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Biomedical subjects

R Patterson

Publications and source records attributed to R Patterson.

At least 433 records · Page 24Linked to original sources

Clinical and immunologic evaluation of trimellitic anhydride workers in multiple industrial settings.

This article described our clinical and immunologic experience in assessing workers exposed to trimellitic anhydride (TMA) in three industrial settings. Since 1977 we have had engaged in a prospective study of workers involved at the site of manufacture of TMA. These studies demonstrate that serologic measurements of total antibody to trimellityl human serum albumin (TM-HSA) and IgE antibody to TM-HSA are predictive of the development of an immunologically mediated respiratory illness and are useful in monitoring workers removed from TMA exposure, in identifying asymptomatic workers who may be at risk in the future, and in defining the nature of sensitization of the work force. In a different industrial setting, we have been able to study workers who mixed previously manufactured TMA powder with epoxy resins. This study indicated that clinical assessments by a plant physician with a standardized questionnaire, along with serologic tests, could establish the presence or absence of an immunologic respiratory illness caused by the inhalation of TMA dust. In a third industrial situation, workers were exposed to both TMA and phthalic anhydride (PA). Here workers were interviewed by a local physician with minimal experience with TMA-related respiratory illness. In this situation a more detailed questionnaire was utilized, along with serologic tests utilizing the enzyme-linked immunosorbent assay to establish the presence of a TMA- or PA-related syndrome. Immunologic studies demonstrated in workers exposed to both TMA and PA that the antibody responses elicited showed little crossreactivity between antibodies directed against TM-HSA or PA-HSA.

Antibodies↗

Immunology and immunopathology of trimellitic anhydride pulmonary reactions.

Inhaled trimellitic anhydride (TMA) reacts with airway proteins to produce trimellityl (TM) proteins. THe TM-proteins result in both systemic and local immune responses, of which various proteins present in the airway can be used for markers. Thus TM-human serum albumin (HSA), TM-IgG, and TM-IgA can be used as hapten-protein complexes for immunologic studies in sera of humans exposed to TMA by inhalation. Various immunologic assays have been established to measure antibodies against TM-proteins and have various purposes. With TM-HSA as a model antigen, total serum antibody may be measured by the ammonium sulfate technique of coprecipitation of TM-125I HSA. By solid-phase radioimmunoassays, IgE, IgG, IgA, and IgM antibodies can be measured. Lymphocyte reactivity can be measured by 3H thymidine uptake of TM-protein-stimulated lymphocytes. Biological effects of IgE antibody can be measured by allergy skin tests and leukocyte histamine release with TM-proteins such as TM-HSA. The reaction of TMA with proteins results in alteration of those proteins that include changes in charge and physical conformation, the latter resulting in an apparent change in molecular size. These changes may relate to the observations that human antibody is not merely directed against the hapten in the hapten-human protein complex but also against new antigenic determinants formed by the TM-protein complex. Correlations have been made with certain human immunologic responses and lung disease after TMA inhalation, as follows: IgE antibody against TM-proteins correlates with TMA-induced rhinitis, conjunctivitis, and asthma; high levels of total antibody, IgG, and IgA antibody appear to correlate with the late respiratory systemic syndrome, probably a variant of hypersensitivity pneumonitis; workers exposed to TMA fumes (rather than TMA powder) have the highest levels of antibody, and this may correlate with occurrence of the hemorrhagic pneumonitis seen in this group of workers; patients with no symptoms or mild irritative symptoms have the lowest or no antibody levels. The immunopathogenetic relationships may be better understood with the further development of animal models to TMA lung disease now available.

Antibody Formation↗

Clinical and immunologic evaluation of trimellitic anhydride-and phthalic anhydride-exposed workers using a questionnaire with comparative analysis of enzyme-linked immunosorbent and radioimmunoassay studies.

Twenty workers exposed to trimellitic anhydride (TMA) powder an phthalic anhydride (PA) fumes concurrently were evaluated by questionnaire and serum antibody studies. The study group was divided into high-an low-exposure groups on the basis of job descriptions and intensity of daily exposure. The questionnaire, which was designed to identify symptoms compatible with TMA-associated rhinitis, asthma, late respiratory systemic syndrome, and irritant responses, was administered to 18 of 20 workers. Total antibody binding was determined by the ammonium sulfate assay, and specific IgG and IgE binding was measured with an enzyme-linked immunosorbent assay (ELISA) to both PA-human serum albumin (PA-HSA) and TMA-human serum albumin (TM-HSA) conjugates. Specific IgE to TM-HSA was measured with the polystyrene-tube radioimmunoassay (PTRIA). The questionnaire identified nonirritant, immunologic symptoms caused by TMA primarily in the high-exposure group. Specific IgG, IgE, and total antibody binding to TM-HSA and PA-HSA were found exclusively in the high-exposure workers. One worker was identified with PA-associated rhinitis, high total antibody binding, and specific IgG and IgE to PA-HSA by means of the ELISA. The ELISA was as sensitive as the PTRIA in detecting the presence of specific IgE to TM-HSA. The present study demonstrates that an itemized questionnaire, combined with ELISA IgG and IgE determinations, may be a sensitive method for identifying workers who have or are at risk for developing TMA-induced respiratory symptoms.

Asthma↗

Bone studies in patients on prolonged systemic corticosteroid therapy for asthma.

Cortical thickness of the second metacarpal bone and lumbar spine fractures were determined radiographically in twenty-one caucasian corticosteroid-dependent asthmatics (mean age, 61.2 years; range 47-73 years). The mean number of prednisone years per patient of continuous corticosteroid treatment averages 9.7 (range 5.0-21.5 years), and the mean accumulated dose of prednisone was 46.7 g (range 10.7-160 g). Thirteen of twenty-one (61.9%) patients had cortical thickness between 1 and 2 standard deviations (s.d.) below the age- and sex-specific mean for normals, but only four (19%) patients fell below 2 s.d. Although the study indicated decreased cortical thickness in the prednisone-treated group, in only one (4.8%) patient were vertebral fractures present, an incidence not unexpected in this group. In serious chronic asthma, concern for bone structure should not prohibit the cautious use of appropriate corticosteroid regimens at the lowest possible maintenance dose.

Adrenal Cortex Hormones↗

Immune response of dogs and rabbits to intrabronchial trimellitic anhydride.

8 dogs and 7 rabbits were immunized intrabronchially with trimellitic anhydride (TMA) using three different immunizing doses. An immune response occurred in both animal species. Predominantly IgG with lower levels of IgM and IgA antibodies against trimellityl-erythrocytes (TM-E) were detected on both dogs and rabbits. Antibody binding of TM125I dog serum albumin (TM125I-DSA) occurred in most dogs and of TM125I rabbit serum albumin (TM125I-RSA) in 1 out of 7 rabbits. Lymphocyte reactivity was present in all 8 dogs. Death occurred in the 2 dogs immunized with the low dose (0.1 mg/kg) of TMA, in 2 of the 4 dogs immunized with the moderate dose (1.0 mg/kg), and in neither of the 2 dogs immunized repeatedly with the high dose (10.0 mg/kg). No correlation of deaths could be made with serum levels of anti-TM-E antibody or anti-TM125I-DSA antibody binding, or lymphocyte reactivity. The deaths occurred early in the TMA immunizations. All antibody levels in the diseased animals were less than those seen in human workers with TMA-related respiratory disease. Autopsy findings in the 4 dogs showed hemorrhagic pneumonitis possibly analogous to the pulmonary lesions seen in the hemorrhagic pneumonitis of some workers exposed to TMA fumes. TMA as used in these experiments was not toxic to dogs as the high doses of TMA (10.0 mg/kg) did not lead to death which did occur at the lower doses. No deaths occurred in the 7 rabbits immunized with 1.0 mg TMA/kg. The immune responses and pathological findings in dogs encourage further work in the development of animal models of TMA immunologic lung disease.

Animals↗

Bronchopulmonary torulopsosis.

A patient had clinical and radiographic findings suggestive of allergic bronchopulmonary aspergillosis. Further studies excluded this diagnosis but indicated that the patient's respiratory disease was due to the yeast Torulopsis glabrata, usually nonpathogenic in normal human hosts. The patient had no evidence of invasive disease. Total serum IgE was elevated but IgE antibody against T. glabrata could not be demonstrated by skin test or radioimmunoassay. Demonstration of elevated IgG antibody against T. glabrata antigen by radioimmunoassay was of value in suggesting the diagnosis. The patient responded to prednisone therapy with clinical and radiographic improvement and with a sharp decline in total serum IgE, and a lesser degree of decline in total serum IgG and IgA. Bronchopulmonary torulopsosis may be rare but should be considered in cases where the diagnosis of allergic bronchopulmonary aspergillosis cannot be established. Because IgE antibody could not be incriminated in this disease the term allergic bronchopulmonary torulopsosis was not used in this case.

Aged↗

Allergic bronchopulmonary aspergillosis: staging as an aid to management.

Five stages of allergic bronchopulmonary aspergillosis were identified in 40 patients studied for several years. The stages are acute, remission, exacerbation, corticosteroid-dependent asthma, and fibrotic. The acute stage has all criteria of the disease and responds to prednisone. The remission stage is free from significant asthma or exacerbations. The exacerbation stage has recurrent flares of acute allergic bronchopulmonary aspergillosis. The corticosteroid-dependent asthma stage may have recurrent exacerbations of allergic bronchopulmonary aspergillosis and severe asthma. The fibrotic stage is an advanced stage of radiographic abnormalities with asthma, irreversible and partially reversible obstructive pulmonary function changes, and poor prognosis. Measurement of IgE and IgG antibodies against Aspergillus fumigatus is of diagnostic value in all stages.

Acute Disease↗

Quantification of ultrastructural variations in enriched blood basophils: correlation of morphological changes and antigen-induced histamine release.

Highly purified preparations of human basophils have been studied ultrastructurally to delineate quantifiably those alterations associated with immunologically-induced histamine release. Of six characteristic variations of basophil morphology, totally degranulated cells, those with some exteriorized granules and those with some extracellular vesicles were almost exclusively associated with antigen challenge. Of these, total degranulation without extracellular granules or vesicles was most frequent. A correlation was found between percentage histamine released and percentage totally degranulated cells present in the samples incubated with antigen. In addition, increased plasma membrane folding and irregularity were more prevalent in stimulated samples than in controls and their mean frequency was related quantifiably to the percentage of histamine released in each group. Cells with empty vesicles or electronlucent intracellular granules or both occurred to the same extent in experimental and control aliquots. The possible of histamine release is discussed.

Antigens, Fungal↗

Steroid therapy in septic shock. Survival studies in a laboratory model.

The efficacy of pharmacologic doses of steroids in the treatment of septic shock was evaluated using a laboratory model. The model produced a septic insult of gradual onset followed by a rapid progression, allowing for the evaluation of postcontamination therapeutic regimens. In Sprague-Dawley rats, the cecum was ligated distal to the ileocecal valve and doubly punctured. Control animals (n = 41) received no postoperative therapy. Mortality was 37 per cent at 24 hours and 90 per cent at 48 hours. Approximately 25 animals were assigned to each of five experimental groups. Pharmacologic doses of methylprednisolone at four and eight hours postoperatively did not alter survival. Short-term gentamicin (STG) at four and eight hours improved early survival, which then declined to control values. Addition of steroid to STG had no effect. Long-term gentamicin (LTG) administered through the third postoperative day produced significant increased survival over controls throughout the study. Pharmacologic doses of steroid at four and eight hours added to LTG resulted in a significant increase (P less than 0.05) in survival rate over the treatment with LTG alone.

Animals↗

Application of enzyme-linked immunosorbent assay (ELISA) in diagnosis of allergic bronchopulmonary aspergillosis.

IgE and IgG antibodies against Af were measured by ELISA in sera from 15 patients with ABPA and compared with antibody levels in six patients with extrinsic asthma and immediate-type skin reactivity to Af (prick skin test 3+ or 4+) but no other evidence for ABPA. The assay used polyvinyl microhemagglutination plates as a solid phase to adsorb antigens of Af and a double-antibody system of class-specific anti-human globulin and alkaline phosphatase-conjugated goat anti-rabbit globulin. IgE-Af and IgG-Af were significantly greater among patients with ABPA than in patients with asthma, suggesting that this assay may be used as an important diagnostic aid. The advantages of ELISA over radioimmunoassay are discussed in regard to early detection of an indolent pulmonary disease.

Antibodies↗

An animal model of occupational immunologic asthma due to diphenylmethane diisocyanate, with multiple systemic immunologic responses.

Inhalation of MDI in the plastics industry may produce hypersensitivity pneumonitis or immediate-type asthma in workers. A suspension of MDI was given intrabronchially to dogs to determine whether any of the clinical and immunologic human responses could be duplicated, Results showed that dogs produce a systemic immune response to MDI-DSA. Serum MDI-125I-DSA binding was shown by the ammonium sulfate binding technique. Antibody activity of IgG, IgA, and IgM antibody classes was shown by a solid-phase enzyme-linked immunoassay. Precipitating antibodies were detected in he dog serum against MDI-DSA. Immediate-type skin reactivity to MDI-DSA consistent with a canine IgE response occurred. The skin reactivity appeared to correlate with an immediate-type airway response characterized by an increase in pulmonary resistance after intrabronchial MDI. There was transient peripheral blood lymphocyte reactivity to MDI-DSA. The results indicate that a large animal model of human immune response to MDI is available for various immunopathogenic studies.

Airway Resistance↗

Idiopathic anaphylactoid reactions. A clinical summary.

Thirty-one patients, aged 6 to 78 years, with anaphylactoid reactions of unknown cause were retrospectively evaluated. All of the patients had life-threatening hypotension, wheezing or upper airway obstruction, and simultaneous angioedema or urticaria. Twenty-six patients also had episodes of angioedema or urticaria alone. In nine patients the initial episode was the most severe. In 16 of 18 patients, medications were effective in controlling or reducing the severity of the symptoms. In ten patients, the reactions were always self-limited and no medications were needed. No deaths occurred in 210 anaphylactoid attacks during 164 patient-years. Remissions lasting more than one year occurred in seven patients. Laboratory studies, food diaries, and skin tests were not helpful in establishing an etiology, although atopy was present in 12 of 15 patients tested.

Adolescent↗

Recurrent Churg-Strauss vasculitis. With exophthalmos, hearing loss, nasal obstruction, amyloid deposits, hyperimmunoglobulinemia E, and circulating immune complexes.

Churg-Strauss vasculitis in remission for 4 1/2 years recurred, with new, previously undescribed features, after a lapse in corticosteroid therapy. Bilateral exophthalmos, unilateral hearing loss, and nasal obstruction accompanied fever, severe asthma, and palpable purpura. Leukocytosis with eosinophilia, an elevated ESR, hyperimmunoglobulinemia E, an pulmonary infiltrates were seen again. Circulating immune complexes were detected, and microamyloid deposits were found in the conjunctiva and skin. All clinical and laboratory manifestations responded to corticosteroid therapy. Monitoring the levels of IgE may add a diagnostic and prognostic feature to the classification of necrotizing vasculitides.

Adult↗

Trimellitic anhydride Toxicity. A cause of acute multisystem failure.

A person exposed to trimellitic anhydride (TMA) an epoxy resin widely used in industry, experienced respiratory failure, anemia, and gastrointestinal bleeding. A lung biopsy specimen demonstrated intra-alveolar hemorrhage and damage to alveolar lining cells. The patient and six co-workers were examined. Results indicated the presence of hemolytic antibodies directed against TMA-haptenized erythrocytes, IgG, IgA, and IgM antibodies directed against TMA-erythrocyte complexes, and antibodies against TMA-human serum albumin. Antibody levels in the patient were greater than in the co-workers. The elevated antibody levels demonstrate the antigenic potential of TMA. However, the cause of the pulmonary and hematologic damage remains uncertain and may represent either immunologic or direct toxic effects of TMA. In patients with multisystem failure of this nature, occupational hazards should be added to the differential diagnosis.

Adult↗

Characterization of hapten-human serum albumins and their complexes with specific human antisera.

Human antisera against trimellityl-human serum albumin or diphenylmethane diisocyanate-human serum albumin were fractionated by Sephadex G200. The fractions containing IgG were pooled and reacted with trimellityl 125I-human serum albumin or diphenylmethane diisocyanate-125I-human serum albumin, and these mixtures were again fractionated through Sephadex G200. The resultant chromatographic profiles showed two peaks. The first peak contained hapten-human serum albumin-antibody as demonstrated by the precipitability of radioactivity with anti-human IgG. During these studies it was found that trimellityl-human serum albumin or diphenylmethane diisocyanate-human serum albumin have different elution profiles and electrophoretic mobilities than human serum albumin. Trimellityl-human serum albumin elutes earlier and migrates farther toward the anode than either diphenylmethane diisocyanate-human serum albumin or human serum albumin. Diphenylmethane diisocyanate-human serum albumin elutes earlier and migrates farther toward the anode than human serum albumin. These results may be explained by swelling of the trimellityl-human serum albumin molecule due to the additional negative charges of the trimellityl carboxyl groups and loss of positive charges at basic amino acid binding sites of trimellityl. The lesser changes in diphenylmethane diisocyanate-human serum albumin may result from only the delection of positive charges on basic amino acids of human serum albumin since diphenylmethane diisocyanate contributes no additional charge.

Antigen-Antibody Reactions↗

Septal myocardial perfusion imaging with thallium-201 in the diagnosis of proximal left anterior descending coronary artery disease.

The use of myocardial perfusion imaging (MPI) to identify obstructive coronary disease of the left anterior descending coronary artery proximal to the first septal perforator (prox LAD) was studied in 60 patients. Perfusion of the septum and anteroapical areas with thallium-201 injected during exercise was compared to results of coronary arteriography. Septal MPI defect was found in 92.3% of patients with obstruction of the proximal LAD, 27.7% of patients with obstruction of LAD distal to first septal perforator, 0% in patients with obstructions involving right or circumflex arteries, and in 10.5% of patients without coronary disease. Anteroapical MPI defects were found with similar frequency in the three groups with obstructive coronary disease. Septal MPI defect had a sensitivity of 92.3% and specificity of 85.4% in the diagnosis of proximal LAD disease. Normal septal perfusion with thallium-201 virtually excluded proximal LAD disease.

Adult↗

Enrichment of human basophils.

A 3-step procedure is described in detail for producing 50% basophils in 50% yield from human blood. Leukocytes from dextran sedimented blood or preferably whole blood are sedimented on Hypaque-Ficoll, then on aqueous Hypaque, followed by adherence and elution from a column of glass beads. The cells appear normal and undergo specific histamine release after incubation with antigen. The procedure is relatively rapid and should allow further study of mechanisms of mediator release with more homogeneous populations of basophils. The first step also provides a 5 min separation of blood into a lymphocyte enriched mononuclear cell fraction and a granulocyte enriched fraction.

Basophils↗