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Inhaled β2 adrenergic receptor (β2-AR) agonists are the mainstay of asthma therapy. The β2-AR protein is encoded by the ADRB2 gene and variants within this gene can have significant consequences for modulating the response to asthma therapy. This cross-sectional study performed at the University Children’s Hospital in Belgrade, included 54 children with asthma. The subjects were genotyped for ADRB2 +46A>G (Arg16Gly, rs1042713) and +79C>G (Gln27Glu, rs 1042714) polymorphisms and the association with asthma severity and response to inhaled salbutamol was examined. In Serbian asthmatic children, allele +46A was detected with a frequency of 41.7% and allele +79G was detected with a frequency of 23.1%. Allele +46G was found to be associated with a better response to inhaled salbutamol (p G may be a determinant of asthma severity and response to salbutamol in children with asthma. We did not find any association of +79C>G polymorphisms with the asthma severity and bronchodilator response to inhaled salbutamol. The results of this study can be potentially useful for personalization of asthma treatment.

Transforming growth factor beta 1 (TGFB1) is a multifunctional cytokine with a key role in asthma airway inflammation and remodeling. Since elevated levels of this cytokine in airways might be associated with response to asthma therapy, the aim of this study was to investigate whether the presence of the polymorphism C-509T in the promoter of the TGFB1 gene is associated with response to montelukast. A group of 102 asthmatic patients was genotyped for the presence of the C-509T polymorphism by DNA sequencing and subjected to induced sputum sampling. Cells from sputum samples and BEAS 2B cells were treated with montelukast and endogenous TGFB1 expression was measured by quantitative real-time polymerase chain reaction. The promoter activity was analyzed by luciferase assays in BEAS 2B cells transfected with constructs carrying variants -509C and -509T of the TGFB1 gene promoter. After treatment with montelukast, the decrease in TGFB1 gene expression was greater for the -509TT genotype (58.9%) than for the -509CC and -509CT genotypes (49.6% and 31.8%, respectively) ( P  = 0.071). In BEAS 2B cells, expression of endogenous TGFB1 was reduced by about 27% after montelukast treatment, while luciferase activity of both promoter variants was increased after montelukast treatment (-509C allele: 48.3%, P  = 0.060; and -509T allele: 100.5%, P  = 0.062). A more intensive response was registered in the promoter containing the -509T allele, which had 135% higher activity than the -509C variant ( P  = 0.035). This study showed that the presence of the -509T allele in the TGFB1 promoter might modulate effects of montelukast on TGFB1 gene expression, but future studies are necessary, taking into consideration other genetic and nongenetic factors. It is of potential importance for clinical management of asthma to clarify the influence of the C-509T polymorphism on the response to treatment with montelukast.

Background: The aim of this study was to investigate polymorphisms in the promoter region of the neutrophil elastase (ELANE) gene as potential modulators of the therapeutic response in children with idiopathic bronchiectasis., Methods: The study included 48 children between 5 and 17 years old who were diagnosed with idiopathic bronchiectasis based on high-resolution computed tomography of the thorax. In all patients therapy included administration of antibiotics, anti-inflammatory drugs, expectorants, and postural drainage. Response to therapy was evaluated by the change in FeNO levels before and after administration of therapy. The ELANE promoter region polymorphisms were analyzed by PCR-direct DNA sequencing., Results: According to the predicted activity of ELANE genotypes, subjects were divided into two groups: low/intermediate activity (n = 18) and high activity (n = 30). Subjects in the group with high-activity genotype had higher initial FeNO levels and this difference was statistically significant (t = 2.906; p = 0.006). The difference between FeNO levels before and after therapy was also statistically significantly higher in children with high-activity genotype (t = 3.329; p = 0.002). Statistically significant correlation was observed between the change in FeNO levels and ELANE genotypes (r = 0.350; p = 0.015)., Conclusion: Children with high-activity genotype had higher initial FeNO levels and showed better response to therapy than children with low/intermediate-activity genotypes.

Background: Mechanical ventilation is a frequently applied therapy in critically ill children and can be lifesaving in many cases. Clinical use of this technique has well documented benefits, but can be associated with different complications and adverse physiologic effects., Objectives: The aim of this study was to investigate the complications and clinical outcome of mechanical ventilation in Serbian pediatric patients., Material and Methods: The study encompassed 42 children with respiratory insufficiency that underwent mechanical ventilation during hospitalization over a period of 12 consecutive months. The influence of clinical and mechanical parameters on the occurrence of complications and clinical outcome were analyzed., Results: The patients were ventilated for a total of 432 days and a total of 61 complications were observed in 42 patients (97 complications per 1000 ventilation days). The most common complications associated with mechanical ventilation in Serbian pediatric patients with respiratory insufficiency were cardiovascular insufficiency (52.4%) and multiple organ failure (35.7%). High values of applied PIP (> 26 cm H 2 O), PEEP (> 6 cm H 2 O) and Tv (> 6 mL/kg) were associated with the occurrence of complications and negative clinical outcome., Conclusions: Complications of mechanical ventilation in the pediatric population occur frequently, but lower volumes/pressures of ventilation contribute to a decrease in incidence. Further studies are needed to examine associated risk factors and strategies to reduce the occurrence of complications and improve clinical outcome.

A 36-year-old woman was stung in the right wrist by a bee, suffered typical anaphylaxis, and was transferred to a local hospital. After a few hours, which corresponded to late-onset reaction, she developed shortness of breath and weakness and was transferred to the emergency department, where the diagnosis of anaphylaxis was confirmed. Serum complement levels, components C3 and C4, were undetectable. Flexible bronchoscopy excluded lung hemorrhage. She was on the ventilator for 4 days and was fully awake during that time. After the treatment, her improvement was rapid, and she fully recovered. Three weeks after she had been stung by a bee, skin prick tests to bee, wasp, and yellow jacket venom were done, and all tests came back negative as well as IgE and IgG4 antibodies to the same venoms. Coagulation factors and the complement, including C1q inhibitor, were normal. Occurrence of complement activation and consumption could point to the immune complexes as basis of pathophysiological mechanism. It remains unclear why such a reaction would involve only the right lung and why no detectable immune complexes were discovered. The clinical picture in the presented case resembled acute respiratory distress syndrome, but the exact nature of lung consolidation remains puzzling. The most likely explanation is a very rare case of airway obstruction. To our knowledge, this is the only reported case of anaphylaxis associated with undetectable serum complement levels. The potential role and diagnostic significance of hypocomplementemia in cases of anaphylaxis should be further investigated.

This study has investigated a potential role of common Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene variants in the etiology of noncystic fibrosis bronchiectasis in Serbian children. The study has encompassed 48 patients (19 male and 29 female, aged between 5 and 18 years, median age 10.6±3.3), diagnosed with idiopathic bronchiectasis based on high-resolution computed tomography of thorax and pathologic examination of lobectomy materials. The CFTR gene analysis was performed on genomic DNA extracted from peripheral blood samples of patients by polymerase chain reaction (PCR)-Mediated Site-Directed Mutagenesis method, Denaturing Gradient Gel Electrophoresis method, and DNA sequencing. Mutation c.1521_1523delCTT (F508del) was detected with an allelic frequency of 1.0%, and c.224G>A (R75Q) variant. Carriers of c.1210-12T[5] (IVS8-5T) allele were significantly more common than in the general population (10.4% vs. 5.0%, P =0.0302). The frequency of homozygotes for Met 470 allele was higher in patients than in the general population (33% vs. 20%), while heterozygotes for p.Met470Val were less frequent (31% vs. 50%), and this difference was statistically significant ( P =0.0222). The results obtained in this study indicate involvement of 2 common CFTR variants, c.1210-12T[5] and c.1408A, in idiopathic bronchiectasis in children, but this observation should be further confirmed by more extensive analysis of the CFTR gene in a larger group of patients.

Aim: The aim of this study was to identify the most appropriate method of surgical treatment of hydrocephalus in preterm infants that is caused by spontaneous intraventricular hemorrhage (IVH) and to identify predictive factors of poor perioperative outcomes., Material and Methods: We present a series of 60 patients with IVH and hydrocephalus, to whom a VP shunt or subcutaneous (Omaya) reservoir was placed, during the period from March 2006 to March 2011., Results: Predictors of poor outcome with VP shunt placement were: gestational age (t=2.323, p=0.024), head circumference at birth (t=2.072, p=0.043), birth weight (t=2.832, p=0.006), Apgar score at birth (t=5.026, p < 0.01), number of days on assisted ventilation (Z=6.203, p < 0.001), peripartal asphyxia (χ < sup > 2 < /sup > =17.376, p < 0.01), respiratory distress (χ < sup > 2 < /sup > =9.176 p=0.002). Predictors of poor outcome in getting Omaya reservoir are: low birth weight (t=2.560, p=0.016), low Apgar scores (t=3.059, p=0.005), an extended number of days on assisted ventilation (Z=4.404, p < 0.001), presence of peripartal asphyxia (χ2=9.977, p=0.002) and cardio-respiratory arrest (χ2=12.804, p < 0.001)., Conclusion: The outcome of hydrocephalus caused by IVH in premature born children is the worst in perinatology. Our results suggest that the main predictive factor is preoperative condition of the child and that the VP shunt and Omaya reservoir are complementary methods of surgical treatment.

Aim: Intracranial aneurysm rupture is followed by high mortality and morbidity. In order to understand the aneurysm's natural course, it is necessary to recognize the predisposing factors for the rupture., Material and Methods: Analysis included 142 operated aneurysms (94 hemorrhaging and 48 unruptured) in the period from 2008 to 2010., Results: The ratio between the width of the aneurysm neck and diameter of the carrying blood vessel - artery in ruptured aneurysms (OR) was 1.58 ± 0.61, and in unruptured aneurysms 1.14 ± 0.52 (p < 0.01). Aspect ratio of ruptured aneurysm was 1.89 ± 0.59, and in unruptured 1:33 ± 0.17. The angle of inclination of ruptured aneurysms was 139.22 ± 21.53, while in unruptured aneurysms it was 101.73 ± 21.26., Conclusion: Based on the results of our research, a predictive model of morphometric characteristics of the vessel bearing the aneurysm to rupture can be identified: an irregular shape of the aneurysm, AR > 1.6, OR > 1.5 and inclination angle > 135 deg.

Aim: Glioblastoma multiforme in the motor area is the surgical challenge because of the need for more radical resection in order to extend the life of the patient, and the risk that radicalism could lead to additional neurological deficit., Material and Methods: We present series of 26 patients with glioblastoma multiforme localized in and around the motor area, who were hospitalized from October 2004 to February 2009. During all operations, we conducted electrostimulation display area of the brain, to the anatomical location of M1 segment of the motor cortex., Results: Distance of the central sulcus in relation to the coronary suture, measured by magnetic resonance imaging (MRI) was 18.38 mm ± 9.564 mm. The volume of electricity required for a motor response was mean 8.79 ± 1.484 mA, with increasing distance from the coronary suture the amperage required to explicit motor responses decreased. The difference (mm) between the distance from the coronary suture measured using MRI and distances measured electrostimulation smaller and power consumption was less (F = 13.285, p < 0.01)., Conclusion: The method of cortical cerebral cortex electrostimulation is simple and safe method and a binding protocol to the patient safe operation glioblastoma multiforme localized in the motor area of the brain.

This paper reports a novel Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene variant, 1811+1G-->T, detected in a 5-year-old girl diagnosed with idiopathic disseminated bronchiectasis and negative sweat chloride test (17 mmol/L). The performed CFTR gene mutation analysis included detection of the F508del mutation, analysis of Tn polymorphism and screening of CFTR exons 3, 10 and 11. The CFTR gene screening has shown the altered band pattern in exon 11. The DNA sequencing of CFTR exon 11 revealed the presence of the novel sequence variation 1811+1G-->T in heterozygous state. This sequence variation was not found in any of 100 control alleles, analyzed by polymerase chain reaction - restriction fragment length polymorphism method. The novel sequence variation 1811+1G-->T is located at the splicing site at the boundary of exon 11 and intron 11 and might be either a sequence variation or a splicing site defect.

Congenital myopathy with uniform type 1 fibers is a rare form of nonprogressive congenital neuromuscular disease. We report a 40 year old woman with proximal muscle weakness, waddling gait and decreased deep tendon reflexes. The serum creatine kinase level was decreased. Peripheral nerve conduction velocity as well as electrocardiogram and echocardiogram were normal. The electromyogram showed myopathic changes. A biopsy specimen from the left deltoid muscle revealed a uniformity of type 1 fibers. This is the first case of congenital myopathy with uniform type 1 fibers reported in Serbia.