A proposed standardized method for bronchoprovocation tests in toluene diisocyanate--induced asthma.
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Biomedical subjects
Publications and source records attributed to H J Schwartz.
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A psychiatric patient's long-term use of antipsychotic medication often results in the irreversible movement disorder, tardive dyskinesia. The author uses a composite case history as a basis for discussing the symptoms, diagnosis, epidemiology, and treatment of tardive dyskinesia. A number of drugs have been used to treat the disorder, but so far none have been effective. While tardive dyskinesia cannot be cured at this time, the author believes that it can be prevented by treating psychoses with the lowest possible dose of the least toxic drug for the shortest length of time.
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The bronchodilator action and cardiovascular toxicity of aerosols of (1) isoetharine, (2) isoetharine in combination with phenylephrine, (3) isoproterenol, and (4) phenylephrine were compared in a group of severe stable ambulatory asthmatics. All preparations except phenylephrine produced reduction in specific airway resistance and increased flow rates which peaked at 15 minutes. The action of isoproterenol and the two isoetharine preparations peaked at 15 minutes while the peak effect of isoetharine and isoetharine in combination with phenylephrine continued for 60 minutes. The difference between isoproterenol and isoetharine alone or in combination with phenylephrine was not statistically significant. None of the drugs produced any cardiovascular side effects. The authors conclude that isoetharine, though less potent than isoproterenol on a weight-for-weight basis, is an effective and safe bronchodilator. Addition of phenylephrine to isoetharine does not potentiate or prolong the action of the latter.
We compared the efficacy of terbutaline with that of metaproterenol, isoproterenol, and placebo aerosols in 16 asthmatic patients. Terbutaline, metaproterenol, and isoproterenol produced equivalent improvements in flow rates. At 5 hr, the effect of terbutaline on tests of small airways, FEF25%--75%, and FEF50%, was greater (p less than 0.05) than that of metaproterenol and isoproterenol. Terbutaline produced no significant change of heart rate or blood pressure.
A survey of the frequency of sensitization to Aspergillus antigens was conducted in a group of asthmatics in Cleveland and compared with a group of asthmatics in London, using common antigens for testing purposes. The two groups were comparable except for earlier onset, longer duration of asthma, and a larger number of males in the London group. Twenty-eight per cent of the asthmatics from Cleveland and 23% from London had immediate skin reactivity to Aspergillus. Seven and one-half percent from the Cleveland group and 10.5% of the London group had Aspergillus precipitins in the serum. Aspergillus skin test reactivity was related to the severity of airways obstruction (p less than 0.01) but was not influenced by other factors. We conclude that sensitization to Aspergillus antigens occur with equal frequency in both the United States and the United Kingdom.
Beta-adrenergic blocking agents are widely used to treat disorders of cardiac rhythm and rate, angina, and hypertension. Propranolol is the most widely used beta-adrenergic blocking agent in this country. Because of its nonselective beta-adrenergic blocking effect, propranolol may be associated with significant bronchoconstriction in asthmatic subjects and in some patients with chronic obstructive pulmonary disease. Since tolamolol, a new beta-adrenergic blocking agent, has cardioselectivity in animals, we studied asthmatic subjects for six hours on three separate days in a double-blind crossover comparison of oral therapy with 40 mg of propranolol, its beta-adrenergic blocking equivalent dose of tolamolol (50 mg), and a high dose of tolamolol (100 mg). All three dosages had equipotent effects on heart rate and systolic pressure. The 50-mg dose of tolamolol had no effect on pulmonary function over six hours; however, both propranolol (40 mg) and the 100-mg dose of tolamolol had equivalent deleterious effects on airway resistance and on rates of expiratory flow. We conclude that the cardioselectivity of tolamolol is dose-limited but is present at the dosage of 50 mg, which is equivalent to the usual antiarrhythmic beta-adrenergic blocking dose of propranolol (40 mg).
The vapor of TDI, a chemical commonly used in the plastics industry, may be associated with pulmonary symptoms at various concentrations. Because of the high volatility and adsorptivity of TDI, it has been difficult to deliver known, dilute concentrations of TDI to test subjects in inhalation challenge studies. A delivery system has been developed which can be calibrated to deliver an air-TDI mixture having a given flow rate and TDI concentration. The delivered gas stream is produced by diluting a gas stream having a low flow rate and a fixed concentration of TDI with a high-flow-rate stream of TDI-free air. A TDI detector continuously monitors the concentration of the resultant mixture, which is delivered to the subject by means of a face mask. For dilute mixtures, the output concentration is proportional to the ratio of the input flow rates; the proportionality factor depends on temperature and the geometry of the system. The flows for the described system could be regulated to produce concentrations in the range 0.0 to 0.08 ppm which remain stable to within +/- 10%.
In surveying the environment of workers in a mattress factory thermophilic actinomycetes as well as phycomycetes and aspergillus species were isolated readily from work room dust, finished bat, sissal and the interior of baled linters. Those persons working with cotton products were shown to have a heavy, daily exposure to organisms known to be implicated in the pathogenesis of hypersensitivity pneumonitis. The authors suggest that further study of the inhaled antigens to which cotton workers are exposed is indicated before discarding immunologic mechanisms to explain the development of byssinosis and other pulmonary disorders to which such workers are subject.
A large-scale multicenter investigation was undertaken in 3 cities with comparable pollen seasons and atmospheric pollen concentrations in order to obtain more definite information about the safety and efficacy of cromolyn sodium in the treatment of pollen-induced seasonal rhinitis. The 9-wk double-blind study was conducted in 104 patiets in Pittsburgh, Pa., Cleveland, Ohio, and Louisville, Ky., during the 1975 ragweed season. It indicated that a nebulized 4% aqueous solution of cromolyn sodium is effective in reducing sneezing, rhinorrhea, nasal congestion, and ocular irritation in ragweed hay fever patients. The efficacy of the drug was notable despite the fact that patients used an average of 52 mg instead of the recommended 62.4 mg daily. Cromolyn sodium did not appear to have a significant effect on transseasonal antiragweed IgE (IgEAR) levels. Patients acceptance of the cromolyn nasal solution was good, and there were no significant adverse reactions. The side effects, which were distributed equally between the drug and placebo groups, were mild and of limited duration.
A patient with occupational asthma caused by phthalic anhydride is described. Inhalation challenges under laboratory control produced immediate and delayed asthmatic responses. Repeat exposure to phthalic anhydride after treatment with cromolyn sodium showed inhibition of the late but not early bronchoconstrictive, asthmatic response.
Of 38 patients with chronic urticaria of unknown etiology who were evaluated for food and drug additive sensitivity, 53% (20/38) had urticaria for 1 yr or more. Total eosinophil counts were not elevated in most patients, and the frequency of atopy was found to be similar to that in a general population. Of these 38 patients, 10 (26%) had a personal history of aspirin intolerance, but elimination of aspirin did not relieve the urticaria. In a double-blind crossover challenge with 0.22 mg of tartrazine and a control, tartrazine sensitivity was found in 8% (3/38) of patients with chronic urticaria and 20% (2/10) of patients with aspirin intolerance.
In order to assess the efficacy and safety of subcutaneous terbutaline 0.25 mg and 0.5 mg as compared to subcutaneous epinephrine, 28 stable asthmatics were studied. After control of environmental exposures in the clinical research facility at the University Hospitals of Case Western Reserve Medical School, the patients were entered into a double-blind crossover placebo-controlled 4-day study. All of the patients showed significant responses to both doses of terbutaline and after epinephrine as compared to placebo (greater than 15% increase in FEV1). In general, the side effects experienced were similar for 0.25 mg epinephrine and 0.25 mg terbutaline. They were slightly more pronounced with 0.5 mg of terbutaline. In terms of duration of action, there was a substantial difference between the duration of effect of subcutaneous epinephrine and subcutaneous terbutaline at both dosages. No cardiovascular side effects of any significance were noted in this study with either agent. We conclude that subcutaneous terbutaline is at least as effective as epinephrine in the management of reversible bronchospasm and may be considered a drug of choice in stable asthmatics.
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A series of 138 patients seen consecutively in an adult allergy clinic were studied to determine serum alpha1-antitrypsin (alpha1-AT) levels and protease inhibitor (Pi) phenotypes. These were compared with a control group of 700 healthy young adult blood donors. Both total serum trypsin inhibitory capacity (STIC) and alpha1-AT levels as determined by immunoelectrophoresis (IEP) were measured. Phenotypes were determined by antigen-antibody-crossed IEP. Alpha1-AT levels in the allergy group were not significantly different from control values. STIC in the allergy group was 1.34 +/- 0.28 mg. trypsin inhibited per ml. serum and in the controls, 1.32 +/- 0.28 mg. IEP values were 205 +/- vs. 200 +/- 36 mg. per dl. Similarly, no increase in Pi phenotypes known to be related to any disease state was observed. Since Pi phenotypes other than the most common MM are rare in Negro populations, phenotype data were corrected to include only Caucasian subjects. In the allergy group adjusted for racial composition we found 2.86% MZ, 5.72% MS; no SZ, SS or ZZ was detected. A comparable control group contained 3.68% MZ, 6.23% MS, 0.71% SZ-SS, but no ZZ Pi phenotype.
The effect of carrageenan on the development of hypersensitivity and foreign body granulomas was examined. Repeated intraperitoneal injections of the polysaccharide caused a strong suppression of the primary, hypersensitivity granulomas forming around the eggs of Schistosoma mansoni worms in the lungs of mice, but had no effect on the secondary, enhanced egg granulomas in the previously sensitized animals. Carrageenan treatment virtually abolished the granulomatous reactions forming around plastic beads or bentonite particles. It is concluded that carrageenan exerted its suppressive effect not through macrophage toxicity but rather by affecting plasma factors which regulate vascular permeability and cellular traffic during the process of inflammation.