Evaluation of an oral analgesia protocol for upper-limb fracture reduction in the paediatric emergency department: Prospective study of 101 patients.

BACKGROUND: Upper limb injuries are common in children. When required, closed fracture reduction can be performed in the emergency department without general anaesthesia but causes pain. The primary objective of this study was to assess an oral analgesia protocol for fracture reduction without general anaesthesia. The secondary objectives were to look for associations linking pain intensity to age, sex, and waiting time and to determine the frequency of secondary displacement requiring closed reduction or internal fixation under general anaesthesia at the 1-week follow-up visit. HYPOTHESIS: An oral analgesia protocol combining a loading dose of morphine with other medications would provide sufficient pain control to obviate the need for general anaesthesia. MATERIAL AND METHODS: A prospective observational single-centre study was conducted over a 15-month period (July 2017-October 2018) in consecutive patients younger than 16 years who required reduction of a displaced upper-limb fracture. All patients received the same oral combination of paracetamol (15mg/kg), ibuprofen (7.5-10mg/kg), and a loading morphine dose (0.5mg/kg, up to 20mg) 1hour before the procedure. Patients given morphine more than 2hours before the procedure and those with persistent pain were given an additional morphine dose (0.2mg/kg, up to 10mg). An equimolar mixture of oxygen and nitrous oxide was administered during reduction. An appropriate scale was used to measure pain intensity before, during, and 15minutes after the procedure. Cases of secondary displacement requiring further reduction or internal fixation under general anaesthesia at the 1-week follow-up visit were recorded. RESULTS: The 101 study patients (73 male and 28 female) had a mean age of 9.4 years (range, 2-15 years). Mean pain scores were 5.0±2.6 at admission and 2.1±2.3, 2.6±3.3, and 1.3±2.2 before, during, and after reduction, respectively. Pain intensity during reduction was significantly associated with age. The analgesia was deemed satisfactory by 94 patients and 90 parents. General anaesthesia for further treatment was required in 10 (9.9%) patients, either on the day after the initial treatment, due to inadequate reduction (n=8), or at the 1-week visit, due to secondary displacement (n=2). DISCUSSION: Oral morphine in a sufficient dosage given in combination with other medications was effective and well tolerated when used to control pain during upper-limb fracture reduction. Pain intensity was not significantly associated with sex. In contrast, pain was significantly more severe in the patients older than 10 years of age. The proportions of patients requiring further reduction or internal fixation were consistent with previously published data. Most patients and parents were satisfied with the analgesia protocol. CONCLUSION: A multimodal oral analgesia protocol provides sufficient pain relief to allow closed reduction of upper-limb fractures in children at the emergency department. This management strategy provided high satisfaction rates in both the patients and their parents. LEVEL OF EVIDENCE: II, prospective observational study.

Insulin resistance and lung function in obese asthmatic pre-pubertal children.

BACKGROUND: Recent findings have supposed that the underlying association between the increased prevalence of both asthma and obesity may be insulin resistance (IR). METHODS: Insulin and glucose serum levels were analyzed to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) for IR in 98 pre-pubertal children. Lung function and allergy status evaluation were performed. The study population was divided into four groups: (1) obese asthmatic children (ObA); (2) normal-weight asthmatic children (NwA); (3) normal-weight non-asthmatic children (Nw) and (4) obese non-asthmatic children (Ob). RESULTS: Forced expiratory volume in 1 s (FEV1) was slightly lower in obese subjects compared with normal-weight subjects and forced vital capacity (FVC) appeared lower in asthmatics, whereas between non-asthmatics subjects, it was lower in the obese group than in the normal-weight one. The post hoc analysis revealed a statistically significant reduction in FEV1, peak expiratory flow (PEF), forced expiratory flows (FEF) between 50% and 25% of the FVC (FEF50 and FEF25) between ObA and Nw and in FEV1, FVC, PEF, FEF50 and FEF25 between NwA and Nw, but no statistically significant differences of lung function parameters were observed between ObA and NwA. We found an inverse relationship between HOMA-IR and all spirometric parameters, although without any statistical significance. We also observed a significantly lower FVC in insulin-resistant children (HOMA-IR>95th percentile) (p=0.03). CONCLUSIONS: This study suggests that lung function could be early altered in obese children, already in pre-pubertal age. Although IR should not manifest its effects on lungs in pre-pubertal obese children, the prevention or treatment of obesity in the pre-pubertal period may prevent definitive negative effects on lungs.

Novel Insights in the Metabolic Syndrome in Childhood and Adolescence.

Metabolic syndrome (MetS) is recognized as an escalating major health risk in adults as well as in children and adolescents. Its prevalence ranges from 6 to 39% depending on the applied definition criteria. To date, there is no consensus on a MetS definition for children and adolescents. However, most authors agree on essential components such as glucose intolerance, central obesity, hypertension, and dyslipidemia; each representing a risk for cardiovascular disease. Recently, associations between MetS and non-alcoholic fatty liver disease, hyperuricemia, and sleep disturbances have emerged. Biomarkers like adipocytokines are a subject of current research as they are implicated in the pathogenesis of the MetS. Epigenetics and gestational programming, especially the role of microRNA, comprise a novel, rapidly developing and promising research focus on the topic of MetS. MicroRNAs are increasingly valued for potential roles in the diagnosis, stratification, and therapeutics of MetS. Early detection of risk factors, screening for metabolic disturbances, and the identification of new therapies are major aims to reduce morbidity and mortality related to MetS. Dietary modification and physical activity are currently the only adopted treatment approaches. Pharmacological therapies and bariatric surgery are still contradictory and, therefore, are only recommended in selected high-risk cases.

Plasma from pre-pubertal obese children impairs insulin stimulated Nitric Oxide (NO) bioavailability in endothelial cells: Role of ER stress.

Childhood obesity is commonly associated with early signs of endothelial dysfunction, characterized by impairment of insulin signaling and vascular Nitric Oxide (NO) availability. However, the underlying mechanisms remain to be established. Hence, we tested the hypothesis that endothelial insulin-stimulated NO production and availability was impaired and related to Endoplasmic Reticulum (ER) in human umbilical vein endothelial cells (HUVECs) cultured with plasma obtained from pre-pubertal obese (OB) children. OB children (N = 28, age: 8.8 ± 2.2; BMI z-score: 2.15 ± 0.39) showed impaired fasting glucose, insulin and HOMA-IR than normal weight children (CTRL; N = 28, age: 8.8 ± 1.7; BMI z-score: 0.17 ± 0.96). The in vitro experiments showed that OB-plasma significantly impaired endothelial insulin-stimulated NO production and bioavailability compared to CTRL-plasma. In parallel, in HUVECs OB-plasma increased GRP78 and activated PERK, eIF2α, IkBα and ATF6 (all ER stress markers). Moreover, OB-plasma increased NF-κB activation and its nuclear translocation. Notably, all these effects proved to be significantly restored by using PBA and TUDCA, known ER stress inhibitors. Our study demonstrate for the first time that plasma from obese children is able to induce in vitro endothelial insulin resistance, which is characterized by reduced insulin-stimulated NO production and bioavailability, endothelial ER stress and increased NF-κB activation.

Being born large for gestational age is associated with earlier pubertal take-off and longer growth duration: a longitudinal study.

AIM: Perinatal factors seem to influence the onset of puberty, but there is limited information on the potential effect of large size at birth on pubertal growth. This study evaluated pubertal growth in children born large for gestational age (LGA) compared to children born appropriate for gestational age (AGA). METHODS: Longitudinal growth data collected from 70 children - 40 AGA and 30 LGA - were analysed. The ages at take-off, peak height velocity, final height and pubertal growth spurts were calculated using the Preece-Baines model I. RESULTS: Large for gestational age children showed an earlier age at take-off compared to AGA children (10.1 ± 1.2 versus 11.0 ± 1.4 years, p = 0.007), whereas the age at peak height velocity and at final height was similar. LGA children showed a longer growth spurt duration (2.5 ± 1 versus 1.5 ± 1.2 years, p < 0.001) and total pubertal duration (5.3 ± 1.2 versus 4.6 ± 1.2 years, p = 0.036) than AGA children. Results were similar when stratified by sex. CONCLUSION: Being born LGA was associated with an earlier pubertal take-off and longer growth duration. These unique findings, due to the lack of studies on pubertal growth patterns in LGA children, might lead the way to novel research and a different approach to LGA children at the onset of pubertal growth.

Physiological and pathophysiological roles of NAMPT and NAD metabolism.

Nicotinamide phosphoribosyltransferase (NAMPT) is a regulator of the intracellular nicotinamide adenine dinucleotide (NAD) pool. NAD is an essential coenzyme involved in cellular redox reactions and is a substrate for NAD-dependent enzymes. In various metabolic disorders and during ageing, levels of NAD are decreased. Through its NAD-biosynthetic activity, NAMPT influences the activity of NAD-dependent enzymes, thereby regulating cellular metabolism. In addition to its enzymatic function, extracellular NAMPT (eNAMPT) has cytokine-like activity. Abnormal levels of eNAMPT are associated with various metabolic disorders. NAMPT is able to modulate processes involved in the pathogenesis of obesity and related disorders such as nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) by influencing the oxidative stress response, apoptosis, lipid and glucose metabolism, inflammation and insulin resistance. NAMPT also has a crucial role in cancer cell metabolism, is often overexpressed in tumour tissues and is an experimental target for antitumour therapies. In this Review, we discuss current understanding of the functions of NAMPT and highlight progress made in identifying the physiological role of NAMPT and its relevance in various human diseases and conditions, such as obesity, NAFLD, T2DM, cancer and ageing.

Progression of cardio-metabolic risk factors in subjects born small and large for gestational age.

BACKGROUND: Subjects born small (SGA) and large (LGA) for gestational age have an increased risk of cardio-metabolic alterations already during prepuberty. Nevertheless, the progression of their cardio-metabolic profile from childhood to adolescence has not been fully explored. Our aim was to assess potential changes in the cardio-metabolic profile from childhood to adolescence in subjects born SGA and LGA compared to those born appropriate (AGA) for gestational age. METHODS: This longitudinal study included 35 AGA, 24 SGA and 31 LGA subjects evaluated during childhood (mean age (± SD) 8.4 ± 1.4 yr) and then re-assessed during adolescence (mean age 13.3 ± 1.8 yr). BMI, blood pressure, insulin resistance (fasting insulin, HOMA-IR) and lipids were assessed. A cardio-metabolic risk z-score was applied and this consisted in calculating the sum of sex-specific z-scores for BMI, blood pressure, HOMA-IR, triglycerides and triglycerides:high-density lipoprotein cholesterol ratio. RESULTS: Fasting insulin and HOMA-IR were higher in SGA and LGA than AGA subjects both during childhood (all P<0.01) and adolescence (all P<0.01). Similarly, the clustered cardio-metabolic risk score was higher in SGA and LGA than AGA children (both P<0.05), and these differences among groups increased during adolescence (both P<0.05). Of note, a progression of the clustered cardio-metabolic risk score was observed from childhood to adolescence within SGA and within LGA subjects (both P<0.05). CONCLUSIONS: SGA and LGA subjects showed an adverse cardio-metabolic profile during childhood when compared to AGA peers, with a worsening of this profile during adolescence. These findings indicate an overtime progression of insulin resistance and overall estimated cardiovascular risk from childhood to adolescence in SGA and LGA populations.

Triglycerides-to-HDL ratio as a new marker of endothelial dysfunction in obese prepubertal children.

OBJECTIVE: To investigate whether there is an association of the triglyceride-to-HDL cholesterol (TG:HDL-C) ratio with cardiovascular risk factors and early signs of vascular damage in obese prepubertal children. DESIGN AND METHODS: In 50 obese (27 boys, 7.8±1.4 years) and 37 normal-weight (20 boys; 7.3±1.5 years) prepubertal children, anthropometric measurements, oxidative stress markers (urinary isoprostanes (PGF2α (prostaglandin F2α)), soluble receptor for advanced glycation end-products (sRAGE)) and insulin sensitivity (homeostasis model assessment of insulin resistance (HOMA-IR) and whole-body insulin sensitivity index (WBISI)) were evaluated. Lipids profile was assessed and the TG:HDL-C ratio was calculated. In addition, high-resolution ultrasound was performed to assess carotid intima-media thickness (cIMT). RESULTS: Obese children showed significantly higher values of the TG:HDL-C ratio (1.9±1.1 vs 1.2±0.6, P=0.002) compared with controls. After dividing the population in tertiles of the TG:HDL-C ratio (<1.04, 1.04-1.67, >1.67), cIMT (P=0.0003), and HOMA-IR (P=0.0001) progressively increased from the lower to the upper tertile, whereas WBISI (P=0.0003) and sRAGE (P=0.05) progressively decreased. In a regression model, the TG:HDL ratio was significantly and positively associated with cIMT (r=0.493; P=0.0005). A cutoff point for TG:HDL-C ratio of 1.12 had 81% sensitivity and 49% specificity in the identification of children with cIMT values in the upper quartile (Area under the curve values from receiver operating characteristic curves=0.633±0.065, P=0.045). CONCLUSION: This study confirms the reliability of the TG:HDL-C ratio as a useful marker of cardiovascular risk. Interestingly, our results underline that the TG:HDL-C ratio is directly related with early signs of vascular damage already present in prepubertal children.

Is asymmetric dimethylarginine associated with being born small and large for gestational age?

Low and high birth weights have been linked to increased susceptibility to cardiovascular and metabolic alterations. However, the natural history of cardiometabolic disturbances in children born small (SGA) and large (LGA) for gestational age is still unclear and no reliable biomarker of cardiovascular risk has definitively been identified in these subjects. Interestingly, asymmetric dimethylarginine (ADMA), antagonist of nitric oxide (NO) production, has been recognized as novel cardiovascular marker able to identify subjects at higher risk of health disturbances. Despite the well-described role of ADMA as a predictor of degenerative disease in adults, its potential application in pediatrics, and specifically in SGA and LGA children, has not been explored as only few data in preterm infants and SGA newborns are available. Therefore, we investigated potential alterations in circulating ADMA and NO levels in SGA and LGA children compared with those born appropriate (AGA) for gestational age. Of note, ADMA was significantly higher in SGA and LGA children than AGA peers. Intriguingly, SGA and LGA categories as well as insulin resistance were independently related to ADMA. Our observations lead to the intriguing hypothesis that ADMA could be involved in the development of cardiometabolic alterations in SGA and LGA children already during the prepubertal age.

Weight loss in obese prepubertal children: the influence of insulin resistance.

BACKGROUND: Insulin resistance (IR), a link of paramount importance between obesity and cardiovascular/metabolic complications, seems to be implicated in weight changes. OBJECTIVE: To determine whether IR could influence weight status during a 1-year intervention program in obese prepubertal children. METHODS: Forty-four children with IR (IR group) and 42 children without IR (NIR group) were enrolled. Body mass index standard deviation score (BMI-SDS), waist circumference (WC), and homeostasis model assessment (HOMA-IR) were evaluated. RESULTS: NIR children showed a significant reduction of BMI-SDS and WC at final assessment (p = 0.009 and p = 0.001, respectively), whereas IR children presented unchanged values. HOMA-IR decreased after intervention in the NIR group (p = 0.0008), but was exacerbated in IR children (p = 0.004). A positive and significant association between HOMA-IR at baseline and BMI at follow-up was found (B ± SE = 0.87 ± 0.24, p = 0.001). HOMA-IR at baseline was also significantly associated with WC at follow-up (B ± SE = 2.12 ± 0.69, p = 0.003). CONCLUSIONS: IR seems to influence adiposity changes in obese prepubertal children. Further longitudinal studies are needed to verify the relationship between IR and weight loss during childhood.

Implications of gastrointestinal hormones in the pathogenesis of obesity in prepubertal children.

BACKGROUND: There is a worsening high prevalence of global obesity. Special attention has been paid to the gut-endocrine system, represented by the regulators of appetite. In particular, it has been suggested that ghrelin ("hunger" peptide), and obestatin and glucagon-like peptide-1 (GLP-1) ("satiety" peptides) could play important roles in the pathogenesis of obesity. OBJECTIVES: The aims of this study were to compare fasting plasma ghrelin, obestatin, and GLP-1 levels between obese and nonobese prepubertal children, and to assess their relations with fatness indexes and insulin resistance (IR). SUBJECTS AND METHODS: Fifty-two prepubertal obese children and 22 controls were enrolled. Fasting levels of gastrointestinal hormones (ghrelin, obestatin, and GLP-1), glucose, and insulin were evaluated. IR was assessed using the homeostasis model assessment of IR (HOMA-IR) index. Analysis was performed by Mann-Whitney U-test, Kruskal-Wallis test, and Spearman's correlation. RESULTS: Obese prepubertal children and normal-weight controls had similar age distribution. Obese children were more insulin resistant when compared to controls (HOMA-IR: p < 0.01 ). GLP-1 levels were significantly lower in obese children than in controls (p < 0.01). Obestatin was significantly higher in obese than normal-weight children (p < 0.01), while ghrelin was not different. There was a negative correlation between GLP-1 and standard deviation score-body mass index (r = -0.36, p = 0.009) and between GLP-1 and waist circumference (r = -0.45, p = 0.001), while no association was observed with HOMA-IR. CONCLUSIONS: GLP-1 levels have been shown to be correlated with adiposity indexes, but not with HOMA-IR, suggesting that this hormone could play an important role in the early development of obesity.

Serum levels of receptors for advanced glycation end products in normal-weight and obese children born small and large for gestational age.

OBJECTIVE: To assess potential alterations in soluble and endogenous secretory receptors for advanced glycation end products (sRAGE and esRAGE) in normal-weight (NW) and obese (Ob) children born small (SGA) and large (LGA) compared with appropriate for gestational age (AGA) subjects and to explore if birth weight (BW), insulin resistance (IR), and obesity represent independent risk factors. RESEARCH DESIGN AND METHODS: We categorized 130 prepubertal children into six groups according to BW and obesity and evaluated sRAGE, esRAGE, and homeostasis model assessment of IR. RESULTS: sRAGE and esRAGE were lower in Ob SGA and LGA children than Ob AGA subjects (all P < 0.05), and in NW SGA and LGA children than NW AGA subjects (all P < 0.05). Interestingly, BW and IR were significantly and independently related to RAGE. CONCLUSIONS: sRAGE and esRAGE are decreased in SGA and LGA children, and BW and IR seem to play an important role in the reduction of RAGE.

Could receptors for advanced glycation end products be considered cardiovascular risk markers in obese children?

Early development of increased cardiovascular risk in obese children and the possible related cardiovascular diseases into adulthood have been shown; however, the underling pathogenetic mechanisms implicated are not yet completely defined. Receptors for advanced glycation end products (RAGE) pathway play a pivotal role in the genesis of abnormality of arterial wall. However, whether obese prepubertal children present impaired levels of endogenous and soluble secretory receptor for advanced glycation end products (esRAGE/sRAGE) and whether an association exists between RAGE levels and carotid intima media thickness (cIMT) are not yet evaluated in this age group. We note that esRAGE and sRAGE were significantly lower in obese children than controls and were independently related to cIMT. Our findings lead to the hypothesis that RAGE system seems to be related to the development of atherosclerosis even in obese prepubertal children.

The possible role of esRAGE and sRAGE in the natural history of diabetic nephropathy in childhood.

The advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We evaluated endogenous secretory (es)RAGE and soluble (s)RAGE concentrations in 64 pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and compared the values with those of 62 controls matched for age, gender and Tanner pubertal stages. We also explored the possible association of their concentrations with early signs of diabetic nephropathy, defined as changes in kidney volume and estimated glomerular filtration rate (eGFR). Significantly lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal (p = 0.003 and p = 0.001) and pubertal (p = 0.002 and p = 0.001) subjects with type 1 diabetes than in the controls. In both groups of patients with type 1 diabetes, the eGFR (pre-pubertal p = 0.01 and pubertal p = 0.01) and the mean value of kidney volume adjusted for body surface (pre-pubertal p = 0.003 and pubertal p = 0.002) were higher than those of the controls. The regression analysis showed an inverse relationship between esRAGE and body surface-adjusted mean kidney volume (p = 0.0004, r = -0.503). esRAGE and sRAGE concentrations were lower in normoalbuminuric youths with type 1 diabetes than in their healthy peers. The inverse association between esRAGE levels and early kidney alterations suggests a potential role of esRAGE in diabetic nephropathy.

Implications for kidney disease in obese children and adolescents.

Increasing attention has been focused on the implications of obesity in adults on the development of kidney disease, but data on the obese pediatric population are lacking. The aim of this study was to investigate whether changes in various renal function indexes/markers, as expressed by the glomerular filtration rate [GFR, as estimated by the Schwartz formula (eGFR)], serum cystatin C (CysC) level, albumin excretion rate (AER), and modifications in nitric oxide (NO; an important modulator of renal function and morphology), urinary isoprostanes (markers of oxidative stress), and blood pressure (BP), can be detected in obese children and adolescents when compared to normal weight controls. Blood and urinary samples were collected to evaluate markers of renal function, serum and urinary NO, and urinary isoprostanes in 107 obese Caucasian subjects and 50 controls. Ambulatory BP monitoring (ABPM) was performed in all cases. Obesity was expressed by the body mass index standard deviation score (SDS-BMI), and insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR). CysC and eGFR did not significantly differ between the two groups; AER was increased in obese children. CysC and GFR were related to HOMA-IR, and AER was related to HOMA-IR and SDS-BMI. Obese subjects had reduced NO levels and increased urinary isoprostanes and BP measurements; all three parameters were related to SDS-BMI and insulin resistance. ABPM showed an increased incidence of hypertension and non-dipping in the obese group. Based on our comparison of obese and nonobese children, we conclude that renal involvement is not an early clinically evident manifestation of adiposity in childhood, since no overt changes in eGFR and only a mild albuminuria were detected. A longer exposure to obesity is probably needed before renal function impairment appears.

Hypophosphatasia in a child with widened anterior fontanelle: lessons learned from late diagnosis and incorrect treatment.

UNLABELLED: Hypophosphatasia is characterized by deficiency of serum alkaline phosphatase with defective bone and teeth mineralization. We report on an 11-month-old boy who developed a complex clinical picture characterized by bulging anterior fontanelle, growth failure, nephrocalcinosis and impaired bone mineralization during high-dose calcium and vitamin D supplementation. This therapy had been started 5 months earlier for a presumed diagnosis of nutritional rickets established on the grounds of isolated widened anterior fontanelle. However, laboratory investigations revealed reduced alkaline phosphatase levels associated with hypercalcemia, hypercalciuria, low PTH and normal 25-hydroxy vitamin D levels. Genetic testing detected a compound heterozygote for the novel mutation (c.262G>A) and the described mutation (c.920C>T) in the ALPL gene. CONCLUSION: High calcium and vitamin D supplementation should not be started in the presence of isolated signs of nutritional rickets without assessing calcium-phosphate metabolism. In fact, in rare bone-mineralizing disorders, this combined therapy might induce severe clinical complications.

What is the significance of soluble and endogenous secretory receptor for advanced glycation end products in liver steatosis in obese prepubertal children?

The endogenous secretory receptor for advanced glycation end products (esRAGE) and soluble RAGE (sRAGE) have been shown in human plasma and have emerged as reliable biomarkers of several pathological conditions, including insulin resistance and liver injury. We examined esRAGE and sRAGE levels in obese prepubertal children with and without liver steatosis. esRAGE and sRAGE levels were significantly lower in obese prepubertal children affected by liver steatosis and were independently related to liver steatosis. These findings suggest that AGE-RAGE pathway plays an independent role in the development of liver injury already present in this age group.

The reciprocal influences of asthma and obesity on lung function testing, AHR, and airway inflammation in prepubertal children.

Although asthma and obesity are among the major chronic disorders their reciprocal or independent influences on lung function testing, airways hyperresponsiveness (AHR) and bronchial inflammation has not been completely elucidated. In 118 pre-pubertal Caucasian children anthropometric measurements functional respiratory parameters (flow/volume curves at baseline and after 6-minute walk test [6MWT]) together with bronchial inflammatory index (FeNO) were assessed. The study population was divided into four groups according to BMI and the presence or absence of asthma: Obese asthmatic (ObA) Normal-weight asthmatic (NwA), Obese non-asthmatic (Ob), non-asthmatic normal-weight children (Nw). Baseline PEF and MEF(75) (%-expected) were significantly different across the four groups with significantly lower values of MEF(75) in ObA and Ob children when compared to Nw children (P = 0.004 and P = .0001, respectively) and this independent role of obesity on upper respiratory flows was confirmed by multiple analysis of covariance. After 6 MWT respiratory parameters decreased only in ObA and NwA children and 12 children presented a positive fall in FEV(1), in contrast no changes of respiratory function testing were detected in Ob and Nw children, and only 2 Ob children presented a significant fall in FEV(1). FeNO analysis demonstrated significantly higher values in ObA and NwA children when compared to Ob (P = 0.008 and P = 0.0002, respectively) and Nw children (P = 0.0001 and P = 0.0003, respectively), although a significant difference was found between Ob and Nw children (P = 0.0004). Multiple analysis of covariance confirmed an independent role of asthma on this parameter. In conclusion while AHR and airway inflammation are clearly associated with an asthmatic status, obesity seems to induce reduction of upper airways flows associated with a certain degree of pro-inflammatory changes.

Weight gain and insulin resistance in children treated with valproate: the influence of time.

This study was undertaken in 2 parts to investigate the relationship between body size and insulin resistance during treatment with valproic acid in children. The cross-sectional part revealed differences in terms of body size and homeostasis model assessment of insulin resistance, which were higher in the group on medication. The longitudinal part showed a major increase in body size and insulin resistance during the first year of therapy. There was a subsequent decrease in insulin resistance in association with the rise of body size, however with a trend to level off. These results might be helpful to enhance the knowledge of valproic acid action on both insulin resistance and weight gain, allowing to plan appropriate approach for the prevention of the consequences of the treatment with valproic acid.

Insulin resistance and oxidative stress in children born small and large for gestational age.

OBJECTIVE: Our aim was to evaluate the effect of BW and obesity on oxidative stress and IR in prepubertal SGA and LGA children compared with appropriate-for-gestational-age (AGA) children. METHODS: We performed a cross-sectional study comparing oxidative stress and IR in 103 children categorized into 6 groups according to BW (26 SGA, 15 AGA, and 16 LGA normal-weight children) and obesity (15 SGA, 15 AGA, and 16 LGA obese children). Indexes of IR (HOMA-IR, G/I) and the marker of oxidative stress (urinary isoprostanes) were evaluated. RESULTS: Homeostasis Model Assessment was higher in both normal-weight SGA and LGA children than in normal-weight AGA children (all P