Search

The treatment of children with asthma has historically relied upon expert opinion using data extrapolated from adult studies. Over the past few years, landmark studies have been completed providing healthcare professionals with evidence on which a reasonable approach can be made for children suffering from this common and serious disease. Asthmatic phenotype in children, unlike adults, tends to differ according to age, which must be taken into account as well as triggers, severity, and level of control. The care of the child with asthma is complex, but accumulating data have demonstrated that we are on the right path for optimizing control while reducing the burden of side effects. The newest Global Initiative for Asthma (GINA) guidelines, as well as recent updates from the landmark CAMP (Childhood Asthma Management Program) study and information from the PACT (Pediatric Asthma Control Trial) and budesonide/formoterol controller and reliever studies, along with recent com- parisons of higher dose inhaled corticosteroids (ICS), and ICS/long-acting 32-adrenoceptor agonist (LABA) combination and leukotriene receptor antagonist (LTRA) therapies in children have clarified a few of the big questions in pediatric asthma. For children with asthma aged 5 years and older, the CAMP trial demonstrated that regular use of ICS reduces the frequency of symptoms; however, height was adversely affected and there is no evidence for altering the natural history of asthma. In patients aged 6 years and over whose asthma is uncontrolled on ICS alone, combination therapy with ICS and a LABA has been recently compared with the use of higher dose ICS and the addition of an LTRA in pediatric patients. The addition of a LABA statistically will be of most benefit; however, some children will have optimal control with doubling the baseline dose of ICS or addition of an LTRA. Use of budesonide/formoterol as a controller and reliever therapy extends the time to first exacerbation versus contemporary use of this medication in patients aged 4 years and older. Ciclesonide, a newer ICS, has demonstrated acceptable efficacy but has the added benefit of not affecting growth. Certainly, with mounting evidence, the care-map in pediatric asthma control is becoming clearer. [ABSTRACT FROM AUTHOR]

Objectives. The Internet permits unprecedented and mostly unrestricted access to medical knowledge; however, concerns exist regarding viewer privacy, accountability of authorship, accuracy of information, and patient safety. To address these issues, the American Medical Association (AMA) has developed guidelines concerning web site content and visitor rights. Cystic fibrosis (CF) is the most common genetically inherited lethal disease in North America. Many Internet sites that provide information on CF have been developed, although adherence to validated guidelines for online health information is not required. The purpose of this study was to assess systematically web sites with content pertaining to CF for adherence to the published AMA guidelines. Methods. The search term "cystic fibrosis" was entered into a commonly used search engine (Google), and the first 100 eligible sites were reviewed. Each site was examined for adherence to the AMA Guidelines for Medical and Health Information Sites on the Internet using a series of adapted questions. There were 15 questions divided into the following main categories: 1) site structure and viewer privacy, 2) author accountability, 3) scientific citation, and 4) patient safety. The number of positives for each question was tabulated. Results. With respect to site structure, fewer than half (45%) of the reviewed sites indicated a date of last revision. Only 11 (11%) carried an explicit privacy policy. A responsible author or group was listed in only 43 (43%) of 100 sites. Presented data regarding CF was supported by references, sources, or expert review in only 38 (38%) of 100 sites. A medical disclaimer noting that information provided does not substitute for evaluation by a health care team was evident in only 37 (37%) sites. Conclusions. The majority of easily accessible CF in-formational web sites do not adhere to guidelines published by the AMA. Patients and... [ABSTRACT FROM AUTHOR]

The ligand Netrin-1 and its receptors DCC and UNC5H2 are critical for the regulation of neuronal migration in nervous system development. Here we demonstrate expression of these molecules in lung development. The mRNA expression profiles of Netrin-1, DCC and UNC5H2 are developmentally regulated during embryonic mouse lung formation. Netrin-1 shows a bimodal expression pattern with elevated mRNA levels early followed by a second peak in late gestation. Peak expression of DCC occurs early in development whereas expression of UNC5H2 peaks late in development. We also demonstrate localization of Netrin-1, DCC and UNC5H2 during the stages of lung development. We present evidence that these proteins are modulated spatially in the mesenchyme and epithelium during lung organogenesis. [Copyright &y& Elsevier]

First described as an axonal guidance cue through its repulsive effect on neurons expressing its receptor Roundabout (Robo), the Slit ligand has effects on cell migration, axon branching and elongation. Indirect evidence implicates Slit and Robo in lung development. We now demonstrate that Slit-2 and Slit-3 are developmentally regulated in embryonic murine lung. Immunohistochemistry demonstrates Slit-2 and Slit-3 expression by the pulmonary mesenchyme and airway epithelium. Robo-1 and Robo-2 are also expressed by the developing mesenchyme and airway epithelium. As lung development progresses, Robo-1 and Robo-2 expression localizes to only the airway epithelium. We conclude Slit/Robo are expressed in temporo-spatially adjacent domains suggesting interactive roles in pulmonary bronchiolar development. [Copyright &y& Elsevier]

Retinoic acid (RA) is an important coordinator of mammalian organogenesis. RA is implicated in critical lung developmental events. Cell proliferation is precisely regulated during development. We investigated the effect of RA on proliferating mesenchymal cells in both whole organ lung cultures and cell cultures. The potential pathways required for the response were studied in cultures of lung mesenchymal cells from embryonic day (e) 12. We observed an RA-dependent reduction in proliferation of mesenchymal cells in both whole organ and in cell culture. In mesenchymal cell cultures, RA decreased proliferation in lung mesenchymal cells by 72%. This was associated with a decrease of erk-1/2 activity by 68%. Mesenchymal cell proliferation is erk-1/2 dependent. Erk-1/2 can be activated by G-protein coupled receptors (GPCR) or tyrosine kinase receptors (RTK). RA treatment altered both the RTK and the GPCR pathways in primary lung mesenchymal cells. The Epidermal Growth Factor (EGF) dependent erk-1/2 activation was increased by 35% whereas the Gi-protein cascade was inhibited by 44% in cells treated with RA. Our results suggest that RA decreases proliferation of lung mesenchyme via a Gi-protein and the erk-1/2 signaling cascade. [ABSTRACT FROM AUTHOR]

Background: Fetal tracheal occlusion (TO) has been investigated as a treatment option for lung hypoplasia secondary to congenital diaphragmatic hernia (CDH). TO increases lung size, but it is unclear whether TO stimulates mature lung growth or simply induces alveolarization without concomitant bronchial development. In this study, we characterize bronchial branch development in fetal rats with CDH with or without TO through conventional histological and morphometric analysis as well as lung casting. Materials and methods: Rat dams were gavaged nitrofen at gestational day 9.5, and 3 to 4 fetuses per dam underwent fetal TO on gestational day 19 (term = 22 days). Fetuses were sacrificed on day 21, the presence of CDH was confirmed, and the lung weight to body weight ratio (LW/BW) was calculated. Lung casts of all research groups were created using liquid silicon and bronchial branches were quantified from lung periphery to carina. Results: CDH fetuses had smaller LW/BW ratios and a lesser percentage (%) of airspace when compared to controls, and manifested less lung branching than controls. Fetuses treated by TO had a greater LW/BW ratio and % airspace, but did not have a different number of branch iterations. Fetuses with CDH and TO demonstrated a restoration in LW/BW ratio to control levels (P = 0.42), but the number of bronchial branch iterations remained less than control animals. Conclusion: The results of this study suggest that TO in this animal model at gestational day 19 promotes distal airway proliferation but does not reverse the underdevelopment of bronchial branching seen in lung hypoplasia due to CDH. [Copyright &y& Elsevier]