Effects of Obesity on Airway and Systemic Inflammation in Asthmatic Children.

BACKGROUND: Obese asthma is a complex syndrome with certain phenotypes that differ in children and adults. There is no clear evidence regarding the presence of additive or synergistic pathological interaction between obesity and asthma in children. OBJECTIVES: Our aim was to demonstrate the interaction of obesity and asthma in children in terms of airway and systemic inflammation by a controlled observational study. METHODS: Four groups were formed: asthma obese (AO), asthma nonobese (ANO), non-AO (NAO), nonasthma nonobese (NANO). Spirometry test, fractional exhaled nitric oxide (FeNO) test, skin prick test, serum inflammatory biomarkers (C-reactive protein, C3, C4, adiponectin, leptin, resistin, periostin, YKL-40, Type 1, and Type 2 cytokines) were conducted and evaluated in all participants. Sputum inflammatory cells (sputum eosinophils and neutrophils) were evaluated in patients who could produce induced sputum and obesity-asthma interactions were determined. RESULTS: A total of 153 participants aged 6-18 years were included in the study, including the AO group (n = 46), the ANO group (n = 45), the NAO group (n = 30), and the NANO group (n = 32). IL-4 (p < 0.001), IL-5 (p < 0.001), IL-13 (p < 0.001), resistin (p < 0.001), and YKL-40 (p < 0.001) levels were higher in patients with asthma independent of obesity. The lowest adiponectin level was found in the AO group and obesity-asthma interaction was detected (p < 0.001). Sputum eosinophilia (p < 0.01), sputum neutrophilia (p < 0.01), and FeNO levels (p = 0.07) were higher in asthmatic patients independent of obesity. In the group with paucigranulocytic inflammation, resistin and YKL-40 levels were significantly lower than in the group without paucigranulocytic inflammation (p < 0.01). CONCLUSION: No interaction was found between obesity and asthma in terms of airway inflammation. Interaction between obesity and asthma was shown in terms of adiponectin level and resistin/adiponectin and leptin/adiponectin ratios. It was found that serum YKL-40 and resistin levels could be associated with airway inflammation.

Sympathetic denervation in patients with ischemic cardiomyopathy and risk on ventricular tachy-arrhythmias. A pilot study.

BACKGROUND: Patients with ischemic cardiomyopathy (ICM) are at risk for ventricular arrhythmias and are protected by an implantable cardioverter defibrillator (ICD). Visualization of cardiac sympathetic innervation may play an additional role to left ventricular ejection fraction (LVEF) in identifying those patients who will benefit from ICD therapy. The purpose of this study was to detect the role of sympathetic denervation in the genesis of ventricular arrhythmias in ICM patients. METHODS: Twenty patients with ICM and LVEF <30% were included in this pilot study. Included patients were equally stratified into two groups: no history of arrhythmias (group A) and recurrent arrhythmias (group B). All patients underwent cardiac sympathetic denervation (using carbon-11 labelled meta-hydroxy-ephedrine ([11C]-mHED)), myocardial ischemia and viability detection. Patients were followed up to one year after the imaging studies. RESULTS: Mean age was 63±7.5 years. Mean global retention of [11C]-mHED was 0.055±0,012 min-1, and was not different between the two patient groups: 0.056±0.011 min-1 vs. 0.054±0.013 min-1 for group A vs. group B, respectively. During follow-up, seven patients developed ventricular arrhythmias, and four patients died. No difference in [11C]-mHED retention was found between patients with and without ventricular arrhythmia during follow-up. However, size of denervated area was larger in patients who died during follow-up: 10±1 segments vs. 6±2 segments, P=0.002. CONCLUSIONS: Cardiac sympathetic innervation is impaired in patients with ischemic cardiomyopathy. All-cause mortality occurred in those patients with large areas of [11C]-mHED defect.

Mutations in FEZF1 cause Kallmann syndrome.

Gonadotropin-releasing hormone (GnRH) neurons originate outside the CNS in the olfactory placode and migrate into the CNS, where they become integral components of the hypothalamic-pituitary-gonadal (HPG) axis. Disruption of this migration results in Kallmann syndrome (KS), which is characterized by anosmia and pubertal failure due to hypogonadotropic hypogonadism. Using candidate-gene screening, autozygosity mapping, and whole-exome sequencing in a cohort of 30 individuals with KS, we searched for genes newly associated with KS. We identified homozygous loss-of-function mutations in FEZF1 in two independent consanguineous families each with two affected siblings. The FEZF1 product is known to enable axons of olfactory receptor neurons (ORNs) to penetrate the CNS basal lamina in mice. Because a subset of axons in these tracks is the migratory pathway for GnRH neurons, in FEZF1 deficiency, GnRH neurons also fail to enter the brain. These results indicate that FEZF1 is required for establishment of the central component of the HPG axis in humans.

Effects of stem cell transplantation on bone mineral density and vitamin D status in children with thalassemia major.

HSCT is a curative treatment in TM, but conditioning and immunosuppressive treatment may affect bone metabolism. In this retrospective study, we aimed to compare BMD, vitamin D status, and growth in children with TM who underwent HSCT to those in children with TD TM. Twenty-three children with TM who underwent HSCT (mean age 7.1 years [1.03-14.7]) and 24 children with TD thalassemia (mean age 9.8 years [1.6-14]) were recruited. Lumbar spine BMD of TD thalassemia patients was higher than those in patients who had HSCT at both baseline and second-year assessments (P=.009, P<.001, respectively). However, BMD Z scores or serum 25-OH vitamin D levels were not different in two groups. Being >10 years of age was a significant risk factor for low BMD, height, and weight Z score for both groups. Patients who underwent HSCT with Pesaro risk class II or III had higher risk for low BMD compared to those risk class I patients (P=.044). In conclusion, children with TM who were >10 years at HSCT are at risk for low BMD and growth retardation. HSCT had no effect on BMD deficit in children with TM.

Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome.

To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups.

Mechanical and electrical dysfunction of Riata implantable cardioverter-defibrillator leads.

AIM: Riata implantable cardioverter-defibrillator leads are prone to failure by conductor externalization and/or electrical dysfunction. The objectives of this study were to determine the predictors of the Riata lead failure, to assess the association of conductor externalization and electrical lead failure, and to analyse the rates of lead failure over time. METHODS AND RESULTS: Of 273 implanted Riata leads in our centre, 197 were investigated according to the Riata recall protocol, including electrical measurements by device interrogation and annually fluoroscopy. During a mean follow-up period of 5.6 ± 1.4 years, Riata lead failure was 18.8% (37 of 197) for externalization and 17.3% (34 of 197) for electrical lead failure. Electrical lead failure was correlated with time after implant. Externalization and electrical dysfunction co-existed in only 6 of 197 (3%) patients and were not related (Phi's coefficient -0.013, P = 0.85). During the second annual screening, 145 (73.6%) patients underwent fluoroscopy and 9 patients had novel externalizations resulting in an incidence of 6.72%/patient/year which was higher than expected based on cross-sectional analysis. Besides, there was a significant increase in the extent of externalization (17.65 ± 11.14 mm vs. 21.77 ± 11.95 mm, P = 0.001). In multivariate Cox regression analysis, non-ischaemic cardiomyopathy and impaired LVEF were independent predictors of externalization, and 7 Fr lead was a predictor of electrical lead failure. CONCLUSION: Riata leads show progressive and high externalization rates without correlation between externalization and electrical lead failure. Non-ischaemic cardiomyopathy and impaired LVEF are independent predictors of structural lead failure in cross-sectional analysis, whereas 7 Fr lead is a predictor of electrical lead failure.

Endocrinopathies in Turkish children with Beta thalassemia major: results from a single center study.

The endocrinological complications in ß-thalassemia major patients do affect the life quality to a large extend. In this study, the endocrinological complications of 47 ß-thalassemia patients, who have been followed-up at our hospital's pediatric hematology department, were evaluated. Out of ß-thalassemia major cases included to this study, the 55.3% was male and 44.7% was female. The patients' mean levels of ferritin, whose mean age was 10.0 ± 4.5 years (2-20 years), were 2497 ± 1469 ng/mL (472-8558 ng/mL). At least one endocrinological pathology in 27 out of 47 (57.4%) and more than one endocrinological pathology in 14 out of 47 (29.7%) thalassemia patients were observed. The most frequently observed complication in followed-up cases was vitamin D insufficiency and deficiency (78.2%). The other complications in decreasing order were pubertal failure (41.6%), growth retardation (25.5%), decreased bone-mineral density (22.2%), secondary hyperparathyroidism (11.5%), overt hypothyroidism (4.25%), subclinical hypothyroidism (2.12%), and impaired glucose tolerance (2.12%). There was no statistically significant difference between serum mean ferritin level and endocrin complications (P > .05). Four patients (8.5%) had decreased signal intensity in pituitary magnetic resonance imaging (MRI) but this finding was not associated with ferritin levels (P = .87). MRI parameters were similar between patients with and without gonadal dysfunction. Mean height of the pituitary gland was 4.98 ± 1.1 mm (3-9 mm) and this was similar to those normal values in the literature. Ferritin levels were not correlated with pituitary height (P > .05). Beta thalassemia major, having the potential of leading to multisystemic complications, is a chronic disease that should be treated and followed-up by a multidisciplinary approach. Due to frequently encountered endocrinological complications, beta thalassemic patients should be followed-up regularly by hematology and endocrinology departments in coordination.

The effect of obesity on the level of fractional exhaled nitric oxide in children with asthma.

BACKGROUND: Several studies have demonstrated a relationship between asthma and obesity. However, the results have been conflicting with regard to the relationship between fractional exhaled nitric oxide (FeNO), used as a marker of airway inflammation in asthmatic patients, and obesity. We aimed to evaluate the association of FeNO with obesity and obesity-related metabolic complications in asthmatic and nonasthmatic children. METHODS: The study population included children aged between 6 and 17 years and consisted of 4 groups: obese asthmatics (n = 52), normal-weight asthmatics (n = 49), obese nonasthmatics (n = 51) and normal-weight nonasthmatics (n = 42). FeNO measurement and spirometry were performed for all patients. To evaluate the metabolic complications, serum lipids, glucose and insulin levels were measured. Insulin resistance (IR) was estimated by the homeostasis model assessment, HOMA-IR. All participants were evaluated for the presence of metabolic syndrome (MS). RESULTS: The mean age for the 194 subjects participating in the study was 11.6 ± 2.5 years. The FeNO level of asthma patients with MS was not different from those without MS (14.5 ± 8.0 and 16.7 ± 8.7, respectively, p = 0.449). In the nonasthmatic group, subjects with MS had a higher FeNO level than subjects without MS (12.5 ± 5.1 and 17.3 ± 8.3, respectively, p = 0.014). Spearman's rank correlation coefficients revealed a positive correlation between FeNO and body mass index (BMI; p = 0.049, r(2): 0.204) in the nonasthmatic group and after multivariate regression analysis, BMI still persisted as an independent risk factor for FeNO. CONCLUSION: We found a positive correlation between BMI and FeNO level which suggests a link between obesity and increased airway inflammation in nonasthmatic children.

Individual and familial factors associated with metabolic control in children with type 1 diabetes.

BACKGROUND: The aim of this study was to determine the individual and familial factors associated with metabolic control in children with type 1 diabetes (T1DM). METHODS: The study was performed in 93 children with T1DM between the ages of 3 and 19 years. Children and their families completed questionnaires on sociodemographics and data associated with diabetes. Medical information from the charts was also recorded. RESULTS: Older age, longer diabetes duration and higher hospitalization rate for acute complications were positively associated with poor metabolic control. Good school performance, regular hospital visits, young maternal age, high paternal education level and fewer numbers of siblings were found to be negatively associated with poor metabolic control. CONCLUSIONS: Multiple individual and family-level factors are associated with metabolic control. These data may aid in identification of diabetic children and adolescents who have a higher risk of poor metabolic control.

The effect of recombinant human growth hormone therapy on left-ventricular chamber size and function in children with growth hormone deficiency.

This study was designed to assess the effect of recombinant human growth hormone (rhGH) therapy on left-ventricular (LV) chamber size and function in children with idiopathic isolated growth hormone deficiency (GHD) using conventional echocardiography and tissue Doppler imaging (TDI). Thirty patients (19 boys and 11 girls) with idiopathic isolated GHD were followed-up for 12 months. Mean age of patients was 11.0 ± 2.6 years (range 6.3-15.5). At baseline and at 3, 6, and 12 months of treatment, the structure of the left ventricle was assessed by conventional echocardiography and myocardial rates and time intervals by TDI. There was a significant increase in LV mass (LVM) compared with pretreatment values. Like LVM, relative wall thickness (RWT) was also increased significantly. The significant increase in LVM indexed to body surface area and RWT became apparent at month 3 of treatment with a significant increase in LVM indexed to height(2.7) at treatment month 6. Normalized LVM increased as early month 3 of treatment, and a steady increase was observed until month 12. However, no patient had LVM > +2 standard deviation scores at month 12 of treatment. No significant differences were observed in functional parameters of the left ventricle and the interventricular septum. The results of this study showed that rhGH therapy causes an increase in myocardial mass without changing the geometry or function of the myocardium. Therefore, the increase in myocardial mass appears to be concentric, thus causing remodeling instead of hypertrophy.

Inguinal ovary as a rare diagnostic sign of Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare syndrome characterized by complete or partial agenesis of the uterus and vagina, due to a congenital defect of the Mullerian duct. Affected individuals have a 46,XX karyotype and a normal female phenotype. MRKH syndrome may be isolated (type I MRKH syndrome) or associated with renal, cardiac, and skeletal anomalies, short stature, and auditory defects. The latter is defined as type II MRKH syndrome or the Müllerian duct aplasia/hypoplasia, renal agenesis/ectopy, and cervicothoracic somite dysplasia (MURCS) association. The majority of patients with MRKH syndrome present with primary amenorrhea. We report a case of type II MRKH syndrome who has been referred by a pediatric surgeon for detection of gonadal function. During an inguinal hernia operation, the left ovary had been observed in the hernia sac. Clinical and radiological evaluation of the patient showed an absence of the uterus and left kidney, and cervical hemi vertebra. Based on these findings, the patient was diagnosed as having type II MRKH syndrome.

Leptin receptor gene Gln223Arg polymorphism is not associated with obesity and metabolic syndrome in Turkish children.

The aim of the study was to investigate the relationship between leptin receptor gene (LEPR) Gln223Arg polymorphism and obesity in Turkish children. Ninety-two obese and 99 lean children (between 5-15 years) were included in the study. Twenty-three of the obese children were diagnosed with metabolic syndrome. Blood samples were collected for morning fasting blood glucose, insulin, leptin, and lipid level measurements. LEPR Gln223Arg polymorphism was analyzed by restriction fragment length polymorphism. Significant differences were observed in anthropometric measurements, fasting blood glucose, insulin, leptin, and lipid levels between obese and lean children. Serum leptin levels were markedly higher in obese children. No significant association was noted between Gln223Arg polymorphism and serum leptin, insulin and lipid levels. There were no differences in the genotype frequencies or allele distribution for Gln223Arg polymorphism among obese, obese with metabolic syndrome and lean children. Our findings suggest that there is no association between Gln223Arg polymorphism and obesity in Turkish children.

Pulmonary hypertension and reopening of the ductus arteriosus in an infant treated with diazoxide.

Diazoxide is the main therapeutic agent for persistent hyperinsulinemic hypoglycemia. Generally, it is tolerated well, but rarely it can cause severe life-threatening complications. We report a neonate who was treated with diazoxide for hyperinsulinemic hypoglycemia. On the 6th day of the treatment we observed sepsis-mimicking symptoms, mild pulmonary hypertension, and re-opening of the ductus arteriosus. All these findings resolved dramatically shortly after discontinuation of treatment. To our knowledge, this is the first reported case of re-opening of the ductus arteriosus due to diazoxide toxicity.

Early cardiac abnormalities and serum N-terminal pro B-type natriuretic peptide levels in obese children.

OBJECTIVE: The aim of this study was to evaluate early cardiac abnormalities in obese children by the conventional echocardiography and to verify whether N-terminal pro B-type natriuretic peptide (NT-proBNP) differ between obese and healthy children. METHODS: We started this study with 68 obese children and 35 healthy controls matched for age and sex. Body mass index (BMI) was calculated. Children with a BMI > or = 95th percentile were considered obese. Thirty children in the obese group were also diagnosed with metabolic syndrome, according to the International Diabetes Federation criteria. Standard echocardiographic study was performed on each patient and control subject. Diastolic filling parameters were evaluated using pulsed-wave tissue Doppler method. Blood samples were taken at 8 a.m. to study blood biochemistry tests, including insulin, lipids, glucose, and NT-proBNP. Serum NT-proBNP levels were measured by a solid-phase, enzyme-labeled chemiluminescent immunometric assay. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Children with HOMA-IR > 3.16 were considered insulin-resistant. RESULTS: There were diastolic filling abnormalities in obese children, as shown by a decreased mitral valve early filling (E) wave/late filling (A) ratio and a prolongation in E-wave deceleration time. The levels of NT-proBNP were not statistically different among the groups. The levels of NT-proBNP were not different between obese children with and without metabolic syndrome, those with and without hypertension, and those with and without insulin resistance, respectively. CONCLUSION: Although there were diastolic filling abnormalities in obese children, their NT-proBNP levels were not different from healthy controls. It seems that there is no diagnostic value in NT-proBNP levels between obese children and healthy controls.

Hypothyroidism-associated testicular enlargement: is it a form of precocious puberty or not? A case report.

In children with untreated hypothyroidism, the onset of puberty is usually delayed, but gonadotropin-independent precocious puberty may occur in children with severe hypothyroidism of long duration. The association of hypothyroidism, delayed bone age and gonadotropin-independent precocious puberty is defined as Van Wyk Grumbach syndrome (VWGS). VWGS has been described mostly in girls, and only seldom in boys. The manifestation of VWGS in boys is only testicular enlargement without substantial Leydig cell stimulation or testosterone secretion. We report a case of testicular enlargement due to obvious hypothyroidism secondary to autoimmune thyroiditis in a boy who presented with obesity. With this case report, we would like to emphasize that VWGS is not a real gonadotropin- independent precocious puberty in boys as it is in girls. Additionally, we would like to emphasize that delayed bone age is a special discriminating feature for differentiation of VWGS from the other causes of precocious puberty.

Assessment of bone density in children with cerebral palsy by areal bone mineral density measurement.

The aim of this cross-sectional study was to investigate the frequency of decreased areal bone mineral density (aBMD) among patients with cerebral palsy (CP), as estimated by using various aBMD Z-score adjustment methods. In addition, this study examined factors related to decreased aBMD scores. One hundred and two children between the ages of 3.2 and 17.8 years were examined. In patients with severe CP, the incidences of decreased aBMD according to various adjusting methods based on decimal age, bone age, height age, and height-for-age Z-score (HAZ) were 79.5%, 69.5%, 51.9%, and 38.3%, respectively. Abnormal levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone, or anticonvulsant were not predictive for a decreased aBMD. Mean aBMD Z-scores were significantly lower in all aBMD Z-score adjustment methods in patients with severe CP compared to patients with mild-to-moderate CP, except for the adjustment method based on HAZ.

Hypopituitarism masquerading as Prasad's syndrome: a case report.

Prasad's syndrome is characterized by geophagia, growth retardation, hypogonadism, and zinc deficiency. We report a 15-year-old boy whose medical history and clinical and laboratory findings were fully compatible with Prasad's syndrome. In addition to severe growth retardation and pubertal delay, iron deficiency anemia and zinc deficiency were determined. His gliadin and endomysium antibodies were negative. The thyroid hormone levels were in normal range but basal gonadotropins and testosterone levels were low for his age. Detailed endocrinological evaluation revealed growth hormone deficiency and hypogonadotropic hypogonadism. Pituitary gland magnetic resonance imaging revealed pituitary hypoplasia. In our opinion, before the diagnosis of Prasad's syndrome, endocrine evaluation should be done in these patients and hypopituitarism should be ruled out. Hypogonadotropic hypogonadism and growth hormone deficiency may be masked by Prasad's syndrome.

What are the cut-off levels for IL-6 and CRP in neonatal sepsis?

Neonatal sepsis, characterized by systemic signs of infection in the first month of life, remains an important clinical syndrome. Despite advances in neonatology, it has high rates of mortality and morbidity. The combine or alone usage of interleukin-6 (IL-6) and C-reactive protein (CRP) has recently been proven to be useful in the early diagnosis of sepsis in newborns. The study included 282 patients; there were 232 in Group I (170 proven and 62 clinical sepsis) and 50 in Group II (control group). The optimum cut-off value in the diagnosis of neonatal sepsis was found to be 24.65 pg/ml for IL-6 and 4.82 mg/l for CRP. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of this IL-6 cut-off for neonatal sepsis were 72, 84, 95, and 42%, respectively. Sensitivity, specificity, PPV, and NPV of the CRP cut-off for neonatal sepsis were 67, 97, 99, and 39%, respectively. The combination of IL-6 (>24.65 pg/ml) and CRP (>4.82 mg/l) in the diagnosis of neonatal sepsis gave sensitivity, specificity, PPV, and NPV of 53, 100, 100, and 33%, respectively. To our knowledge, this is the largest reported study seeking to determine cut-off levels for IL-6 and CRP in the diagnosis of neonatal sepsis. In conclusion, we think that it is useful to evaluate IL-6 and CRP, in combination, for the early diagnosis of neonatal sepsis.

Scarcity despite wealth: osteopetrorickets.

Infantile malignant osteopetrosis is a rare and genetically autosomal recessive disease characterized by osteoclast malfunction. Decreased osteoclast-mediated bone resorption may be inadequate to maintain a normal serum calcium-phosphorus balance in the extracellular fluid. Consequently, despite markedly positive total body calcium balance, patients with osteopetrosis paradoxically could develop rickets. The concurrence of osteopetrosis and rickets has been termed "osteopetrorickets". We report here a 3-month-old boy who was diagnosed with osteopetrorickets with clinical features. Although osteopetrorickets is defined as a rare paradoxical feature of infantile malignant osteopetrosis in some studies, it seems to be more common than was previously known. Coexistence of rickets and osteopetrosis may have adverse effects on clinical response to stem cell transplantation. Therefore, a diagnosis of rickets must be considered in patients with osteopetrosis and then for better results, prior to the SCT, the rickets should be completely treated.