Showing papers by "William W. Busse published in 1981"

Parainfluenza 3 infection blocks the ability of a beta adrenergic receptor agonist to inhibit antigen-induced contraction of guinea pig isolated airway smooth muscle.

Abstract: Guinea pigs, actively sensitized to ovalbumin, were inoculated by nasal insufflation with parainfluenza 3 or virus growth medium 4 d before performing in vitro pharmacological studies on tracheal and bronchial smooth muscle. In each airway segment, cumulative dose-response effects of ovalbumin were obtained in the absence and presence of a maximally effective concentration of a beta adrenergic receptor agonist, sulfonterol. Sulfonterol shifted the dose-response curve to the right and reduced the maximum smooth muscle contractile response to ovalbumin. Virus infection did not alter the dose-response effects of ovalbumin. However, the magnitude of the inhibitory effects of sulfonterol was smaller in segments taken from animals inoculated with virus. Blockade by virus infection of the inhibitory effect of sulfonterol was reversed when the concentrations of beta agonist were increased. Sulfonterol did not alter the dose-response effects of histamine at any of the concentrations that markedly antagonized the effects of ovalbumin. Virus infection did not alter the sensitivities to sulfonterol or papaverine in producing relaxation in either airway segment. The magnitude of relaxation produced by papaverine was significantly larger in bronchial rings taken from animals infected with virus for 4 d, but there was no alteration by virus of the dose-response effects of histamine or carbachol. In experiments measuring antigen-induced release of slow reacting substance of anaphylaxis and histamine from minced lung, virus infection did not alter the sensitivity or the maximum effects of ovalbumin. Also, the ability of sulfonterol to inhibit the release of slow reacting substance of anaphylaxis and histamine was not affected by virus infection.These results demonstrate that infection of guinea pigs with respiratory virus results in a selective blockade of the beta adrenergic-mediated inhibition of antigen-induced contraction of airway smooth muscle. The guinea pig may serve as a useful model in physiological studies of virus-induced asthma.

A multicenter study on skin-test reactivity of human volunteers to venom as compared with whole body Hymenoptera antigens☆

Abstract: Twenty-four control and 104 stinging insect-allergic patients were tested in this multicenter study, which compared the utility of individual venom and whole body extract (WBE) preparations for diagnosis. This study indicates that venom skin testing is more specific and more reliable than is testing with WBE. There was a high rate of WBE skin-test reactivity among controls. False-positive skin testing with venom was not a problem at concentrations of 1 microgram/ml or less. Only one mild and easily treated adverse reaction occurred in this study.

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

Abstract: 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.

Altered luminol-dependent granulocyte chemiluminescence during an in vitro incubation with an influenza vaccine.

Abstract: Polymorphonuclear leukocyte particle phagocytosis stimulates the ”respiratory burst.“ The changes in oxidative metabolism are associated with the release of highly reactive species, superoxide, hyd...

Development of allergic bronchopulmonary aspergillosis during treatment of severe asthma with systemic corticosteroids

Abstract: Rapid clinical improvement of allergic bronchopulmonary aspergillosis (ABPA) is usually noted with corticosteroid therapy. We report a case of ABPA that developed in a patient who was being treated with prednisone on a maintenance basis for severe asthma. Recovery from the short-term episode of ABPA was protracted and required higher doses of corticosteroids for control of the syndrome than usually necessary. It is suggested that corticosteroids do not prevent the development of ABPA, and that patients who develop the syndrome while on corticosteroids may have a protracted course with poor response to the usually effective doses of corticosteroids.

The granulocyte response to the phosphodiesterase inhibitor RO 20-1724 in asthma☆

Abstract: Isolated human granulocytes secrete the lysosomal enzyme beta glucuronidase when incubated with complement-activated zymosan particles. Isoproterenol inhibits this release, and the beta adrenergic response is associated with an increase in granulocyte cyclic adenosine monophosphate (cAMP) levels. In asthma, the beta adrenergic responsiveness is impaired. Cyclic AMP concentration in the granulocyte is also influenced by phosphodiesterase hydrolysis of this cyclic nucleotide. We found that the potent phosphodiesterase inhibitor, RO 20-1724, inhibited zymosan-stimulated beta glucuronidase release from granulocytes in a dose-dependent fashion (10(-8) to 10(-4) M). The inhibition of lysosomal enzyme release by RO 20-1724 was associated with an increase in granulocyte cAMP. Granulocytes were also isolated from asthmatic patients and the RO 20-1724 inhibition of beta glucuronidase release was compared with the response in normal subjects. The negative log molar median effective dose (ED50) value (mean +/- SE) was 5.98 +/- 0.69 in normal subjects and 5.90 +/- 0.63 in asthmatics. These observations suggest that the granulocyte metabolism modulated by the RO 20-1724-sensitive phosphodiesterase is equally responsive to this potent phosphodiesterase inhibitor in normal and asthmatic leukocytes.

Analysis of granulocyte beta-adrenergic response in cystic fibrosis: correlation of decreased responsiveness with disease severity.

Abstract: Granulocytes from 21 nonasthmatic cystic fibrosis (CF) patients were isolated and the effects of isoproterenol, histamine, and prostaglandin E1 upon zymosan-induced beta-glucuronidase release was measured. Granulocytes from CF patients contained significantly less total beta-glucuronidase activity compared with those from control subjects, but response to zymosan stimulation was normal. Compared with those from control subjects, the granulocytes from CF patients with severe airway disease (% predicted FEV1 less than 60) had significantly reduced responsiveness to isoproterenol, which correlated with both the % predicted FEV1 values and the NIH clinical score. In this same population of CF patients, granulocyte responsiveness to PGE1 was also decreased compared with that of the control subjects, but the degree of impairment was not as severe as that observed with isoproterenol nor did it correlate with disease severity. Histamine responsiveness, however, was normal. Our findings suggest that abnormal beta-adrenergic responses may reflect the severity of airway disease and clinical score.

Cortisol protection of the granulocyte response to isoproterenol during an in vitro influenza virus incubation

Abstract: Isolated human polymorphonuclear leukocytes (PMNs) release beta glucuronidase (BG) lysosomal enzyme during incubation with complement-activated zymosan particles. In asthma, isoproterenol (ISO) and histamine (HIS) inhibition of PMN lysosomal enzyme release is impaired while the prostaglandin E1 (PGE1) response is normal. During a respiratory infection provoking asthma, the PMN response to ISO is further impaired. The PMN response to ISO, HIS, and PGE1 is similarly impaired following an in vitro incubation with a live influenza bivalent (A + B) vaccine. In the following study, granulocytes were isolated from normal (n = 10) and asthma patients (n = 29). The isolated cells were incubated with the bivalent influenza vaccine (1 PMN:1 egg infective dose50) for 30 min. Following this in vitro virus incubation, granulocytes from normal and asthma patients had an imparied response to ISO, HIS, and PGE1. Granulocytes from asthma patients having a history of wheezing with respiratory illnesses did not have a greater impairment in the agonist response following virus incubation than normals or allergic asthma patients. However, in asthma patients (n = 6) receiving prednisone (10 to 20 mg/day), the in vitro vaccine incubation did not impair the PMN ISO response. A similar protective effect was found if granulocytes were incubated with hydrocortisone (1,4 X 10(-4) M) prior to exposure to the influenza vaccine.