Search PubMed⌕ Search

Biomedical subjects

R K Bush

Publications and source records attributed to R K Bush.

At least 55 records · Page 3Linked to original sources

Soybean flour asthma: detection of allergens by immunoblotting.

A 43-year-old woman developed asthma 6 years after beginning work in a food-processing plant in which soybean flour was used as a protein extender. Symptoms of sneezing, coughing, and wheezing would begin within minutes of exposure to soybean flour and resolve 2 hours after exposure ceased. Skin tests were positive to a soy extract prepared from the flour. Airway hyperreactivity was confirmed by a positive bronchial challenge to methacholine. Bronchial challenge with soybean flour produced an immediate increase in specific airway resistance from 5.0 to 22.7 L. cm of H2O/L/sec. There was no response to challenge with lactose. The patient's allergic response to soy-flour extract was further characterized by several immunologic methods. IgE binding to soy-flour protein by direct RAST was 5.98 times that of a normal control serum. The soy-flour extract was separated by dodecyl sulfate-polyacrylamide gel electrophoresis. Twenty-four protein bands were detected in the crude soy-flour extract. After immunoblotting and subsequent autoradiography, nine proteins with molecular weights ranging from 54,500 to 14,875 were found. Cross-reactivity studies with other legumes demonstrated apparent immunologic identity between a component in green pea extract and a soybean protein with a molecular weight of 17,000. The clinical significance of this cross-reactivity is not known. We conclude that in this case of occupational asthma to soybean flour, multiple allergens were involved. Immunoblotting may be useful in identifying the allergens involved in occupational asthma.

Adult↗

Standardization of fungal allergens.

The ability of various fungi to induce human IgE-mediated disease, especially allergic asthma, has been well established. The relative clinical importance of fungal aeroallergens varies considerably in different geographic areas. The magnitude of exposure to fungal aeroallergens can be quantitated more precisely by newer immunochemical assays than by more traditional fungal cultures or quantitation of fungal spores by microscopy. Although the wide variations in biologic potency among commercial mold allergenic extracts have been appreciated for decades, only recently have laboratory technologic advances and the production of international reference extracts permitted the development of standardized fungal extracts of defined potency. Future efforts should be directed toward documenting the expected diagnostic and therapeutic advantages of such standardized fungal extracts.

Allergens↗

Detection of Alternaria allergens by Western blotting.

The technique of Western blotting (immunoblotting) is being increasingly recognized as a means of identifying and characterizing allergens in complex mixtures. Because the allergens are immobilized on nitrocellulose paper, they can be probed for binding of IgE from patients' sera. In addition, the blotting technique provides useful biochemical information, such as the molecular weight of the allergen being studied. In this study we used sodium dodecyl sulfate-polyacrylamide gel electrophoresis to separate antigens in a crude Alternaria preparation, electrophoretically transferred these antigens to nitrocellulose, and incubated the nitrocellulose strips with individual serum and pooled sera from 13 Alternaria-sensitive subjects, sera from three nonallergic individuals, and sera from three individuals allergic to ragweed but not Alternaria. The strips were then washed, incubated with 125I-labeled antihuman IgE, washed again, and exposed to autoradiography film. We observed IgE binding to 20 allergens. Five or more sera from Alternaria-sensitive patients recognized allergens in four molecular weight regions: 55,000 to 60,000, 40,000 to 45,000, 35,000 to 40,000, and 15,000 to 20,000. With pooled sera, the most intense IgE binding was directed at allergens with molecular weights above 40,000. No IgE binding was observed with sera from individuals who were not sensitive to Alternaria. We conclude that Western blotting is an effective method for detecting allergens in complex fungal mixtures.

Allergens↗

Multicenter study of bitolterol and isoproterenol nebulizer solutions in nonsteroid-using patients.

Bitolterol mesylate, 1.0 mg, or isoproterenol hydrochloride, 1.5 mg, was administered three times daily for 3 months in a double-blind, multicenter study via closed-port, intermittent-flow, compressor-driven nebulizer system (CPIF) to 182 nonsteroid-using patients with asthma. Mean baseline FEV1 was approximately 60% of predicted normal for both groups. Pulmonary function tests and vital signs were measured before and for up to 8 hours after treatments on test days 1, 30, 60, and 90. Mean maximum increases in FEV1 were 51%, 54%, 52%, and 55% for bitolterol versus 48%, 46%, 50%, and 43% for isoproterenol on these monthly test days. The mean FEV1 response remained greater than 15% over zero time (baseline) for greater than or equal to 8 hours after medication with bitolterol on each of four monthly pulmonary function test days and 2 1/2 to 5 hours for isoproterenol. Median durations of bronchodilator activity for bitolterol were 7.3, 6.5, 6.5, and 6.0 hours versus 4.0, 1.7, 3.7, and 1.9 hours for isoproterenol on the monthly test days. On these test days, 37% to 49% of the patients treated with bitolterol had a duration of action of at least 8 hours compared with 16% to 29% after isoproterenol treatment. The onset of activity was within 5 minutes for both drugs. Bitolterol provided superior bronchodilator activity with fewer adverse effects compared with isoproterenol, and there was no evidence for drug tolerance during this 3-month study.

Adult↗

Comparison of the bronchodilator effects of nebulized bitolterol mesylate and isoproterenol hydrochloride in steroid-dependent asthma.

This study of 183 ambulatory patients with steroid-dependent asthma was conducted to evaluate the efficacy and safety of nebulized bitolterol mesylate solution (0.2%) compared to isoproterenol hydrochloride solution (0.3%). A double-blind, randomized, parallel-group, repetitive-dose design was followed at nine centers for 3 months. Patients received either 1.0 mg of bitolterol or 1.5 mg of isoproterenol three times a day with a closed, intermittent-flow nebulization system. Pulmonary function was evaluated on four 8-hour office visits at approximately 30-day intervals. Efficacy was based on a 15% increase in FEV1 over baseline. Both medications resulted in bronchodilatation within 5 minutes, whereas nebulized bitolterol was statistically superior (p less than 0.05) to nebulized isoproterenol in terms of duration of action and area under the curve. The mean FEV1 response to bitolterol therapy remained greater than 15% over baseline for 5 to 8 hours on the four test days compared to 2 to 4.75 hours for isoproterenol therapy. Both medications were well tolerated. Adverse reactions were transient, and most were mild to moderate. Tremor was the most frequent side effect occurring in approximately 30% of the patients in both groups. There were no clinically significant laboratory changes or electrocardiographic findings. Nebulized bitolterol mesylate was found to be a safe and effective bronchodilator in steroid-dependent patients with asthma.

Adult↗

Production of an international reference standard alternaria extract. I. Testing of candidate extracts.

As part of a program to establish international standards of selected allergens, 6 coded extracts of Alternaria were assessed in 6 laboratories by immunochemical, biochemical and physicochemical procedures. Direct RAST, RAST inhibition, quantitative skin tests and leukocyte histamine release were used to assign relative orders of potency to the 6 extracts. The composition and major allergen content was tested by thin-layer isoelectric focusing and quantitative immunoelectrophoresis (crossed immunoelectrophoresis and crossed radioimmunoelectrophoresis). Three laboratories determined the quantity of purified allergens in each of the preparations. In addition, source materials were sent to an expert Alternaria taxonomist for independent identification. The results showed considerable variation with respect to total allergenic potency and content of individual allergens. Source materials could not be confirmed as Alternaria in some instances. Based on fulfillment of written specifications and assay results, extract No. 6 was recommended by the Alternaria Working Group as the candidate international standard to the Steering Committee of the Allergen Standardization Subcommittee of the International Union of Immunological Societies.

Allergens↗

Food allergens: structure and immunologic properties.

Few of the food allergens have been purified and characterized. Complex mixtures of allergens seem to exist in some commonly allergenic foods. Much further research will be necessary to develop any detailed understanding of the chemistry of food allergens.

Administration, Oral↗

Use of ipratropium bromide in asthma. Results of a multi-clinic study.

A multi-center, double-blind, 90-day study compared an ipratropium bromide metered-dose inhaler (40 microgram four times a day) with a metaproterenol metered-dose inhaler (1,500 micrograms four times a day) in 164 patients with asthma; of the 144 patients who completed the study, 71 received ipratropium and 73 received metaproterenol. Our results suggest that both drugs were equally effective bronchodilators. Although the shape of the pulmonary function response curves suggested that ipratropium has different bronchodilator kinetics than metaproterenol (in that it has a slower onset of action and a more prolonged duration), comparison of the areas under the curves for the two drugs showed that there was no statistical difference between ipratropium or metaproterenol. The only significant side effects noted with ipratropium were cough and exacerbation of symptoms; no anticholinergic side effects were noted.

Administration, Inhalation↗

Prevalence of sensitivity to sulfiting agents in asthmatic patients.

Ingestion of sulfiting agents can induce wheezing in some asthmatic patients. However, neither the prevalence of sulfite sensitivity nor the clinical characteristics of the affected asthmatic population are known. In a prospective single-blind screening study, 120 non-steroid-dependent and 83 steroid-dependent asthmatic patients underwent challenge with oral capsules of potassium metabisulfite. Five non-steroid-dependent and 16 steroid-dependent asthmatic patients experienced a greater than 20 percent reduction in their one-second forced expiratory volume within 30 minutes following the oral challenge. Twelve of these sulfite reactors were rechallenged with metabisulfite capsules in a double-blind protocol. Under these conditions, only three of seven steroid-dependent patients had a positive response. Moreover, only one of five non-steroid-dependent patients had a response to double-blind challenge. On the basis of this challenge study, the best estimate of the prevalence of sulfite sensitivity in the asthmatic patients studied is 3.9 percent. This population, however, contained a larger number of steroid-dependent asthmatic patients than would be found in the general asthmatic population. It is concluded, therefore, that the prevalence of sulfite sensitivity in the asthmatic population as a whole would be less than 3.9 percent and that steroid-dependent asthmatic patients are most at risk.

Adult↗

The use of a single daily theophylline dose and metered-dose albuterol in asthma treatment.

Sustained-release, 24-hour theophylline preparations have been formulated and may provide for convenient once-a-day dosing, although the use of such products in clinical asthma has yet to be fully established. This study compared single daily versus twice daily dosing with a 24-hour theophylline, Uniphyl, in asthma and further evaluated for the additional effect of metered-dose albuterol on each theophylline regimen. Twenty-eight patients with asthma were enrolled in this randomized crossover trial. Before enrollment, all demonstrated at least a 15% improvement in FEV1 after a beta-adrenergic aerosol and had serum theophylline levels ranging from 5 to 20 micrograms/ml with a predetermined 800 mg daily dose of Uniphyl. The patients were then randomly entered into four treatment regimens for one week each: Uniphyl, 800 mg four times a day (qd); metered-dose albuterol, active, 180 micrograms four times a day (qid); Uniphyl, 400 mg twice daily; metered-dose albuterol, active, 180 micrograms qid; Uniphyl, 800 mg qd; placebo, two puffs qid; and Uniphyl, 400 mg twice daily; placebo, two puffs qid. On the morning of the seventh day of each treatment regimen, pulmonary functions and a trough serum theophylline level were measured. The patient then received the same medication that he had taken for the preceding week. Spirometry was measured hourly, and a serum theophylline level was measured 6 hours later. The daily symptom scores, peak flow values, and pulmonary functions on the test day were similar with either single or twice daily Uniphyl dosing. Routine administration of albuterol by metered dose did not enhance asthma control in an unequivocal fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of morning and evening dosing with a 24-hour sustained-release theophylline, Uniphyl, for nocturnal asthma.

Sixteen adults who had chronic asthma with nocturnal symptoms were selected to evaluate and compare the effectiveness of 7 A.M. versus 7 P.M. single daily dosing with the 24-hour sustained-release theophylline Uniphyl. The study was a randomized, double-blind, placebo-controlled trial in which the patients were given 800 mg of Uniphyl at either 7 A.M. or 7 P.M. for one week each. Serum theophylline levels showed significantly higher peak (18.1 +/- 1.8 micrograms/ml versus 12.7 +/- 1.2 microgram/ml) and trough (12.4 +/- 1.3 microgram/ml versus 7.6 +/- 1.0 microgram/ml) concentrations during evening dosing. Furthermore, daily peak flow values were higher in the morning when Uniphyl was given at 7 P.M. Thus, nocturnal dosing with Uniphyl gives higher serum theophylline concentrations and, with this, better control of nocturnal asthma.

Adult↗

Monkey dander asthma.

We recently cared for two patients who experienced acute asthma with exposure to dander of the cotton top tamarin, a species of New World monkey. Both patients had serologic evidence for an IgE antibody to monkey dander as determined by RAST and a positive immediate skin test response to an extract prepared from monkey dander. Furthermore, by RAST we were able to determine that cotton top tamarin urine and newborn cotton top tamarin dander had antigens that reacted with IgE in the serum of the affected patients. Thus we report two patients with asthma to monkey dander that appears to be mediated by an IgE mechanism. We also found that serum from a subject exposed to another species of New World monkey, the capuchin, yielded a positive RAST to the cotton top tamarin, suggesting that allergenic cross-reactivity may exist between the two species.

Acute Disease↗

Soybean oil is not allergenic to soybean-sensitive individuals.

We have previously demonstrated that peanut oil is not allergenic to peanut-sensitive individuals. Seven soybean-sensitive patients were enrolled in a double-blind crossover study to determine whether ingestion of soybean oil can induce adverse reactions in such patients. All subjects had histories of systemic allergic reactions (urticaria, angioedema, wheezing, dyspnea, and/or vomiting) after soybean ingestion and had positive puncture skin tests with a 1:20 w/v glycerinated-saline whole soybean extract. Sera from six of the seven subjects were tested by RAST assay for the presence of specific IgE antibodies to soybean allergens. All patients had elevated levels of serum IgE antibodies to the crude soybean extract; binding values ranged from 2.3 to 28.1 times that of a negative control serum. Before the oral challenges, all patients demonstrated negative puncture skin tests to three commercially available soybean oils and to olive oil (control). On four separate days, patients were challenged with the individual soybean oils and olive oil in random sequence. At 30-minute intervals, under constant observation, patients ingested 2, 5, and 8 ml of one of the soybean oils or olive oil contained in 1 ml capsules. No untoward reactions were observed with either the commercially available soybean oils or olive oil. Soybean oil ingestion does not appear to pose a risk to soybean-sensitive individuals.

Antibodies, Anti-Idiotypic↗

Beclomethasone dipropionate nasal aerosol spray in allergic rhinitis: a comparison of three delivery systems.

In this 3-way crossover study, the currently marketed beclomethasone dipropionate aerosol canister was sprayed intranasally through three different delivery adapters by 48 adult patients with allergic rhinitis. The adapters were evaluated and compared for force of spray, ease of use, preferred length of nozzle, and effectiveness. While all three were considered effective for symptom relief, there was a clear preference for both of the new longer, snout-like nozzle adapters over the currently available delivery system.

Adult↗

Assessment of tachyphylaxis following prolonged therapy of asthma with inhaled albuterol aerosol.

Controversy exists concerning possible tachyphylaxis of the acute bronchodilating effect of albuterol, especially with regard to the duration of its acute bronchodilating action. We evaluated 140 patients with bronchial asthma in a prospective double-blind controlled study of possible tachyphylaxis to albuterol aerosol as compared to isoproterenol aerosol. We demonstrated statistically significant tachyphylaxis with regard to duration of acute bronchodilating effect. We believe that this tachyphylaxis is not clinically significant because there was no tachyphylaxis with regard to peak bronchodilating effect and because the duration of bronchodilating effect remains significantly greater, both quantitatively and statistically, when compared to isoproterenol aerosol. Moreover, it appeared that most of the tachyphylaxis was present at four weeks of therapy. There was a small increment of tachyphylaxis after eight weeks of therapy, but no further increase in tachyphylaxis was demonstrated after 13 weeks of inhaled albuterol therapy. We therefore feel that clinically significant tachyphylaxis to inhaled albuterol aerosol must be quite unusual and that chronic therapy with inhaled albuterol aerosol is probably both safe and efficacious for bronchospastic disorders.

Adolescent↗

Detection of Alternaria allergens by crossed radioimmunoelectrophoresis.

Allergens involved in sensitivity to Alternaria have not been well defined. We used crossed radioimmunoelectrophoresis (CRIE) to study antigens in a crude A. alternata extract, which were capable of binding IgE in human serum. Sera from 35 patients sensitive to Alternaria, 10 not sensitive to Alternaria, and five normal controls were examined. CRIE with hyperimmune rabbit sera demonstrated 22 antigens in the Alternaria extract. After exposure of CRIE gels sequentially with patient serum and 125I-labeled anti-human IgE, autoradiography demonstrated that three of the antigens bound IgE in sera of Alternaria-sensitive subjects. Our results suggest that multiple allergens are involved in A. alternata sensitivity.

Allergens↗