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Biomedical subjects

A L Boner

Publications and source records attributed to A L Boner.

At least 127 records · Page 7Linked to original sources

Theophylline levels after single daily and divided dosing of a once-a-day theophylline preparation in asthmatic children.

Twelve children with chronic asthma were treated with a single dose of sustained-release theophylline once-a-day taken after supper at 9 PM. During the steady-state period after 15 days of treatment, serum theophylline levels were measured one and two hours after dosing and then every two hours until 9 PM the following day. The peak concentration (mean +/- SD) of serum theophylline (20.9 +/- 6.5 micrograms/mL) was observed eight hours after dosing while the through concentration (4.34 +/- 2.62 micrograms/mL) was measured 24 hours after dosing; the percent fluctuation (mean +/- SD) was 966.45 +/- 1105.55%. Another 15 children were treated with the same preparation administered at 8 AM after breakfast and at 8 PM after supper. Serum samples for theophylline concentration were obtained immediately before dosing at 8 AM and then every two hours for the following 12 hours. The mean theophylline level observed immediately before dosing at 8 AM was 10.16 +/- 3.84 micrograms/mL while the mean level at 8 PM was 9.39 +/- 4.77 micrograms/mL. The peak serum level was 13.07 +/- 5.13 micrograms/mL at 2 PM, while the trough was 9.31 +/- 3.71 micrograms/mL at 10 AM, with a percent fluctuation of 155.21 +/- 147.95%. Few side effects were seen in both groups. The results of our study clearly demonstrated that in children the percent fluctuation and peak-trough differences are far greater with once daily than with twice daily dosing and this should be considered when planning theophylline treatment in asthmatic children. The administration of a once-a-day preparation every 8-12 hours can however result in overlapping absorption patterns.

Adolescent↗

Comparison of the protective effect and duration of action of orally administered clenbuterol and salbutamol on exercise-induced asthma in children.

Clenbuterol (C), a long-acting beta 2-selective bronchodilator was compared with salbutamol (S) in exercise-induced asthma (EIA) at two premedication time levels. Sixteen asthmatic children with EIA living at an altitude of 1,750 m were treated with C (0.001 mg/kg) and S (0.12 mg/kg), administered randomly in a double-blind cross-over study 90 and 300 minutes before exercise tests of running on a treadmill for 6 minutes. Pulmonary functions were evaluated prior to the administration of the drugs and immediately before, at the end of, and 2, 5, 10, 15, 20, and 25 minutes after exercise tests. In the preliminary screening exercise test the mean fall of FEV1 was 41.1%, but it was 21.0% and 27.1% after S and 21.9% and 19.9% after C administered 90 and 300 min prior to the test, respectively. Salbutamol administered 300 minutes before the test was statistically less effective than the same drug administered 90 minutes before the test or C administered 300 minutes before the test. Therefore, we can conclude that clenbuterol provides a more lasting protection than salbutamol in EIA.

Administration, Oral↗

Plasma fibronectin concentrations in healthy newborns and in children.

Plasma fibronectin (FN) concentrations were measured by an immunonephelometric method in cord blood from 76 healthy newborns (45 full term and 31 preterm), in 181 healthy children, from 1 month-15 years old, divided by age into seven groups and in 81 control adults. FN levels in newborns were 35% of those of adults. There was no difference between plasma FN in term and preterm (gestational age greater than 30 weeks) infants. Preterm newborns below the gestational age of 30 weeks showed particularly low FN levels. No clear correlation was seen with birth weight. In the child population, a strong increase in FN values was noted in the first 6 months of life, rising to 65% of the normal adult values. No further increase occurred until puberty.

Adolescent↗

Effect of food on the bioavailability of a slow-release theophylline formulation.

A study was conducted in two groups of healthy volunteers to assess whether the time of administration (10 min before the meal versus 60 min after the meal) influences the pharmacokinetics and absorption kinetics of a slow-release theophylline product (Teonova). In the first group (Group A, n = 10), the drug was given in a paired-sample design as a single dose of 600 mg before and after breakfast with an interval of at least 1 week between the two administrations. In the second group (Group B, n = 10), Teonova was given by the same study design before and after dinner. In all cases, time curves of theophylline plasma levels were determined by collecting serial blood samples 24 h after dosing and analysed pharmacokinetically through model-independent methods. In Group A, curves obtained before and after the meal were fully superimposable, and no difference was found between the pharmacokinetic parameters determined in either condition. The same result was obtained in Group B. Our results indicate that, after single dose, the two different times of administration that we tested were equivalent in pharmacokinetic terms.

Adult↗

Efficacy and duration of action of placebo responses in the prevention of exercise-induced asthma in children.

Exercise-induced bronchoconstriction, a common phenomenon in asthmatic children, may be prevented by the administration of appropriate drugs. In this study we evaluated the effect and duration of action of placebo (Freon gasses) administered to the patients as a protective drug. The maximum decrease in forced expiratory volume in 1 second (FEV1) after exercise testing was 40.3% +/- 3.10 at the initial screening session and, on different study days, 23.3% +/- 3.57, 28.8% +/- 3.86, and 33.7% +/- 3.71 30, 120, and 240 minutes, respectively, after the administration of Freon gasses. There was a linear trend indicating a reduction in protection with time. The placebo effect was marked 30-120 minutes after treatment (p less than 0.01) and completely disappeared after 4 hours. The placebo effect should always be considered in the evaluation of any new antiasthmatic drug.

Adolescent↗

Spinhaler specific bronchoprovocation challenges: short interval administration of micronized freeze-dried allergen in children with bronchial asthma. III.

Two different methods of antigen bronchial challenge, with micronized freeze-dried extract of D. pteronyssinus administered as a powder by a spinhaler, were evaluated in 15 asthmatic children, who were skin test positive and RAST positive for house dust mite D. pteronyssinus. In one method, daily increasing dose method (DIDM), a single antigen challenge was performed every day successively. In the other method, cumulative dose method (CDM), the antigen doses were administered successively with 7-minute intervals. The tests were considered positive when there was a fall of FEV1 greater than or equal to 20% of the baseline value. The DIDM showed a greater incidence of isolated late bronchoconstrictions. The CDM revealed a great incidence of biphasic reactions (early and late) and of laryngeal spasm. Two patients showed discordant results (positive with one method and negative with the other) suggesting problems related to intrasubject reproducibility.

Adolescent↗

Comparison of the effects of inhaled calcium antagonist verapamil, sodium cromoglycate and ipratropium bromide on exercise-induced bronchoconstriction in children with asthma.

Fifteen children with exercise-induced asthma (EIA) participated in a double-blind trial comparing the protective effects of inhaled sodium cromoglycate (20 mg/2 ml), ipratropium bromide (500 micrograms/2 ml) and verapamil (5 mg/2 ml). Saline was used as control. There was no significant difference in base line pulmonary function before and after the administration of each agent. After exercise the maximal percentage fall in the forced expiratory volume in 1 s (FEV-1) (means and SD) were 40.9 +/- 17.2 after inhalation of saline, 15.3 +/- 11.7 after sodium cromoglycate, 36.2 +/- 21.4 after verapamil and 21.7 +/- 17.7 after ipratropium bromide. The inhibitory effects of sodium cromoglycate and ipratropium bromide were significant whereas verapamil failed to produce any effect. To see if a double dose of verapamil is more effective, nine different children with EIA were provoked by the same standardized treadmill running after giving a placebo (4 ml saline) and after verapamil (10 mg in 4 ml). Despite the double dose, again verapamil was ineffective even though the protection index doubled that obtained with the lower dose. The results suggest that the calcium antagonist (verapamil) had almost no effect on the prevention of EIA in the children studied.

Administration, Inhalation↗

Clinical and immunological findings in four infants with Omenn's syndrome: a form of severe combined immunodeficiency with phenotypically normal T cells, elevated IgE, and eosinophilia.

We report four cases of Omenn's syndrome (OS), an autosomal recessive disease characterized by early erythrodermia, protracted diarrhea, severe infections, lymphadenopathy, hepatosplenomegaly, failure to thrive, and leukocytosis with marked eosinophilia. The immunological investigations revealed B lymphopenia with increased levels of serum IgE and marked depression of T-cell activation, not restored by the addition of exogenous interleukin 2 (IL-2). IL-2 and interferon-gamma (IFN-gamma) production in vitro were very low or absent. One patient was treated with HLA-identical bone marrow transplant with a complete remission of the clinical picture and the immunological defect. The infant died of graft versus host disease 4 months after the graft. For the remaining three infants the outcome was also fatal within the first year of life. In conclusion, OS should be considered a severe combined immunodeficiency disease with peculiar clinical, immunological, and histological findings.

Antibody Formation↗

Nebulised sodium cromoglycate and verapamil in methacholine induced asthma.

Fifteen children with asthma underwent challenges with methacholine on separate days after double blind administration by nebuliser of either verapamil (5 mg), cromoglycate (20 mg), or saline (placebo). The provocation doses that produced a 20% fall in forced expiratory volume in one second (PD20) were analysed. There was variation in the protective effects of verapamil and cromoglycate among the patients. Although cromoglycate produced an increase in PD20 in 53% of the children tested, the protection was not significant when compared with the placebo. Verapamil was partially protective, however, in 80% of children and achieved significantly better results than the placebo. We suggest that this is likely to be due to a direct effect on bronchial smooth muscle.

Adolescent↗

Effects of different dosages of the calcium antagonist verapamil in exercise- and methacholine-induced bronchospasm in children with chronic asthma.

The protective effect of 5 mg/2 ml and 10 mg/4 ml of the calcium antagonist verapamil on methacholine challenge and exercise were evaluated in two groups of asthmatic children. Saline solution was used as placebo. No significant differences were seen in baseline pulmonary function in and within groups. There was a minimal but significant bronchodilation 30 minutes after inhalation of verapamil 5 mg/2 ml. The drug did not reduce methacholine sensitivity at any dosage. After exercise, verapamil 5 mg/2 ml showed a significant change in the maximum percentage drop in forced expiratory volume in 1 second (FEV1) compared with placebo. This was not the case for the group treated with a double dosage. At this time, there is no evidence for a major role of verapamil in the treatment of childhood asthma.

Adolescent↗

Oral clenbuterol and procaterol. A double-blind comparison of bronchodilator effects in children with chronic asthma.

In a double-blind crossover study, clenbuterol at a dose of 0.75 micrograms/kg, procaterol at a dose of 1.5 micrograms/kg, and placebo, all administered orally, were compared for bronchodilation efficacy. Twelve children aged from 6 to 13 years, with moderate to severe asthma, participated in the trial. Pulmonary function, heart rate, blood pressure, and tremor were evaluated at 30, 60, 90, and 120 minutes and then hourly for 8 hours after administration. Both clenbuterol and procaterol induced a significant change over their baseline values for all the pulmonary function parameters considered. For clenbuterol, the same was also observed in comparison with placebo, while for procaterol this was true only for FEV1 and FEF25-75, while no difference resulted from FVC and PEF. Mild and transient tremor was the only side effect observed. Oral clenbuterol and procaterol were both demonstrated to be safe and effective. However, at the doses studied, clenbuterol had a significantly higher bronchodilator activity lasting up to 8 hours.

Administration, Oral↗

Salbutamol and ipratropium bromide solution in the treatment of bronchospasm in asthmatic children.

The effects of the beta 2-adrenergic agonist salbutamol (0.02 mL/kg of a 0.5% solution) and the cholinergic antagonist ipratropium bromide (2 mL of a 0.025% solution), administered alone or in combination at different doses, were evaluated in 48 asthmatic children using a single-dose, double-blind, crossover design. Spirometric measurements were taken before and 10, 30, 60, 120, 180, 240, 300, and 360 minutes after administration of the drugs. All regimens produced significant bronchodilatation 10 to 30 minutes after administration. The improvement began to decline three to four hours after inhalation, particularly when ipratropium bromide was administered alone. The administration of the salbutamol plus ipratropium combination did not significantly improve pulmonary function values as compared to salbutamol alone. The effects of salbutamol and ipratropium bromide in half-dose or full-dose combinations were indistinguishable. No significant adverse effects on blood pressure or heart rate were observed.

Adolescent↗

A new sustained-release theophylline suspension for asthmatic children: evaluation of serum theophylline concentrations.

Theophylline level variability obtained with standard slow-release theophylline tablets was compared to that obtained with a new sustained-release theophylline suspension in asthmatic children. The sustained-release preparations were administered every 12 hours and serum samples were collected after ten days of treatment during the steady-state period. In this crossover study, the sequence of the two regimens (slow-release tablets versus slow-release suspension) was selected at random. Both preparations of theophylline were administered at a mean dosage (+/- s.d.) of 19.3 +/- 1 mg/kg/day. The results of our study demonstrated that theophylline serum levels remain within the therapeutic range for both preparations, but there was a greater fluctuation with theophylline suspension compared to the tablets. The tolerability of the two drugs was satisfactory.

Adolescent↗

Comparison of two new controlled-release theophylline formulations in the management of asthma in children and reliability of salivary theophylline concentration.

Two slow-release preparations of theophylline have been compared in an open crossover trial in the treatment of 20 asthmatic children. Theophylline concentrations were measured in both serum and saliva. Although the treatment preference of both patients and clinicians was for Somofillina Ritardo, there was no significant difference between the two treatments in respect to either serum and salivary concentrations. Nor did their mean bioavailabilities differ significantly. The results indicated that concentration in saliva was not a useful indicator of the serum concentration.

Administration, Oral↗

Ceftazidime in pediatric infections unsuccessfully treated with other antibiotics: an evaluation of its efficacy and tolerability in compromised host.

Ceftazidime (C) is a cephalosporine active against Gram-positive and especially negative bacteria. The aim of the study was to evaluate efficacy and tolerance of C in the treatment of children suffering from infections previously treated unsuccessfully with different antibiotics. We examined 20 children, administering a dosage of C 30 to 100 mg/kg intravenously or intramuscularly for a mean treatment duration of 8.6 days. A favorable response was observed in all the children: of the 20 patients 13 were cured and 7 improved. A transient elevation of liver enzymes was noted in three children. The study confirms the efficacy of C in the treatment of severe infections. Since 9 of the 20 patients were neonates, we suggest the possible role of C in the newborns' infections.

Bacterial Infections↗

The efficacy of ketotifen in a controlled double-blind food challenge study in patients with food allergy.

The effectiveness of oral ketotifen was compared with that of placebo in 26 patients with food allergy in a randomized, double-blind parallel study. Patients were selected on the basis of food allergy as established by history, clinical improvement after an exclusion diet, and reappearance of the symptoms after a challenge with the food. Thirteen patients were given ketotifen and 13, placebo. Ketotifen or placebo were administered twice daily for 1 month after the first oral provocation test and the last dose was given 12 hours before the second oral provocation test. Ketotifen protected patients (7/13) significantly more than placebo (2/13; P less than .05). The results of this study suggest that ketotifen may be useful for some patients with food allergy.

Adolescent↗

Simplified spinhaler method for antigen-specific bronchoprovocation in children with bronchial asthma. I.

Specific bronchial challenge has been performed using a micronized, freeze-dried allergen extract of D. pteronyssinus administered as a powder at increasing concentrations (0, 50, 100, 200, 400, 600, 800, and 1,000 Allergenic Units) by a cromolyn spinhaler delivery system. The test was performed in ten asthmatic children with house mite D. pteronyssinus skin test and RAST positivity and in six non-allergic asthmatic children. A positive early reaction to bronchial challenge occurred in eight out of ten allergic children. A ninth child of this allergic group presented only the late reaction. Five patients of the control group (skin test and RAST negative for D. pteronyssinus had negative results while one child had a positive response both with early and late reactions. A significant increase in methacholine sensitivity was observed in the allergic group the day following the specific challenge. The modified spinhaler procedure (Hypoinhal, Lofarma) used for specific bronchial challenge showed a good correlation with skin test and RAST positivity in patients as well as in the control population. The method provides advantages of simplicity, ease of performance and cost effectiveness.

Administration, Intranasal↗

Comparative study of two methods for spinhaler-specific bronchoprovocation challenges. II.

Two different methods of performing specific bronchial challenge using a micronized freeze-dried extract of D. pteronyssinus administered as a powder by a spinhaler have been evaluated in 11 children with chronic asthma and skin test RAST positive for house dust mite D. pteronyssinus. In the first method, "Cumulative Dose Method" (CDM), the test doses of antigen [0, 50, 100, 200, 400, 600, 800, and 1,000 Allergenic Units (A.U.)] were successively administered in 30-minute intervals. With the other method, "Daily Increasing Dose Method" (DIDM), a single antigen challenge (only one cup) was performed every day successively. The tests were considered positive when FEV1 values dropped below 20% of the value obtained immediately before the inhalation of the antigen. The early FEV1 fall was 36.6% +/- 10.8% with CDM and 29.1% +/- 11.5% with DIDM. There was a mean late fall of FEV1 52% +/- 17% and 35.3% +/- 12.2%, respectively, after a mean antigen administration of 270 +/- 149 A.U. with CDM and of 290 +/- 202 A.U. with DIDM. An increase in non-specific bronchial reactivity was observed after specific challenge performed with both methods. The CDM offers the advantage of obtaining information more quickly. The DIDM offers the advantage of administering a lower daily dose of antigen. Our results indicate that a modification of CDM with a shorter interval of administration may further improve this method of antigen administration.

Antigens↗