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Biomedical subjects

I L Bernstein

Publications and source records attributed to I L Bernstein.

At least 145 records · Page 8Linked to original sources

Attenuated sodium appetite in response to sodium deficiency in Fischer-344 rats.

Fischer-344 (F-344) rats avoid NaCl solutions which are preferred by other strains. The present studies examined Na appetite induced by two methods: maintenance on a Na-deficient diet, and Na depletion by injection of furosemide. In comparison with outbred Wistar rats, F-344 rats showed no evidence of Na appetite induced by Na-deficient diet after the first 15 min (study 1) and demonstrated attenuated Na appetite in response to the natriuretic effects of furosemide (study 2). Since Na loss by Wistar and F-344 rats was similar, it is likely that this reduced Na appetite was due to hedonic differences between the strains rather than to differential renal response to furosemide or Na-deficient diet.

Animals↗

Amiloride-sensitive sodium channels and expression of sodium appetite in rats.

Lingual application of amiloride hydrochloride blocks a sodium transport system in the mammalian gustatory system. Effects of exposure to amiloride on subsequent licking for 3% NaCl by rats were found to differ as a function of the animal's sodium balance. Licking for 3% NaCl was significantly increased in sodium-replete rats and significantly decreased in sodium-deplete rats by amiloride pretreatment. In fact, expression of sodium appetite was virtually eliminated by pretreatment with amiloride. This suggests that the recognition of sodium solutions in animals with a sodium deficit is dependent on amiloride-sensitive sodium transport at the taste bud.

Amiloride↗

Bronchial reactivity increases soon after the immediate response in dual-responding asthmatic subjects.

To determine whether bronchial reactivity is augmented soon after an allergen-induced immediate asthmatic response, we compared reactivity to histamine before and immediately upon resolution of the immediate asthmatic response in seven subjects with mild asthma who were known to develop dual asthmatic responses after inhalation of Kentucky bluegrass allergen. Using a body plethysmograph and quiet breathing technique, specific airway resistance (SRaw) and reactivity to aerosol histamine were assessed on two days prior to allergenic challenge. The dose of histamine that doubled SRaw (PC200His) was determined by interpolation from histamine dose-response curves. On the day of allergenic challenge, each subject inhaled a concentration that was sufficient to induce a dual asthmatic response. Upon resolution of the immediate asthmatic response (45 to 105 minutes) after allergen, the PC200His in all cases had decreased more than 50 percent of its original value (PC200His for the group was 0.29 +/- 1.42 mg/ml [mean +/- SE], compared to 0.84 +/- 1.23 mg/ml initially). Seven or more days after the allergen, each subject had a PC200His comparable to original values. Our data indicate that airway reactivity in dual-responding asthmatic subjects markedly increases soon after the immediate asthmatic response and much before the late asthmatic response manifests clinically. Whether this early increase in bronchial reactivity is a putative requirement for, or shares common characteristics with the late asthmatic response requires further study.

Adult↗

Occupational asthma caused by himic anhydride.

Acid anhydride compounds are reactive chemicals that have been previously associated with immunoglobulin E (IgE) mediated occupational asthma. Twenty workers with exposure to himic anhydride powder used for the manufacture of a synthetic flame retardant were questioned about respiratory symptoms. The study was initiated after one individual from the plant developed asthma. A test for serum-specific IgE to human serum albumin conjugates of himic anhydride, phthalic anhydride, hexahydrophthalic anhydride and trimellitic anhydride was performed for seven workers with respiratory symptoms associated with himic anhydride exposure. Three of the seven symptomatic workers who reported wheezing at work exhibited elevated specific IgE to two or more acid anhydride-human serum albumin conjugates. Radioallergosorbent inhibition studies performed with sera containing high levels of himic anhydride-human serum albumin specific IgE from a symptomatic worker demonstrated cross-allergenicity between himic anhydride-human serum albumin and hexahydrophthalic anhydride-human serum albumin allergenic determinants. This study demonstrated that himic anhydride can elicit IgE-mediated sensitization in the workplace.

Adult↗

Studies on alternaria allergens. VI. Stability of the allergen components of Alternaria tenuis extracts under a variety of storage conditions.

The allergenic potencies of samples of two commercial Alternaria tenuis extracts stored under various conditions were compared at 3 months intervals over a period of 1 year. Aliquots of the extracts at 5.12 mg/ml were maintained in: saline; 50% glycerol-saline mixture; 0.4% phenol-saline; 0.4% phenol-saline containing 0.03% human serum albumin, and samples were also kept in lyophilized form. The samples were stored at -20, 4, 24, 37 and 56 degrees C. Their potency was measured by radioallergosorbent inhibition assay and by mouse IgE passive cutaneous anaphylaxis (PCA) tests. The lyophilized extracts fully maintained their activity at all temperatures for 12 months. Aqueous extracts with or without preservatives also maintained their potency if stored at -20, 4 and 24 degrees C, but showed a significant loss of PCA activity at 56 degrees C, after 3 months. A deleterious effect of phenol was observed in one of the extracts stored at -20 degrees C for 3 months, by PCA tests. The use of preservatives to retain potency over a period of 12 months is therefore unnecessary and may be deleterious. The results indicate that, while storage of A. tenuis in a lyophilized form is best at all temperatures, aqueous extracts are also remarkedly stable when stored at -20, 4 and 24 degrees C, over a 12-month period.

Allergens↗

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

The risk of anaphylaxis in candidates for chemonucleolysis for herniated lumbar discs is approximately 1%. An investigation was designed to eliminate or reduce the incidence of chymopapain anaphylaxis. The procedure was to restrict chemonucleolysis to patients who are prick test-negative to chymopapain at a concentration of 10 mg/ml. The authors skin-tested 292 chemonucleolysis candidates; five were positive and 287 were negative. None of the positive patients were injected with chymopapain. There were no instances of unequivocal chymopapain anaphylaxis in the skin test-negative group. This 0% incidence of anaphylaxis in skin test-negative patients was compared with a population estimate of 1%, based on historical data. The resulting value of p = 0.08 value fell short of the conventional level of significance of 0.05. The p value will reach 0.05 when the series of skin test-negative patients without anaphylaxis reaches 360. It is important that this information is readily available to physicians concerned about anaphylactic reactions to chymopapain.

Adult↗

Etiology of anorexia in cancer.

Although the causes of cancer anorexia remain poorly understood, it now seems evident that the symptoms of appetite and weight loss which occur in cancer patients are multiply-determined. Thus, the actual causes of specific clinical problems will depend on the type of disease and treatment involved. This report examines research aimed at understanding the mechanisms responsible for cancer anorexia. Particular emphasis is placed on studies examining the contribution of learned food aversions to the anorexia induced by tumors and antitumor therapy. Evidence from the clinic and the laboratory indicates that learned food aversions occur as a result of the association of foods with symptoms induced by chemotherapy and/or tumor growth. The role these aversions play in the etiology of cancer anorexia is discussed and studies aimed at developing methods for preventing them are described.

Adult↗

Estrogens and the Leydig LTW(m) tumor syndrome: anorexia and diet aversions attenuated by area postrema lesions.

The development of learned aversions to the available diet has been shown to contribute to the anorexia and weight loss which accompany the growth of certain tumors, including the Leydig LTW(m) tumor. Estradiol infusions were found to closely mimic the effects on food intake and food preference seen after Leydig LTW(m) tumor implants. That is, reductions in food intake and the development of severe aversions to a target diet available during hormone infusions were seen. Lesions of the area postrema greatly attenuated these effects of estradiol infusions. Similar lesions have been shown to have parallel effects on the LTW(m) tumor syndrome. These findings strongly implicate the elevations of circulating estrogens which accompany the growth of LTW(m) tumors in generating the symptoms of anorexia and diet aversions.

Animals↗

Influence of taste stimulation during the suckling period on adult taste preference in rats.

Effects of taste deprivation and selective taste exposure during the suckling period on adult preference for flavored solutions was examined. Taste deprivation was achieved by rearing rat pups "artificially," in individual cups with intragastric feeding from Postnatal Days 4 through 17 or 18. In the first study the effects of artificial rearing on male Long-Evans rats were examined. In the second study female Wistar rats were exposed to a single tastant, sucrose, which was introduced on a background of taste deprivation. Results of both studies were similar. No differences in taste sensitivity or preference were detected between animals subjected to taste deprivation or selective taste exposure and their normally reared littermates. These results suggest that suckling stimulation is not necessary for normal taste development and that the taste system of the rat is not particularly susceptible to the influence of early experience. Other interpretations of these results are also discussed.

Animal Population Groups↗

Delayed anaphylactoid reaction in a worker exposed to chromium.

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.

Adult↗

Efficacy and safety of astemizole, a long-acting and nonsedating H1 antagonist for the treatment of chronic idiopathic urticaria.

The efficacy and safety of astemizole (AST), a new long-acting H1 antagonist with minimal sedative or anticholinergic side effects, were studied in an 8-week double-blind trial of 51 patients with chronic idiopathic urticaria. Patients with chronic idiopathic urticaria were randomized to AST-treated (10 mg every day) or placebo-treated groups. Patients were followed at weekly intervals and evaluated for pruritus, erythema, extent of wheals, frequency of urticarial episodes, and total control of urticaria. Only three of 27 AST-treated patients stopped the double-blind phase before 8 weeks because of inadequate response as compared to 11 of 24 placebo-treated subjects (p = 0.027). On the last evaluable visit of the double-blind phase of the study, 85% of the AST-treated patients reported an excellent or good response compared to 30% of the placebo-treated group (p = 0.0001). AST-treated patients also reported significant improvement compared to placebo-treated patients in pruritus (p = 0.0001), erythema (p = 0.0001), and extent of wheals (p = 0.003). Mild sedative effects were observed in only two of 27 patients receiving AST. It was concluded that AST is a potent and safe drug for symptomatic control of chronic idiopathic urticaria.

Adult↗

Toluene diisocyanate-induced airway hyperreactivity and pathology in the guinea pig.

We assessed the nature and progression of airway mucosal disease and histaminic reactivity in English short-haired guinea pigs at 2, 24, 72, 168, and 504 hours after toluene diisocyanate (TDI) exposure (4 hours of 3 ppm of TDI for 5 consecutive days). To also determine whether TDI-specific, IgE-like antibodies developed in TDI-exposed animals, passive cutaneous anaphylaxis testing was done 28 days after TDI. Bronchial reactivity was determined serially by measuring specific airway conductance as a function of increasing doses of aerosolized histamine in six exposed and three control animals studied intact and unanesthetized. The remaining 10 exposed and 10 control guinea pigs were sacrificed in groups of two at each time point to obtain airway tissue for light microscopic examination. We found that airway hyperreactivity to histamine occurred after TDI in all animals tested. It was maximal 2 hours after the 5-day exposure and remitted by 72 hours. In addition, marked airway obstruction occurred after TDI that persisted for at least 168 hours. There were dramatic signs of airway mucosal damage associated with the bronchial hyperreactivity that included substantial decreases in epithelial cilia, mucin content, and mast cells, as well as squamous metaplasia, numerous mitotic figures, and a prominent polymorphonuclear leukocytic infiltrate. Passive cutaneous anaphylaxis tests in exposed animals were negative. Our results suggest that TDI-induced bronchial hyperreactivity may be related to airway mucosal injury and inflammation.

Airway Resistance↗

Prevalence of house dust mites in nursing homes in southwest Ohio.

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.

Aged↗

Persistent airways disease caused by toluene diisocyanate.

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.

Asthma↗

Ozone enhancement of platinum asthma in a primate model.

Three groups of adult male cynomolgus monkeys (Macaca fascicularis) were exposed to either 200 micrograms/m3 ammonium hexachloroplatinate [(NH4)2PtCl6], 200 micrograms (NH4)2PtCl6 concurrently with 1 ppm ozone (O3), or to 1 ppm O3 only. The animals were exposed by inhalation for 6 h per day, 5 days per week for 12 wk. The experimental design included methacholine preexposure and Na2PtCl6 bronchoprovocation challenge evaluations, Na2PtCl6 threshold skin tests, and sera for analyses of antibodies. Two weeks after the 12-wk exposures, these same indices were reevaluated. Baseline pulmonary function was not significantly affected by the exposure regimens; however, the combination of exposure to O3 and (NH4)2PtCl6 significantly reduced the concentration of platinum (Pt) salt and methacholine necessary to increase average pulmonary flow resistance (RL) 200% (EC200 RL). Ozone or Pt exposure alone had no significant effect on these parameters. Platinum and methacholine EC200 RL values were highly correlated for both Pt-exposed groups after exposure. These data indicated that combined O3 and Pt exposure significantly increased specific (Pt) and nonspecific (methacholine) bronchial hyperreactivity more often than did exposure to either O3 or the Pt salt alone. Combined O3 plus Pt exposure also significantly increases the incidence of positive Pt skin tests when compared with the other exposure groups. Similar to the human experience, radioallergosorbent testing (RAST) for Pt-specific antibodies was not as sensitive as direct skin testing in identifying allergic persons.

Animals↗

Chronic asthma due to toluene diisocyanate.

Twelve subjects were studied with inhalation challenge testing to toluene diisocyanate (TDI) because of suspected TDI asthma based on a consistent clinical and occupational history. In seven cases, TDI asthma was documented by a positive inhalation challenge to low levels of TDI. Six of the seven TDI reactors had persistent respiratory symptoms and required daily treatment even though they had been removed from isocyanate exposure for intervals as long as 12 years (mean 4.5 years). These six TDI reactors had either dual (four cases) or late bronchospasm (two cases) to less than 20 ppb TDI, and all had a positive methacholine or cold air challenge prior to study. The one TDI reactor with a negative methacholine challenge had a positive (immediate) bronchospastic response to a TDI challenge performed one week after removal from isocyanate exposure. Five workers had a negative TDI challenge, two of whom had persistent respiratory symptoms and positive methacholine challenges at the time of TDI inhalation testing. We conclude that respiratory symptoms may persist following long-term removal from occupational exposure to TDI and are associated with nonspecific bronchial hyperreactivity. The TDI sensitivity may also persist for a long time even in the absence of any additional occupational exposure. Long-term prospective studies of symptomatic isocyanate workers are needed to fully define the extent of this problem.

Adult↗