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Biomedical subjects

B Hegardt

Publications and source records attributed to B Hegardt.

13 recordsLinked to original sources
PubMed1985

Effects of long-term treatment with low dose cimetidine on allergen-induced airway responses and selected immunological parameters in atopic asthmatics.

Twenty asymptomatic atopic asthmatics were treated with either cimetidine 100 mg orally (13 patients) or placebo (7 patients) once a day for 4 weeks. Bronchial challenges were performed with the pertinent allergen immediately before and 2 and 4 weeks after the initiation of treatment and, finally, 4 weeks after the cessation of treatment. Before each challenge blood was drawn for the determination of specific IgE antibody levels (RAST procedure) and total IgE (PRIST), allergen- and anti-IgE-induced basophil histamine release, and mitogen-induced lymphocyte (3H)-thymidine incorporation. Patients treated with cimetidine were found to be significantly (P less than 0.05) less responsive to bronchial allergen challenge during the treatment than before it; patients treated with placebo were more reactive (P less than 0.05) 14 days after the initiation of treatment. The difference in responsiveness to treatment between the placebo and the cimetidine groups was significant 14 days (P less than 0.01) and 4 weeks (P less than 0.05) after the initiation of treatment; no significant difference in allergen responsiveness was recorded between the groups 1 month after cessation of treatment. No clear-cut changes in specific IgE antibody or total IgE levels, histamine release capacity, or mitogen-induced lymphocyte responsiveness were observed in either group, except that lymphocytes from cimetidine-treated patients tended to show an increased ratio of PHA- to PMA-induced thymidine incorporation. Thus, it was found that the treatment of asymptomatic atopic asthmatics with low-dose cimetidine reduced their allergen sensitivity in bronchial provocation tests by a mechanism which remains to be elucidated.

Adult↗
PubMed1983

Pharmacological modulation of mediator release: therapeutic significance?

The therapeutic significance of modulation of mediator release with drugs like DSCG, beta-agonists, xanthine derivatives, anti-histamines and glucocorticosteroids is not yet fully known. There is ample evidence that DSCG operates via mechanisms other than, or in addition to, mast cell stabilization. The main clinical usefulness of beta-agonists seems to be related to bronchodilatation, probably in combination with other effects. This may also be the case with xanthine derivatives. The role of anti-histamines in asthma generally is still under evaluation. Finally, corticosteroids may exert a large part of their clinical effect by modulating the arachidonic acid cascade. However, this is not yet clinically proven.

Adrenergic beta-Agonists↗
PubMed1982

The protective property of equipotent bronchodilating doses of inhaled KWD 2131 and terbutaline against allergen-induced bronchospasm.

The anti-allergic capacity of nebulized KWD 2131 in inhibiting allergen-induced bronchospasm was compared with that of terbutaline in equipotent bronchodilating doses. It was a double-blind cross-over and randomized study also including placebo. Twelve symptom-free extrinsic asthmatics participated in the trial. Equipotent bronchodilating doses of the two beta-receptor-agonists were established in a histamine challenge procedure before the start of the study. Allergen challenge was performed with double concentration steps every 10 min until a greater than or equal to 20% decrease in FEV1 was achieved. Significantly (P less than 0.001) more allergen dose steps could be used after pretreatment with KWD 2131 and terbutaline than with placebo. No difference could be observed between the active compounds. The same allergen log dose gave a 20% decrease in FEV1 after pretreatment with KWD 2131 and terbutaline. The active compounds' protective properties did not differ at a lower degree of allergen challenge. The plasma histamine level was not significantly changed at any point of allergen challenge after pretreatment with either placebo or the active compounds. Therefore, plasma histamine determination was of no value for evaluating the inhibition of mediator release by these drugs. It is concluded that the anti-allergic property of KWD 2131 at allergen challenge does not give any further clinical value besides the bronchodilating property.

Administration, Intranasal↗
PubMed1981

Inhibitory effect of KWD 2131, terbutaline, and DSCG on the immediate and late allergen-induced bronchoconstriction.

Beta-adrenoceptor stimulants exhibit both bronchodilating and anti-allergic activities. KWD 2131 is a new beta-agonist with preferably anti allergic property. In an earlier study, nebulized KWD 2131 in a non-bronchodilating dose (0.25--0.50 mg) did not give significant protection against immediate reaction. The present study evaluated whether an increased nebulized dose of the new compound (5 mg) could protect against either immediate and/or late responses. The response was compared with a nebulized dose of terbutaline (5 mg) and with twice the recommended dose DSCG (40 mg). The study included 10 patients with known allergic asthma. It was designed as a single-blind cross-over trial with randomized allocation of the drugs. Lung functions were measured spirometrically and by body-plethysmograph; flow volume curves were drawn. KWD 2131 gave no significant protection against immediate reaction. Both terbutaline and DSCG did so, terbutaline being more efficient. Contrary to the beta-agonists, DSCG also gave protection against late response.

Adrenergic beta-Agonists↗
PubMed1981

Evaluation of the inhibition of allergen-induced intracutaneous reactions by a new beta-agonist, KWD 2131, and by terbutaline.

In a double-blind crossover study, the wheal inhibiting effect of a new beta-agonist, KWD 2131, and terbutaline was evaluated. The substances were given intracutaneously in five different concentrations, each together with specific allergen or with histamine. During the 2 days' study, 10 patients with known type I-allergy in the skin were randomly assigned to the KWD 2131 or terbutaline group. Both substances gave a dose-dependent inhibition of the allergen-induced wheals. They were, in this respect, equipotent. The greatest protective effect was obtained with the highest doses of both substances (250 micrograms KWD 2131; 25 micrograms terbutaline). In these doses, the inhibition with KWD 2131 and terbutaline was 55 and 45%, respectively (P less than 0.001). Significant inhibition was also seen with the two following lower doses of both substances i.e. 100 and 25 micrograms KWD 2131 and 10 and 2.5 micrograms terbutaline (P less than 0.001-0.01). KWD 2131 and terbutaline did not show any dose-dependent inhibition of histamine-induced wheals. Statistically significant protection against histamine was only reached with the highest dose KWD 2131 (250 micrograms) (P less than 0.05). We conclude that the inhibitory effect of KWD 2131 and of terbutaline on allergen-induced wheal formation in the dose-range tested, is of a selected anti-allergic quality.

Adrenergic beta-Agonists↗
PubMed1980

New beta-agonist, KWD 2131, compared with terbutaline in asthmatics. A cumulative dose-response study.

The equipotent bronchodilating doses of terbutaline and a new beta-agonist KWD 2131 with a relatively stronger anti-allergic (inhibition of mediator release) than bronchodilating effect given in nebulized form was estimated in eight patients with intrinsic asthma. The subthreshold bronchodilating dose of KWD 2131 was also evaluated. The study was a 2-day, single-blind cross-over comparison between cumulative doses of KWD 2131 (0.5 mg to 12 mg) and terbutaline (0.05 mg to 1.2 mg). Both drugs gave a dose-dependent bronchodilating effect as measured spirometrically. It was already statistically significant at the 0.05 mg dose of terbutaline, but not until the cumulative 1.5 mg dose (0.5 + 1 mg) of KWD 2131. The median value of the bronchodilating potency of terbutaline relative to KWD 2131 was 30. The influence of the two substances on tremor and the cardiovascular system was minimum and clinically unimportant. The search for the subthreshold bronchodilating dose of KWD 2131 was of interest, as this dose was to be used in a subsequent antigen provocation study in order to selectively evaluate KWD 2131's anti-allergic property. The mean subthreshold bronchodilating dose of KWD 2131 was 1 mg. However, four of the eight patients showed bronchodilatation at the 1 mg dose, and two of the four also at 0.5 mg.

Adrenergic beta-Agonists↗
PubMed1980

Histamine-induced bronchospasm. Its reproducibility and usage in clinical evaluation of the sub-threshold bronchodilating dose of a new beta-agonist, KWD 2131.

The reproducibility of the histamine challenge in seven asymptomatic patients with extrinsic asthma, provoked four times each with 1-2 weeks interval, was investigated. The method was thereafter used in order to find the sub-threshold bronchodilating dose of a new beta-agonist KWD 2131 with a preferably anti-allergic property. Selection of patients and methodology of the histamine challenge procedure were carefully standardized. Histamine was administered during quiet breathing at 3-min intervals in a step-wise cumulative manner up to a point where greater than 20% decrease in FEV 1.0 was reached. The pooled intra-individual standard deviation was 4.6% in FEV 1.0, 5.0% in PEFR, and 4.7% in FVC. Pretreatment with KWD 2131, before histamine challenge, showed that the subthreshold dose for bronchodilatation was 0.5 mg in nine patients and 0.25 mg in three patients compared with 1 mg in patients with intrinsic asthma. It was important to perform individualized dose-titration of the sub-threshold bronchodilating dose of KWD 2131 before initiation of a subsequent allergen provocation study.

Adrenergic beta-Agonists↗
PubMed1980

Evaluation of the protective effect of a new beta-agonist, KWD 2131, on allergen-induced bronchospasm.

The selective anti-allergic effect of a new beta-agonist, KWD 2131, in inhibiting allergen-provoked asthma was compared with that of placebo in a double-blind crossover study. Non-bronchodilating doses were given by inhalation to 12 asymptomatic patients with extrinsic asthma. KWD 2131 showed a marginal anti-allergic effect. A significantly better effect than that with placebo was obtained at only one time of measurement after challenge (P < 0.05). The reproducibility of the allergen challenge was also evaluated. The mean maximum decrease in FEV1 during three different allergen-challenge procedures was 37, 31, and 38%, respectively. The difference was not statistically significant.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Effects of topical use of beta-adrenoceptor stimulants of nasal mucosa. Rhinomanometric evaluations in experiments with terbutaline and KWD 2131.

The effects of nasal airway resistance of the beta-adrenoceptor stimulants terbutaline (Bricanyl) and KWD 2131 intranasally have been studied by means of posterior rhinomanometry in 16 healthy volunteers and 13 asymptomatic patients with allergic rhinitis. The study was performed as randomized, placebo-controlled, double-blind crossover trial. No obvious changes in nasal resistance were revealed. This makes the nasal muscosa a suitable organ for testing the capacity of beta-adrenoceptor stimulants to reduce the release of mediators from mast cells after allergen challenges.

Administration, Topical↗
PubMedDate not supplied

Influence of a beta-adrenoceptor stimulant, KWD 2131, in nasal histamine provocation tests. Rhinomanometric evaluations in normal persons and patients with hay fever.

Nasal histamine provocation was performed in ll asymptomatic (out of season) patients with hay fever and in ll normal controls. Posterior rhinomanometry was used for objective evaluation. The histamine challenges caused nasal symptoms as well as increased nasal airway resistance. The differences in response between the two groups of subjects were not significant. KWD 2131, a beta-adrenoceptor-stimulating drug which was ascribed an antiallergic effect in a previous allergen provocation study, did not block the effects of histamine challenge in a randomized, placebo-controlled, double-blind, crossover evaluation. The absence of protective action against histamine-induced effects with KWD 2131, supports a mast-cell-stabilizing effect of the substance in allergen provocation.

Adolescent↗