Browsing by Author "Damjanovic, S. (7003775804)"

Objective: To evaluate cardiac autonomic control in patients with myasthenia gravis (MG) and thymoma. Materials and methods: The study was performed on 21 patients with MG and thymoma and the same number of matched healthy volunteers. Standard cardiovascular reflex tests according to Ewing and baroreflex sensitivity (BRS) at rest was applied. Spectral analysis of heart rate variability (HRV) at rest was assessed using a 20-minute ECG recording (normalized low- and high-frequency bands-LFnu-RRI, HFnu-RRI and LF/HF-RRI) Time-domain analysis of HRV was derived from 24-hour ECG monitoring. Results: Overall autonomic score according to Ewing was significantly increased in patients with MG and thymoma (p < 0.05), mostly due to parasympathetic dysfunction. Time-domain parameters representing the overall and long-term sympathetic activity of HRV did not differ significantly between the two groups (p > 0.05), but there was a significant decrease in measures of the short-term vagal variations in HRV (p < 0.01). HFnu-RRI was lower, while LFnu-RRI and LF/HF-RRI were higher in patients with MG and thymoma in comparison to healthy controls but these differences were not of statistical significance (p > 0.05). BRS at rest was highly significantly reduced in patients group (p < 0.01). Conclusions: Our results showed mainly parasympathetic cardiac impairment in patients with myasthenia gravis and thymoma. Since autonomic dysfunction may lead to cardiac conduction abnormalities and sudden death, the investigation of autonomic nervous system function in these patients may be significant in everyday clinical practice. © 2011 Elsevier B.V. All rights reserved.

Objective: To evaluate cardiac autonomic control in patients with myasthenia gravis (MG) and thymoma. Materials and methods: The study was performed on 21 patients with MG and thymoma and the same number of matched healthy volunteers. Standard cardiovascular reflex tests according to Ewing and baroreflex sensitivity (BRS) at rest was applied. Spectral analysis of heart rate variability (HRV) at rest was assessed using a 20-minute ECG recording (normalized low- and high-frequency bands-LFnu-RRI, HFnu-RRI and LF/HF-RRI) Time-domain analysis of HRV was derived from 24-hour ECG monitoring. Results: Overall autonomic score according to Ewing was significantly increased in patients with MG and thymoma (p < 0.05), mostly due to parasympathetic dysfunction. Time-domain parameters representing the overall and long-term sympathetic activity of HRV did not differ significantly between the two groups (p > 0.05), but there was a significant decrease in measures of the short-term vagal variations in HRV (p < 0.01). HFnu-RRI was lower, while LFnu-RRI and LF/HF-RRI were higher in patients with MG and thymoma in comparison to healthy controls but these differences were not of statistical significance (p > 0.05). BRS at rest was highly significantly reduced in patients group (p < 0.01). Conclusions: Our results showed mainly parasympathetic cardiac impairment in patients with myasthenia gravis and thymoma. Since autonomic dysfunction may lead to cardiac conduction abnormalities and sudden death, the investigation of autonomic nervous system function in these patients may be significant in everyday clinical practice. © 2011 Elsevier B.V. All rights reserved.

OBJECTIVE: The goal of our study was to determine the rate of neoplasms in patients with other pituitary adenomas (non-functioning and prolactinomas) in comparison with acromegaly which is known to favour the development of neoplasia. DESIGN AND PATIENTS: We reviewed clinical records for 220 patients with acromegaly, 151 patients with non-functioning pituitary adenoma (NF) and 98 patients with prolactinomas. Incidence rates of cancer for patients with pituitary tumours were calculated per person-years of follow-up study. These rates were then compared with sex and age adjusted incidence rates reported by National Tumour Registry. An internal control group of 163 subjects with a nonneoplastic condition, i.e. Graves' disease followed chronically in the same clinic was also studied. The ratios observed to expected were expressed as standardized incidence rates (SIR). The only significant difference between the acromegalic and other pituitary tumours patients was in hypopituitarism, present in 18.2% (acromegaly) 47% (NF) and 18.6% (prolactinomas). RESULTS: Twenty-three malignant tumours were registered in 19 acromegalics (1 Hodgkin disease, 1 myelogenous leukaemia, 1 lymphocytic leukaemia, 3 papillary thyroid carcinomas, 1 ovarian carcinoma, 2 colorectal carcinoma, 1 renal cell carcinoma, 4 cervical carcinoma, 2 skin cancers, 2 pancreatic carcinoma, 4 breast carcinoma, 1 bladder carcinoma). Three acromegalics harboured two malignancies. Patients with acromegaly had a 3.39- fold increased rate of malignant tumours compared with the general population and a 3.21-fold increased rate compared with our internal control group. Eleven malignant tumours were found in patients with NF-pituitary adenomas and 2 in prolactinoma patients (1 lymphoma, 1 multiple myeloma, 1 colonic cancer, 1 renal cell cancer, 1 stomach cancer, 2 lung cancers, 1 cervix carcinoma, 1 breast cancer, 1 testicular carcinoma and 3 melanoma). Patients with NF pituitary adenomas had a 3.91-fold increased rate of malignant tumours compared with the general population and 4.07-fold increase compared with the internal control group. Patients harbouring prolactinomas did not have an increased incidence rate of malignancy compared with the general population or our internal controls. Female patients with acromegaly and male patients with NF-pituitary adenoma had higher incidences of neoplasia. CONCLUSION: We have demonstrated that the overall incidence of malignant tumours in patients with non-functioning pituitary adenomas and acromegaly is significantly higher than expected for general population and for our internal control group.

OBJECTIVE: The goal of our study was to determine the rate of neoplasms in patients with other pituitary adenomas (non-functioning and prolactinomas) in comparison with acromegaly which is known to favour the development of neoplasia. DESIGN AND PATIENTS: We reviewed clinical records for 220 patients with acromegaly, 151 patients with non-functioning pituitary adenoma (NF) and 98 patients with prolactinomas. Incidence rates of cancer for patients with pituitary tumours were calculated per person-years of follow-up study. These rates were then compared with sex and age adjusted incidence rates reported by National Tumour Registry. An internal control group of 163 subjects with a nonneoplastic condition, i.e. Graves' disease followed chronically in the same clinic was also studied. The ratios observed to expected were expressed as standardized incidence rates (SIR). The only significant difference between the acromegalic and other pituitary tumours patients was in hypopituitarism, present in 18.2% (acromegaly) 47% (NF) and 18.6% (prolactinomas). RESULTS: Twenty-three malignant tumours were registered in 19 acromegalics (1 Hodgkin disease, 1 myelogenous leukaemia, 1 lymphocytic leukaemia, 3 papillary thyroid carcinomas, 1 ovarian carcinoma, 2 colorectal carcinoma, 1 renal cell carcinoma, 4 cervical carcinoma, 2 skin cancers, 2 pancreatic carcinoma, 4 breast carcinoma, 1 bladder carcinoma). Three acromegalics harboured two malignancies. Patients with acromegaly had a 3.39- fold increased rate of malignant tumours compared with the general population and a 3.21-fold increased rate compared with our internal control group. Eleven malignant tumours were found in patients with NF-pituitary adenomas and 2 in prolactinoma patients (1 lymphoma, 1 multiple myeloma, 1 colonic cancer, 1 renal cell cancer, 1 stomach cancer, 2 lung cancers, 1 cervix carcinoma, 1 breast cancer, 1 testicular carcinoma and 3 melanoma). Patients with NF pituitary adenomas had a 3.91-fold increased rate of malignant tumours compared with the general population and 4.07-fold increase compared with the internal control group. Patients harbouring prolactinomas did not have an increased incidence rate of malignancy compared with the general population or our internal controls. Female patients with acromegaly and male patients with NF-pituitary adenoma had higher incidences of neoplasia. CONCLUSION: We have demonstrated that the overall incidence of malignant tumours in patients with non-functioning pituitary adenomas and acromegaly is significantly higher than expected for general population and for our internal control group.

To get more insight into molecular mechanisms underlying oxidative stress and its link with insulin resistance, oxidative stress parameters, as well as, antioxidant enzyme activities were studied in young, non-obese women with polycystic ovary syndrome (PCOS). Study was performed in 34 PCOS women and 23 age and body mass index (BMI)-matched healthy controls. Plasma nitrotyrosine and malondialdehyde (MDA), representative byproducts of protein and lipid oxidative damage, were determined by enzyme immunoassay. Antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Insulin resistance was calculated using homeostasis assessment model (HOMA-IR). Plasma nitrotyrosine and MDA were increased, but only nitrotyrosine was signifi cantly higher (p < 0.05) in PCOS women compared to controls. Uric acid (surrogate marker of × antine oxidase) was also signifi cantly elevated in PCOS (p < 0.05). Both plasma SOD and GPX activity showed no statistically significant difference between PCOS and controls. Indices of insulin resistance (insulin and HOMAIR) were significantly higher in PCOS group and positively correlated with level of MDA (r = 0.397 and r = 0.523, respectively; p < 0.05) as well as GPX activity (r = 0.531 and r = 0.358, respectively; p < 0.05). Our results indicate that insulin resistance could be responsible for the existence of subtle form of oxidative stress in young, nonobese PCOS women. Hence, presence of insulin resistance, hyperinsulinemia and oxidative damage are likely to accelerate slow development of cardiovascular disease in PCOS. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

To get more insight into molecular mechanisms underlying oxidative stress and its link with insulin resistance, oxidative stress parameters, as well as, antioxidant enzyme activities were studied in young, non-obese women with polycystic ovary syndrome (PCOS). Study was performed in 34 PCOS women and 23 age and body mass index (BMI)-matched healthy controls. Plasma nitrotyrosine and malondialdehyde (MDA), representative byproducts of protein and lipid oxidative damage, were determined by enzyme immunoassay. Antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Insulin resistance was calculated using homeostasis assessment model (HOMA-IR). Plasma nitrotyrosine and MDA were increased, but only nitrotyrosine was signifi cantly higher (p < 0.05) in PCOS women compared to controls. Uric acid (surrogate marker of × antine oxidase) was also signifi cantly elevated in PCOS (p < 0.05). Both plasma SOD and GPX activity showed no statistically significant difference between PCOS and controls. Indices of insulin resistance (insulin and HOMAIR) were significantly higher in PCOS group and positively correlated with level of MDA (r = 0.397 and r = 0.523, respectively; p < 0.05) as well as GPX activity (r = 0.531 and r = 0.358, respectively; p < 0.05). Our results indicate that insulin resistance could be responsible for the existence of subtle form of oxidative stress in young, nonobese PCOS women. Hence, presence of insulin resistance, hyperinsulinemia and oxidative damage are likely to accelerate slow development of cardiovascular disease in PCOS. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Context. Insulin-like growth factor-1 (IGF-1) is main serum surrogate marker of growth hormone (GH) secretion, used in diagnostics and treatment of GH deficiency (GHD) and acromegaly. Regional, ethnic, racial or nutritional factors obscure cross-population applicability of IGF-1 reference values. Establishment of population-and assay-specific reference values requires sizable representative cohort of healthy subjects. Subjects and Methods. In representative sample of healthy adult population of Serbia (N=1200, 21-80 years, 1:1 male:female) serum IGF-1 was analyzed by Siemens Immulite 2000 assay under uniform laboratory conditions. Upper and lower limit of reference range (5th-95th percentile) were calculated for each of the 12 quinquennial age intervals. IGF-1 distribution was normalized and standard deviation score (SDS) calculated by Logarithmic and LMS methods. Results. IGF-1 and age correlated significantly, with most prominent decline at 21-50 years, followed by a plateau up to age of 70. Gender differences were not significant overall. Plateau in age-related IGF-1 decline was less prominent in women. Correlations of IGF-1 with body mass index (BMI) or waist to hip ratio (WHR) were insignificant. Superior IGF-1 SDS transformation was achieved with LMS method, while logarithmic method was simpler to use. Conclusions. Normative age-specific serum IGF-1 reference values were established on a representative cohort of healthy adults in Serbia. Our results support recommendations against necessity for gender-specific or BMI-and WHR-specific reference ranges. Population-based data serve to generate IGF-1 SDS, which is valuable in rational application of consensus guidelines, proper longitudinal follow-up, advancement in efficacy and safety and personalization of treatment targets. © 2021, Acta Endocrinologica Foundation. All rights reserved.

Context. Insulin-like growth factor-1 (IGF-1) is main serum surrogate marker of growth hormone (GH) secretion, used in diagnostics and treatment of GH deficiency (GHD) and acromegaly. Regional, ethnic, racial or nutritional factors obscure cross-population applicability of IGF-1 reference values. Establishment of population-and assay-specific reference values requires sizable representative cohort of healthy subjects. Subjects and Methods. In representative sample of healthy adult population of Serbia (N=1200, 21-80 years, 1:1 male:female) serum IGF-1 was analyzed by Siemens Immulite 2000 assay under uniform laboratory conditions. Upper and lower limit of reference range (5th-95th percentile) were calculated for each of the 12 quinquennial age intervals. IGF-1 distribution was normalized and standard deviation score (SDS) calculated by Logarithmic and LMS methods. Results. IGF-1 and age correlated significantly, with most prominent decline at 21-50 years, followed by a plateau up to age of 70. Gender differences were not significant overall. Plateau in age-related IGF-1 decline was less prominent in women. Correlations of IGF-1 with body mass index (BMI) or waist to hip ratio (WHR) were insignificant. Superior IGF-1 SDS transformation was achieved with LMS method, while logarithmic method was simpler to use. Conclusions. Normative age-specific serum IGF-1 reference values were established on a representative cohort of healthy adults in Serbia. Our results support recommendations against necessity for gender-specific or BMI-and WHR-specific reference ranges. Population-based data serve to generate IGF-1 SDS, which is valuable in rational application of consensus guidelines, proper longitudinal follow-up, advancement in efficacy and safety and personalization of treatment targets. © 2021, Acta Endocrinologica Foundation. All rights reserved.

Aim. The aim of this study was to extend the analysis of the systolic right ventricular (RV) adaptation to combined endurance and strength training, to assess the utility of tissue Doppler imaging in detecting the degree of these changes and to find independent RV predictors of the maximal functional capacity. Methods. Standard Doppler and TDI were used to assess cardiac parameters at rest in 37 elite male athletes (16 wrestlers, 21 water polo players) and 20 sedentary subjects of similar age. Progressive maximal test on treadmill was used to assess VO2max The obtained parameters were adjusted for HR, FFM, and BSA. Results. Wrestlers showed higher VO 2max than controls, but lesser than water polo players. RV diameter was larger in athletes. Right atrial pressure (RVE/e) was higher in water polo players than in other groups. Systolic function assessed by tricuspid annular plane systolic excursion (TAPSE) and RVs' was the highest in wrestlers. Global RV systolic parameters myocardial performance index (MPI) and preejection time/ ejection time index (PET/ET) were similar. On multivariate analysis systolic parameters were independent predictors of VO2max only in wrestlers: RVs' (beta=3.18, P=0.001) and RV ET (beta=2.32, P=0.001). RVE/e correlated with RVs' (r=-0.57, P=0.000). TAPSE correlated with RV ET (r=0.32, P=0.015) and RVs (beta=0.28, P=0.033). Conclusion. Systolic function assessed by TAPSE and RVs has more improved in less endurance athletes. RVs and TDI ejection time predict VO2max in wrestlers, and possibly in other athletes with lesser right atrial pressure. TDI enables quantifying RV adaptation degree in athletes, but complementary to M-mode technique.

Aim. The aim of this study was to extend the analysis of the systolic right ventricular (RV) adaptation to combined endurance and strength training, to assess the utility of tissue Doppler imaging in detecting the degree of these changes and to find independent RV predictors of the maximal functional capacity. Methods. Standard Doppler and TDI were used to assess cardiac parameters at rest in 37 elite male athletes (16 wrestlers, 21 water polo players) and 20 sedentary subjects of similar age. Progressive maximal test on treadmill was used to assess VO2max The obtained parameters were adjusted for HR, FFM, and BSA. Results. Wrestlers showed higher VO 2max than controls, but lesser than water polo players. RV diameter was larger in athletes. Right atrial pressure (RVE/e) was higher in water polo players than in other groups. Systolic function assessed by tricuspid annular plane systolic excursion (TAPSE) and RVs' was the highest in wrestlers. Global RV systolic parameters myocardial performance index (MPI) and preejection time/ ejection time index (PET/ET) were similar. On multivariate analysis systolic parameters were independent predictors of VO2max only in wrestlers: RVs' (beta=3.18, P=0.001) and RV ET (beta=2.32, P=0.001). RVE/e correlated with RVs' (r=-0.57, P=0.000). TAPSE correlated with RV ET (r=0.32, P=0.015) and RVs (beta=0.28, P=0.033). Conclusion. Systolic function assessed by TAPSE and RVs has more improved in less endurance athletes. RVs and TDI ejection time predict VO2max in wrestlers, and possibly in other athletes with lesser right atrial pressure. TDI enables quantifying RV adaptation degree in athletes, but complementary to M-mode technique.

Background: Medullary thyroid carcinoma (MTC) is a type of thyroid neoplasm which originates from parafollicular cells, and it is commonly diagnosed by calcitonin screening. Besides the sporadic form, the heritable form of MTC is characterized by constitutive activation of the RET (REarranged during Transfection) proto-oncogene caused by different mutations. Method: We collected data regarding RET genetic screening performed in the Center for Endocrine Surgery in Belgrade during a 20-year-period. The study group included 249 MTC patients who were genetically tested for RET mutations by Sanger’s sequencing method. Results: Genetic screening of the study population revealed nine different mutations of the RET gene in 42 carriers. The most common mutation was C634F, and it has been detected in 31 % (13/42) of individuals, while C618R, L790F, and S904S were present in only 2 % (1/42) each in the study group. Detected mutations were unequally distributed in different RET gene exons. Among MTC patients, 67 % (28/42) had mutation harbored in exon 11, while the rarest mutation was located in exons 10 and 15, each present in only 2 % (1/42) of patients. Conclusions: The RET gene mutation profile has a unique distribution in this study population when compared with the other European populations. The mutations in codon 634 are most common; therefore the cost-reducing genetic screening should primarily target this codon, and if the negative outcome appears, then other codons should be examined in the order that depends on their occurrence. © 2016, Lithografia Antoniadis I - Psarras Th G.P. All rights reserved.

Our aim was to assess clinical utility of 99mTc-EDDA/HYNIC-TOC scintigraphy for evaluation of lung lesions in patients with neuroendocrine tumors (NETs). Single photon emission computed tomography (SPECT) of the thorax and whole body scintigraphy were performed in 34 patients using 99mTc-EDDA/HYNIC-TOC. Visual assessment was complemented by semiquantitative evaluation based on tumor to non-tumor (T/NT) ratio. Clinical, laboratory, and histological findings served as the standard for comparison. Enhanced tracer uptake was observed on both SPECT and whole body scintigraphy in 29 of 34 patients (88% sensitivity). T/NT ratios were significantly higher on SPECT than whole body images (2.96±1.07 vs.1.70±0.43, p<0.01) and did not correlate with NET proliferation index Ki-67 (r= - 0.36, p=0.27). Conclusion: 99mTc-EDDA/ HYNIC-TOC scintigraphy is useful for evaluation of NET tissue in the lungs. SPECT provides better visualization of lung lesions than whole body scintigraphy. The intensity of tracer uptake, however, does not relate to the proliferation rate of NETs. 99mTc-EDDA/HYNIC-TOC scintigraphy may be helpful for selecting and monitoring treatment options, particularly when radiolabeled somatostatin analogue therapy becomes available.