Role of cystic fibrosis transmembrane conductance regulator in patients with chronic sinopulmonary disease.

BACKGROUND: Previous studies report a high frequency of mutations in the cystic fibrosis (CF) transmembrane conductance regulator gene (CFTR) in patients with idiopathic bronchiectasis. However, most studies have based their findings on preselected patient groups or have performed limited testing for CF transmembrane conductance regulator (CFTR) dysfunction. The objective of our study was to evaluate the prevalence of CFTR gene mutations and/or CFTR-related ion channel abnormalities among subjects with idiopathic chronic sinopulmonary disease and the prevalence of CF or a CFTR-related disorder in this population. METHODS: We evaluated 72 prospectively enrolled patients from 1995 to 2005 at the Hospital for Sick Children and St. Michael's Hospital with idiopathic chronic sinopulmonary disease for evidence of CFTR-mediated abnormalities. We performed CFTR genotyping and assessed CFTR function using sweat testing and nasal potential difference testing. The results were compared with data from healthy control subjects, CF heterozygotes, and patients with CF. RESULTS: The CFTR functional tests in idiopathic sinopulmonary patients showed a continuous spectrum, ranging from normal to values typically seen in individuals with CF. Forty-eight patients (66%) demonstrated CFTR mutations and/or abnormalities of CFTR function. Twenty-two (31%) fulfilled criteria for a diagnosis of CF and 26 (36%) for a CFTR-related disorder with a strong female preponderance. Functional tests, more than genotyping, were instrumental in establishing a CF diagnosis. Clinical features failed to distinguish subjects with CF from those with CFTR-related or idiopathic disease. CONCLUSIONS: The high prevalence of CF and CFTR dysfunction among patients with idiopathic chronic sinopulmonary disease underscores the need for extensive diagnostic evaluation for CF.

Chest radiographic manifestations of severe acute respiratory syndrome in health care workers: the Toronto experience.

OBJECTIVE: The purpose of this article is to describe the chest radiographic manifestations of severe acute respiratory syndrome (SARS) in previously uninfected health care workers during the early stages of an outbreak in Toronto, Canada. CONCLUSION: The study group was composed of 13 patients from a single institution. Three distinct chest radiographic patterns were observed: focal peripheral air-space disease at presentation with gradual resolution (most common pattern, 10/13 patients), normal findings on chest radiography at presentation followed by focal air-space disease (2/13 patients), and normal findings on chest radiography at presentation followed by a "round" pneumonia pattern (1/13 patients). There was no evidence of pleural reaction, lymphadenopathy, or interstitial changes.

Stability and preservative effectiveness of treprostinil sodium after dilution in common intravenous diluents.

The stability of treprostinil sodium after dilution in three common i.v. infusion vehicles was assessed. The chemical stability of treprostinil sodium was tested over a 48-hour period at 40 degrees C and 75% relative humidity after dilution in each of three diluents: sterile water for injection, 0.9% sodium chloride injection, and 5% dextrose injection, and after passage through an i.v. delivery system. Chemical analysis was conducted by using a validated stability-indicating high-performance liquid chromatographic assay, visually inspecting the solutions, and measuring the pH of each solution. The preservative effectiveness of the solutions was tested by the recovery of inoculations of compendial microorganisms after 48 hours in dilute solutions of treprostinil sodium. All assay results for treprostinil were within 90.0% to 110.0% of the prepared solutions diluted at 0.004 and 0.13 mg/mL treprostinil sodium in sterile water for injection and 0.9% sodium chloride injection. The assay results were the same for dilute treprostinil solutions in 5% dextrose injection at concentrations of 0.02 and 0.13 mg/mL. The pH values for these solutions remained within acceptable values of 6.0 to 7.2 for the stability study. No change in physical appearance or any visible particulate matter was observed. Approximately 70% of metacresol, the preservative, in the dilute treprostinil sodium solutions was removed before reaching the terminal end of the tubing. None of the dilute treprostinil sodium solutions supported microbial growth in the cassette reservoirs for the organisms considered. Treprostinil sodium 0.13 mg/mL solution in sterile water for injection, 0.9% sodium chloride for injection, and 5% dextrose for injection appeared to be stable after storage in controlled ambulatory drug-delivery systems for 48 hours at 40 degrees C and 75% relative humidity. Treprostinil sodium 0.004 mg/mL in sterile water and 0.9% sodium chloride for injection and 0.02 mg/mL in 5% dextrose injection was also stable under the same conditions. None of the solutions showed signs of microbial growth.