Effects of Growth Hormone (GH) Supplementation on Dermatoscopic Evolution of Pigmentary Lesions in Children with Growth Hormone Deficiency (GHD).

Recent reports have confirmed higher levels of growth hormone (GH) receptor (GHR) transcripts in malignant melanomas (MM), yet the role of GH in the pathogenesis of MM remains controversial. Although melanocytes appear to be hormonally responsive, the effects of GH on MM cells are less clear. A direct correlation between GH administration and the development of melanoma seems possible. Our study aimed to assess whether GH supplementation in children with growth hormone deficiency (GHD) could induce changes in the melanocytic lesions both from a dimensional and dermoscopic point of view. The study population consisted of 14 patients sorted into two groups. The experimental group consisted of seven GHD pediatric patients who underwent dermatological examination with epiluminescence through the use of digital video recording of all melanocytic lesions before and after 12 months of GH supplementation, whilst the control group consisted of seven healthy pediatric patients matched for age, sex and phototype. All patients were evaluated according to auxological and dermatological features. A total of 225 melanocytic lesions were examined in the experimental group and 236 in the control group. Our study shows a significant increase in the mean size values of the lesions in the study group but not in the control group. Increases in the dermoscopic ABCD Score and in BMI correlated to an increase in the size of the melanocytic lesions and the dermoscopic parameters. The increase in SDS Height correlated with ABCD Score changes and with dermoscopic score structures. No differences were found compared to the control group. Dimensional/structural modifications in melanocytic lesions of patients treated with GH were closely related to weight and statural growth and can be considered a normal physiological process induced by GH supplementation.

ABCD1 gene mutation in an Italian family with X-linkedadrenoleukodystrophy: case series.

SUMMARY: Adrenoleukodystrophy is a peroxisomal X-linked recessive disease caused by mutations in the ABCD1 gene, located on the X-chromosome (Xq28). Gene mutations in patient with adrenoleukodystrophy induce metabolic alterations characterized by impaired peroxisomal beta-oxidation and accumulation of very long chain fatty acid (VLCFA) in plasma and in all tissues. Although nutritional intervention associated with a various mixture of oil prevents the accumulation of VLCFA, to date no causal treatment is available. Therefore, haematopoietic stem cell transplantation (HSCT) and gene therapy are allowed only for very early stages of cerebral forms diagnosed during childhood.We reported a case series describing five family members affected by X-linked adrenoleukodystrophy caused by a novel mutation of the ABCD1 gene. Particularly, three brothers were affected while the sister and mother carried the mutation of the ABCD1 gene. In this family, the disease was diagnosed at different ages and with different clinical pictures highlighting the wide range of phenotypes related to this novel mutation. In addition, these characteristics stress the relevant role of early diagnosis to properly set a patient-based follow-up. LEARNING POINTS: We report a novel mutation in the ABCD1 gene documented in a family group associated to an X-ALD possible Addison only phenotype. All patients present just Addison disease but with different phenotypes despite the presence of the same mutations. Further follow-up is necessary to complete discuss the clinical development. The diagnosis of ALD needs to be included in the differential diagnosis in all patients with idiopathic PAI through accurate evaluation of VLCFA concentrations and genetic confirmation testing. Early diagnosis of neurological manifestation is important in order to refer timely to HSCT. Further follow-up of these family members is necessary to characterize the final phenotype associated with this new mutation.

Non-Alcoholic Fatty Liver Disease in Obese Youth With Insulin Resistance and Type 2 Diabetes.

Currently, Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent form of chronic liver disease in children and adolescents worldwide. Simultaneously to the epidemic spreading of childhood obesity, the rate of affected young has dramatically increased in the last decades with an estimated prevalence of NAFLD of 3%-10% in pediatric subjects in the world. The continuous improvement in NAFLD knowledge has significantly defined several risk factors associated to the natural history of this complex liver alteration. Among them, Insulin Resistance (IR) is certainly one of the main features. As well, not surprisingly, abnormal glucose tolerance (prediabetes and diabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. In addition, other factors such as genetic, ethnicity, gender, age, puberty and lifestyle might affect the development and progression of hepatic alterations. However, available data are still lacking to confirm whether IR is a risk factor or a consequence of hepatic steatosis. There is also evidence that NAFLD is the hepatic manifestation of Metabolic Syndrome (MetS). In fact, NAFLD often coexist with central obesity, impaired glucose tolerance, dyslipidemia, and hypertension, which represent the main features of MetS. In this Review, main aspects of the natural history and risk factors of the disease are summarized in children and adolescents. In addition, the most relevant scientific evidence about the association between NAFLD and metabolic dysregulation, focusing on clinical, pathogenetic, and histological implication will be provided with some focuses on the main treatment options.

Plasma from obese children increases monocyte-endothelial adhesion and affects intracellular insulin signaling in cultured endothelial cells: Potential role of mTORC1-S6K1.

Childhood obesity is characterized by the loss of vascular insulin sensitivity along with altered oxidant-antioxidant state and chronic inflammation, which play a key role in the onset of endothelial dysfunction. We previously demonstrated a reduced insulin-stimulated Nitric Oxide (NO) bioavailability in Human Umbilical Vein Endothelial cells (HUVECs) cultured with plasma from obese pre-pubertal children (OB) compared to those cultured with plasma of normal-weight children (CTRL). However, mechanisms underlying endothelial dysfunction in childhood obesity remains poorly understood. Hence, the present study aimed to better investigate these mechanisms, also considering a potential involvement of mammalian Target Of Rapamycin Complex1 (mTORC1)-ribosomal protein S6 Kinase beta1 (S6K1) pathway. OB-children (N = 32, age: 9.2 ± 1.7; BMI z-score: 2.72 ± 0.31) had higher fasting insulin levels and increased HOMA-IR than CTRL-children (N = 32, age: 8.8 ± 1.2; BMI z-score: 0.33 ± 0.75). In vitro, HUVECs exposed to OB-plasma exhibited significant increase in Reactive Oxygen Species (ROS) levels, higher vascular and intercellular adhesion molecules exposure, together with increased monocytes-endothelial interaction. This was associated with unbalanced pro- and anti-atherogenic endothelial insulin stimulated signaling pathways, as measured by increased Mitogen Activated Protein Kinase (MAPK) and decreased Insulin Receptor Substrate-1 (IRS-1)/protein kinase B (Akt)/ endothelial NO Synthase (eNOS) phosphorylation levels, together with augmented S6K1 activation. Interestingly, inhibition of mTORC1-S6K1 pathway using rapamycin significantly restored the IRS-1/Akt/eNOS activation, suggesting a feedback regulation of IRS-1/Akt signal through S6K1. Overall, our in vitro data shed light on new mechanisms underlying the onset of endothelial dysfunction in childhood obesity.

Role of urinary NGAL and KIM-1 as biomarkers of early kidney injury in obese prepubertal children.

Objectives Childhood obesity is an important cause of end-stage renal disease. To date, available markers do not characterize kidney changes, especially in the early stages. kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are already detected before the onset of proteinuria or alterations of glomerular filtration rate and thus might represent biomarkers that directly reflect kidney injury. Methods We characterize kidney injury in a group of 40 obese-prepubertal children compared to 29-healthy age- and gender matched-peers. Anthropometric measurements and body composition were determined. Fasting blood samples were collected for measurement of insulin, glucose, lipid profile, transaminases, cystatin C and creatinine. Urine samples were collected to assess urinary NGAL, KIM-1 and urinary isoprostanes. Kidney length was measured with ultrasound evaluation. Differences between the two groups were evaluated by Mann-Whitney U test, and Spearman correlation analysis was used to explore relationship between variables. Results Triglycerides, alanine transaminase (ALT), glucose, insulin, homeostasis model assessment insulin resistance, triglycerides/high-density lipoprotein (HDL)-cholesterol ratio and cystatin C values were significantly higher in obese children than normal weight peers. Creatinine values were normal and similar between the two groups, while isoprostanes were higher in obese. Obese children had larger kidney sizes, indicating organ hypertrophy. NGAL and KIM-1 were increased in obese children compared to controls. A significant association between NGAL and KIM-1 with adiposity indices, insulin status and markers of oxidative stress postulated a possible effect of obesity in inducing kidney abnormalities. KIM-1 and NGAL are directly related respectively to cystatin C and isoprostanes, supporting the ability of these biomarkers in reflecting early kidney damages in obese subjects. Conclusions These findings suggest that obese subjects exhibit a certain degree of renal damage before kidney function loss.

Successful lung response after surgical repair in an infant with right-sided congenital diaphragmatic hernia.

Congenital diaphragmatic hernia is a rare condition associated with pulmonary complications as the abdominal viscera herniated into the chest may affect lungs development. We present the case of a male newborn baby with a prenatal diagnosis of a posterolateral defect (Bochdalek hernia) involving the right side. The infant underwent surgical repair at 3 days of life, and the post-surgery chest X-ray did not reveal morpho-structural alterations of the lungs and diaphragmatic profile. Our clinical case shows that patients may have a better lung outcome despite an initial unfavorable picture. Prenatal diagnosis is essential in identifying infants with congenital diaphragmatic hernia, especially those cases at higher risk for the worse outcomes, to optimize their clinical and surgical management.

Role of THRB, ARG1, and ADRB2 Genetic Variants on Bronchodilators Response in Asthmatic Children.

Background: An interindividual variability in response to short-acting bronchodilator drugs (short-acting inhaled ß2-agonists, SABA) exists and this is linked in part to genetic factors. The aim of this study was to verify the influence of single nucleotide polymorphisms (SNPs) of a previously studied gene (ADRB2) and of new candidate genes (THRB and ARG1) on the acute response to SABA in children with asthma. Methods: One hundred asthmatic children (mean age 9.6 ± 3.0 years, 77 boys) underwent allergological and lung function evaluations. Spirometry was performed before and after bronchodilation test (BD test). The ADRB2 region containing the Arg16Gly (rs1042713) and Gln27Glu (rs1042714) variants were amplified by polymerase chain reaction, whereas ARG1 rs2781659 (A>G) and THRB rs892940 (G>A) SNPs were genotyped by high-resolution melting (HRM) analysis. Results: Seventy-seven percent of children developed asthma in the first 6 years of life. Allergic sensitization was observed in 92% (total immunoglobulin G: 529.8 ± 477. kU/L). All patients exhibited respiratory allergy: 43% has multiple respiratory, 22% to single respiratory, and 27% multiple respiratory and food allergies. Fifty four percent children showed positive BD response (forced expiratory volume in 1 second [FEV1] > 12%). Presence of Arg/Gly or Gly/Gly genotypes in position 16 of ADRB2 was significantly associated to a worse BD response (post-BD FEV1: 108.68% ± 15.62% in Arg/Arg vs. 101.86% ± 14.03% in Arg/Gly or Gly/Gly patients, p = 0.02). No significant association was found between spirometric parameters before and after BD for the other three examined SNPs. Conclusion: The influence of genetic variability on responsiveness to drugs could become a key parameter to optimize a tailored therapy for young patients with asthma, especially if drug-resistance occurs.

Methylprednisolone-induced hepatotoxicity in a 16-year-old girl with multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease with demyelination of the central nervous system. High-dosage corticosteroids are the first-line therapy in the acute relapsing of MS. We report a case of severe high-dose methylprednisolone-induced acute hepatitis in a patient with a new diagnosis of MS. A 16-year-old girl was admitted for urticaria, angioedema, nausea and vomiting a month later she had been diagnosed with MS and treated with high-dosage methylprednisolone. Laboratory investigations showed hepatic insufficiency with grossly elevated liver enzymes. A liver biopsy showed focal centrilobular hepatocyte necrosis with interface hepatitis. Methylprednisolone-induced hepatotoxicity can confuse the clinical picture of patients with MS and complicate the differential diagnosis. We believe that each specialist should know it and monitor patients with MS taking high doses of methylprednisolone. As there is no screening model that predicts idiosyncratic hepatotoxicity, we promote screening for potential liver injury following pulse steroid therapy.

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.

Pyomyositis is not only a tropical pathology: a case series.

BACKGROUND: Pyomyositis is an acute bacterial infection of skeletal muscle that results in localized abscess formation. This infection was thought to be endemic to tropical countries, and is also known as "tropical pyomyositis". However, pyomyositis is increasingly recognized in temperate climates and is frequently associated with an immunosuppressive condition, such as human immunodeficiency virus, malignancy, and diabetes mellitus. It is also found in healthy and athletic people after strenuous or vigorous exercise or following localized and possibly unnoticed trauma. It can be primary or secondary to neighboring or remote infection. Primary pyomyositis is a rare condition that can affect children and adolescents. Diagnosis can be delayed because the affected muscle is deeply situated and local signs are not apparent. This delay in diagnosis can result in increased morbidity and a significant mortality rate. The pediatric population, which comprises 35% of the reported pyomyositis cases, is an especially difficult subset of patients to diagnose. CASE PRESENTATION: In our series, we describe the cases of four previously healthy Caucasian children who were admitted to our Pediatric Department with different clinical presentations. Pyomyositis in our patients was related to factors affecting the muscle itself, including strenuous exercise and direct muscle trauma. Therapy was started with a cephalosporin antibiotic and teicoplanin was subsequently added. The minimum length of therapy was 3 weeks. CONCLUSIONS: The diagnosis of pyomyositis in our patients, none of whom were immune-compromised, is confirmation that this disease is not an exclusive pathology of tropical countries and demonstrates that there is an increasing prevalence of pyomyositis in temperate climates.

Incidence of infants born small- and large-for-gestational-age in an Italian cohort over a 20-year period and associated risk factors.

BACKGROUND: We assessed the incidence of infants born small-for-gestational-age (SGA) and large-for-gestational-age (LGA) in an Italian cohort over 20 years (1993-2013). Furthermore, we investigated maternal factors associated with SGA and LGA births. METHODS: A retrospective review of obstetric records was performed on infants born in Chieti (Italy) covering every 5(th) year over a 20-year period, specifically examining data for 1993, 1998, 2003, 2008, and 2013. Infants with birthweight <10(th) percentile were defined as SGA, and those with birthweight >90(th) percentile as LGA. Data collected included newborn anthropometry, birth (multiple vs singleton), maternal anthropometry, previous miscarriage, gestational diabetes, hypertension, and smoking during pregnancy. RESULTS: There were a pooled total of 5896 live births recorded across the 5 selected years. The number of SGA (+60.6 %) and LGA (+90.2 %) births increased considerably between 1993 and 2013. However, there were no marked changes in the incidence of SGA or LGA births (8.3 % and 10.8 % in 1993 versus 7.6 % and 11.7 % in 2013, respectively). Maternal factors associated with increased risk of SGA infants included hypertension, smoking, and previous miscarriage (all p < 0.05), while greater pre-pregnancy BMI and gestational diabetes were risk factors for LGA births (all p < 0.05). CONCLUSIONS: There was an increase in the number of SGA and LGA births in Chieti over the last two decades, but there was little change in incidence over time. Most maternal factors associated with increased odds of SGA and LGA births were modifiable, thus incidence could be reduced by targeted interventions.

The effect of obesity and type 1 diabetes on renal function in children and adolescents.

BACKGROUND: Early signs of renal complications can be common in youths with type 1 diabetes (T1D). Recently, there has been an increasing interest in potential renal complications associated with obesity, paralleling the epidemics of this condition, although there are limited data in children. HYPOTHESIS: Obese children and adolescents present signs of early alterations in renal function similar to non-obese peers with T1D. SUBJECTS: Eighty-three obese (age: 11.6 ± 3.0 yr), 164 non-obese T1D (age: 12.4 ± 3.2 yr), and 71 non-obese control (age: 12.3 ± 3.2 yr) children and adolescents were enrolled in the study. METHODS: Anthropometric parameters and blood pressure were measured. Renal function was assessed by albumin excretion rate (AER), serum cystatin C, creatinine and estimated glomerular filtration rate (e-GFR), calculated using the Bouvet's formula. RESULTS: Obese and non-obese T1D youths had similar AER [8.9(5.9-10.8) vs. 8.7(5.9-13.1) µg/min] and e-GFR levels (114.8 ± 19.6 vs. 113.4 ± 19.1 mL/min), which were higher than in controls [AER: 8.1(5.9-8.7) µg/min, e-GFR: 104.7 ± 18.9 mL/min]. Prevalence of microalbuminuria and hyperfiltration was similar between obese and T1D youths and higher than their control peers (6.0 vs. 8.0 vs. 0%, p = 0.02; 15.9 vs. 15.9 vs. 4.3%, p = 0.03, respectively). Body mass index (BMI) z-score was independently related to e-GFR (r = 0.328; p < 0.001), and AER (r = 0.138; p = 0.017). Hemoglobin A1c (HbA1c) correlated with AER (r = 0.148; p = 0.007) but not with eGFR (r = 0.041; p = 0.310). CONCLUSIONS: Obese children and adolescents show early alterations in renal function, compared to normal weight peers, and they have similar renal profiles than age-matched peers with T1D.

Spectrum of phenotypic anomalies in four families with deletion of the SHOX enhancer region.

BACKGROUND: SHOX alterations have been reported in 67% of patients affected by Léri-Weill dyschondrosteosis (LWD), with a larger prevalence of gene deletions than point mutations. It has been recently demonstrated that these deletions can involve the SHOX enhancer region, rather that the coding region, with variable phenotype of the affected patients.Here, we report a SHOX gene analysis carried out by MLPA in 14 LWD patients from 4 families with variable phenotype. CASE PRESENTATION: All patients presented a SHOX enhancer deletion. In particular, a patient with a severe bilateral Madelung deformity without short stature showed a homozygous alteration identical to the recently described 47.5 kb PAR1 deletion. Moreover, we identified, for the first time, in three related patients with a severe bilateral Madelung deformity, a smaller deletion than the 47.5 kb PAR1 deletion encompassing the same enhancer region (ECR1/CNE7). CONCLUSIONS: Data reported in this study provide new information about the spectrum of phenotypic alterations showed by LWD patients with different deletions of the SHOX enhancer region.

Etanercept improves lipid profile and oxidative stress measures in patients with juvenile idiopathic arthritis.

OBJECTIVE: To investigate the effect of 1-year treatment with the anti-tumor necrosis factor-α (TNF-α) drug etanercept on lipid profile and oxidative stress in children and adolescents with juvenile idiopathic arthritis (JIA). METHODS: Thirty children with JIA (22 females; mean age 12.3 ± SD 5.7 yrs), all eligible for anti-TNF-α treatment, were assessed at baseline and after 6- and 12-month treatment with etanercept. Disease activity was determined using the Juvenile Arthritis Disease Activity Score (JADAS). Blood samples were drawn to measure the acute-phase reactants C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), lipids, and the proinflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6 and interferon-γ. To measure the oxidative stress marker 8-iso-prostaglandin F2α, 24-h urine samples were collected. RESULTS: Inflammatory indicators (CRP and ESR) and JADAS scores improved significantly after 1 year of etanercept treatment (all p < 0.001). Proinflammatory cytokines showed significant reduction during the study period (all p < 0.001). Similar reductions were detected in total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p = 0.04), and triglycerides (p < 0.001), whereas no significant change was found in high-density lipoprotein cholesterol. No side effects were observed during the treatment period. CONCLUSION: This study shows for the first time that anti-TNF-α therapy for JIA is associated not only with a beneficial effect on clinical disease activity and inflammatory indexes, but also with improved lipid profile and oxidative stress. These findings suggest that TNF-α blockers might reduce atherosclerotic risk in children with JIA.

Growth failure in children with cystic fibrosis.

Poor linear growth and inadequate weight gain are very common problems in cystic fibrosis (CF) children. The most important factors involved in growth failure are undernutrition or malnutrition, chronic inflammation, lung disease, and corticosteroid treatment. Nutritional support and pharmacological therapy with recombinant human growth hormone are essential for a good management of children with CF, although these children are shorter and lighter than healthy children, and despite the catch-up growth observed after diagnosis, deficit in length/height and weight continues to be seen until adulthood. Early diagnosis is essential to ensure better nutritional status and growth, potentially associated with better respiratory function and prognosis. The aims of this review are try to explain etiology and pathogenetic mechanisms of growth failure in CF children and clarify their role in the disease morbidity and in clinical outcome, especially in relation to progressive decline of pulmonary function.

Array-CGH characterization of a de novo t(X;Y)(p22;q11) in a female with short stature and mental retardation.

We report the clinical and molecular investigations in a girl with 46,X,-X,+der(X)t(X;Y)(p22;q11) de novo karyotype who presented an intricate phenotype characterized by mental retardation and facial dysmorphisms in combination with short stature. The structure of the derivative X chromosome was studied using BAC array-CGH which disclosed the Xp22 breakpoint between the STS and the VCX3A gene and the presence of the Yq11.1qter chromosome. It is common that females with Xp;Yq translocations present only short stature and are normal in every other aspect. Thus, this would be the first case in which a girl with Xp;Yq translocation presents an unusual phenotype with intermediate male clinical features with Xp;Yq translocations. The risk of developing gonadoblastoma in females with Y chromosome material is also discussed and, to this effect, different explanations related to this apparent variation are also presented.

US in the diagnosis of gastroesophageal reflux in children.

Several techniques have been used to diagnose gastroesophageal reflux (GER) in children, but no single test is sufficiently accurate to completely investigate the problem. Gastroesophageal US has been described as a widely available, noninvasive and sensitive method. It provides morphological and functional information, but its role in the diagnosis of GER in children is still debated. In this paper we review diagnostic approaches to GER in children. We focus on current use of US in the management of children with suspected GER. Reports suggest that US allows exclusion of several non-GER causes of symptoms and that it provides morphological and functional data with high sensitivity and positive predictive value for the diagnosis of GER. Sonographic assessment of findings such as abdominal esophageal length, esophageal diameter, esophageal wall thickness and gastroesophageal angle provide important diagnostic indicators of reflux and related to the degree of GER. There is a need for standardization of the procedure and for defining diagnostic criteria.

Inflammatory cytokines and growth in childhood.

PURPOSE OF REVIEW: In this review we report an update on the current knowledge on growth disorders in children with chronic inflammatory diseases, mainly inflammatory bowel disease and juvenile idiopathic arthritis, with a particular focus on the role of inflammatory cytokines as mediators of growth impairment. RECENT FINDINGS: Growth disorders are common among patients with inflammatory diseases. Several factors can contribute to growth failure: poor nutrition, immobilization, drugs, disease activity, duration and severity. There is extensive evidence suggesting that inflammatory cytokines are key players in mediating growth failure. Recent studies have confirmed a direct association between levels of inflammatory cytokines, such as tumour necrosis factor-α and interleukin-6, and reduced growth velocity, as well as impaired body composition. Recent studies have also highlighted the beneficial effect of new drugs, such biologics, not only in controlling disease activity, but also in improving growth. SUMMARY: Growth retardation remains a major problem in patients with chronic inflammatory diseases, and proinflammatory cytokines are key players in this context. New drugs, specifically targeting inflammatory cytokines appear to be promising for their effect on growth. Further studies are required to better characterize the cytokine profile in children with inflammatory disease and help in developing effective treatment strategies.

Long-term outcome of epilepsy in Kabuki syndrome.

UNLABELLED: PURPOSES AND METHODS: Kabuki syndrome (KS) is a rare dysmorphic disorder characterized by multiple congenital anomalies and mental retardation. Although epilepsy is one of the most common clinical complications associated with KS, few studies have evaluated its electroclinical aspects and long-term outcome. Therefore, we describe here a clinical series of 10 Caucasian KS patients who developed epilepsy in childhood. We followed all children for at least 5 years. RESULTS: All patients presented partial seizures and interictal EEGs revealed focal epileptic paroxysms with prevalent involvement of temporo-occipital areas. Seven children had no central nervous system abnormalities, but enlargement of lateral ventricles, corpus callosum hypoplasia, and adenohypophysis hypoplasia were revealed in three. Although antiepileptic drug (AED) treatment was effective in controlling seizures and normalizing EEG abnormalities in 8 patients, the other 2 cases were resistant to multiple AEDs. In one of these two patients, withdrawal of AED resulted in status epilepticus and death. CONCLUSIONS: Partial seizures and temporo-occipital abnormalities on interictal EEG are common features of KS patients who suffer from epilepsy. Prognosis of this epilepsy is favourable in the majority of cases with complete disappearance of seizures and EEG abnormalities.

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.