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Biomedical subjects

G G Shapiro

Publications and source records attributed to G G Shapiro.

At least 91 records · Page 5Linked to original sources

Pharmacokinetics of theophylline in acute asthma.

Serum theophylline concentrations were measured in 17 children and adolescents with acute asthma who received an aminophylline loading dose of 7 mg/kg and a constant infusion of 15 mg/kg/24 hours. The mean total theophylline clearance rate was 1.32 +/- S.D. 0.66 ml/min/kg. Hypoxia, and in two patients, acidosis, did not appear to significantly influence theophylline clearance rates. Inter-individual differences in clearance rates were great. No child experienced symptoms or signs of theophylline toxicity during the study. If serum theophylline concentrations cannot be monitored readily, an aminophylline infusion rate of 15 mg/kg/24 hours can be used safely in patients with acute asthma, but in most patients this infusion rate will not provide serum theophylline concentrations in the desired therapeutic range of 10-20 microgram/ml. Monitoring of serum theophylline concentrations during aminophylline infusion is desirable in order to individualize infusion rates, and achieve optimal bronchodilation without toxicity.

Acute Disease↗

Exercise, induced bronchospasm in asthmatic children as a dose-response model for theophylline.

Efficacy and dose-response activity of oral theophylline were evaluated in 21 asthmatic children, using inhibition of exercise-induced bronchospasm (EIB) as a therapeutic marker. An aqueous theophylline suspension free of alcohol, sugar, and dye was found to be effective for prevention of EIB when given in usual maintenance doses of 4 to 6 mg/kg every 6 hours for 3 weeks, following single loading doses of 8 mg/kg. Pulmonary function measurements (FEV1, FEF25%-75%, PEFR) following standardized treadmill exercise stress were signifcantly improved during both acute and chronic theophylline administration compared to pre-drug control evaluations. There were no signs of developing tolerance to theophylline. The drug produced at least 50% inhibition of EIB in 16 to 21 patients treated. Individualized adjustment of maintenance dosage resulted in optimal theophylline serum concentrations of 10 to 18 microgram/ml in 17 patients. Signs of drug toxicity were observed only when serum levels exceeded 20 microgram/ml following loading doses in 6 patients. Although some children required higher maintenance dosage because of variability in theophylline pharmacokinetics, no child experienced adverse effects after dosage adjustment. Serum half-life ranged between 86 and 351 minutes (mean, 259 minutes); mean peak serum concentration of theophylline after 3 weeks of treatment was 14.9 microgram/ml.

Adolescent↗

A double-blind evaluation of the use of nebulized metaproterenol and isoproterenol in hospitalized asthmatic children and adolescents.

This study compared two beta-adrenergic agents in the treatment of severe asthma of children and adolescents. Thirty patients admitted to Children's Orthopedic Hospital and Medical Center with acute asthma were treated with either isoproterenol 0.05% (iso) or metaproterenol 0.5% (meta) nebulized in physiologic saline and delivered with O2 in addition to intravenous hydration, aminophylline, and corticosteroids. Vital signs, blood gases, and pulmonary function were monitored frequently. No adverse reactions to the study drugs were encountered. Pulse rates increased similarly after treatments with both drugs. Patients treated with meta had somewhat higher rates than those treated with iso. Diastolic blood pressure decreased significantly from admission in the meta group compared to the iso group. For FVC and FEV1, the meta group had greater percentage increases from admission than the iso group at all times, with the difference being significant (p less than 0.05) at 1 and 12 hr. The same trend occurred for FEF 25%-75%. Though iso seemed to cause greater increases in flow immediately after administrations, these changes were transient compared to improvement caused by meta. Thus, meta seemed to be more effective than iso in reversing bronchospasm as measured by certain pulmonary function parameters.

Adolescent↗

Safety of influenza vaccination in allergic children.

One hundred forty-two allergic children aged three to 18 years were studied for evaluation of the usefulness of skin testing with influenza vaccine as a means of identifying those children who could be immunized safely despite their allergies to chickens, eggs, or feathers. One hundred twenty-eight children were fully immunized with bivalent influenza A/New Jersey/76-A/Victoria/75 vaccine. Twelve children had positive skin tests and were not immunized, and two developed positive skin tests after their first injection. One child had urticaria 8 hr later, one had a nonspecific reaction, and one had a self-limited erythema multiforme reaction eight days after the second injection. All others tolerated the procedure well. History of sensitivity to eggs was not as reliable an indication of vaccine sensitivity as skin testing with vaccine. A negative result of an intradermal skin test with a 1:100 dilution of the vaccine in saline appeared to be a reliable indicator of allergic subjects who could be immunized against influenza without fear of life-threatening acute allergic reactions.

Adolescent↗

Acute and chronic theophylline therapy in exercise-induced bronchospasm.

This study examined the effectiveness of theophylline therapy in modifying exercise-induced bronchospasm (EIB) in children with perennial asthma and evaluated whether tolerance to theophylline developed with prolonged use. Twenty-one children between 7 and 16 years of age were studied by a standardized treadmill exercise test carried out before administration of theophylline, 90 minutes after administration of theophylline, and again after three weeks of round-the-clock theophylline treatment. Changes in forced expiratory volume at one second, forced expiratory flow between 25% and 75% of vital capacity, and peak expiratory flow rate were measured before and after each exercise test. Theophylline inhibited EIB in 20 of 21 subjects. There was considerable intersubject variation in the response to theophylline, however, ranging from complete inhibition in five subjects to no inhibition at all in one subject, even though theophylline controlled perennial asthma in all subjects, and all but one had theophylline levels between 10 and 22 microgram/ml when tested. On repeated testing after three weeks of therapy, no tolerance developed to theophylline. These findings suggest that EIB and perennial asthma may result from different causes and tha theophylline's ability to control asthma will not predict its effect on EIB. Subjects who have severe EIB should be retested after theophylline pretreatment of evaluate the effectiveness of therapy.

Acute Disease↗

Physiology of steroid dependent and non-steroid dependent asthmatic youths.

This study was designed to compare physical findings, pulmonary function and pituitary-adrenal function in steroid dependent (SD) and non-steroid dependent (NSD) children and adolescents in order to clarify similarities and differences between these groups. Study patients included 20 steroid dependent and 14 non-steroid dependent subjects. Abnormalities confined to the SD group included growth suppression, bone age retardation and cataracts. Pulmonary function abnormalities were severe in both groups. While the SD group also showed a degree of pituitary-adrenal abnormality. This suggests that chronic pulmonary disease may have physiologic consequences extending beyond the pulmonary tree.

Adolescent↗

Growth, pulmonary, and endocrine function in chronic asthma patients on daily and alternate-day adrenocorticosteroid therapy.

Growth, pulmonary, and adrenal-pituitary function were assessed in 20 steroid-dependent asthmatic children and adolescents while they were on daily prednisone therapy. The patients were then switched to equivalent daily methylprednisolone or twice equivalent alternate-day methylprednisolone for a 3-mo period, after which time studies were repeated. The steroid regimens were then crossed so that those patients taking daily methylprednisolone were switched to alternate-day therapy and the alternate-day therapy patients were switched to daily medication for another 3-mo interval, after which studies were repeated again. Abnormal growth, bone maturation, and cataracts were identified. Mean symptom scores at each evaluation were similar. Pulmonary function tests and shunt studies showed little difference between methylprednisolone and prednisone. Endocrine function tests showed a high incidence of disturbed pituitary and adrenal function. A 3-mo period of alternate-day therapy did not alter this.

17-Hydroxycorticosteroids↗

The paradoxical effect of adrenergic and methylxanthine drugs in cystic fibrosis.

This study examined the effect of aerosolized isoproterenol and oral theophylline on pulmonary function in cystic fibrosis (CF) to determine how often these drugs are beneficial and whether there is a correlation between response to isoproterenol and response to oral theophylline. After obtaining baseline pulmonary function tests before and after isoproterenol aerosol, 12 patients with CF were put on a double-blind trial of high-dosage theophylline (10 mg/kg three times per day) or placebo for four weeks and were then switched to the alternate regimen for the next four weeks. Patients had weekly evaluations of pulmonary function and plasma theophylline determinations. Gastrointestinal side effects were common with theophylline. The responses to aerosolized bronchodilators were inconsistent from week to week. After aerosolized bronchodilator, five of 12 patients had an average increase of 10% or more in FEF45%-55% and FEF70%-80%. While taking oral theophylline, five patients had a 10% or more decrease in FEF 45%-55% and six patients had a decrease in FEF70%-80%. We conclude that there was no concordance between response to isoproterenol and theophylline, and that adrenergic and methylxanthine drugs must be used with caution in patients with CF.

Administration, Oral↗

Exercise-induced asthma. Pharmacological assessment of single drugs and drug combinations.

The relative effectiveness of ephedrine, theophylline, and hydroxyzine hydrochloride and their combinations was studied in a two-part investigation of 16 youths who has asthma and exercise-induced asthma. The beneficial and adverse effects of the drugs in the control of asthma were studied in the first part of the investigation. Both theophylline and ephedrine were judged superior to placebo when given alone. When combined they were somewhat more effective than either agent alone, although adverse effects precluded their use in almost half of the subjects. The addition of hydroxyzine diminished the side effects sufficiently to make the combination acceptable to four subjects who refused to take ephedrine/theophylline. In the second part of the study, the relief of exercise-induced asthma was evaluated. Ephedrine had no effect, hydroxyzine had a weak effect on hastening recovery, but theophylline modified the postexercise response significantly. The three drugs together produced an additive effect superior to that of theophylline alone.

Adolescent↗

The pharmacological assessment of single drugs and drug combinations in exercise-induced asthma.

The relative effectiveness of ephedrine, theophylline, hydroxyzine, and their combinations in relieving cycloergometer exercise-induced asthma were studied in 16 children and adolescents. Ephedrine had no effect on post-exercise asthma, hydroxyzine had weak effect on hastening recovery, while theophylline modified on the post-exercise response significantly. The three drugs together produced an additive effect superior to that of theohylline alone.

Adolescent↗

The effect of cromolyn sodium on exercise-induced bronchospasm using a free running system.

This study was designed to assess the effectiveness of comolyn sodium in modifying exercise-induced bronchospasm (EIB). Twenty children and adolescents with EIB were given either cromolyn or placebo in a prerandomized double-blind fashion. They then performed a free running maneuver. Pulmonary function tests were obtained before and after this exercise. Patients returned one week later to repeat the same precedure. This time subjects took placebo if they had previously taken cromolyn and vice versa. Significant beneficial effects of cromolyn were noted in forced vital capacity and forced expiratory volume in one second measurements but not in forced expiratory fhis suggests that larger airway disease is preferentially helped by cromolyn when subjects are stressed maximally as with a free running system. Subjects who received placebo on study day 1 and cromolyn on study day 2 showed the most striking benefit from cromolyn. This may be related to the better baseline status of subjects on day 2 as well as to familiarity with the procedure and medication.

Adolescent↗

Cromolyn sodium: a review.

Cromolyn is a white crystalline powder which is poorly absorbed from the gastrointestinal tract. Its therapeutic value lies in its functions as an inhaled or topically applied agent. Cromolyn has been approved in the United States for asthma therapy since 1973. It was marketed at that time as a drug to reduce the corticosteroid requirements of severe asthmatics. It clearly did not live up to that claim. Initial enthusiasm for cromolyn was replaced by disillusionment. In the last few years, investigators have taken another look at cromolyn and have a renewed interest in it. Cromolyn's mechanisms of action remain only partially understood. It appears to block allergic mediator release from certain mast cells. It may also decrease bronchial hyperreactivity. The frequency of drug toxicity at customary dosages is extremely low. Adverse effects tend to be mild, short-lived and without sequelae. Currently, cromolyn is a first line therapy for mild to moderate asthma requiring chronic treatment. It is also of proven efficacy in the treatment of allergic rhinitis, allergic conjunctivitis and vernal keratoconjunctivitis.

Administration, Intranasal↗