A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis.

A more complete understanding of aberrant oncogenic signaling in neuroblastoma, a malignancy of the developing sympathetic nervous system, is paramount to improving patient outcomes. Recently, we identified LIN28B as an oncogenic driver in high-risk neuroblastoma. Here, we identify the oncogene RAN as a LIN28B target and show regional gain of chromosome 12q24 as an additional somatic alteration resulting in increased RAN expression.

Clinical significance of the infection-free interval in the management of acute bacterial exacerbations of chronic bronchitis.

Rational and appropriate antibiotic use for patients with acute exacerbation of chronic bronchitis (AECB) is a major concern, as approximately half of these patients do not have a bacterial infection. Typically, the result of antimicrobial therapy for patients with acute bacterial exacerbation of chronic bronchitis (ABECB) is not eradication of the pathogen but resolution of the acute symptoms. However, the length of time before the next bacterial exacerbation can be another important variable, as the frequency of exacerbations will affect the overall health of the patient and the rate of lung deterioration over time.

Clinical efficacy and tolerability of grepafloxacin in lower respiratory tract infection.

Studies in community-acquired pneumonia (CAP) have compared grepafloxacin, 600 mg o.d. for 7--10 days, with amoxycillin, 500 mg t.

Effective delivery of particles with the HandiHaler dry powder inhalation system over a range of chronic obstructive pulmonary disease severity.

The HandiHaler is a dry powder breath activated inhaler system developed for inhalation therapy for patients with airway disease. Its operation is based on the evacuation of powder from a pierced capsule. We sought to document the inspiratory flow rates attained by patients inspiring through the HandiHaler with various degrees of airflow limitation.

Pharmacokinetic/pharmacodynamic predictors of time to clinical resolution in patients with acute bacterial exacerbations of chronic bronchitis treated with a fluoroquinolone.

Forty nine subjects with acute bacterial exacerbations of chronic bronchitis (ABECB) treated with grepafloxacin were evaluated for parameters predictive of clinical outcome. Signs and symptoms associated with ABECB were serially collected and evaluated for changes. Coughs per day, sputum volume and the percentage of sputum neutrophils were associated with clinical outcome.

Short-course moxifloxacin therapy for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.

Chronic bronchitis is common among adults and infectious exacerbations contribute considerably to morbidity and mortality. We aimed to compare the safety and efficacy of moxifloxacin to clarithromycin for the treatment of patients with acute bacterial exacerbations of chronic bronchitis (ABECB) using a prospective, randomized, double-blind, parallel group trial. Between November 21, 1996 and April 7, 1998, 936 patients with acute exacerbations of chronic bronchitis (AECB) were enrolled at 56 centers across the United States of which 491 (52%) had ABECB (i.

Efficacy of oral ciprofloxacin vs. clarithromycin for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.

In this prospective, multicenter, double-blind study, the efficacy of ciprofloxacin was compared with that of clarithromycin as therapy for patients with acute bacterial exacerbations of chronic bronchitis (ABECB) from whom a pretherapy pathogen was isolated; the efficacy was measured by the infection-free interval. Clinical and microbiological responses at the end of therapy were secondary efficacy variables. Patients randomly received either ciprofloxacin or clarithromycin (500 mg twice a day for 14 days).

Randomized, double-blind study of ciprofloxacin and cefuroxime axetil for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.

In a prospective, multicenter, double-blind study, the interval to clinical relapse in patients with acute bacterial exacerbations of chronic bronchitis from whom a pretherapy pathogen was isolated was compared following treatment with ciprofloxacin or cefuroxime axetil. Clinical and microbiological responses at the end of therapy were secondary efficacy variables. Outpatients randomly received either ciprofloxacin or cefuroxime axetil (500 mg twice a day for 14 days).

Sparfloxacin vs ofloxacin in the treatment of acute bacterial exacerbations of chronic bronchitis: a multicenter, double-blind, randomized, comparative study. Sparfloxacin Multicenter ABECB Study Group.

Study Objective: Comparison of efficacy and safety of sparfloxacin vs ofloxacin for treatment of acute bacterial exacerbations of chronic bronchitis (ABECB).

Design: Multicenter, double-blind, randomized study.

Setting: Sixty-eight private offices and outpatient clinics in the United States and Canada.

Pharmacokinetics and pharmacodynamics of oral grepafloxacin in patients with acute bacterial exacerbations of chronic bronchitis.

This analysis was designed to characterize the population pharmacokinetics and pharmacodynamics of oral grepafloxacin (OPC-17,116) in patients with acute bacterial exacerbations of chronic bronchitis (ABECB). The study group included 76 patients (43 male, 33 female) between 23 and 81 years of age, who were part of a multicentre, randomized, double-blind, dose-response study. Patients were randomly assigned to receive oral regimens of grepafloxacin, 200, 400 or 600 mg, each administered once daily for 14 days.

Efficacy and safety of a 10-day course of 400 or 600 milligrams of grepafloxacin once daily for treatment of acute bacterial exacerbations of chronic bronchitis: comparison with a 10-day course of 500 milligrams of ciprofloxacin twice daily.

A randomized, prospective, double-blind, double-dummy, multicenter study investigated the efficacy and safety of 10 days of oral therapy with grepafloxacin at 400 mg once daily, grepafloxacin at 600 mg once daily, or ciprofloxacin at 500 mg twice daily in 624 patients with acute bacterial exacerbations of chronic bronchitis. At the end of treatment, clinical success (cure or improvement) was achieved for 93% (140 of 151), 88% (137 of 156), and 91% (145 of 160) of patients in the groups receiving grepafloxacin at 400 mg, grepafloxacin at 600 mg, and ciprofloxacin, respectively (clinically evaluable population). At follow-up (14 to 28 days posttreatment), the clinical success rates were 87% (124 of 143), 81% (122 of 151), and 80% (123 of 154) in the groups receiving grepafloxacin at 400 mg and 600 mg and ciprofloxacin, respectively.

Pharmacokinetics of [18F]fleroxacin in patients with acute exacerbations of chronic bronchitis and complicated urinary tract infection studied by positron emission tomography.

The pharmacokinetics of fleroxacin, a new broad-spectrum fluoroquinolone, were measured by positron emission tomography (PET) with [18F]fleroxacin in five patients with acute bacterial exacerbations of chronic bronchitis and in five patients with symptomatic, complicated urinary tract infection. Two studies were performed with each patient, one within 24 h of the initiation and one within 24 h of the completion of a 7-day course of fleroxacin, 400 mg/day. For each study, the patient received an infusion of that day's therapeutic dose of fleroxacin (400 mg) supplemented with approximately 740 MBq of [18F]fleroxacin, and serial PET images and blood samples were collected for 6 to 8 h starting at the initiation of the infusion.

Efficacy of fleroxacin versus amoxicillin in acute exacerbations of chronic bronchitis.

In a multicenter study the efficacy and safety of oral fleroxacin at 400 mg once a day and amoxicillin at 500 mg three times daily for 7 days were compared for the treatment of patients with acute bacterial exacerbations of chronic bronchitis due to drug-susceptible bacteria. A total of 194 patients were enrolled, 102 in the fleroxacin group and 92 in the amoxicillin group. Of those enrolled, 22 in the fleroxacin group and 30 (29 for clinical efficacy) in the amoxicillin group were included in the efficacy analysis.

Sputum eosinophilia negates need to perform sputum Gram's stain.

A total of 1878 sputum specimens were evaluated to assess the potential of encountering a sputum Gram's stain with clinically useful positive data in the presence of sputum eosinophilia. Wet preparations were used to assess the adequacy of the specimen and to quantitate eosinophils. Quantitative sputum Gram's stains were performed.

Treatment of acute exacerbations of chronic bronchitis: state of the art.

Effective treatment of acute bacterial exacerbations of chronic bronchitis (ABE) reduces the number of such exacerbations in such patients and may decrease or eliminate background symptoms and improve pulmonary function. The pathologic and physiologic abnormalities of the bronchial system in chronic bronchitis that predispose to bacterial infection probably include impaired mucociliary clearance, obstructed bronchioles, and bacterial infections of the bronchial epithelium. Exacerbations of bronchopulmonary symptoms are usually observed with ABE, although these symptoms are not unique to ABE.

Use of quinolones for the treatment of acute exacerbations of chronic bronchitis.

The availability of a new generation of quinolones expands the choices of antimicrobials for therapy of acute exacerbations of chronic bronchitis. These agents have broad antimicrobial activity, including good in vitro activity against respiratory pathogens, and advantageous pharmacokinetic characteristics, including bronchial tissue penetration. Ciprofloxacin, enoxacin, ofloxacin, and temafloxacin have been evaluated in a number of clinical trials, compared to the reference agents ampicillin, amoxicillin (with and without clavulanate), cefaclor, doxycycline, and erythromycin.

Temafloxacin compared with ciprofloxacin in mild to moderate lower respiratory tract infections in ambulatory patients. A multicenter, double-blind, randomized study.

The efficacy and safety of oral temafloxacin (600 mg) and ciprofloxacin (500 mg) twice daily for seven days were compared in patients with mild to moderate lower respiratory tract infections. Fifty-eight of 64 (91 percent) patients who received temafloxacin and 63 of 67 (94 percent) patients who received ciprofloxacin had clinical cure or improvement; bacteriologic cure occurred in 61 (95 percent) and 63 (94 percent), respectively. All 14 patients with pneumonia were clinically cured or improved and bacteriologically cured; 11 had complete resolution of roentgenographic evidence of pneumonia.

Comparison of ciprofloxacin with ampicillin in acute infectious exacerbations of chronic bronchitis. A double-blind crossover study.

Two separate acute bacterial exacerbations of chronic bronchitis and/or asthma were treated in 22 patients in a double-blind crossover study. One course of treatment consisted of 750 mg of ciprofloxacin twice daily and the other of 500 mg of ampicillin four times a day; each drug was given for 14 days. Patients were observed initially, every three to four days during therapy, and weekly during the post-therapy period.

Prazosin in hypertensive patients with chronic bronchitis and asthma: a brief report.

The effects of prazosin therapy were recently evaluated in ambulatory patients with essential hypertension and chronic obstructive pulmonary disease. Both the ability of prazosin to control high blood pressure and its effects on pulmonary function were observed. Systolic and diastolic blood pressures were significantly reduced at the end of the maintenance period.

Comparative effects of pirbuterol acetate, metaproterenol, and placebo aerosols on pulmonary function and incidence of cardiac ectopy.

This single-center, double-blind, randomized study compared the efficacy and safety of single-dose pirbuterol aerosol (0.2 mg and 0.4 mg) with metaproterenol (1.

Comparative trials of doxycycline versus amoxicillin, cephalexin and enoxacin in bacterial infections in chronic bronchitis and asthma.

The comparative efficacy of doxycycline versus amoxicillin, cephalexin, cefaclor and enoxacin was examined in four separate cross-over and blinded studies of acute bacterial bronchitis in chronic bronchitis and asthma. The efficacy of doxycycline over the eleven-year period (1975-1986) covered by these studies also was examined. Patients with acute bacterial exacerbations, defined by increased chest symptoms, increased bacteria and sputum neutrophilia, were randomly entered.

The effects of dilevalol, metoprolol, and placebo on ventilatory function in asthmatics.

Dilevalol combines a nonselective blocking action on beta-receptors with selective beta 2-agonist activity. In this double-blind, three-way, crossover study, the effects of relatively high single doses of dilevalol (400 mg), metoprolol (200 mg), a placebo on pulmonary function and their interaction with isoproterenol (160 and 480 micrograms) were evaluated in 16 patients with reversible bronchial asthma [isoproterenol-induced increase in forced expiratory volume in 1 s (FEV1) of greater than or equal to 15%]. When the lowest or minimum values observed during the 2 h postdrug evaluation period were considered, there was no significant difference from baseline in the percentage change in FEV1 after placebo (-4.

Acute bacterial exacerbations in bronchitis and asthma.

Symptomatic exacerbations are frequent problems in the management of chronic bronchitis and bronchial asthma. Identification of a bacterial etiology as the cause of specific exacerbations should be based on changes in clinical symptoms and documentation of significant bronchial bacterial flora and a neutrophilic inflammatory response. Most acute bacterial exacerbations in patients with bronchitis or asthma are caused by Hemophilus influenzae, Streptococcus pneumoniae, or Branhamella catarrhalis.

A multicenter trial of the prophylactic effect of ketotifen, theophylline, and placebo in atopic asthma.

Three hundred seventy-four patients with asthma were entered into a year-long, double-blind, double-placebo controlled study comparing the prophylactic effect of ketotifen (229 patients), theophylline (73 patients), and placebo (72 patients). The ketotifen group was larger to allow the accumulation of additional long-term safety data. The primary measure of therapeutic effect was a decrease in concomitant medication without a significant increase in symptomatology or a decrement in pulmonary functions.