Search PubMed⌕ Search

Biomedical subjects

I L Bernstein

Publications and source records attributed to I L Bernstein.

At least 163 records · Page 9Linked to original sources
PubMed1985

Pulmonary responsiveness to methacholine and disodium hexachloroplatinate (Na2PtCl6) aerosols in cynomolgus monkeys (Macaca fascicularis).

Hyperreactivity of the airways is a common finding in human asthma, and responsiveness to inhaled methacholine aerosols is routinely used for assessing airway irritability. Workers in precious metal refineries demonstrate pulmonary signs suggestive of asthma, presumably related to exposure to soluble platinum salts. In these workers, evidence of physiologic dysfunction precedes immunologic evidence (skin test) of disease, suggesting an initial pharmacologic mechanism. With a primate animal model for the screening of occupational asthmogens, 24 Cynomolgus monkeys were evaluated for their comparative pulmonary responsiveness to inhaled aerosols of methacholine and sodium hexachloroplatinate (Na2PtCl6). Average pulmonary flow resistance (RL), dynamic compliance (CLdyn), maximum expiratory flow volume (MEFV), and respiratory frequency changes were evaluated after bronchoprovocation challenge. Both agents produced dose-dependent increases in RL, dose-dependent decreases in CLdyn and MEFV, and no effect on respiratory rates. Analyses of the correlation between concentration effects of the two agents showed no association between cholinergic airway irritability status and Na2PtCl6-induced bronchoconstriction. Na2PtCl6 bronchoprovocation produced significantly greater flow impairment at lower lung volumes when compared to methacholine concentrations with equipotent effects on RL and CLdyn. These compounds have differential effects on peripheral airway function. The lack of respiratory rate change seen on bronchoprovocation with these compounds, in comparison to the rapid shallow breathing in anesthetized monkeys following irritant or histamine challenge, indicates that neither aerosol stimulated pulmonary irritant receptors.

Airway Resistance↗
PubMed1985

Targets of learned food aversions in humans.

In order to determine whether some nutrients are more salient targets than others for the development of learned taste aversions a large group of normal human subjects were surveyed about their experiences with such aversions. The targets of these spontaneously occurring food aversions were identified and classified into general food categories. A prominent category for human aversions proved to be foods which were protein sources. This finding was similar to our observations in the clinical setting as well as those we have obtained using an animal model. It suggests that taste and/or postingestive properties of protein foods may make them particularly salient targets for food aversion learning.

Animals↗
PubMed1985

Detection of IgE-mediated respiratory sensitization in workers exposed to hexahydrophthalic anhydride.

Twenty-seven workers with occupational exposure to hexahydrophthalic anhydride (HHPA) from an epoxy resin molding system were studied to evaluate the nature of their reported respiratory complaints. The workers were evaluated by questionnaire, pulmonary function tests, and serologic investigations. The presence of serum-specific IgE and IgG to an HHPA-human serum albumin (HSA) conjugate was measured by use of RAST and ELISA assays. Estimates of exposure to HHPA were made for each worker on the basis of job description and environmental sampling. Seven workers reported symptoms of asthma and rhinitis; four workers had symptoms consistent with occupational asthma. Fourteen of the remaining 20 workers reported nasal or ocular symptoms while they were at work. No worker demonstrated a significant (greater than 20%) pre-to postshift decrement in FEV1. Twelve workers had significant levels of specific IgE to HHPA-HSA; 11 had elevated levels of specific IgG to HHPA-HSA. A group of workers estimated to have higher exposures to HHPA had a significantly higher mean total IgE level (p less than 0.05) and significant titers of HHPA-HSA-specific IgE or IgG, or both (p = 0.048) as compared to a group with lower exposure to the anhydride. All four workers with occupational asthma/rhinitis had significant levels of specific IgE to HHPA-HSA (ranging from 8.7% to 23.4% RAST binding); three workers did not work directly in the HHPA area but were located in nearby sections of the plant with lower exposures to HHPA. Three workers with symptoms of asthma not clearly associated with the workplace did not have significantly elevated specific IgE levels. Another radioimmunoassay with the use of beads coated with mouse monoclonal antihuman IgE was used to quantitate the amount of specific anti-HHPA-HSA binding (range 1.0 ng to 32.6 ng/ml) present in workers' sera. The solid-phase bead radioimmunoassay was inhibited by the homologous HHPA-HSA conjugate but not by HHPA hapten alone in two workers, suggesting that these workers were sensitized to new antigenic determinants. We conclude that HHPA is a potent industrial sensitizer and is capable of inducing IgE-mediated disease. Prospective investigations are required to define the incidence and severity of clinical sensitivity.

Antibody Specificity↗
PubMed1985

Treatment decisions of asthma based on a paradigm of clinical severity.

The optimal treatment of asthma is amenable to modern decision analysis. One of the simplest decision models is the decision diamond. Components of the asthma decision diamond include the asthma data base, past clinical experience, latest clinical research developments, and clinical judgment. These factors are integrated into the final treatment decision. The treatment decision itself is also related to a clinical staging paradigm that can be classified into mild, moderate, and severe stages of asthma. Combined clinical and physiologic assessment determines the proper staging classification. Various treatment modalities can be used preferentially in each of the stages of asthma; these are reviewed in detail. Proper choices of pharmacologic agents at appropriate times during the natural course of asthma should be based on analytic decision making in the context of the rank order of asthma severity.

Adrenal Cortex Hormones↗
PubMed1985

Cromolyn sodium in the treatment of asthma: coming of age in the United States.

Cromolyn sodium has matured as a first-line drug in the management of asthma in the United States. New pharmacokinetic assays reveal that it exerts classic dose-response effects both in vitro and in vivo. The protective effect of cromolyn sodium is due chiefly to its ability to inhibit mediator release from mast cells, but there is considerable evidence that it may affect reflex-induced asthma and bronchial hyperreactivity. It may also reduce the number of inflammatory effector cells such as eosinophils and decrease the IgE-mediated local immune response. Two formulations are currently available in the United States: the powdered Spinhaler apparatus and a solution that can be aerosolized by a nebulizer. A metered-dose aerosol preparation containing 1 mg/drug per activation is being investigated in other parts of the world and appears to be equally as effective as the powdered and nebulized forms of cromolyn. Recent controlled studies reveal that cromolyn sodium and theophylline have equal efficacy in the first-line management of asthma, but troublesome cardiovascular and psychoneurologic side effects are often observed after theophylline therapy. If used properly, cromolyn sodium is a valuable agent in the pharmacologic treatment of asthma.

Aerosols↗
PubMed1985

Prospective evaluation of chymopapain sensitivity in patients undergoing chemonucleolysis.

Immediate anaphylactic reactions after intradiscal chymopapain (CP) injection may occur in 1% of patients undergoing chemonucleolysis (CN). Skin prick testing to CP (10 mg/ml), a prescreening history, and CP serum-specific IgE determinations by the RAST method were performed in order to identify patients presensitized to CP before CN. Follow-up repeat CP skin testing and serum-specific IgE were done 2 to 6 weeks after CN to detect CP IgE-mediated sensitization resulting from the injection. Three of 84 patients who exhibited positive skin tests to CP before CN did not receive CP injections. Only one of the three patients (33%) was detected with elevated CP serum-specific IgE before CN. No immediate severe anaphylactic reactions caused by CP injection were encountered in the remaining 81 patients with negative CP skin tests and RASTs before CN. Eight (10%) nonlife-threatening immediate and late reactions were associated with conversion from negative skin tests and RASTs before CN to positive skin tests or RASTs after CN. Overall, 19 of 52 (37%) patients who returned for follow-up testing developed cutaneous sensitization to CP after CN. Despite the fact that RAST values after CN in these patients were significantly higher (p less than 0.002) than those with negative skin tests after CN, the sensitivity of the RAST was only 72% for identifying patients who developed positive CP skin tests after CN. This study demonstrated that CP skin testing is essential for prescreening patients because it was more sensitive than RAST for identification of CP sensitivity both before and after CN. Late allergic reactions and cutaneous sensitization to CP were common sequelae of CN.

Anaphylaxis↗
PubMed1985

The diversity of reaginic immune responses to platinum and palladium metallic salts.

As part of a National Institute for Occupational Safety and Health health hazards evaluation, workers employed in a precious metal refinery exposed to platinum (Pt), palladium (Pd), and other group VIII metallic salts were evaluated for direct skin test sensitivity to Pt. Current (107) and former (30) workers who quit or were discharged because of Pt-related health problems were prick tested with ammonium hexachloroplatinate ([NH4]2 PtCl6). Of the 107 currently exposed workers, 15 (14%) exhibited positive skin tests, as indexed by immediate reactivity at a dose of 10(-3) gm/ml or less. Eight (27%) of the 30 former workers no longer exposed to Pt also demonstrated positive Pt skin tests. Sera obtained from the workers were assessed for transferable antibodies to Pt and Pd salts by monkey passive cutaneous anaphylaxis. In addition, Pt-specific antibodies were evaluated by RAST. Results of these studies suggested that short- and long-term passive cutaneous anaphylaxis immune responses occur after exposure to both Pt and Pd compounds. Results of RAST analysis for Pt-specific antibodies indicated that significantly higher (p less than 0.001) levels were present in the sera of skin test-positive workers as compared to control sera from Pt-exposed, skin test-negative workers or nonexposed control subjects. Evidence was also obtained that Pt or Pt-protein adducts present in the sera of exposed workers may compete for IgE-binding sites in the RAST assay. The specificity of the Pt-specific RAST system was proved by inhibition experiments.

Animals↗
PubMed1985

Tumor growth in rats: conditioned suppression of food intake and preference.

Rats with experimental tumors developed strong aversions to a novel diet they consumed during tumor growth. Aversions were not evident when the food available during tumor growth was familiar laboratory chow. The impact of learned food aversions on tumor anorexia was evidenced by more severe and long-lasting hypophagia in tumor-bearing animals maintained on a novel diet than in those maintained on laboratory chow. Thus, when a diet is a salient target for the development of learned aversions, the aversions that develop to it can make substantial contributions to the overall syndrome of tumor anorexia. In addition, frequent changes of the diet offered to tumor-bearing rats was associated with milder anorexia than that produced by maintaining tumor-bearing rats on a constant diet. Apparently, the prevention of learned food aversions, or the repeated replacement of aversive foods, can minimize the impact of learned food aversions and attenuate anorexia in tumor-bearing animals.

Animals↗
PubMed1985

Learned food aversions in the progression of cancer and its treatment.

The studies included in this chapter examine the learned food aversions that develop as a result of cancer and cancer treatment. Clinical studies have shown that cancer patients can develop learned aversions to a novel ice cream flavor when it is consumed before drug treatments that produce nausea and vomiting. They also provided evidence that patients can acquire aversions to food in their usual diets when these foods are eaten before similar drug treatments. Observations in the clinic, supported by complementary studies with animal models, suggest that learned aversions are more likely to arise to protein foods than to other nutrient sources and that the presentation of a novel food in association with drug treatments may act as a "scapegoat" in blocking the development of aversions to foods in the normal diet. Laboratory studies using transplantable tumors in rats have shown that tumor growth can be associated with the development of strong aversions to the available diet. These aversions are specific to the diet eaten during tumor growth and they appear to play a causal role in the development of tumor-induced anorexia. The food aversions apparent in animals with certain experimental tumors point to physiological consequences of tumor growth that act as unconditioned stimuli in taste aversion conditioning. The identification of these changes and development of methods for correcting them are the current goals of our research in this area.

Animals↗
PubMed1985

Area postrema mediates tumor effects on food intake, body weight, and learned aversions.

Growth of a Leydig cell [LTW (m)] tumor in rats is associated with the development of significant hypophagia and severe aversions to the available diet. Lesions of the area postrema and nearby caudal medial area of the solitary tract were found to block or greatly attenuate the anorexia and food aversions that typically accompany the growth of this tumor. Thus these tumor-induced symptoms may be associated with the detection of blood-borne chemicals by cells located in or near the area postrema.

Aging↗
PubMed1985

Absence of sodium chloride preference in Fischer-344 rats.

Preference for NaCl solutions as a function of concentration was examined in three inbred strains of rats (Munich-Wistar, Buffalo, and Fischer-344) and outbred Wistar rats. Fischer-344 rats were found to differ markedly from the other strains in that they failed to prefer any concentration of NaCl solution to water. This difference did not appear to be due to an insensitivity to the taste of NaCl since they significantly avoided solutions at concentrations (greater than 0.7%) that were strongly preferred by other rat strains. Differences between Fischer-344 and other rat strains also did not appear to be due to a generally anomalous taste system since their intake and preference for prototypes of other basic tastes (sweet, sour, and bitter) were generally similar to those of other strains. Although Fischer-344 rats were somewhat slower than Wistar to excrete a sodium load, it is unlikely that this difference can provide a direct explanation of the aversion of Fischer-344 rats for NaCl.

Animals↗
PubMed1985

Cromolyn sodium.

Cromolyn sodium is a valuable agent in the pharmacologic management of asthma. In addition to its established effects of inhibiting mediator release, it now appears that it is a useful drug for diminishing the effects of reflex-mediated asthma, nonspecific bronchial hyperreactivity, and diurnal swings of bronchial lability. Because of these unique prophylactic properties, the availability of a nebulized aqueous solution delivery system and recent clinical reports showing that its efficacy is comparable to theophylline, cromolyn sodium should be reconsidered as a first-line antiasthmatic drug in the United States.

Administration, Intranasal↗
PubMed1985

Reactive airways dysfunction syndrome (RADS). Persistent asthma syndrome after high level irritant exposures.

Ten individuals developed an asthma-like illness after a single exposure to high levels of an irritating vapor, fume, or smoke. In most instances, the high level exposure was the result of an accident occurring in the workplace or a situation where there was poor ventilation and limited air exchange in the area. In all cases, symptoms developed within a few hours and often minutes after exposure. We have designated the illness as reactive airway dysfunction syndrome (RADS) because a consistent physiologic accompaniment was airways hyperreactivity. When tested, all subjects showed positive methacholine challenge tests. No documented preexisting respiratory illness was identified nor did subjects relate past respiratory complaints. In two subjects, atopy was documented, but in all others, no evidence of allergy was identified. In the majority of the cases, there was persistence of respiratory symptoms and continuation of airways hyperreactivity for more than one year and often several years after the incident. The incriminated etiologic agent varied, but all shared a common characteristic of being irritant in nature. In two cases, bronchial biopsy specimens were available, and an airways inflammatory response was noted. This investigation suggests acute high level, uncontrolled irritant exposures may cause an asthma-like syndrome in some individuals which is different from typical occupational asthma. It can lead to long-term sequelae and chronic airways disease. Nonimmunologic mechanisms seem operative in the pathogenesis of this syndrome.

Adult↗
PubMed1985

Studies on Alternaria allergens. V. Comparative biochemical and immunological studies of three isolates of Alternaria tenuis cultured on synthetic media.

Six extracts were prepared from Alternaria tenuis isolated ATCC 6663, ATCC 16086 and DAOM (Agriculture Canada) 183905 grown separately on two synthetic media, revised tobacco and Czapek's, and their biochemical and immunological properties were examined. High-performance liquid chromatography revealed considerable variations in UV absorbance and carbohydrate profiles among extracts from the different isolates. These differences were less marked among samples of the same isolate cultured on different media. Enzyme screening showed that all extracts contained large amounts of phosphatases and glucosidases and moderate quantities of esterases. Only the alpha-galactosidase activity showed any correlation with allergenic activity. No significant variation was observed in isoelectric focusing patterns. Extensive antigenic cross-reactivity even between the different isolates was found in precipitin studies. In mouse IgE passive cutaneous anaphylaxis tests, all extracts gave reactions of similar intensity. In direct RAST and RAST inhibition assays, ATCC 16086 grown on revised tobacco medium was found to be the most potent and approached the activity of an extract from a commercial material (B-I). DAOM 183905 grown on either medium was next in potency while ATCC 6663 samples were the least potent. The results indicate that it is possible to obtain extracts of high allergenic potency for standardization purposes from growth of selected A. tenuis isolates on a chemically defined medium.

Allergens↗
PubMed1985

Reactive airways dysfunction syndrome. Case reports of persistent airways hyperreactivity following high-level irritant exposures.

Two individuals developed an asthma-like illness after a single exposure to high levels of an irritating aerosol, vapor, fume, or smoke. Symptoms developed within a few hours. A consistent physiologic accompaniment was airways hyperreactivity, with the two subjects showing positive methacholine challenge tests. No documented preexisting respiratory illness was identified, nor did subjects relate past respiratory complaints. Respiratory symptoms and airways hyperreactivity persisted for at least four years after the incident. The incriminated etiologic agents all shared a common characteristic of being irritant in nature. Bronchial biopsy specimens showed an airways inflammatory response. This report suggests that acute high-level irritant exposures may produce an asthma-like syndrome in some individuals, with long-term sequelae and chronic airways disease. Nonimmunologic mechanisms seems to be operative in the pathogenesis of this syndrome.

Adult↗
PubMed1984

Successful long-term immunotherapy for human seminal plasma anaphylaxis.

Anaphylactic sensitivity to her husband's seminal fluid occurred in a 46-year-old woman six weeks after a hysterectomy. Her husband was azoospermic as a result of an elective vasectomy. A pooled sample of his seminal fluid was used for skin and laboratory tests. Fractionating (Sephadex G100) chromatography was also performed on his seminal fluid. The patient showed positive intracutaneous skin tests to his unfractionated seminal plasma and a Sephadex G100 fraction designated No. 3. This fraction was also passively transferable to a nonallergic volunteer and it stimulated histamine release from the patient's leukocytes. The dose-response effects of this fraction compared with unfractionated seminal plasma in these assays showed greater bioactivity. After informed consent was obtained, the patient was immunized to fraction 3 in a classic desensitization protocol. Two weeks after the final dose of immunotherapy, intercourse was performed without condoms in a medical facility and under the supervision of a physician. No adverse symptoms were experienced by the patient on this occasion. Regular and frequent sexual activity is required to maintain her tolerant state.

Anaphylaxis↗