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Biomedical subjects

C W Bierman

Publications and source records attributed to C W Bierman.

At least 37 records · Page 2Linked to original sources

Otitis media.

Otitis media with effusion is a common disorder in children and occurs more frequently in adults than has been generally appreciated. Laboratory tools have permitted a more specific characterization of this disorder by objective means. These laboratory tests include specific ear tests (pneumatic otoscopy, pure tone, and impedance audiometry), nasal tests (inflammatory cytology), functional tests for obstruction (airway resistance measurements), and anatomic tests of obstruction and inflammation (radiographic of nose and paranasal sinuses). Immunologic tests define the presence of hypersensitivity (skin testing, RAST) and immunodeficiency in this disorder.

Adolescent↗

Diseases of the ear.

Otitis media with effusion is a major disorder in children and the most common cause for both major surgery (adenoidectomy with or without tonsillectomy) and minor surgery (middle ear ventilating tubes) in both the United States and Britain. It is frequently associated with respiratory allergy. Medical evaluation, diagnosis, and therapy are discussed. Environmental control measures and pharmacotherapy are reviewed, with a critical review of published appropriately designed studies for its treatment and prevention.

Adult↗

Cognitive and behavioral findings in children taking theophylline.

In a prior pilot study involving six children, we noted improved memory and concentration and improved behavior when these children were switched from theophylline to cromolyn sodium therapy. We now report the findings in 29 children (24 boys and five girls), aged 7 to 12 years. In this study, a double-blind, double-dummy randomized design was used so that half the subjects continued to receive theophylline and the other half was actually switched from theophylline to cromolyn sodium therapy. Assessment again consisted of the revised Wechsler Intelligence Scale for Children, the Selective Reminding test, the Benton Visual Retention test, Stroop tests I and II, and the Child Behavior Checklist. The group receiving placebo theophylline/active cromolyn sodium therapy demonstrated greater improvement on all tests of memory and concentration, with greatest significance for the Stroop test (p less than 0.03 by analysis of covariance). There were also significant correlations between length of time theophylline was taken and scores on the depression (p less than 0.03) and the obsessive-compulsive (p less than 0.04) subscales of the Child Behavior Checklist. These results support the findings of the previous pilot study but, in addition, raise concern about depression and anxiety as possible long-term side effects of long-term theophylline therapy.

Asthma↗

Double-blind evaluation of nebulized cromolyn, terbutaline, and the combination for childhood asthma.

To evaluate whether the potency of a long-acting selective beta 2-agonist negates the need for cromolyn, 27 children, aged 6 to 12 years, with mild to moderate asthma requiring long-term medication, were assessed for the therapeutic effects of cromolyn and/or terbutaline by jet nebulizer. Patients received either cromolyn, 20 mg, terbutaline, 0.1 mg/kg up to 4 mg, or the combination, three times daily. The study design was double-blind, crossover with each patient receiving the three treatment regimens in randomized order for a period of 8 weeks each. Daily diary mean scores generally demonstrated best symptom control with cromolyn or the combination than with terbutaline alone. Cough was significantly less with cromolyn than with terbutaline (p less than 0.05). Morning peak flow measures were higher with combination therapy than with terbutaline (p less than 0.05). Evening peak flow measures were higher with the combination and cromolyn alone than with terbutaline alone (p less than 0.01). Methacholine challenge demonstrated less bronchial hyperreactivity with the combination or cromolyn alone than with terbutaline alone (p less than 0.02). The effectiveness of the nebulizer regimen for children with chronic asthma is better when cromolyn is used alone or in combination with terbutaline than when the beta-agonist is used alone.

Asthma↗

Therapeutic range cromolyn dose-response inhibition and complete obliteration of SO2-induced bronchoconstriction in atopic adolescents.

Eight atopic adolescent subjects with exercise-induced bronchospasm were studied to determine whether cromolyn sodium could inhibit or block sulfur dioxide (SO2)-induced bronchoconstriction. Cromolyn or placebo were administered by turboinhaler 20 minutes before 10 minutes of SO2 exposure at 1.0 ppm during continuous moderate exercise on a treadmill. The exercise level that was chosen did not in itself produce bronchoconstriction. The cromolyn doses were 0 (placebo), 20, 40, and 60 mg. Pulmonary functions (FEV1, and total respiratory resistance) were measured before and after drug administration and after exposure. SO2 exposure after placebo produced significant bronchoconstriction. Pretreatment with 20 mg of cromolyn did not change the SO2 response, 40 mg significantly inhibited the response, and 60 mg completely abolished the pulmonary function changes. These results demonstrate for the first time a dose-response inhibition of SO2-induced bronchoconstriction in atopic subjects within a clinically acceptable dosage range and complete obliteration of SO2 sensitivity in this group with 60 mg of cromolyn pretreatment.

Adolescent↗

Sugar "allergy" and children's behavior.

Sixteen children whose behavior was said to become aggressive, overly active, loud, and noncompliant when ingesting sugar were tested. Sugar-free home diet was maintained and an "open" challenge to a large dose (3 g/kg) of candy bar sucrose was given. Subsequent behavior was noted by actometer, quantitative playroom observation using several standard behavioral tests, and ability to do maze drawings. No significant changes were found on the open challenge test. A slight change from baseline was noted in seven cases on three or four behavioral parameters. Five of these children agreed to a double-blind challenge test utilizing lemon-flavored slushes of sucrose, honey, tapioca starch, or aspartame, administered after a standard lunch free of sucrose. One child reacted to both sucrose and honey and another child reacted only to sucrose. These two children were challenged a second time. The child who reacted to honey again did so according to actometer readings, but this time not by Stony Brook test. To sugar, he reacted only at the 70-minute Stony Brook. The other child reacted to placebo instead of sucrose when rechallenged. The results indicate that high doses of sugar are not related to abnormal behavior. "Open" challenge was sufficient to rule out such a relationship in most instances. A repeated double-blind challenge confirmed the absence of a sugar effect in cases showing initial possibility of response.

Carbohydrates↗

Double-blind, dose-response study of metaproterenol inhalant solution in children with acute asthma.

One hundred children, aged 6 to 12 years, with acute asthma received nebulized therapy with saline, 5, 10, or 15 mg of metaproterenol aerosol solution according to a prerandomized, double-blind protocol. Pulmonary function and cardiac function were assessed for 60 minutes. All patients then received 5 mg of metaproterenol aerosol solution, and observation continued for another 30 minutes. The best response to therapy in terms of rise in FEV1, forced expiratory flow rate between 25% and 75% of FVC, and area under the curve (change in lung function with time) occurred with 5 and 10 mg of metaproterenol. The highest dose, 15 mg, produced significantly less bronchodilation. Although there were no electrocardiographic abnormalities, pulse rate was significantly higher with 10 and 15 mg of metaproterenol than with 5 mg. Five milligrams of metaproterenol aerosol solution is the optimal bronchodilating dose for treating acute asthma in children. Repeating this dose provides some additional bronchodilation and is well tolerated.

Administration, Inhalation↗

The effects of albuterol on sulfur dioxide-induced bronchoconstriction in allergic adolescents.

Ten allergic subjects with exercise-induced bronchospasm were studied to determine whether albuterol could prevent sulfur dioxide (SO2)-induced bronchoconstriction. Albuterol or placebo (180 micrograms) were administered by metered-dose inhaler 20 minutes before a 10-minute exposure to SO2 or clean air during moderate exercise on a treadmill at an exercise level that by itself did not produce exercise-induced bronchospasm. Pulmonary functions (FEV1 and total respiratory resistance [RT]) were measured before the drug, after the drug, and after exposure to SO2 or clean air. Albuterol treatment produced significant bronchodilation and also prevented SO2-induced bronchoconstriction. Following SO2 inhalation after placebo, FEV1 decreased 15% (p less than 0.02) and RT increased 50% (p less than 0.03). Following SO2 inhalation after albuterol treatment, neither FEV1 or RT changed significantly. We conclude that albuterol, a beta 2-agonist, inhibits SO2-induced bronchoconstriction. This result suggests that the adrenergic nervous system or mast cell degranulation are involved in SO2-induced bronchoconstriction.

Adolescent↗

Application of stable isotope methodology in the evaluation of sustained-release theophylline dosage forms.

We compared the kinetics of a single daily dosage form of theophylline (Theo-24) with the kinetics of a twice daily dosage form (Theo-Dur) while we controlled for intrasubject variation in theophylline clearance by use of stable isotope-labeled intravenous theophylline. The stable isotope methodology allowed correction for changes in patient clearance, which allowed more precise estimates of the bioavailability characteristics of these sustained-release theophylline products.

Biological Availability↗

Bitolterol mesylate in exercise-induced asthma.

Exercise-induced asthma is a useful model for evaluating the activity and duration of action of pharmacologic agents of asthma. The main objective of this double-blind, crossover study was to determine the effect of the aerosolized beta-adrenergic agent, bitolterol mesylate, on exercise-induced asthma while its efficacy was being compared with isoproterenol and placebo. Twelve subjects with exercise-induced asthma performed cycloergometer exercise 45 minutes after three inhalations of bitolterol mesylate aerosol (1050 micrograms), or isoproterenol (255 micrograms), or placebo in random sequence. Bitolterol mesylate aerosol was very effective in protecting against exercise-induced asthma. The mean percent maximal decrease of FEV1 after exercise was 5.0% for bitolterol, 22.2% for isoproterenol, and 23.2% for placebo. Subjects experienced skeletal muscle tremor with both bitolterol mesylate (four subjects) and isoproterenol (three subjects), but not with placebo. No other side effects were noted.

Adolescent↗

Blinded comparison of maxillary sinus radiography and ultrasound for diagnosis of sinusitis.

The correlation of Waters view radiographs and A-mode ultrasound for diagnosing sinusitis was evaluated in 75 subjects with allergic rhinitis who presented with signs and symptoms suggesting sinus disease. All patients had Waters view radiographs, which were read by a radiologist (E. G.) who was not provided with historical information. Ultrasound tracings were obtained by registered nurses who were trained to perform this procedure. Tracings were interpreted by two representatives of American Electromedics Corporation, the manufacturer of the Echosine ultrasound machine used in this study. Most common symptoms among the patients were cough and rhinorrhea. The complaint of headache correlated negatively (p = 0.001) with an abnormal radiograph, whereas physical findings of copious and purulent rhinorrhea correlated positively (p = 0.05 and 0.001, respectively). Middle ear abnormalities on examination and tympanometry were more common in those with abnormal radiographs, p less than 0.05 and p less than 0.01, respectively. If the radiograph is considered to be a "gold standard," sensitivity of ultrasound varied from 44% to 58% and specificity from 55% to 61%, dependent on which criteria are applied to the radiograph to consider it normal. A-mode ultrasound is not sufficiently comparable to radiography to be used as its substitute for diagnosing sinus disease.

Adolescent↗

Induction of eustachian tube dysfunction with histamine nasal provocation.

This study assessed changes in nasal airway resistance and nasal airway power as well as eustachian tube function after histamine nasal provocation in 12 atopic subjects and 10 nonatopic subjects. Results demonstrated that subjects could not be placed in the atopic or nonatopic group on the basis of prechallenge nasal resistance and power measurements. Atopic subjects demonstrated a statistically significant difference in nasal airway power after histamine provocation (p less than 0.05). Nine of 12 atopic subjects demonstrated tympanometric changes indicative of eustachian tube dysfunction, whereas none of 10 nonatopic subjects had these changes (p less than 0.001). These results suggest a differential sensitivity of nonatopic and atopic individuals to histamine, which may be an important pathogenetic mechanism leading to the development of eustachian tube dysfunction and possible subsequent development of otitis media with effusion in the atopic group.

Adult↗

Albuterol syrup in the treatment of asthma.

This study evaluated the administration of albuterol syrup (0.1 mg/kg/6 hr) or placebo to 2- to 6-year old children whose extrinsic asthma was treated with maintenance theophylline in a prerandomized, double-blind crossover study design. Albuterol/theophylline treatment produced peak expiratory flow rates 2 hours after administration that were significantly higher than in the theophylline/placebo-treated group (119.3 L/min versus 83 L/min) p less than 0.01. The theophylline/placebo-treated group also required higher serum concentrations of theophylline to control wheezing, 10.5 micrograms/ml versus 5.0 micrograms/ml (p less than 0.01). The average symptom scores for the albuterol/theophylline-treated patients (72.5) were less than that of theophylline/placebo-treated group (97.6) p less than 0.02. Side effects such as tremor, irritability, or insomnia occurred in only two of 17 patients. Serial EKG recordings demonstrated no evidence of cardiotoxicity, such as arrhythmias, or indication of myocardial injury. The addition of albuterol to theophylline improved control of severe asthma in children 2 to 6 years of age demonstrated by improvement in pulmonary function, decrease in theophylline dosage requirement, and improvement in symptoms. It was free of any known cardiotoxicity.

Albuterol↗

Identification of exercise-induced asthma among intercollegiate athletes.

Nine hundred eight-three new intercollegiate athletes were evaluated to estimate the frequency of exercise-induced asthma (EIA). Medical history was obtained using a specifically structured interview. Athletes were selected for exercise testing based on positive responses to questions regarding symptoms of respiratory distress after strenuous exercise. Exercise testing was performed in a controlled laboratory setting using a standard exercise protocol. A laboratory diagnosis of EIA was made if the forced expiratory volume in one second (FEV1) fell greater than or equal to 10%, forced expiratory flow at 25% to 75% of vital capacity (FEF25-75%) fell greater than or equal to 20%, and/or peak expiratory flow rate (PEFR) fell greater than or equal to 12.5% after exercise. The frequency of EIA was 2.8%; only nine of the 28 athletes with EIA were detected prior to arrival at college.

Adolescent↗

Characterization of the late response in exercise-induced asthma.

Nine young adult subjects who developed asthma after a standard treadmill exercise test were studied. Pulmonary function tests were performed before and after exercise and serially for at least 6 hr afterwards. The subjects performed pulmonary function tests while breathing room air and after breathing an oxygen-helium mixture with each test. Although pulmonary function returned to normal within 3 hr after exercising in all subjects, eight of the nine had late asthmatic reactions 3 to 5 hr afterward. In general the late response was less severe than the initial response. Two subjects, however, noticed clinical asthma. In the immediate response, eight of the nine subjects were helium "responders," suggesting that the immediate response involved both large and small airways. In the late response, seven of eight subjects were helium "nonresponders," suggesting that the late response occurred primarily in small airways.

Adult↗