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Mandrik O.,Erasmus University Rotterdam | Mandrik O.,Lviv National Medical University | Severens J.L.,Erasmus University Rotterdam | Doroshenko O.,Ukrainian Institute for Strategic Research | And 9 more authors.
Journal of Multidisciplinary Healthcare | Year: 2013

This study evaluates the impact of hypoglycemia on the lives of Ukrainian patients with type 2 diabetes mellitus. The secondary objective was to explore patient-physician relationships and the attitudes of patients towards various informational resources on diabetes management. Three focus groups with 26 patients were conducted. Qualitative information was evaluated using content analysis. The results show that patients with type 2 diabetes mellitus in Ukraine are adapting to potential attacks of hypoglycemia; however, they still experience periodic manifestations of hypoglycemia that significantly affect their psychological well-being. This result is similar to observations made in other countries. Ukrainian patients >40 years old mainly receive information on disease management from endocrinologists, and rarely use internet resources on diabetes management. Information provision was especially important at the early stage of the disease, when patients lack information on hypoglycemia manifestations and could therefore fail to identify and manage it properly. © 2013 Mandrik et al, publisher and licensee Dove Medical Press Ltd.

Sofiadis A.,Karolinska University Hospital | Becker S.,Karolinska University Hospital | Hellman U.,Uppsala University | Hultin-Rosenberg L.,Karolinska University Hospital | And 10 more authors.
European Journal of Endocrinology | Year: 2012

Objective: Thyroid proteomics is a new direction in thyroid cancer research aiming at etiological understanding and biomarker identification for improved diagnosis. Methods: Two-dimensional electrophoresis was applied to cytosolic protein extracts from frozen thyroid samples (ten follicular adenomas, nine follicular carcinomas, ten papillary carcinomas, and ten reference thyroids). Spots with differential expression were revealed by image and multivariate statistical analyses, and identified by mass spectrometry. Results: A set of 25 protein spots significant for discriminating between the sample groups was identified. Proteins identified for nine of these spots were studied further including 14-3-3 protein beta/alpha, epsilon, and zeta/delta, peroxiredoxin 6, selenium-binding protein 1, protein disulfide-isomerase precursor, annexin A5 (ANXA5), tubulin alpha-1B chain, and a1-antitrypsin precursor. This subset of protein spots carried the same predictive power in differentiating between follicular carcinoma and adenoma or between follicular and papillary carcinoma, as compared with the larger set of 25 spots. Protein expression in the sample groups was demonstrated by western blot analyses. For ANXA5 and the 14-3-3 proteins, expression in tumor cell cytoplasm was demonstrated by immunohistochemistry both in the sample groups and an independent series of papillary thyroid carcinomas. Conclusion: The proteins identified confirm previous findings in thyroid proteomics, and suggest additional proteins as dysregulated in thyroid tumors. © 2012 European Society of Endocrinology.

Tsymbaliuk I.,Shupyk National Medical Academy of Postgraduate Education | Tsymbaliuk I.,Kyiv City Teaching Endocrinological Center | Unukovych D.,Bogomolets National Medical University | Unukovych D.,Karolinska Institutet | And 4 more authors.
PLoS ONE | Year: 2015

Background: Graves' disease (GD) is a common cause of hyperthyroidism resulting in development of thyrotoxic heart disease (THD). Objectives: to assess cardiovascular disorders and health related quality of life (HRQoL) in patients with THD secondary to GD. Patients and Methods: All patients diagnosed with THD secondary to GD between January 2011 and December 2013 were eligible for this study. Clinical assessment was performed at baseline and at the follow-up visit after the restoring of euthyroid state. HRQoL was studied with a questionnaire EQ-5D-5L. Results: Follow-up data were available for 61 patients, but only 30 patients with THD secondary to GD were consented to participate in investigation of their HRQoL. The frequency of cardiovascular complications was significantly reduced as compared before and after the antithyroid therapy as follows: resting heart rate (122 vs. 74 bpm), blood pressure: systolic (155 vs. 123 mm Hg), diastolic (83 vs. 66 mm Hg), supraventricular premature contractions (71% vs. 7%), atrial fibrillation (72% vs. 25%), congestive heart failure (69% vs. 20%), thyrotoxic cardiomyopathy (77% vs. 26%), all p <0.01. Anti-TSH receptor antibodies were determined as independent predictor of left ventricular geometry changes, (b-coefficient = 0.04, 95%CI 0.01-0.07, p = 0.02). HRQoL was improved in all domains and self-rated health increased from 43 to 75 units by visual analogue score (p<0.001). Conclusions: Restoring of euthyroid state in patients with GD is associated with significant elimination of cardiovascular disorders and improvement of HRQoL. To our knowledge this is the first study evaluating Ukrainian patients with THD secondary to GD with focus on HRQoL. © 2015 Tsymbaliuk et al.

Sofiadis A.,Karolinska University Hospital | Dinets A.,Karolinska University Hospital | Dinets A.,Kyiv City Teaching Endocrinological Center | Orre L.M.,Karolinska Institutet | And 12 more authors.
Thyroid | Year: 2010

Background: The accurate diagnosis of thyroid tumors is challenging. Proteomics has emerged as a promising approach for the discovery of molecular diagnostic markers as a potential complement to routine diagnostics. Methods: Protein fractions from 29 frozen thyroid tumor tissue samples (10 papillary carcinomas, 9 follicular carcinomas, and 10 follicular adenomas) as well as from normal thyroid tissue were analyzed by surface enhanced laser desorption/ionization time-of-flight mass spectrometry followed by validation by Western blotting and immunohistochemistry. Results: A Ca2+-binding protein belonging to the S100 family, S100A6, was differentially expressed between papillary and follicular thyroid tumors. Moreover, two posttranslationally modified forms of S100A6 were observed and verified by liquid chromatography-coupled tandem mass spectrometry. Validation by Western blotting displayed a significantly higher expression of S100A6 in papillary thyroid carcinoma (PTC) in comparison with the other tumor groups or normal tissue (p<0.05). Immunohistochemical analysis on 98 tumors showed that PTC cases had a significantly stronger cytosolic staining and a larger proportion of stained nuclei than follicular tumors. BRAF gene mutation was not significantly associated with S100A6 protein levels. Conclusion: This study supports a role of S100A6 in thyroid tumorigenesis and as a potential aid in the discrimination between follicular thyroid tumors and PTC. © Copyright 2010, Mary Ann Liebert, Inc.

Dinets A.,Karolinska University Hospital | Dinets A.,Kyiv City Teaching Endocrinological Center | Hulchiy M.,Kyiv City Teaching Endocrinological Center | Sofiadis A.,Karolinska University Hospital | And 5 more authors.
European Journal of Endocrinology | Year: 2012

Background: Increased incidence of papillary thyroid carcinoma (PTC) is observed as a consequence of radiation exposure in connection to the Chornobyl nuclear plant accident in 1986. In this study, we report a cohort of adult Ukrainian patients diagnosed with PTC from 2004 to 2008 following exposure at the age of 18 years or younger. Methods: In total, 70 patients were identified and clinically characterized. The common BRAF 1799T>A mutation was assessed by pyrosequencing, the RET/PTC1 and RET/PTC3 (NCOA4) rearrangements by RT-PCR, and the expression of Ki-67 (MIB-1 index), BCL2, cyclin A, and cyclin D1 by immunohistochemistry. Results: In total, 46/70 (66%) cases carried a BRAF mutation and/or a RET/PTC rearrangement. A BRAF mutation was detected in 26 tumors, RET/PTC1 in 20 cases, and RET/PTC3 in four cases. In four of these cases, BRAF mutation and RET/PTC rearrangement were coexisting. The BRAF mutation was underrepresented among PTCs with accompanying chronic lymphocytic thyroiditis (CLT) compared with PTCs without this feature (12 vs 44%). MIB-1 proliferation index determined by double staining with leukocyte common antigen was low (mean 0.8%; range 0.05-4.5%). Moreover, increased expression of cyclin A was observed in PTCs with a tumor size >2 cm compared with PTCs ≤2 cm (1.2 vs 0.6%). BCL2 and cyclin D1 showed frequent expression but without associations to clinical characteristics or amplification of the CCND1 locus. Conclusions: Our results suggest that this cohort has frequent BRAF mutation, RET/PTC1 rearrangement, and low proliferation index. Furthermore, BRAF 1799T>A was underrepresented in PTCs with CLT, and cyclin A expression was associated with increased PTC tumor size. © 2012 European Society of Endocrinology.

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