A murine model to study vasoreactivity and intravascular flow in lung isograft microvessels.

Intravital microscopy of orthotopic lung tissue is technically demanding, especially for repeated investigations. Therefore, we have established a novel approach, which allows non-invasive repetitive in vivo microscopy of ectopic lung tissue in dorsal skinfold chambers. Syngeneic subpleural peripheral lung tissue and autologous endometrium (control) were transplanted onto the striated muscle within dorsal skinfold chambers of C57BL/6 mice.

Sequential Inhalational Tobramycin-Colistin-Combination in CF-Patients with Chronic P. Aeruginosa Colonization - an Observational Study.

Background/aims: In cystic fibrosis (CF), chronic microbial lung infections are difficult to treat and cause morbidity and increased mortality.

Methods: In a multicentre, open-label, exploratory, non-interventional study, inhaled tobramycin (300 mg twice daily) and colistin (1 million I.U.

Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline.

Background/aims: Several recent clinical studies revealed an accumulation of ceramide in bronchial epithelial cells of patients with cystic fibrosis (CF). Degradation of ceramide concentrations in lungs of CF patients employing the functional acid sphingomyelinase inhibitor amitriptyline revealed a benefit in lung function, weight and exacerbation rates.

Methods: To test for a beneficial effect of amitriptyline in vivo, we performed two phase II randomised, double-blind, placebo-controlled studies.

Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study.

Background: Individuals with cystic fibrosis (CF) receive antibiotics continuously throughout their entire life which leads to drug resistant microbial lung infections which are difficult to treat. Nitric oxide (NO) gas possesses antimicrobial activity against a wide variety of microorganisms in vitro, in vivo in animal models and a phase I study in healthy adults showed administration of intermittent 160 ppm NO to be safe.

Methods: We assessed feasibility and safety of inhaled NO in eight CF patients who received 160 ppm NO for 30 min, three times daily for 2 periods of 5 days.

BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs.

Background: A clinical study to investigate the leukotriene B(4) (LTB(4))-receptor antagonist BIIL 284 in cystic fibrosis (CF) patients was prematurely terminated due to a significantly increased risk of adverse pulmonary events. We aimed to establish the effect of BIIL284 in models of Pseudomonas aeruginosa lung infection, thereby contributing to a better understanding of what could have led to adverse pulmonary events in CF patients.

Methods: P.

Inhalation treatment with glutathione in patients with cystic fibrosis. A randomized clinical trial.

Rationale: Glutathione is the major antioxidant in the extracellular lining fluid of the lungs and depleted in patients with cystic fibrosis (CF).

Objectives: We aimed to assess glutathione delivered by inhalation as a potential treatment for CF lung disease.

Methods: This randomized, double-blind, placebo-controlled trial evaluated inhaled glutathione in subjects with CF 8 years of age and older and FEV1 of 40-90% of predicted.

Therapy of CF-patients with amitriptyline and placebo--a randomised, double-blind, placebo-controlled phase IIb multicenter, cohort-study.

Background/aims: Several recent studies revealed an accumulation of ceramide in bronchial, tracheal and intestinal epithelial cells of mice and patients with cystic fibrosis (CF). Normalization of ceramide concentrations in lungs of CF mice employing the functional acid sphingomyelinase inhibitor amitriptyline also normalized mucociliary clearance, chronic inflammation and infection susceptibility to pulmonary P. aeruginosa in these mice.