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Biomedical subjects

I L Bernstein

Publications and source records attributed to I L Bernstein.

At least 127 records · Page 7Linked to original sources

Pulmonary and immunologic evaluation of foundry workers exposed to methylene diphenyldiisocyanate (MDI).

A cross-sectional evaluation was performed of workers in a steel foundry in which methylene diphenyldiisocyanate (MDI) was used as a component of a binder system used to make cores and molds. Preshift and postshift spirometry and clinical evaluations were performed on 26 currently exposed (group I), on six formerly exposed (group II), and on 14 nonexposed workers to MDI (group III). Serum samples were assayed for total antibody binding, specific IgG by ELISA, and specific IgE by the RAST method to MDI-human serum albumin (HSA). Symptoms compatible with occupational asthma were elicited from seven (27%) of 26 group I workers and from three of six group II workers. No symptoms were reported by group III workers. Intrashift change in FEV1 (a mean decrease of 0.049 L) in group I workers was significantly decreased compared to that in unexposed group III workers (a mean increase of 65 ml; p = 0.043). Specific IgG and total antibody responses to MDI-HSA were detected only in workers with current or former exposure to MDI. Only one worker was identified with IgE-mediated occupational asthma exhibiting a positive prick test and elevated RAST to MDI-HSA of 25.5% bound. In this occupational setting, polyclonal immune responses to MDI-HSA and clinical sensitization to MDI were demonstrated to occur.

Adult↗

An open study of auranofin in the treatment of steroid-dependent asthma.

To determine the efficacy of oral gold in asthma, 20 patients with steroid-dependent asthma received auranofin at a dose of 3 mg by mouth, twice daily, in a 24-week open clinical trial. Prospective evaluation of bronchial responsiveness to methacholine was determined before and 8 and 16 weeks after initiation of auranofin therapy. Serial spirometry (FEV1 and FVC), lung volumes, and diffusing capacities (single breath carbon monoxide diffusing capacity of the lungs) were measured before and at 10 and 20 weeks after treatment. All subjects were required to record concomitant medications, symptom scores, and morning and evening peak expiratory flow rates. In vitro immunologic studies performed before and after 8 and 20 weeks of auranofin therapy included leukocyte histamine release in response to antihuman IgE, lymphocyte blast transformation in response to concanavalin A and phytohemagglutinin, and leukocyte inhibitory factor activity in response to Candida albicans and tetanus toxoid antigens. In 18 patients evaluated, there were no significant differences between baseline and posttreatment spirometry, single breath carbon monoxide diffusing capacity of the lungs, and lung volumes. At week 16 of treatment, the steroid cumulative dose or the total prednisone dose administered from 7 days before through 10 days after each methacholine test day decreased from a mean of 293 +/- 125 mg at baseline to 192 +/- 115 mg. At week 16, nine of 18 patients (50%) exhibited decreased methacholine responsiveness as defined by a more than one-half log10 increase in the concentration of methacholine causing a 20% decrease in FEV1. A significant correlation (r = 0.60) was observed between the increase in the concentration of methacholine causing a 20% decrease in FEV1 and the decrease in steroid cumulative dose after 16 weeks of treatment. Leukocyte histamine release to anti-IgE exhibited significant reductions from baseline at week 20 to 10(-2) (p less than 0.002) and at 10(-3) (p less than 0.005) dilutions. At week 20, leukocyte inhibitory factor activity in response to Candida increased from baseline at the 0.1 mg per well (p = 0.025) and 1 mg per well (p = 0.05) concentrations; similarly, the responses to tetanus toxoid increased at the 1 mg per well (p less than 0.05) and 0.1 mg per well (p less than 0.01) concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Strain differences in taste reactivity to NaCl.

The taste reactivity test was used to determine whether strain differences in response to NaCl revealed by preference tests were attributable to taste or postoral factors. Taste reactivity data revealed significant differences between sodium-replete Fischer 344 (F-344) and Wistar strains in response to NaCl for both aversive and ingestive oral motor behaviors. Because the taste reactivity test analyzed the immediate response to orally applied chemical stimuli, these data support a strain difference based on taste factors. Taste reactivity data also indicate strain differences in ingestive but not aversive scores to other normally ingested chemical stimuli, water, and two sucrose concentrations. In response to normally avoided quinine, F-344 and Wistar strains did not differ in either ingestive or aversive score. To investigate whether strain differences revealed when rats were tested while sodium replete would persist in the sodium-deficient state, both strains were treated with the diuretic furosemide. Taste reactivity tests revealed that in response to sodium deficiency both F-344 and Wistar strains shift their oral motor response profile to NaCl; strains did not differ in either ingestive or aversive score when sodium deficient. NaCl intake and preference measures also support the fact that both strains demonstrate a sodium appetite. Interpretive limitations based on ceiling and floor effects within taste reactivity and preference data were discussed.

Animals↗

Prevention of chymopapain anaphylaxis by screening chemonucleolysis candidates with cutaneous chymopapain testing.

With chymopapain at a concentration of 10 mg/ml, the authors skin tested 540 chemonucleolysis candidates; six were positive, and 534 were negative. None of the positive patients received therapeutic injections of chymopapain. There were no instances of unequivocal anaphylaxis to chymopapain in the patients with negative skin tests treated with chymopapain. When this 0% incidence of systemic reactions in skin test negative patients is compared with the historical rate of 1%, this difference is statistically significant (p less than 0.05). Restriction of chymopapain treatment to patients with negative prick tests can reduce the incidence of systemic reactions.

Anaphylaxis↗

Candy as a scapegoat in the prevention of food aversions in children receiving chemotherapy.

The effectiveness of a method for reducing the incidence of chemotherapy-induced learned food aversions was examined. Candy (coconut or rootbeer Lifesavers) was used as a scapegoat and given between the consumption of a meal and the administration of chemotherapy to determine whether this would lead to a greater willingness to consume items in that meal at a future test. This procedure produced evidence that the scapegoat had a significant protective effect: children were twice as likely to eat some portion of their test meal at the time of assessment if they had received the scapegoat at conditioning than when there was no intervention. Thus, the consumption of strongly flavored candies before chemotherapy appears to be a simple and effective way to reduce the impact of chemotherapy on preference for normal menu items.

Adolescent↗

Salt preference in the preweaning rat.

Salt (NaCl) preference of 5-20-day-old rats was examined using a method which elicits independent ingestive responses. Rats were placed in a warm, moist incubator on toweling which was saturated with water or test solutions. Active mouthing responses were seen which were directed toward the towel soaked with solution and weight gain in a 25-min test was taken as an index of ingestion. At most ages pups preferred hypertonic saline solutions to water and at 10 days of age rats appeared particularly insensitive to the aversiveness of concentrated (4-8%) NaCl solutions. In contrast to the 10-, 15-, and 20-day-old rats, the 5-day-old rats never preferred NaCl solutions to water and avoided them at concentrations which older rats preferred. This pattern of NaCl preference cannot easily be explained in terms of the known increases in sensitivity of the rat's taste system to NaCl stimulation with age. Ingestion of NH4Cl solutions was also examined and at 10 days of age significant preference for concentrated NH4Cl solutions was evident which contrasts markedly with the behavior of older pups and adult rats when presented with NH4Cl solutions. The relationship between the present findings and available electrophysiological data from the chorda tympani and nucleus of the solitary tract are discussed.

Age Factors↗

Tumor-induced diet aversions persist after successful excision of an anorexigenic tumor.

LTW(m) Leydig cell tumors were removed from Wistar Furth rats after the animals had developed anorexia and strong aversions to a novel diet consumed during tumor growth. Previous studies had reported recovery from anorexia within 24-48 hr of tumor excision but had not measured diet preference to find out if food aversions persisted beyond recovery. In the present study, which allowed the rats to choose freely between the aversive diet and a nonaversive diet for several weeks, aversions persisted from four to 25+ days. No signs of anorexia were evident during this testing phase, which followed 10 days of post-operative recuperation in which the rats were restricted to a diet of familiar laboratory chew. These results are consistent with the hypothesis that certain anorexigenic tumors, such as the LTW(m), can substantially affect food selection long after their direct effects on appetite have dissipated.

Animals↗

Cockroach sensitization in laboratory workers.

Six laboratory workers who were exposed to American cockroaches (AC) and German cockroaches (GC) while they were performing immunologic experiments were evaluated for cockroach hypersensitivity. Prick skin testing and RAST were performed with whole body extracts (1:20 wt/vol) of AC, brown-banded (BB), and GC species as well as hemolymph and fecal (F) extracts of AC. Three of six workers reported work-related nasal and ocular symptoms associated with xenografting and bleeding of cockroaches. All three symptomatic workers exhibited cutaneous reactivity to at least one cockroach antigen. Elevated RAST binding was observed in one of the three symptomatic workers. A nasal provocation to AC was positive in the most symptomatic worker at a provocative dose of 3.2 X 10(-3) mg causing a 50% decrease of nasal flow rate from baseline. After pretreatment with nasal cromolyn, the provocative dose causing a 50% decrease from baseline increased to 2.6 X 10(-1) mg. Nasal provocation with the same concentrations of AC were negative in two skin test negative subjects. RAST-inhibition studies demonstrated cross inhibition of the serum-specific IgE binding to AC-hemolymph by AC, GC, and BB whole body extracts. However, specific IgE binding to AC-F was inhibited by AC-F and AC but not by GC or BB whole body extracts, suggesting there was greater specificity of the F allergens. This study demonstrated that cockroach allergens elicit IgE-dependent upper respiratory sensitization in the workplace.

Adult↗

Multicenter study of bitolterol and isoproterenol nebulizer solutions in nonsteroid-using patients.

Bitolterol mesylate, 1.0 mg, or isoproterenol hydrochloride, 1.5 mg, was administered three times daily for 3 months in a double-blind, multicenter study via closed-port, intermittent-flow, compressor-driven nebulizer system (CPIF) to 182 nonsteroid-using patients with asthma. Mean baseline FEV1 was approximately 60% of predicted normal for both groups. Pulmonary function tests and vital signs were measured before and for up to 8 hours after treatments on test days 1, 30, 60, and 90. Mean maximum increases in FEV1 were 51%, 54%, 52%, and 55% for bitolterol versus 48%, 46%, 50%, and 43% for isoproterenol on these monthly test days. The mean FEV1 response remained greater than 15% over zero time (baseline) for greater than or equal to 8 hours after medication with bitolterol on each of four monthly pulmonary function test days and 2 1/2 to 5 hours for isoproterenol. Median durations of bronchodilator activity for bitolterol were 7.3, 6.5, 6.5, and 6.0 hours versus 4.0, 1.7, 3.7, and 1.9 hours for isoproterenol on the monthly test days. On these test days, 37% to 49% of the patients treated with bitolterol had a duration of action of at least 8 hours compared with 16% to 29% after isoproterenol treatment. The onset of activity was within 5 minutes for both drugs. Bitolterol provided superior bronchodilator activity with fewer adverse effects compared with isoproterenol, and there was no evidence for drug tolerance during this 3-month study.

Adult↗

Comparison of the bronchodilator effects of nebulized bitolterol mesylate and isoproterenol hydrochloride in steroid-dependent asthma.

This study of 183 ambulatory patients with steroid-dependent asthma was conducted to evaluate the efficacy and safety of nebulized bitolterol mesylate solution (0.2%) compared to isoproterenol hydrochloride solution (0.3%). A double-blind, randomized, parallel-group, repetitive-dose design was followed at nine centers for 3 months. Patients received either 1.0 mg of bitolterol or 1.5 mg of isoproterenol three times a day with a closed, intermittent-flow nebulization system. Pulmonary function was evaluated on four 8-hour office visits at approximately 30-day intervals. Efficacy was based on a 15% increase in FEV1 over baseline. Both medications resulted in bronchodilatation within 5 minutes, whereas nebulized bitolterol was statistically superior (p less than 0.05) to nebulized isoproterenol in terms of duration of action and area under the curve. The mean FEV1 response to bitolterol therapy remained greater than 15% over baseline for 5 to 8 hours on the four test days compared to 2 to 4.75 hours for isoproterenol therapy. Both medications were well tolerated. Adverse reactions were transient, and most were mild to moderate. Tremor was the most frequent side effect occurring in approximately 30% of the patients in both groups. There were no clinically significant laboratory changes or electrocardiographic findings. Nebulized bitolterol mesylate was found to be a safe and effective bronchodilator in steroid-dependent patients with asthma.

Adult↗

Investigations of culture medium-free house dust mites. III. Antigens and allergens of body and fecal extract of Dermatophagoides farinae.

Crossed immunoelectrophoresis (CIE) and crossed radioimmunoelectrophoresis (CRIE) were used to characterize antigens (Ags) and allergens derived from Dermatophagoides farinae (DF) culture media-free mite body and mite fecal matter extracts. CIE of DF body and DF feces extracts revealed the presence of 35 and 20 Ags, respectively. CRIE experiments demonstrated IgE binding by 14 and seven DF body and DF feces Ags, respectively, when CIE gels were incubated with reference sera from clinically mite-sensitive patients. Binding of specific IgE to the various Ags in the two extracts varied significantly both in frequency and in strength from patient to patient and within the same patient's serum. Sera from some patients demonstrated IgE binding predilection for specific DF body Ags, whereas other sera exhibited greater binding preference for DF feces Ags. Homologous, heterologous, and intermediate gel CIE and CRIE clearly demonstrated that DF bodies and DF feces share some common Ags or epitopes, but the two different extracts also were quantitatively different. Some Ags and allergens originate from mite body material and are not present in mite feces. These results indicate that only extracts containing high concentrations of both body and fecal allergens should be used in clinical testing and therapy.

Allergens↗

Investigations of culture medium-free house dust mites. IV. Cross antigenicity and allergenicity between the house dust mites, Dermatophagoides farinae and D. pteronyssinus.

Heterologous crossed immunoelectrophoresis (CIE) analysis demonstrated that Dermatophagoides pteronyssinus body and D. farinae body extracts contained up to 21 cross-reacting antigens (Ags). Incubation of CIE gels with two mite-sensitive individual sera and a serum pool of mite-sensitive patients indicated that up to nine cross-reacting Ags bound mite-specific IgE on crossed radioimmunoelectrophoresis and were common allergens. Likewise, heterologous CIE analysis of D. pteronyssinus feces and D. farinae feces extracts demonstrated approximately 13 cross-reacting Ags. Up to eight of these cross-reacting fecal Ags bound mite feces-specific human IgE. Additional cross antigenicity and allergenicity was evident between body extract of one species and feces extract of the other species. The amount of specific IgE binding to cross-reacting Ags in interspecific extracts varied both between and within individual sera. Different cross-reacting Ags contained potent allergens, and these varied from patient to patient. Also of major significance was the fact that body and fecal extracts of each species contained Ags and allergens that were unique and species specific.

Allergens↗

Flavor, not postingestive, cues contribute to the salience of proteins as targets in aversion conditioning.

Proteins have proven to be more salient targets for aversion conditioning than carbohydrates. The present studies examined the contribution of flavor and postingestive factors to the salience of proteins as targets in aversion conditioning in the rat. Two methods for separating flavor and postingestive cues were used, sham feeding and intragastric gavage. Both methods agreed in indicating that postingestive consequences of protein consumption were neither necessary nor sufficient for the development of more severe protein than carbohydrate aversions. Differences in palatability did not appear likely to be the basis of protein salience because when acceptability or palatability of the nutrient solutions was matched, aversions to protein continued to be more severe. Differences in odor intensity of nutrient solutions may be important because when an odorant was added to a carbohydrate solution, the severity of aversions to protein and carbohydrate was no longer different. These results indicate that the presence of both taste and odor cues in target nutrients may contribute importantly to their salience.

Animals↗