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Biomedical subjects

J N Fink

Publications and source records attributed to J N Fink.

At least 73 records · Page 4Linked to original sources

Myocardial infarction induced by coronary vasospasm after self-administration of epinephrine.

A case of a 30-year-old man who developed a myocardial infarction after self-administering an Epi-Pen for an episode of idiopathic anaphylaxis is reported. The patient had numerous risk factors for coronary artery disease, and it was suspected that epinephrine-induced coronary spasm caused the infarct. The Epi-Pen Junior may be indicated in such adults with numerous risk factors for coronary artery disease who are at risk for recurrent anaphylaxis.

Adult↗

Cognitive dysfunction in a patient with long-term occupational exposure to ethylene oxide. Role of ethylene oxide as a causal factor.

This case illustrates a comprehensive approach to assessing causality in a woman with apparent cognitive dysfunction, as measured by neuropsychological testing, and a 10-year history of occupational exposure to ethylene oxide. The analysis included a multidisciplinary examination of the patient, which took place several years after the termination of her exposure. In addition, all of the patient's prior medical and psychiatric records were reviewed, as were the records of her employer to ascertain her exposure history. Our evaluation revealed a pattern of neuropsychological findings not consistent with nervous system damage secondary to an organic effect of ethylene oxide. A more likely causal hypothesis is adopted: the patient's apparent cognitive dysfunction had a psychiatric etiology. This case also illustrates the potential impact of a patient's involvement in legal proceedings related to claims of neurocognitive dysfunction.

Adult↗

Monoclonal antibodies bind identically to both spores and hyphae of Aspergillus fumigatus.

Immunoelectron microscopy (IEM) was used to determine the binding of six monoclonal antibodies (MoAbs) produced against Aspergillus fumigatus antigens present on or within the conidia and hyphae of the fungus. Antigen-antibody complexes were demonstrated in EM using labelled colloidal gold particles (15 nm). Three out of 6 MoAbs (C9, F12 and H10) reacted only with the cytoplasmic components of A. fumigatus while the remaining three (B12, F6G5 and D6E6) showed reactivity to both cytoplasm and cell wall of the conidia and hyphae. The results indicate that IEM is of considerable value in determining and selecting monoclonal antibodies having specific reactivity with diverse antigenic components.

Antibodies, Fungal↗

Aspergillus antigen-induced eosinophil differentiation in a murine model.

Eosinophilia is a prominent feature of the cellular response in allergic and parasitic diseases. Allergic bronchopulmonary aspergillosis due to colonization of the lungs of some asthmatics with Aspergillus fumigatus is characterized by high levels of serum immunoglobulin E and peripheral blood (PB) and lung eosinophilia. This study investigates the role of eosinophils in the pathogenesis of allergic bronchopulmonary aspergillosis by using a mouse model. BALB/c mice were immunized intranasally and intraperitoneally with A. fumigatus antigens (Ag), and the eosinophils in PB and bone marrow (BM) were enumerated. Eosinophilopoiesis in BM cultures was studied in the presence of murine recombinant interleukin-5 (mrIL-5) and supernatants from pokeweed mitogen-stimulated spleen cells as the source of eosinophil differentiation factors. Eosinophils were quantitated by direct counting and by estimating eosinophil peroxidase activity. The results indicate that the percentage of eosinophils in the PB (5.77 +/- 1.17) and the BM (11.19 +/- 4.31) of mice exposed to A. fumigatus Ag was higher than in controls (PB, 2.42 +/- 0.76; BM, 5.12 +/- 2.79; P less than 0.01 for both). Similarly, a significant increase in eosinophils was observed in the BM population from mice exposed to A. fumigatus Ag compared with that in controls when cultured with murine recombinant interleukin-5 (23.13 +/- 7.14 versus 13.77 +/- 5.79, P less than 0.01), indicating that the mice exposed to A. fumigatus Ag had significantly greater numbers of eosinophil precursors in their BM. This study demonstrates that A. fumigatus Ag may be involved in the in vivo commitment of stem cells in the eosinophil differentiation pathway.

Animals↗

Hypersensitivity pneumonitis.

Hypersensitivity pneumonitis is a syndrome caused by sensitization to any of a wide variety of environmental antigens and results in a pulmonary immunologic inflammatory process. The clinical syndrome occurs in a temporal relationship to exposure to the offending agent with resultant systemic or respiratory symptoms with defined chest radiographic and pulmonary function abnormalities. Definitive immune responses include those of the humoral and cellular system. Avoidance of exposure as treatment results in reversal of the clinical abnormalities.

Allergens↗

Concanavalin A-nonbinding Aspergillus fumigatus antigen: a major immunogen in allergic bronchopulmonary aspergillosis.

Humoral immune responses in allergic bronchopulmonary aspergillosis (ABPA) have been well studied. However, reports of cell-mediated immune responses in ABPA are conflicting and not well documented, perhaps because well-characterized antigens are not available. In the present study, we assessed the role of peripheral blood mononuclear cells (PBMCs) from patients with ABPA in their ability to respond to both crude and semipurified Aspergillus fumigatus antigens by in vitro proliferation and immunoglobulin E synthesis. Eight patients with ABPA, eight patients with immediate wheal and flare skin reactivity to A. fumigatus, and ten healthy control subjects with nonreactive skin tests were included in this study. Four A. fumigatus antigens were tested in vitro. Antigens included culture filtrate, mycelial extract, concanavalin A-nonbinding, and concanavalin A-binding antigens. There was a wide range of response to each antigen by each group of subjects. However, PBMCs from patients with ABPA showed greater response to the antigens than did those from the healthy control subjects when evaluated by lymphoproliferation (tritiated thymidine uptake) and immunoglobulin E synthesis (isotype-specific enzyme-linked immunosorbent assay). The concanavalin A-nonbinding antigen fraction had the ability to specifically stimulate proliferation of PBMCs from seven of eight patients with ABPA and from four of eight skin-reactive subjects; none of the healthy control subjects responded. Significantly high levels of immunoglobulin E were detected in unstimulated PBMC cultures from five patients with ABPA when compared with those from healthy control subjects. These results indicate that concanavalin A-nonbinding A. fumigatus antigens may be significant in the cellular immune response of ABPA; such results are similar to those from previous humoral studies of the disease.

Antigens, Fungal↗

Ultrastructural demonstration of specific IgG and IgE antibodies binding to Aspergillus fumigatus from patients with aspergillosis.

Aspergillus-induced diseases usually demonstrate elevated circulating antibodies belonging to different isotypes. The antigens currently used to detect antibodies are crude culture filtrate and mycelial extracts of A. fumigatus (Af). Most Af-associated diseases result from the inhalation of the spores of the organisms present in the environment. However, it is not known whether specific circulating antibodies directed only against spore or mycelia of Af exist in the sera of patients with Af-induced diseases. With colloidal gold we have investigated thin sections of spores and hyphae of Af for their reactivity with Af-specific IgG and IgE antibodies. The results indicate that both spores and hyphae reacted identically with IgG and IgE antibodies from patients. None of the sera from normal control subjects reacted in this system, although low levels of antibodies were detected in the sera by ELISA. Sera from both patients with allergic bronchopulmonary aspergillosis or aspergilloma reacted with cell envelope antigens, whereas sera from patients with invasive aspergillosis also bound to cell sap. This method therefore demonstrates localization of antigens binding to different isotypes in the sera from different clinical forms of aspergillosis and may be useful in purifying specific antigens for immunodiagnosis.

Antibodies, Anti-Idiotypic↗

Characterization of a monoclonal antibody against concanavalin A binding antigen of Aspergillus fumigatus.

A monoclonal antibody was produced against a Concanavalin A (Con A) binding major epitope of Aspergillus fumigatus using a novel method of immunization. The antigen was purified using monoclonal antibody affinity chromatography reacted with specific antibodies present in human sera. Both allergic bronchopulmonary aspergillosis and aspergilloma showed high levels of antibody, against this purified antigen, when compared to normal controls. Similar results were obtained when the monoclonal antibody was used in a capture antigen assay. The antibody reacted with several A. fumigatus extracts in rocket electrophoresis demonstrating a single precipitin arc, which disappeared when Con A intermediate gel was used. This monoclonal antibody demonstrated reactivity only with cytoplasmic components of hyphae and spores of A. fumigatus, when a colloidal gold was used as a probe in immunoelectron microscopy.

Animals↗

Screening for occupational asthma: a word of caution.

The diagnosis of occupational asthma may be difficult due to the complex mechanisms inducing the disorder. Identification of the offending agent after historical documentation may be difficult without bronchial challenge. The hallmark of asthma is bronchial hyperreactivity as detected by methacholine challenge, and this test could be considered as a screening test for asthma in the workplace. Four cases are presented that document changes in methacholine airway reactivity dependent on temporal association with exposure to the workplace or the specific offending agent. This indicates a need for a careful evaluation of symptoms relative to exposure in patients suspected for workplace asthma as well as serial determinations of methacholine response to detect potential variability in the airway reactivity.

Adult↗

Exercise-induced asthma in adolescent gym class population.

The prevalence of exercise-induced asthma (EIA) was determined in a population of 12- and 13-year-old schoolchildren whose parents returned a questionnaire regarding a previous diagnosis of asthma, recent asthmatic symptoms and symptoms of allergic rhinitis. EIA was defined as a greater than 15% fall in peak expiratory flow rate (PEFR) following 6 min of free running in a gymnasium. Among the 201 children studied, 18 (8.9%) demonstrated EIA. Of 21 children with symptomatic asthma in the 6 months prior to study, 9 (43%) developed EIA compared to none of 6 children with asymptomatic asthma (p less than 0.0001). Among 48 children with a history of allergic rhinitis alone, 7 (14.6%) demonstrated EIA. The mean postexercise changes in PEFR were 14.9% for 16 children with both asthma and allergic rhinitis, 6.4% among 48 children with allergic rhinitis only, and 1.8% among 125 normal children. Recent symptoms of asthma and a history of allergic rhinitis appeared to be risk factors for EIA. EIA was readily demonstrated in a gym class setting; the use of such screening may facilitate its diagnosis and treatment.

Adolescent↗

Metaproterenol (Alupent) metered dose inhaler in children 5-12 years of age.

This multiclinic study was performed to evaluate the safety and efficacy of metaproterenol sulfate (Alupent) metered dose inhaler in children with asthma ages 5 to 12 years. A total of 268 children completed this study according to the protocol, having received either metaproterenol or placebo for 30 consecutive days. Full spirometric testing was done pre- and postdose on Days 1 and 30 for a total duration of 6 hours on each day. The results showed that metaproterenol was consistently superior to placebo in all pulmonary function parameters measured on Days 1 and 30. This difference was statistically significant for peak values and areas under the curves for both FEV1 and FEF25-75%. There were no significant side effects noted. We conclude that metaproterenol metered dose inhaler is safe and effective in the treatment of asthma in children ages 5 to 12 years.

Administration, Inhalation↗

Circulating antibodies against thermophilic actinomycetes in farmers and mushroom workers.

Sera from individuals exposed to moldy hay, mushroom compost and unexposed individuals, were studied for antibodies against thermophilic actinomycetes and Aspergillus fumigatus. Antigens extracted from Thermoactinomyces vulgaris strains isolated from China were used in the study along with antigens from standard strains to screen the sera of individuals exposed to farms and unexposed controls from both China and the United States. It was found that very little antibody response to A. fumigatus and F. rectivirgula was demonstrated in the sera of both individuals exposed to farm environments and unexposed controls. On the other hand, antibodies to Thermoactinomyces vulgaris and T. candidus strains were seen in the sera of both exposed and unexposed individuals from China, indicating that these organisms are prevalent in all the environments of China. The results also indicate that antigenicity of the strains vary considerably in their reactivity with sera.

Agricultural Workers' Diseases↗

Detection of IgG and IgE antibodies to Aspergillus fumigatus in human sera by immunogold assay.

An immunogold assay (IGA) was developed to detect IgG and IgE antibodies to Aspergillus fumigatus. Sixteen sera from patients with allergic bronchopulmonary aspergillosis (ABPA), aspergilloma, and normal controls were studied. All sera were also evaluated for antibodies against A. fumigatus by biotin-avidin linked enzyme immunosorbent assay (BALISA) and by agar gel double diffusion method. A. fumigatus specific IgG and IgE antibodies could be detected by IGA in all the patients' sera but not in the sera of normal controls. Both IgG and IgE antibodies to A. fumigatus could be demonstrated in all the sera by BALISA and normal controls showed only low levels of these antibodies. There was a positive correlation between the degree of reactivity detected by IGA, the BALISA titer and the precipitins by agar gel diffusion. It can be concluded that IGA is a reliable, sensitive and simple method capable of detecting both IgG and IgE antibodies against A. fumigatus in patient serum.

Antibodies, Fungal↗

A multicenter trial of nedocromil sodium, 1% nasal solution, compared with cromolyn sodium and placebo in ragweed seasonal allergic rhinitis.

This study was a double-blind, parallel-group study to evaluate a new medication, nedocromil sodium, 1%, in comparison with placebo and cromolyn sodium, 4%, for treatment of ragweed seasonal allergic rhinitis. Two hundred thirty-three patients (aged 12 to 65 years) from eight centers were randomized to treatment, one spray per nostril, four times daily, with nedocromil sodium, cromolyn sodium, or matched placebo (80, 76, and 77 patients, respectively). All patients had at least a 2-year history of ragweed seasonal allergic rhinitis. Treatment was for 8 weeks during the ragweed season, and daily pollen counts were used to identify the peak 3-week period. Clinic examinations were made before and after the 1-week baseline and after 1, 3, 5, and 8 weeks of treatment. Rhinitis symptoms were recorded each day by the patients. Nedocromil sodium was more effective than placebo (p less than 0.05) in relieving symptoms as recorded by the patients. Cromolyn sodium was also more effective than placebo, but the difference was not usually significant. Similarly, the active treatments were both better than placebo for clinical parameters measured at visits and for global opinions of treatment, and more rescue therapy was used by the placebo-treated group. There was no significant difference between the two active treatments, but the trend throughout was in favor of nedocromil sodium. Our findings demonstrated nedocromil sodium to be at least as effective as an established therapy (cromolyn sodium) in reducing symptoms of rhinitis during the peak ragweed pollen season.

Adolescent↗

Immunopathological response of C57BL/6 and C3H/HeN mice to Aspergillus fumigatus antigens.

C3H/HeN and C57BL/6 mice were exposed to culture filtrate (CF) and mycelial extracts (ME) of Aspergillus fumigatus (Af) intranasally. Animals received 6, 8 or 10 biweekly doses and were sacrificed 2 weeks after the last dose was administered. Specific antibodies against Af were detected in their sera by biotin-avidin-linked immunosorbent assay (BALISA). Antibodies against Af belonging to all isotypes showed an increase in both strains of mice. A progressive increase in IgG and IgA antibody isotypes against both CF and ME antigens was detected in C3H/HeN mice during the entire experimental period, whereas most antibody levels peaked after the 8th dose and remained steady or decreased slightly in the C57BL/6 strain. Lung lavage studies showed a relative decrease in the number of macrophages and an increase in the number of lymphocytes after the 6th and 8th instillation of Af antigens in both strains of mice. Histology of the lung demonstrated a progressive inflammatory reaction in C57BL/6 mice during the experimental period. On the other hand, the C3H/HeN mice showed a negligible inflammatory pulmonary reaction. The antibody responses and inflammatory changes detected in the lungs of mice exposed to Af antigens are comparable to allergic bronchopulmonary aspergillosis (ABPA) in humans and hence this model will be of value in understanding the disease mechanism in ABPA and related diseases.

Animals↗