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Inflammatory Injury to the Neonatal Brain - What Can We Do?
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Itai Berger , Noa Ofek-Shlomai
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract Perinatal brain damage is one of the leading causes of life long disability. This damage could be hypoxic–ischemic, inflammatory, or both. This mini-review discusses different interventions aiming at minimizing inflammatory processes in the neonatal brain, both before and after insult. Current options of anti-inflammatory measures for neonates remain quite limited. We describe current anti-inflammatory intervention strategies such as avoiding perinatal infection and inflammation, and reducing exposure to inflammatory processes. We describe the known effects of anti-inflammatory drugs such as steroids, antibiotics, and indomethacin, and the possible anti-inflammatory role of other substances such as IL-1 receptor antagonists, erythropoietin, caffeine, estradiol, insulin-like growth factor, and melatonin as well as endogenous protectors, and genetic regulation of inflammation. If successful, these may decrease mortality and long-term morbidity among term and pre-term infants.
DOI : doi:10.3389/fped.2014.00030
Cilt :2
ISSN :2296-2360
Sınıflandırma :
2
Obstetric Pharmacokinetic Dosing Studies are Urgently Needed.
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Frontiers in Pediatrics
Yazar(lar) :
Brookie M Best , Shelley A McCormack
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract Use of pharmacotherapy during pregnancy is common and increasing. Physiologic changes during pregnancy may significantly alter the overall systemic drug exposure, necessitating dose changes. A search of PubMed for pharmacokinetic clinical trials showed 494 publications during pregnancy out of 35,921 total pharmacokinetic published studies (1.29%), from the late 1960s through August 31, 2013. Closer examination of pharmacokinetic studies in pregnant women published since 2008 (81 studies) revealed that about a third of the trials were for treatment of acute labor and delivery issues, a third included studies of infectious disease treatment during pregnancy, and the remaining third were for varied ante-partum indications. Approximately, two-thirds of these recent studies were primarily funded by government agencies worldwide, one-quarter were supported by private non-profit foundations or combinations of government and private funding, and slightly <10% were supported by pharmaceutical industry. As highlighted in this review, vast gaps exist in pharmacology information and evidence for appropriate dosing of medications in pregnant women. This lack of knowledge and understanding of drug disposition throughout pregnancy place both the mother and the fetus at risk for avoidable therapeutic misadventures – suboptimal efficacy or excess toxicity – with medication use in pregnancy. Increased efforts to perform and support obstetric dosing and pharmacokinetic studies are greatly needed.
DOI : doi:10.3389/fped.2014.00009
Cilt :2
ISSN :2296-2360
3
My Tribute to Mary Ellen Avery.
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Frontiers in Pediatrics
Yazar(lar) :
John Steven Torday
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract None
DOI : doi:10.3389/fped.2014.00031
Cilt :2
ISSN :2296-2360
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4
Pediatric Critical Care: Grand Challenges for a Glowing Future.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Kanwaljeet J S Anand
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract None
DOI : doi:10.3389/fped.2014.00035
Cilt :2
ISSN :2296-2360
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5
Plasma Natriuretic Peptides in Children and Adolescents with Obstructive Sleep Apnea and Their Changes Following Intervention.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Yun Kwok Wing , Dennis Lip Yen Lee , Michael Ho Ming Chan , Kate Ching Ching Chan , Jodie Y Zhu , Chun Ting Au , Albert Martin Li
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract Objective: This study aimed to evaluate circulating natriuretic peptides (NP) concentration in obese and non-obese children and adolescents with and without obstructive sleep apnea (OSA), and their levels following OSA treatment.Methods: Subjects with habitual snoring and symptoms suggestive of OSA were recruited. They underwent physical examination and overnight polysomnography (PSG). OSA was diagnosed if obstructive apnea–hypopnea index (OAHI) was ≥1/h. Fasting serum atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were taken after overnight PSG. The subjects were divided into obese, non-obese, with and without OSA groups for comparisons.Results: One hundred fourteen children (77 were boys) with a median [interquartile range (IQR)] age of 10.8 (8.3–12.7) years (range: 2.4–11.8 years) were recruited. Sixty-eight subjects were found to have OSA. NP levels did not differ between subjects with and without OSA in both obese and non-obese groups. Stepwise multiple linear regressions revealed that body mass index (BMI) z-score was the only independent factor associated with NP concentrations. Fifteen children with moderate-to-severe OSA (OAHI >5/h) underwent treatment and there were no significant changes in both ANP and BNP levels after intervention.Conclusion: Body mass index rather than OSA was the main determinant of NP levels in school-aged children and adolescents.
DOI : doi:10.3389/fped.2014.00022
Cilt :2
ISSN :2296-2360
Sınıflandırma :
6
Red Man Syndrome Following Intraperitoneal Vancomycin in a Child with Peritonitis.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Michael L Moritz , Melissa J Domis
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract Red man syndrome (RMS) has frequently been reported to occur with intravenous vancomycin therapy. However, there have been few reports of this complication during intraperitoneal (IP) treatment with vancomycin. This report describes an 11-year-old boy with end stage renal disease who developed RMS 45 min into the initial loading dose of IP vancomycin for the treatment of bacterial peritonitis with a vancomycin level of 38.8 mcg/mL. The patient developed this adverse reaction despite appropriate initial loading dose per ISPD guidelines for continuous treatment (1000 mg/L). This case emphasizes the importance of monitoring for adverse reactions of vancomycin therapy, and raises dosing considerations that differ slightly from the currently recommended ISPD guidelines for IP vancomycin treatment in the treatment of bacterial peritonitis.
DOI : doi:10.3389/fped.2014.00055
Cilt :2
ISSN :2296-2360
Sınıflandırma :
7
Epigenetic Modifications in Pediatric Acute Lymphoblastic Leukemia.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Teena Bhatla , Michael J Burke
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract Aberrant epigenetic modifications are well-recognized drivers for oncogenesis. Pediatric acute lymphoblastic leukemia (ALL) is no exception and serves as a model toward the significant impact these heritable alterations can have in leukemogenesis. In this brief review, we will focus on the main aspects of epigenetics, which control leukemogenesis in pediatric ALL, mainly DNA methylation, histone modification, and microRNA alterations. As we continue to gain better understanding of the driving mechanisms for pediatric ALL at both diagnosis and relapse, therapeutic interventions directed toward these pathways and mechanisms can be harnessed and introduced into clinical trials for pediatric ALL.
DOI : doi:10.3389/fped.2014.00042
Cilt :2
ISSN :2296-2360
8
Involvement of Synaptic Genes in the Pathogenesis of Autism Spectrum Disorders: The Case of Synapsins.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Fabio Benfenati , Anna Fassio , Anna Corradi , Silvia Giovedi
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders characterized by deficits in social interaction and social communication, restricted interests, and repetitive behaviors. Many synaptic protein genes are linked to the pathogenesis of ASDs, making them prototypical synaptopathies. An array of mutations in the synapsin (Syn) genes in humans has been recently associated with ASD and epilepsy, diseases that display a frequent comorbidity. Syns are pre-synaptic proteins regulating synaptic vesicle traffic, neurotransmitter release, and short-term synaptic plasticity. In doing so, Syn isoforms control the tone of activity of neural circuits and the balance between excitation and inhibition. As ASD pathogenesis is believed to result from dysfunctions in the balance between excitatory and inhibitory transmissions in neocortical areas, Syns are novel ASD candidate genes. Accordingly, deletion of single Syn genes in mice, in addition to epilepsy, causes core symptoms of ASD by affecting social behavior, social communication, and repetitive behaviors. Thus, Syn knockout mice represent a good experimental model to define synaptic alterations involved in the pathogenesis of ASD and epilepsy.
DOI : doi:10.3389/fped.2014.00094
Cilt :2
ISSN :2296-2360
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Biyotıp %100
Nörokimya %99
9
Associations between Infant Feeding Practices and Length, Weight, and Disease in Developing Countries.
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Frontiers in Pediatrics
Yazar(lar) :
Patrick Detzel , Benjamin T Allaire , Benjamin O Yarnoff
Yıl :
2013
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This article is from Frontiers in Pediatrics, volume 1. Abstract The health benefits of exclusive breastfeeding are well-known, but the relative detrimental impacts of other foods on infant health are unknown. Because infants in developing countries are fed a wide range of food, quantifying the burden of these diverse feeding practices on infant health is essential for public health policy. We used data from the Demographic Health Survey from 20 developing countries over multiple years to examine the independent association of six different types of food (exclusive breastfeeding, non-exclusive breastfeeding, infant formula, milk liquids, non-milk liquids, and solid foods) with five measures of infant health (length, weight, diarrhea, fever, and cough). We estimated associations with regression analysis, controlling for confounding factors with infant, mother, and household factors and community-year fixed effects. We used these estimates in a simulation model to quantify the burden of different combinations of food on infant health. We show that for an infant younger than 6 months old, following current guidelines and exclusively breastfeeding instead of giving the infant solid foods may increase length by 0.75 cm and weight by 0.25 kg and decrease diarrhea, fever, and cough prevalence by 8, 12, and 11%, respectively. We found that the burden on infant health of some feeding practices is less than others. Although all other feeding practices are associated with worse health outcomes than exclusive breastfeeding, breastfeeding supplemented with liquids has a lower burden on infant health than solid foods and infant formula has a lower burden than milk or non-milk liquids as measured by four of five health metrics. Providing specific quantified burden estimates of these practices can help inform public health policy related to infant feeding practices.
DOI : doi:10.3389/fped.2013.00021
Cilt :1
ISSN :2296-2360
Sınıflandırma :
10
Designing a Pediatric Severe Sepsis Screening Tool.
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Frontiers in Pediatrics
Yazar(lar) :
Samir H Shah , Arno L Zaritsky , Christine S Bovat , Christopher D Mangum , Sandip A Godambe , Robert J Sepanski
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract We sought to create a screening tool with improved predictive value for pediatric severe sepsis (SS) and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric emergency department (ED). “Gold standard” SS cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over 2 months. The tool’s identification of SS was initially based on International Consensus Conference on Pediatric Sepsis (ICCPS) parameters that were refined by an iterative, virtual process that allowed us to propose successive changes in sepsis detection parameters in order to optimize the tool’s predictive value based on receiver operating characteristics (ROC). Age-specific normal and abnormal values for heart rate (HR) and respiratory rate (RR) were empirically derived from 143,603 children seen in a second pediatric ED over 3 years. Univariate analyses were performed for each measure in the tool to assess its association with SS and to characterize it as an “early” or “late” indicator of SS. A split-sample was used to validate the final, optimized tool. The final tool incorporated age-specific thresholds for abnormal HR and RR and employed a linear temperature correction for each category. The final tool’s positive predictive value was 48.7%, a significant, nearly threefold improvement over the original ICCPS tool. False positive systemic inflammatory response syndrome identifications were nearly sixfold lower.
DOI : doi:10.3389/fped.2014.00056
Cilt :2
ISSN :2296-2360
Sınıflandırma :
11
Reducing Maladaptive Behaviors in Preschool-Aged Children with Autism Spectrum Disorder Using the Early Start Denver Model.
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Frontiers in Pediatrics
Yazar(lar) :
Sally Rogers , Amelia Walter , Rudi Crncec , Valsamma Eapen , Elizabeth Fulton
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract The presence of maladaptive behaviors in young people with autism spectrum disorder (ASD) can significantly limit engagement in treatment programs, as well as compromise future educational and vocational opportunities. This study aimed to explore whether the Early Start Denver Model (ESDM) treatment approach reduced maladaptive behaviors in preschool-aged children with ASD in a community-based long day care setting. The level of maladaptive behavior of 38 children with ASD was rated using an observation-based measure on three occasions during the intervention: on entry, 12 weeks post-entry, and on exit (post-intervention) over an average treatment duration of 11.8 months. Significant reductions were found in children’s maladaptive behaviors over the course of the intervention, with 68% of children showing a treatment response by 12 weeks and 79% on exit. This change was accompanied by improvement in children’s overall developmental level as assessed by the Mullen scales of early learning, but not by significant changes on the Vineland Adaptive Behavior Scales-II or Social Communication Questionnaire. Replication with a larger sample, control conditions, and additional measures of maladaptive behavior is necessary in order to determine the specific factors underlying these improvements; however, the findings of the present study suggest that the ESDM program may be effective in improving not only core developmental domains, but also decreasing maladaptive behaviors in preschool-aged children with ASD.
DOI : doi:10.3389/fped.2014.00040
Cilt :2
ISSN :2296-2360
Sınıflandırma :
12
Mapping Pathological Phenotypes in Reelin Mutant Mice.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Maria Luisa Scattoni , Giovanni Laviola , Rossella Canese , Silvana Gaetani , Gaurav Bedse , Paolo Castelluccio , Angela Caruso , Luisa Altabella , Emilia Romano , Caterina Michetti
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract Autism Spectrum Disorders (ASD) are neurodevelopmental disorders with multifactorial origin characterized by social communication deficits and the presence of repetitive behaviors/interests. Several studies showed an association between the reelin gene mutation and increased risk of ASD and a reduced reelin expression in some brain regions of ASD subjects, suggesting a role for reelin deficiency in ASD etiology. Reelin is a large extracellular matrix glycoprotein playing important roles during development of the central nervous system. To deeply investigate the role of reelin dysfunction as vulnerability factor in ASD, we assessed the behavioral, neurochemical, and brain morphological features of reeler male mice. We recently reported a genotype-dependent deviation in the ultrasonic vocal repertoire and a general delay in motor development of reeler pups. We now report that adult male heterozygous (Het) reeler mice did not show social behavior and communication deficits during male–female social interactions. Wildtype and Het mice showed a typical light/dark locomotor activity profile, with a peak during the central interval of the dark phase. However, when faced with a mild stressful stimulus (a saline injection) only Het mice showed an over response to stress. In addition to the behavioral studies, we conducted high performance liquid chromatography and magnetic resonance imaging and spectroscopy to investigate whether reelin mutation influences brain monoamine and metabolites levels in regions involved in ASD. Low levels of dopamine in cortex and high levels of glutamate and taurine in hippocampus were detected in Het mice, in line with clinical data collected on ASD children. Altogether, our data detected subtle but relevant neurochemical abnormalities in reeler mice supporting this mutant line, particularly male subjects, as a valid experimental model to estimate the contribution played by reelin deficiency in the global ASD neurobehavioral phenotype.
DOI : doi:10.3389/fped.2014.00095
Cilt :2
ISSN :2296-2360
Sınıflandırma :
13
Barium Aspiration in an Infant: A Case Report and Review of Management.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Alan F Isles , I B Masters , A Sarikwal , K Choo , V Goyal , N Kapur , M Jackson
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract We describe a case of bilateral inhalation of barium in an infant following a barium swallow for investigation of dusky spells associated with feeds. A bronchoscopy subsequently revealed the presence of a mid-tracheal tracheo-esophageal cleft. To date, little has been reported on barium aspiration in children and there is no consensus for management. We review the literature on barium aspiration, its consequences, and make recommendations for management.
DOI : doi:10.3389/fped.2014.00037
Cilt :2
ISSN :2296-2360
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14
GABAergic Signaling as Therapeutic Target for Autism Spectrum Disorders.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Enrico Cherubini , Giada Cellot
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract γ-Aminobutyric acid (GABA), the main inhibitory neurotransmitter in the adult brain, early in postnatal life exerts a depolarizing and excitatory action. This depends on accumulation of chloride inside the cell via the cation–chloride importer NKCC1, being the expression of the chloride exporter KCC2 very low at birth. The developmentally regulated expression of KCC2 results in extrusion of chloride with age and a shift of GABA from the depolarizing to the hyperpolarizing direction. The depolarizing action of GABA leads to intracellular calcium rise through voltage-dependent calcium channels and/or N-methyl-d-aspartate receptors. GABA-mediated calcium signals regulate a variety of developmental processes from cell proliferation migration, differentiation, synapse maturation, and neuronal wiring. Therefore, it is not surprising that some forms of neuro-developmental disorders such as autism spectrum disorders (ASDs) are associated with alterations of GABAergic signaling and impairment of the excitatory/inhibitory balance in selective neuronal circuits. In this review, we will discuss how changes of GABAA-mediated neurotransmission affect several forms of ASDs including the Fragile X, the Angelman, and Rett syndromes. Then, we will describe various animal models of ASDs with GABAergic dysfunctions, highlighting their behavioral deficits and the possibility to rescue them by targeting selective components of the GABAergic synapse. In particular, we will discuss how in some cases, reverting the polarity of GABA responses from the depolarizing to the hyperpolarizing direction with the diuretic bumetanide, a selective blocker of NKCC1, may have beneficial effects on ASDs, thus opening new therapeutic perspectives for the treatment of these devastating disorders.
DOI : doi:10.3389/fped.2014.00070
Cilt :2
ISSN :2296-2360
Sınıflandırma :
15
High-Resolution Melting Curve Analysis, a Rapid and Affordable Method for Mutation Analysis in Childhood Acute Myeloid Leukemia.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Weili Sun , Shuhong Shen , Paul S Gaynon , Jing Chen , Huiliang Xue , Peter Wakamatsu , Jingyan Tang , Yin Liu
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract Background: Molecular genetic alterations with prognostic significance have been described in childhood acute myeloid leukemia (AML). The aim of this study was to establish cost-effective techniques to detect mutations of FMS-like tyrosine kinase 3 (FLT3), nucleophosmin 1 (NPM1), and a partial tandem duplication within the mixed-lineage leukemia (MLL-PTD) genes in childhood AML.Procedure: Ninety-nine children with newly diagnosed AML were included in this study. We developed a fluorescent dye SYTO-82 based high-resolution melting (HRM) curve analysis to detect FLT3 internal tandem duplication (FLT3-ITD), FLT3 tyrosine kinase domain (FLT3-TKD), and NPM1 mutations. MLL-PTD was screened by real-time quantitative PCR.Results: The HRM methodology correlated well with gold standard Sanger sequencing with less cost. Among the 99 patients studied, the FLT3-ITD mutation was associated with significantly worse event-free survival (EFS). Patients with the NPM1 mutation had significantly better EFS and overall survival. However, HRM was not sensitive enough for minimal residual disease monitoring.Conclusion: High-resolution melting was a rapid and efficient method for screening of FLT3 and NPM1 gene mutations. It was both affordable and accurate, especially in resource underprivileged regions. Our results indicated that HRM could be a useful clinical tool for rapid and cost-effective screening of the FLT3 and NPM1 mutations in AML patients.
DOI : doi:10.3389/fped.2014.00096
Cilt :2
ISSN :2296-2360
Sınıflandırma :
16
Focus on Apoptosis to Decipher How Alcohol and Many Other Drugs Disrupt Brain Development.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
John W Olney
Yıl :
2014
Frontiers in Pediatrics
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This article is from Frontiers in Pediatrics, volume 2. Abstract None
DOI : doi:10.3389/fped.2014.00081
Cilt :2
ISSN :2296-2360
Sınıflandırma :
Apoptoz %98
17
Potential Contribution of Type I Alveolar Epithelial Cells to Chronic Neonatal Lung Disease.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Henry J Rozycki
Yıl :
2014
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This article is from Frontiers in Pediatrics, volume 2. Abstract The alveolar surface is covered by large flat Type I cells (alveolar epithelial cells 1, AEC1). The normal physiological function of AEC1s involves gas exchange, based on their location in approximation to the capillary endothelium and their thinness, and in ion and water flux, as shown by the presence of solute active transport proteins, water channels, and impermeable tight junctions between cells. With the recent ability to produce relatively pure cultures of AEC1 cells, new functions have been described. These may be relevant to lung injury, repair, and the abnormal development that characterizes bronchopulmonary dysplasia (BPD). To hypothesize a potential role for AEC1 in the development of lung injury and abnormal repair/development in premature lungs, evidence is presented for their presence in the developing lung, how their source may not be the Type II cell (AEC2) as has been assumed for 40 years, and how the cell can be damaged by same type of stressors as those which lead to BPD. Recent work shows that the cells are part of the innate immune response, capable of producing pro-inflammatory mediators, which could contribute to the increase in inflammation seen in early BPD. One of the receptors found exclusively on AEC1 cells in the lung, called RAGE, may also have a role in increased inflammation and alveolar simplification. While the current evidence for AEC1 involvement in BPD is circumstantial and limited at present, the accumulating data supports several hypotheses and questions regarding potential differences in the behavior of AEC1 cells from newborn and premature lung compared with the adult lung.
DOI : doi:10.3389/fped.2014.00045
Cilt :2
ISSN :2296-2360
Sınıflandırma :
18
Assessing the Need for a Specialist Service for People with Intellectual Disabilities and Mental Health Problems Living in Israel: A Qualitative Study.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Mike Stawski , Shirli Werner , Amanda Sinai
Yıl :
2013
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This article is from Frontiers in Pediatrics, volume 1. Abstract Background: It is well established that people with intellectual disabilities are at higher risk of developing mental illnesses. This study aimed to assess the need for a specialized service for people (children and adults) with intellectual disabilities and mental health problems living in Israel.Methods: Our research question was: is there a need for a specialist mental health service for people with intellectual disabilities living in Israel and, if so, what type of service would be most appropriate? We conducted a qualitative study using semi-structured interviews with 14 major stakeholders to identify key themes in response to our research question. The data were coded and themes were identified.Results: Participants were generally not satisfied with current mental health care for people with intellectual disabilities and there was a general agreement that services are in need of improvement. We identified three major themes from the data. These were: current services, future services, and ways to facilitate change.Conclusion: We hope that our findings will be instrumental in shaping the ongoing debate about the best form of delivery of services to this population in Israel. Specifically, we suggest the development of a more specialized system, with the formation of multidisciplinary regional assessment and treatment units in parallel with improved relevant training for all mental health workers and the possibility of referral to specialized teams in more complex cases.
DOI : doi:10.3389/fped.2013.00049
Cilt :1
ISSN :2296-2360
Sınıflandırma :
19
Mesenchymal Stromal Cell Dependent Regression of Pulmonary Metastasis from Ewing's.
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Frontiers in Pediatrics
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Frontiers in Pediatrics
Yazar(lar) :
Charles S Cox , Peter Walker , Yong Xin Wang , Andrea Hayes-Jordan
Yıl :
2014
Frontiers in Pediatrics
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This article is from Frontiers in Pediatrics, volume 2. Abstract Introduction: Ewing’s sarcoma (ES) is the second most common bone tumor in children. Survival has not improved over the last decade and once pulmonary metastatic disease is present, survival is dismal. Mesenchymal stromal cell (MSC) therapy has shown potential benefit for Kaposi’s sarcoma; however, the role of progenitor cell therapies for cancer remains controversial. MSC treatment of ES or pulmonary metastatic disease has not been demonstrated. We have developed an orthotopic xenograft model of ES in which animals develop spontaneous pulmonary metastases. Within this model, we demonstrate the use of MSCs to target ES lung metastasis.Materials and Methods: Human ES cells were transfected with luciferase and injected into the rib of nude mice. Development of pulmonary metastases was confirmed by imaging. After flow cytometry based characterization, MSCs were injected into the tail vein of nude mice with established local ES tumor or pulmonary metastasis. Mice were treated with intravenous MSCs weekly followed by bioluminescent imaging.Results: The intravenous injection of MSCs in an ES model decreases the volume of pulmonary metastatic lesions; however, no effect on primary chest wall tumor size is observed. Thus verifying the MSC preferential homing to the lung. MSCs are found to “home to” the pulmonary parenchyma and remain engrafted up to 5 days after delivery.Discussion: MSC treatment of ES slows growth of pulmonary metastasis. MSCs have more affinity for pulmonary metastasis and can effect a greater decrease in tumor growth in the lungs compared to the primary tumor site.
DOI : doi:10.3389/fped.2014.00044
Cilt :2
ISSN :2296-2360
Sınıflandırma :
20
Non-Invasive Cardiac Output Measurement in Low and Very Low Birth Weight Infants: A Method Comparison.
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Internet Archive Books
Dergi:
Frontiers in Pediatrics
Yayıncı:
Frontiers in Pediatrics
Yazar(lar) :
Patricia Gonzalez , Oswin Grollmuss
Yıl :
2014
Frontiers in Pediatrics
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This article is from Frontiers in Pediatrics, volume 2. Abstract Background: Cardiac output (CO) measurement in low (LBW) and very low (VLBW) birth weight infants is difficult. Hitherto, sporadical transthoracic echocardiography (TTE) is the only non-invasive measurement method. Electrical velocimetry (EV) has been evaluated as an alternative in normal weight newborns.Objectives: The study was designed to evaluate if EV could be interchangeable with TTE even in LBW and VLBW infants.Methods: In 28 (17 LBW, 11 VLBW) pre-mature newborns, n = 228 simultaneous TTE (trans-aortic Doppler), and EV measurements (134 LBW, 94 VLBW) of stroke volume (SV) and heart rate (HR) were performed, thereof calculating body weight indexed SV (=SV*) and CO (=CO*) for all patients and the subgroups. Method comparison was performed by Bland–Altman plot, method precision expressed by calculation of the coefficient of variation (CV).Results: Mean CO* in all patients was 256.4 ± 44.8 (TTE) and 265.3 ± 48.8 (EV) ml/kg/min. Bias and precision were clinically acceptable, limits of agreement within the 30% criterion for method interchangeability (17). According to their different anatomic dimensions and pathophysiology, there were significant differences of SV(*), HR, and CO* for LBW and VLBW infants as well for inotropic treatment and ventilation mode.Conclusion: Extending recent publications on EV/TTE comparison in newborns, this study suggests that EV is also applicable in LWB/VLBW infants as a safe and easy to handle method for continuous CO monitoring in the NICU and PCICU.
DOI : doi:10.3389/fped.2014.00016
Cilt :2
ISSN :2296-2360
Sınıflandırma :
21
Oxygen, Gastrin-Releasing Peptide, and Pediatric Lung Disease: Life in the Balance.
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Kaynak :
Internet Archive Books
Dergi:
Frontiers in Pediatrics
Yayıncı:
Frontiers in Pediatrics
Yazar(lar) :
Mary E Sunday
Yıl :
2014
Frontiers in Pediatrics
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This article is from Frontiers in Pediatrics, volume 2. Abstract Excessive oxygen (O2) can cause tissue injury, scarring, aging, and even death. Our laboratory is studying O2-sensing pulmonary neuroendocrine cells (PNECs) and the PNEC-derived product gastrin-releasing peptide (GRP). Reactive oxygen species (ROS) generated from exposure to hyperoxia, ozone, or ionizing radiation (RT) can induce PNEC degranulation and GRP secretion. PNEC degranulation is also induced by hypoxia, and effects of hypoxia are mediated by free radicals. We have determined that excessive GRP leads to lung injury with acute and chronic inflammation, leading to pulmonary fibrosis (PF), triggered via ROS exposure or by directly treating mice with exogenous GRP. In animal models, GRP-blockade abrogates lung injury, inflammation, and fibrosis. The optimal time frame for GRP-blockade and the key target cell types remain to be determined. The concept of GRP as a mediator of ROS-induced tissue damage represents a paradigm shift about how O2 can cause injury, inflammation, and fibrosis. The host PNEC response in vivo may depend on individual ROS sensing mechanisms and subsequent GRP secretion. Ongoing scientific and clinical investigations promise to further clarify the molecular pathways and clinical relevance of GRP in the pathogenesis of diverse pediatric lung diseases.
DOI : doi:10.3389/fped.2014.00072
Cilt :2
ISSN :2296-2360
Sınıflandırma :
Biyotıp %100
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22
Reducing Auditory Hypersensitivities in Autistic Spectrum Disorder: Preliminary Findings Evaluating the Listening Project Protocol.
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Kaynak :
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Dergi:
Frontiers in Pediatrics
Yayıncı:
Frontiers in Pediatrics
Yazar(lar) :
Gregory F Lewis , Edwin H Cook , Keri J Heilman , Yevgeniya Sorokin , Nancy Carlson , Elgiz Bal , Olga V Bazhenova , Stephen W Porges
Yıl :
2014
Frontiers in Pediatrics
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This article is from Frontiers in Pediatrics, volume 2. Abstract Auditory hypersensitivities are a common feature of autism spectrum disorder (ASD). In the present study, the effectiveness of a novel intervention, the listening project protocol (LPP), was evaluated in two trials conducted with children diagnosed with ASD. LPP was developed to reduce auditory hypersensitivities. LPP is based on a theoretical “neural exercise” model that uses computer altered acoustic stimulation to recruit the neural regulation of middle ear muscles. Features of the intervention stimuli were informed by basic research in speech and hearing sciences that has identified the specific acoustic frequencies necessary to understand speech, which must pass through middle ear structures before being processed by other components of the auditory system. LPP was hypothesized to reduce auditory hypersensitivities by increasing the neural tone to the middle ear muscles to functionally dampen competing sounds in frequencies lower than human speech. The trials demonstrated that LPP, when contrasted to control conditions, selectively reduced auditory hypersensitivities. These findings are consistent with the polyvagal theory, which emphasizes the role of the middle ear muscles in social communication.
DOI : doi:10.3389/fped.2014.00080
Cilt :2
ISSN :2296-2360
Sınıflandırma :
23
Rethinking Molecular Mimicry in Rheumatic Heart Disease and Autoimmune Myocarditis: Laminin, Collagen IV, CAR, and B1AR as Initial Targets of Disease.
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Kaynak :
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Dergi:
Frontiers in Pediatrics
Yayıncı:
Frontiers in Pediatrics
Yazar(lar) :
Robert Root-Bernstein
Yıl :
2014
Frontiers in Pediatrics
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This article is from Frontiers in Pediatrics, volume 2. Abstract Rationale: Molecular mimicry theory (MMT) suggests that epitope mimicry between pathogens and human proteins can activate autoimmune disease. Group A streptococci (GAS) mimics human cardiac myosin in rheumatic heart disease (RHD) and coxsackie viruses (CX) mimic actin in autoimmune myocarditis (AM). But myosin and actin are immunologically inaccessible and unlikely initial targets. Extracellular cardiac proteins that mimic GAS and CX would be more likely.Objectives: To determine whether extracellular cardiac proteins such as coxsackie and adenovirus receptor (CAR), beta 1 adrenergic receptor (B1AR), CD55/DAF, laminin, and collagen IV mimic GAS, CX, and/or cardiac myosin or actin.Methods: BLAST 2.0 and LALIGN searches of the UniProt protein database were employed to identify potential molecular mimics. Quantitative enzyme-linked immunosorbent assay was used to measure antibody cross-reactivity.Measurements: Similarities were considered to be significant if a sequence contained at least 5 identical amino acids in 10. Antibodies were considered to be cross-reactive if the binding constant had a Kd less than 10-9 M.Main results: Group A streptococci mimics laminin, CAR, and myosin. CX mimics actin and collagen IV and B1AR. The similarity search results are mirrored by antibody cross-reactivities. Additionally, antibodies against laminin recognize antibodies against collagen IV; antibodies against actin recognize antibodies against myosin, and antibodies against GAS recognize antibodies against CX. Thus, there is both mimicry of extracellular proteins and antigenic complementarity between GAS-CX in RHD/AM.Conclusion: Rheumatic heart disease/AM may be due to combined infections of GAS with CX localized at cardiomyocytes that may produce a synergistic, hyperinflammatory response that cross-reacts with laminin, collagen IV, CAR, and/or B1AR. Epitope drift shifts the immune response to myosin and actin after cardiomyocytes become damaged.
DOI : doi:10.3389/fped.2014.00085
Cilt :2
ISSN :2296-2360
Sınıflandırma :
24
Mary Ellen Avery's Research Career - Remembrance of Things Past.
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Kaynak :
Internet Archive Books
Dergi:
Frontiers in Pediatrics
Yayıncı:
Frontiers in Pediatrics
Yazar(lar) :
John Steven Torday
Yıl :
2014
Frontiers in Pediatrics
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This article is from Frontiers in Pediatrics, volume 2. Abstract Mary Ellen Avery’s research is recognized as a milestone in biomedical research. She had discovered the underlying cause of hyaline membrane disease, surfactant deficiency, fostering ever more vigorous efforts to reduce neonatal mortality in the burgeoning practice of Neonatology. Neonatology is the only clinical discipline that began as an experiment, making it a model for biomedical research. Avery knew that the concerted effort to treat preterm newborns could potentially do more harm than good, violating her oath to Hippocrates, if not held to the highest scientific standards. She remained true to that pledge throughout her career, as recounted in this Review.
DOI : doi:10.3389/fped.2014.00034
Cilt :2
ISSN :2296-2360
Sınıflandırma :
25
A Comparison of the Different Animal Models of Fetal Alcohol Spectrum Disorders and Their Use in Studying Complex Behaviors.
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Dergi:
Frontiers in Pediatrics
Yayıncı:
Frontiers in Pediatrics
Yazar(lar) :
Brian R Christie , Christine J Fontaine , Anna R Patten
Yıl :
2014
Frontiers in Pediatrics
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This article is from Frontiers in Pediatrics, volume 2. Abstract Prenatal ethanol exposure (PNEE) has been linked to widespread impairments in brain structure and function. There are a number of animal models that are used to study the structural and functional deficits caused by PNEE, including, but not limited to invertebrates, fish, rodents, and non-human primates. Animal models enable a researcher to control important variables such as the route of ethanol administration, as well as the timing, frequency and amount of ethanol exposure. Each animal model and system of exposure has its place, depending on the research question being undertaken. In this review, we will examine the different routes of ethanol administration and the various animal models of fetal alcohol spectrum disorders (FASD) that are commonly used in research, emphasizing their strengths and limitations. We will also present an up-to-date summary on the effects of prenatal/neonatal ethanol exposure on behavior across the lifespan, focusing on learning and memory, olfaction, social, executive, and motor functions. Special emphasis will be placed where the various animal models best represent deficits observed in the human condition and offer a viable test bed to examine potential therapeutics for human beings with FASD.
DOI : doi:10.3389/fped.2014.00093
Cilt :2
ISSN :2296-2360
Sınıflandırma :
26
Minimally Invasive Surgery for Pediatric Tumors - Current State of the Art.
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Kaynak :
Internet Archive Books
Dergi:
Frontiers in Pediatrics
Yayıncı:
Frontiers in Pediatrics
Yazar(lar) :
Steven W Warmann , Guido Seitz , Jurgen F Schafer , Martin Ebinger , Luana Schafbuch , Jorg Fuchs
Yıl :
2014
Frontiers in Pediatrics
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This article is from Frontiers in Pediatrics, volume 2. Abstract During recent years, minimally invasive surgery (MIS) has become the standard approach for various operations in infants and children. This also holds true for surgery in children with solid tumors. Meanwhile, more and more oncological biopsies and resections are being performed laparoscopically or thoracoscopically. Despite its increasing role in pediatric tumor surgery, the different national and international multicenter trial groups have not yet implemented MIS within guidelines and recommendations in most of the current treatment protocols. An increasing number of reports describe a potential role of MIS in the different entities of pediatric surgical oncology. Over the time, there has been a diverse development of this approach with regard to the different neoplasms. The aim of this article is to give an overview and to describe the current state of the art of MIS in pediatric solid tumors.
DOI : doi:10.3389/fped.2014.00048
Cilt :2
ISSN :2296-2360
Sınıflandırma :
27
Epidemiology of Pediatric Acute Respiratory Distress Syndrome in Singapore: Risk Factors and Predictive Respiratory Indices for Mortality.
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Kaynak :
Internet Archive Books
Dergi:
Frontiers in Pediatrics
Yayıncı:
Frontiers in Pediatrics
Yazar(lar) :
Jan Hau Lee , Yee Hui Mok , Joo Guan Yeo , Daniela Testoni , Tsee Foong Loh , Judith Ju-Ming Wong
Yıl :
2014
Frontiers in Pediatrics
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This article is from Frontiers in Pediatrics, volume 2. Abstract Aim: Acute respiratory distress syndrome (ARDS) represents the most severe form of acute lung injury. The aim of our study is to describe the epidemiology of pediatric ARDS in Singapore and compare the outcomes of ARDS using the following respiratory indices: PaO2/FiO2 ratio (P/F ratio), SpO2/FiO2 ratio (S/F ratio), oxygenation index (OI), and oxygen saturation index (OSI).Methods: We examined medical records of patients admitted to the Children’s Intensive Care Unit in KK Women’s and Children’s Hospital from 2009 to 2012. Those who fulfilled criteria for the American-European Consensus Conference definition for ARDS were identified. Demographic, clinical, and radiographic information were extracted and analyzed.Results: We identified 70 patients with ARDS. Median age (interquartile range) was 6.2 (1.4, 10.4) years. The most common risk factor was pneumonia [50 (71%)]. Overall mortality was 44 (63%) patients. Thirty-two (56%) patients had an underlying chronic comorbidity; 18 (46%) were hematology–oncology conditions. Fifty-six (80%) patients had multiorgan dysfunction. Adjunct therapies used in our patients included inhaled nitric oxide [5 (7%)], prone position [22 (31%)], steroids [26 (37%)], and neuromuscular blockade [26 (37%)]. A high OI and low PF ratio after 24 h of diagnosis of ARDS were associated with mortality. From day 3 onward, all four respiratory indices appropriately differentiated survivors from non-survivors. Severity based on the S/F ratio and OSI demonstrated association with decreased ventilator free days and ICU free days.Conclusion: Risk factors for mortality included having an underlying comorbidity, multiorgan dysfunction, a low PF ratio, and high OI at 24 h of ARDS. Abnormal SpO2-based measurements were reliable markers of poor outcomes in pediatric ARDS.
DOI : doi:10.3389/fped.2014.00078
Cilt :2
ISSN :2296-2360
28
On Preventing the Extinction of the Physician-Scientist in Pediatric Pulmonology.
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Dergi:
Frontiers in Pediatrics
Yayıncı:
Frontiers in Pediatrics
Yazar(lar) :
James L Kreindler , Ronald C Rubenstein
Yıl :
2014
Frontiers in Pediatrics
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This article is from Frontiers in Pediatrics, volume 2. Abstract While the founders of Pediatric Pulmonology recognized the necessity of research as a vital part of the developing sub specialty, the field has struggled to develop and maintain physician-scientists and investigators. The clinical growth in Pediatric Pulmonology has resulted in significant challenges in career development faced by physician-scientists who aim to establish or maintain independent investigative programs. Such challenges may only be overcome with changes in how both trainees and established physician-scientists in Pediatric Pulmonology are supported.
DOI : doi:10.3389/fped.2014.00004
Cilt :2
ISSN :2296-2360
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