Efficacy of salmeterol xinafoate in the treatment of COPD

STUDY OBJECTIVES: To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD. DESIGN: A stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel group clinical trial. SETTING: Multiple sites at clinics and university medical centers throughout the United States. PATIENTS: Four hundred eleven symptomatic patients with COPD with FEV1 < or = 65% predicted and no clinically significant concurrent disease. Interventions: Comparison of inhaled salmeterol (42 microg twice daily), inhaled ipratropium bromide (36 microg four times a day), and inhaled placebo (2 puffs four times a day) over 12 weeks. RESULTS: Salmeterol xinafoate was significantly (p < 0.0001) better than placebo and ipratropium in improving lung function at the recommended doses over the 12-week trial. Both salmeterol and ipratropium reduced dyspnea related to activities of daily living compared with placebo; this improvement was associated with reduced use of supplemental albuterol. Analyses of time to first COPD exacerbation revealed salmeterol to be superior to placebo and ipratropium (p < 0.05). Adverse effects were similar among the three treatments. CONCLUSIONS: These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.     

Salmeterol vs theophylline: sleep and efficacy outcomes in patients with nocturnal asthma.

STUDY OBJECTIVES: To compare the efficacy, safety, and effects on sleep quality of salmeterol and extended-release theophylline in patients with nocturnal asthma. DESIGN: Randomized, double-blind, double-dummy, three-period crossover. SETTING: Outpatients at a single center. Patients spent 1 night during screening and 2 nights during each study period in a sleep laboratory for completion of sleep studies. PATIENTS: Male and female patients who were at least 18 years old with nocturnal asthma (baseline FEV1, 50 to 90% of predicted) and who required regular bronchodilator therapy. Patients on inhaled corticosteroids, cromolyn, and nedocromil were allowed into the study if their dosing remained constant throughout the study. INTERVENTIONS: Inhaled salmeterol (42 microg per actuation), extended-release oral theophylline (titrated to serum levels of 10 to 20 microg/mL), and placebo taken twice daily. MEASUREMENTS AND RESULTS: Efficacy measurements included nocturnal spirometry, nocturnal polysomnography, sleep questionnaires, and daily measurements of lung function and symptoms. Salmeterol was superior to theophylline (p < or = 0.05) in maintaining nocturnal FEV1 levels and was superior to placebo (p < or = 0.05) in improving morning and evening peak expiratory flow (PEF) and in decreasing nighttime albuterol use. The use of salmeterol significantly increased the percentage of days and nights with no albuterol use and decreased daytime albuterol use compared with theophylline and placebo (p < or = 0.05). Sleep quality global scores significantly improved with salmeterol and placebo (p < 0.001) but not with theophylline. The effects on sleep architecture were similar across treatment groups. CONCLUSIONS: Salmeterol (but not theophylline) was associated with sustained improvements in morning PEF, protection from nighttime lung function deterioration, reductions in albuterol use, and improvements in patient perceptions of sleep. No differences were seen in polysomnographic measures of sleep quality.     

Control of bud activation by an auxin transport switch

In many plant species only a small proportion of buds yield branches. Both the timing and extent of bud activation are tightly regulated to produce specific branching architectures. For example, the primary shoot apex can inhibit the activation of lateral buds. This process is termed apical dominance and is dependent on the plant hormone auxin moving down the main stem in the polar auxin transport stream. We use a computational model and mathematical analysis to show that apical dominance can be explained in terms of an auxin transport switch established by the temporal precedence between competing auxin sources. Our model suggests a mechanistic basis for the indirect action of auxin in bud inhibition and captures the effects of diverse genetic and physiological manipulations. In particular, the model explains the surprising observation that highly branched Arabidopsis phenotypes can exhibit either high or low auxin transport.     

Dosimetric impact of breast density in breast tomosynthesis: A comparative study

A radiation dose survey has been undertaken involving 256 patients to investigate the dosimetric impact of breast tomosynthesis screening by employing different breast densities estimated by the Dance model, 50‐50 breast model, and patient‐specific density software: Volpara. Mean glandular dose (MGD) based on the Dance model provided the most realistic dose estimate with an average difference of ?3.3 ± 4.8% from the patient‐specific estimation. Average differences of ?8.2 ± 6.5% and ?7.3 ± 4.7% were observed for the 50‐50 breast model and console MGD, respectively. We conclude that the Dance model should be used for dose calculations in radiation dose surveys and establishing diagnostic reference levels (DRL).