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Biomedical subjects

C E Reed

Publications and source records attributed to C E Reed.

At least 127 records · Page 7Linked to original sources

Timing of once-a-day theophylline dose to match peak blood level with diurnal variation in severity of asthma.

To test the hypothesis that nighttime and early morning signs and symptoms of air flow obstruction in patients with moderately severe asthma would be better controlled by theophylline given on a once-a-day evening dosing schedule chosen to provide a peak blood level in the early morning than by the traditional twice-a-day dosing schedule designed to maintain levels more constant throughout the 24-hour period, the effects on nocturnal asthma of Uniphyl once a day and Theo-Dur twice a day were studied in 14 patients with moderately severe asthma. Although both regimens were effective, more patients preferred the Uniphyl dosing schedule. Nighttime symptoms were better controlled, without an increase in daytime symptoms or significant side effects. Optimal timing of theophylline dosing is an important consideration in the management of asthma.

Asthma↗

Immunologic response to aerosols of affinity-purified antigen in hypersensitivity pneumonitis.

On epidemiologic grounds, respirable particles from chilled-water air-conditioning systems in textile production plants have been implicated as a cause of hypersensitivity pneumonitis. We have purified the antigen from scum growing in this chilled water by antibody-affinity chromatography by use of IgG isolated from a pool of serum obtained from three workers with disease. Two patients with the disease, three coworkers without the disease, and two unexposed control subjects inhaled a dose of the purified antigen approximately equivalent to that amount calculated to be inhaled during an 8-hour work shift. Both workers with disease experienced fever, malaise, cough, and dyspnea 6 to 8 hours after the aerosol challenge. In these two patients the exposure evoked a transient decrease in circulating lymphocytes, predominantly T cells. Before challenge the patients' peripheral blood mononuclear cells demonstrated a blastogenic response to the antigen. The responding cells had disappeared from the circulation 24 hours after the challenge. Seventy-two hours after the challenge, mononuclear cells that were producing large amounts of specific IgG antibody appeared in the circulation. We conclude that the same antigen(s) that react with IgG antibody produced an acute episode of the disease, that specific antigen-recognition cells disappear from the peripheral blood after exposure to the antigen (presumably because they are attracted to the lung), and that antibody-forming cells appear in the peripheral blood approximately 2 days after a challenge. These antigen-specific reactions of circulating mononuclear cells may be specific for the disease, but studies on a larger number of cases are needed to be certain.

Aerosols↗

Food skin testing in patients with idiopathic anaphylaxis.

Avoidance is the key treatment of anaphylaxis if an allergen exists; thus, we have evaluated 102 patients with the initial diagnosis of idiopathic anaphylaxis with a battery of 79 food-antigen skin prick tests selected to include foods reported or suspected of provoking anaphylaxis. Only those patients whose episodes consisted of at least two of the following were included in the study: angioedema with or without hives, laryngeal edema leading to severe dyspnea, hypotension, or loss of consciousness. Detailed history, physical examination, and conventional laboratory tests ruled out known causes of anaphylaxis. Thirty-two patients (31%) had positive tests to one or more food antigens. In five of these patients, subsequently eating a food that elicited a positive test provoked an anaphylactic reaction. Two patients eliminated the foods completely, stopped having reactions, and refused challenge. In these seven patients, 10 different antigens provoked anaphylaxis: aniseed, cashew nut, celery, flaxseed, hops, mustard, mushroom, shrimp, sunflower, and walnut. We conclude that a battery of selected food-antigen skin prick tests provided a useful method for identifying an offending antigen in these patients and that some (7% in our series) cases of "idiopathic" anaphylaxis by history are not truly idiopathic.

Adolescent↗

Airway responses to inhaled ouabain in subjects with and without asthma.

Challenges with ouabain and histamine were performed a week apart in 10 patients with asthma and 5 normal subjects. Concentrations were increased cumulatively until specific airway conductance decreased by 30% or the maximal concentration of 1.0% was reached. At low concentrations, ouabain induced bronchodilatation in six patients who had asthma. Bronchodilatation gradually decreased with increasing concentrations and was followed by bronchoconstriction in two patients with asthma who had high airway sensitivity to histamine. Ouabain caused only bronchoconstriction in three patients with severe asthma. The normal subjects showed mild bronchodilatation or no response to ouabain. Several possible biochemical mechanisms may be responsible for the bronchodilatory response to low doses of ouabain, such as stimulation of adenylate cyclase or (Na+,K+)-adenosine triphosphatase. The absence of a bronchodilatory response to ouabain in patients with severe asthma suggests an impairment in the activity of these enzymes.

Adult↗

Nocturnal asthma and timing of treatment.

Nocturnal deterioration of pulmonary function in asthmatic patients is a well-recognized and well-documented phenomenon. The mechanism of this "morning dip," however, remains uncertain. Although the circadian rhythms of body temperature, corticosteroid, catecholamine, histamine, and opiate peptide levels, and even sleep itself have been shown to be in phase with the diurnal variation in asthma, a causal relationship has yet to be established. Increased nighttime bronchial reactivity to histamine, acetylcholine, and house dust allergen have been demonstrated. In general, continuous treatment with theophylline, beta-adrenergic agonists, or corticosteroids attenuates the degree of morning dip but does not completely eliminate the circadian rhythm of asthma. The significance of nocturnal asthma is emphasized by the observation that asthma deaths occur more frequently during nighttime hours and are often preceded by large daily swings in peak expiratory flow. Further studies examining the etiology and treatment of nocturnal asthma are needed.

Adrenergic beta-Antagonists↗

Adrenergic bronchodilators: pharmacology and toxicology.

Advances in the understanding of catecholamine metabolism and adrenergic receptor biochemistry have permitted the development of a number of potent and relatively selective sympathomimetic drugs that are active after oral administration as well as when administered by injection or inhalation. Their toxicity derives solely from their effect as adrenergic agonists, and their appropriate use is based on understanding their pharmacology.

Abnormalities, Drug-Induced↗

An immunochemical approach to indoor aeroallergen quantitation with a new volumetric air sampler: studies with mite, roach, cat, mouse, and guinea pig antigens.

We describe a new high-volume air sampler for determining antigen concentrations in homes and illustrate its use for quantitating airborne house dust mite, cat, cockroach, mouse, and guinea pig antigens. The concentration of house dust-mite antigen was similar from houses in Rochester, Minn. and tenement apartments in Harlem, N. Y., but cockroach and mouse urinary proteins were present only in Harlem. The amount of cat or guinea pig antigen varied as expected with the number of pets in the home. In calm air the airborne concentration of mite and cat antigen was similar throughout the house but increased greatly in a bedroom when bedding was changed. In calm air most of the cat and mite antigens were associated with respirable particles less than 5 microns mean aerodynamic mass diameter, but in air sampled after the bedding was changed, more cat antigen was found in particles greater than 5 microns. The apparatus and technique described can provide objective data concerning the magnitude and the relative distribution and duration of suspended particles of defined sizes, which contain allergen activity.

Air Pollutants↗

Double-blind crossover study comparing doxepin with diphenhydramine for the treatment of chronic urticaria.

Fifty patients with chronic idiopathic urticaria were studied to compare responses to treatment with doxepin (10 mg three times a day) and with diphenhydramine (25 mg three times a day). All patients had an evaluation that failed to disclose a cause for their disease. Therapeutic response was assessed according to the suppression of symptoms and symptom diary scores of daily itching and frequency, number, size, and duration of hives. Total clearing of the pruritus and urticarial lesions occurred in 43% of the patients while receiving doxepin and in only 5% while receiving diphenhydramine (p less than 0.001). Partial or total control of the pruritus and hives was noted in 74% of the patients receiving doxepin and in only 10% of those receiving diphenhydramine (p less than 0.001). Doxepin induced markedly less sedation (22%) than diphenhydramine (46%) (p less than 0.05). Dermatopathologic categories included (1) urticaria simplex, (2) lymphocytic urticaria, and (3) leukocytoclastic urticaria. Patients with urticaria simplex had a more favorable response to doxepin than the two other groups.

Adolescent↗

Increased numbers of hypodense eosinophils in the blood of patients with bronchial asthma.

We investigated the density of blood eosinophils from patients with asthma using polyvinylpyrrolidone-coated silica gel (Percoll) discontinuous density gradient centrifugation of peripheral blood leukocytes. Ten patients with allergic asthma, 10 normal subjects, and 2 patients with the hypereosinophilic syndrome (HES) were studied. The density distribution profiles of eosinophils from normal subjects showed: (1) peaks at densities of 1.085 to 1.090 g/ml and (2) inflection points or nadirs near 1.082 g/ml, below which only 10% of eosinophils were found. On the basis of these results, we divided eosinophils into 2 subpopulations: normodense (greater than 1.082 g/ml) and hypodense (less than 1.082 g/ml). Densities of eosinophils from patients with asthma and HES peaked at 1.083 and 1.076 g/ml (mean values), respectively, significantly lighter than eosinophils from normal donors (p less than 0.005 and p less than 0.001, respectively). The proportions of hypodense eosinophils in patients with asthma and HES were 35 and 95%, respectively, and were significantly greater than that in normal donors (p less than 0.002 and p less than 0.001, respectively). The density distribution profiles of a normal subject were stable over time, but those of asthmatic patients varied with time. For the 22 participants, there was a positive correlation between log-transformed blood eosinophil counts and the percentage of hypodense eosinophils (r = +0.86, p less than 0.001). Similarly, for 15 of them, plasma eosinophil granule major basic protein correlated with the numbers of peripheral blood eosinophils (r = +0.92, p less than 0.0005) and hypodense eosinophils (r = +0.92, p less than 0.0005). Thus, a portion of the eosinophils in asthmatic patients and most of the eosinophils in patients with HES are hypodense.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Calcium ionophore A23187 calcium-dependent cytolytic degranulation in human eosinophils.

The divalent cation ionophore A23187 is frequently used for studies of eosinophil degranulation. Nonetheless, the mechanism whereby A23187 induces degranulation in human eosinophils is still unclear. In the present experiments, A23187 caused human eosinophils to release a granule protein, eosinophil-derived neurotoxin (EDN) and a membrane-associated protein, Charcot-Leyden crystal (CLC) protein in a calcium and a concentration-dependent manner. However, A23187 at a concentration (1 microgram/ml) that caused 15% EDN release and 30% CLC protein release also produced release of the cytoplasmic enzyme lactic dehydrogenase (LDH) and loss of cell viability, both of which were calcium dependent. CLC protein release preceded EDN release and was detectable even at 15 min after the addition of 1 microgram/ml A23187, whereas EDN release occurred after a lag period of 30 min, and coincided with LDH release. At 1 microgram/ml A23187, neither the release of LDH nor the loss of viability occurred with purified neutrophils obtained in the same blood sample as a by-product of eosinophil purification. Electron microscopic examination demonstrated that exposure to A23187 for 15 min resulted in an increase and elongation of microridges on the cell surface, and exposure for 45 min caused cell disruption followed by extrusion of membrane-bound granules through breaks in the plasma membrane. Only once was granule exocytosis observed. These results indicate that A23187 treatment of eosinophils causes an initial release of membrane-associated CLC protein by a noncytolytic mechanism, and causes degranulation as a result of eosinophil lysis.

Blood Proteins↗

Airborne ragweed allergens: association with various particle sizes and short ragweed plant parts.

These investigations were undertaken to size airborne particles by use of a high-volume sampler and to measure the short ragweed allergen activity of airborne particles of different sizes. We found both in vitro and in vivo short ragweed allergen activity in particles of all size ranges including greater than 6, 3 to 6, 1.8 to 3, 1 to 1.8, and 0.3 to 1.0 micron in diameter. Furthermore, we investigated various parts of the short ragweed plant as possible sources of allergen. Plant parts collected before, during, and after the pollination season demonstrated significant in vitro and in vivo allergen activities. We demonstrated allergen activity in various plant parts, especially the inflorescence, as late as November 30. Appreciable ragweed allergenic activity was also associated with particles less than 1 micron in diameter. Collectively, these observations suggest persistent ragweed plant debris in different sized particles as a source of allergen in the air before and after the ragweed pollination season. This may contribute to out-of-season symptoms observed in highly ragweed-sensitive individuals.

Air Pollution↗

Bronchial challenge with formaldehyde gas: lack of bronchoconstriction in 13 patients suspected of having formaldehyde-induced asthma.

We studied 13 selected patients with symptoms suggestive of asthma who suspected exposure to formaldehyde as a cause. These patients had a history of exposure to formaldehyde gas which either coincided with the onset of or aggravated their symptoms of asthma. The levels of exposure at their homes or at work ranged from 0.1 to 1.2 parts per million (ppm) of formaldehyde gas. The patients were tested with bronchial challenges of 0.1-, 1-, and 3-ppm concentrations of formaldehyde gas and randomly interspersed room-air placebos. The formaldehyde gas or placebo was delivered via a Dynacalibrator . The period of exposure to formaldehyde gas or placebo with each challenge was 20 minutes. Pulmonary function was measured before and for 24 hours after each bronchial challenge. No patient had a significantly greater decrease in the forced expiratory volume in 1 second after exposure to formaldehyde than after exposure to air. In no case were we able to substantiate that exposure to formaldehyde gas (3 ppm or less) was indeed causing or aggravating the asthmatic symptoms.

Adolescent↗