Sting challenges as criteria for venom immunotherapy.
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Biomedical subjects
Publications and source records attributed to H S Novey.
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Systemic reactions resembling anaphylaxis have occurred after intravenous (IV) iron-dextran administration, a treatment modality that has acquired increased acceptance following the use of erythropoietin for the anemia of patients with chronic renal diseases. Three such patients sustained anaphylactoid reactions immediately after receiving IV test doses of iron-dextran which were their only known exposures. In an effort to determine the mechanism of their reactions, we applied tests for (1) basophil degranulation by iron-dextran, basophil histamine release; (2) a type I anaphylactic reaction, specific IgE antibodies; and (3) an immune complex activation, specific IgG antibodies against iron-dextran. Six other patients with renal diseases served as controls, three of whom had tolerated IV iron-dextran, and three without known exposure. One patient only had any test abnormalities. Her initial positive basophil histamine release and specific IgG antibodies reversed and declined respectively at a 4-month follow-up study. She had developed anaphylaxis, and her studies had been performed at a time after anaphylaxis earlier than the other two. The mechanisms of iron-dextran anaphylaxis may be multiple and not be detectable several months after the incident. Prospective studies will probably be required for a predictive test to be developed.
BACKGROUND: Despite widespread acceptance of metered-dose inhalers (MDIs) in the treatment of asthma, many patients fail to operate these devices correctly. Inability to properly coordinate activation with onset of inhalation is regarded as the major factor in suboptimal MDI therapy. METHODS: We evaluated Autohaler Inhalation Device (3M Pharmaceuticals, St. Paul, Minn.), a breath-activated MDI that is typically activated at a triggering flow rate of approximately 0.5 L/sec. We compared bronchodilator effect of pirbuterol acetate (Maxair), inhaled from Autohaler and a standard MDI, under conditions that ensured optimal technique in 20 patients with asthma. Spirometric variables (forced expiratory volume in 1 second [FEV1], forced expiratory flow between 25% and 75% of vital capacity [FEF25-75], forced vital capacity [FVC]) were measured before and at 15, 30, 60, and 90 minutes after two inhalations of full inspiratory reserve volume for each device. RESULTS: Both devices produced significant and similar bronchodilation. Mean FEV1 increased 32% above baseline 60 minutes after use of Autohaler and 31% after use of a standard MDI. Similar changes were noted in FEF25-75 and FVC for the two devices. Differences between devices for all spirometric variables were not statistically significant. CONCLUSION: Autohaler provides a promising alternative to the standard MDI by overcoming breath-hand discoordination.
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The Quidel allergy screen is a relatively rapid (less than 2 hours) multiallergen dipstick method for detecting specific immunoglobin E antibodies in serum. It was developed to answer the need of primary physician nonspecialists in allergy for a convenient in-office screening test for diagnosing allergy. The new test was evaluated against the benchmark diagnostic skin tests and the radioallergosorbent serologic tests for sensitivity, specificity, accuracy, and technical feasibility in an office setting. It was found that while the Quidel allergy screen lacks the specificity of the standard tests, its overall sensitivity, as defined by the percentage of patients with positive skin reactions who also tested positive with the Quidel screen (68%), its ease of use, and its rapidity warrant its consideration as a screening tool for confirming a possible case of allergy.
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Seasonal allergic rhinitis is usually easily diagnosed by the seasonal nature of characteristic symptoms combined with evidence of appropriate specific IgE antibodies. Perennial allergic rhinitis, however, may present a diagnostic challenge. The physician may find IgE antibodies to allergens perennially encountered by the patient and should look for other causes of chronic rhinitis. Examination of nasal secretions can be a diagnostic aid, but measurements of eosinophils and total IgE in serum have limited diagnostic value.
Sensitization to HMW allergens is a relatively common immunopathogenic factor in occupational asthma. The mechanism of sensitization is an IgE-mediated, type I reaction. High molecular weight allergen refers to proteins and polymers of organic compounds over 5 kd and usually in the 20 to 50 kd range. In most cases diagnosis requires: 1. A high index of suspicion of job-related asthma. 2. Exposure to HMW compounds and clinical findings associated with such an exposure. 3. Confirmation of sensitization by appropriate in vitro or in vivo tests. 4. Confirmation of a pathogenic role by physiologic measurements in either a natural setting or during laboratory-controlled challenges.
In general, a history of exposure to "moldy" hay, birds, or other incriminated occupational or environmental inhalants in a patient with clinical and radiologic features consistent with HSP should lead to the demonstration of serum precipitins to the suspected antigen and an established diagnosis, confirmed by avoidance of the agent involved. Occasionally, other diagnostic procedures are required. The diagnosis is often difficult in domestic exposures, such as humidification and air conditioning systems. A careful environmental history is essential, and at times the physician must inspect the patient's environment personally. In most cases, the diagnosis is established if (1) the history and physical findings and pulmonary function tests indicate an interstitial lung disease, (2) the x-ray film is consistent, (3) there is exposure to a recognized cause, and (4) there is antibody to that antigen. In other exceptional circumstances, bronchoalveolar lavage may help. Biopsy is rarely needed. Special environmental studies and identification of new antigens require research facilities. Provocation tests are research procedures, not necessary for the diagnosis, and not needed in contested workmen's compensation adjudications.
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Sustained-release theophylline compounds given once (Uniphyl) or twice (Theodur) daily were compared in adult asthmatics. Following a single dose of oral medication, large and peripheral airways bronchodilation occurred; response to theophylline correlated significantly with the log plasma theophylline concentration. Cardiac output and stroke volume, measured noninvasively using the acetylene technique, also increased significantly. During maintenance therapy, both preparations caused similar improvements in pulmonary function and symptoms; however, side effects were less with once-daily therapy.
The ability to harvest spore-rich isolates of molds permitted quantitative studies of their role in the pathogenesis of asthma. Alternaria and Penicillium were selected as examples of ubiquitous molds that readily induce IgE antibodies and are of contrasting sizes. Extracts from those spores were prepared for skin tests and aerosol bronchial challenges. Intact spores were used in the same subjects in bronchial challenges delivered by a Spinhaler. Seven patients with a history of mild asthma received a total of 16 bronchial challenges with the mold to which they had been sensitized. Provocative doses in spore equivalents for a 35% drop in SGaw, 20% drop in FEV1, or 25% drop in PEFR were sought for each challenge. Density dependence-flow rates were also determined. Environmental spore survey data were obtained and compared with the challenge doses for these spores. It was found that immediate-type asthma was readily provoked by both whole spores and by their extracts, in some subjects fewer intact than extracted spores were required, delayed-type asthma occurred only after whole spore challenges, SGaw was the most sensitive and equally specific of the pulmonary function tests, and provocative doses of spore equivalents were within natural exposure ranges. The study confirmed that Alternaria and Penicillium spores in relatively natural states and numbers were potent immunopathogens for asthma.
Seven patients had anaphylactoid reactions after ingesting tolmetin sodium. In each case the reaction followed readministration of the drug after an interrupted period of at least three days and within 90 minutes of taking a single 400-mg capsule. None of the patients had had prior anaphylaxis and none were judged atopic. Skin tests to an extract of the drug (0.02 mg) were uniformly negative, whereas a higher concentration produced a nonspecific irritant reaction. In vitro tests in one patient for IgE antibodies to tolmetin and for complement activation were negative.
The relationship between adverse reactions to chrysotherapy and specific IgE antibodies to sodium aurothiomalate (auIgE) was studied in 67 patients with rheumatoid arthritis (62) or psoriatic arthritis (5). Thirty patients (45 percent) had such antibodies versus none of the 27 control patients. Of the 34 patients in whom reactions to chrysotherapy developed, 23 (68 percent) had auIgE versus 7 (21 percent) without reactions (p less than 0.001). Mucocutaneous lesions were significantly associated with auIgE (p less than 0.001). All five patients with thrombocytopenia, but only one of five with the nephrotic syndrome, had auIgE. The patients with IgE response had higher total serum IgE levels (p less than 0.005), were more likely to be atopic (four to one), and had more recently received chrysotherapy (mean 2.8 +/- 1.95 years versus 7.0 +/- 5.75 years, p less than 0.001) than those without response, but did not differ by either the gold product or the total dose used. Chrysotherapy is associated with the production of specific IgE antibodies to a gold salt, and some mucocutaneous and hematologic reactions may be immunologically mediated.
A variety of systemic reactions associated with exercise are increasingly being recognized. We studied an atopic individual whose job-related activities involved strenuous running that often terminated in an episode of syncope and hypotension preceded by cutaneous pruritus, warmth, urticaria, and angioedema. These attacks occurred only after meals, but no foods appeared to elicit symptoms without subsequent exercise. The subject underwent three exercise challenges in the laboratory under the following conditions: (1) fasting state, with heat-dissipating clothing. (2) fasting, with heat-retention clothes, and (3) after a meal. Blood pressure decreases and minimum skin reactivity were observed for (1) and (2), and reproduction of syncope, hypotension, and further cutaneous manifestation were observed only after (3). Venous and arterial plasma determinations for complement activation (C4, C4d, and CH50) and histamine before, during, and after exercise were not abnormal. Although other vasodepressor mediators may have been liberated, at least part of the mechanism for postprandial exercise-related syncope may be attributed to a shift of blood flow to the splanchnic as well as skeletal muscle vasculature.