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Biomedical subjects

W Busse

Publications and source records attributed to W Busse.

34 records · Page 2Linked to original sources

The effect of azelastine on neutrophil and eosinophil generation of superoxide.

Azelastine is a new investigational drug used to treat rhinitis and asthma. In addition to described actions that include inhibition of immunologic release of histamine from mast cells and basophils, blockade of smooth muscle contraction to various spasmogenic mediators, and relaxation of airway smooth muscle, azelastine has been ascribed anti-inflammatory properties. To understand further the mechanisms by which azelastine may regulate inflammation, its effect on neutrophil and eosinophil superoxide (O2-) generation was evaluated. Purified suspension of neutrophils (greater than 95% pure) and eosinophils (greater than 85% pure) were isolated from human peripheral blood samples by continuous density gradients of Percoll. The isolated granulocyte suspensions (1 x 10(5) cells) were added to 96-well microtiter plates in the presence of cytochrome c, activated by either N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, calcium ionophore A23187, or opsonized zymosan particles; O2- generation was measured by the reduction of cytochrome c. We found that azelastine significantly inhibited both neutrophil and eosinophil generation of O2- in a dose-dependent fashion (10(-7) to 10(-5) mol/L) with each activator except zymosan. Furthermore, the degree to which azelastine suppressed O2- was similar in neutrophils and eosinophils. Thus, azelastine, in concentrations achieved therapeutically, inhibited granulocyte generation of O2-. This anti-inflammatory effect may also be beneficial in the treatment of asthma.

Adult↗

New directions and dimensions in the treatment of allergic rhinitis.

Physicians who treat patients with allergic rhinitis have a number of therapeutic options, including antihistamines, decongestants, cromolyn, anticholinergics, corticosteroids, and immunotherapy. Antihistamines are widely used for the treatment of mild allergic rhinitis and are often effective, although more severe cases will require other medications. The newer antihistamines may induce less drowsiness, which is the most prominent side effect of the older antihistamines. Topical nasal decongestants give fast relief from nasal congestion, but their overuse may result in rebound congestion. Because their efficacy in allergic rhinitis is variable, oral decongestants are usually used in combination with antihistamines. Nasal cromolyn is effective for many patients with allergic rhinitis, but its effect is variable and it is useful in severe allergic rhinitis.

Administration, Topical↗

A comparison of intranasal and oral flunisolide in the therapy of allergic rhinitis. Evidence for a topical effect.

Intranasal flunisolide is an effective treatment for allergic rhinitis. Flunisolide has high bioavailability when administered to normal subjects (50% of an intranasal dose reaches the systemic circulation) with minimal systemic effects. Bioavailability in patients with active rhinitis averages 62.4 +/- 15.7%. The oral dose bioequivalent to 100 micrograms intranasally is 500 micrograms. To define the comparative trial and systemic effects of intranasal flunisolide in patients with active allergic rhinitis, a multicenter, randomized, double-blind, placebo-controlled study was conducted during the 1983 ragweed hayfever season. Ninety-nine patients with ragweed hayfever for greater than or equal to 2 years and positive prick skin tests to ragweed were randomly allocated to one of three treatment groups: 0 = oral flunisolide 500 micrograms b.i.d. and intranasal placebo b.i.d.; N = intranasal flunisolide 50 micrograms per nostril b.i.d. and oral placebo b.i.d.; P = intranasal and oral placebo b.i.d. Treatment continued for 4 weeks. Patients kept daily symptom scores. Patients were evaluated by a blinded observer every 2 weeks and were globally evaluated at the study's end. Data were analyzed for each center and pooled. There were no significant differences in symptom severity of sneezing, nasal congestion, and throat itch in the 0 (oral flunisolide) and P (placebo) groups. N (nasal flunisolide) was significantly more effective than O or P (P less than or equal to 0.005) for each symptom for at least one 2-week period. Global evaluation demonstrated control of overall hayfever severity for N (nasal flunisolide) but not for O (oral flunisolide). We conclude that the therapeutic efficacy of flunisolide is achieved by topical and not by systemic action.

Administration, Intranasal↗

Short-term efficacy trial and twenty-four-month follow-up of flunisolide nasal spray in the treatment of perennial rhinitis.

Seventy-eight patients with perennial rhinitis underwent a double-blind, placebo-controlled. 12-wk trial with flunisolide nasal spray, a new potent topical steroid. Eighteen of these patients were followed in an open study and evaluated at intervals for side effects and dosage of spray used. Baseline and plasma cortisol concentrations were performed before and at the end of the 12-wk, double-blind period. Adrenocorticotropic hormone (ACTH) stimulation testing was performed on six patients after 1 yr of flunisolide therapy at 300 micrograms/day or less. Flunisolide was found to be safe and effective over a short period. Over a 2-yr follow-up there were no serious side effects or evidence of adrenal suppression. Ten patients with perennial rhinitis continue to obtain subjective benefit after 2 yr of therapy with flunisolide nasal spray.

Administration, Intranasal↗

Anaphylaxis to wine.

Anaphylaxis following the ingestion of wine was found in a non-atopic woman. The reaction occurred within 15 min of wine ingestion but did not follow other alcoholic beverages. An immediate skin test response to the offending wine was found but specific IgE levels could not be measured by radioallergosorbent testing.

Adult↗

Effects of experimental rhinovirus 16 infection on airways and leukocyte function in normal subjects.

We infected 7 normal volunteers with rhinovirus 16. In general, the symptoms and alterations in airways were minimal although all subjects had upper respiratory symptoms. Three subjects developed in addition lower respiratory and systemic symptoms accompanied by either an increase in the volume of isoflow or a positive methacholine response. Furthermore, these three had a decrease in beta adrenergic and H2 histamine receptor responses of their granulocytes. Since the peripheral airway obstruction and decreased beta adrenergic and H2 histamine responses occurred together, these two phenomenon may have a common cause. All seven subjects had a decrease in number of circulating E rosette-forming lymphocytes, and in 6 of 7, there was a decrease in the antibody-dependent cellular cytotoxicity capacity of mononuclear cell preparations. It is not clear whether these changes reflect redistribution of mononuclear cells or alteration of their function.

Adult↗