnolo, Denise (The University of Arizona., 2012-04-30)
      Objectives: To investigate second-year medical students’ change in comfort level after a disabilities-focused interactive session, with regards to disability etiquette and greeting, interviewing, and examining patients with disabilities. Setting: The University of Arizona College of Medicine, Phoenix Campus, doctoring suites. Students interacted in a clinical setting with volunteers with disabilities, including volunteers with blindness, deafness, mobility impairment, and language impairment. Students received 3 surveys during the study duration: the first before the event, the second after they had prepared for the event with didactic materials, and the third after the event. Participants: 46 second-year medical students participated in the event, and 29 students completed all surveys. Methods: Survey data was analyzed using paired t-tests wherever possible, with P <0.05 being interpreted as significant. Results: Comfort level for disability etiquette and greeting, interviewing, and examining patients with disabilities improved significantly for patients with blindness, deafness, mobility impairment, and language impairment. Although this change was significant for most measures from pre-event to post-event, it was significant for every measure from post-materials to post-event. Conclusion: A pre-clinical disabilities event in which second-year medical students interact with people with disabilities is effective in increasing student comfort level.
    • Three Cases in Pediatric Neuroradiology: Athabascan Brainstem Dysgenesis Syndrome, Aicardi Goutières Syndrome, and Aplasia of the Parotid Glands

      Higley, Meghan; The University of Arizona College of Medicine - Phoenix; Towbin, Richard (The University of Arizona., 2012-04-30)
      Summary: The human HOXA1 mutation syndromes commonly present with abnormalities of the inner ear and internal carotid arteries. Previous cases describe varying degrees of hypoplasia or aplasia of the affected structures, often with asymmetrical involvement. We present imaging findings documenting complete absence of the internal carotid arteries bilaterally with bilateral Michel aplasia of the inner ear, which, to our knowledge, has not been previously reported. Based on the number of cases identified and birth rates within studied populations, we estimated the incidence of ABDS at 0.5-1:1000 live births on the White River Apache Reservation and 1:3000 live births in the Navajo population. If accurate, this suggests a carrier frequency similar to that for cystic fibrosis in Caucasian populations. ABDS may represent a significantly underrecognized disorder among Athabaskan Native Americans, raising questions of the possible benefit of genetic counseling for affected families. However, cultural considerations in this population bring into question the possible conflict between counseling based on gene theory and traditional beliefs.
    • Defining 1H-MRS Criteria Used to Differentiate Brain Tumor from Radiation Necrosis

      Crain, Ian; The University of Arizona College of Medicine - Phoenix; Preul, Mark (The University of Arizona., 2012-04-30)
      An effective modality for differentiating recurrent brain tumor from post-treatment radiation effect remains elusive. The average survival time after diagnosis of high grade brain tumors is one year. It is imperative to maximize currently available interventions to increase survival. One potential imaging technique to differentiate tumor recurrence from treatment effect is 1H-MRS. It is currently unknown how this imaging modality performs this task in the clinical setting. This study presents a variety of cases that represent the spectrum of 1H-MRS use, interpretation, and outcomes of patients with gliomas at a high volume tertiary treatment facility. The state of 1H-MRS use for differentiating tumor recurrence from radiation necrosis demonstrates a need for better techniques and criteria for interpretation of acquired 1H-MRS information.
    • 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.
    • 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.
    • 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.
    • 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.
    • Diffusion-based Heterogeneity Models in Magnetic Resonance Imaging for Characterization of Brain Tumors: An Introductory Study

      Goettl, Christopher; The University of Arizona College of Medicine - Phoenix; Karis, John (The University of Arizona., 2012-04-30)
      Recently developed diffusion-based magnetic resonance (MR) protocols have proven useful in assessing the heterogeneity of water diffusion in neural tissues, including brain tumors1. Based on theoretical increase in tumor cell heterogeneity compared to healthy brain2, these emerging imaging modalities offer several potentially useful applications, such as in identifying tumor margins, establishing tumor type and grade, and for differentiating tumor recurrence from post-treatment effect. In this study an introductory subset of five patients were scanned using a multi b-value Diffusion-Weighted Image (DWI) sequence, fitted with two previously described higher-order diffusion models. The first utilized a stretched exponential model (α-DWI)3; the second applied a cumulant expansion model (Diffusional Kurtosis Image, DKI)4. These models quantified water diffusion heterogeneity using the fitted parameters α and Kapp, respectively. The intent of this project was to gauge the potential utility of these MR models to apply diffusion heterogeneity information for characterization of brain tumors. Early results confirmed initial 6 hypotheses for high-grade gliomas, that (1) diffusion heterogeneity appeared greater in tumoral regions than in surrounding tissue, (2) high-grade tumors exhibited a relatively more heterogeneous diffusion pattern (lower α and higher K app) compared with low-grade glioma, and (3) the metastatic tumor had unique diffusion behavior compared to the primary tumors. Overall, this introductory study generally supports the potential ability of higher-order diffusion heterogeneity models to characterize brain tumors. More detailed investigation of this application across a larger subset of patients and tumor types may be beneficial.
    • 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.
    • 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.
    • GWAS for Bipolar Disorder in a European Cohort with CNV Discovery

      Mitropanopoulos, Sotiris; The University of Arizona College of Medicine - Phoenix; Craig, David (The University of Arizona., 2012-04-30)
      Background: Bipolar disorder (BD) is a disabling disorder whereby individuals suffer from episodes of mania and depression. The mode of inheritance of BD is complex and likely multifactorial. The specific number of susceptibility loci, the recurrence risk ratio attributable to each locus, and the degree of interaction between loci are unknown. By determining whether single nucleotide polymorphisms (SNPs) or copy number variants (CNVs) predispose individuals to bipolar disorder, therapeutics and diagnostic tests may be developed. Method: A Genome Wide Association Study (GWAS) was performed using cases of bipolar disorder and normal controls hybridized on Affymetrix 6.0 Genome-Wide Human SNP Arrays. Data preprocessing removed 595 individuals from 2205 arrays. The probe intensities of the remaining 880 cases and 730 controls were normalized. A modified t-test algorithm was used to determine p-values for each SNP. A sliding window analysis was performed on SNPs ordered by chromosome and locus. The mean probe intensities of the cases and controls from regions of significance were then reanalyzed for differences. Results: Analysis yielded several SNPs and CNVs that may have involvement in the pathophysiology of bipolar disorder. One region was 15kbp within the Neuron Navigator 2 (NAV2) gene. A second region was found in the Down Syndrome Cell Adhesion Molecule Like 1 (DSCAML1) gene. A third region was within the Voltage-dependent Calcium Channel Alpha 1G (CACNA1G). Conclusion: Multiple SNPs and CNVs may play a role in the phenotype of Bipolar Disorder. A convergent functional genomics approach with a gene network analysis maybe warranted elucidating possible pathophysiologies involving the gene products found to be significant in this study.
    • 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.