Impact of hypoxia on IGF-I, IGF-II, IGFBP-3, ALS and IGFBP-1 regulation and on IGF1R gene expression in children

Hypoxia is one of many factors involved in the regulation of the IGF system. However, no information is available regarding the regulation of the IGF system by acute hypoxia in humans. Objective: The aim of this study was to evaluate the effect of acute hypoxia on the IGF system of children. Design: Twenty-seven previously health children (14 boys and 13 girls) aged 15 days to 9.5 years were studied in two different situations: during a hypoxemic state (HS) due to acute respiratory distress and after full recovery to a normoxemic state (NS). In these two situations oxygen saturation was assessed with a pulse-oximeter and blood samples were collected for serum IGF-I, IGF-II, IGFBP-1, IGFBP-3, ALS and insulin determination by ELISA; fluoroimmunometric assay determination for GH and also for IGF1R gene expression analysis in peripheral lymphocytes by quantitative real-time PCR. Data were paired and analyzed by the Wilcoxon non-parametric test. Results: Oxygen saturation was significantly lower during HS than in NS (P<0.0001). IGF-I and IGF-II levels were lower during HS than in NS (P<0.0001 and P=0.0004. respectively). IGFBP-3 levels were also lower in HS than in NS (P=0.0002) while ALS and basal GH levels were higher during HS (P=0.0015 and P=0.014, respectively). Moreover, IGFBP-1 levels were higher during HS than in NS (P=0.004). No difference was found regarding insulin levels. The expression of IGF1R mRNA as 2(-Delta Delta CT) was higher during HS than in NS (P=0.03). Conclusion: The above results confirm a role of hypoxia in the regulation of the IGF system also in humans. This effect could be direct on the liver and/or mediated by GH and it is not restricted to the hepatocytes but involves other cell lines. During acute hypoxia a combination of alterations usually associated with reduced IGF action was observed. The higher expression of IGF1R mRNA may reflect an up-regulation of the transcriptional process. (C) 2012 Elsevier Ltd. All rights reserved.

QUANTIFICATION OF LEFT VENTRICULAR MYOCARDIAL COLLAGEN SYSTEM IN CHILDREN, YOUNG ADULTS, AND THE ELDERLY

Studies on the collagen system of the human myocardium are still limited compared to those on small laboratory animals. The aim of this work was to observe the collagen tissue of the myocardium of the human heart as a function of age. The types of collagen, as well as the density of collagen tissue and the diameter of collagen fibrils, were examined. Fragments of the left ventricular wall from 15 hearts, 5 from children, 5 from young adults, and 5 from elderly individuals, were analyzed by using the Picrosirius-polarization method and by transmission electron microscopy (TEM). The results showed the presence of collagen type III and collagen type I, both in the endomysium and perimysium of the 3 groups studied. Measurements of collagen content in myocardial tissue displayed that both endomysial and perimysial collagen increase in number and thickness in the adult and elderly. These histochemical results coincided with the observations obtained with the electron microscope in showing an increase in the number of collagen fibrils with a large diameter in the adult and elderly hearts. The present results on cardiac collagen may be important for assessing the pathogenesis of several cardiopathies in the hearts of children, young adults, and the elderly.

Variations in peak expiratory flow measurements associated to air pollution and allergic sensitization in children in Sao Paulo, Brazil

Background In the last 20 years, there has been an increase in the incidence of allergic respiratory diseases worldwide and exposure to air pollution has been discussed as one of the factors associated with this increase. The objective of this study was to investigate the effects of air pollution on peak expiratory flow (PEF) and FEV1 in children with and without allergic sensitization. Methods Ninety-six children were followed from April to July, 2004 with spirometry measurements. They were tested for allergic sensitization (IgE, skin prick test, eosinophilia) and asked about allergic symptoms. Air pollution, temperature, and relative humidity data were available. Results Decrements in PEF were observed with previous 24-hr average exposure to air pollution, as well as with 310-day average exposure and were associated mainly with PM10, NO2, and O3 in all three categories of allergic sensitization. Even though allergic sensitized children tended to present larger decrements in the PEF measurements they were not statistically different from the non-allergic sensitized. Decrements in FEV1 were observed mainly with previous 24-hr average exposure and 3-day moving average. Conclusions Decrements in PEF associated with air pollution were observed in children independent from their allergic sensitization status. Their daily exposure to air pollution can be responsible for a chronic inflammatory process that might impair their lung growth and later their lung function in adulthood. Am. J. Ind. Med. 55:10871098, 2012. (c) 2012 Wiley Periodicals, Inc.

Nebulized 0.5, 2.5 and 5 ml L-epinephrine for post-extubation stridor in children: a prospective, randomized, double-blind clinical trial

Nebulized l-epinephrine has been recommended for the treatment of viral croup. However, the few studies assessing its effect on post-extubation stridor (PES) have shown conflicting results. We compared the efficacy and safety of nebulized l-epinephrine at three different doses for the treatment of PES. We conducted a prospective, randomized, double-blind trial including all consecutive children with a PES score of a parts per thousand yen4 (Westley score). The primary efficacy outcome was change in PES score at 40 min. A reduction of a parts per thousand yen2 points in stridor score was defined as clinically significant. A total of 96 patients were randomly assigned to receive one of three doses of nebulized l-epinephrine upon achieving a PES score of 4 or more following extubation. Stridor score and vital signs were recorded before treatment, and at 20, 40, 60 and 180 min after nebulization. Baseline characteristics were similar among all study groups. No significant difference was detected among the treatments based on change in Westley score by intent-to-treat analysis. In addition, the difference in the number of patients who clinically improved among the treatment groups was not significant (p = 0.54). Patients receiving 5 ml nebulized epinephrine had a significant increase of systolic and diastolic blood pressure at 40 and 180 min. Nebulized l-epinephrine at doses of 0.5, 2.5 and 5 ml demonstrated a lack of dose response in effect on PES and a modestly clinically significant increase in undesired side effects (heart rate and blood pressure) at higher doses.

Comparison of screening methods for conductive hearing loss identification in children: low-cost proposal

Objective To evaluate the effectiveness of two screening methods (imitanciometry screening and questionnaire) to identify children at risk for conductive hearing loss, comparing this data with complete audiologic evaluation. Methods Of 507 children aged between three and six, 111 completed all procedures. The observational methods used were: imitanciometry screening, a questionnaire to identify risk factors for hearing loss and complete audiologic evaluation. Results obtained in the first two instruments were compared with results from complete audiologic evaluation (gold standard). From these comparisons, sensitivity and specificity, accuracy, positive and negative predictive values, and odds ratio were determined for the two screening methods and for the combination of both methods. Results The two methods applied in series (questionnaire and after imitanciometry screening) showed a greater odds ratio and better correlation between sensitivity and proportion of false-positives (ROC curve). Conclusion Combining the two tests in series improved screening accuracy. This combination was the best tool for identifying children at risk for conductive hearing loss.

TOMOGRAPHIC ANALYSIS OF ANATOMICAL PARAMETERS OF THE AXIS IN CHILDREN

Objective: To carry out an anatomical study of the axis with the use of computed tomography (CT) in children aged from two to ten years, measuring the lamina angle, lamina and pedicle length and thickness, and lateral mass length. Methods: Sixty-four CTs were studied from patients aged 24 to 120 months old, of both sexes and without any cervical anomaly. The measurements obtained were correlated with the data on age and sex of the patients. Statistical analysis was performed using the Students "t" tests. Results: We found that within the age range 24-48 months, 5.5% of the lamina and 8.3% of the pedicles had thicknesses of less than 3.5mm, which is the minimum thickness needed for insertion of the screw. Between 49 and 120 months, there were no lamina thicknesses of less than 3.5mm, and 1.2% of the pedicle thicknesses were less than 3.5mm values. Neither of the age groups had any lamina and pedicle lengths of less than 12mm, or lateral mass lengths greater than 12mm. Conclusion: The analysis of the data obtained demonstrates that most of the time, is possible to use a 3.5mm pedicle screw in the laminas and pedicles of the axis in children. Level of Evidence: II, Development of diagnostic criteria in consecutive patients.

Retrolabyrinthine approach for surgical placement of auditory brainstem implants in children

Conclusion: The extended retrolabyrinthine approach (RLA) is a safe and reliable approach for auditory brainstem placement in children. The surgical landmarks to reach cochlear nucleus are adequately exposed by this approach. Objective: To describe a new approach option for auditory brainstem implants (ABIs) in children, highlighting the anatomical landmarks to appropriately expose the foramen of Luschka. Methods: Three prelingually deafened children consecutively operated for ABIs via the RLA. Results: ABI placement via the RLA was successfully performed in all children without any further complications except multidirectional nystagmus in one child. The RLA we employed differed from that used for vestibular schwannoma only in the removal of the posterior semicircular canal. The lateral and superior semicircular canals and the vestibule remained intact, and there was no need to expose the dura of the internal auditory meatus. The jugular bulb was completely exposed to allow adequate visualization of the ninth cranial nerve and cerebellar flocculus.

Incidental mild hyperglycemia in children: two MODY 2 families identified in Brazilian subjects

Maturity-onset diabetes of the young (MODY) is characterized by an autosomal dominant mode of inheritance, early onset of hyperglycemia, and defects of insulin secretion. MODY subtypes described present genetic, metabolic, and clinical differences. MODY 2 is characterized by mild asymptomatic fasting hyperglycemia, and rarely requires pharmacological treatment. Hence, precise diagnosis of MODY is important for determining management and prognosis. We report two heterozygous GCK mutations identified during the investigation of short stature. Case 1: a prepubertal 14-year-old boy was evaluated for constitutional delay of growth and puberty. During follow-up, he showed abnormal fasting glucose (113 mg/dL), increased level of HbA1c (6.6%), and negative beta-cell antibodies. His father and two siblings also had slightly elevated blood glucose levels. The mother had normal glycemia. A GCK heterozygous missense mutation, p.Arg191Trp, was identified in the proband. Eighteen family members were screened for this mutation, and 11 had the mutation in heterozygous state. Case 2: a 4-year-old boy investigated for short stature revealed no other laboratorial alterations than elevated glycemia (118 mg/dL); beta-cell antibodies were negative. His father, a paternal aunt, and the paternal grandmother also had slightly elevated glycemia, whereas his mother had normal glycemia. A GCK heterozygous missense mutation, p.Glu221Lys, was identified in the index patient and in four family members. All affected patients had mild elevated glycemia. Individuals with normal glycemia did not harbor mutations. GCK mutation screening should be considered in patients with chronic mild early-onset hyperglycemia, family history of impaired glycemia, and negative beta-cell antibodies. Arq Bras Endocrinol Metab. 2012;56(8):519-24

Factors associated with overweight in children living in the neighbourhoods of an urban area of Brazil

Objective: The present study aimed to investigate the individual and family determinants of being overweight among children younger than 10 years of age. Design: Cross-sectional survey. Direct data on children's age, food intake, physical activity, type of transportation used and anthropometric measurements, as well as the education level of the mothers, were collected by trained interviewers. Setting: Population-based study in the city of Santos, Brazil. Subjects: A total of 531 children under 10 years of age (302 aged <6 years, >= 6 aged years), living in the city of Santos. Results: The overall prevalence of overweight and obesity (BMI-for-age Z-score >1) was 35.4% for children under 6 years and 38.9% for children aged 6-10 years. The socio-economic status of the family was associated with being overweight for both age groups. Logistic regression analysis showed that the lower the socio-economic status, the higher the likelihood of being overweight, among both younger children (OR = 7.73; P = 0.02) and older children (OR = 1.98; P = 0.04). The use of active transportation was associated with a lower likelihood of being overweight, but only among younger children (OR = 1.70; P = 0.05). Conclusions: Socio-economic status seems to be an important individual-level determinant of overweight in children. Public policies should consider promoting the use of active transportation, as the results showed it to have a positive effect on reducing overweight issues. The high prevalence of overweight in younger children suggests that this age group should be a priority in health-promoting interventions.

Immune response and tolerability of varicella vaccine in children and adolescents with systemic lupus erythematosus previously exposed to varicella-zoster virus

Objectives The aim of the present paper is to evaluate the immune response and tolerability of varicella vaccine in children and adolescents with systemic lupus erythematosus previously exposed to varicella-zoster virus. Methods We performed a prospective and controlled study on a group of 54 SLE patients that were chosen at random to be or not to be vaccinated (28 were vaccinated and 26 were not). Twenty-eight healthy controls, of matching age and sex were also vaccinated. All were submitted to a questionnaire, physical evaluation and laboratory assays: lymphocyte immuno-phenotyping by flow cytometry, plasma varicella zoster virus (VZV) serology by ELISA and in vitro interferon gamma (IFN gamma) production by T-cells after stimulus with VZV antigen. They were evaluated before vaccination and at 30, 45, 180 and 360 days afterwards. Results We did not observe any differences in the frequency of adverse events in both vaccinated groups. At study entry, all individuals were seropositive for VZV antibodies. The serum VZV antibody titres similarly increased after vaccination. The frequency of flares and the SLEDAI score were also similar among the patients. Thirty days after vaccination the production of IFN gamma specific to VZV was lower in the SLE group compared to healthy, controls. In the follow-up we observed 4 cases of herpes zoster in the SLE unvaccinated group, but no zoster in the vaccinated group. Conclusion The varicella vaccine was well tolerated in SLE group, who had pre-existing immunity to varicella. The varicella vaccine immunogenicity measurement by serum antibody titres was appropriate. The incidence of HZ was lower in the vaccinated lupus group.

Weight and neuro-psycho-motor development in children discharged from neonatal intensive care unit

Background: Low birth weight affects child growth and development, requiring the intensive use of health services. There are conversely proportional associations between prematurity and academic performance around the world. In this study we evaluated factors involved in weight and neuropsychomotor profile in one and two years old discharged from Intensive Care Units (ICU). Methods/Design: We investigated 203 children from the ICU who were followed for 24 +/- 4 months. The research was conducted by collecting data from medical records of patients in a Follow-up program. We investigated the following variables: inadequate weight at one year old; inadequate weight at two years old and a severe neurological disorder at two years old. Results: We observed increase of almost 20% in the proportion of children which weighted between the 10th and 90th percentiles and decrease of around 40% of children below the 15th percentile, from one to two years old. In almost 60% of the cases neuropsychomotor development was normal at 2 years old, less than 15% of children presented abnormal development. Variables that remained influential for clinical outcome at 1 and 2 years old were related to birth weight and gestational age, except for hypoglycemia. Neurological examination was the most influential variable for severe neurological disturbance. Conclusion: Hypoglycemia was considered a new fact to explain inadequate weight. The results, new in Brazil and difficult in terms of comparison, could be used to identify risk factors and for a better approach of newborn discharged from ICUs.

Prediction of tolerance in children with IgE mediated cow's milk allergy by microarray profiling and chemometric approach

The sera of a retrospective cohort (n = 41) composed of children with well characterized cow's milk allergy collected from multiple visits were analyzed using a protein microarray system measuring four classes of immunoglobulins. The frequency of the visits, age and gender distribution reflected real situation faced by the clinicians at a pediatric reference center for food allergy in 530 Paulo, Brazil. The profiling array results have shown that total IgG and IgA share similar specificity whilst IgM and in particular IgE are distantly related. The correlation of specificity of IgE and IgA is variable amongst the patients and this relationship cannot be used to predict atopy or the onset of tolerance to milk. The array profiling technique has corroborated the clinical selection criteria for this cohort albeit it clearly suggested that 4 out of the 41 patients might have allergies other than milk origin. There was also a good correlation between the array data and ImmunoCAP results, casein in particular. By using qualitative and quantitative multivariate analysis routines it was possible to produce validated statistical models to predict with reasonable accuracy the onset of tolerance to milk proteins. If expanded to larger study groups, the array profiling in combination with the multivariate techniques show potential to improve the prognostic of milk allergic patients. (C) 2012 Elsevier B.V. All rights reserved.

The Effects of Oxybutynin on Urinary Symptoms in Children with Williams-Beuren Syndrome

Purpose: Williams-Beuren syndrome is a genomic disorder caused by a hemizygous contiguous gene deletion on chromosome 7q11.23. Lower urinary tract symptoms are common in children with Williams-Beuren syndrome. However, there are few data on the management of voiding symptoms in this population. We report our experience using oxybutynin to treat urinary symptoms in children with Williams-Beuren syndrome. Materials and Methods: We prospectively analyzed 42 patients with Williams-Beuren syndrome and significant lower urinary tract symptoms due to detrusor overactivity diagnosed on urodynamics in a 12-week, open-label study. Urological assessment included symptomatic evaluation, the impact of lower urinary tract symptoms on quality of life, frequency-volume chart, urodynamics and urinary tract sonography. After 12 weeks of treatment with 0.6 mg/kg oxybutynin per day given in 3 daily doses, patients were assessed for treatment efficacy and side effects. Results: A total of 17 girls and 19 boys completed medical therapy and were assessed at 12 weeks. Mean +/- SD patient age was 9.2 +/- 4.3 years (range 3 to 18). The most common urinary complaint was urgency, which occurred in 31 patients (86.1%), followed by urge incontinence, which was seen in 29 (80.5%). Compared to baseline, urinary symptoms were substantially improved. The negative impact of storage symptoms on quality of life was significantly decreased from a mean +/- SD of 3.3 +/- 1.7 to 0.5 +/- 0.9 (p <0.001). Mean +/- SD maximum urinary flow improved from 14.2 +/- 15.0 to 20.5 +/- 6.4 ml per second (p <0.001). Conclusions: A total of 12 weeks of therapy with 0.6 mg/kg oxybutynin daily resulted in improvement of lower urinary tract symptoms, quality of life and maximum flow rate in most patients with Williams-Beuren syndrome.

Laparoscopic Adrenalectomy in Children for Neuroblastoma: Report of Case Series

Background: Neuroblastoma is one of the most common solid tumors in the pediatric population and the adrenal gland is the main abdominal site of this tumor. The laparoscopic approach has become the standard of care for most benign adrenal tumors in adults, but the role of laparoscopic adrenalectomy in children for malignant tumor is still a point of controversy. However, there is a growing experience with laparoscopic neuroblastoma resection of small lesions and the use of minimally invasive techniques for the initial management of infiltrative neuroblastoma in the last years. The aim of this study is to describe our initial experience with laparoscopic adrenalectomy for neuroblastoma in children, based on surgical outcomes. Methods: A retrospective review of 7 laparoscopic adrenalectomies performed in a single institution between October 2008 and October 2009. We focused our analysis on early surgical outcomes. Results: The mean tumoral size was 2.8 +/- 0.9 cm, the average surgical time was 38.6 +/- 65.5 minutes, and the mean hospital stay was 2.9 +/- 1.6 days. One stage IV patient was submitted to conversion due to bleeding and needed blood transfusion. There were no late complications or deaths and the mean follow-up time was 18.8 +/- 6.1 months. Conclusions: The laparoscopic approach for adrenal neuroblastoma resection is feasible in children with good outcomes, but should be reserved to patients with small, well-circumscribed adrenal lesions, without invasive or infiltrative disease.