PubMed Health⌕ Search

Biomedical subjects

Warren E Regelmann

Publications and source records attributed to Warren E Regelmann.

6 recordsLinked to original sources
PubMed2006

Staphylococcal alpha-toxin causes increased tracheal epithelial permeability.

Staphylococcus aureus is an important cause of pulmonary infections. The role of S. aureus alpha-toxin as a virulence factor is unclear. We hypothesized that airway epithelium is a target of S. aureus alpha-toxin and that exposure of airway epithelium to alpha-toxin results in damage to the airway epithelium. To examine the hypothesis that alpha-toxin is capable of independently producing airway epithelium damage as measured by permeability and morphometry, an isolated whole mouse trachea test apparatus was developed. In vitro epithelial permeability (P) was calculated and digital micrographs were analyzed morphometrically. Purified S. aureus alpha-toxin produced a significant increase in tracheal epithelial P (P < 0.05). Morphometric analysis revealed the ratio of adherent tracheal epithelium attached to the basement membrane divided by the total length of the basement membrane decreased in a dose-dependent manner with 1 microg/ml alpha-toxin and 10 microg/ml alpha-toxin (P < 0.05). We developed a novel isolated whole mouse trachea test apparatus for the measurement of tracheal epithelium damage. Increased P and separation of the tracheal epithelium from the basement membrane occurred after S. aureus alpha-toxin exposure. We conclude that mammalian airway epithelium is a target of S. aureus alpha-toxin.

Animals↗
PubMed2006

Inflammatory cytokines and the development of pulmonary complications after allogeneic hematopoietic cell transplantation in patients with inherited metabolic storage disorders.

Patients with inherited metabolic storage disorders are at a higher risk of developing pulmonary complications after hematopoietic cell transplantation (HCT). This single-center prospective study of 48 consecutive inherited metabolic storage disorder patients was performed to identify risk factors for the development of pulmonary complications after HCT. Before HCT, subjects underwent bronchoalveolar lavage (BAL) for cell count, culture, nitrite levels, and analysis of proinflammatory cytokines and chemokines. The overall incidence of pulmonary complications was 52% (infectious, 23%; noninfectious, 29%) over a period of 4 years. Diffuse alveolar hemorrhage was the most frequent noninfectious complication and occurred in 19% of patients, all of whom had a diagnosis of mucopolysaccharidosis (Hurler and Maroteaux-Lamy syndromes). Levels of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha, macrophage inflammatory protein 1alpha, and granulocyte colony-stimulating factor in BAL fluid samples obtained before HCT were higher in patients with mucopolysaccharidoses than in patients with leukodystrophies. In addition, levels of IL-1beta, IL-6, IL-8, and granulocyte colony-stimulating factor were increased in the BAL fluid of patients who developed noninfectious pulmonary complications compared with those who did not develop pulmonary complications. It is interesting to note that most noninfectious pulmonary complications occurred in patients with mucopolysaccharidoses, especially diffuse alveolar hemorrhage, which occurred exclusively in patients with mucopolysaccharidoses. Higher levels of bronchial proinflammatory cytokines and chemokines may be predictive of the development of subsequent posttransplantation noninfectious complications in patients with mucopolysaccharidoses, especially those with Hurler syndrome. Larger studies will be required to further elucidate etiologic mechanisms and predictive factors.

Adolescent↗
PubMed2004

Pulmonary exacerbations in cystic fibrosis.

The clinical characteristics most relevant to the decision to treat for a pulmonary exacerbation with antibiotics in cystic fibrosis patients were determined. Variables including age, increased cough frequency and sputum production, new crackles and wheezing, asthma, symptomatic sinusitis, hemoptysis, decreased lung function, weight loss, and new acquisition of Pseudomonas aeruginosa were collected in a large prospective multicenter database (Epidemiologic Study of Cystic Fibrosis). During a 12-month baseline period, data from 11692 patients were compared with data collected during the subsequent 6-month study period. Because pulmonary function assessments were unavailable for patients <6 years of age, separate analyses were done for those <6 and >or=6 years of age. The outcome of interest was any antibiotic treatment in the 6-month study period reported as indicated for an exacerbation. Characteristics with the most discriminatory power were determined using stepwise multiple logistic regression. For patients <6 years of age, the strongest independent associations with treatment for a pulmonary exacerbation were new crackles, increased cough frequency, decline in weight, and increased sputum production. For those patients >or=6 years of age, the strongest independent associations were a relative decrease in percent predicted forced expired volume in 1 sec, increased cough frequency, new crackles, and hemoptysis. The presence of three or more of these key characteristics was strongly associated with the occurrence of a treated exacerbation. The reproducibility of the model over time was confirmed by application to a subsequent set of data. This model has potential for use as an outcome measure in clinical trials, and to assist in treatment decisions for individual patients.

Adolescent↗
PubMed2004

Peroxidase activity within circulating neutrophils correlates with pulmonary phenotype in cystic fibrosis.

Excess neutrophils are present in the airways of patients with cystic fibrosis (CF). Myeloperoxidase (MPO) activity of acid extracts of sputum is directly correlated with airflow obstruction in CF patients. We hypothesized that the sputum MPO was derived from the MPO of neutrophils that entered the airways from the circulation. Active MPO without protease activity injures airways. If MPO activity from circulating neutrophils that emigrate into the airways of these patients causes increased airway epithelial permeability and mucus-gland secretion, then (1) those patients with greater MPO activity per circulating neutrophil would be more likely to produce sputum and (2) the MPO activity per circulating neutrophil would positively correlate with airflow obstruction. We determined the MPO activity for both circulating and sputum neutrophils. Spirometry and respiratory cultures were obtained simultaneously with blood and sputum samples. CF patients with more MPO activity within their circulating neutrophils were more likely to produce sputum ( P =.001, chi 2 test), and the MPO activity per circulating neutrophil was positively correlated with airflow obstruction as measured on the basis of the ratio of 1-second forced expiratory volume to forced vital capacity ( P <. 03, Kruskal-Wallace test). These associations were independent of age, sex, the results of respiratory-tract culture, or protease activity in the circulating neutrophils. MPO activity in circulating neutrophils from CF patients homozygotic for the deletion of phenylalanine at position 508 in the CF transmembrane regulator protein is directly related to the severity of these patients' pulmonary disease. Our results are consistent with the hypothesis that circulating neutrophils deliver active MPO to the airway, producing airway injury and airflow obstruction in homozygotic delF508 CF patients.

Adolescent↗
PubMed2002

A phase I randomized, multicenter trial of CPX in adult subjects with mild cystic fibrosis.

CPX (8-cyclopentyl-1,3-dipropylxanthine) is a novel compound currently under development as a potential treatment for cystic fibrosis (CF). The drug has been shown to increase chloride efflux and CFTR trafficking in vitro in CF airway cells. This phase I multicenter, single-dose, placebo-controlled trial was performed at four institutions. Thirty-seven subjects homozygous for the Delta F(508) allele were studied in an escalating dose protocol of seven single-dose cohorts (1, 3, 10, 30, 100, 300, and 1,000 mg) to evaluate the safety, pharmacokinetics, and efficacy of CPX. Efficacy was determined using nasal transepithelial potential difference and sweat chloride measurements prior to dosing and at 1, 2, and 4 hr postdose. The incidence of adverse events in the treatment group was similar to that with placebo, indicating safety of the single doses studied. One serious adverse event (an acute pulmonary exacerbation) occurred 13 days after dosing, and was not considered related to the study drug. The maximal plasma CPX concentration and total amount of CPX absorbed appeared to be linearly related to dose, but was highly variable throughout the dose range studied, suggesting inconsistent absorption. There was no apparent effect of single-dose administration on either nasal transepithelial potential difference or sweat chloride measurements. The positive safety and pharmacokinetic findings of this study support continued development of CPX as a potential therapeutic for CF.

Adolescent↗