79 results on '"Mitrovic K"'
Search Results
2. Type 2 diabetes mellitus and impaired glucose regulation in overweight and obese children and adolescents living in Serbia
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Vukovic, R, Mitrovic, K, Milenkovic, T, Todorovic, S, and Zdravkovic, D
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- 2012
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3. Gonadal function after haematopoietic stem cell transplantation: the single-centre experience: P587
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Vujic, D., Milenkovic, T., Zdravkovic, D., Sedlecki, K., Todorovic, S., Mitrovic, K., Perovic, S., Stankovic, Z., Mazibrada, I., Jevtic, D., and Zecevic, Z.
- Published
- 2011
4. Factor analysis of variables associated with oxidative stress status in paediatric patients with type 1 diabetes mellitus
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Vekic, J., primary, Bogavac-Stanojevic, N., additional, Kacarevic, D., additional, Bojanin, D., additional, Mihajlovic, M., additional, Stefanovic, A., additional, Kotur-Stevuljevic, J., additional, Milenkovic, T., additional, Vukovic, R., additional, Todorovic, S., additional, Mitrovic, K., additional, and Spasojevic-Kalimanovska, V., additional
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- 2019
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5. P164 How can continuous glucose monitoring system impact on therapy of Cystic Fibrosis-Related Diabetes (CFRD) in youth
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Todorovic, S., primary, Milenkovic, T., additional, Minic, P., additional, Mitrovic, K., additional, Sovtic, A., additional, Rodic, M., additional, and Rade, V., additional
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- 2018
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6. Live birth rates are satisfactory following multiple IVF treatment cycles in poor prognosis patients
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Mustafa, K., Keane, Kevin, Walz, N., Mitrovic, K., Hinchliffe, P., Yovich, John, Mustafa, K., Keane, Kevin, Walz, N., Mitrovic, K., Hinchliffe, P., and Yovich, John
- Abstract
This seven-year retrospective study analysed the live birth rate (LBR) for women undergoing IVF treatment with various antral follicle counts (AFC). The LBR decreased with lower AFC ratings, and in 290 treatment cycles for women in the poorest AFC category, ≤4 follicles (group E), the LBR was the lowest at 10.7%. The pregnancy loss rate (PLR) significantly increased with poorer AFC categories, from 21.8% in AFC group A (≥20 follicles), to 54.4% in AFC group E (p < 0.0001). This trend was repeated with advancing age, from 21.6% for younger women ( < 35 years), to 32.9, 48.5 and 100% for ages 35–39, 40–44 and ≥45 years, respectively (p < 0.0001). However, LBR within the specific AFC group E cohort was also age-dependent and decreased significantly from 30.0% for <35 years old, to 13.3, 3.9 and 0% for patients aged 35–39, 40–44 and ≥45 years, respectively. Most, importantly, LBR rates within these age groups were not dependent on the number of IVF attempts (1st, 2nd, 3rd or ≥4 cycles), which indicated that cycle number should not be the primary deciding factor for cessation of IVF treatment in responding women <45years old.
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- 2017
7. Germinal Centers in the Tonsilla Caecalis — Relationship to the Thymus and the Bursa of Fabricius
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Janković, B. D., Mitrović, K., Cottier, H., editor, Odartchenko, N., editor, Schindler, R., editor, and Congdon, C. C., editor
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- 1967
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8. Anthropological research on coming of age and 'extended youth': Youth 'well-spent' in Serbia
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Mitrović Katarina M.
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youth ,serbia ,extended youth ,cultural representation ,life course ,Demography. Population. Vital events ,HB848-3697 - Abstract
While focusing on the phenomenon of “extended youth”, this paper presents the results of anthropological research on coming of age: classical and contemporary. The paper questions the parameters of “normality” when it comes to “extending” phases, youth in particular. While examining what it means to be young, the paper emphasises anthropological contributions to life course research. First of all, the paper focuses on research that highlights concepts seen as universal and biological. Moreover, it approaches classical anthropological research that analyses lifecycle customs and rites of passage. By emphasising classic anthropological works, such as the contributions of Margaret Mead, the paper shows how ethnographic examples have helped present the diversity of the perception of “adequate”, “normal”, and “good” when it comes to life stages or transitions from one life stage to another. In addition to the work of Mead, special attention is paid to the work of Arnold van Gennep, whose research on rites of passage had a great influence on generations of Serbian ethnologists and anthropologists. Van Gennep’s scheme of successive stages made up of the pattern of rites of passage (separation, transition/liminality, and aggregation) has been particularly important in the context of the transition into adulthood. Finally, this paper analyses how young people in Serbia perceive their youth and life stages in the contemporary context. The presented results are part of a qualitative research study based on in-depth interviews conducted in 2019 and 2020. The results highlight the cultural representations of the “normal” life course and life stage transitions, then present how some young people manage their transition to adulthood in order to perceive their youth as “well-spent”. The conclusion examines how time, life phases, and expectations have been constructed in the local context. Moreover, the paper highlights the layers of the transition to adulthood and autonomy (residential, financial, emotional etc.) that, furthermore, show the complexity of the phenomenon of “extended youth”. By questioning the mainstream explanations of extended youth as an exclusive consequence of structural factors and political crisis, the paper offers an alternative explanation of extended youth through the analysis of cultural logic.
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- 2022
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9. Mortality of COVID-19 pneumonia during anticancer treatment in lung cancer patients
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Bursać Daliborka, Zarić Bojan, Bokan Darijo, Kovačević Tomi, Stojšić Vladimir, Petkov Svetlana, Mitrović Kosana, and Stojanović Goran
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antineoplastic agents ,comorbidity ,covid-19 ,lung neoplasms ,mortality ,neoplasms staging ,Medicine (General) ,R5-920 - Abstract
Background/Aim. The coronavirus disease 2019 (COVID-19) pandemic has multiple impacts on the management of cancer patients. Treatment of malignancies, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy, can suppress the immune system and lead to the development of severe complications of COVID-19. The aim of this study was to determine the mortality of lung cancer (LC) patients in whom the COVID-19 was confirmed during active antitumor treatment. Methods. This retrospective study was conducted at the Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia. All patients included in the study underwent active anticancer treatment at the time of diagnosis of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was determined by a polymerase chain reaction (PCR) test. Patient data were collected using the institutional database and the observed period was from November 20, 2020, to June 5, 2021. Statistical analysis of the derived patient data used multivariate and univariate testing. Results. Out of 828 observed COVID-19 hospitalized patients, 81 were LC patients on active antitumor treatment. Patients were predominantly male (67.9%), smokers (55.6%), and with an average age of 66.5 years (range 43–83). The majority of patients (50.6%) had the Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1, and 83.9% had at least one comorbidity. The most common comorbidities were arterial hypertension (66.7%), chronic obstructive pulmonary disease (COPD) (28.4%), and diabetes mellitus (21%). Obesity, congestive heart failure, and other cardiovascular diseases were present in 11%, 6.2%, and 7.4% of patients, respectively. The most common was adenocarcinoma (33.3%), followed by squamous (30.9%) and small-cell LC (24.7%). Predominantly, 63% of the patients were in stage III of the disease, and 33.3% were in stage IV. Metastases were most commonly present in the contralateral lung/pleura (14.8%), brain (6.2%), bone (3.7%), and liver (3.7%). Systemic anticancer therapy was applied in 37 out of 81 patients (45.6%), chest radiotherapy in 35 (43.2%), concurrent chemo-radiotherapy in 1 (1.2%), and other types of radiotherapy in 8 (9.87%) patients. The most common forms of systemic therapy were chemotherapy (35.8%), immunotherapy (7.4%), and targeted therapy (2.4%). The most common chemotherapy was a cisplatin-based regiment applied in 34.6% of patients. The mortality from COVID-19 was 19.8%. The statistical significance in relation to the type of treatment was not observed. Statistical significance was observed between mortality and the ECOG PS (p = 0.011). Conclusion. LC patients are dependent on antitumor treatment and, at the same time, highly susceptible to potential infection. In this study, we did not find statistically significant differences in mortality related to the type of antitumor treatment in COVID-19 positive LC patients. Further detailed research on a larger scale is needed in order to explore the effects of SARS-CoV-2 on cancer patients. All possible methods of protection against SARS-CoV-2 virus should be performed in order to minimize the risk of infection in all but especially in immunocompromised cancer patients.
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- 2022
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10. Introduction to the anthropology of photography in Serbia
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Naumović Slobodan, Brujić Marija, and Mitrović Katarina M.
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anthropology of photography ,ethnology and anthropology of photography in serbia ,visual turn ,visual culture ,visual anthropology ,Anthropology ,GN1-890 - Abstract
Despite significant strides from the beginning of the 20th century, there was no systematic or institutionalized reflection on photography in Serbian ethnology and anthropology until the 1980s. Until then, photography was mainly used as an additional technical tool for field recording, documenting, and presenting field materials in museums or scientific institutions. However, since the end of the 20th, and especially at the beginning of the 21st century, an increasing number of social scientists have included photography in their works, either through historical and theoretical reflection or through practical use in specific research. This step can be related to the institutionalization of the sub discipline of visual anthropology in Serbia. The paper presents the assumption that both flows are part of a broader process called the visual turn, and the associated flourishing of systematic thinking about visual culture. In this paper, we aim to reconstruct the main features of the visual turn in the local academic community and point out some of its consequences. In addition, our goal is to present the most important achievements related to the mentioned turn, and consider their impact on recent examples of thinking about photography, i.e. its use in ethnological and anthropological research in Serbia. This paper emphasizes the examples that are important in the theoretical, methodological, or applied-scientific framework.
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- 2021
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11. Together alone: Opportunities and limitations of mature coresidency during the COVID-19 pandemic
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Mitrović Katarina M.
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extended youth ,mature coresidency ,belgrade ,youth ,covid-19 ,Anthropology ,GN1-890 - Abstract
The subject of this paper are cultural representations of disease, care and dependence in households of the so-called “mature coresidency”. This concept refers to families in which parents live with their adult children and focuses on the phenomenon of “extended youth” - longer transition to adulthood, economic and residential dependence of young people in the parental home. The life of young people with their parents, in research and narratives, is often perceived as a forced, conditioned by the political and economic situation in the country. Having in mind the circumstances under which the situation with the COVID-19 pandemic developed and changed, from months of fear and panic to formal closure in the form of quarantine, I discuss family dynamics, division of labor, and possible changes in the roles of family members responsible for household maintenance, grocery shopping etc. Furthermore, I analyze whether the attitude towards living together has changed in the situation of the COVID-19 pandemic, by examining how interlocutors interpret their own roles, obligations within the household and care for its members. The aim of this paper is to review the opportunities and limitations of family cohabitation while examining whether young people and their parents perceive coresidency during the pandemic as a positive and strategic, or a negative and dangerous circumstance. Moreover, it will be discussed if young people, perceived as a risk in public sphere, are also perceived as a risk within their own households. The paper relies on the results of a qualitative research conducted in Belgrade since April 2020 among young adults their parents.
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- 2021
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12. 29. Unusual presentation of spinal muscular atrophy
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Vlahovic, G., primary, Zamurovic, D., additional, Ostojic, S., additional, Lalic, T., additional, and Mitrovic, K., additional
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- 2011
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13. Srebrica Knežević: Academic and pedagogical framework in ethnology and anthropology
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Mitrović Katarina M.
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Srebrica Knežević ,ethnology ,folk medicine ,nutrition ,world ethnology ,Anthropology ,GN1-890 - Abstract
This paper reviews the life and work of Srebrica Knežević (1930-2012) in order to present her career, achievements and fields of study that she contributed to. Special attention will be paid to the importance of her role in pioneer research of folk medicine, nutrition and world ethnology, as well as comprehension of the significance of interdisciplinary approach in Serbian ethnology. Also, this paper will depict Srebrica Knežević as a researcher loyal to her ethnographic field, therefore indicating the compromises she had to make for her very frequent trips and researches. Finally, I will speak of Srebrica Knežević as a lecturer and a professor who adjusted her impressions for the classroom setting and her students, during four decades of work at the Department of Ethnology and Anthropology of the Faculty of Philosophy in Belgrade. As a gifted lecturer who implemented innovations in the classroom, she is remembered as a creative, passionate and dedicated professor, who brought distant topics and ethnographic fields to life. The life and work of Srebrica Knežević are presented and analyzed based on the relevant literature and conversations with her colleagues, students, friends and family.
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- 2018
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14. Molecular genetic study of congenital adrenal hyperplasia in Serbia: novel p.Leu129Pro and p.Ser165Pro CYP21A2gene mutations
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Milacic, I., Barac, M., Milenkovic, T., Ugrin, M., Klaassen, K., Skakic, A., Jesic, M., Joksic, I., Mitrovic, K., Todorovic, S., Vujovic, S., Pavlovic, S., and Stojiljkovic, M.
- Abstract
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease characterized by impaired adrenal steroidogenesis and most often caused by CYP21A2gene mutations. For the first time, we reported complete spectrum and frequency of CYP21A2gene mutations in 61 unrelated patients with classical and non-classical CAH from Serbia. Direct DNA sequencing of whole CYP21A2gene and polymerase chain reaction with sequence-specific primers for detection of CYP21A1P/CYP21A2chimeras were combined. We identified 18 different pathogenic alleles—two of them novel. Mutation detection rate was highest in patients with salt-wasting form of CAH (94.7 %). The most prevalent mutation was intron 2 splice site mutation, c.290-13A/C>G (18.5 %). Other mutation frequencies were: CYP21A1P/CYP21A2chimeras (13 %), p.P30L (13 %), p.R356W (11.1 %), p.G110fs (7.4 %), p.Q318X (4.6 %), p.V281L (4.6 %), p.I172N (2.8 %), p.L307fs (2.8 %), p.P453S (1.9 %), etc. Mainly, frequencies were similar to those in Slavic populations and bordering countries. However, we found 6.5 % of alleles with multiple mutations, frequently including p.P453S. Effects of novel mutations, c.386T>C (p.Leu129Pro) and c.493T>C (p.Ser165Pro), were characterized in silico as deleterious. The effect of well-known mutations on Serbian patients’ phenotype was as expected. The first comprehensive molecular genetic study of Serbian CAH patients revealed two novel CYP21A2mutations. This study will enable genetic counseling in our population and contribute to better understanding of molecular landscape of CAH in Europe.
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- 2015
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15. Problems in diabetes managment in school setting in children and adolescents with type 1 diabetes in Serbia
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Ješić Maja D., Milenković Tatjana, Mitrović Katarina, Todorović Slađana, Zdravković Vera, Ješić Miloš M., Bošnjović-Tucaković Tatjana, Marković Slavica, Vorgučin Ivana, Stanković Sandra, and Sajić Silvija
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diabetes mellitus, type 1 ,child ,Serbia ,schools ,questionnaires ,preventive health services ,Medicine (General) ,R5-920 - Abstract
Background/Aim. Children with type 1 diabetes typically spend one-third of the day in school and they should achieve the same level of diabetes management there as they do outside the school environment. The aim of this study was to identify problems in diabetes management in children with type 1 diabetes at school according to the perceptions reported by children and parents. Methods. This crosssectional survey was carried out at nine public hospitals in Serbia with a cohort of 6-18-year old children/adolescents. The parents were personally informed about the objectives of the survey and the necessity to involve their children. The self-reporting questionnaire included demographic information as well as some questions that helped to evaluate the general situation of children with type 1 diabetes at school. Results. The obtained results show that not all children test blood glucose levels at school (50% of children in the 6-10- year-old age group and 67.3% in the age group over 11 years) and that not all children receive insulin at school (81.1% vs 18.9%, and 57.7% vs 42.3%, respectively). The frequency of severe hypoglycemia was 2.7% in children and 3.3% in adolescents. A high proportion of teachers did not have diabetes training. Conclusion. This brief report about problems in children and adolescents with type 1 diabetes at school in Serbia indicates what happens in the school setting and suggests how to improve control of this disease and facilitate the complete integration of children with diabetes at school.
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- 2016
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16. Teachings of the two major world systems of law on legality and their unification
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Mitrović Kosta D.
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principle of legality ,rechtsstaat ,rule of law ,unification of the law ,Social pathology. Social and public welfare. Criminology ,HV1-9960 - Abstract
In contemporary legal theory, there are two main meanings attributed to the concept of legality. They conform to the underlying ideas of the two major contemporary world systems of the law: the civil-law system and the Anglo-American system. The former gives preference to the formal and normative concept of legality, and the latter to its concept referring to its content personified in Rechtsstaat and the rule of law. Today, the differences between the civil-law system and the Anglo- American system of law are consciously and deliberately being softened and are fading out as a result of the unification of the different areas of the law, the wide usage of legal transplants, etc. For example, in the civil-law system, case law becomes an increasingly important source of the law, while in the Anglo-American system it is law. Gradual softening of the original differences between the two systems of law and their approximation, a good example of which is exactly Rechtsstaat and the rule of law, render possible for one to conclude that those two systems are going to become merged into one and a single world system of law in the foreseeable future.
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- 2014
17. Subclinical hypothyroidism in children and adolescents after hematopoietic stem cells transplantation without irradiation
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Milenković Tatjana, Vujić Dragana, Vuković Rade, Zečević Željko, Soldatović Ivan, Mitrović Katarina, Todorović Slađana, and Zdravković Dragan
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hematopoietic stem cell transplantation ,child ,adolescent ,hypothyroidism ,radiotherapy ,Medicine (General) ,R5-920 - Abstract
Background/Aim. Although total body irradiation (TBI) was considered to be the primary cause of thyroid dysfunction following hematopoietic stem cells transplantation (HSCT), a significant prevalence of subclinical hypothyroidism after HSCT with chemotherapy-only conditioning regimens has been observed in several studies. The aim of this study was to assess changes in thyroid stimulating hormone (TSH) levels in children after HSCT, without the use of irradiation at any time in the course of the treatment. Methods. Our cohort consisted of 41 children and adolescents who underwent autologous or allogeneic HSCT and were available for follow-up for at least one year after transplantation. Irradiation was not performed in any of the subjects, neither during pretransplatation therapy, nor during conditioning. The median duration of follow-up was 2.9 years. The indications for HSCT were hematologic malignancy (41.5%), solid malignant tumor (34.1%), and other disorders (24.4%). The thyroid status of all the subjects was assessed prior to HSCT and after follow-up period. Results. Thyroid dysfunction after HSCT was present in 27 (65.8%) subjects. Subclinical hypothyroidism was the most common abnormality, presenting in 23 (56.1%) patients, primary hypothyroidism was present in one (2.4%) patient, while 3 (7.3%) subjects had low free T4 with normal TSH values. Significantly (p < 0.01) higher elevations in TSH levels were present in the patients who received chemotherapy for the underlying disease prior to HSCT. Conclusion. Our findings emphasize the need for long-term monitoring of thyroid function following HSCT, regardless of whether or not irradiation was used.
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- 2014
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18. Glycaemic control and prevalence of hypoglycaemic events in children and adolescents with type 1 diabetes mellitus treated with insulin analogues
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Plavšić Ljiljana, Mitrović Katarina, Todorović Slađana, Vuković Rade, Milenković Tatjana, and Zdravković Dragan
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diabetes melitus ,type 1 ,child ,adolescent ,hypoglycemia ,insulin ,treatment outcome ,Medicine (General) ,R5-920 - Abstract
Background/Aim. An ideal insulin regimen for children and adolescents with type 1 diabetes mellitus (T1DM) should be physiological, flexibile and predictable, protecting against hypoglycaemia. The aim of this study was to evaluate the influence of insulin analogues on glycaemic control and the occurrence of hypoglycaemic episodes in children and adolescents with T1DM. Methods. The study group consisted of 151 children and adolescents (90 boys, 61 girls) treated with human insulins for at least 12 months before introducing insulin analogues. All the patients were divided into two groups: the group I consisted of 72 (47.7%) patients treated with three injections of regular human insulin before meals and long-acting analogue (RHI/LA), and the group II of 79 (52.3%) patients treated with a combination of rapid-acting and long-acting analogue (RA/LA). The levels of glycated hemoglobin (HbA1c) and the number of hypoglycaemic episodes were assessed at the beginning of therapy with insulin analogues, and after 6 and 12 months. Results. The mean HbA1c was significantly lower in the group I (RHI/LA) after 6 months (9.15% vs 8.20%, p < 0.001) and after 12 months (9.15% vs 8.13%, p < 0.001) as well as in the group II (RA/LA) after 6 months (9.40% vs 8.24%, p < 0.001) and after 12 months of insulin analogues treatment (9.40% vs 8.38%, p < 0.001). The frequency of severe hypoglycaemia was significantly lower in both groups after 6 months (in the group I from 61.1% to 4.2% and in the group II from 54.4% to 1.3%, p < 0.001), and after 12 months (in the group I from 61.1% to 1.4% and in the group II from 54.4% to 1.3%, p < 0.001). Conclusion. Significantly better HbA1c values and lower risk of severe hypoglycaemia were established in children and adolescents with T1DM treated with insulin analogues.
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- 2014
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19. Experimental Transfer of Allergic Information in Laboratory Animals
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Podvinec, S., Andric, R., Savic, V., Mitrovic, K., and Anojcic, M.
- Abstract
In three series of experiments on guinea pigs the authors have transferred sensitization to ovalbumin from sensitized animals to normal animals by means of a temporary skin graft which was explanted after staying in the recipient for 7 days. In the same way desensitization could also be transferred as an immunological information to sensitized animals. The authors conclude that sensitization and desensitization are coded and memorized in cell elements and can be transferred to a homologous animal in the shape of a molecular graft which becomes incorporated into the genetic system of immunologically competent cells.
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- 1969
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20. Etiology of growth hormone deficiency in children and adolescents
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Mitrović Katarina, Milenković Tatjana, Todorović Slađana, Vuković Rade, Rakočević Ivana, and Zdravković Dragan
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children ,adolescents ,growth hormone deficiency ,hypopituitarism ,Medicine - Abstract
Introduction. Growth hormone deficiency (GHD) can be isolated or associated with deficiency of other pituitary gland hormones. According to age at diagnosis, causes of GHD are divided into congenital or acquired, and according to etiology into recognized and unknown. Objective. We analyzed etiology and prevalence of GHD, demographic data at birth, age, body height (BH) and bone age at diagnosis as well as the frequency of other pituitary hormone deficiencies. Methods. The study involved 164 patients (109 male). The main criterion for the diagnosis of GHD was inadequate response of GH after two stimulation tests. The patients were classified into three groups: idiopathic, congenital and acquired GHD. Results. Idiopathic GHD was confirmed in 57.9% of patients, congenital in 11.6% and acquired in 30.5%. The mean age at diagnosis of GHD was 10.1±4.5 years. The patients with congenital GHD had most severe growth retardation (-3.4±1.4 SDS), while the patients with idiopathic GHD showed most prominent bone delay (-3.6±2.3 SDS). The prevalence of multiple pituitary hormone deficiency was 56.1%, in the group with congenital GHD 73.7%, acquired GHD 54.0% and idiopathic GHD 53.7%. The frequency of thyrotropin deficiency ranged from 88.2-100%, of adrenocorticotrophin 57.1-68.8% and of gonadotrophins deficiency 57.1- 63.0%, while deficiency of antidiuretic hormone was 2.0-25.0%. Conclusion. Although regular BH measurements enable early recognition of growth retardation, patients’ mean age and degree of growth retardation indicate that GHD is still diagnosed relatively late. A high incidence of other pituitary hormone deficiencies requires a detailed investigation of the etiology of disorders and evaluation of all pituitary functions in each child with confirmed GHD.
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- 2013
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21. Metabolic phenotype in obese children and adolescents with preserved insulin sensitivity
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Zdravković Dragan, Vuković Rade, and Mitrović Katarina
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obesity ,children ,insulin resistance ,Medicine - Abstract
Rising prevalence of childhood obesity is accompanied by the increased risk of associated metabolic complications and other comorbidities. Nevertheless, a distinct subgroup of the obese appear to have a normal metabolic phenotype, and these individuals are referred to as the metabolically healthy obese. Prevalence of metabolically healthy individuals within the population of the obese is estimated up to 44%. Metabolically healthy obese are at lesser risk for impaired glucose regulation, dyslipidemia, non-alcoholic fatty liver disease and hypertension, and the preserved insulin sensitivity is the most frequently used criterion in identification of these individuals. Results of the research conducted in Institute for Mother and Child Health Care of Serbia 'Dr Vukan Čupić' indicate that a subgroup with low prevalence of metabolic complications of obesity is also present within population of obese children and adolescents in Serbia. A significant association of preserved insulin sensitivity with favorable metabolic phenotype is also supported by the results. Known data suggest the need for a different approach in the treatment of obesity in the subpopulation of the metabolically healthy obese. Due to differences in terms of complications and treatment, these individuals should also be regarded as a separate entity in further research.
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- 2012
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22. Dijagnostički postupak i terapija adolescentne gojaznosti
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Zdravković Dragan, Milenković Tatjana, Mitrović Katarina, Živanović Slađana, and Vuković Rade
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obesity ,adolescents ,diagnosis ,treatment ,Medicine - Abstract
The increasing incidence of obesity among children and adolescents has become a problem in Serbia as in the rest of the world. Obesity is defined as a BMI of 97 or more percentile specific for sex and age, calculated as an individual's weight divided by the square of their height. Overweight is defined as a BMI greater than 90. percentile. The differentiation between simple exogenous obesity and morbid obesity is based mostly on clinical findings. The investigation of obese adolescent includes the recognition of related comorbidities and complications. Given its detrimental affects on public health and the costs of its management, prevention of obesity and its treatment in childhood and adolescence has gained significance. Dietary and exercise advice remains the mainstay of the medical management of obesity. In these respects, the prescription of minimally one hour of daily physical activity for obese children and adolescents and the maintenance of this regimen has become one of the two most important measures. Physical exercise facilitates weight loss by increasing energy expenditure and increasing basal metabolic rate through an increase in muscle mass. The second most important measure is dietary control. Unfortunately, lifestyle interventions alone rarely result in long-term weight loss and the majority of obese patients return to baseline weight within 3-5 years. In the midst of obesity-related health crisis, the case for safe and efficacious pharmacotherapies is clear. Unfortunately, drugs currently available for long-term weight management are limited in number and efficacy. At present, the most effective means of significant and sustained weight loss for obese patients is bariatric surgery. An effective treatment of obesity at early ages has a greater success rate as compared to interventions in adulthood.
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- 2011
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23. The first case of papillary thyroid carcinoma in an adolescent with congenital dyshormonogenetic hypothyroidism in Serbia
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Eremija Jelena, Milenković Tatjana, Mitrović Katarina, Todorović Slađana, Vuković Rade, and Plavšić Ljiljana
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congenital hypothyroidism ,thyroid neoplasms ,carcinoma, papillary ,thiroidectomy ,child ,treatment outcome ,Serbia ,Medicine (General) ,R5-920 - Abstract
Introduction. Differentiated thyroid carcinoma (DTC) is a rare childhood malignancy, as it represents 0.3-0.4% of pediatric malignancies. Papillary carcinoma is the most common type of pediatric DTC and it represents about 90% of all DTC patients. Although rare, DTC arising from dyshormonogenetic goiter is the most serious complication of congenital hypothyroidism. Case report. We presented the development of thyroid papillary carcinoma in a 15-year-old girl diagnosed with congenital dyshormonogenetic hypothyroidism at neonatal age. Considering the early initiation and proper dosage of hormonal substitution, normal levels of thyreotropin and thyroid hormones were achieved quickly and maintained through a follow-up period. The girl remained euthyroid and asymptomatic until 13.8 years of age, when she presented with a large multinodular goiter. The patient underwent total thyroidectomy. Pathological examination revealed intrathyroid microcarcinoma in the right lobe. Conclusion. Although differentiated thyroid carcinoma is a rare pediatric malignancy, it is of great importance to have a certain degree of clinical caution and provide a multidisciplinary approach during the follow-up of patients with dyshormonogenetic hypothyroidism.
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- 2014
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24. Ovarian cysts and tumors as the cause of isosexual pseudoprecocious puberty
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Mitrović Katarina, Zdravković Dragan, Milenković Tatjana, Sedlecki Katarina, and Stanković Zoran
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girls ,pseudoprecocious puberty ,ovarian cyst ,juvenile granulosa cell tumor ,Medicine - Abstract
Introduction. Precocious puberty in girls is generally defined as appearance of secondary sexual characteristics before eight years of age. Menarche before the ninth birthday may serve as an additional criterion. Precocious puberty is divided in central precocious puberty and pseudoprecocious puberty. Central precocious puberty (GnRH dependent) occurs because of premature activation of hypothalamic-pituitarygonadal axis and activity of gonadotrophins. Pseudoprecocious puberty (GnRH independent) is caused by activity of sexual steroids that are not the result of gonadotrophin activity. Objective. Objective of our study was to examine the etiology, clinical and laboratory manifestations of isosexual pseudoprecocious puberty in girls. Method. In the period between 1995 and 2004, clinical and laboratory sings of 34 girls with precocious puberty were studied at the Endocrine Department of the Institute of Mother and Child Health Care of Serbia. Initial evaluations included height measurement, staging of puberty, bone age assessment and pelvic ultrasound. Important diagnostic sonographic parameters of precocious puberty were the volumes of ovaries and uterus as well as ovarian structure. The initial hormonal evaluation included measuring of plasma oestradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH). The luteinizing hormone releasing hormone (LHRH) stimulation test was used to evaluate LH and FSH responsiveness (60 μg/m2 LHRH- Relefact LHRH®, Ferring). Blood samples were collected at 0, 20 and 60 minutes. Basal and GnRH stimulated LH and FSH were determined by immunoradiometric assay. Estradiol concentration was measured using the fluoroimmunometric assay. Results. Thirty-four girls aged 6 months to 9 years (mean age 4.5 years) with precocious puberty were studied during the period of 9 years. Eleven girls presented with breast development, six with vaginal bleeding and seventeen with signs of puberty. On the basis of clinical signs, bone age, estradiol levels and LHRH test, premature the larche was diagnosed in eleven patients (32.4%), premature menarche in six (17.6%) and central precocious puberty in ten girls (29.4%). Seven girls (20.6%) presented with pseudoprecocious puberty. Pelvic ultrasound examination revealed unilateral ovarian cysts in six patients and granulosa cell tumor in one. Elevated estrogen serum levels and failure of gonadotropin responses after gonadotropin releasing hormone were the classical findings in patients with isosexual pseudoprecocious puberty during the acute period of disease. In four patients, the cyst decreased spontaneously after several months, while in two patients, the cyst was removed by laparotomy. Surgical treatment was performed in a patient with granulosa cell tumor. Conclusion. Our work demonstrates that autonomous functional ovarian follicle cyst is the most often cause of isosexual pseudoprecocious puberty. Short period of observation is suggested because the cyst can resolve spontaneously. On the other hand, juvenile granulosa cell tumor, as highly malignant tumor, should be removed as soon as diagnosis is established.
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- 2006
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25. In Vitro Cross-Reacting Antibodies from Rabbit Antisera to Rat Brain Synaptic Membranes and Thymocytes
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JANKOVIC, B. D., primary, HORVAT, J., additional, MITROVIC, K., additional, and MOSTARICA, M., additional
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- 1977
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26. ANTIGENIC DETERMINANTS SHARED BY RAT LYMPHOCYTES AND RAT BRAIN SUBCELLULAR FRACTIONS
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JANKOVIC, B. D., primary, HORVAT, J., additional, MITROVIC, K., additional, and MOSTARICA, M., additional
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- 1975
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27. Novel glucokinase mutation in a boy with maturity-onset diabetes of the young
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Milenković Tatjana, Zdravković Dragan, and Mitrović Katarina
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diabetes ,MODY ,glucokinase ,novel mutation ,Medicine - Abstract
INTRODUCTION Maturity-onset diabetes of the young (MODY) is a heterogenous group of disorders characterized by an early onset of insulin-independent diabetes mellitus, an autosomal dominant mode of inheritance and a primary defect in beta-cell. There are six subtypes of MODY. MODY2 and MODY3 are the most frequent. CASE OUTLINE We present a nine-year-old boy with intermittent hyperglycaemia. According to family history, the diagnosis of MODY2 was suspected. Molecular analysis revealed novel missense mutation R250c in exon 7 of glucokinase gene. Mutation (c.748 C>T) is the result of substitution of aminoacid cysteine by arginine (p.Arg250Cys). This is the first pediatric patient with MODY2 in Serbia whose diagnosis is established at molecular level. CONCLUSION Molecular diagnosis of MODY has important consequences in terms of prognosis, therapy and family screening of the disorder. Investigation of other patients with MODY2 in our country is important to establish prevalence and nature of mutations in glucokinase gene.
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- 2008
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28. Effects of intraventricularly injected anti-brain antibodies on delayed alteration and visual discrimination tests performance in rhesus monkeys
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Mihailović, Lj., Divac, I., Mitrović, K., Milos̀ević, D., and Janković, B.D.
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- 1969
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29. Very early and severe presentation of Triple A syndrome - case report and review of the literature.
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Cehic M, Mitrovic K, Vukovic R, Milenkovic T, Kovacevic G, Todorovic S, Panic Zaric S, Cvetkovic D, Paripovic A, Huebner A, Koehler K, and Quitter F
- Subjects
- Humans, Infant, Nuclear Pore Complex Proteins genetics, Severity of Illness Index, Child, Preschool, Adrenal Insufficiency diagnosis, Adrenal Insufficiency genetics, Adrenal Insufficiency pathology, Esophageal Achalasia diagnosis, Esophageal Achalasia genetics, Esophageal Achalasia pathology
- Abstract
Triple A syndrome (TAS), also known as Allgrove syndrome (OMIM#231550), is a rare, autosomal recessive disorder characterized by the triad of alacrima, achalasia, and adrenal insufficiency. Additional neurological features may be present in two-thirds of patients, involving central, peripheral, and autonomic nervous system manifestations. TAS is caused by genetic alterations in the AAAS gene on chromosome 12q13, which encodes the nuclear pore complex protein termed ALADIN (ALacrima, Achalasia, aDrenal Insufficiency, and Neurologic disorder). ALADIN plays a crucial role in nucleocytoplasmic transport of specific proteins, including the transport of DNA repair proteins. TAS exhibits significant phenotypic variability in terms of symptom onset, frequency, and severity, often presenting with a progressive clinical course indicative of an underlying degenerative process. In this study, we report the case of an infant with exceptionally early and severe manifestations of triple A syndrome, with a review of the literature. Our patient exhibited the complete classical triad of TAS at six months of age, being among the youngest reported cases of the syndrome. The clinical course was complicated by severe involvement of the autonomic nervous system, neurogenic bladder, and recurrent urinary tract infections. Subsequently, the patient developed acute pancreatitis, leading to multiorgan dysfunction and a fatal outcome at 25 months of age. This case underscores the potential for atypical disease presentations and the need for clinical awareness in diagnosing and managing patients with TAS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cehic, Mitrovic, Vukovic, Milenkovic, Kovacevic, Todorovic, Panic Zaric, Cvetkovic, Paripovic, Huebner, Koehler and Quitter.)
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- 2024
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30. A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT.
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Mitrovic K, Zivotic I, Kolic I, Zakula J, Zivkovic M, Stankovic A, and Jovanovic I
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- Humans, Down-Regulation, HEK293 Cells, RNA, Messenger, MicroRNAs genetics, MicroRNAs metabolism, Urogenital Abnormalities, Vesico-Ureteral Reflux
- Abstract
Background: The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro., Methods: Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets)., Results: Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts., Conclusions: Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT., (© 2024. The Author(s).)
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- 2024
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31. Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT.
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Macak N, Jovanovic I, Zivkovic M, Mitrovic K, Cvetkovic M, Kostic M, and Stankovic A
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- Humans, Child, Down-Regulation, Gene Expression Profiling, Fibrosis, Kidney metabolism, MicroRNAs genetics, MicroRNAs metabolism, Urinary Tract metabolism
- Abstract
Congenital anomalies of the kidney and urinary tract (CAKUT) represent structural and functional urinary system malformations and take place as one of the most common congenital malformations with an incidence of 1:500. Ureteral obstruction-induced hydronephrosis is associated with renal fibrosis and chronic kidney diseases in the pediatric CAKUT. We aimed to construct interaction network of previously bioinformatically associated miRNAs with CAKUT differentially expressed genes in order to prioritize those associated with fibrotic process and to experimentally validate the expression of selected miRNAs in CAKUT patients compared to control group. We constructed interaction network of hsa-miR-101-3p, hsa-miR-101-5p and hsa-miR-29c-3p that showed significant association with fibrosis. The top enriched molecular pathway was extracellular matrix-receptor interaction (adjusted p = .0000263). We experimentally confirmed expression of three miRNAs (hsa-miR-29c-3p, hsa-miR-101-3p and hsa-miR-101-5p) in obstructed ureters (ureteropelvic junction obstruction and primary obstructive megaureter) and vesicoureteral reflux. The hsa-miR-29c-3p was shown to have lower expression in both patient groups compared to controls. Relative levels of hsa-miR-101-5p and hsa-miR-101-3p showed significant positive correlations in both groups of patients. Statistically significant correlation was observed between hsa-miR-101 (-3p and -5p) and hsa-miR-29c-3p only in the obstructed group. The significant downregulation of anti-fibrotic hsa-miR-29c-3p in obstructive CAKUT could explain activation of genes involved in fibrotic processes. As miRNAs are promising candidates in therapeutic approaches our results need further measurement of fibrotic markers or assessment of extent of fibrosis and functional evaluation of hsa-miR-29c.
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- 2023
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32. Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT.
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Mitrovic K, Zivotic I, Kolic I, Djordjevic A, Zakula J, Filipovic Trickovic J, Zivkovic M, Stankovic A, and Jovanovic I
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- Humans, HEK293 Cells, RNA, Messenger genetics, DNA Copy Number Variations genetics, MicroRNAs genetics, MicroRNAs metabolism
- Abstract
Rare copy number variants (CNVs) are among the most common genomic disorders underlying CAKUT. miRNAs located in rare CNVs represent well-founded functional variants for human CAKUT research. The study aimed to identify and functionally interpret miRNAs most frequently affected by rare CNVs in CAKUT and to estimate the overall burden of rare CNVs on miRNA genes in CAKUT. The additional aim of this study was to experimentally confirm the effect of a rare CNV in CAKUT on candidate miRNA's expression and the subsequent change in mRNA levels of selected target genes. A database of CAKUT-associated rare CNV regions, created by literature mining, was used for mapping of the miRNA precursors. miRNAs and miRNA families, most frequently affected by rare CAKUT-associated CNVs, have been subjected to bioinformatic analysis. CNV burden analysis was performed to identify chromosomes with over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT. A functional study was performed on HEK293 MIR484
+/- KO and HEK293 WT cell lines, followed by the analysis of relative miRNA and mRNA target gene levels. 80% of CAKUT patients with underlying rare CNV had at least one miRNA gene overlapping the identified CNV. Network analysis of the most frequently affected miRNAs has revealed the dominant regulation of the two miRNAs, hsa-miR-484 and hsa-miR-185-5p. Additionally, miR-548 family members have shown substantial enrichment in rare CNVs in CAKUT. An over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT was observed in multiple chromosomes, such as chr16, chr20, and chr21. A significant 0.37 fold downregulation of hsa-miR-484, followed by a notable upregulation of MDM2 and APAF1 and downregulation of NOTCH3 was detected in HEK293 MIR484+/- KO compared to HEK293 WT cell lines, supporting the study hypothesis. miRNA genes are frequently affected by rare CNVs in CAKUT patients. Understanding the potential of CNV-affected miRNAs to participate in CAKUT as genetic drivers represent a crucial implication for the development of novel therapeutic approaches., (© 2022. The Author(s).)- Published
- 2022
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33. Triptorelin stimulated luteinizing hormone concentrations for diagnosing central precocious puberty: study of diagnostic accuracy.
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Vukovic R, Milenkovic T, Soldatovic I, Pekic S, Mitrovic K, and Todorovic S
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- Female, Follicle Stimulating Hormone, Gonadotropin-Releasing Hormone, Humans, Luteinizing Hormone, Prospective Studies, Puberty, Precocious diagnosis, Puberty, Precocious drug therapy, Triptorelin Pamoate
- Abstract
Purpose: Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). However, intravenous GnRH is not always readily available. The aim of the present study was to evaluate the diagnostic accuracy of triptorelin-stimulated luteinizing hormone (LH) concentrations in the diagnosis of CPP among girls presenting with premature thelarche compared to the gold standard GnRH test., Methods: A prospective, case-control (CPP vs isolated premature thelarche), clinical study evaluating the diagnostic accuracy of triptorelin-stimulated LH concentrations in 60 girls with premature thelarche was performed. All girls underwent stimulation with subcutaneous triptorelin injection and intravenous GnRH in a randomized order. During the stimulation test with triptorelin, LH and FSH were measured at time 0, 30, 60, 90, 120, and 180 min after the injection. Estradiol was sampled 24 h after the injection. During the GnRH test, LH and FSH were measured at time 0, 30, 45, and 60 min. Girls with peak GnRH-stimulated LH concentrations ≥5.0 IU/L were classified as having CPP. Area under the curve (AUC) for triptorelin-stimulated LH concentrations was assessed using the receiver operating characteristic (ROC) analysis., Results: Triptorelin-stimulated LH concentrations were significantly higher in girls who had CPP according to the GnRH test (53.3%). LH peaked at 180 min after the triptorelin injection. The highest diagnostic accuracy for CPP (AUC = 0.973, sensitivity 96.9%, specificity 89.3%) at 180 min was at a LH concentration ≥3.4 IU/L. The 24 h estradiol concentration did not improve the predictive model., Conclusions: Measuring LH concentrations 180 min after triptorelin injection with a cut-off value of ≥3.4 IU/L demonstrated a high diagnostic accuracy compared to the GnRH test. Thus, stimulation with triptorelin can be used as a reliable alternative for diagnosing CPP in girls with premature thelarche., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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34. Clinical and genetic characteristics of patients with congenital hyperinsulinism in 21 non-consanguineous families from Serbia.
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Raicevic M, Milenkovic T, Hussain K, Djordjevic M, Martic J, Todorovic S, Mitrovic K, Sarajlija A, and Vukovic R
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- Child, Child, Preschool, Consanguinity, Humans, Infant, Infant, Newborn, Mutation, Retrospective Studies, Serbia epidemiology, Sulfonylurea Receptors genetics, Congenital Hyperinsulinism genetics, Hyperinsulinism
- Abstract
Persistent hypoglycaemia in newborns and infants is most commonly caused by congenital hyperinsulinism (CHI). Most CHI studies report outcomes in children from both consanguineous and non-consanguineous families which can affect the phenotype-genotype analysis. The aim of this study was to analyze characteristics of patients with CHI in 21 non-consanguineous families from Serbia. This retrospective cohort study included a total of 21 patients with CHI treated in the Mother and Child Healthcare Institute of Serbia during the past 20 years. The prevalence of macrosomia at birth was very low in our cohort (4.8%). Median age at presentation was 6 days, with seizures as the presenting symptom in 76% of patients. Only four patients (19%) were diazoxide unresponsive, and eventually underwent pancreatectomy. Genetic testing was performed in 15 patients and genetic diagnosis was confirmed in 60%, with all patients being heterozygous for detected mutations. The ABCC8 gene mutations were detected in 55.6%, GLUD1 in three patients (33.3%) with HIHA syndrome and one patient had HNF4A gene mutation and unusual prolonged hyperglycaemia lasting 6 days after diazoxide cessation. Neurodevelopmental deficits persisted in 33% of patients.Conclusion: This is the first study regarding CHI patients in Serbia. It suggests that in countries with low consanguinity rate, majority of CHI patients are diazoxide responsive. The most common mutations were heterozygous ABCC8, followed by GLUD1 and HNF4A mutations, suggesting the potential benefit of population-tailored genetic analysis approach, targeting the mutations causing CHI via dominant inheritance model in regions with low consanguinity rates. What is Known: • Persistent hypoglycaemia during infancy and early childhood is most commonly caused by congenital hyperinsulinism (CHI). • Consanguinity is a very important factor regarding the genetics and phenotype of CHI, increasing the risk of autosomal recessive genetic disorders, including the severe, diazoxide-unresponsive forms caused by recessive inactivating mutations in ABCC8 and KCNJ11. What is New: • Results of the present study which included CHI patients from 21 non-consanguineous families suggest that in countries with low consanguinity rates, majority of CHI patients can be diazoxide responsive, with most common mutations being heterozygous ABCC8, followed by GLUD1 and HNF4A mutations. • Unusually prolonged hyperglycaemic reaction to diazoxide treatment in a patient with HNF4A mutation was also described in the present study., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2021
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35. Mapping the journey of transition: a single-center study of 170 childhood-onset GH deficiency patients.
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Doknic M, Stojanovic M, Soldatovic I, Milenkovic T, Zdravkovic V, Jesic M, Todorovic S, Mitrovic K, Vukovic R, Miljic D, Savic D, Milicevic M, Stanimirovic A, Bogosavljevic V, Pekic S, Manojlovic-Gacic E, Djukic A, Grujicic D, and Petakov M
- Abstract
Objective: To analyze metabolic parameters, body composition (BC), and bone mineral density (BMD) in childhood-onset GH deficiency (COGHD) patients during the transition period (TP)., Design: Single- center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2 ± 2.0 years, range 16-25) transferred after growth completion from two pediatric clinics to the adult endocrine unit. Two separate analyses were performed: (i) cross-sectional analysis of hormonal status, metabolic parameters, BC, and BMD at first evaluation after transfer from pediatrics to the adult department; (ii) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP., Results: COGHD was of a congenital cause (CONG) in 50.6% subjects, tumor-related (TUMC) in 23.5%, and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (P < 0.01) and lower Z score at L-spine (P < 0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to the rhGH-untreated group (P < 0.01). Three years of rhGH after growth completion resulted in a significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with a decrease in FM (5.2%)., Conclusion: The effect of rhGH in childhood is invaluable for metabolic status, BC, and BMD in transition to adulthood. Tumor-related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition, and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BC and BMD in patients with persistent COGHD.
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- 2021
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36. First report on the nationwide prevalence of paediatric type 1 diabetes in Serbia and temporal trends of diabetes ketoacidosis at diagnosis-a multicentre study.
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Stankovic S, Vukovic R, Vorgucin I, Zdravkovic V, Folic N, Zivic S, Ignjatovic A, Rancic N, Milenkovic T, Todorovic S, Mitrovic K, Jesic M, Sajic S, Bojic V, Katanic D, Dautovic S, Cvetkovic V, Saranac L, Markovic S, Tucakovic T, Lesovic S, Ljubojevic M, Ilic T, Vrebalov M, Mikic M, Jelenkovic B, Petrovic R, Saric S, Simić D, Cukanovic M, and Stankovic M
- Subjects
- Blood Glucose analysis, Child, Child, Preschool, Diabetic Ketoacidosis blood, Diabetic Ketoacidosis diagnosis, Diabetic Ketoacidosis etiology, Female, Follow-Up Studies, Glycated Hemoglobin analysis, Humans, Male, Prevalence, Prognosis, Retrospective Studies, Risk Factors, Serbia epidemiology, Biomarkers blood, Diabetes Mellitus, Type 1 complications, Diabetic Ketoacidosis epidemiology, Severity of Illness Index
- Abstract
We aimed to collect data on all paediatric patients who were diagnosed with type 1 diabetes mellitus (T1DM) between the years 2000 and 2019 in Serbia and estimate for the first time its prevalence. Also, the trends of diabetes ketoacidosis (DKA) occurrence at the time of diagnosis are monitored. We collected and retrospectively analysed the data of patients <19 years with newly diagnosed T1DM. T1DM was diagnosed in 3134 patients (53.2% male). Total number of youth <19 years with T1DM was 1735 with prevalence of 135.25/100000 at the end of study period. T1DM was diagnosed most frequently between the ages of 5 and 11 years (42.1%). At the time of diagnosis, 35.7% presented in DKA. The incidence and severity of DKA were more significant at the youngest age (p<0.001). There were significant annual percentage increase (2.2%) in the number of new cases of DKA (p=0.007). Conclusion: This first report of nationwide prevalence of T1DM in youth shows that Serbia is among countries with high prevalence of T1DM in youth. System changes are needed in order to provide better quality of health care to these patients., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)
- Published
- 2020
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37. Factors associated with oxidative stress status in pediatric patients with type 1 diabetes mellitus.
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Kacarevic D, Bogavac-Stanojevic N, Spasojevic-Kalimanovska V, Bojanin D, Milenkovic T, Stefanovic A, Mihajlovic M, Vujcic S, Vukovic R, Zeljkovic A, Todorovic S, Mitrovic K, and Vekic J
- Subjects
- Adolescent, Biomarkers blood, Child, Cholesterol blood, Cross-Sectional Studies, Diabetes Mellitus, Type 1 blood, Female, Glycated Hemoglobin metabolism, Humans, Male, Triglycerides blood, Blood Glucose metabolism, Diabetes Mellitus, Type 1 metabolism, Oxidative Stress physiology
- Abstract
Background Oxidative stress is implicated in both, the onset and the progression of type 1 diabetes mellitus (T1DM). There is accumulated evidence of increased biomarkers of oxidative stress in newly diagnosed, T1DM patients without complications, and in those with advanced disease. In this cross-sectional study, we investigated factors affecting oxidative stress status in pediatric patients with T1DM. Methods Advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), total sulfhydryl (SH) groups, and superoxide dismutase (SOD) activity were determined in 170 children and adolescents with T1DM. Principal component analysis was used to investigate clustering of clinical and laboratory variables associated with elevated oxidative stress and reduced antioxidative defense biomarkers. Results Factor analysis extracted five factors, interpreted as (1) "weight status factor" including age, BMI, waist and hip circumferences; (2) "proatherogenic factor" that included LDL-cholesterol, non-HDL-cholesterol, and triglycerides; (3) "metabolic control factor" including glucose and HbA1c; (4) "renal marker factor" with positive loading of urinary albumin excretion rate and negative loading of GFR; and (5) "antiatherogenic factor" that included HDL-cholesterol. High AOPP levels were independently predicted by "proatherogenic" (OR: 2.32; 95% CI: 1.44-3.71; p < 0.001), "metabolic control" (OR: 2.24; 95% CI: 1.35-3.73; p < 0.01), and "renal marker" (OR: 1.65; 95% CI: 1.03-2.65; p < 0.05) factors. "Renal marker factor" was a significant predictor of PAB (OR: 0.52; 95% CI: 0.34-0.81; p < 0.01). Regarding antioxidative defense markers, reduced SH groups were predicted by "proatherogenic factor" (OR: 0.56; 95% CI: 0.34-0.94; p < 0.05), while "weight status factor" predicted lower SOD activity (OR: 1.66; 95% CI: 1.03-2.67; p < 0.05). Conclusions Cardiometabolic risk factors and renal function are associated with oxidative stress in pediatric T1DM patients.
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- 2020
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38. Association between proprotein convertase subtilisin/kexin 9 (PCSK9) and lipoprotein subclasses in children with type 1 diabetes mellitus: Effects of glycemic control.
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Bojanin D, Vekic J, Milenkovic T, Vukovic R, Zeljkovic A, Stefanovic A, Janac J, Ivanisevic J, Mitrovic K, Miljkovic M, and Spasojevic-Kalimanovska V
- Subjects
- Adolescent, Cardiovascular Diseases blood, Cardiovascular Diseases complications, Child, Cholesterol blood, Cholesterol, HDL blood, Cholesterol, LDL blood, Cross-Sectional Studies, Diabetes Mellitus, Type 1 complications, Dyslipidemias blood, Female, Humans, Insulin therapeutic use, Lipoproteins, HDL metabolism, Male, Multivariate Analysis, Blood Glucose metabolism, Diabetes Mellitus, Type 1 blood, Lipoproteins, LDL metabolism, Proprotein Convertase 9 blood
- Abstract
Background and Aims: Dyslipidemia in type 1 diabetes mellitus (T1DM) is characterised by altered distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses. Recent studies suggested that proprotein convertase subtilisin/kexin 9 (PCSK9) may contribute to the development of dyslipidemia in T1DM. In this cross-sectional study, we investigated the association between PCSK9 and lipoprotein subclasses in young T1DM patients, with respect to glycemic control., Methods: Plasma PCSK9 and lipoprotein subclasses were determined in 207 patients with T1DM (106 boys and 101 girls), aged 13.9 ± 3.0 years and treated by intensive insulin therapy., Results: Plasma PCSK9 levels significantly increased with worsening of glycemic control (p < 0.001). T1DM patients with poor glucoregulation had the highest proportion of small, dense LDL (sdLDL) and smaller HDL particles, as well. PCSK9 was positively associated with markers of glucose homeostasis and serum lipid parameters only in patients with suboptimal/poor glucoregulation. In well-controlled T1DM, plasma PCSK9 level was inversely associated with a relative proportion of sdLDL particles (p < 0.01) and this association remained significant in multivariate analysis. In T1DM patients with suboptimal/poor glycemic control, PCSK9 was positively associated with the proportion of the smallest HDL3c particles (p < 0.001), but negatively with HDL size (p < 0.05)., Conclusions: The extent of achieved metabolic control modifies the association between PCSK9 and lipoprotein subclasses in T1DM. Further investigations are needed to reveal whether the observed effects of glycemic control on PCSK9 and sdLDL levels have causal consequences on CVD risk in young patients with T1DM., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2019
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39. Thirty years of the newborn screening program in Central Serbia: the missed cases of congenital hypothyroidism.
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Milenkovic T, Vukovic R, Radojicic B, Mitrovic K, Todorovic S, and Zatezalo L
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- Adolescent, Child, Child, Preschool, Congenital Hypothyroidism epidemiology, False Negative Reactions, Female, Humans, Infant, Infant, Newborn, Male, Medical Errors, Retrospective Studies, Serbia epidemiology, Specimen Handling adverse effects, Congenital Hypothyroidism diagnosis, Missed Diagnosis statistics & numerical data, Neonatal Screening
- Abstract
Milenkovic T, Vukovic R, Radojicic B, Mitrovic K, Todorovic S, Zatezalo L. Thirty years of the newborn screening program in Central Serbia: the missed cases of congenital hypothyroidism. Turk J Pediatr 2019; 61: 319- 324. Newborn Screening (NS) program for congenital hypothyroidism (CH) has completely changed the natural history of this devastating disorder for the vast majority of children with CH. However, cases of missed CH do happen, and it is important to keep this possibility in mind during every day clinical practice. The objective of this study was to analyze the recognized cases of undiagnosed CH by the NS program in Central Serbia in order to evaluate the reasons for such omissions. Data regarding the recognized missed cases of CH between the years of 1983 and 2013 were collected and analyzed. During 30 years of the NS program for CH on the territory of Central Serbia, 1,547,122 newborns were screened, and during this period, 14 children with CH were missed by the NS. Five missed cases were children with athyreosis (35.8%), 8 had ectopic thyroid gland (57.1%) and one child had dyshormonogenesis (7.1%). The median age at diagnosis of CH in these missed cases was 1.12 years (range 0.08-13.5 years). In the group of children with missed diagnosis of CH, 71.4% were missed due to errors during sample collection, and 28.6% of patients were missed due to false negative screening results. Continuous education of neonatologists as well as nurses in neonatal units of maternity hospital are necessary to avoid errors in sample collection. It is of high importance to notice in a discharge list if a child is referred to the hospital before the sample is taken in a maternity hospital. On the other hand, the maternity hospital has to inform the screening laboratory about any child who was referred to another hospital if the blood samples for screening are not taken. Parents should be better informed that each child has to be included in the NS which is obligatory in Serbia. In addition, awareness amongst pediatricians in primary care should be raised regarding the possibility of missed cases of CH.
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- 2019
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40. Pediatric siMS score: A new, simple and accurate continuous metabolic syndrome score for everyday use in pediatrics.
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Vukovic R, Milenkovic T, Stojan G, Vukovic A, Mitrovic K, Todorovic S, and Soldatovic I
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- Adolescent, Child, Child, Preschool, Female, Humans, Male, Principal Component Analysis, Metabolic Syndrome metabolism
- Abstract
Background: The dichotomous nature of the current definition of metabolic syndrome (MS) in youth results in loss of information. On the other hand, the calculation of continuous MS scores using standardized residuals in linear regression (Z scores) or factor scores of principal component analysis (PCA) is highly impractical for clinical use. Recently, a novel, easily calculated continuous MS score called siMS score was developed based on the IDF MS criteria for the adult population., Objective: To develop a Pediatric siMS score (PsiMS), a modified continuous MS score for use in the obese youth, based on the original siMS score, while keeping the score as simple as possible and retaining high correlation with more complex scores., Subjects and Methods: The database consisted of clinical data on 153 obese (BMI ≥95th percentile) children and adolescents. Continuous MS scores were calculated using Z scores and PCA, as well as the original siMS score. Four variants of PsiMS score were developed in accordance with IDF criteria for MS in youth and correlation of these scores with PCA and Z score derived MS continuous scores was assessed., Results: PsiMS score calculated using formula: (2xWaist/Height) + (Glucose(mmol/l)/5.6) + (triglycerides(mmol/l)/1.7) + (Systolic BP/130)-(HDL(mmol/l)/1.02) showed the highest correlation with most of the complex continuous scores (0.792-0.901). The original siMS score also showed high correlation with continuous MS scores., Conclusion: PsiMS score represents a practical and accurate score for the evaluation of MS in the obese youth. The original siMS score should be used when evaluating large cohorts consisting of both adults and children.
- Published
- 2017
- Full Text
- View/download PDF
41. Postprandial hyperinsulinemic hypoglycemia in a child as a late complication of esophageal reconstruction.
- Author
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Vukovic R, Milenkovic T, Djordjevic M, Mitrovic K, Todorovic S, Sarajlija A, and Hussain K
- Subjects
- Child, Female, Humans, Hyperinsulinism pathology, Hypoglycemia pathology, Obesity, Morbid complications, Postprandial Period, Prognosis, Risk Factors, Esophageal Atresia surgery, Gastric Bypass adverse effects, Hyperinsulinism etiology, Hypoglycemia etiology, Obesity, Morbid surgery, Postoperative Complications, Plastic Surgery Procedures adverse effects
- Abstract
Background: Postprandial hyperinsulinemic hypoglycemia (PHH) is an increasingly recognized complication of gastric bypass surgery in obese adults, distinct from the "dumping syndrome"., Case Presentation: Upon birth, primary repair of esophageal atresia was performed, and at the age of 14 months definite esophageal reconstruction was performed. At the age of 3 years, recurrent brief episodes of symptomatic hypoglycemia started. At the age of 5.7 years the girl was admitted to our clinic and investigations indicated hyperinsulinemic hypoglycemia. Oral glucose tolerance test (OGTT) and continuous glucose monitoring results revealed frequent postprandial hypoglycemic events, which were always preceded by early postprandial hyperglycemia. It was concluded that the patient had PHH caused by a delayed and hyperinsulinemic response to carbohydrate intake as a result of esophagogastric surgery. Treatment with acarbose was titrated using flash glucose monitoring, which resulted in satisfactory glucose regulation., Conclusions: This is the first described case of a child with PHH following esophageal reconstruction.
- Published
- 2017
- Full Text
- View/download PDF
42. Alpha coma in an adolescent with diabetic ketoacidosis.
- Author
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Ostojic S, Vukovic R, Milenkovic T, Mitrovic K, Djuric M, and Nikolic L
- Subjects
- Adolescent, Brain Edema diagnosis, Brain Edema therapy, Coma therapy, Diabetic Ketoacidosis therapy, Electroencephalography, Female, Fluid Therapy methods, Humans, Insulin therapeutic use, Intensive Care Units, Mannitol therapeutic use, Tomography, X-Ray Computed, Brain Edema complications, Coma etiology, Diabetic Ketoacidosis complications
- Abstract
Ostojic S, Vukovic R, Milenkovic T, Mitrovic K, Djuric M, Nikolic L. Alpha coma in an adolescent with diabetic ketoacidosis. Turk J Pediatr 2017; 59: 318-321. This is the first report of alpha coma (AC) caused by brain edema in a patient with diabetic ketoacidosis (DKA). A previously healthy 15-year-old girl was admitted to the intensive care unit due to altered state of consciousness during the course of treatment for DKA. Patient was in a coma, intubated and had tachycardia with poor peripheral perfusion. Results of laboratory analyses indicated severe DKA and computed tomography scan indicated diffuse brain edema. The EEG pattern showed uniform alpha activity. Treatment with intravenous fluids, insulin and mannitol was started. Patient`s state of consciousness gradually improved and on the third day she was extubated. On the fifth day, her neurologic status and EEG findings were completely normal with no residual neurological deficits. In conclusion, although AC is associated with a high fatality rate, favorable outcome can be achieved with prompt recognition and treatment of cerebral edema in pediatric patients with DKA.
- Published
- 2017
- Full Text
- View/download PDF
43. Early Presentation of Hyperinsulinism/Hyperammonemia Syndrome in Three Serbian Patients.
- Author
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Sarajlija A, Milenkovic T, Djordjevic M, Mitrovic K, Todorovic S, Kecman B, and Hussain K
- Subjects
- Cognition Disorders genetics, DNA Mutational Analysis, Epilepsy genetics, Female, Genotype, Humans, Hyperinsulinism complications, Hypoglycemia complications, Infant, Infant, Newborn, Male, Mutation, Phenotype, Serbia, Glutamate Dehydrogenase genetics, Hyperinsulinism genetics, Hypoglycemia genetics
- Abstract
Hyperinsulinism/hyperammonemia (HI/HA) syndrome is considered as the second most common type of hereditary HI. Correlation of genotype and phenotype in HI/HA syndrome has been described in several studies. We present three Serbian patients with HI/HA syndrome with emphasis on a possible correlation between genotype and clinical manifestations. Patient 1 was heterozygous for a de novo mutation p.S445L in the GLUD1 gene, while patients 2 and 3 (son and mother) both carry the p.R221C mutation. Early onset of hypoglycaemia with generalized seizures was recorded in infancy in all three patients. The two male patients had mild developmental delay, while the female patient presented with epilepsy. Analysis of Serbian patients with HI/HA syndrome confirms the association of p.S445L and p.R221C mutations with hypoglycaemic seizures noted within the first three months of life and with subsequent risk for cognitive impairment and/or epilepsy.
- Published
- 2016
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44. Changes in the incidence and etiology of congenital hypothyroidism detected during 30 years of a screening program in central Serbia.
- Author
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Mitrovic K, Vukovic R, Milenkovic T, Todorovic S, Radivojcevic J, and Zdravkovic D
- Subjects
- Female, Humans, Incidence, Infant, Newborn, Male, Retrospective Studies, Serbia epidemiology, Congenital Hypothyroidism epidemiology, Congenital Hypothyroidism etiology, Neonatal Screening methods, Thyrotropin blood
- Abstract
Congenital hypothyroidism (CH) is the most frequent congenital endocrine disorder. The purpose of the present study was to determine the incidence of CH in Central Serbia from 1983 to 2013. Newborn screening for CH was based on measuring neonatal thyroid-stimulating hormone (TSH) using a 30 mU/l cutoff (CO) until 12/1987 (P1), 15 mU/l until 12/1997 (P2), 10 mU/l until 12/2006 (P3), and 9 mU/l thereafter (P4). During the study period, there were 1,547,122 live births screened for CH. Primary CH was detected in 434 newborns, with incidence of 1:3728. With gradual lowering of the CO, the incidences of CH increased from 1:5943 in P1 to 1:1872 in P4 (p < 0.001). Incidence of CH with ectopic and enlarged gland doubled (p < 0.001), while prevalence of athyreosis remained relatively constant. The most prominent finding was the increase in the transient CH from none in P1 to 35 % of all CH patients in P4., Conclusion: The overall incidence of CH in Central Serbia during study period nearly tripled, with a significant increase in almost all etiological categories, and was associated with lowering TSH cutoffs as well as other yet unidentified factors. Further studies are needed to identify other factors associated with increasing incidence of CH., What Is Known: Congenital hypothyroidism (CH) is the main cause of preventable mental retardation. Recent reports have indicated a progressive increase in the incidence of primary CH throughout the world, partially explained by lowering of the TSH cutoff values., What Is New: During the study period associated with lowering of the TSH cutoffs, the overall incidence of CH in Serbia tripled, including transient CH, ectopy, and dyshormonogenesis, while prevalence of athyreosis remained stable during 30 years. Significant increase in the incidence of both permanent and transient CH was observed, associated with lowering of TSH cutoffs as well as other yet unidentified factors.
- Published
- 2016
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45. Preserved insulin sensitivity predicts metabolically healthy obese phenotype in children and adolescents.
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Vukovic R, Milenkovic T, Mitrovic K, Todorovic S, Plavsic L, Vukovic A, and Zdravkovic D
- Subjects
- Adolescent, Child, Child, Preschool, Female, Glucose Tolerance Test, Humans, Male, Metabolic Syndrome physiopathology, Pediatric Obesity physiopathology, Phenotype, Sensitivity and Specificity, Insulin Resistance, Metabolic Syndrome diagnosis, Pediatric Obesity diagnosis
- Abstract
Available data on metabolically healthy obese (MHO) phenotype in children suggest that gender, puberty, waist circumference, insulin sensitivity, and other laboratory predictors have a role in distinguishing these children from metabolically unhealthy obese (MUO) youth. The goal of this study was to identify predictors of MHO phenotype and to analyze glucose and insulin metabolism during oral glucose tolerance test (OGTT) in MHO children. OGTT was performed in 244 obese children and adolescents aged 4.6-18.9 years. Subjects were classified as MHO in case of no fulfilled criterion of metabolic syndrome except anthropometry or as MUO (≥2 fulfilled criteria). Among the subjects, 21.7 % had MHO phenotype, and they were more likely to be female, younger, and in earlier stages of pubertal development, with lower degree of abdominal obesity. Insulin resistance was the only independent laboratory predictor of MUO phenotype (OR 1.59, CI 1.13-2.25), with 82 % sensitivity and 60 % specificity for diagnosing MUO using HOMA-IR cutoff point of ≥2.85. Although no significant differences were observed in glucose regulation, MUO children had higher insulin demand throughout OGTT, with 1.53 times higher total insulin secretion., Conclusion: Further research is needed to investigate the possibility of targeted treatment of insulin resistance to minimize pubertal cross-over to MUO in obese children., What Is Known: • Substantial proportion of the obese youth (21-68 %) displays a metabolically healthy (MHO) phenotype. • Gender, puberty, waist circumference, insulin sensitivity, and lower levels of uric acid and transaminases have a possible role in distinguishing MHO from metabolically unhealthy obese (MUO) children., What Is New: • Insulin resistance was found to be the only significant laboratory predictor of MUO when adjusted for gender, puberty, and the degree of abdominal obesity. • Besides basal insulin resistance, MUO children were found to have a significantly higher insulin secretion throughout OGTT in order to maintain glucose homeostasis.
- Published
- 2015
- Full Text
- View/download PDF
46. Lack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD).
- Author
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Sanyal M, Morimoto M, Baradaran-Heravi A, Choi K, Kambham N, Jensen K, Dutt S, Dionis-Petersen KY, Liu LX, Felix K, Mayfield C, Dekel B, Bokenkamp A, Fryssira H, Guillen-Navarro E, Lama G, Brugnara M, Lücke T, Olney AH, Hunley TE, Polat AI, Yis U, Bogdanovic R, Mitrovic K, Berry S, Najera L, Najafian B, Gentile M, Nur Semerci C, Tsimaratos M, Lewis DB, and Boerkoel CF
- Subjects
- Adolescent, Adult, Arteriosclerosis metabolism, Arteriosclerosis pathology, Cells, Cultured, Child, Child, Preschool, DNA Helicases genetics, DNA Methylation, Flow Cytometry, Gene Expression, Humans, Immunohistochemistry, Immunologic Deficiency Syndromes metabolism, Immunologic Deficiency Syndromes pathology, Interleukin-17 pharmacology, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Mutation, Nephrotic Syndrome metabolism, Nephrotic Syndrome pathology, Osteochondrodysplasias metabolism, Osteochondrodysplasias pathology, Primary Immunodeficiency Diseases, Promoter Regions, Genetic genetics, Pulmonary Embolism metabolism, Pulmonary Embolism pathology, Receptors, Interleukin-7 metabolism, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Young Adult, Arteriosclerosis genetics, Immunologic Deficiency Syndromes genetics, Nephrotic Syndrome genetics, Osteochondrodysplasias genetics, Pulmonary Embolism genetics, Receptors, Interleukin-7 genetics, T-Lymphocytes metabolism
- Abstract
Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal childhood disorder associated with skeletal dysplasia, renal dysfunction, and T-cell immunodeficiency. This disease is linked to biallelic loss-of-function mutations of the SMARCAL1 gene. Although recurrent infection, due to T-cell deficiency, is a leading cause of morbidity and mortality, the etiology of the T-cell immunodeficiency is unclear. Here, we demonstrate that the T cells of SIOD patients have undetectable levels of protein and mRNA for the IL-7 receptor alpha chain (IL7Rα) and are unresponsive to stimulation with IL-7, indicating a loss of functional receptor. No pathogenic mutations were detected in the exons of IL7R in these patients; however, CpG sites in the IL7R promoter were hypermethylated in SIOD T cells. We propose therefore that the lack of IL7Rα expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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- View/download PDF
47. Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors.
- Author
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Vukovic R, Zdravkovic D, Mitrovic K, Milenkovic T, Todorovic S, Vukovic A, and Soldatovic I
- Subjects
- Adolescent, Adult, Blood Glucose, Body Mass Index, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Insulin Resistance, Male, Obesity physiopathology, Prevalence, Prognosis, Risk Factors, Serbia epidemiology, Young Adult, Metabolic Syndrome epidemiology, Metabolic Syndrome etiology, Obesity complications
- Abstract
Objective: To assess the prevalence of metabolic syndrome (MS) in obese children and adolescents in Serbia., Subjects and Methods: The study group consisted of 254 subjects (148 female and 106 male), aged 4.6-18.9 years with diet-induced obesity (body mass index ≥95th percentile). Presence of MS using the International Diabetes Federation definition was assessed in all subjects, as well as oral glucose tolerance test and insulin resistance indices., Results: Overall prevalence of MS in all subjects aged ≥10 years was 31.2%, namely, 28.7% in children aged 10 to <16 years and 40.5% in adolescents ≥16 years. When adjusted for age, gender and pubertal development, higher degree of obesity was a strong predictor of MS. Multivariate analysis showed that taller subjects and those with higher degree of insulin resistance were at significantly higher risk of MS, independent of the degree of obesity., Conclusions: High prevalence of MS emphasizes the need for prevention and treatment of childhood obesity.
- Published
- 2015
- Full Text
- View/download PDF
48. Ontogenetic changes of craniofacial complex in Turner syndrome patients treated with growth hormone.
- Author
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Juloski J, Glisic B, Scepan I, Milasin J, Mitrovic K, and Babic M
- Subjects
- Adolescent, Age Determination by Skeleton, Cephalometry methods, Cervical Vertebrae growth & development, Child, Child, Preschool, Facial Bones drug effects, Female, Humans, Mandible drug effects, Mandible growth & development, Maxilla drug effects, Maxilla growth & development, Nasal Bone drug effects, Nasal Bone growth & development, Retrognathia physiopathology, Sella Turcica drug effects, Sella Turcica growth & development, Skull drug effects, Skull Base drug effects, Skull Base growth & development, Facial Bones growth & development, Human Growth Hormone therapeutic use, Maxillofacial Development drug effects, Skull growth & development, Turner Syndrome drug therapy
- Abstract
Objective: The present study assessed changes of craniofacial complex in Turner syndrome (TS) patients treated with growth hormone (GH) during development. The objective was to examine the growth rate and pattern of craniofacial structures and to establish effects of GH on craniofacial development., Materials and Methods: The study population consisted of 15 TS patients treated with GH aged 5-18.5 years (13.3 ± 4.4) and corresponding control group of 45 females aged 6.8-18.7 (11.4 ± 2.6). According to the stage of cervical vertebral maturation, subjects were categorized into pre-growth (5 TS and 15 controls) and growth (10 TS and 30 controls) subgroups. The cephalometric analysis comprised angular and linear variables, measured on lateral cephalometric radiographs., Results: The mandibular corpus/anterior cranial base ratio increased significantly only in controls during development. In growth period, ramus/corpus ratio was significantly larger in TS group. SNA and SNB angles were significantly smaller in TS growth subgroup compared to corresponding controls. Among other variables, no statistically significant differences were revealed., Conclusions: In TS patients treated with GH, growth capacities of cranial base and maxilla are adequate which can be attributed to GH treatment. Shape of mandible is altered due to decreased growth of corpus and overdeveloped ramus. Both maxillary and mandibular retrognathism are becoming more expressed during development., Clinical Relevance: Favorable influence of GH on craniofacial complex growth rate and altered growth pattern revealed in this study should be considered while planning both orthodontic treatment and retention.
- Published
- 2013
- Full Text
- View/download PDF
49. Insulin-sensitive obese children display a favorable metabolic profile.
- Author
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Vukovic R, Mitrovic K, Milenkovic T, Todorovic S, Soldatovic I, Sipetic-Grujicic S, and Zdravkovic D
- Subjects
- Adolescent, Child, Child, Preschool, Cholesterol, HDL blood, Cholesterol, LDL blood, Female, Health Status Indicators, Humans, Male, Insulin Resistance physiology, Obesity blood, Obesity physiopathology
- Abstract
Unlabelled: Most of what is known about the metabolically healthy obese phenomenon is derived from studies in the adult population and no standardized criteria to identify these individuals exist to date. The aim of this study was to determine if the preserved insulin sensitivity evaluated by homeostatic model assessment of insulin resistance (HOMA-IR) index is associated with favorable metabolic profile in the obese children. We studied a group of 248 children and adolescents (150 female, 98 male), aged 5.9-18.9 years with diet-induced obesity (BMI >95th percentile). The entire cohort was divided into quartiles based on levels of insulin resistance determined by HOMA-IR index. Subjects in the lower quartile of HOMA-IR were classified as insulin-sensitive group (ISG), whereas children in the upper quartile were categorized as insulin-resistant group (IRG). The ISG subjects had values of HOMA-IR ≤2.75 while the children from the IRG group had HOMA-IR ≥6.16. Subjects from ISG group had lower basal β-cell activity and were less likely to have impaired fasting glucose or impaired glucose tolerance. Concentrations of LDL and total cholesterol, triglycerides, and transaminases were lower and HDL cholesterol levels were higher in ISG subjects. Findings obtained by the use of Matsuda index correlated well with the findings obtained by the use of HOMA-IR., Conclusion: Lower HOMA-IR values were significantly associated with favorable metabolic profile in studied children, which correlates with findings in the adult population and emphasizes the need for further, longitudinal studies of insulin resistance development in childhood obesity.
- Published
- 2013
- Full Text
- View/download PDF
50. Triple A syndrome: 32 years experience of a single centre (1977-2008).
- Author
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Milenkovic T, Zdravkovic D, Savic N, Todorovic S, Mitrovic K, Koehler K, and Huebner A
- Subjects
- Adrenal Insufficiency diagnosis, Adrenal Insufficiency genetics, Adrenal Insufficiency metabolism, Child, Child, Preschool, Chromosomes, Human, Pair 12, Esophageal Achalasia diagnosis, Esophageal Achalasia genetics, Esophageal Achalasia metabolism, Female, Follow-Up Studies, Genotype, Humans, Infant, Male, Nerve Tissue Proteins metabolism, Nuclear Pore Complex Proteins metabolism, Retrospective Studies, Time Factors, DNA genetics, Mutation, Nerve Tissue Proteins genetics, Nuclear Pore Complex Proteins genetics
- Abstract
Triple A syndrome is an autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and neurodegeneration. Mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN have been reported in these patients. Over the period 1977-2008 we evaluated ten subjects with the clinical diagnosis of triple A syndrome. Molecular analysis was performed in seven patients and revealed that all except one are compound heterozygotes for two mutations in the AAAS gene. Two novel mutations were detected: c.123+2T>C resulted in splice defect while c.1261_1262insG mutation resulted in a truncated protein (p.V421fs), which most probably is not functional. Genotype-phenotype correlation could not be established. In all our patients, except one sibling of previously diagnosed brother and sister, genetic analysis was performed when at least two symptoms were present, usually alacrima and achalasia. Based on our experience, we recommend that in case of the presence of alacrima and at least one more symptom of triple A syndrome, adrenal function testing and molecular analysis should be performed. In all children with mutation in AAAS gene, regular follow up of adrenal function is necessary to avoid adrenal crisis and start substitution therapy as soon as adrenal insufficiency is noted.
- Published
- 2010
- Full Text
- View/download PDF
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