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Biomedical subjects

H S Nelson

Publications and source records attributed to H S Nelson.

At least 55 records · Page 3Linked to original sources

Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract.

BACKGROUND: Immediate hypersensitivity to peanuts is a frequent cause of anaphylactic reactions and deaths in children and adults. Currently, preventive treatment consists of avoidance, which is difficult because of the widespread and often disguised use of peanuts in the food industry. METHODS: Twelve patients with immediate hypersensitivity to ingestion of peanuts were recruited. Half were treated with injections of peanut extract: a maintenance level of tolerance was first achieved by a rush protocol, then maintained with weekly injections for at least 1 year. The other six were untreated control subjects. All patients underwent double-blind, placebo-controlled, oral peanut challenges initially, after approximately 6 weeks, and after 1 year. RESULTS: All treated patients achieved the maintenance dose of 0.5 ml of 1:100 wt/vol peanut extract by the rush injection protocol. All experienced increased tolerance to double-blind, placebo-controlled peanut challenge and decreased sensitivity on titrated skin prick testing with peanut extract, whereas the threshold to oral peanut challenge and cutaneous reactivity to peanut extract were unchanged in the untreated control subjects. Systemic reactions were common in the treated group both during rush immunotherapy and with maintenance injections. Only three patients remained tolerant of the full maintenance dose. The increased tolerance to oral peanut challenge was maintained in the three subjects who received full maintenance doses, but there was partial (n = 2) or complete (n = 1) loss of protection in the patients who required dose reduction because of systemic reactions. CONCLUSIONS: Injections of peanut extract increase the tolerance of patients with peanut allergy to oral ingestion of peanuts. Injections result in repeated systemic reactions in most patients, even during maintenance injections. For clinical application of this method of treatment, a modified peanut extract is needed.

Administration, Oral↗

Nasal immunotherapy in weed-induced allergic rhinitis.

BACKGROUND: Nasal immunotherapy with single allergen extracts, following premedication with cromolyn, has been reported to be effective in treating seasonal and perennial allergic rhinitis. METHODS: We conducted a double-blind, placebo-controlled study to assess the efficacy, tolerability, and mechanism of action of nasal immunotherapy for allergic rhinitis caused by weed pollens from three unrelated families. Twenty-seven weed-allergic patients underwent baseline nasal provocation and titrated skin test with a mixed weed extract containing ragweed, sage, and Chenopod extracts. Patients were randomized to receive either mixed weed extract or placebo. Nasal immunotherapy was self-administered daily to alternate nostrils preceded by 5.2 mg intranasal cromolyn. Beginning with 1:2500 wt/vol the concentration was increased to 1:10 wt/vol over an average period of 36 days. The maintenance dose (1:10 wt/vol) was administered daily for 12 to 16 weeks through the weed pollen season. Patients recorded nasal and eye symptoms and the use of rescue medications throughout the study. A nasal lavage for cytokine levels and nasal scraping with Rhinoprobe for nasal cytology were performed at the peak of the weed season. Nasal provocation and titrated skin tests with mixed weed extract were repeated after the weed season. Nasal lavage and scraping were also performed before and 24 hours after the final nasal provocation. RESULTS: During the peak weeks of the weed season the group receiving mixed weed extract by nasal instillation, compared with those treated with placebo, had significantly lower total nasal symptom scores, total eye symptom scores, and symptom medication scores. There were no significant differences in the nasal cytology or cytokines levels between the two groups, except for elevated IL-10 in the nasal lavage in the treated group at the peak of the season. Nasal symptoms and medication use were higher preseasonally in the active treatment group. CONCLUSION: Nasal immunotherapy with aqueous mixed weed extract administered with cromolyn sodium pretreatment for 17 to 21 weeks was effective in reducing both nasal and ocular symptoms of weed pollen-induced allergic rhinitis. There were increased nasal symptoms in the treated group preseasonally.

Administration, Intranasal↗

Studies of allergen extract stability: the effects of dilution and mixing.

BACKGROUND: However potent the allergy extracts provided by manufacturers, they are subject to deterioration with storage, especially after dilution or mixture with other extracts. OBJECTIVE: This study was performed to assess separately the deterioration during storage in allergen extract potency caused by dilution or by mixture with allergen extracts that have been reported to contain proteases. METHODS: To assess the effect of dilution, three serial 10-fold dilutions of cat, short ragweed, Bermuda grass, and Dermatophagoides farinae extracts were prepared alone or combined with other extracts. They were stored at 4 degrees C for 3 and 12 months. To assess the effect of mixing with other extracts that have been reported to contain proteases, extracts of timothy grass, Bermuda grass, short ragweed, Russian thistle, white oak, box elder, D. farinae, and cat were stored alone or combined with one or more extracts of American cockroach, Alternaria spp., Cladosporium spp., Penicillium spp., and a house dust mite mix for 3 months at 4 degrees C. RESULTS: Bermuda grass, cat, and house dust mite extracts incurred significant loss of potency at all dilutions with storage. Short ragweed was stable at all dilutions. Potency of extracts of timothy grass, Bermuda grass, Russian thistle, white oak, box elder, and cat were all reduced by combination with one or more extracts potentially containing proteases. Only short ragweed and D. farinae, which was in a final concentration of 25% glycerin, were resistant. Alternaria extract was most frequently responsible for loss of potency, followed by cockroach and Cladosporium extracts. Combination with extracts of Penicillium and a house dust mite mix did not reduce the potency of any extract. CONCLUSIONS: Both dilution alone and mixture with extracts reported to contain proteases caused loss of potency of most extracts tested. Ragweed was uniquely resistant under both conditions of storage.

Allergens↗

An assessment of the role of intradermal skin testing in the diagnosis of clinically relevant allergy to timothy grass.

BACKGROUND: Immediate skin testing is generally the preferred method for establishing the presence of allergy in clinical practice. There is no agreement, however, as to whether intradermal testing should be routinely performed if skin prick test results are negative. PURPOSE: The study was done to address the value of intradermal skin testing in the diagnosis of clinically significant sensitivity to grass pollen in patients exhibiting negative skin prick test responses to timothy extract. METHODS: Four groups were studied. Group I had a history of seasonal allergic rhinitis, negative skin prick test responses to timothy and Bermuda grass, but positive intradermal skin test responses to timothy grass. Group II had a history of seasonal allergic rhinitis and positive skin prick test responses to timothy grass. Group III had a history of seasonal allergic rhinitis but had negative responses to both prick and intradermal testing with timothy and Bermuda grass. Group IV had no history of rhinitis, had negative responses to skin testing with a panel of locally important allergens, as well as Bermuda and timothy grass, and had a serum IgE value of less than 20 IU/ml. Clinical sensitivity to grass was assessed by two methods: (1) nasal challenge with threefold increasing amounts of timothy pollen performed out of the pollen season and (2) correlation of subjects' daily symptom and medication scores with daily grass pollen counts during the grass pollen season. RESULTS: On the basis of nasal challenge with timothy grass, pollen allergic reactions were present in 11% of group I, 68% of group II, 11% of group III, and 0% of group IV. As determined by correlation of symptoms during the grass pollen season with grass pollen counts, 22% of group I, 64% of group II, 21% of group III, and 0% of group IV were considered allergic. If both criteria were required for a diagnosis of clinical allergy to grass, the percent positive was 0 for group I, 46 for group II, 0 for group III, and 0 for group IV. CONCLUSION: Under the conditions of this study the presence of a positive intradermal skin test response to timothy grass (1000 AU/ml) in the presence of a negative skin prick test response to timothy grass (100,000 AU/ml) did not indicate the presence of clinically significant sensitivity to timothy grass, and by inference, to other cross-reacting grasses.

Adult↗

Effect of distance between sites and region of the body on results of skin prick tests.

BACKGROUND: Two variables in skin prick testing were examined: the effect of a positive reaction to histamine or allergen on adjacent negative test sites and the relative size of reactions to allergen and histamine on the back and forearm. METHODS: Fifty-two subjects were tested on the back and arm with an allergen extract to which they reacted with a wheal of 8 mm or greater in diameter and with 50% glycerin at sites ranging from 2 to 7.5 cm distant from the allergen test site. A similar study was performed in 50 subjects by using 1.8 mg/ml histamine base to produce the positive reaction. The data were analyzed for the effect of a positive reaction on an adjacent negative control site and also for the relative size of positive reactions on the back and forearm. Data from a second study were also examined for the difference in reactivity on the back and arm. In this study 77 subjects underwent skin prick testing (in duplicate) with seven allergen extracts, 50% glycerin, and 1.8 mg/ml histamine base on the forearm and back. RESULTS: Positive reactions at the 50% glycerin sites were observed at a rate of 0.52% when defined as wheals of 3 mm in diameter or greater and at a rate of 1.11% when defined as flares of 10 mm in diameter or greater. There was no increase in the rate of false-positive reactions over the range of 2 to 5 cm distance from the sites of positive reactions to allergen or histamine. Fewer reactions were present at the 50% glycerin sites, 7.5 cm from the positive sites. The diameters of the reactions to allergen in the primary study were significantly (p < 0.001) smaller on the forearms than on the back (27% less for the wheal and 14% less for the flare). The mean diameter of the wheals induced by histamine did not vary between back and arm (p = 0.3); however, the mean diameter of the flares on the forearm with histamine were 8% smaller than those on the back (p = 0.003). In the second study the reactions to cat extract (n = 59) were significantly smaller on the forearm than on the back (mean wheal diameter 16% less, mean flare diameter 14% less, p < 0.001 for both). The reactions to histamine (n = 76) in this study were also significantly smaller on the forearm (mean wheal diameter 6% less, p = 0.027, and mean flare diameter 14% less, p < 0.001). CONCLUSION: If a relatively nontraumatic technique for skin testing is used, adjacent positive test reaction sites of moderate size, which are 2 cm or more from the site of the prick test, are unlikely to cause false-positive reactions on either the back or forearm. Skin test reactivity is less notable on the forearm than on the back for both histamine and allergen. This effect was more pronounced for allergen tests (16% to 27% decrease in mean wheal diameter) than for histamine tests.

Adolescent↗

New developments in bronchodilator therapy.

Generally favorable literature was published regarding the contributions of bronchodilators to asthma therapy. Analysis of asthma mortality data suggested that the risk of death from asthma was primarily associated with the use of fenoterol rather than beta-adrenergic bronchodilators as a class, or reflected the severity of the underlying asthma, which resulted in increasing beta-agonist use. Salmeterol was shown to outperform oral beta-adrenergic agonists and individual dose-titrated theophylline in controlling asthma symptoms while causing fewer adverse effects. When salmeterol was added to low-dose inhaled corticosteroids, the combination outperformed moderate-dose inhaled corticosteroids alone. Regular use of salmeterol, but not albuterol, improved the quality of life for patients with asthma to a clinically significant degree. Finally, theophylline, at relatively low blood levels, was clearly shown to improve asthma control, even in patients receiving moderately high-dose inhaled corticosteroids. More importantly, this symptomatic response was accompanied by decreases in activated lymphocytes, eosinophils, and proinflammatory cytokines in bronchial biopsy results.

Administration, Inhalation↗

Delivery of glucocorticoids by jet nebulization: aerosol characteristics and output.

BACKGROUND: Since inflammation has been identified as a critical factor in the pathogenesis of asthma, use of inhaled glucocorticoids has increased. Because young children are often unable to coordinate properly the use of metered-dose inhalers and no glucocorticoids preparations for nebulization have been approved in the United States, parenteral and intranasal glucocorticoids preparations are occasionally administered by nebulization. METHODS: We examined whether a parenteral preparation (triamcinolone acetonide [TAA]; Kenalog) could be delivered by nebulization. TAA, 1000 micrograms (0.1 ml), was placed in the nebulizer bowl (MB5 [MeFar, Brescia, Italy] or Pari-Jet [Dura Pharmaceuticals, San Diego, Calif.]), then diluted with 2.9 ml normal saline solution for a total volume fill of 3 ml. Using a laser particle analyzer, high-performance liquid chromatography, and cascade impactor, we examined the percentage of aerosol volume produced with particles in the respirable range of 1 to 5 microns in diameter, actual TAA output (in micrograms) and concentration of TAA contained in the particles within the respirable range. RESULTS: Laser particle analysis indicated that 34% +/- 3% (mean +/- SEM) (MB5) and 47 +/- 3% (Pari-Jet) of the total aerosol volume produced were within the respirable range of 1 to 5 microns in diameter, and this remained consistent throughout nebulization. The nebulizer was stopped serially for determination of TAA output with high-performance liquid chromatography. TAA output (1000 micrograms less the amount in micrograms remaining after nebulization) was essentially complete after 2 minutes with the Pari-Jet and within 4 minutes with the MB5 and totaled 352 +/- 19 micrograms and 367 +/- 9 micrograms, respectively. Finally, cascade impactor studies confirmed that 33.4% of the TAA aerosol generated by the MB5 nebulizer was contained in particles in the respirable range. CONCLUSION: Approximately 35% (Pari-Jet) and 37% (MB5) of the initial 1000 micrograms of TAA was delivered with the two nebulizers tested. The particles generated within the respirable range were limited to 34% (MB5) and 47% (Pari-Jet) of the amount delivered. TAA was equally distributed in the particles generated. The theoretic amount delivered in the respirable range was approximately 12.5% for the MB5 nebulizer on the basis of the cascade impactor and 16.5% for the Pari-Jet (assuming TAA distribution equivalence) of the TAA placed in each of the nebulizers. Additional clinical studies are needed to define efficacy and safety in view of the excipients used in preparing the parenteral preparation.

Aerosols↗

Characterization of Chenopodiales (Amaranthus retroflexus, Chenopodium album, Kochia scoparia, Salsola pestifer) pollen allergens.

Pollen extracts of the four taxonomically related weeds, Amaranthus retroflexus (Ama r), Chenopodium album (Che a), Kochia scoparia (Koc s), and Salsola pestifer (S. kali) (Sal p), were characterized by various methods including crossed immunoelectrophoresis (CIE), crossed radioimmunoelectrophoresis (CRIE), and SDS-PAGE immunoblotting. The allergen profiles were determined by CRIE and SDS-PAGE IgE immunoblotting. CRIE detected from one to four important allergens, while SDS showed up to four bands that bound IgE from a number of patient sera. CRIE and SDS-PAGE immunoblotting did not recognize the same number of important allergens in the individual weeds, and the number of allergens detected by the two methods differed considerably, suggesting that IgE-binding epitopes may be denatured during SDS-PAGE. However, it was possible to correlate the identity of some of the important allergens detected by CRIE and SDS-PAGE immunoblotting in all four weeds.

Allergens↗

Prevalence of house dust mites in the Rocky Mountain states.

BACKGROUND: Due to low rainfall and high elevation the ten Rocky Mountain states would not be expected to have the indoor humidity required to support the growth of significant numbers of house dust mites. Nevertheless, a recent survey reported that house dust mite allergen levels were not significantly different in the various regions of the United States, including the arid and mountainous regions. METHODS: Each summer for 5 years (1988-92) patients with bronchial asthma scheduled to be evaluated at the National Jewish Center for Immunology and Respiratory Medicine were invited to submit a dust sample from their mattress or bedroom carpet for mite analysis. RESULTS: Fifty-eight patients from the ten Rocky Mountain states submitted dust specimens. Forty-eight contained no mites, five had levels of mites considered clinically insignificant (less than 100 mites/g dust), three contained 100 mites/g of dust, a level at the threshold of significance, and two had high levels of mites (1,000 and 3,000 mites/g). Both of the homes with high mite levels had specific sources of excess moisture. Twenty-eight patients from adjacent states also submitted dust specimens. Significant levels of mites were encountered in specimens from these states reflecting the transition to zones of greater humidity and lower elevation. CONCLUSION: Except in homes with unusual sources of humidity, significant levels of house dust mites are rarely encountered in homes in the ten Rocky Mountain states.

Allergens↗

Analysis of meteorologic variables and seasonal aeroallergen pollen counts in Denver, Colorado.

BACKGROUND: The observation of low levels of weed pollens following a freeze and an early autumn snowfall in Denver, Colorado led to this analysis of meteorologic variables and pollen counts. OBJECTIVE: The purpose of this study was to examine, in depth, the relationship between observed pollen counts and a selection of independent meteorologic variables. METHODS: We prospectively studied in 1991 daily high and low temperature, relative humidity, precipitation, barometric pressure, percent sunshine, wind velocity and direction, tree, grass, and weed pollen, as well as dates of the first frost/freeze. Similar data were retrospectively analyzed for 1987-1990. RESULTS: Correlation coefficients for the prospective data were as high as .611 for high temperature and cottonwood and .718 for high temperature and maple (P < .001). High and low temperature showed strong correlations with the combined weed counts (.598 and .628, respectively, P < .001). CONCLUSIONS: Denver weed pollens appear impacted more by temperature and less by precipitation and humidity, while the converse is true for tree and grass pollen. However, weed pollen, especially sage, may appreciably rebound after freezing temperatures. While separate meteorologic variables may have high correlations with specific pollen counts in a given year, such effect is not consistent and varies from year to year.

Allergens↗

Suppression of the skin reaction to histamine by ebastine.

BACKGROUND: Ebastine is a nonsedating histamine H-1 antagonist undergoing evaluation for treatment of allergic rhinitis and urticaria. OBJECTIVE: To compare the suppression of prick and intradermal skin reactions to histamine over a period of 24 hours produced by a single dose of ebastine. Also to record side effects and assess changes in the electrocardiogram, particularly the QTc interval. METHOD: Single doses of 1, 3, 10, and 30 mg of ebastine or placebo were administered double-blind at approximately 8 AM after baseline measurement of the reaction to intradermal testing with 5 micrograms histamine base and prick skin testing with three concentrations of histamine. Intradermal testing with histamine was repeated hourly for four hours, every two hours for eight hours, and after 24 hours. Titrated prick skin testing with histamine was performed at 6, 12, and 24 hours. Potential side effects were recorded each time skin testing was performed. Electrocardiograms were repeated at 4 and 24 hours. RESULTS: Intradermal skin test reactions were suppressed between 4 and 24 hours and prick skin tests to 10 mg/mL histamine base were suppressed between 6 and 24 hours with all doses of ebastine. Prick skin test reactions were significantly smaller at 12 and 24 hours in the group receiving the 30 mg dose of ebastine than in all other groups. CONCLUSION: Ebastine is a potent antihistamine that suppresses skin reactions to histamine for 24 hours following single doses in the doses tested (1 to 30 mg). No differences from placebo were noted in either the incidence of side effects or in the QTc intervals of serial electrocardiograms.

Adult↗

Flow cytometry of liver fine needle aspirates.

Fine needle aspiration analysis of intraabdominal masses is increasing in frequency. This study was designed to evaluate whether flow cytometry could be of value in the cytopathology interpretation of such specimens. Over a 4-year time span, 129 consecutive liver fine needle aspirates were evaluated by flow cytometry for DNA content, ploidy, and proliferation rate. Only excess cells remaining in the needle after cytology samples were prepared were included in this study. Overall sensitivity was 75% and specificity was 94%. In addition, flow cytometry results were pivotal for at least two specimens in achieving the appropriate diagnosis. For these reasons, it was concluded that flow cytometry could be a valuable adjunctive technology, to the cytopathologist in the interpretation of liver fine needle aspirates.

Biopsy, Needle↗

Safety and efficacy of oral immunotherapy with standardized cat extract.

Fifty-three subjects with positive skin prick test results to cat extract and rhinoconjunctival symptoms on exposure to cat dander were enrolled in a double-blind, placebo-controlled study of oral cat immunotherapy. Responses were assessed by development of symptoms and nasal blockage on exposure to an apartment contaminated with cat dander, by titrated skin prick tests, and by cat-specific IgG and IgE. A total cumulative dose of 2.5 x 10(6) allergy units or 436 U Fel d I were administered over a period of 3 months. Both groups of subjects had significantly fewer symptoms on exposure to cat dander during the course of the study, but there was no significant difference between active and placebo groups. There were no significant changes in either group in nasal blockage, skin prick test results, or specific IgG levels. Both groups had significant increases in cat-specific IgE, but there were no differences between groups. Subjects receiving active treatment had a slight excess of gastrointestinal complaints. Two subjects receiving active treatment experienced systemic symptoms: one had pulmonary edema, and the other had persistent asthma and urticaria, which may have represented reactions to the treatment. We conclude that oral cat immunotherapy with the preparation and doses used in this study is not effective.

Administration, Oral↗