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Biomedical subjects

L C Altman

Publications and source records attributed to L C Altman.

At least 37 records · Page 2Linked to original sources
PubMed1990

An outbreak of illness among aerospace workers.

A multispecialty panel of physicians evaluated a case series of 53 composite-materials workers in a large aircraft manufacturing facility who filed workers' compensation claims for illness labeled by the media as the "aerospace syndrome." Possible skin and respiratory tract exposures included formaldehyde, phenol, particulates, epoxy resins, and trace organic solvents, but measured concentrations were well below all regulatory and consensus standards. Most workers had histories of transient skin or respiratory tract irritation consistent with the known potential toxicity of these materials. None of the workers tested had immunoglobulin IgG or IgE antibodies to human serum albumin complexed with formaldehyde. A majority (74%) met DSM-III-R [Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised] criteria for major depression, panic disorder, or both. Most of these psychiatric disorders were of a recent onset, correlating in time with the use of phenol- and formaldehyde-impregnated composite material. Psychosocial factors were thought to have played a major role in the high prevalence of illness in this group and should be evaluated directly in well-controlled epidemiologic studies of similar crisis-building situations in the future.

Air Pollutants, Occupational↗
PubMed1990

Effects of albuterol and procaterol on exercise-induced asthma.

Procaterol and albuterol, beta agonists, were studied using a placebo-controlled, repeated exercise challenge design in order to assess their duration of effectiveness in both bronchodilation and in modifying exercise-induced asthma (EIA). Fifty-three subjects aged 12 to 50 years who had at least a 20% drop in FEV1 during a screening exercise tolerance test were entered. Subjects took two inhalations of procaterol (10 micrograms/inhalation), albuterol (90 micrograms/inhalation), or placebo. Thirty minutes later they exercised on a treadmill at a workload sufficient to induce greater than or equal to 80% aerobic O2 consumption for six minutes. Pulmonary function was measured before and serially for 30 minutes after exercise. The same exercise challenge was repeated three, six, and nine hours after drug administration. Both procaterol and albuterol bronchodilated and modified EIA at 30 minutes and three hours, mean drops in FEV1 being 8.2 and 9.7% respectively at 30 minutes and 16.8 and 16.3% at three hours. This was compared with placebo falls of 30% and 26%. At six hours the subjects' response was similar after both procaterol and albuterol, and fewer subjects had a 20% fall in FEV1 than with placebo, although protection afforded by both beta agonists was substantially less than at three hours. Both drugs were tolerated well.

Adolescent↗
PubMed1989

The toxicity of constituents of cedar and pine woods to pulmonary epithelium.

Occupational exposure to cedar and pine woods and pine resin (colophony) can cause asthma and chronic lung disease. Prior studies suggest that plicatic and abietic acids are responsible for the asthmatic reactions that occur in cedar-wood and colophony workers; however, the etiologic mechanism(s) of the chronic lung disease is unknown. To determine if plicatic acid from cedar wood and abietic acid from pine resin could directly damage lung cells, we exposed monolayers of rat type II and human A549 alveolar epithelial cells, intact rat lungs, and rat tracheal explants to solutions of plicatic and abietic acids. As indices of injury, we measured lysis of alveolar epithelial cells with a 51Cr technique, quantitative desquamation of epithelial cells from tracheal explants, and histologic alterations in tracheal explants and intact lungs. Plicatic and abietic acids both caused dose- and time-dependent lysis of alveolar epithelial cells. Instillation of plicatic and abietic acids into rat lungs produced bronchial epithelial sloughing. Abietic acid also caused destruction of the alveolar epithelium. The addition of either acid to rat tracheal explants caused epithelial desquamation that was dose- and time-dependent. Our results suggest that plicatic acid, a unique constituent of cedar wood, and abietic acid, the major constituent in pine resin, can produce lytic damage to alveolar, tracheal, and bronchial epithelial cells. We hypothesize that repeated occupational exposure to these substances might promote the chronic lung damage observed in some cedar- and pine-wood workers and in electronic workers exposed to colophony.

Abietanes↗
PubMed1989

Pulmonary effects of sulfur dioxide exposure and ipratropium bromide pretreatment in adults with nonallergic asthma.

In this study we examined the potential short-term effect of sulfur dioxide (SO2) on total respiratory resistance and forced expiratory volume in patients with nonallergic asthma. A group of nine adult subjects with nonallergic asthma, 55 years of age or older, were exposed to SO2 at 0, 0.5, and 1.0 ppm for 20 minutes at rest followed by 10 minutes during light-moderate exercise. The measures of pulmonary function assessed were FEV1, specific total respiratory resistance (SRT), and maximal expiratory flow rates at 50% (Vmax50) and 75% (Vmax75) of expired vital capacity. Measurements were made before exposure to SO2 (baseline), postresting exposure, postexercising exposure, and at 30 minutes thereafter (recovery). Repeat measure analysis of variance revealed a statistically significant dose-response effect of SO2 inhalation on FEV1 (p = 0.008), SRT (p = 0.033), Vmax50 (p = 0.017), and Vmax75 (p = 0.048). Eight subjects had repeat exposure to SO2 at 1.0 ppm after treatment with either placebo or ipratropium bromide, 60 micrograms by metered-dose inhaler. Inpratropium bromide treatment, compared to placebo treatment, resulted in a statistically significant improvement in all baseline measures of pulmonary function: FEV1 (p = 0.017), SRT (p = 0.027), Vmax50 (p = 0.018), and Vmax75 (p = 0.035). However, this drug did not significantly alter the proportionate change in pulmonary function caused by SO2 inhalation in these subjects. These findings indicate that adults with nonallergic asthma are sensitive to short-term low-level SO2 exposure and that treatment with 60 micrograms of ipratropium bromide causes significant bronchodilation but does not protect, completely, these patients from the effect of SO2 inhalation.

Aged↗
PubMed1989

Injurious effect of the eosinophil peroxide-hydrogen peroxide-halide system and major basic protein on human nasal epithelium in vitro.

Tissue injury is observed in allergic and nonallergic eosinophilic rhinitis, but the mechanism of this injury is unclear. Because eosinophils are prominent in biopsy specimens in these conditions, we hypothesized that they may participate in the injury process. Initially, we developed techniques to isolate and purify human nasal epithelial cells from turbinate biopsies to use as target cells for eosinophil granule products. Primary cultures from explants were characterized by electron microscopy and indirect immunofluorescence with a panel of primary monoclonal and polyclonal antibodies. These studies revealed the homogeneity of the cells and confirmed their epithelial nature. Cultured nasal epithelial cells were then exposed to either purified human eosinophil peroxidase, bromide, and glucose plus glucose oxidase, as a continuous source of hydrogen peroxide, or eosinophil major basic protein. Neither eosinophil peroxidase alone nor glucose plus glucose oxidase in the absence of eosinophil peroxidase were injurious, but the combined addition of eosinophil peroxidase, glucose/glucose oxidase, and bromide produced marked target cell lysis. This effect was time- and eosinophil peroxidase dose-dependent. Catalase and azide significantly inhibited the lysis of these cells, suggesting the eosinophil peroxidase-catalyzed products of halide oxidation mediated this form of injury. The addition of purified human eosinophil major basic protein also caused dose- and time-dependent lysis of the nasal epithelial cells but required longer incubation periods to effect injury. We hypothesize that the eosinophil peroxidase-hydrogen peroxide-halide system and major basic protein may injure the nasal epithelium in inflammatory conditions such as allergic and nonallergic eosinophilic rhinitis.

Blood Proteins↗
PubMed1989

A specific LTD4/LTE4-receptor antagonist improves pulmonary function in patients with mild, chronic asthma.

LY171883 is a new selective LTD4/LTE4-receptor antagonist. To evaluate the efficacy of LY171883, we studied 138 nonsmoking asthmatic patients, 18 to 65 yr old, in a double-blind, randomized block-design study. All patients were required to demonstrate a greater than or equal to 15% increase in FEV1 after inhaled bronchodilator use and were then randomly assigned to either LY171883 (600 mg) or placebo twice daily for 6 weeks. Assessment of efficacy was measured by inhaled metaproterenol use (mg/wk), symptoms, twice-daily peak expiratory flow, and weekly FEV1 measurements. LY171883-treated patients had improved FEV1 values upon completion of the treatment period compared with placebo recipients (p = 0.003). Metaproterenol use decreased in both groups, but treatment differences, though not statistically significant, favored LY171883 (p = 0.089). Of patients who used at least 23 mg/wk of metaproterenol (36 inhalations) at initiation of the study, those who received LY171883 used significantly less metaproterenol than those who received placebo (p = 0.007). LY171883 was well tolerated and reduced the need for a bronchodilator drug while improving pulmonary function. Results of this study support the hypothesis that leukotrienes LTD4 and/or LTE4 may be important in the pathogenesis of asthma in humans.

Acetophenones↗
PubMed1989

Human nasal epithelium: characterization and effects of in vitro exposure to sulfur dioxide.

Human nasal turbinate tissue from surgical specimens was dissected free of connective tissue, and primary epithelial cultures were established by explant techniques. Transmission electron microscopy revealed that cultured cells retained homogeneous cytoplasmic granules, tonofilaments, and desmosomes and formed a homogeneous monolayer. The epithelial cells stained positively with cytokeratin antibodies AE1, AE3, and 35BH11 but failed to stain with two other cytokeratin antibodies, AE2 and 34BE12. Staining was also positive with anti-desmoplakin I and II but negative with antivimentin (43BE8), anti-desmin, and anti-human factor VIII antibodies. Cultured cells were exposed to filtered air or sulfur dioxide at 1-5 ppm for 30-60 min. Although there was no increase in cell lysis as measured by chromium-51 release, SO2 exposure significantly inhibited [3H]leucine incorporation compared to air exposure. This effect was dependent on both SO2 concentration and exposure duration. Control experiments revealed that these SO2 effects were not caused by the [H+] load produced by SO2 exposure. Electron microscopy of cells exposed to air or SO2 did not show any significant morphological differences.

Adolescent↗
PubMed1989

Terfenadine blockade of exercise-induced bronchospasm.

Terfenadine, in doses of 60, 120, and 180 mg, provided significant bronchodilation for up to four hours after administration. In addition, when the same doses were given four hours prior to exercise, the drug demonstrated significant blockade of exercise-induced bronchospasm at two and five minutes postexercise. These effects on exercise-induced bronchospasm followed a dose-response curve; 180 mg had the most significant effect. All dosing levels, however, produced both bronchodilation and a significant degree of blockade of exercise-induced bronchospasm. No patients were bothered by adverse effects during this single-dose study. Eight of the 11 subjects who completed the study also noted some improvement in their nasal congestion during the testing period when they were on the active drug.

Adolescent↗
PubMed1989

Studies of neutrophil chemotactic factor of anaphylaxis in metabisulfite sensitivity.

The mechanism(s) of adverse reactions to sulfites remains unclear. To determine whether mast cell degranulation is involved in sulfite sensitivity, we performed single-blind, placebo-controlled oral aqueous challenges with potassium metabisulfite in 13 patients with histories suggestive of sulfite sensitivity. Ten patients were also skin tested with potassium metabisulfite at 10 mg/mL and all had negative reactions. Serum samples were obtained from all the patients before the challenge and for 180 minutes after the challenge. The samples were tested for the presence of neutrophil chemotactic factor of anaphylaxis, using both a 51chromium microchamber chemotaxis assay and a leukocyte polarization technique. Six of 13 patients had positive challenges as defined by a fall equal to or greater than 20% in their forced expiratory volume in one second. No significant increase in neutrophil chemotactic factor activity was detected in the postchallenge serum samples from patients who experienced positive or negative challenges. We conclude that sensitivity to aqueous metabisulfite is not associated with mast cell degranulation in metabisulfite skin test-negative patients.

Adult↗
PubMed1988

Prevalence of basidiospore allergy in the Pacific Northwest.

Mold spore-induced respiratory allergy has been incompletely studied, and only a limited number of Fungi Imperfecti are well established as aeroallergens. Basidiomycetes, a complex and common group of fungi, which include mushrooms, rusts, smuts, brackets, and puffballs, have not been well studied. Although basidiospores can be present in high atmospheric concentrations, little is known of their aeroallergen potential. To examine this question, we performed skin prick and RASTs in 33 adult residents of Washington State using a panel of 15 common inhalant allergents that included four Fungi Imperfecti and 15 basidiospore extracts. Thirty-one of 33 (94%) subjects had positive immediate reactions to two or more common inhalants. Nine of 33 (27%) subjects responded to at least one Fungi Imperfecti; reactions were most common to Aspergillus sp. (21%), and least common to Penicillium sp., which were positive in 6%. Positive responses to basidiospore extracts were observed in 10 of 33 (30%) subjects. The prevalence of basidiospore reactivity was similar to that of Fungi Imperfecti, ranging from 18% for Scleroderma sp. to 6% for four different spore extracts. These results demonstrate that a significant number of subjects with respiratory allergies have skin test reactivity to basidiospore extracts, suggesting that these spores could be important aeroallergens in the Pacific Northwest.

Adult↗
PubMed1987

The injurious effect of eosinophil peroxidase, hydrogen peroxide, and halides on pneumocytes in vitro.

Recent data suggest that eosinophils may cause lung injury. To determine if the eosinophil peroxidase (EPO)-hydrogen peroxide (H2O2)-halide system could mediate this injury, we added human EPO, H2O2 (or glucose and glucose oxidase as a continuous source of H2O2), and various halides to monolayers of 51Cr-labeled human A549 and rat type II pneumocytes. Cell lysis was measured as soluble 51Cr release. In initial experiments, EPO in solution did not induce lysis under these conditions. Therefore, in subsequent experiments, pneumocytes were preincubated with EPO for 15 minutes, washed to remove unbound enzyme, and then glucose, glucose oxidase, and the halides were added. EPO alone was not injurious, nor was the addition of glucose and glucose oxidase in the absence of EPO. In contrast, the combined addition of EPO, glucose, glucose oxidase, and chloride produced marked target-cell lysis. This effect was time and EPO dose dependent and was enhanced by the addition of iodide. Catalase and azide substantially inhibited the lysis produced by the EPO-H2O2-halide system, suggesting that EPO-catalyzed products of halide oxidation mediated this form of injury. Finally, the addition of eosinophil major basic protein at 10(-5) mol/L to EPO-coated pneumocytes incubated with glucose, glucose oxidase, and halides failed to enhance or inhibit lysis. We hypothesize that the EPO-H2O2-halide system may injure the lung in asthma and eosinophilic pulmonary syndromes.

Animals↗
PubMed1987

Basidiomycete allergy: measurement of spore-specific IgE antibodies.

RAST with 12 basidiospore extracts demonstrated that a significant percent of 42 individuals with symptoms of perennial rhinitis and/or asthma and skin reactivity to at least one spore extract had spore-specific IgE antibodies. These antibodies were not demonstrable in 14 atopic, symptomatic, skin test negative control subjects nor in five nonatopic, asymptomatic control subjects. There was a statistically significant association between RAST and skin test results for all but three of the spore extracts. A statistically significant association was also observed between RAST results obtained with most of the different spore extracts. A similar association was present for skin test results with different spore extracts. These results provide evidence that basidiospore extracts are suitable allergens for use in diagnostic studies of respiratory disease associated with exposure to basidiomycetes.

Adult↗
PubMed1986

Cotton dust-mediated lung epithelial injury.

To determine if constituents of cotton plants might play a role in byssinosis by injuring pulmonary epithelium, we added extracts of cotton dust, green bract, and field-dried bract to human A549 and rat type II pneumocytes. Injury was measured as pneumocyte lysis and detachment, and inhibition of protein synthesis. Extracts of cotton dust and field-dried bract produced significant dose- and time-dependent lysis and detachment of both target cells, while green bract extract was less damaging. Extracts treated with polyvinylpolypyrrolidone to remove tannins produced significantly less injury. In contrast, purified 5,7,3',4'-tetrahydroxy-flavan 3,4-diol (THF), a tannin in cotton dust and bract, caused substantial cell damage. Field-dried bract extract and THF also produced dose-dependent inhibition of pneumocyte protein synthesis. Endotoxin levels did not correlate with observed injury. THF added to rat tracheal explants caused epithelial disruption and desquamation, whereas endotoxin did not. Instillation of cotton dust and field-dried bract extract in rat lungs produced disruption of bronchial epithelium and smooth muscle constriction, while polyvinylpolypyrrolidone-treated cotton dust extract produced no injury. These findings suggest that extracts of cotton plants are toxic to alveolar, tracheal, and bronchial epithelium and that THF or other tannins may be the responsible agents.

Animals↗
PubMed1986

The value of skin testing for penicillin allergy diagnosis.

Skin testing is reliable and useful to rule out penicillin allergy in most patients who have a history of previous reactions. When we tested 291 inpatients in the University of Washington hospitals for the presence or absence of penicillin allergy, of 97 with a history of penicillin allergy, 12 (12.4%) had positive skin tests. Of 194 patients with no or an unknown history, only 4 (2%) had positive skin tests. Two of the 16 who had positive skin tests (12.5%) reacted only to minor determinant mixtures. Of the skin test-negative patients, 261 were treated with one of the penicillins and only two had any reactions.

Drug Hypersensitivity↗
PubMed1985

Cell-mediated immunity in human herpesvirus infection: analysis by monoclonal antibodies.

Peripheral blood lymphocytes (PBL) were obtained from heterosexual patients during the first or recurrent episodes of genital herpes simplex type 2 (HSV-2) infections. These cells were incubated with a panel of lymphocyte-specific monoclonal antibodies and examined by indirect immunofluorescence and flow cytometry. Lymphocyte proliferative responses to inactivated HSV-2 (UV-HSV-2) were also determined on repeat occasions using PBL obtained from patients with first episodes of infection. Flow cytometry analysis indicated that PBL obtained within 1 week after the onset of symptoms of first episode genital herpes exhibited significantly lower OKT 4 helper/OKT 8 suppressor T-cell ratios (1.26 +/- 0.12) than cells from either normal controls (2.44 +/- 0.3, P less than 0.01) or patients with recurrent genital HSV-2 infection (2.58 +/- 0.40, P less than 0.01). This lowered ratio was due to a decrease in OKT 4-positive helper T cells present early during initial infection (30.2 +/- 2.9, P less than 0.01 compared to recurrent disease patients or controls) and was not caused by a concomitant increase in OKT 8-positive T cells. No variation was observed during the course of infection in the proportion of total T cells as determined by EAET rosette formation or reactivity with the T-cell specific monoclonal antibody 9.6. PBL obtained from patients within 1 week after symptom onset exhibited a poor proliferative response to UV-HSV-2. Maximal proliferative responses occurred 6-9 weeks after disease onset and required the presence of OKT 4-positive T lymphocytes. The results of these experiments indicate that at different stages of disease, HSV infection is accompanied by fluctuations in the ratio of helper to suppressor T cells and alterations in antigen-specific lymphocyte proliferation. These findings suggest that variations in lymphocyte proliferative responses during the course of first episode genital herpes infection may reflect disease related variations in either the number or activity of circulating OKT 4-positive T lymphocytes.

Adult↗
PubMed1985

Eosinophil- and eosinophil granule-mediated pneumocyte injury.

The function of the eosinophil in eosinophilic pulmonary syndromes and asthma is uncertain. To determine if eosinophils might play a harmful role in these conditions, we cocultured purified human eosinophils, eosinophil major basic protein (MBP), and chromatographically eluted eosinophil granule fractions with human A549 and rat type II pneumocytes. Damage to these target cells was measured as cell lysis and nonlethal cell detachment. We found that unstimulated intact eosinophils affected minimal lysis or detachment of either pneumocyte target, but eosinophils stimulated with phorbol myristate acetate and other activators produced time- and dose-dependent nonlytic detachment of both targets. In contrast, supernatants from activated eosinophils did not produce significant injury, suggesting that close apposition of the effector and target cells was required. Catalase and superoxide dismutase did not inhibit the detaching activity of eosinophils, suggesting that hydrogen peroxide and superoxide anion were not activity of eosinophils, suggesting that hydrogen peroxide and superoxide anion were not responsible for mediating this form of injury. In contrast to our findings with intact eosinophils, we observed that the addition of purified eosinophil MBP to pneumocytes caused marked cytolysis with little detachment. When sequential fractions of eosinophil granules separated by Sephadex G-50 chromatography were added to A549 and rat type II pneumocyte targets, it was found that different fractions produced distinct forms of injury. Higher molecular weight fractions containing lysosomal enzymes and eosinophil peroxidase produced predominantly detachment, whereas fractions enriched in MBP produced lysis. These results indicate that intact eosinophils can produce nonlytic detachment of alveolar pneumocytes that is probably not dependent on the generation of toxic oxygen radicals but rather appears to be mediated by granule-associated products, possibly lysosomal enzymes. Furthermore, although intact eosinophils are not capable of lysing alveolar epithelial cells under the conditions of our assay, MBP has the potential to do so when the protein is released in high enough concentrations. The in vivo relevance of these findings in eosinophilic lung diseases may be that eosinophils, by producing both desquamation and death of alveolar epithelium cells, may increase the permeability of the alveolus to fluid and cells. Moreover, these forms of damage might also enhance the ingress of inhaled antigens across the pulmonary epithelial barrier, thus increasing immunologic sensitization.

Animals↗