Positive regulatory domain containing 16 (PRDM16) protein represents the key regulator of brown adipose tissue (BAT) development. It induces brown fat phenotype and represses white adipose tissue ...specific genes through the association with
-terminal binding co-repressor proteins (CtBP1 and CtBP2). In healthy adults presence of BAT has been associated with lower glucose, total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Our aim was to analyze the association of
gene (rs12409277) and
gene (rs1561589) polymorphisms with body mass index (BMI), fasting glucose level and lipid profile of adolescents.
Our study included 295 healthy school children, 145 boys (49.2%) and 150 girls (50.8%), 15 years of age. Genotypes for the selected polymorphisms were detected by the real-time PCR method. Age, gender, height, weight, lipid profile (total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, triglycerides) and fasting glucose levels were recorded.
We did not find a statistically significant association of rs12409277 and rs1561589 polymorphisms with BMI, fasting glucose and lipid profile of adolescents. We further analyzed the combined effect of the two SNPs and the statistical analysis showed that carriers of CT genotype of rs12409277 polymorphism and GG genotype of rs1561589 polymorphism had significantly lower total cholesterol (
= 0.001) and LDL cholesterol (
= 0.008) levels compared to all other groups of genotypes.
Our study suggests that rs12409277 and rs1561589 polymorphism might have an influence on total and LDL cholesterol levels in adolescents. Larger studies should be performed in order to confirm our results.
Abstract Objectives: This study was conducted to determine the effects of carvedilol adjunct to standard treatment on left ventricular function (LVF), estimated as ejection fraction (EF) and ...fractional shortening (FS) on echocardiography, in children with idiopathic dilated cardiomyopathy (DCM). A secondary end point was to characterize the antioxidant potential of carvedilol. Methods: Hospitalized children aged ≤16 years with clinically stable DCM and advanced congestive heart failure (HF) with modified New York Heart Association Classification for Children (NYHAC) functional classes II to IV and EF <40% were enrolled in this prospective, 12-month, 2-center, open-label study. Oral carvedilol was added to a standard regimen of an angiotensin-converting enzyme inhibitor, a diuretic, and digoxin in a dose-escalation design. Systolic and diastolic blood pressure (BP), heart rate (HR), and modified NYHAC were assessed before (baseline) and at 1, 3, 6, and 12 months of adjunct carvedilol treatment. EF and FS were analyzed before and at 6 and 12 months of carvedilol treatment. At each study visit, tolerability was assessed in terms of adverse events (AEs), treatment emergent signs and symptoms, physical examination including vital sign measurement (BP, HR, and body temperature), and laboratory analysis. Antioxidative enzyme activity was evaluated by measuring erythrocyte copper/zinc superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activity at baseline and 1, 3, 6, and 12 months of adjunct carvedilol treatment. For assessment of antioxidative enzyme activity, a control group comprised 29 age-matched healthy children. Results: Twenty-one children (12 boys, 9 girls; age range, 7 months to 16 years; 100% white) completed the study. Four patients discontinued carvedilol at the beginning of the study due to severe arrhythmia which required amiodarone therapy (2 patients), bradycardia and hypotension (1), and bronchospasm (1). Carvedilol (0.4 mg/kg/d in children ≤62.5 kg or 25 mg/d in children >62.5 kg) was associated with significant decreases from baseline in systolic BP (130 4 vs 123 3 mm Hg; P < 0.05), diastolic BP (85 4 vs 77 4 mm Hg; P < 0.05), and HR (81 4 vs 65 4 bpm; P < 0.001) after the first month of addition to standard therapy. At 6 months, there were significant improvements from baseline in EF (37.2% 2.4% vs 50.2% 2.3%; P < 0.001) and FS (18.37% 2.00% vs 23.58% 0.90%; P < 0.001). Modified NYHAC class was significantly improved in 80% of children (2.9 vs 2.3; P < 0.001) at 12 months. The highest dose of carvedilol (0.8 mg/kg/d in children ≤62.5 kg or 50 mg/d in children >62.5 kg) was well tolerated in all 21 children. No serious AEs that necessitated study drug discontinuation (tiredness, headache, vomiting) were observed. At baseline, mean (SE) erythrocyte SOD activity (2781 116 vs 2406 102 U/g Hb; P < 0.05) and GR activity (5.3 0.3 vs 3.0 0.2 μmol nicotinamide adenine dinucleotide phosphate NADPH/min/g Hb; P < 0.001) were significantly higher in children with DCM who received standard therapy compared with healthy controls.CAT activity (12.70.9 vs 18.5 1.0U/g Hb; P < 0.001) was significantly lower, while GSH-Px was unchanged. At 6 and 12 months of therapy, carvedilol plus standard treatment was associated with significant decreases from baseline in SOD (2516 126 and 2550 118, respectively, vs 2781 116 U/g Hb; both, P <0.001) and GR (4.7 0.3 and 4.1 0.2, respectively, vs 5.3 0.2 μmol NADPH/min/g Hb; P < 0.05 and P < 0.001) and increased CAT (16.9 1.0 and 16.4 0.7, respectively, vs 12.7 0.9 U/g Hb; both, P < 0.001). Conclusions: These pediatric patients with DCM treated for 12 months with carvedilol (up to 0.8 mg/kg/d in children ≤62.5 kg or 50 mg/d in children >62.5 kg) were found to have significant improvements in LVF and symptoms of HF. Twelve months of carvedilol therapy was associated with antioxidant enzyme activities near those observed in healthy children.
The aim of the study was to analyze changes of systolic and diastolic blood pressure values over five and ten years separately boys and girls and to estimate correlation between them. Three age ...groups from 8 centers in Serbia were evaluated: Group 1: 10 year old patients, Group 2: 15 year old and Group 3: 20 year old. Group with normal blood pressure values, prehypertensive and hypertensive group were analyzed. Regarding the period of follow-up we analyzed: 10/15 years period-children between 10 and 15 years, 15/20 years period-children between 15 and 20 years, and 10/20 years period-children between 10 and 20 years. Significant increase of diastolic blood pressure was noticed for both genders in 10/15 years period of prehypertensive population, while in hypertensive children, boys showed decline in frequency for systolic and diastolic blood pressure and girls only for diastolic. In 15/20 years period there was significant decrease of prehypertensive and significant increase of hypertensive diastolic blood pressure frequency. In 10/20 years period significant reduction in frequency of prehypertensive systolic blood pressure was noticed, while only hypertensive group of boys showed significant reduction regarding systolic blood pressure frequency. Prehypertensive diastolic and hypertensive systolic blood pressure fluctuations are more related to age.
Athersclerosis is a multifactorial disease that begins in childhood. There are few reports regarding influence of risk factors on the atherosclerotic processes in early period of life and ...adolescence.
The aim of this study was to present and analyze risk factor trends in school children over a 10-year period that were included and followed-up by the Yugoslav Study of Atherosclerosis Precursors in School Children (YUSAD Study).
There were three examinations of selected population from 13 centres. The first examination was performed when children were 10 years of age (first group; N = 6381 participants), the second examination on the same population when they were 15 years of age (second group; N = 5017) and third when children were 19/20 years of age (third group; N = 1293). Evaluated parameters included: BMI, waist circumference (WaC) and lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride).
A significant elevation of values (p < 0.001) of BMI, WaC and triglycerides and a significant decline (p < 0.001) of total cholesterol and LDL cholesterol in boys over 5 and 10-year period was noticed. There was a significant elevation (p < 0.001) of BMI, WaC and HDL values and a significant decline in LDL cholesterol values in girls over the 5 and 10-year period.
Our results point out that girls between 10 and 19/20 years have a better lipid profile during growth. It should be stressed out that childhood and adolescence can be more beneficial in the observation of risk factor influences on pathological, genetic and clinical levels.
It is observed that there is a lack of physical activity and exercise in children, stressing higher prevalence of childhood obesity. The purpose of the study was to evaluate duration of physical ...activity in a child population and correlation of dynamics in physical activity during 5 years of follow-up in the same population.
We evaluated 3243 school children from 12 regional centres across Serbia. The first examination was done when the children were 10 years old (baseline group), while the second examination was done on the same population when children were 15 years old. Physical activity was classified as recreational activity after school. We analysed 3 groups regarding physical activity: a group of children who were physically active less than 1 hour per day (group I), a second group active from 1 hour to < 3 hours per day (group II), and a third group active ≥ 3 hours per day (group III).
In our study we have found on examination that the majority of children were physically active between 1 and 3 hours per day. Our results indicate that there is significant movement from groups I and III toward group II on the second examination regarding the proportion in the baseline group. There is a significant increase in the number of children in group I as they get older.
School children in Serbia are physically active predominantly between 1 and 3 hours per day at the age between 10 and 15 years.
Background: Reduction of heart rate variability as a consequence of heart disease and postural change has been well documented. However, the data on the effect of postural change in pediatric ...patients are incomplete and the effect is not fully understood. The aim of the study was to investigate effect of postural change on heart rate variability in relation to the extent of severity of heart disease.
Methods: The dependence of heart rate variability on posture in 41 children and young adults (8–20 years) with heart disease has been investigated and compared with control. Short-term electrocardiograms (ECGs) were assessed in supine rest and active standing, and spectral measures of heart rate variability were determined.
Results: Two types of response to the change of supine to standing posture were determined in both healthy and diseased subjects. In majority of subjects, the increased heart rate induced by standing was accompanied by a decrease in high-frequency power. However, in about 30% of all subjects, increased heart rate during standing was accompanied by an increased high-frequency power. Independently of posture and disease, high-frequency and low-frequency power were positively correlated. In subjects characterized by a reduction of heart rate variability in standing, the high-frequency power in both postures is reduced in diseased subjects compared to control.
Conclusions: These results demonstrate that in this age range, the response to posture is not unique because of the difference in high-frequency power, which implies a variety of vagal modulations of heart rate.
The presence of cardiovascular risk factors in children may be important in the development of atherosclerosis in adulthood. Adequate control of blood pressure is a cornerstone in atherosclerosis ...prevention. The aim of the Yugoslav Study of the Precursors of Atherosclerosis in School Children (YUSAD) was to identify risk factors for elevated blood pressure in school children.
The YUSAD study is a multicentre follow-up study comprised of two cross-sectional surveys conducted five years apart. At baseline, 10-year-old children (3226 boys and 3074 girls n=6300) were randomly selected during periodical visits to primary health care centres. The risk factors measured were heart rate, weight, body mass index (BMI), waist-to-hip ratio, grade point average and current smoking status.
Significant age and sex differences were identified in systolic blood pressure, diastolic blood pressure and all investigated independent variables. In a multivariate analysis, diastolic blood pressure in 10-year-old boys was directly and significantly related to total cholesterol and height, whereas it was inversely related to weight. At follow-up, in the multivariate model, only BMI was a significant predictor of diastolic blood pressure in boys. In girls at baseline in the multivariate regression analysis, the only significant predictor of diastolic blood pressure was total cholesterol. In 15-year-old girls, diastolic blood pressure was significantly and directly related to BMI and heart rate, whereas it was inversely related to weight. For both 10- and 15-year-old male and female participants, none of the variables by multivariate analysis were a significant predictor of systolic blood pressure.
Age, sex, heart rate, cholesterol and weight are the most important predictors of blood pressure in school children.
Background: The idea to enter the normal pericardial sac safely was unrealistic until recently. The development of a novel instrument (PerDUCER® pericardial access device) for percutaneous access to ...the pericardium could potentially have a significant impact, not only on patients with pericardial diseases but even more, or primarily, on diagnosis and treatment of myocardial and coronary disease and arrhythmias.
Hypothesis: The overall objective of the present study was to evaluate the feasibility and safety of the percutaneous pericardial access with PerDUCER in patients with pericardial disease, and to analyze our initial experience with this new technique, with particular emphasis on sequential procedural steps.
Methods: The device was studied in five patients with pericardial disease (two men, mean age 50.4 years, range 30–68, four with normal body mass index). The procedure consists of two distinct techniques: (1) access to the mediastinal space, and (2) pericardial capture, puncture, and insertion of the guidewire. Access to the mediastinal space includes the introduction of a blunt cannula, a 0.038 guidewire, a dilator‐introducer sheath set, and insertion of the PerDUCER device. Key points of the PerDUCER procedure are as follows: introduction of the blunt cannula without resistance, placement of the dilator‐introducer sheath at the upper third of the heart, systolic movements of the PerDUCER device, successful vacuum and capture of pericardium, puncture and introduction of the intrapericardial guidewire.
Results: Access to the mediastinal space was accomplished in four of five patients, as were pericardial capture and probably puncture. However, despite numerous successful captures and probably punctures of pericardium, we were not able to confirm introduction of the intrapericardial guidewire into the pericardial cavity in any of our patients (0/5). The procedure was very well tolerated in all patients (5/5). No major complications developed during the procedure, bearing in mind that the intrapericardial placement of the guidewire was not achieved. Minor complications included pain at the dilator‐introducer sheath entry site (5/5) and mild transient fever (2/5).
Conclusions: According to the present experience, we believe that, with minor modifications, the PerDUCER device could be successfully implemented for pericardial entry in patients with pericardial disease. Further studies are needed to evaluate the feasibility and safety of this new instrument in patients with a normal pericardium. This could open a most exciting spectrum of possible implementations of the device in the future.
Objectives. This study was designed to assess the clinical, hemodynamic and diagnostic effects of the addition of dobutamine to dipyridamole echocardiography.
Background. Pharmacologic stress ...echocardiography with either dipyridamole or dobutamine has gained acceptance because of its safety, feasibility, diagnostic accuracy and prognostic power. The main limitation of the two tests is a less than ideal sensitivity in some patient subsets, such as those with limited coronary artery disease. We hypothesized that two pharmacologic stresses might act synergistically in the induction of ischemia by combining the mechanisms of inappropriate coronary vasodilation (with dipyridamole) and an increase in myocardial oxygen consumption (with dobutamine).
Methods. One hundred fifty patients (mean ±SD age 51 ± 11 years) referred for stress echocardiography were initially studied by dipyridamole-dobutamine echocardiography. The test was stopped during the dipyridamole step in 95 patients for achievement of a predetermined end point (obvious dyssynergy induced by lower or higher dipyridamole dose), and dipyridamoledobutamine tests were performed in 55 patients (negative dipyridamole echocardiographic test). In the same 150 patients the dobutamine echocardiographic test (up to 40 μg/kg body weight per min) was performed on a separate day.
Results. Significant coronary artery disease (>50% diameter stenosis of at least one major coronary vessel by quantitative coronary arteriography) was present in 131 patients (one vessel in 115; two vessels in 10, three vessels in 6), with normal coronary arteriography in 19. The feasibility of the dipyridamoledobutamine test was 96%. Self-limiting side effects occurred in 5% of patients. The peak rate-pressure product was lowest during the dipyridamole test (132 ± 30) and was comparable during the dobutamine (186 ± 59) and dipyridamole-dobutamine tests (179 ± 45, p = NS vs. dobutamine; p < 0.01 vs. dipyridamole). Sensitivity was 71% for dipyridamole, 75% for dobutamine and 92% for dipyridamole-dobutamine echocardiography (dipyridamole vs. dipyridamole-dobutamine, p < 0.01; dobutamine vs. dipyridamole-dobutamine, p < 0.01; dipyridamole vs. dobutamine, p = NS), whereas specificity was 89% for dipyridamole, 79% for dobutamine and 89% for dipyridamole-dobutamine echocardiography (p = NS for all).
Conclusions. Routine dobutamine addition to dipyridamole stress testing is clinically useful and well tolerated. It expands the spectrum of the disease detectable by pharmacologic stress echocardiography and allows documentation of milder forms of coronary artery disease that can be missed by conventional dipyridamole or dobutamine stress echocardiography.
INTRODUCTION. Recurrent coarctation is a complication which is seen at a
consistent rate following repair for coarctation of the aorta in young
infants. OBJECTIVE. This retrospective analysis was ...carried out to compare
the results between resection with end-to-end anastomosis (ETE), and
resection with extended end-to-end anastomosis (E-ETE), in this age group
during late follow-up period. The role of ductus arteriosus is not clearly
defined and the second objective of this study was to analyze intimal
thickening in aortic coarctation. MATERIAL AND METHODS. From 1999 to 2003, 45
patients less than 3 months of age un?derwent repair of aortic coarctation.
Mean age was 24 days (2-89 days), average weight was 3.5?0.6 kg (2.4-5.2 kg).
The method of repair was ETE in 14 (31.1%) patients, E-ETE in 29 (64.4%)
patients and other techniques were applied in 2 cases. Demographic,
morphometric, clinical and operative variables were analyzed for correlation
with recurrent arch obstruction. In order to characterize the components of
intimal thickening in coarctation, narrowed segments of aorta resected from
16 neonates during surgery were examined immunocytochemically and by electron
microscopy. For light microscopy, the specimens were dehydrated in graded
ethanol (70-100%), cleared in xylol and embedded in paraffin.
Immunocytochemical staining was performed in 5 ?m sections from
formaldehyde-fixed paraffin-embedded blocks, using a labeled
streptavidin-biotin method with an LSkit (Dako). RESULTS. Early mortality
was 6.7% (CI 95%, 2.9%-10.4%). All early deaths (3 patients) occurred in
infants with associated ventricular septal defects (p<0.05). The mean
follow-up for all patients was 30?21 months (range 1.5-63 months). During
mean follow-up of 2 months, recurrent arch obstruction was diagnosed in 9
patients (21.4%). Two patients with associated complex heart defects died
before reintervention, one had mild gradient on catheterization (20 mm Hg)
and one is waiting for catheterization. Five patients were reoperated and the
mean time to reintervention was 4 months (range 2.6-6 months). Kaplan-Meier
freedom from recoarctation was 78.1?6.4% at 5 years in the whole group.
Freedom from recoarctation was 60.6?15.4% at 25 months in ETE group and
86.2?6.4% at 60 months in E-ETE group (p=0.062). Factors associated with
recoarctation, obtained by univariable Cox regression, included abnormal
right subclavian artery (p=0.003), hypoplastic proximal transverse aortic
arch (Z?-2, p=0.025) and weight at op?eration ?3 kg (p=0.02). Abnormal origin
of the right subclavian artery was the only independent predictor of
recoarctation obtained by multivariable Cox regression analysis. DISCUSSION.
All examined specimens had intimal thickening of the posterior aortic wall,
with accumulation of smooth muscle cells (SMC) with ? smooth muscle actin
(?-SMA) and vimentin-immunoreactivity (but not desmin and MHC) and also
expressed PCNA and S-100. In the inner media of the anteromedial wall of the
aorta, all specimens had large number of SMC expressing desmin and MHC. SMC
in the inner media exhibit contractile phenotype and their origin could be
ductal. CONCLUSION. Both procedures are effective for coarctation repair in
young infants. Risk of recoarctation is a function of the complex anatomy of
the arch, while residual ductal tissue may play a significant role.
nema
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