218 results match your criteria: "Pediatric Heart Lung Center[Affiliation]"

Purpose: To prospectively examine the relationship between prenatal events, postnatal airway host response and microbiota, and clinical outcomes.

Materials And Methods: Tracheal aspirates collected at seven days of age from 71 mechanically ventilated infants (median gestational age (GA), 25 weeks [range 23-28]) were simultaneously processed for a 12-plex protein assay and bacterial identification by 16S rRNA sequencing. Phenotypes were determined by unsupervised clustering of the protein analytes.

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Optical tissue clearing has revolutionized researchers' ability to perform fluorescent measurements of molecules, cells, and structures within intact tissue. One common complication to all optically cleared tissue is a spatially heterogeneous refractive index, leading to light scattering and first-order defocus. We designed C-DSLM (cleared tissue digital scanned light-sheet microscopy) as a low-cost method intended to automatically generate in-focus images of cleared tissue.

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Quantifying three-dimensional rodent retina vascular development using optical tissue clearing and light-sheet microscopy.

J Biomed Opt

July 2017

University of Colorado Denver, Department of Physics, Denver, Colorado, United StatesbUniversity of Colorado Anschutz Medical Campus, Pediatric Heart Lung Center, Department of Pediatrics, Aurora, Colorado, United States.

Retinal vasculature develops in a highly orchestrated three-dimensional (3-D) sequence. The stages of retinal vascularization are highly susceptible to oxygen perturbations. We demonstrate that optical tissue clearing of intact rat retinas and light-sheet microscopy provides rapid 3-D characterization of vascular complexity during retinal development.

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Pediatric pulmonary vascular disease (PVD) and pulmonary hypertension (PH) represent phenotypically and pathophysiologically diverse disease categories, contributing substantial morbidity and mortality to a complex array of pediatric conditions. Here, we review the multifactorial nature of pediatric PVD, with an emphasis on improved recognition, phenotyping, and endotyping strategies for pediatric PH. Novel tailored approaches to diagnosis and treatment in pediatric PVD, as well as the implications for long-term outcomes, are highlighted.

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Objectives: To determine the assessment and inter-rater reliability of echocardiographic evaluations of pulmonary vascular disease (PVD) in preterm infants at risk for bronchopulmonary dysplasia.

Study Design: We prospectively studied echocardiograms from preterm infants (birthweights 500-1250 g) at 7 days of age and 36 weeks postmenstrual age (PMA). Echocardiograms were assessed by both a cardiologist on clinical service and a single research cardiologist.

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Rationale: Mechanisms contributing to chronic lung disease after preterm birth are incompletely understood.

Objectives: To identify antenatal risk factors associated with increased risk for bronchopulmonary dysplasia (BPD) and respiratory disease during early childhood after preterm birth, we performed a prospective, longitudinal study of 587 preterm infants with gestational age less than 34 weeks and birth weights between 500 and 1,250 g.

Methods: Data collected included perinatal information and assessments during the neonatal intensive care unit admission and longitudinal follow-up by questionnaire until 2 years of age.

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Airway Microbial Community Turnover Differs by BPD Severity in Ventilated Preterm Infants.

PLoS One

August 2017

The Pediatric Heart-Lung Center, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, Colorado, United States of America.

Preterm birth exposes the developing lung to an environment with direct exposure to bacteria, often facilitated by endotracheal intubation. Despite evidence linking bacterial infections to the pathogenesis of bronchopulmonary dysplasia (BPD), systematic studies of airway microbiota are limited. The objective was to identify specific patterns of the early respiratory tract microbiome from tracheal aspirates of mechanically ventilated preterm infants that are associated with the development and severity of BPD.

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Unlabelled: Intrauterine growth restriction (IUGR) increases the incidence of adult cardiovascular disease (CVD). The sex-specific developmental mechanisms for IUGR-induced and Western high-fat diet (HFD) modification of CVD remain poorly understood. We hypothesized a maternal HFD in the Sprague-Dawley rat would augment IUGR-induced CVD in the offspring through decreased cardiac function and increased extracellular matrix (ECM) remodeling and stiffness in a sex-specific manner.

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Preeclampsia (PE) is a pregnancy-specific disease characterized by the new onset of hypertension and proteinuria. Mothers with PE are known to develop endothelial dysfunction, but its effect on infants has been understudied, as newborns are often asymptomatic. Recent studies indicate that infants born from preeclamptic pregnancies develop endothelial dysfunction including higher blood pressure during childhood and an increased risk of stroke later in life.

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Bronchopulmonary dysplasia (BPD) is the chronic lung disease associated with premature birth, characterized by impaired vascular and alveolar growth. In neonatal rats bleomycin decreases lung growth and causes pulmonary hypertension (PH), which is poorly responsive to nitric oxide. In the developing lung, through Rho kinase (ROCK) activation, ET-1 impairs endothelial cell function; however, whether ET-1-ROCK interactions contribute to impaired vascular and alveolar growth in experimental BPD is unknown.

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Objectives: To determine the frequency of histologic features of impaired lung vascular and alveolar development and to identify the presence of intrapulmonary bronchopulmonary anastomoses (IBA) in infants and children who died with Down syndrome.

Study Design: A retrospective review of autopsy reports and lung histology from 13 children with Down syndrome (ages: 0-8 years) was performed. Histologic features of abnormal lung development were identified and semiquantified, including the presence of IBA.

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New guidelines for managing pulmonary hypertension: what the pediatrician needs to know.

Curr Opin Pediatr

October 2016

Pediatric Heart Lung Center, Section of Pediatric Pulmonary Medicine, Department of Pediatrics, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.

Purpose Of Review: Pediatric pulmonary vascular disease contributes to morbidities and death in diverse clinical settings, ranging from idiopathic or heritable forms of pediatric arterial hypertension, congenital heart disease, developmental lung disorders, chronic lung disease, left heart disease, sickle cell disease, oncologic disease, and systemic disorders. Despite its impact on the clinical courses in so many diseases, information is limited on how to best approach the diagnosis and evaluation of pediatric pulmonary hypertension.

Recent Findings: To address this issue, a group of clinical experts from several subspecialties, including pulmonology, cardiology, neonatology, and others, were selected to form a task force to tackle this topic with support from the American Heart Association and American Thoracic Society.

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Background And Aims: Infants with Down syndrome (DS) or Trisomy 21, are at high risk for developing pulmonary arterial hypertension (PAH), but mechanisms that increase susceptibility are poorly understood. Laboratory studies have shown that early disruption of angiogenesis during development impairs vascular and alveolar growth and causes PAH. Human chromosome 21 encodes known anti-angiogenic factors, including collagen18a1 (endostatin, ES), ß-amyloid peptide (BAP) and Down Syndrome Critical Region 1 (DSCR-1).

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There Is No "I" in Team: New Challenges for Career Development in the Era of Team Science.

J Pediatr

October 2016

Pediatric Heart Lung Center, Section of Pulmonary Medicine, Department of Pediatrics, University of Colorado, School of Medicine, Aurora, CO.

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 The clinical needs of infants with severe bronchopulmonary dysplasia (BPD) that remain ventilator-dependent are complex, and management strategies that optimize survival and long-term outcomes controversial. We hypothesized that an interdisciplinary ventilator care program (VCP), committed to the care of this population will improve survival through standardized approaches to cardiopulmonary care and related comorbidities, enhanced communication, and continuity of care.  Retrospective chart reviews were performed on patients at Children's Hospital Colorado's neonatal intensive care unit, who underwent tracheostomy placement between 2000 and 2013.

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Impaired vascular endothelial growth factor (VEGF) signaling contributes to the pathogenesis of bronchopulmonary dysplasia (BPD). We hypothesized that the effects of VEGF on lung structure during development may be mediated through its downstream effects on both endothelial nitric oxide synthase (eNOS) and hepatocyte growth factor (HGF) activity, and that, in the absence of eNOS, trophic effects of VEGF would be mediated through HGF signaling. To test this hypothesis, we performed an integrative series of in vitro (fetal rat lung explants and isolated fetal alveolar and endothelial cells) and in vivo studies with normal rat pups and eNOS(-/-) mice.

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Objective: Children who require chronic mechanical ventilation via tracheostomy are medically complex and require prolonged hospitalization, placing a heavy burden on caregivers and hospital systems. We developed an interdisciplinary Ventilator Care Program to relieve this burden, through improved communication and standardized care. We hypothesized that a standardized team approach to the discharge of tracheostomy- and ventilator-dependent children would decrease length of stay (LOS), reduce patient costs, and improve safety.

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Pulmonary Hypertension and Vascular Abnormalities in Bronchopulmonary Dysplasia.

Clin Perinatol

December 2015

Section of Pulmonary Medicine, Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado, School of Medicine, Mail Stop B395, 13123 East 16th Avenue, Aurora, CO 80045, USA.

Despite advances in the care of preterm infants, these infants remain at risk bronchopulmonary dysplasia (BPD), which results in prolonged need for supplemental oxygen, recurrent respiratory exacerbations, and exercise intolerance. Recent investigations have highlighted the important contribution of the developing pulmonary circulation to lung development, showing that these infants are also at risk for pulmonary vascular disease (PVD), including pulmonary hypertension (PH) and pulmonary vascular abnormalities. Several epidemiologic studies have delineated the incidence of PH in preterm infants and the impact on outcomes.

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VEGF and endothelium-derived retinoic acid regulate lung vascular and alveolar development.

Am J Physiol Lung Cell Mol Physiol

February 2016

Department of Medicine, University of California, San Francisco, San Francisco, California; and

Prevention or treatment of lung diseases caused by the failure to form, or destruction of, existing alveoli, as observed in infants with bronchopulmonary dysplasia and adults with emphysema, requires understanding of the molecular mechanisms of alveolar development. In addition to its critical role in gas exchange, the pulmonary circulation also contributes to alveolar morphogenesis and maintenance by the production of paracrine factors, termed "angiocrines," that impact the development of surrounding tissue. To identify lung angiocrines that contribute to alveolar formation, we disrupted pulmonary vascular development by conditional inactivation of the Vegf-A gene during alveologenesis.

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High pulmonary vascular resistance (PVR), proximal pulmonary artery (PA) impedance, and right ventricular (RV) afterload due to remodeling contribute to the pathogenesis and severity of pulmonary hypertension (PH). Intra-amniotic exposure to endotoxin (ETX) causes sustained PH and high mortality in rat pups at birth, which are associated with impaired vascular growth and RV hypertrophy in survivors. Treatment of ETX-exposed pups with antenatal vitamin D (vit D) improves survival and lung growth, but the effects of ETX exposure on RV-PA coupling in the neonatal lung are unknown.

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We examined lung histology from 8 infants who died with meconium aspiration syndrome in order to determine the presence of intrapulmonary bronchopulmonary anastomotic pathways. Each infant required mechanical ventilation to treat hypoxemic respiratory distress. Lung histology from each infant shows evidence of prominent bronchopulmonary vascular connections.

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Vitamin D [vit D; 1,25-(OH)2D] treatment improves survival and lung alveolar and vascular growth in an experimental model of bronchopulmonary dysplasia (BPD) after antenatal exposure to endotoxin (ETX). However, little is known about lung-specific 1,25-(OH)2D3 regulation during development, especially regarding maturational changes in lung-specific expression of the vitamin D receptor (VDR), 1α-hydroxylase (1α-OHase), and CYP24A1 during late gestation and the effects of antenatal ETX exposure on 1,25-(OH)2D3 metabolism in the lung. We hypothesized that vit D regulatory proteins undergo maturation regulation in the late fetal and early neonatal lung and that prenatal exposure to ETX impairs lung growth partly through abnormal endogenous vit D metabolism.

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