Yavuz Coşkun

Mediators of inflammation in children with type I diabetes mellitus: cytokines in type I diabetic children

OBJECTIVES Recent evidence favors primary role of cellular autoimmunity and its humoral mediators in pathogenesis and following Type I diabetes mellitus (DM). The present study was carried out to investigate serum concentrations of C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha in children with type I DM. Potential role of lipid metabolism, glycemic control, body mass index (BMI) and disease duration were evaluated. DESIGN AND METHODS Thirty-five children with type I DM and 30 age and gender matched nondiabetic controls were recruited for this study. RESULTS Circulating IL-8 levels were elevated in children with type I DM (12.7 +/- 1.7 pg/mL) compared with nondiabetic controls (5.5 +/- 0.3 pg/mL) and the difference remained significant after adjustment for cofactors and covariates (p: 0.033). Although statistically insignificant serum CRP concentrations were slightly higher in diabetic children (p: 0.075). Serum TNF-alpha and IL-6 levels were comparable in diabetic and nondiabetic groups. However newly diagnosed (<1 yr) cases had higher TNF-alpha and IL-6 levels compared to cases with longer standing DM. In diabetic children BMI was independently associated with an increase in serum IL-8 levels. Serum CRP, lipids, apolipoproteins and glycemic control were not significant predictors of cytokine concentrations in children with type I DM. CONCLUSION Circulating levels of IL-8 were elevated and were correlated with BMI in children with type I DM, hinting perhaps at adipose tissue as a site of production. Elevated systemic IL-6 and TNF-alpha were limited to newly diagnosed cases suggesting activation of the inflammatory immune response system at early stages of the disease.

A prospective study of etiology of childhood acute bacterial meningitis, Turkey.

Vaccines to prevent bacterial meningitis in this region must provide reliable protection against serogroup W-135.

Inappropriate antimicrobial use in Turkish pediatric hospitals: A multicenter point prevalence survey

OBJECTIVES Although well-defined principles of rational antimicrobial use are available, inappropriate prescribing patterns are reported worldwide. Accurate information on the usage of antimicrobials, including factors associated with and influencing their use, is valuable for improving the quality of prescription practices. METHODS In this cross-sectional point prevalence survey, data on patients hospitalized in 12 different childrens hospitals were collected on a single day. Appropriateness of prescription was compared between the types of antimicrobials prescribed, indications, wards, and presence of/consultation with an infectious disease physician (IDP). RESULTS A total 711 of 1302 (54.6%) patients evaluated were receiving one or more antimicrobial drugs. The antimicrobial prescription rate was highest in pediatric intensive care (75.7%) and lowest in the surgery wards (37.0%). Of the 711 patients receiving antimicrobials, 332 patients (46.7%) were found to be receiving at least one inappropriately prescribed drug. Inappropriate use was most frequent in surgery wards (80.2%), while it was less common in oncology wards (31.8%; p<0.001). Respiratory tract infection was the most common indication for antimicrobial use (29.4%). Inappropriate use was more common in deep-seated infections (54.7%) and respiratory infections (56.5%). Fluoroquinolones were used inappropriately more than any other drugs (81.8%, p=0.021). Consultation with an IDP appears to increase appropriate antimicrobial use (p=0.008). CONCLUSIONS Inappropriate antimicrobial use remains a common problem in Turkish pediatric hospitals. Consultation with an IDP and prescribing antimicrobial drugs according to microbiological test results could decrease the inappropriate use of antimicrobials.

Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005–2012 in Turkey: A multicenter prospective surveillance study

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤ 18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.

PREVALENCE AND HEMATOLOGICAL CHARACTERISTICS OF β-THALASSEMIA TRAIT IN GAZIANTEP URBAN AREA, TURKEY

Thalassemia is one of the most common hereditary disorders in the Mediterranean region and studies have shown that the prevalence of β-thalassemia trait is high in the southern part of Turkey. Gaziantep is a city located near this region and, therefore, the authors investigated the prevalence and hematological characteristics of the β-thalassemia traits in primary school students in Gaziantep. Sixty primary schools were selected from a list of all primary schools using a systematic sampling method. Data were collected by a face-to-face questionnaire. Osmotic fragility testing (OFT) using single-tube 0.36% NaCl solution was used for the screening of β-thalassemia. Students who were positive in regard to OFT went through a series of testing, including a complete blood count, serum ferritin levels, serum iron, and hemoglobin electroforesis. Chi-square test was used in statistical analysis. Of the 2439 students enrolled to the study from the selected 60 classrooms, 1353 (55.5%) were male and 1086 (44.5%) were female. The OFT was positive in 115 (4.7%) of the participants. CEA and confirmatory HPLC results of the students who were positive OFT indicated that 70 (60.8%) had normal results, 33(28.7%) showed high HbA2 levels, 7 (6.1%) showed high HbA2 and HbF levels, 5(5.2%) showed high HbA2 and Fe-deficiency anemia, and none showed increased HbF levels. The overall prevalence of β-thalassemia trait was 1.84%. No gender differentials and highest rates among the Kahramanmaras (3.5%) and Sanliurfa (1.7%) born students were the other significant findings of this study. Implementation of a routine carrier-screening program offering genetic counseling, prenatal diagnosis, and selective termination of affected fetuses would be a wise approach to eliminate this disease from the region.

Big Data and Ethics Review for Health Systems Research in LMICs: Understanding Risk, Uncertainty and Ignorance—And Catching the Black Swans?

Health systems research (HSR) is an indispensable compass to steer development policy and diplomacy in 21st century knowledge societies (Kickbusch and Kökény 2013; Özdemir 2013; Özdemir et al. 2013). The World Health Organization (WHO) defines HSR as “the purposeful generation of knowledge that enables societies to organize themselves to improve health outcomes and health services” (World Health Organization 2009). Traditional clinical trials and academic research are situated proximal on the “lab to society” translation continuum, for example, for discovery of new therapeutics. In contrast, HSR engages with the knowledge trajectory in its distal end, by examining and organizing health services and public health infrastructures. HSR data can also help select rational targets for investments in health attuned to community values in lowand middleincome countries (LMICs); these investments have reached nearly

Trends in the Frequency of HLA DR-DQ Haplotypes Among Children and Adolescents with Type 1 Diabetes Mellitus in the Southeast Region of Turkey

28 billion in global health by 2011 (Leach-Kemon et al. 2012). Today HSR is a real-world and systems-oriented large-scale activity with cross-cutting social, economic, and

The efficacy of single-high dose inhaled corticosteroid versus oral prednisone treatment on exhaled leukotriene and 8-isoprostane levels in mild to moderate asthmatic children with asthma exacerbation

Objective: The aim of this study was to determine the frequency of HLA DR-DQ haplotypes in children with type 1 diabetes mellitus (T1DM) in the Southeast Region of Turkey. Methods: Eighty children and adolescents with T1DM and eighty control subjects participated in the study. HLA-DR, DQ was typed using polymerase chain reaction and sequence-specific priming technique. Results: HLA DRB1*03 allele was significantly more common in patients than in control subjects. HLA DRB1*11, HLA DRB1*13 and HLA DRB1*14 allele frequencies were significantly lower in patients than in controls. DQB1*02 allele was more common in patients, whereas DQB1*03 allele was more frequent in control subjects. HLA DRB1*03-DQB1*02 haplotype was more frequently observed among patients. Conclusion: These results confirm the similar potential trends in the frequency distribution of HLA susceptibility genes with T1DM previously observed in Turkey and in other Caucasian populations. Conflict of interest:None declared.

Relationship between exhaled leukotriene and 8-isoprostane levels and asthma severity, asthma control level, and asthma control test score.

BACKGROUND The anti-inflammatory effect of high-dose inhaled corticosteroids (ICS) in children with asthma exacerbation is unknown. We aimed to investigate the efficacy of single-high dose ICS versus oral prednisone treatment followed by a course of six day high-dose ICS or oral prednisone (P) treatment on the concentrations of Cys-LTs and 8-isoprostane levels in the exhaled breath condensate (EBC) of children with asthma exacerbation. METHODS Ninety-four children with moderate-severe asthma exacerbation were evaluated with asthma scores, peak expiratory flow rate (PEF), forced expiratory volume in first second (FEV1) and exhaled Cys-LT and 8-isoprostane levels before and after treatment. EBC was collected from 52 patients before and four hours after treatment with inhaled fluticasone propionate (FP) (4000 μg) or P and after six days of treatment with FP-1000 μg/day or P. Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit. RESULTS Both single high-dose FP (n=59) and p (n=35) treatment resulted in a significant improvement in asthma score (p<0.0001), PEF (p<0.0001), and FEV1 (p<0.0001). Cys-LT concentration in the EBC decreased significantly both after the initial treatment (p=0.001), and at the end of the six-day period in the FP group (p<0.0001). 8-Isoprostane concentration was lower only after six days of treatment with FP-1000 μg/day in the FP group (p=0.023). There was a significant decrease in exhaled Cys-LTs after four hours (p=0.012) and six days of P treatment (p=0.018) in children with asthma exacerbation. CONCLUSIONS High-dose ICS treatment may be useful in the treatment of children with asthma exacerbation. The effects start as early as after four hours. The suppression of Cys-LTs production contributes to the early effects. Suppression of both Cys-LTs and oxidants may favourably contribute to the effects observed later.

Exhaled RANTES and interleukin 4 levels after exercise challenge in children with asthma

OBJECTIVE Exhaled breath condensate (EBC) is a completely non-invasive method for the collection of airway secretions to measure intense inflammation in the airways of asthmatics. It has been shown that the childhood asthma control test (c-ACT) is a good tool for use in the evaluation of asthmatics. Whether the c-ACT score and asthma control level correlate with the airway inflammation is not well known. We aimed to evaluate the relationship between exhaled cysteinyl leukotrienes (Cys-LTs) and 8-isoprostane levels and asthma severity, asthma control level and c-ACT score in asthmatic children. METHODS Thirty asthmatic children were evaluated with c-ACT score and pulmonary function tests. Asthma severity and asthma control level were assessed according to GINA. EBC was collected and Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit. RESULTS Exhaled 8-isoprostane level in patients with moderate persistent asthma [114 (55-146)pg/ml] was higher than in the mild persistent group [52 (21-91)pg/ml] (p=0.05, Mann-Whitney U [MWU]). EBC 8-isoprostane in children with 1-4 asthma exacerbations/year [52 (16-80)pg/ml] was significantly lower than in children with >4 asthma exacerbations/year [114 (57-129)pg/ml] (p<0.05, MWU). No significant relation was determined between exhaled 8-isoprostane and Cys-LTs levels and c-ACT score and asthma control level. Exhaled 8-isoprostane correlated negatively with bronchodilator response (p=0.015, r=-0.45). CONCLUSIONS Exhaled 8-isoprostane, as an oxidative stress specifier, was found to be increased in relation with asthma exacerbation frequency and oxidative stress increases with the severity of asthma. In contrast to asthma severity level, c-ACT score and asthma control level may not reflect airway inflammation.