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Biomedical subjects

G G Shapiro

Publications and source records attributed to G G Shapiro.

At least 37 records · Page 2Linked to original sources

Effects of albuterol and procaterol on exercise-induced asthma.

Procaterol and albuterol, beta agonists, were studied using a placebo-controlled, repeated exercise challenge design in order to assess their duration of effectiveness in both bronchodilation and in modifying exercise-induced asthma (EIA). Fifty-three subjects aged 12 to 50 years who had at least a 20% drop in FEV1 during a screening exercise tolerance test were entered. Subjects took two inhalations of procaterol (10 micrograms/inhalation), albuterol (90 micrograms/inhalation), or placebo. Thirty minutes later they exercised on a treadmill at a workload sufficient to induce greater than or equal to 80% aerobic O2 consumption for six minutes. Pulmonary function was measured before and serially for 30 minutes after exercise. The same exercise challenge was repeated three, six, and nine hours after drug administration. Both procaterol and albuterol bronchodilated and modified EIA at 30 minutes and three hours, mean drops in FEV1 being 8.2 and 9.7% respectively at 30 minutes and 16.8 and 16.3% at three hours. This was compared with placebo falls of 30% and 26%. At six hours the subjects' response was similar after both procaterol and albuterol, and fewer subjects had a 20% fall in FEV1 than with placebo, although protection afforded by both beta agonists was substantially less than at three hours. Both drugs were tolerated well.

Adolescent↗

Evaluation of symptom relief, nasal airflow, nasal cytology, and acceptability of two formulations of flunisolide nasal spray in patients with perennial allergic rhinitis.

A new formulation of intranasal flunisolide containing less propylene glycol was compared with the original formulation for efficacy and acceptability in more than 200 patients with symptoms of perennial allergic rhinitis. In this multicenter, randomized, double-blind, parallel group study, symptomatic patients were treated with either the new or the original formulation of 0.025% solution of intranasal flunisolide for 4 weeks to provide 200 micrograms flunisolide daily. Both formulations were highly effective in decreasing symptom scores as evident from patient diary reports before and after treatment (P less than .001). Similarly, nasal airflow was improved with each treatment as measured by anterior rhinomanometry (P less than .0002) and the number of patients with nasal eosinophilia decreased (P less than .01). Finally, fewer patients using the new formulation reported nasal burning or stinging and the acceptability rating of the new formulation was higher.

Administration, Topical↗

Clinical expression of bronchial hyperreactivity in children.

Airway hyperreactivity is a consistent finding in most children with asthma and is responsible for many clinical manifestations of asthma. BH in children has been elicited by bronchial challenge with methacholine and histamine, cold air (isocapnic hyperventilation), and exercise. Pharmacologic agents employed in therapy of childhood asthma, which may modulate both the late asthmatic reaction and bronchial hyperreactivity, include cromolyn sodium, glucocorticoids, and possibly ketotifen. Beta adrenergic agonists, though effectively blocking the early asthmatic response, had no effect on the late response and did not alter bronchial hyperreactivity. Theophylline, in both children and adults, and enprophylline (not yet studied in children) may modify both the early and late responses, but do not appear to have an effect on bronchial hyperreactivity. New drugs that may have potential value in reducing bronchial hyperreactivity include calcium channel blockers and PAF antagonists.

Airway Resistance↗

Terfenadine blockade of exercise-induced bronchospasm.

Terfenadine, in doses of 60, 120, and 180 mg, provided significant bronchodilation for up to four hours after administration. In addition, when the same doses were given four hours prior to exercise, the drug demonstrated significant blockade of exercise-induced bronchospasm at two and five minutes postexercise. These effects on exercise-induced bronchospasm followed a dose-response curve; 180 mg had the most significant effect. All dosing levels, however, produced both bronchodilation and a significant degree of blockade of exercise-induced bronchospasm. No patients were bothered by adverse effects during this single-dose study. Eight of the 11 subjects who completed the study also noted some improvement in their nasal congestion during the testing period when they were on the active drug.

Adolescent↗

Is a uniform round-the-clock theophylline blood level necessary for optimal asthma therapy in the adolescent patient?

Twenty-one patients, 12 to 18 years of age, with nocturnal asthma controlled with sustained-release theophylline administered twice daily, were enrolled in a 10-week, double-blind, two-way crossover study that compared Theo-Dur tablets administered twice daily with an equivalent daily dose of Uniphyl tablets administered once daily at bedtime. Seventeen patients completed the study. The mean morning theophylline serum level obtained with Uniphyl tablets was significantly higher than that obtained with Theo-Dur tablets (13.1 versus 9.6 micrograms/ml, p = 0.02). The mean evening serum level was significantly lower with Uniphyl tablets (6.3 versus 10.1 micrograms/ml, p = 0.003). Despite these differences in serum concentrations, morning and evening pulmonary function test values (forced expiratory volume in one second and peak expiratory flow rate) and symptom scores were nearly identical for the two preparations, as was the supplemental use of aerosol bronchodilators. Once-daily dosing with Uniphyl tablets may benefit adolescent patients with nocturnal asthma by increasing compliance and providing better asthma control. In addition, the lower daytime theophylline levels produced by this preparation may also reduce long-term adverse effects on behavior and cognition.

Adolescent↗

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↗

The role of nasal airway obstruction in sinus disease and facial development.

Allergic rhinitis in children is often complicated by bacterial sinusitis, which can lead to chronic illness and dysfunction. Sinus disease manifests differently in children than in adults, with cough, rhinorrhea, and middle ear disease being common and pain, headache, and fever being uncommon. Sinusitis may exacerbate asthma, and as many as 70% of children with allergy and chronic rhinitis have abnormal findings on sinus x-ray studies. Nasal cytologic specimens showing large numbers of polymorphonuclear cells with intracellular bacteria are also evidence of sinusitis. Obstruction of the nasal airways by allergic rhinitis or enlarged adenoids can lead to deviations in facial growth, specifically increased facial length. With the removal of the obstruction and a return to nasal breathing, facial length may become more normal. Sinusitis in children is treated with antibiotics, usually for 3 to 4 weeks, to eliminate the infection. Adjunctive therapy with antihistamines, decongestants, cromolyn, and corticosteroids may also be helpful. Topical steroids, such as flunisolide and beclomethasone, can be very useful in pediatric patients. These steroids decrease edema and prevent the release of allergic mediators that may be responsible for an environment favoring the bacterial infection causing sinusitis.

Airway Obstruction↗

Sinusitis in children.

Sinusitis is common in allergic children. We are now aware that the commonest presentation of this disorder in the pediatric age group is persistent cough and purulent rhinorrhea. Headache and facial tenderness, frequently noted in adults with sinusitis, are not common. Much remains to be learned about diagnostic techniques and therapy of sinusitis. Nasal cytology can be valuable for discriminating between allergic and infectious disease, but lacks both sensitivity and specificity. Although there is a high correlation between radiographs showing significant sinus membrane thickening or clouding and recovery of bacteria from antral taps, it is possible to see positive films in asymptomatic individuals. Similarly, films may be unremarkable, although the history and physical examination yield convincingly positive evidence for sinus infection. The clinician must sometimes decide on therapy when the diagnosis is not definitive. Antimicrobial therapy for sinusitis should be given for 3 to 4 weeks in many cases. Amoxicillin remains a good choice for therapy, but antibiotics capable of clearing infections by beta lactamase-producing bacteria should be considered in refractory situations. The value of antihistamines, decongestants, nasal steroids, and cromolyn sodium are unstudied at this time. If several antibiotic courses fail to alleviate the signs and symptoms of sinusitis, surgery is indicated. Antral lavage and creation of nasoantral windows is the usual approach in children. Patients with sinusitis often have concurrent middle ear disease. Patients with current sinusitis have a higher incidence of immunoglobulin disorders than found in a normal pediatric sample. It appears that patients with sinusitis are more often allergic than would be expected from 2 typical population distribution. More evaluation is needed to clarify these associations.

Amoxicillin↗

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 perennial allergic rhinitis on dental and skeletal development: a comparison of sibling pairs.

This study analyzed the effect of perennial allergic rhinitis on dental and facial skeletal characteristics. Twenty-five allergic children who were apparent mouth breathers, their 25 siblings who did not have the disease and were apparent nose breathers, and 14 nasal breathing control subjects were examined medically, dentally, and cephalometrically. Compared with their siblings, the allergic subjects had more nasal mucosal edema, a higher proportion of eosinophils in their nasal secretions, and greater nasal power. The allergic subjects were characterized by deeper palatal height, retroclined mandibular incisors, increased total anterior facial height and lower facial height, a larger gonial angle, and greater SN, palatal, and occlusal planes to mandibular plane angles. All of these measures except gonial angle were also significantly different between the allergic children and the nonconsanguineous controls. Also, the allergic subjects compared with controls had smaller SNB and SN-pogonion angles and an increased overjet. Both allergic and nonallergic sibling groups showed larger mean adenoid size on radiographs than controls. For most variables the nonallergic siblings fell between the allergic children and the control subjects. Overall, the allergic children had longer, more retrusive faces than controls. This retrusive characteristic was present in nonallergic siblings and cannot be ascribed to the apparent breathing mode at the time of the study. These results confirm earlier reports that allergic rhinitis may be associated with altered facial growth. Controlled longitudinal studies to analyze a possible cause-and-effect relationship and the effects of medical and surgical treatments should be undertaken.

Adolescent↗

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↗