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Based upon previous clinical data suggesting that the potential therapeutic benefits of hyperimmune specific IgG could involve neutralization and regulatory effects, this cooperative study evaluated the efficacy and safety of combined active and passive immunotherapy in previously untreated ragweed-sensitive patients. Symptom scores and indices of patients receiving ragweed-specific globulin plus rush desensitization with ragweed extract were significantly reduced (p less than 0.05), as compared to control patients treated with albumin and active rush immunotherapy. Postseasonal RAST levels were either unchanged or decreased in 28 of 33 patients receiving hyperimmune gamma-globulin. These data were significantly different from those in albumin-treated patients (p less than 0.002). The usual anamnestic rise of ragweed-specific IgE was modified without affecting the ongoing synthesis of ragweed specific IgG. Mild constitutional symptoms were observed in patients undergoing rush immunization, but the overall procedure was relatively well tolerated and no serious or treatment-refractory constitutional problems were encountered. This clinical trial suggests that ragweed immune gamma-globulin might be a useful therapeutic adjunct when administered in close association with optimal amounts of allergen.

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.

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.

Dermatophagoides spp house dust mites were found to be prevalent in geriatric nursing homes in southwestern Ohio. Mite density was lower in nursing homes than in private homes in comparable dust-sampling areas and at similar times of the year. Generally, fewer mattresses, floors, and articles of furniture were mite positive in nursing homes by comparison to private homes. Lower institutional mite levels were attributed to frequent linen and mattress cover changes and rigorous cleaning practices, coupled with the lack of a favorable mite environment provided by high ambient temperatures, low relative humidity, tiled or vinyl-covered floors and furniture, and covered or encased mattresses.

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.

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.

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.

Mealworms are larvae of the Tenibrio molitor (Tm) beetle and are widely used as fishing bait. Four of five bait handlers in a warehouse who were exposed to particulates of Tm exoskeletons reported immediate-onset asthma, rhinitis, or contact urticaria while unwrapping and packaging the larvae. Positive cutaneous prick tests to Tm extract were detected in all four symptomatic workers. Specific IgE against Tm antigens of 14.6% and 22.5% were found by the RAST method in the two workers with Tm-induced asthma. Specificity of Tm-IgE binding was confirmed by RAST inhibition of 73%, 58%, and 37% by 2 X 10(-1), 2 X 10(-2) and 2 X 10(-3) dilutions of Tm antigen. No significant inhibition of Tm-IgE binding by mite and cockroach antigen or by extracts of three other larval species of the Diptera and Lepidoptera orders, to which the workers were also exposed, was detected. Bronchial provocation challenge with Tm antigen performed in the two workers with asthma exhibited an immediate fall in FEV1 of more than 20% at provocation-dose dilutions of 2 X 10(-3) and 2 X 10(-5), respectively. In the latter worker, pretreatment with disodium cromoglycate inhibited the bronchial response to 2 X 10(-4) dilution of Tm antigen. This study demonstrates that inhaled particulates from Tm exoskeletons are potent sensitizers and elicit IgE-mediated occupational asthma. Allergenic cross-reactivity between orders of insects was not observed. This occupational setting serves as a model for the prospective study of insect allergy.

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.

Earlier, it was reported that most of the allergenic activity of Alternaria tenuis seemed to reside in the last Sephadex G-100 fraction (G3, molecular weight approximately 20,000). These conclusions were based on results obtained by the in vitro techniques of radioallergosorbent tests (RAST) and RAST inhibition. In the present studies, the allergenic activity of A. tenuis fractions was measured in vivo. It was found that fraction G3 was neither capable of inducing reaginic (IgE) antibodies in rats nor eliciting a skin reaction in rats sensitized with reagins against A. tenuis non-dialyzable fraction (MW greater than 12,000). On the other hand, subfractions G2D3 and G2D4 obtained from the middle fraction of G-100 (G2, MW approximately 30,000-40,000) followed by ion-exchange chromatography on DEAE-cellulose, showed the greatest allergenic activity in vivo, giving high titered reaginic antibodies in rats. When compared by RAST inhibition, the activities of fractions G2D3 and G2D4 were slightly lower than that of G3. Fraction G3 was immunogenic in rabbits. In immunodiffusion tests, G2D3, G2D4 and G3 appeared to be identical and they were cross-inhibiting in RAST inhibition tests. It was concluded that the sizes and multivalent properties of G2 and G3 antigens exerted a strong influence on their allergenic activities in rats (IgE antibody production) but this factor was of little importance for their antigenic activity in rabbits (precipitin antibody production) and their behaviour in the in vitro tests.

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.

Abnormalities of second-wave platelet aggregation were demonstrated in 17 of 33 asthmatic patients in whom drug and diet intake were controlled in the hospital. Mean abnormal responses were significantly greater after epinephrine- (p less than 0.001), adenosine diphosphate-(less than 0.001), collagen- (p = 0.01), and thrombin- (p less than 0.001) induced platelet aggregation in patients with immunologically mediated asthma and serum IgE levels greater than 250 U/ml as compared to patients without immunologic factors and/or normal controls. Mean pollen-specific radioallergosorbent (RAST) binding was also significantly higher in patients with abnormal aggregation as compared to normal platelet responders (p = 0.02). Release of serotonin generally reflected abnormal aggregation patterns in asthmatic patients. Platelet factor 4 release was significantly decreased in the same groups of patients. These results suggest that the allergic state may affect platelet membrane responsiveness to multiple aggregating agents.

Leukocyte migration inhibitory factor assay was employed as an in vitro diagnostic aid in nickel dermatitis, the second most common contact dermatitis in North America. 15 patch test-positive and 5 patch test-negative patients, all giving a past history suggestive of nickel dermatitis, were investigated. Significant inhibition of leukocyte migration in both groups of patients was obtained only with nickel sulfate-albumin conjugate and not with unconjugated nickel sulfate. Specificity of this system was tested by utilizing an unrelated metallic albumin complex, and no inhibition was found. When patch testing is equivocal or contraindicated, this in vitro technique may be a practical alternative.

Extracts of Alternaria tenuis and Alternaria solani were separated into dialyzable (molecular weight less than 10,000) and non-dialyzable forms. The latter was further fractionated by gel filtration through Sephadex G-100 followed by ion-exchange chromatography on DEAE-cellulose. The dialyzable material was fractionated by gel filtration through Sephadex G-50. The allergenic activities of the fractions obtained from the A. tenuis extract was measured in vitro by the radioallergosorbent test assay and the allergenic potency was measured by radioallergosorbent test inhibition assay. Allergenic activity was detected in most of the non-dialyzable fractions, the majority of the activity being in the last G-100 fraction (MW approximately 20,000) which was predominantly protein in nature. The same component may be responsible for the activity found in the dialyzate and its first G-50 fraction since the immunodiffusion studies indicated that the last G-100 fraction has antigenic components in common with those of the first G-50 fraction. In addition, cross-reactions between A. tenuis and A. solani extracts show that the two species share common antigenic determinants.

A worker with occupational asthma due to toluene diisocyanate (TDI) was studied. Detailed immunologic studies, including those for p-tolyl isocyanate IgE antibodies and the presence of leukocyte inhibition factor for isocyanate antigen, were negative. Clinically, the subject noted more pronounced symptoms beginning on Monday morning, followed by weekend off work, and lessening of her symptoms over the working week. Methacholine challenges were negative when performed on three separate occasions, including the time when maximum symptoms were present, and again six months later, before and after bronchial challenge testing. A dose-related response to TDI was observed on bronchial provocation testing using nonirritating concentrations of TDI of 0.0165 and 0.030 ppm. This case provides evidence that the response of the airway to TDI may not always be accompanied by hyperreactivity to methacholine. Screening programs utilizing methacholine challenges may not always identify sensitized workers, since a negative methacholine challenge test does not exclude TDI sensitization.

Diminished platelet aggregation responses to one or more aggregating agents were found in 25 of 32 patients with nasal allergy studied at the peak of the allergy season. Abnormal in-season platelet aggregation induced by epinephrine and collagen was significantly improved when repeated out-of-season, while incomplete platelet aggregation induced by adenosine diphosphate (ADP) and thrombin was unchanged. Recombination of an in-season serum factor with autologous, out-of-season normally aggregating platelets caused market inhibition of platelet aggregation. Mean bleeding times of 20 symptomatic patients were also prolonged during the height of the pollination season. These data suggest that the allergic diathesis is a model for the study of cyclic, nondrug induction of platelet dysfunction.

We assessed the effect of prednisone pretreatment (50 mg/day for three days) on the development of the early increase in histamine reactivity that occurs soon after resolution of the immediate response in allergic humans. Four allergic subjects who were known to develop only isolated immediate responses upon Kentucky bluegrass inhalation, as well as four mild allergic asthmatic subjects known to develop typical dual phase responses, were evaluated. All testing was done more than nine weeks after the grass pollen season had ended. Allergen inhalation produced an immediate response in all subjects. However, upon resolution of the immediate response to allergen in these pretreated subjects, the PC200His in all dual responding asthmatics and in three of the four isolated immediate responders had substantially increased above baseline values. We conclude that prednisone pretreatment leads to histaminic hyporeactivity soon after resolution of the immediate allergic response in both dual responding asthmatics and isolated immediate responders. It would seem that this prednisone effect is independent of its potential influence on the influx of inflammatory cells into diseased airways.

This is a case report of a patient who developed IgE-mediated sensitization and subsequently ocular angioedema and conjunctivitis from papain contained in a commercial contact lens cleansing solution. Serum-specific IgE and positive cutaneous prick tests to papain and chymopapain were detected. When the lens solution containing papain was stopped, there was resolution of her allergic symptoms. Recognition of this route of papain-induced sensitization may be important in those patients undergoing chemonucleolysis with chymopapain who may be at greater risk to develop a systemic allergic reaction after injection of this enzyme.

The radioallergosorbent test was compared with currently accepted allergy diagnostic techniques in ragweed-sensitive and unselected patients. The radioallergosorbent test was positive in 28 of 30 patients with proved histories, positive scratch tests, and positive nasal provation tests to ragweed. The radioallergosorbent test was also positive in 69 per cent of 40 clinically sensitive patients whose diagnoses were corroborated by scratch tests alone. In unselected patients evaluated by intracutaneous testing with short ragweed extract, 10 minus 3 g per ml, the incidence of positive radioallergosorbent test scores was reduced to 43 per cent. No false positive results were encountered in these studies. A good relationship was observed between radioallergosorbent test scores and the maximal tolerable dose of ragweed administered during a course of "rush" immunotherapy in clinically allergic patients. These results suggest that the radioallergosorbent test has several unique advantages in assessing clinical sensitivity to ragweed.

Four groups of four Macaca fascicularis monkeys were administered 10 consecutive weekly subcutaneous injections of 2 mg aluminum hydroxide plus one of the following: 200 micrograms of phthalic anhydride (PA)-monkey serum albumin (PA-MSA, group 1); 200 micrograms of PA dissolved in ethanol-saline (EtOH-sal, group 2); 200 micrograms of MSA (group 3); or EtOH-sal alone (group 4). Direct intracutaneous tests to PA-MSA, PA-EtOH-sal, MSA, and EtOH-sal were applied at biweekly intervals throughout the course of the immunization. Serum-specific IgG to PA-MSA and specific IgE to PA-MSA were determined at 2-week intervals according to the ELISA and RAST methods, respectively. The prevalence of cutaneous sensitivity to PA-MSA in the PA-MSA-immunized group (group 1) was significantly greater after 4 and 6 (p less than 0.01) and 8 and 10 (p less than 0.05) weeks, compared with the other treatment groups. Significantly elevated (p less than 0.01) PA-MSA-specific IgG was also observed in monkeys in group 1 compared with the other treatment groups. No significant changes in PA-MSA RAST or total IgE were observed in any group during the study. These results indicate that parenteral sensitization to PA in subhuman primates requires the presence of new antigenic determinants formed by PA on protein carriers.

In this multicentre, double-blind, randomized, parallel group study, 315 patients with allergic or vasomotor rhinitis were treated on a twice daily dosing schedule with either a 60 mg terfenadine-120 mg pseudoephedrine hydrochloride combination or 120 mg pseudoephedrine hydrochloride (extended release) for 2 weeks. No clinically significant differences between the two groups were noted in body weight, temperature, respiration rate or blood pressure following the treatment period. An increase in mean heart rate of approximately 5 beats/min from entry to the final clinic visit was noted in both treatment groups. No clinically significant changes were noted in either treatment group when pre- and post-treatment electrocardiograms were compared. There were also no clinically significant alterations in laboratory values, which included serum chemistry, haematology and urinalysis, within or between either group. The adverse events profiles for both groups were similar. The most frequent adverse event was insomnia, in 40 (25.3%) patients given the terfenadine-pseudoephedrine combination and in 42 (26.8%) of those given pseudoephedrine. No unusual or unexpected adverse events were reported.

Clinical sensitization to phthalic anhydride occurred in a worker who developed symptoms of rhinorrhea, lacrimination, and wheezing after exposure to this chemical. Positive skin tests, provocative bronchial challenges, and a high serum titer of specific IgE (by the radioallergosorbent test) to phthalic anhydride corroborated his clinical hypersensitivity. Bronchial provocation studies using alcoholic-saline solutions of phthalic anhydride and phthalic anhydride dust resulted in immediate airway obstruction. The successful identification of specific IgE by the radioallergosorbent test demonstrates that this can be a useful in vitro technique for corroborating sensitization to this chemical.

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.

The pulmonary and dermal effects of exposure to Na2PtCl6 were investigated in cynomolgus monkeys (Macaca fascicularis) exposed by the nose-only inhalation and percutaneous routes. Separate inhalation exposures were performed in monkeys at 200 micrograms/m3 and 2 mg/m3 (4 hr/day, biweekly for 12 weeks), while another group of monkeys was percutaneously exposed biweekly by an open patch method. After a 2-week refractory period, serial Na2PtCl6 bronchoprovocation challenges and intradermal Na2PtCl6 sensitivity evaluations were performed. Na2PtCl6 bronchoprovocation in naive control monkeys yielded significant impairments in post-challenge pulmonary mechanics and ventilatory function. These results indicate a pharmacologic or irritant-mediated bronchoconstriction mechanism for acute exposure to this compound. When the post-challenge pulmonary function of animals exposed for the 12-week exposure regimen (across treatments) was compared to pulmonary deficits observed in control animals upon challenge, significantly greater pulmonary deficits were seen in animals exposed at the 200 micrograms/m3 concentration. Exposure at this concentration yielded significant changes in post-challenge average pulmonary flow resistance (RL) and forced expiratory volume in 0.5 sec corrected for vital capacity (FEV0.5/FVC) when compared to control monkey responses. Animals exposed by the percutaneous route or at 2 mg/m3 showed no significant post-challenge pulmonary deficits when compared to control animals. Intradermal Na2PtCl6 sensitivity was found not to be exposure related in the conditions of this experiment.

Cephalic phase insulin release (CPIR) was examined in women with anorexia nervosa and in lean, age matched controls. Following an overnight fast, a palatable food was presented to subjects and plasma insulin was measured at baseline and every minute for a 10 minute period following the presentation of the food. Elevation in plasma insulin occurred five minutes after food presentation in the anorexic group only. The finding of a significant CPIR in anorexics but not controls was unexpected and tends to rule out a deficient cephalic insulin response as a contributor to the self-starvation observed in anorexia nervosa.

Subdiaphragmatic vagotomy produces hypophagia and weight loss in normal rats and can reverse the hyperphagia and obesity of rats with ventromedial hypothalamic lesions. Vagotomy surgery can also produce symptoms of nausea and discomfort. Since such symptoms are highly effective as unconditioned stimuli in food aversion conditioning, the present studies examined whether some of the depression in food intake observed in rats with vagotomy could be due to the development of aversions to the foods eaten after their surgery. In the first study, significant aversions developed to the specific novel diet consumed after vagotomy, results indicating that the symptoms associated with vagotomy can serve as effective unconditioned stimuli in the acquisition of learned food aversions. The second study compared vagotomized animals consuming familiar laboratory chow with those consuming a novel diet. In contrast to the novel diets, learned aversions did not develop to the familiar chow, and hypophagia was less persistent and severe. It is concluded that learned food aversions can contribute to the appetite and weight loss exhibited by vagotomized animals. Consideration of the conditions under which these aversions arise after vagotomy surgery may allow for the design of studies so as to minimize the aversions and thereby separate these nonspecific effects from direct regulatory deficits produced by vagotomy.

The natural history of isocyanate-induced asthma is not well documented. We evaluated a patient who developed persistent shortness of breath, wheezing, and cough after a massive exposure to toluene diisocyanate (TDI). Despite no further occupational exposures to isocyanates, he continued to have symptoms of asthma and variable airway obstruction 12 yr later. A methacholine inhalation challenge test was markedly positive, and a bronchial challenge test to TDI produced a dual asthmatic response. This report demonstrates that sensitivity to TDI can persist for many years in the absence of further occupational exposure and suggests that some patients with TDI-induced asthma do not recover from their disease after being removed from isocyanate exposure.

A learned food aversion paradigm was developed to investigate characteristics of aversion learning likely to be involved in nutrient selection. The development of aversions to a relatively familiar, complete food was examined in rats with continuous access to that food. Learned food aversions were observed which were specific to the particular diet present during a sequence of toxic drug injections. In subsequent studies, novel liquids and solids were introduced in association with drug treatment to examine their effectiveness as interference stimuli. Flavored solutions, which have previously been reported to interfere with conditioned taste aversions, had little or no effect on learned aversions to the diet. This lack of interference by novel flavored liquids was coupled with significant conditioned aversions to the novel liquids themselves. Novel flavored solutions were contrasted with novel foods, which were extremely effective as interference stimuli in this paradigm. Possible bases for the observed differences in interference effects of foods and drinks are examined.

Abundance of the house dust mites, Dermatophagoides farinae and D. pteronyssinus, in various sites in the homes of dust-sensitive patients was sequentially monitored at approximately 3 wk intervals for 2 yr, and mite density was correlated with indoor physical and climatic factors. Significantly higher mite levels occurred on the most heavily used fabric-upholstered furniture and carpeted floor areas of the living/family room and bedrooms. Mattresses were not found to be the major foci for mites. No significant positive correlation was noted between mite abundance and frequency or thoroughness of cleaning, amount of dust, and age of furnishings or dwelling. Significantly higher mite levels occurred on carpeted floors than on noncarpeted floors. Successive vacuuming did not significantly reduce mite abundance. Mite density exhibited a seasonal fluctuation, with highest density occurring in the humid summer months and the lowest density during the dryer, late heating season. Live mites were more abundant than dead mites during the period when total abundance was high. In homes inhabited by both species, D. farinae was the dominant species, except in one home that had a significantly higher relative humidity.

Previous work has suggested that aversions to foods are relatively resistant to interference effects. Although these findings have been interpreted as reflecting the potency of foods as targets in aversion conditioning, resistance to interference could more generally characterize intense conditioned aversions. In the present studies with Wistar rats we examined whether interference with food aversion conditioning could be demonstrated by reducing either the drug dose (cyclophosphamide; 20 vs 40 mg/kg) or the number of conditioning trials. In both cases interference was produced; that is, the presence of a second food did interfere with the conditioning of aversions to the first or "target" food. Thus, under conditions which would be expected to produce slower or weaker conditioning, interference with food aversions was facilitated.

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.

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.

Preabsorptive insulin release was examined in bulimic women and in matched controls who diet. A palatable food was presented to subjects after an overnight fast and plasma insulin and glucose were measured at baseline, during presentation of the food and after it had been tasted. Food presentation and consumption were associated with significant elevations in plasma insulin levels prior to elevations in blood glucose, but not prior to actual tasting and consumption of the food. Insulin levels of bulimic and dieting women did not differ significantly at any time. The results indicate that when dietary restraint and body weight are controlled, bulimics do not display abnormal patterns of insulin release in response to foods.

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.

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.

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.

A 29-year-old male welder reported systemic reactions after exposure to chromium. Inhalation challenge testing to 29 micrograms/m3 of sodium chromate aerosol resulted in late appearing systemic urticaria, angioedema, and severe bronchospasm that occurred at the same time as a threefold rise in plasma histamine. A direct leukocyte inhibitory factor test to 5.5 X 10(-6)mol/L Na2CrO4 was positive. Although the mechanism of this reaction is unknown, the positive leukocyte inhibitory factor and the general acceptance of hexavalent chromium as a contact skin sensitizer suggest that cell-mediated mechanisms could be involved.

The crossed antigenicity and allergenicity of the storage mite Tyrophagus putrescentiae (TP) and the house dust mite Dermatophagoides farinae (DF) were characterized by means of crossed immunoelectrophoresis and crossed radioimmunoelectrophoresis. DF extracts exhibited 32 antigens and as many as eight were demonstrated to be allergens. DF feces exhibited 20 antigens and six of these were allergens. Twenty antigens and two allergens were demonstrated for TP. Two antigenic and allergenic determinants were shared by DF and TP, and two determinants were also shared by DF feces and TP feces. TP feces and DF shared two antigenic and allergenic determinants. Our results demonstrated that the two mites and their feces extracts contain multiple antigens and allergens.