A. Francine Tryka

Clinical utility of flexible bronchoscopy and bronchoalveolar lavage in young children with recurrent wheezing.

OBJECTIVE The objective of this study was to determine in young children with recurrent wheezing poorly responsive to bronchodilator therapy whether flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) provide clinically useful information, whether age-specific differences are present in bronchoscopic and BAL fluid (BALF) findings, and whether differential cellular analysis of BALF is useful in suggesting an infectious or inflammatory process. DESIGN This was a retrospective case series with descriptive and analytical components. The study population included children referred to a large tertiary care childrens hospital subspecialty service for further evaluation of recurrent wheezing. Clinical and demographic data and findings of FB and BALF studies were collected from chart review. For purposes of data analysis patients were divided into 0- to 6-, 7- to 12-, and 13- to 18-month age groups. RESULTS Thirty otherwise healthy children, 0 to 18 months of age with recurrent wheezing, who had undergone FB were identified; and 28 were found to have positive diagnostic findings. Airway abnormalities were found in 17 (57%) and tended to be more common in the 0- to 6-month age group. In the 27 who also had BAL performed, 3 (11%) had a positive bacterial culture, 9 (33%) a positive viral culture, and 5 (19%) an elevated lipid-laden macrophage index suggesting aspiration. Differential cellular analysis was abnormal in 11 (41%), a finding that was significantly associated with a positive bacterial culture, a positive viral culture, or an elevated lipid-laden macrophage index. CONCLUSIONS In this population of young children with recurrent wheezing poorly responsive to bronchodilator therapy, FB and BAL yielded useful diagnostic findings in most children studied. In addition, in the presence of an infectious or inflammatory process, differential cellular analysis of BALF revealed an increased percentage of neutrophils.

Absence of Lamellar Bodies with Accumulation of Dense Bodies Characterizes a Novel Form of Congenital Surfactant Defect

Two female sibling full-term newborns developed respiratory distress shortly after birth, which progressed to respiratory failure. Tracheal lavage demonstrated presence of surfactant protein A (SP-A), but little surfactant protein B (SP-B), without aberrant surfactant protein C (SP-C). On a lung biopsy performed in both infants, prominent type II pneumocyte hyperplasia was evident. Through ultrastructural examination an absence of normally formed lamellar bodies was determined, with numerous irregular electron dense bodies within the type II pneumocytes. These electron dense bodies could also be identified in the alveolar spaces and alveolar macrophages. No alveolar tubular myelin was present. Abnormally high immunoreactivity for surfactant proteins SP-A, proSP-B, SP-B, and proSP-C was demonstrated by light microscopy. Presence of incompletely processed immunopositive proSP-B, but not proSP-C was observed in the alveolar lumina. No mutations in either the SP-B or SP-C gene were identified by sequence analysis of amplified cDNA. We conclude that these siblings exhibit an inherited surfactant deficiency characterized by abnormal accumulations of surfactant proteins within the pneumocytes. This abnormal accumulation may be due to a primary secretory defect, a defect in surfactant phospholipids, or an abnormal interaction between the phospholipids and surfactant proteins.

Cytogenetic Distinction among Benign Fibro-osseous Lesions of Bone in Children and Adolescents: Value of Karyotypic Findings in Differential Diagnosis

Benign fibro-osseous lesions of bone (BFOL) comprise a group of clinically distinct entities with significant histologic overlap and often occur in children and adolescents. Because of prior studies indicating that these lesions possess distinct karyotypic abnormalities, we conducted a retrospective review of cytogenetic analyses performed in a series of 16 BFOL in children and adolescents diagnosed at two institutions. These comprised five cases with the diagnosis of ossifying fibroma, four with osteofibrous dysplasia, and seven with fibrous dysplasia arising in the skeleton of 16 children and adolescents. All cases were analyzed using standard G-banding techniques on fresh tumors explanted in tissue culture media. Spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) were used to analyze selected metaphases of a talar lesion with the histologic features of ossifying fibroma. All four confirmed ossifying fibromas, including the talar lesion, contained clonal aberrations fusing breakpoints on Xq26 and 2q33, and one case with dissimilar histology did not. Three of four osteofibrous dysplasias contained multiple copies of chromosomes 8, 12, and/or 21. All but two fibrous dysplasia cases exhibited either a completely normal karyotype or single cell aberrations. One fibrous dysplasia had subtle chromosomal abnormalities not seen in other cases in the series, and another had complex abnormalities involving multiple chromosomes. Our current and published results indicate that cytogenetics might be of ancillary use in the diagnosis of BFOL and that a characteristic chromosomal arrangement is associated with ossifying fibroma.

Pulmonary macrophage antimicrobial activity in canine endotoxin shock and lung injury.

Bacterial sepsis and pneumonia are common complications of lung injury and predispose the host to a poor resolution. We studied the functional integrity of pulmonary macrophages derived from minced lung preparations in a canine model of endotoxin-induced shock with acute lung injury. Dogs given 2 mg/kg of Escherichia coli endotoxin 055:B5 developed classic shock symptoms with concomitant acute lung injury; control animals given saline showed no physiological or pathological abnormalities. Compared to previous work with this canine model, the lung injury in this extended time period (6 h) had progressed to include alveolar edema. Six hours after endotoxin infusion, the left lung was lavaged, perfused, and the resulting lung minced for isolation of pulmonary macrophages. The endotoxic-model pulmonary macrophages showed several significant functional differences from controls. Although they elicited greater production of H2O2 (p less than 0.05), both phagocytosis of radiolabeled Staphylococcus aureus and E. coli (p less than 0.05) and bactericidal activity (p less than 0.05) were diminished compared to controls. Compared to alterations previously described in alveolar macrophages, these cells produced less H2O2 and demonstrated abnormal bacterial killing at all time points. These observations suggest that the functional alterations of pulmonary macrophages that follow acute lung injury contribute to the ineffective cell-mediated antimicrobial response. These derangements may promote an increased risk of nosocomial pneumonia, the high mortality often observed subsequent to pneumonia, or the propagation of acute lung injury that facilitates respiratory failure.

Emergent Radio frequency Ablation of the AV Node in a Neonate with Unstable, Refractory Supraventricular Tachycardia

Supraventricular tachycardia due to accessory atrioventricular connections in infants is usually well‐tolerated. Rarely an infant can have Supraventricular tachycardia that is incessant and refractory to medical therapy. We describe a patient with Supraventricular tachycardia detected prenatally that caused severe cardiac dysfunction and hemodynamic instability after birth.

The effect of ibuprofen on endotoxin-induced injury in sheep

The reversible cyclooxygenase inhibitor, ibuprofen, has been found to have beneficial effects on the hemodynamic alterations of endotoxemia in several animal species. We investigated the effect of ibuprofen posttreatment on the hemodynamic and histologic alterations of endotoxin induced injury in awake sheep. Three groups of sheep were treated with either an infusion of Escherichia coli endotoxin followed five minutes later by saline, an infusion of E. coli endotoxin followed five minutes later by the administration of 10 mg/kg of ibuprofen, or saline infusions in controls. Hemodynamic parameters were monitored for six hours, and the sheep were then observed for an additional 18 hours. Ibuprofen treatment reversed the early pulmonary hypertensive changes and early hemodynamic alterations associated with endotoxemia. Associated with the hemodynamic improvement was significant inhibition of thromboxane synthesis as measured by the stable metabolite, thromboxane B 2 . All endotoxintreated animals had histologic evidence of acute lung injury at 24 hours as manifested by pulmonary endothelial and alveolar epithelial injury. Ibuprofen treatment decreased the mononuclear and interstitial macrophage cellular infiltrate compared to endotoxin alone. These results suggest that thromboxane may be involved in the pathogenesis of the early hemodynamic derangements of endotoxemia. Endotoxemia was associated with histologic and ultrastructural evidence of lung injury. A single dose of ibuprofen did not alter the degree of histologic lung injury observed.

A computer aided approach to electron energy loss spectroscopy and imaging

In this paper we present the design and configuration of an imaging system for electron energy loss spectroscopy (EELS) and electron spectrographic imaging (ESI). The interfacing of commercial off-the-shelf hardware, custom software and a transmission electron microscope containing integrated spectrographic capabilities produces results that are well suited for clinical applications. The custom design and integration of this system allows for full control over all of the methods and procedures employed. This full control and knowledge of the procedures used is not always possible with commercial packages. This custom software allowed for the definition and testing of a new procedure for the determination of the theoretical background image, and hence the ability to refine the overall sensitivity for elemental detection. To further the proof of elemental detection, a procedure for continuous scan of an area of interest while varying delta E can also be performed with this system.