ABOUT THE COLLECTION

The Scholarly Project (SP) Course represents a four-year mentored research project for each student. The SP prepares students for lifelong learning and critical thinking. Through the SP, students develop advanced inquiry and problem-solving skills to support clinical practice and future research endeavors throughout their careers. The formal curriculum is embedded in this course, is referred to as the SP Learning Community (SPLC) in which all students participate. The SPLC curriculum is most intense in the first-year during which the students are exposed to issues that relate to information literacy, research methodology, ethical behavior in research, statistics and research proposal and grant writing. In addition, the students receive assistance in how to choose areas they wish to investigate, design a research hypothesis and find a mentor. By the end of the second semester of the first year each student is expected to have his/her project designed and approved and to have selected a mentor who will guide and oversee the progress of the project. Both the SPLC and the independent scholarly activity are monitored by a variety of periodic assessments to assure appropriate guidance and advancement.


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More information is found here: http://medicine.arizona.edu/education/phoenix-track/scholarly-project

Recent Submissions

  • MRI Findings Common to Infantile Hemangiomas

    Patel, Nirav; The University of Arizona College of Medicine - Phoenix; O'Haver, Judith, PhD; Price, Harper, MD; Towbin, Richard, MD (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.
  • The Cryptic Peptides, Prepro-Thyrotropin Releasing Hormone 186-199 and 194-199, Suppress Anterior Pituitary Prolactin Secretion in vivo and in vitro

    Shortridge, Emily; The University of Arizona College of Medicine - Phoenix; Handa, Robert, PhD (The University of Arizona., 2012-05-02)
    Prepro-thyrotropin releasing hormone (ppTRH)-176-199 is one of several peptide fragments cleaved during TRH synthesis and has been implicated as a regulator of neuroendocrine function. ppTRH 176-199 has been shown to acutely inhibit the stress-induced rise in ACTH, corticosterone (CORT), and prolactin (PRL) in the rat. The receptor for ppTRH 176-199 currently remains unknown. In this study we sought to characterize the active domain of ppTRH 176-199 and, using in vivo and in vitro approaches, determine its role in regulating anterior pituitary secretion of PRL. The 186-199, 194-199, and 186-191 amino acid fragments of ppTRH were administered I.P. to adult male Sprague-Dawley rats 15 min. prior to a 20 min restraint stress to determine the peptide’s active moiety in regulating prolactin secretion. Animals were euthanized and plasma was saved for assay of circulating PRL using enzyme immunoassay (EIA). ppTRH 186-199 significantly attenuated the stress-induced rise in prolactin in male rats in a dose-responsive fashion. This effect was mimicked by ppTRH 194-199 but not by ppTRH 186-191. At the highest dose (10 mg/kg BW), ppTRH 194-199 also reduced the stress-induced rise in plasma CORT. Additionally, in vitro studies were performed using the rat growth hormone (GH)/PRL –secreting MMQ cell line. MMQ cells were treated with ppTRH 186-199 and media was assayed for PRL levels. Cells were harvested and examined for changes in PRL mRNA. Within 30 minutes following treatment of estradiol-stimulated MMQ cells with ppTRH 186-199 there was a decrease in media levels of PRL compared to vehicle. Furthermore, in MMQ cells that were primed with 10nM estradiol for 48 hours there was an increase in media PRL levels, which was reduced following ppTRH 186-199 treatment. After 4 hrs of treatment, the inhibitory effect of ppTRH 186-199 on PRL secretion from MMQ cells was only seen on estradiol-stimulated cells. There were no effects of ppTRH 186-199 when examined after 24 hrs of treatment. There were no effects of ppTRH 186-199 or 194-199 of PRL mRNA levels. These data suggest that the carboxy terminal fragment of preproTRH 178-199 contains all the activity of this ppTRH cryptic peptide for regulation of PRL and corticosterone secretion. This suggests a potential moiety responsible for interaction with the peptide’s receptor. The inhibitory effect of ppTRH 186-199 and 194-199 on media PRL levels and not on mRNA synthesis implicates it as an effector of hormone secretion rather than protein synthesis. The short-lived duration of its effects supports a role as 6 an acute effector of the PRL system. The target receptor of the ppTRH 178-199 fragment remains uncertain. However the use of ppTRH 194-199 as a peptide bait may prove useful in identifying the receptor.
  • Validation of the Confusion Assessment Method in the Intensive Care Unit in the Post-Anesthesia Care Unit

    Townsend, Nichole L.; The University of Arizona College of Medicine - Phoenix; Murray, Michael, MD, PhD (The University of Arizona., 2012-05-02)
    Introduction: Patients who develop delirium while hospitalized are increasingly recognized as at risk for the development of long term cognitive impairment. We became interested in the contribution of delirium to the development of post-operative cognitive dysfunction (POCD) when we found that patients at Mayo Clinic in Arizona, compared to patients at the Mayo facilities in Rochester, MN, were 17 times more likely to receive the drug physostigmine (Antilirium®) for the treatment of delirium in the Post Anesthesia Care Unit (PACU). However, before we could examine the relationship between delirium and POCD we needed to validate a tool we could use to quickly assess the presence of delirium in patients emerging from anesthesia in the PACU. Hypothesis: The Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) can be used in the PACU to identify patients with delirium. Methods: Patients 65 years of age or greater who were going to have a standardized general anesthetic for a surgical procedure were identified on the day of surgery and consent to participate in the study was obtained. The CAM-ICU was used preoperatively to determine study eligibility (patients who scored less than 7 [scale of 1-10], indicating delirium, on the test were not followed further) and postoperatively, one hour after the patient was admitted to the PACU, to assess for delirium. The CAM-ICU was administered after we asked the patient’s nurse whether or not he or she had determined that the patient was delirious. Results: 168 patients, mean age 75 ± 7 (SD) with the majority of participants having urologic or orthopedic procedures were assessed pre- and post-operatively with the CAM-ICU, and post-operatively by a nursing assessment for delirium. The CAM-ICU took little time to administer and was easy for patients to understand and use. The nurse at the bedside identified 5 of 168 patients as delirious (prevalence of 2.98%). The CAM-ICU was positive for delirium in 11 of 168 (6.55%). The CAM-ICU had a sensitivity of 60% (3/5) and a specificity of 95% (155/163). Conclusion: In this investigation, the CAM-ICU was easy to use and had a high specificity for identifying post-operative delirium.
  • Renal Cell Carcinoma in Arizona American Indians/Alaska Natives

    Winegard, Billie; The University of Arizona College of Medicine - Phoenix; Flood, Timothy, MD (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.
  • Relationship Between Maternal Expectations of Perinatal Care and Postpartum Depression

    Williams, Danielle; The University of Arizona College of Medicine - Phoenix; Mattox, John, MD (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
  • Current Usage of Helicopter Ambulances Services in the State of Arizona

    Williams, Andrew R.; The University of Arizona College of Medicine - Phoenix; Campos-Outcalt, Douglas, MD, MPA (The University of Arizona., 2012-05-01)
    The overall goals of this research project were threefold: to characterize how the Helicopter Ambulance system in Arizona is used for trauma, comparison of Ground and Helicopter Ambulance usage, and recommendations to facilitate effective use of the Helicopter Ambulance system. Data for this project were obtained from the Arizona Department of Health Services Trauma Registry. Analysis included descriptive statistics, crosstabulation, calculation of two-year usage rates, and Z-score (for proportions) comparison between Ground and Helicopter Ambulance for statistical significance (using SPSS18/20). The American Indian/Alaska Native population was the most frequently transported (two-year rate 1572.3/100,000 population; all transport methods). Gila County and Yuma County had the highest rates of Ground Ambulance transport (Gila 1016.8/100,000, Yuma 1161.7/100,000) whereas Maricopa County was much lower (431/100,000). For Helicopter Ambulance use, the most common counties of transport were Navajo and Gila (414.1/100,000 and 606.4/100,000) whereas Maricopa county was much lower (24.2/100,000). 5 The significance of this project comes in the area of recommendations for system improvement. Recommendations include ground-based triage areas to determine whether a patient should be transported to a Level I trauma center (or whether a lower level of care is acceptable), as well as how the patient should be transported (Helicopter v. Ground Ambulance).
  • Modulation of Alzheimer’s Disease related APP Trafficking via Protein Kinase C

    Vithana, Rukmalee; The University of Arizona College of Medicine - Phoenix; Valla, Jon PhD (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.
  • Imaging Evaluation of the Solitary Pulmonary Nodule

    Van Tassel, Lora; The University of Arizona College of Medicine - Phoenix; Korn, Ronald, MD, PhD (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, MD (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.
  • Comparison of Common High-risk Pregnancy Conditions Between Health Start and Non-Health Start Participants

    Stump, Marla Krysteen; The University of Arizona College of Medicine - Phoenix; Lopez, Ana, MD, MPH (The University of Arizona., 2012-05-01)
    Context: Health Start is a program run by the Arizona Department of Health Services (ADHS) that utilizes community health workers to educate at-risk pregnant women and new mothers throughout many of the underserved regions of Arizona. The Health Start Curriculum - the tool used to educate community health workers on prenatal and infant care - is currently undergoing a revision. This project is intended to examine medical risk factors and birth outcomes unique to Health Start participants in order to provide information that will be considered when revising the curriculum. Objective: To compare the prevalence of medical risk factors and selected birth outcomes of women actively enrolled in Health Start to their age-matched, race/ethnicity-matched, and delivery method-of-payment-matched counterparts. Methods: A cross-sectional study was conducted at the Arizona Department of Health Services Bureau of Women’s and Children’s Health using the birth certificate data from women who gave birth in Arizona in 2009. A relative risk for each medical risk factor and birth outcome parameter was tabulated using chi-square analysis, and the 5 statistical significance was determined utilizing a p-value of 0.05 as the cutoff for statistical significance. Results: Overall the study revealed a significantly lower rates of anemia in active Health Start participants compared to inactive Health Start enrollees (1.4% vs. 7.2%, p-value = 0.001). The low relative risk of pre-term delivery for Health Start participants compared to matched controls approached statistical significance (5.8% vs. 10.1%, p-value = 0.057), but the power of the test was limited due to small sample size. Other medical risk factors and birth outcomes did not reveal a statistically significant difference between active Health Start participants and matched controls or active Health Start Participants and inactive Health Start enrollees. Conclusions: Active enrollment in the Health Start program is associated with significantly lower rates of anemia and notably lower rates of pre-term delivery. A follow-up study with a larger sample size is indicated to increase the power of the study.
  • 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, MS (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.
  • TRP1 Peptide Requires Internalization and is Partially Dependent on GILT for Efficient Presentation on MHC Class II

    Sjursen, Anne Marie; The University of Arizona College of Medicine - Phoenix; Hastings, Karen, MD, MPH (The University of Arizona., 2012-05-01)
    Tyrosinase-related protein 1 (TRP1) is a melanosomal integral membrane protein and melanocyte differentiation antigen that contributes to the synthesis of melanin in melanocytes. Present in both benign and malignant melanocytes, it has been implicated in the autoimmune development of vitiligo and melanoma antitumor immunity. Since a naturally occurring MHC class II-restricted TRP1 epitope contains cysteine residues, we hypothesized that this epitope will require internalization and reduction by gamma-interferon-inducible lysosomal thiol reductase (GILT) for presentation on class II. GILT is known to catalyze the reduction of protein disulfide bonds in the endocytic pathway and contribute to antigen processing and presentation of certain MHC class I and class II epitopes. We have previously shown that GILT is required for efficient class II-restricted presentation of TRP1. Here, we found that TRP1 peptide presentation is partially dependent on GILT and that TRP1 peptide requires internalization for efficient presentation on class II. We also determined that antigen presentation increased with increasing peptide dose and increasing APC:T cell ratio. Compared to other TRP1-specific T cells, primary TRP1-specific T cells from TRP1BwRAG-/- 5 TRP1tg mice produce maximal IL-2 in response to presentation of TRP1. These results further illustrate the importance of GILT in the processing and presentation of TRP1. Thus, GILT may play a role in both the development of autoimmune vitiligo and anti-melanoma immune responses.
  • The CLASE Study: Endovascular Management of the Superficial Femoral Artery

    Shieh, Hester F.; The University of Arizona College of Medicine - Phoenix; Rodriguez, Julio, MD (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.
  • Trends In Unintentional Drug Overdose-related Deaths

    Sharer, Rustan; The University of Arizona College of Medicine - Phoenix; Petitti, Diana, MD, MPH (The University of Arizona., 2012-05-01)
    Since undergoing a radical paradigm shift in prescribing trends in the late 80s/early 90s, the therapeutic use and non-therapeutic abuse of controlled prescription drugs (specifically opioids) has reached prolific levels in the US. Despite seemingly widespread awareness of such trends and associated dangers, mortality and morbidity associated with such medications continues to escalate in the face of rapidly increasing prescribing patterns. This investigation attempts to further characterize time trends of accidental deaths secondary to overdoses of various drugs (primarily comparing Arizona to national trends with respect to various demographic identifiers). Utilizing publicly available data sources, a statistical analysis was performed on yearly mortality rates for selected drug-overdose related causes of death between 1999 and 2007. Arizona consistently exhibited higher death rates--with Pinal County claiming the highest among all urbanizations--(but lower annual rates of increase) than the national trends. Men were also shown to have much higher death rates than women (although women’s rates are increasing much faster than men). Furthermore, Hispanics demonstrated significantly lower death rates than non-Hispanics (whose death rates were shown to be increasing three times faster than Hispanics). Rapidly increasing death rates pose a significant concern at both the state and national levels.
  • 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, PhD (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.
  • Segmental Glomerulosclerosis in Pima Indians with Type 2 Diabetes

    Seidel, Ruthanna; The University of Arizona College of Medicine - Phoenix; Weil, E. Jennifer, MD (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.
  • A Comparison of Depression Screening Tools in Parkinson’s Disease and Normal Community Controls Using a Brain and Body Donation Database

    Rosen, Amanda; The University of Arizona College of Medicine - Phoenix; Shill, Holly, MD (The University of Arizona., 2012-05-01)
    The purpose of this study was to review and compare a variety of depression inventories in Parkinson’s disease (PD) and normal controls (NC) to look for patterns or trends to help with clinical management of these patients. The study population consisted of subjects enrolled in a brain and body donation program who were receiving annual neurological and neuropsychiatric assessments. Statistical models were applied to the data to compare trends between screening tools, medications, and demographics. The frequency of depression was greater in PD cases than NC across the inventories. The greatest frequency of positive screens came from the Neuropsychiatric Inventory (NPI). Because the NPI requires an informant to administer, and had the highest percent of positive screens in both PD and NC groups, this study suggests that a caregiver or partner may be a helpful addition in clinical practice during depression screening in elderly patients with and without PD.
  • 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, PhD (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.
  • 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, PhD (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.
  • 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

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