Infant lung function testing in the intensive care unit.

As a result of the previous shortage of tools to assess objectively the overall physiological status of the respiratory system in infants and young children, it has been difficult to measure the degree of physiological disorder or the response to therapy in respiratory diseases such as BPD, the pediatric version of ARDS, bronchiolitis, pneumonia, asthma and croup in this patient population. The newborn- four-year old child is particularly difficult to study because of their lack of cooperation and size. The recent progress in computer technology made pulmonary function testing available for this age range and opened up new possibilities for monitoring changes in disease processes affecting the respiratory system.

Albuterol responsiveness in infants with respiratory failure caused by respiratory syncytial virus infection.

Objective: To assess the bronchodilator effect of inhaled albuterol in the acute stage of severe respiratory syncytial virus (RSV) infection.

Design: Prospective, nonrandomized study of previously healthy infants who underwent intubation and whose lungs were ventilated because of respiratory failure caused by RSV infection. Ten infants with an endotracheal tube in place and without lung disease were matched for age and weight and served as normal control subjects.

Successful use of transesophageal echocardiography during extracorporeal membrane oxygenation in infants after cardiac operations.

We report the use of transesophageal echocardiography in infants after cardiac operations while supported on extracorporeal membrane oxygenation. In all patients transesophageal echocardiography provided valuable information when standard transthoracic echocardiographic evaluation was limited by poor acoustic windows. This report describes the application of transesophageal echocardiography during extracorporeal membrane oxygenation after cardiac operations.

Vertebral size in elderly women with osteoporosis. Mechanical implications and relationship to fractures.

Reductions in bone density are a major determinant of vertebral fractures in the elderly population. However, women have a greater incidence of fractures than men, although their spinal bone densities are comparable. Recent observations indicate that women have 20-25% smaller vertebrae than men after accounting for differences in body size.

Ventilatory responses to repeated short hypercapnic challenges.

In early phases of respiratory disease, patients are more likely to experience intermittent hypercapnia than a continuous increase in PCO2. The effect of intermittent arterial PCO2 elevation on subsequent breathing patterns is unclear. To examine this issue, a series of six ventilatory challenges (CH1-CH6), consisting of 2 min of breathing 5% CO2 in O2, followed by 5 min in room air (RA) were performed in 10 naive healthy subjects (age 12-39 yr).

Validation of the phase angle technique as an objective measure of upper airway obstruction.

Thoraco-abdominal asynchrony (TAA) during upper airway obstruction (UAO) in small children can be documented by phase angle analysis of the Lissajous figure from the output of a noncalibrated respiratory inductance plethysmograph. Phase angle measurements have not been related to levels of inspiratory resistance, nor to the effect of breathing a 79% helium-21% oxygen mixture (heliox) during inspiratory resistance. We examined the effects of graded inspiratory loading (5-1000 cm H2O/L/sec) on TAA as measured by phase angle in 10 male, anesthetized, and intubated Rhesus monkeys, breathing room air and heliox.

Differential expression of cyclin D2 and cdc2 genes in proliferating and nonproliferating alveolar epithelial cells.

Alveolar epithelial cells (AEC) proliferate during embryonic and fetal life, while in the adult lung AEC form a highly differentiated population that does not usually divide. Herein, we tested the hypothesis that differential expression of specific cell cycle control genes may occur during AEC development and transformation. We compared normal rat AEC in primary culture with transformed AEC for the expression of D-type G1 cyclins and cyclin-dependent protein kinases (cdc2 and cdk2).

Thalamic NMDA receptors in the gamma-hydroxybutyrate model of absence seizures: a cerebral microinjection study in rats.

The possible role of thalamic NMDA receptors in the generation of experimental absence-like seizures was studied in rats. Bilaterally synchronous spike wave discharges were induced by gamma-hydroxybutyric acid (GHB) and were recorded simultaneously from different thalamic nuclei and the layers I-IV of frontoparietal cortex. Bilateral infusions of NMDA into thalamic mediodorsal nucleus, the intralaminar central lateral/paracentral nucleus, ventroposterolateral, or reticular nucleus of the thalamus in conscious rats, prior to GHB administration suppressed GHB-induced SWD in a dose dependent manner.

Identification, assay, and purification of a Cdc2-activating threonine-161 protein kinase from human cells.

The biological activities of cyclin-dependent, proline-directed protein kinases (PDPKs) are highly regulated by a complex series of protein phosphorylation/dephosphorylation reactions involving both catalytic and regulatory subunits. In this paper we report on the enzymatic activation of p34cdc2/p58Cyclin A PDPK by a protein kinase present in human cells that targets threonine-161 of Cdc2. An assay for this Cdc2 kinase-kinase (PK161) was developed and specific enzyme activity was detected in a variety of mammalian cells and tissues.

Bactericidal/permeability-increasing protein protects vascular endothelial cells from lipopolysaccharide-induced activation and injury.

Bactericidal/permeability-increasing protein (BPI), a human neutrophil granule protein, has been shown to bind lipopolysaccharide (LPS) and neutralize LPS-mediated cytokine production in adherent monocytes and the whole-blood system. In this study we investigated the ability of recombinant human BPI (rBPI) to inhibit LPS-induced vascular endothelial cell (EC) injury and activation. rBPI inhibited significantly both rough and smooth LPS-mediated injury for cultured bovine brain microvessel ECs, as measured by lactic dehydrogenase release, and blocked the LPS-induced interleukin-6 (IL-6) release from human umbilical vein ECs in a dose-dependent manner.

Transesophageal echocardiography in the postoperative child with an open sternum.

We report the use of transesophageal echocardiography in 3 children whose sternums remained open for several days postoperatively. In these patients transesophageal echocardiography provided critical information when transthoracic echocardiography was ineffective due to limited acoustic windows. This report points out the application of transesophageal echocardiography in children with chest wall distortion.

Cuffed endotracheal tubes in pediatric intensive care.

We prospectively studied 282 consecutive tracheal intubations (243 patients) in a pediatric intensive care unit during a 7-month period to compare cuffed and uncuffed endotracheal tube (ETT) utilization and outcome. The incidence of postextubation stridor in each ETT group was the major outcome measure after controlling for various patient risk factors. Patients whose ETTs were inserted in the operating room, who were less than 1 year of age, or who had ETTs in place for less than 72 hours were more likely to have had insertion of an uncuffed ETT.

Maturational differences in step vs. ramp hypoxic and hypercapnic ventilatory responses.

The influence of the speed of stimulus presentation on hypoxic and hypercapnic ventilatory responses (step vs. ramp) is not known. Furthermore, it is unclear whether children and adults respond similarly.

Cell cycle-dependent expression of cyclin D1 and a 45 kD protein in human A549 lung carcinoma cells.

Cyclin D1, which is suggested to have a role in G1 control during the cell cycle, is genetically linked to BCL-1 and is widely overexpressed in parathyroid, breast, and squamous cancer cells. We postulated that cyclin D1 regulation may also be important in lung cancer. Therefore, we characterized the cell cycle-dependent expression of cyclin D1 at both mRNA and protein levels in synchronized human A549 lung carcinoma cells.

Protein tyrosine phosphatase inhibitors block myeloid signal transduction through the Fc gamma RI receptor.

Fc-receptor stimulation in certain myeloid cells results in an increase in oxygen consumption termed the respiratory burst. In this report we examine the effects of protein tyrosine phosphatase inhibitors on the Fc gamma receptor-induced myeloid respiratory burst. Antiphosphotyrosine immunoblotting of neutrophils stimulated with opsonized oil particles shows that Fc-receptor stimulation is associated with the tyrosine phosphorylation of cellular proteins.

Ventilatory responses during wakefulness in children with obstructive sleep apnea.

The pathophysiology of the obstructive sleep apnea syndrome (OSAS) is not fully understood. In children, airway obstruction secondary to tonsilloadenoidal hypertrophy is the leading cause of OSAS. However, not all children with tonsilloadenoidal hypertrophy develop OSAS.

Predictors of neonatal mortality in 1,500-1,999 g premature infants with respiratory failure. Basis for ECMO Therapeutic Trial.

Despite the introduction of new ventilation techniques and surfactant therapy, some premature infants still experience severe respiratory failure and either die or survive with severe bronchopulmonary dysplasia. Extracorporeal membrane oxygenation is currently not offered for preterm infants with a birth weight less than 2,000 g, mainly because of the potential high risk for intracranial hemorrhage. The aim of this study was to determine risk predictors for mortality alone and for mortality or major lung morbidity in 1,500-1,999 g premature infants with respiratory failure.

Developmental pattern of hypercapnic and hypoxic ventilatory responses from childhood to adulthood.

The developmental pattern of ventilatory responses, through childhood and puberty into adulthood, is not known. Therefore we studied hypercapnic (HCVR) and hypoxic ventilatory responses (HOVR) in 59 subjects (29 males and 30 females) 4-49 yr of age, of whom 35 were children ( < 18 yr old). There was a significant correlation between HCVR and weight (r = 0.

Pediatric renal cell carcinoma: a complete response to recombinant interleukin-2 in a child with metastatic disease at diagnosis.

Renal cell carcinoma is a rare pediatric malignancy that appears to have a similar clinical outcome in children and adults. We review the experience of Childrens Hospital Los Angeles and compare it with the published pediatric series, reporting on seven cases from 1954 to the present. As in earlier pediatric series, we find that Stage I/II patients do well (five of five complete responses with prolonged disease-free survival) with surgical resection.

Umbilical cord blood cell transduction by retroviral vectors: preclinical studies to optimize gene transfer.

Human umbilical cord blood (UCB) can be a source of hematopoietic stem cells for gene therapy, as an alternative to allogeneic bone marrow transplantation, for the treatment of a number of genetic diseases. To determine conditions that yield maximal gene transfer into UCB progenitor cells, we examined a number of variables. We used cell-free retroviral vector supernatants that convey neomycin (G418) resistance and measured the percentage of G418-resistant progenitor-derived colonies.

Development of a shape vector that identifies critical forms assumed by human polymorphonuclear neutrophils during chemotaxis.

Human polymorphonuclear neutrophils undergo characteristic shape changes that are critical to their ability to move and ingest their targets. We present here the construction of a simple shape vector, calculated from the coordinates of the cell perimeter, that can identify critical forms that a neutrophil assumes during the course of ameboid movement. The vector can be used to find neutrophils of a specific shape from the image analyzer data produced during a typical neutrophil tracking experiment.

Effect of hypogonadism and deficient calcium intake on bone density in patients with galactosemia.

Forty children and adults with classic galactosemia had vertebral bone density determined by standard quantitative computed tomography at 3.4 to 44.2 years of age.

Role of epidermal growth factor expression in early mouse embryo lung branching morphogenesis in culture: antisense oligodeoxynucleotide inhibitory strategy.

Epidermal growth factor (EGF) expression and branching morphogenesis were inhibited using a 5' 15-mer antisense oligodeoxynucleotide (ODN) directed against EGF precursor mRNA in embryonic mouse lung in culture under chemically defined, serumless conditions. Antisense EGF ODN resulted in > 90% inhibition of EGF immunoreactive peptide synthesis, 75% reduction in branching morphogenesis, 73% decrease in DNA content, 64% decrease in RNA content, 73% decrease in protein synthesis, and 65% decrease in [3H]thymidine incorporation into DNA compared to Embryonic Day 11 controls in culture for 4 days. Sense ODN results were similar to control.

Cyclin A expression in normal and transformed alveolar epithelial cells.

The mature adult alveolar epithelial cell (AEC) is a highly differentiated phenotype that does not readily divide and exhibits numerous specialized functions. Yet, transformed AEC proliferate aggressively in certain forms of lung cancer. Normal AEC also proliferate but in a coordinated manner during embryonic growth and fetal development as well as during lung repair.