Inconsequential role for chemerin-like receptor 1 in the manifestation of ozone-induced lung pathophysiology in male mice.

We executed this study to determine if chemerin-like receptor 1 (CMKLR1), a G protein-coupled receptor expressed by leukocytes and non-leukocytes, contributes to the development of phenotypic features of non-atopic asthma, including airway hyperresponsiveness (AHR) to acetyl-β-methylcholine chloride, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Accordingly, we quantified sequelae of non-atopic asthma in wild-type mice and mice incapable of expressing CMKLR1 (CMKLR1-deficient mice) following cessation of acute inhalation exposure to either filtered room air (air) or ozone (O), a criteria pollutant and non-atopic asthma stimulus. Following exposure to air, lung elastic recoil and airway responsiveness were greater while the quantity of adiponectin, a multi-functional adipocytokine, in bronchoalveolar lavage (BAL) fluid was lower in CMKLR1-deficient as compared to wild-type mice.

Interleukin-11 receptor subunit α-1 is required for maximal airway responsiveness to methacholine after acute exposure to ozone.

Interleukin (IL)-11, a multifunctional cytokine, contributes to numerous biological processes, including adipogenesis, hematopoiesis, and inflammation. Asthma, a respiratory disease, is notably characterized by reversible airway obstruction, persistent lung inflammation, and airway hyperresponsiveness (AHR). Nasal insufflation of IL-11 causes AHR in wild-type mice while lung inflammation induced by antigen sensitization and challenge, which mimics features of atopic asthma in humans, is attenuated in mice genetically deficient in IL-11 receptor subunit α-1 (IL-11Rα1-deficient mice), a transmembrane receptor that is required conjointly with glycoprotein 130 to transduce IL-11 signaling.

Chest compression by two-thumb encircling method generates higher carotid artery blood flow in swine infant model of cardiac arrest.

Objective: Two-Thumb(TT) technique provides superior quality chest compressions compared with Two-Finger(TF) in an instrumented infant manikin. Whether this translates to differences in blood flow, such as carotid arterial blood flow(CABF), has not been evaluated. We hypothesized that TT-CPR generates higher CABF and Coronary Perfusion Pressure(CPP) compared with TF-CPR in a neonatal swine cardiac arrest model.

Characteristics and Outcomes of Children with Clinical History of Atopic Non-atopic Asthma Admitted to a Tertiary Pediatric Intensive Care Unit.

Background: Children admitted to the Pediatric Intensive Care Unit (PICU) with status asthmaticus have variable clinical courses, and predicting their outcomes is challenging. Identifying characteristics in these patients that may require more intense intervention is important for clinical decision-making.

Objective: This study sought to determine the characteristics and outcomes, specifically length of stay and mortality, of atopic non-atopic asthmatics admitted to a PICU with status asthmaticus.

Chemokine (C-C Motif) Receptor-Like 2 is not essential for lung injury, lung inflammation, or airway hyperresponsiveness induced by acute exposure to ozone.

Inhalation of ozone (O), a gaseous air pollutant, causes lung injury, lung inflammation, and airway hyperresponsiveness. Macrophages, mast cells, and neutrophils contribute to one or more of these sequelae induced by O Furthermore, each of these aforementioned cells express chemokine (C-C motif) receptor-like 2 (Ccrl2), an atypical chemokine receptor that facilitates leukocyte chemotaxis. Given that Ccrl2 is expressed by cells essential to the development of O-induced lung pathology and that chemerin, a Ccrl2 ligand, is increased in bronchoalveolar lavage fluid (BALF) by O, we hypothesized that Ccrl2 contributes to the development of lung injury, lung inflammation, and airway hyperresponsiveness induced by O To that end, we measured indices of lung injury (BALF protein, BALF epithelial cells, and bronchiolar epithelial injury), lung inflammation (BALF cytokines and BALF leukocytes), and airway responsiveness to acetyl--methylcholine chloride (respiratory system resistance) in wild-type and mice genetically deficient in Ccrl2 (Ccrl2-deficient mice) 4 and/or 24 hours following cessation of acute exposure to either filtered room air (air) or O In air-exposed mice, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice.

Ventricular Fibrillation-Induced Cardiac Arrest Results in Regional Cardiac Injury Preferentially in Left Anterior Descending Coronary Artery Territory in Piglet Model.

. Decreased cardiac function after resuscitation from cardiac arrest (CA) results from global ischemia of the myocardium. In the evolution of postarrest myocardial dysfunction, preferential involvement of any coronary arterial territory is not known.

Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone.

Expression of plasminogen activator inhibitor (PAI)-1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O), a gaseous air pollutant. PAI-1 regulates expression of interleukin (IL)-6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O Given these observations, we hypothesized that PAI-1 contributes to the severity of the aforementioned sequelae by regulating expression of IL-6, KC, and MIP-2 following acute exposure to O To test our hypothesis, wild-type mice and mice genetically deficient in PAI-1 (PAI-1-deficient mice) were acutely exposed to either filtered room air or O (2 ppm) for 3 h. Four and/or twenty-four hours following cessation of exposure, indices of lung injury [bronchoalveolar lavage fluid (BALF) protein and epithelial cells], pulmonary inflammation (BALF IL-6, KC, MIP-2, macrophages, and neutrophils), and airway responsiveness to aerosolized acetyl-β-methylcholine chloride (respiratory system resistance) were measured in wild-type and PAI-1-deficient mice.

Is There a Role for the Enteral Administration of Serum-Derived Immunoglobulins in Human Gastrointestinal Disease and Pediatric Critical Care Nutrition?

Twenty years ago, there was profound, international interest in developing oral human, bovine, or chicken egg-derived immunoglobulin (Ig) for the prevention and nutritional treatment of childhood malnutrition and gastrointestinal disease, including acute diarrhea and necrotizing enterocolitis. Although such Ig products were shown to be effective, with both nutritional and antidiarrheal benefits, interest waned because of their cost and because of the perceived risk of bovine serum encephalitis (BSE). BSE is no longer considered a barrier to use of oral Ig, because the WHO has declared the United States to be BSE-free since the early 2000s.

Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure.

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF.

Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice.

Atopic, obese asthmatics exhibit airway obstruction with variable degrees of eosinophilic airway inflammation. We previously reported that mice obese as a result of a genetic deficiency in either leptin (ob/ob mice) or the long isoform of the leptin receptor (db/db mice) exhibit enhanced airway obstruction in the presence of decreased numbers of bronchoalveolar lavage fluid (BALF) eosinophils compared with lean, wild-type mice following antigen (ovalbumin; OVA) sensitization and challenge. To determine whether the genetic modality of obesity induction influences the development of OVA-induced airway obstruction and OVA-induced pulmonary inflammation, we examined indices of these sequelae in mice obese as a result of a genetic deficiency in carboxypeptidase E, an enzyme that processes prohormones and proneuropeptides involved in satiety and energy expenditure (Cpe(fat) mice).

Use of impedance threshold device in conjunction with our novel adhesive glove device for ACD-CPR does not result in additional chest decompression.

Objective: To evaluate the hemodynamic effects of using an adhesive glove device (AGD) to perform active compression-decompression CPR (AGD-CPR) in conjunction with an impedance threshold device (ITD) in a pediatric cardiac arrest model.

Design: Controlled, randomized animal study.

Methods: In this study, 18 piglets were anesthetized, ventilated, and continuously monitored.

Endogenous osteopontin promotes ozone-induced neutrophil recruitment to the lungs and airway hyperresponsiveness to methacholine.

Inhalation of ozone (O₃), a common environmental pollutant, causes pulmonary injury, pulmonary inflammation, and airway hyperresponsiveness (AHR) in healthy individuals and exacerbates many of these same sequelae in individuals with preexisting lung disease. However, the mechanisms underlying these phenomena are poorly understood. Consequently, we sought to determine the contribution of osteopontin (OPN), a hormone and a pleiotropic cytokine, to the development of O₃-induced pulmonary injury, pulmonary inflammation, and AHR.

Conivaptan therapy in an infant with severe hyponatremia and congestive heart failure.

Conivaptan is a nonspecific arginine vasopressin receptor antagonist that has been used as therapy in adults who have hypervolemic hyponatremia due to congestive heart failure. Its use in children with congestive heart failure has not been reported. We describe the use of conivaptan in a 4-month-old infant girl with severe hypervolemic hyponatremia and heart failure.

Novel adhesive glove device (AGD) for active compression-decompression (ACD) CPR results in improved carotid blood flow and coronary perfusion pressure in piglet model of cardiac arrest.

Objective: ACD-CPR improves coronary and cerebral perfusion. We developed an adhesive glove device (AGD) and hypothesized that ACD-CPR using an AGD provides better chest decompression resulting in improved carotid blood flow as compared to standard (S)-CPR.

Design: Prospective, randomized and controlled animal study.

Two-thumb technique is superior to two-finger technique during lone rescuer infant manikin CPR.

Objective: Infant CPR guidelines recommend two-finger chest compression with a lone rescuer and two-thumb with two rescuers. Two-thumb provides better chest compression but is perceived to be associated with increased ventilation hands-off time. We hypothesized that lone rescuer two-thumb CPR is associated with increased ventilation cycle time, decreased ventilation quality and fewer chest compressions compared to two-finger CPR in an infant manikin model.

Improved chest recoil using an adhesive glove device for active compression-decompression CPR in a pediatric manikin model.

Objective: We developed an adhesive glove device (AGD) to perform ACD-CPR in pediatric manikins, hypothesizing that AGD-ACD-CPR provides better chest decompression compared to standard (S)-CPR.

Design: Split-plot design randomizing 16 subjects to test four manikin-technique models in a crossover fashion to AGD-ACD-CPR vs. S-CPR.

Effect of alternative chest compression techniques in infant and child on rescuer performance.

Objective: Current chest compression (CC) guidelines for an infant recommend a two-finger (TF) technique with lone rescuer and a two- thumb (TT) technique with two rescuers, and for a child either an one hand (OH) or a two hand (TH) technique with one or two rescuers. The effect of a 30:2 compression:ventilation ratio using these techniques on CC quality and rescuer fatigue is unknown. We hypothesized that during lone rescuer CC, TT technique, in infant and TH in child achieve better compression depth (CD) without additional rescuer fatigue compared with TF and OH, respectively.

Transient ventricular dysfunction after an asphyxiation event: stress or hypoxia?

Objective: This report of a pediatric patient with acute upper airway obstruction causing asphyxiation emphasizes the need to maintain clinical suspicion for acquired myocardial dysfunction, despite the presumed role of noncardiogenic causes for pulmonary edema after an acute upper airway obstruction.

Design: Case report.

Setting: A tertiary pediatric intensive care unit.

Outcome following cardiopulmonary arrest.

This article summarizes the current state of outcomes and outcome predictors following pediatric cardiopulmonary arrest with special emphasis on neurologic outcome. The authors briefly describe the factors associated with outcome and review clinical signs, electrophysiology, neuroimaging, and biomarkers used to predict outcome after cardiopulmonary arrest. Although clinical signs, imaging, and somatosensory evoked potentials are best associated with outcome, there are limited data to guide clinicians.

Chest compression quality and rescuer fatigue with increased compression to ventilation ratio during single rescuer pediatric CPR.

Objective: The effects of the recommended 30:2 compression:ventilation (C:V) ratio on chest compression rate (CR), compression depth (CD), compression pressure (CP) and rescuer fatigue is unknown during pediatric CPR. We hypothesized that a 30:2 C:V ratio will decrease compression depth and compression pressure and increase rescuer fatigue compared with a 15:2 ratio.

Design: Randomized crossover observational study.

Analysis of the evidence for the lower limit of systolic and mean arterial pressure in children.

Objective: Systolic blood pressure (SBP) and mean arterial pressure (MAP) are essential evaluation elements in ill children, but there is wide variation among different sources defining systolic hypotension in children, and there are no normal reference values for MAP. Our goal was to calculate the 5th percentile SBP and MAP values in children from recently updated data published by the task force working group of the National High Blood Pressure Education Program and compare these values with the lowest limit of acceptable SBP and MAP defined by different sources.

Design: Mathematical analysis of clinical database.

Ventilator Y-piece pressure compared with intratracheal airway pressure in healthy intubated children.

Objective: Compare airway pressure measurements at the ventilator Y-piece of the breathing circuit (P( Y )) to intratracheal pressure measured at the distal end (P( T )) of the endotracheal tube (ETT) during mechanical ventilation and spontaneous breathing of intubated children.

Methods: Thirty children (age range 29 days to 5 years) receiving general anesthesia were intubated with an ETT incorporating a lumen embedded in its sidewall that opened at the distal end to measure P( T ). Peak inflation pressure (PIP) was measured at P( Y ) and P( T ) during positive pressure ventilation.

Pediatric critical care community survey of knowledge and attitudes toward therapeutic hypothermia in comatose children after cardiac arrest.

Objective: Therapeutic hypothermia improves neurologic outcome and survival after adult out-of-hospital cardiac arrest. To help us design a prospective hypothermia trial in children, we developed a survey to assess current knowledge and attitude of pediatric critical care providers regarding therapeutic hypothermia and potential impediments to implementing a prospective study.

Design: Anonymous survey.

Intravascular infusion of acid promotes intrapulmonary inducible nitric oxide synthase activity and impairs blood oxygenation in rats.

Objective: To test the hypothesis that intravascular acid infusion promotes intrapulmonary nitric oxide formation by promoting inducible nitric oxide synthase (iNOS) and inhibiting endothelial nitric oxide synthase (eNOS) expression in rats.

Design: Prospective, placebo controlled, randomized laboratory study.

Setting: University laboratory.

Dexamethasone suppresses iNOS yet induces GTPCH and CAT-2 mRNA expression in rat lungs.

The in vivo mechanisms by which glucocorticoids inhibit nitric oxide expression await detailed investigation. In cell culture experiments, glucocorticoids have been shown to inhibit inducible nitric oxide synthase (iNOS) formation and activity. Glucocorticoids can inhibit iNOS activity in cultured cells by blocking arginine transport and inhibiting tetrahydrobiopterin biosynthesis.