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Sivaprasad S.,King's College | Gupta B.,King's College | Gulliford M.C.,King's College London | Mann S.,St Thomas Hospital Nhs Foundation Trust | And 2 more authors.
PLoS ONE | Year: 2012

Purpose: To provide estimates of visual impairment in people with diabetes attending screening in a multi-ethnic population in England (United Kingdom). Methods: The Diabetic Retinopathy In Various Ethnic groups in UK (DRIVE UK) Study is a cross-sectional study on the ethnic variations of the prevalence of DR and visual impairment in two multi-racial cohorts in the UK. People on the diabetes register in West Yorkshire and South East London who were screened, treated or monitored between April 2008 to July 2009 (London) or August 2009 (West Yorkshire) were included in the study. Data on age, gender, ethnic group, visual acuity and diabetic retinopathy were collected. Ethnic group was defined according to the 2011 census classification. The two main ethnic minority groups represented here are Blacks ("Black/African/Caribbean/Black British") and South Asians ("Asians originating from the Indian subcontinent"). We examined the prevalence of visual impairment in the better eye using three cut-off points (a) loss of vision sufficient for driving (approximately <6/9) (b) visual impairment (<6/12) and (c) severe visual impairment (<6/60), standardising the prevalence of visual impairment in the minority ethnic groups to the age-structure of the white population. Results: Data on visual acuity and were available on 50,331individuals 3.4% of people diagnosed with diabetes and attending screening were visually impaired (95% confidence intervals (CI) 3.2% to 3.5%) and 0.39% severely visually impaired (0.33% to 0.44%). Blacks and South Asians had a higher prevalence of visual impairment (directly age standardised prevalence 4.6%, 95% CI 4.0% to 5.1% and 6.9%, 95% CI 5.8% to 8.0% respectively) compared to white people (3.3%, 95% CI 3.1% to 3.5%). Visual loss was also more prevalent with increasing age, type 1 diabetes and in people living in Yorkshire. Conclusions: Visual impairment remains an important public health problem in people with diabetes, and is more prevalent in the minority ethnic groups in the UK. © 2012 Sivaprasad et al.

Haymart M.R.,Endocrinology and Diabetes | Haymart M.R.,University of Michigan | Haymart M.R.,North Campus Research Complex | Banerjee M.,University of Michigan | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Little is known about practice patterns in thyroid cancer, a cancer that is increasing in incidence. Objective: Wesought to identify aspects of thyroid cancer management that have the greatest variation. Design/Setting/Participants: We surveyed 944 physicians involved in thyroid cancer care from 251 hospitals affiliated with the US National Cancer Database. Physicians were asked questions in the following four domains: thyroid surgery, radioactive iodine use, thyroid hormone replacement postsurgery, and long-term thyroid cancer management. We calculated the ratio of observed variation to hypothetical maximum variation under the assumed distribution of the response. Ratios closer to 1 indicate greater variation. Results: We had a 66% response rate. We found variation in multiple aspects of thyroid cancer management, including the role of central lymph node dissections (variation, 0.99; 95% confidence interval [CI], 0.98-1.00), the role of pretreatment scans before radioactive iodine treatment (variation, 1.00; 95% CI, 0.98-1.00), and all aspects of long-term thyroid cancer management, including applications of ultrasound (variation, 0.97; 95% CI, 0.93-0.99) and radioactive iodine scans (variation, 0.99; 95% CI, 0.97-1.00). For the management of small thyroid cancers, variation exists in all domains, including optimal extent of surgery (variation, 0.91; 95% CI, 0.88-0.94) and the role of both radioactive iodine treatment (variation, 0.91; 95% CI, 0.89-0.93) and suppressive doses of thyroid hormone replacement (variation, 1.00; 95% CI, 0.99-1.00). Conclusion: We identified areas of variation in thyroid cancer management. To reduce the variation and improve the management of thyroid cancer, there is a need for more research and more research dissemination. Copyright © 2013 by The Endocrine Society.

PubMed | University of Michigan, Endocrinology and Diabetes and Endocrinology and Diabetes.
Type: Journal Article | Journal: European journal of endocrinology | Year: 2016

Co-secretion of cortisol and aldosterone can be observed in adrenal adenomas. The aim of this study was to investigate the molecular characteristics of a co-existing aldosterone- and a cortisol-producing adenoma (CPA) in the same patient.Two different adenomas within the same adrenal gland from a 49-year-old female patient with primary aldosteronism (PA) and Cushings syndrome (CS) were studied. Multiple formalin-fixed paraffin-embedded tumor blocks were used for the analysis. Immunohistochemistry (IHC) was performed using a specific antibody against aldosterone synthase (CYP11B2). DNA and RNA were isolated separately from CYP11B2-positive and -negative tumor regions based on CYP11B2 IHC results.CYP11B2 IHC clearly demonstrated that three pieces from one adenoma were positive for CYP11B2 and the remaining three from the other adenoma were negative for CYP11B2. In quantitative real-time RT-PCR, CYP11B2 mRNA was upregulated in CYP11B2-positive tumor specimens (219-fold vs CYP11B2-negative tumor specimens). Targeted next-generation sequencing (NGS) detected novel KCNJ5 gene mutations (p.T148I/T149S, present in the same reads) and a PRKACA gene hotspot mutation (p.L206R) in the CYP11B2-positive and -negative tumors, respectively. Sanger sequencing of DNA from each tumor specimen (CYP11B2-positive tumor, n=3; CYP11B2-negative tumor, n=3) showed concordant results with targeted NGS.Our findings illustrate the co-existence of two different adrenocortical adenomas causing the concurrent diagnosis of PA and CS in the same patient. Molecular analysis was able to demonstrate that the two diseases resulted from independent somatic mutations seen in double adrenocortical adenomas.

The International Association of HealthCare Professionals is pleased to welcome Jorge A. Pino, MD, Endocrinologist, to their prestigious organization with his upcoming publication in The Leading Physicians of the World. Dr. Jorge A. Pino is a highly trained and qualified physician with an extensive expertise in all facets of his work, especially in endocrinology, internal medicine, diabetes, and metabolism. Dr. Pino has been in practice for more than 35 years and is currently serving patients within Diabetes and Endocrinology Associates in Birmingham, Alabama. He is also affiliated with St. Joseph Hospital. Dr. Jorge A. Pino graduated with his Medical Degree in 1964 from the Universidad del Valle in Cali, Columbia. Upon relocating to the United States, Dr. Pino completed his Endocrinology and Diabetes residency at the Southeast Louisiana Veterans Health Care System, before undertaking an additional residency at the University of Alabama at Birmingham. Dr. Pino is double board certified in Endocrinology and Internal Medicine, and in addition to his clinical practice, he serves as a Clinical Professor at the University of Alabama at Birmingham. He attributes his success to his great education, constantly learning, and his excellent mentors. In his free time, Dr. Pino likes to relax by reading and traveling. Learn more about Dr. Pino by reading his upcoming publication in The Leading Physicians of the World. is a hub for all things medicine, featuring detailed descriptions of medical professionals across all areas of expertise, and information on thousands of healthcare topics.  Each month, millions of patients use FindaTopDoc to find a doctor nearby and instantly book an appointment online or create a review. features each doctor’s full professional biography highlighting their achievements, experience, patient reviews and areas of expertise.  A leading provider of valuable health information that helps empower patient and doctor alike, FindaTopDoc enables readers to live a happier and healthier life.  For more information about FindaTopDoc, visit

Rubio D.M.,University of Pittsburgh | Schoenbaum E.E.,Yeshiva University | Lee L.S.,Duke University | Schteingart D.E.,Endocrinology and Diabetes | And 6 more authors.
Academic Medicine | Year: 2010

Because translational research is not clearly defined, developers of translational research programs are struggling to articulate specific program objectives, delineate the knowledge and skills (competencies) that trainees are expected to develop, create an appropriate curriculum, and track outcomes to assess whether program objectives and competency requirements are being met. Members of the Evaluation Committee of the Association for Clinical Research Training (ACRT) reviewed current definitions of translational research and proposed an operational definition to use in the educational framework. In this article, the authors posit that translational research fosters the multidirectional and multidisciplinary integration of basic research, patient-oriented research, and population-based research, with the long-term aim of improving the health of the public. The authors argue that the approach to designing and evaluating the success of translational training programs must therefore be flexible enough to accommodate the needs of individual institutions and individual trainees within the institutions but that it must also be rigorous enough to document that the program is meeting its short-, intermediate-, and long-term objectives and that its trainees are meeting preestablished competency requirements. A logic model is proposed for the evaluation of translational research programs. © 2010 Association of American Medical Colleges.

Yoshimoto F.K.,Endocrinology and Diabetes | Peng H.-M.,Endocrinology and Diabetes | Zhang H.,University of Michigan | Anderson S.M.,Endocrinology and Diabetes | And 2 more authors.
Biochemistry | Year: 2014

Some cytochrome P450 enzymes epoxidize unsaturated substrates, but this activity has not been described for the steroid hydroxylases. Physiologic steroid substrates, however, lack carbon-carbon double bonds in the parts of the pregnane molecules where steroidogenic hydroxylations occur. Limited data on the reactivity of steroidogenic P450s toward olefinic substrates exist, and the study of occult activities toward alternative substrates is a fundamental aspect of the growing field of combinatorial biosynthesis. We reasoned that human P450c17 (steroid 17-hydroxylase/17,20-lyase, CYP17A1), which 17- and 16α-hydroxylates progesterone, might catalyze the formation of the 16α,17-epoxide from 16,17-dehydroprogesterone (pregna-4,16-diene-3,20-dione). CYP17A1 catalyzed the novel 16α, 17-epoxidation and the ordinarily minor 21-hydroxylation of 16,17-dehydroprogesterone in a 1:1 ratio. CYP17A1 mutation A105L, which has reduced progesterone 16α -hydroxylase activity, gave a 1:5 ratio of epoxide:21-hydroxylated products. In contrast, human P450c21 (steroid 21-hydroxylase, CYP21A2) converted 16,17-dehydroprogesterone to the 21-hydroxylated product and only a trace of epoxide. CYP21A2 mutation V359A, which has significant 16α-hydroxylase activity, likewise afforded the 21-hydroxylated product and slightly more epoxide. CYP17A1 wild-type and mutation A105L do not 21- or 16α-hydroxylate pregnenolone, but the enzymes 21-hydroxylated and 16α,17-epoxidized 16,17-dehydropregnenolone (pregna-5,16-diene-3β-ol-20-one) in 4:1 or 12:1 ratios, respectively. Catalase and superoxide dismutase did not prevent epoxide formation. The progesterone epoxide was not a time-dependent, irreversible CYP17A1 inhibitor. Our substrate modification studies have revealed occult epoxidase and 21-hydroxylase activities of CYP17A1, and the fraction of epoxide formed correlated with the 16α-hydroxylase activity of the enzymes. (Chemical Equation Presented). © 2014 American Chemical Society.

Moraitis A.G.,endocrinology and Diabetes | Rainey W.E.,endocrinology and Diabetes | Rainey W.E.,University of Michigan | Auchus R.J.,endocrinology and Diabetes
Application of Clinical Genetics | Year: 2014

Primary aldosteronism (PA) is the most common form of secondary hypertension, found in about 5% of all hypertension cases, and up to 20% of resistant hypertension cases. The most common forms of PA are an aldosterone-producing adenoma and idiopathic (bilateral) hyperaldosteronism. Rare genetic forms of PA exist and, until recently, the only condition with a known genetic mechanism was familial hyperaldosteronism type 1, also known as glucocorticoid-remediable aldosteronism (FHA1/GRA). FHA type 3 has now been shown to derive from germline mutations in the KCNJ5 gene, which encodes a potassium channel found on the adrenal cells. Remarkably, somatic mutations in KCNJ5 are found in about one-third of aldosterone-producing adenomas, and these mutations are likely to be involved in their pathogenesis. Finally, mutations in the genes encoding an L-type calcium channel (CACNA1D) and in genes encoding a sodium-potassium adenosine triphosphatase (ATP1A1) or a calcium adenosine triphosphatase (ATP2B3) are found in other aldosterone-producing adenomas. These fndings provide a working model, in which adenoma formation and/or aldosterone production in many cases derives from increased calcium entry, which drives the pathogenesis of primary aldosteronism. © 2014 Moraitis et al.

Else T.,Endocrinology and Diabetes | Williams A.R.,University of Michigan | Sabolch A.,University of Michigan | Jolly S.,University of Michigan | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Adrenocortical carcinoma is a rare malignant endocrine neoplasia. Studies regarding outcomeandprognostic factors relyonfairly small studies. Herewesummarize the experience with patients with a diagnosis of adrenocortical carcinoma from a large tertiary referral center. Objective: The objective of the study was to identify prognostic factors in patients with adrenocortical carcinoma and evaluate adjuvant treatment strategies. Design: Patient datawerecollected in a retrospective single-center study. Epidemiological, patient, and tumor characteristics were analyzed for prognostic factors regarding overall and recurrencefree survival in Cox regression models (multivariable and univariable). Results: Three hundred ninety-one adult patients with the diagnosis of adrenocortical carcinoma were identified. Median overall survival was 35.2 months. Cortisol production [hazard ratio (HR) 1.4, HR 1.5], tumor stage (HR stage 3 of 2.1 and 2.1, HR stage 4 of 4.8), and tumor grade (HR 2.4 and 2.0) were identified as negative prognostic factors (HR for death, HR for recurrence). Mitotane therapy increases recurrence-free survival, an effect that was significantly further improved by adjuvant radiation therapy but did not impact overall survival. Patients with open adrenalectomy had improved overall survival. Conclusions: This study increases the evidence for adverse risk factors (cortisol production, high tumor stage, and high tumor grade) and suggests the following therapy approach: adrenocortical carcinoma patients should be treated with open adrenalectomy. Adjuvant therapy, particularly mitotane therapy in conjunction with radiation, should be considered to delay tumor recurrence. Copyright © 2014 by the Endocrine Society.

PubMed | University of Michigan and Endocrinology and Diabetes
Type: Journal Article | Journal: Current diabetes reports | Year: 2016

Diabetic neuropathies (DNs) are one of the most prevalent chronic complications of diabetes and a major cause of disability, high mortality, and poor quality of life. Given the complex anatomy of the peripheral nervous system and types of fiber dysfunction, DNs have a wide spectrum of clinical manifestations. The treatment of DNs continues to be challenging, likely due to the complex pathogenesis that involves an array of systemic and cellular imbalances in glucose and lipids metabolism. These lead to the activation of various biochemical pathways, including increased oxidative/nitrosative stress, activation of the polyol and protein kinase C pathways, activation of polyADP ribosylation, and activation of genes involved in neuronal damage, cyclooxygenase-2 activation, endothelial dysfunction, altered Na(+)/K(+)-ATPase pump function, impaired C-peptide-related signaling pathways, endoplasmic reticulum stress, and low-grade inflammation. This review summarizes current evidence regarding the role of low-grade inflammation as a potential therapeutic target for DNs.

Papaleontiou M.,Endocrinology and Diabetes | Haymart M.R.,Endocrinology and Diabetes and Hematology Oncology
Current Opinion in Oncology | Year: 2014

PURPOSE OF REVIEW: Numerous staging and scoring systems exist for differentiated thyroid cancer (DTC), but all harbor limitations. This has prompted investigation for new factors with prognostic implications for DTC. RECENT FINDINGS: Several new factors that may be involved in DTC risk stratification have emerged, such as thyroid stimulating hormone and molecular markers. In addition, others are controversial and being challenged, such as age, sex and lymph node involvement. SUMMARY: The purpose of this review is to present recent updates in the literature on new potential risk stratification predictors for DTC. © Lippincott Williams & Wilkins.

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