This study demonstrated a higher rate of VPI after T&A in PW children as compared to another at-risk cohort, T21 patients. While the OAHI decreased after T&A in both groups, a significant number of children with PW or T21 had persistent OSA. Further investigation into the optimal management of OSA, while preventing treatment complications such as VPI, is needed for children with these high-risk conditions.

Cachexia and anorexia commonly occur in patients with cystic fibrosis (CF), particularly those with severe pulmonary compromise and heavy tracheobronchial colonization with Pseudomonas aeruginosa. Current understanding of the pathophysiology of cachexia attributes much of the anorexia and weight loss to the effects of the cytokine tumor necrosis factor (TNF), which is secreted by endotoxin-stimulated macrophages. It has further been suggested that TNF may play a role in the pathobiochemistry of CF cachexia, secondary to the localized inflammatory response in the lung or wider systemic activation of cells of the monocyte-macrophage series in response to endotoxin. This study investigates TNF production and gene expression by peripheral blood monocyte-derived macrophages from CF patients, compared with normals (NL). The results indicate that although both cell populations responded dose-dependently to lipopolysaccharide (LPS); CF macrophages, upon stimulation with LPS at concentrations of 1 to 1,000 ng/ml, consistently produced substantially higher amounts of TNF than NL macrophages. At the molecular level, Northern blot analysis also revealed that both macrophage populations expressed TNF mRNA in response to LPS in a dose-dependent manner. However, at the same LPS concentrations, CF macrophage TNF mRNA expression was 2- to 4-fold greater than that of NL macrophages. LPS had no effect in either macrophage population on mRNA for CHO-B, a constitutive probe. To investigate differences between NL and CF macrophage TNF regulation, nuclear run-on/half-life studies as well as studies addressing potential differences in LPS membrane interactions and signal transduction were performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric oxide (NO) appears to play an important role in regulating several biologic functions in the lung, including modulation of pulmonary arterial and bronchial smooth muscle tone. Recent studies have shown that relatively high concentrations of inhaled NO reduce the bronchoconstrictor effect of methacholine in animal models. This raises the possibility that NO inhalation might have therapeutic potential as an alternative bronchodilator. Although investigation of this potential in adults with airway reactivity or bronchial asthma has been reported, data are lacking on the role of NO in the pediatric asthma population. We therefore performed spirometry on 12 children with asthma (mean age 11.1 yrs) at baseline (B), immediately after inhaling 40 ppm NO (NO-1), 10 min after inhaling NO (NO-10), and after inhalation of a standard beta 2-agonist, albuterol (A). Baseline pulmonary functions (% predicted +/- SEM) were FVC of 103.2 +/- 5.6, FEV1 of 82.2 +/- 3.3, FEF-max of 97.0 +/- 3.6, and FEF25-75% of 53.5 +/- 3.3. There were no statistically significant differences between baseline and NO-1 or NO-10 between any of the four pulmonary function parameters measured. Inhaled albuterol, however, resulted in significant improvement (% predicted +/- SEM) in FVC to 109.8 +/- 3.5, FEV1 to 99.7 +/- 2.9, FEFmax to 106.5 +/- 5.1, and FEF25-75% to 84.4 +/- 6.4 compared with the baseline and NO inhalation groups. We conclude that NO inhaled at 40 ppm has no apparent bronchodilatory effect in pediatric subjects with asthma and mild airways disease. The clinical application of this gas as a therapeutic modality under these conditions is questionable.

UT 84 132, U.S.A.Our interest in the regulation of xanthine dehydrogenase/xanthine oxidase (XDH/XO) stems from studies suggesting a role for the enzyme in the pathobiochemistry of cellular Abbreviations used: HUVEC, human umbilical-vein endothelial cell; IL, interleukin; ROS, reactive oxygen species; XDH, xanthine dehydrogenase; XO, xanthine oxidase. *To whom correspondence should be addressed. injury in a wide variety of disorders including ischaemia-reperfusion [ 13, viral pneumonia [Z], sepsis [3] or haemorrhagic shock [4]. Most studies investigating the role of XDH/XO in pathogenesis have applied the axiom that the significance of XDH/XO as a mechanism for generation of reactive oxygen species (ROS) in tissues is determined primarily by the rate of conversion of XDH into XO (reviewed in [S]). However, recent molecular and biochemical approaches Volume 25

Reactive oxygen species have been implicated in the tissue injury and loss of epithelial barrier function associated with a number of clinical disorders in which disregulated inflammation seems to be a dominant event, such as endotoxemia and viral syndromes. In these disorders, xanthine oxidase (XO) contained within the epithelial cell has been proposed as a major source of injurious reactive oxygen species. This study was undertaken in an effort to understand the regulation of xanthine dehydrogenase (XDH)/XO expression at both the activity and gene expression levels in the epithelial cell under conditions associated with the inflammatory response. The results indicate that TNF, IFN-gamma, IL-6, IL-1, and dexamethasone induce XDH/XO activity in bovine renal epithelial cells (MDBK). This pattern of XDH/XO regulation by cytokines and steroids is analogous to the profile of response seen by acute phase reactants. Metabolic labeling and immunoprecipitation revealed the increase in XDH/XO activity requires new protein synthesis. By Northern analysis, all cytokines and dexamethasone increased the level of the 5-kb XDH/XO mRNA. This increase was not detectable in the presence of actinomycin D but was further induced in the presence of cycloheximide, consistent with the major site of XDH/XO up-regulation occurring at the transcriptional level. XDH/XO mRNA was very stable, with no indication that the rates of transcript degradation contributed to differences in mRNA accumulation or ultimate activity levels. In addition to providing information on the regulation of XDH/XO, the data presented furthers the understanding of the epithelial cell's potential to actively respond to immunomodulators associated with injury/inflammation.