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Biomedical subjects

A B Becker

Publications and source records attributed to A B Becker.

At least 73 records · Page 4Linked to original sources
PubMed1989

Formoterol, a new long-acting selective beta 2-adrenergic receptor agonist: double-blind comparison with salbutamol and placebo in children with asthma.

We compared the protective effect and duration of action of inhaled formoterol, a new, long-acting, selective beta 2-agonist, to inhaled salbutamol and placebo in a double-blind, randomized, crossover study in 16 children with asthma with a mean age of 10.3 +/- 0.4 years. Mean baseline FEV1 was 96 +/- 3% predicted and mean provocative concentration of methacholine (milligrams per milliliter) required to decrease FEV1 by 20% (PC20) was 0.81 +/- 0.25 mg/ml of methacholine. On the 4 study days, baseline FEV1 was within 10% of the FEV1 on visit 1, and baseline PC20 was within one doubling dose of visit 1. Each day patients inhaled either placebo, salbutamol, 200 micrograms, formoterol, 12 micrograms, or formoterol, 24 micrograms. FEV1 and PC20 were measured repeatedly during 12 hours. After placebo inhalation, mean FEV1 did not change significantly during 12 hours. After salbutamol inhalation, the mean FEV1 was significantly increased for less than 3 hours, but after formoterol inhalation, 12 or 24 micrograms, the mean FEV1 was significantly increased for 12 hours. After placebo treatment, mean PC20 did not change significantly. After salbutamol inhalation, mean PC20 was significantly increased for only 3 hours, but after formoterol inhalation, 12 or 24 micrograms, mean PC20 was significantly increased for 12 hours. Protection by formoterol, 12 and 24 micrograms at 12 hours, was equivalent to protection by salbutamol at 3 hours. Inhaled formoterol is a potent, long-acting bronchodilator and provides significantly better antiasthma protection than inhaled salbutamol.

Adrenergic beta-Agonists↗
PubMed1989

Development of chronic airway hyperresponsiveness in ragweed-sensitized dogs.

We studied dogs neonatally sensitized to ragweed and their littermate controls at 4, 6, 8, 10, 12, and 15 mo of age. Acute allergic airway response to inhalation of ragweed in the sensitized dogs was marked (greater than 12-fold increase from base line) and reproducible at all times. Nonallergic airway responsiveness, measured as the concentration of acetylcholine required to increase airway resistance by 5 cmH2O.l-1.s (PC5), increased in sensitized and decreased in nonsensitized dogs from 4 to 15 mo of age (P less than 0.01). Before antigen, at 12 and 15 mo, sensitized dogs were significantly (P less than 0.05) more responsive to acetylcholine than controls. Six hours after antigen, sensitized dogs were 11-fold more responsive (P less than 0.005) than controls at those times. More eosinophils and mast cells and fewer macrophages (P less than 0.05) were present in bronchoalveolar lavage (BAL) from 12- and 15-mo-old sensitized dogs than their controls. BAL fluid histamine was higher (P less than 0.05) in sensitized than control dogs. Regression analysis revealed r = -0.75 (P = 0.003) between BAL mast cells and PC5 in sensitized dogs and R2 = 0.89 for PC5 and BAL mast cells, macrophages, and eosinophils. Neonatally sensitized dogs represent an excellent animal model in which to study the pathophysiology of asthma.

Airway Resistance↗
PubMed1988

Comparison of ipratropium solution, fenoterol solution, and their combination administered by nebulizer and face mask to children with acute asthma.

In a randomized, double-blind, parallel-group trial, 47 children with acute asthma received a combination of ipratropium bromide solution (250 micrograms) and fenoterol hydrobromide solution (625 micrograms), fenoterol solution (625 micrograms) alone, or ipratropium solution (250 micrograms) alone, administered by face mask and nebulizer, with the dose repeated 60 minutes later. The groups did not differ significantly with regard to age, pulmonary function at baseline, or any other variable. They were monitored at 30, 60, 90, and 120 minutes by use of a clinical score, oxygen saturation, and pulmonary function tests. At the end of the study, albuterol was administered to assess residual bronchoconstriction. Clinical scores improved significantly after treatment in all groups at all times compared with baseline. The greatest improvement in FEV1 was seen in the patients treated with ipratropium/fenoterol, whether considered as absolute change, change in percent predicted, or percent change from baseline. Ipratropium/fenoterol was significantly better than fenoterol alone only when considered as percent change from baseline. Improvement in flow at mid and low lung volumes was significantly greater for the ipratropium/fenoterol combination than for ipratropium alone; no significant differences were noted between ipratropium/fenoterol and fenoterol for flow at mid and low lung volumes. Treatment with albuterol did not significantly improve pulmonary function in the groups receiving ipratropium/fenoterol or fenoterol alone, but it did increase flow at all lung volumes in the group receiving ipratropium alone. No patient complained spontaneously of any adverse reactions, and no clinically significant changes in heart rate or systolic or diastolic blood pressures occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Cutaneous allergic response in atopic dogs: relationship of cellular and histamine responses.

We studied the cutaneous response to intradermal antigen using clinical, histologic, and physiologic criteria in ragweed-sensitized dogs. The clinical response was measured early (the wheal at 20 minutes) and late (induration at 6 hours). We assessed cutaneous responsiveness to histamine before and 6 hours after injection (intradermally) of ragweed (n = 5, antigen group) and diluent (n = 4, 10% glycerin in 0.9% NaCl, sham group); we measured the wheal in response to histamine (1.0 ng to 0.1 mg, intradermally), constructed a dose-response curve, and interpolated the provocative dose (milligrams) of histamine required to create a wheal 10 mm larger than the response to saline control. Skin biopsy specimens were obtained before and after injection of either ragweed or diluent. Consistent with the human late-phase response, neutrophils and eosinophils were present in the dermis at 1 hour, maximal at 6 hours, and decreased at 24 hours. Mononuclear cells increased significantly at 6 hours and were the predominant cells present at 24 hours after antigen. The late clinical response correlated only with influx of eosinophils (rs = 0.85; p less than 0.005). Histamine responsiveness increased markedly after antigen (p less than 0.0001), did not change after glycerin diluent (sham), and was correlated with the intensity of neutrophil influx at 6 hours (rs = 0.69; p less than 0.05), and to a much greater degree with mononuclear cell influx at 6 hours (rs = 0.85; p less than 0.005).

Animals↗
PubMed1986

Cutaneous mast cell heterogeneity: response to antigen in atopic dogs.

Because mast cells (MCs) in skin of atopic dogs are heterogeneous with respect to tissue fixation and staining properties, we determined the effect of antigen on each type of MC in vivo. Skin biopsies were done in anesthetized, ragweed-sensitized dogs before and at 1, 3, 6, and 24 hours after intradermal injections of ragweed antigen (n = 5) or glycerin diluent (n = 4). In each case, one biopsy specimen was fixed with formalin, and a second specimen from an adjacent abdominal site was fixed with basic lead acetate. In sections stained with Alcian blue, 49.7% more MCs (p less than 0.05) were detected in tissue fixed with basic lead acetate ("typical" plus "atypical" MCs: 2916 +/- 581/mm3; mean +/- SEM) than in tissue fixed with formalin ("typical" MCs: 1955 +/- 537/mm3). After antigen, the number of "typical" MCs detectable in tissue sections progressively decreased during the 24-hour period, whereas the number of "atypical" MCs was lowest at 1 hour and had increased at 24 hours. After diluent, MC numbers did not change significantly over time. A late-phase response (LPR), detected clinically as induration and edema, was present 6 hours after antigen in four of five dogs, but LPR was not detected after diluent. The size of LPR was correlated (r = 0.85; p less than 0.05) with the decrease in the number of "typical" MCs at 6 hours. We conclude that the response of the "typical" and "atypical" MC to antigen in vivo differs markedly. The "atypical" MCs participate in the early, acute response to antigen, and the "typical" MCs may be associated with the development of the LPR.

Animals↗
PubMed1986

Inhibition of antigen-induced airway hyperresponsiveness by a thromboxane synthetase inhibitor (OKY-046) in allergic dogs.

To determine the role of thromboxane A2 in the airway hyperresponsiveness induced by antigen challenge, we studied the effect of a thromboxane synthetase inhibitor, OKY-046, i.e., sodium (E)-3-[4-(1-imidazolylmethyl)-phenyl]-2-propanoate, in 6 ragweed-sensitized dogs. Airway responsiveness was assessed with dose-response curves of acetylcholine aerosol versus total pulmonary resistance before and 6 and 24 h after inhalation with ragweed antigen. This procedure was repeated in each dog during intravenous infusion of OKY-046 (100 micrograms/kg/min). OKY-946 did not alter the acute increase in total pulmonary resistance after antigen. At 6 h, there was a 7-fold increase in airway responsiveness, an effect that was prevented by OKY-046 (p less than 0.001). At 24 h, 18 h after OKY-046 was stopped, hyperresponsiveness was still significantly inhibited. OKY-046 did not alter the influx of neutrophils recovered by bronchoalveolar lavage performed at 6 h after antigen challenge. Antigen-induced airway hyperresponsiveness in dogs may depend upon the thromboxane A2 generation from inflammatory cells (e.g., neutrophils).

Acrylates↗
PubMed1985

Mast cell heterogeneity in dog skin.

The degree of metachromasia of mast cell granules is known to vary with the type of tissue fixation and among different tissues and species. The present study sought to determine whether mast cells in dog skin are heterogeneous with respect to fixation and staining properties. We performed skin biopsies in six anesthetized, atopic dogs and one mongrel dog. One biopsy was fixed in formalin and a second, from a parallel abdominal site, was fixed in basic lead acetate (Mota's solution). Adjacent sections from each biopsy were stained with alcian blue (1%, pH 0.5) or for chloroacetate esterase activity. In alcian blue-stained sections, one-third fewer mast cells were detected in skin fixed in formalin (1,836 +/- 454 mast cells/mm3, mean +/- SEM) than in skin fixed in basic lead acetate (2,684 +/- 527 mast cells/mm3) (P less than 0.05). The chloroacetate esterase reaction detected the larger number of mast cells regardless of the fixative used. We conclude that mast cell heterogeneity, as demonstrated by metachromatic staining following different types of tissue fixation, exists in dog skin. "Typical" mast cells stain with alcian blue regardless of fixation; however, "atypical" mast cells exhibit metachromasia only after fixation in basic lead acetate. Both the typical and atypical types of mast cells have chloroacetate esterase activity.

Alcian Blue↗
PubMed1985

The bronchodilator effect and pharmacokinetics of theobromine in young patients with asthma.

The bronchodilator effect of a 10 mg/kg dose of theobromine (3,7-dimethylxanthine) was compared with that of 5 mg/kg of theophylline (1,3-dimethylxanthine) in young patients with asthma. Bronchodilation, as assessed by forced vital capacity, forced expiratory volume in the first second, forced expiratory flows at 25%, 50%, and 75% of vital capacity, and percent of forced expiratory volume in the first second/forced vital capacity did not differ significantly between the two drugs. After each drug bronchodilation peaked at 2 hours and lasted for 6 hours, although it was not always statistically significant for theobromine. The mean peak serum concentrations of both drugs, the time at which peak serum concentrations occurred, and elimination half-life values were similar for theobromine and theophylline.

Adolescent↗
PubMed1985

Antigen-induced airway hyperresponsiveness and pulmonary inflammation in allergic dogs.

We studied whether antigen-induced airway hyperresponsiveness was associated with pulmonary inflammation in 11 anesthetized ragweed-sensitized dogs. Airway responsiveness to acetylcholine aerosol was determined before and at 2, 6, and 24 h after ragweed or sham aerosol challenge. Pulmonary inflammation was assessed by bronchoalveolar lavage (BAL) performed at either 2 or 6 h. Total pulmonary resistance increased 11-fold at 5 min after ragweed. Airway responsiveness was unchanged at 2 h but was increased 6.6-fold at 6 h in 8 of 11 dogs (P less than 0.001); hyperresponsiveness persisted from 4 days to 4 mo. Airway responsiveness was unchanged by aerosols of diluent. Neutrophils in BAL fluid increased approximately sixfold at 2 h (P less than 0.02) and at 6 h (P less than 0.02) after antigen challenge. There were fewer eosinophils in fluid recovered at 6 h after antigen compared with 2 h lavages (P less than 0.05). In three nonresponders, BAL showed no significant changes in neutrophils and eosinophils after antigen. Thus antigen-induced hyperresponsiveness is associated with the presence of pulmonary inflammation, presumably arising from the airways and involving both neutrophils and eosinophils.

Acetylcholine↗
PubMed1985

Terbutaline by metered-dose inhaler: conventional inhaler versus tube spacer for children with asthma.

We compared terbutaline administered through an 80-mL, 10 X 3.2-cm tube spacer versus a conventional metered-dose inhaler in 34 asthmatic patients, aged 8 to 16 years. In this double-blind, single-dose study, three groups of children (spacer active, conventional active, and placebo) were assessed clinically and with spirometry before and at one-half hour intervals for two hours after therapy. One investigator taught inhaler use and monitored patients' errors in technique. Compared with placebo, terbutaline delivered by either the tube spacer or the conventional inhaler significantly improved pulmonary function from one-half to two hours after treatment. Both the spacer and conventional inhaler were equally effective in improving pulmonary function from the baseline state. Only 4/34 (11.7%) children used both inhalers without any error. Adverse effects were mild, transient, and infrequent and did not differ between the groups. Terbutaline aerosol, whether delivered by the tube spacer or conventional actuator, provides effective bronchodilation for children with asthma, in spite of frequent errors in technique of inhaler use.

Aerosols↗
PubMed1984

The bronchodilator effects and pharmacokinetics of caffeine in asthma.

We compared the bronchodilator effects and pharmacokinetics of orally administered caffeine (10 mg per kilogram of body weight) and theophylline (5 mg per kilogram) in a double-blind, single-dose study in asthmatic patients 8 to 18 years of age. After 48 hours of withdrawal of all methylxanthines, 13 patients received caffeine and 10 received theophylline. Significant improvements in forced vital capacity, forced expiratory volume in one second, and forced expiratory flow rates occurred from one to six hours after administration of either caffeine or theophylline. The bronchodilator effect of caffeine did not differ significantly from that of theophylline and was maximal two hours after ingestion of each drug. Peak serum levels of caffeine (13.5 +/- 2.9 mg per liter) occurred at one hour, and peak levels of theophylline (8.4 +/- 1.7 mg per liter) at 2.2 +/- 0.8 hours. The mean serum half-time for caffeine was 3.9 +/- 1.4 hours and that for theophylline was 5.8 +/- 1.7 hours. All patients receiving caffeine metabolized it to paraxanthine, theobromine, and theophylline. Mild, transient side effects were seen after both caffeine and theophylline. Vital signs did not change significantly after either drug. We conclude that caffeine, a commonly available chemical, is an effective bronchodilator in young patients with asthma.

Adolescent↗
PubMed1984

The pulmonary index. Assessment of a clinical score for asthma.

We used a clinical score, the pulmonary index (PI), in the emergency room assessment of children with acute asthma. The PI was derived from respiratory rate, wheezing, inspiratory-expiratory ratio, and use of accessory muscles. Patients were treated with a beta-adrenergic drug and were assessed before and at 15-minute intervals after treatment using clinical examination, PI, and spirometry. The PI before treatment correlated significantly with the mean percent of forced expiratory volume in the first second to forced vital capacity ratio. The PI 30 minutes after treatment correlated significantly with all tests of pulmonary function performed. The PI is a simple score that is easily derived from clinical observation.

Acute Disease↗
PubMed1984

Pharmacokinetics and antipruritic effects of hydroxyzine in children with atopic dermatitis.

We studied the pharmacokinetics and antipruritic effects of hydroxyzine hydrochloride in 12 children, mean age 6.1 +/- 4.6 years, with severe atopic dermatitis. After a single 0.7 mg/kg orally administered dose of the drug, the mean peak serum hydroxyzine concentration of 47.4 +/- 17.3 ng/ml occurred at a mean time of 2.0 +/- 0.9 hours. The mean elimination half-life was 7.1 +/- 2.3 hours, the mean clearance rate was 32.08 +/- 11.05 ml/min/kg, and the mean apparent volume of distribution was 18.5 +/- 8.6 L/kg. The elimination half-life increased with increasing age (r = 0.83). Pruritus was significantly suppressed from 1 to 24 hours after the administration of the dose, with greater than 85% suppression from 2 to 12 hours. The only adverse effect reported was sedation. In a subsequent double-blind, crossover, multiple-dose study of 2 weeks' duration, hydroxyzine 0.7 mg/kg three times daily was as effective as hydroxyzine 1.4 mg/kg three times daily in relieving pruritus and promoting resolution of the skin lesions. The 0.7 mg/kg tid dose caused significantly less sedation than the 1.4 mg/kg tid dose.

Antipruritics↗
PubMed1983

Inhaled salbutamol (albuterol) vs injected epinephrine in the treatment of acute asthma in children.

In a double-blind trial we compared the efficacy and safety of inhaled salbutamol (albuterol), nebulized with oxygen by face mask, and subcutaneous epinephrine in 40 children with acute asthma. No significant difference between salbutamol and epinephrine was seen at any time for clinical score, respiratory rate, heart rate, blood pressure. PaO2, PaCO2, FVC, FEV1, FEV1/FVC, or FEF25-75%. PaO2 remained unchanged after salbutamol but increased significantly (P less than 0.05) after epinephrine. No significant difference occurred between the groups for repeat treatment, admission on initial visit, return to emergency room, admission on return, or total admissions. Significantly (P less than 0.01) increased adverse effects were seen within the group given epinephrine. We conclude that inhaled nebulized salbutamol and subcutaneous epinephrine are equally effective. In view of the lack of adverse effects and noninvasiveness of inhaled salbutamol, we recommend its use for the treatment of acute asthma in children.

Acute Disease↗
PubMed1982

Ketotifen: a new drug for prophylaxis of asthma in children.

Ketotifen, an orally active, prophylactic anti-asthmatic drug, was compared with placebo in a double-blind, three-month parallel-group trial in 20 children. Children receiving ketotifen were more likely to reduce concomitant medications and had significant improvement over time in asthma scores and mean flows at 75%, 50%, and 25% of vital capacity. They also had a significantly increased incidence of dry mouth and significant weight gain compared to those receiving placebo. In some children with asthma, ketotifen may be a useful alternative to existing drugs.

Acute Disease↗
PubMedDate not supplied

Potential therapeutic efficacy of allergen-monomethoxypolyethylene glycol conjugates for in vivo inactivation of sensitized mast cells responsible for common allergies and asthma.

Skin sites of rats, which had been systemically sensitized to ovalbumin (OVA) were injected intradermally with murine anti-DNP IgE mAbs or with murine polyspecific IgE to recombinant Bet v 1. Injection of OVA(mPEG)10-11 conjugates into these skin sites inhibited passive cutaneous anaphylaxis (PCA) on subsequent intravenous challenge with DNP44-BSA and rBet v 1; by contrast, neither OVA nor an unrelated mPEG conjugate affected the PCA reactions. In dogs sensitized to both OVA and ragweed pollen extract (RAG), inhalation of either allergen (AL) caused a dramatic increase in airway resistance (Rrs). By contrast, administration of an aerosol of OVA(mPEG) caused no change in Rrs. Moreover, thereafter, (1) in spite of repeated challenges with aerosolized OVA over many months, the increase in Rrs on inhalation of OVA was blocked and (2) insufflation of RAG resulted in increase in Rrs of only about 50% in relation to that prior to inhalation of the conjugate; this dog's anti-RAG hyperreactivity remained blunted over many months. It is concluded that AL-mPEG conjugates of optimal composition inactivate sensitized mast cells and basophils, as manifested by a significant decrease of cutaneous or airway responses on subsequent challenge with the respective AL(s).

Allergens↗