• 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.
    • 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
    • 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.
    • Trends In Unintentional Drug Overdose-related Deaths

      Sharer, Rustan; The University of Arizona College of Medicine - Phoenix; Petitti, Diana (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.
    • 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 (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.
    • 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 (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.