Showing papers in "The Journal of Allergy and Clinical Immunology in 1981"
TL;DR: The measurement of nonspecific bronchial responsiveness by inhalation tests with histamine or methacholine and its relationship to the occurrence and severity of asthma is discussed.
Abstract: Bronchial responsiveness is the term used to describe the tendency of the airways to bronchoconstrict to specific stimuli such as allergens and isocyanates, which select a limited population of apparently sensitized subjects, and to nonspecific (nonallergic) stimuli, which affect most asthmatic persons. Specific bronchial responsiveness to allergic stimuli is difficult to quantitate because commonly available allergen extracts are not well standardized for the number and concentration of components. Nonspecific responsiveness can be quantitated by inhalation tests with histamine or methacholine, by exercise, or by isocapnic hyperventilation of cold air, and may be increased in asthma and other conditions such as chronic obstructive bronchitis and cystic fibrosis. In this article we will discuss the measurement of nonspecific bronchial responsiveness by inhalation tests with histamine or methacholine and its relationship to the occurrence and severity of asthma.
691 citations
TL;DR: IgE in some human sera reacted with an antigen present in a large number of unrelated foods: potato, spinach, wheat, buckwheat, peanut, honey and others, which was periodate-sensitive and heat-stable.
Abstract: IgE in some human sera reacted with an antigen present in a large number of unrelated foods: potato, spinach, wheat, buckwheat, peanut, honey and others. The antigen, which was periodate-sensitive and heat-stable, was also found in pollen. Even more surprisingly, these antibodies often reacted in vitro with bee and vespid venom and were sometimes apparently induced by Hymenoptera stings.
393 citations
TL;DR: Both age and sex, in addition to atopic status, relate to IgE level, and males have higher levels than females at any given age, and women over age 75 yr have the lowest levels.
Abstract: The distribution of total serum IgE determined by the paper radioimmunosorbent test (PRIST) is examined in a large random stratified community population. Prior to logarithmic conversion the distribution of this immunoglobulin is not normal, with almost 40% of values below 20 IU/ml. A normal distribution occurs following such conversion, with a geometric mean value of 32.1 IU/ml. Both age and sex, in addition to atopic status, relate to IgE level. In both sexes highest levels occur among 6- to 14-year-olds, and males have higher levels than females at any given age. Women over age 75 yr have the lowest levels (geometric mean 9.2 IU/ml). Subjects with positive skin test results have several times the concentration of IgE as their nonatopic counterparts.
327 citations
TL;DR: The position that testing with PPL, PA, and Pen G is a rapid, safe, and effective method for identifying patients atrisk, or not at risk, for allergic reactions to penicillin is supported.
Abstract: Skin testing for penicillin allergy with penicillin G (Pen G), penicilloic acid (PA), and penicilloyl poly-L-lysine (PPL) was performed on 740 subjects, and the results were assessed from epidemiologic and immunologic perspectives. Approximately 95% of these patients had histories of apparent allergic reactions to beta-lactam antibiotics, and 63% were skin-test positive. The prevalence of positive skin tests was related to the time that had elapsed between clinical reactions and skin testing. Ninety-three percent were skin-test positive 7 to 12 mo after reactions, and 22% were positive 10 yr or more after reactions. Patients under 30 yr of age had a prevalence of positive skin tests 1.7-fold higher than older patients. Testing with PPL, PA, and Pen G detected 76.3%, 55.3%, and 57.1% of the positive patients, respectively. Omission of PPL, PA, or Pen G would have led to a failure to detect 25.6%, 7.2%, and 6.2% of the positive patients, respectively. Subjects with skin tests positive to penicillin often reacted to skin tests with other beta-lactam antibiotics; 73% (41 of 56) reacted to ampicillin and 51% (38 of 74) reacted to cephalothin. No serious allergic reactions were provoked by testing. None of the 83 skin test--negative patients treated with beta-lactam antibiotics immediately after testing experienced acute allergic reactions. Two patients developed mild urticaria beginning 3 and 5 days into therapy. One skin test--negative patient experienced urticaria 3 hr after receiving oral penicillin 6 mo after skin testing. This patient's skin-test status immediately before therapy was unknown. These results support the position that testing with PPL, PA, and Pen G is a rapid, safe, and effective method for identifying patients at risk, or not at risk, for allergic reactions to penicillin.
285 citations
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276 citations
TL;DR: The results emphasize the importance of keeping nebulizer output and pattern of breathing constant when performing inhalation provocation tests if consistent results are to be obtained.
Abstract: Standardization of inhalation tests requires a knowledge of factors that will affect the response We measured the output and particle size of six types of nebulizers used for inhalation tests Output varied considerably between nebulizers of different types (012 to 159 ml/min) and to a lesser extent between nebulizers of the same type Particle size varied between 08 and 52 μm aerodynamic mass median diameter (AMMD) The influence of these two properties on bronchial response to inhaled methacholine was examined Nebulizer output but not particle size (between 13 and 36 μm AMMD) altered the response We also examined the effect of change in inspiratory time during inhalation from residual volume to total lung capacity on lung deposition of radiolabeled aerosol and on the provocative concentration of histamine required to reduce the 1-sec forced expiratory volume (FEV 1 ) by 20% (PC 20 ) A reduction in inspiratory time from 8 to 2 sec resulted in a lower total lung dose, relatively more aerosol deposited in central airways, and a higher PC 20 The results emphasize the importance of keeping nebulizer output and pattern of breathing constant when performing inhalation provocation tests if consistent results are to be obtained
203 citations
TL;DR: It seems likely that additional asthmatic subjects have such sensitivities but are currently assumed to have "food allergies" and oral K2S2O5 challenges can identify asthmatics who are sensitive.
Abstract: While ingesting selected foods and drinks in restaurants, four asthmatic patients reported the sudden onset of severe wheezing and associated anaphylactoid symptoms and signs. Single-blind placebo and potassium metabisulfite (K2S2O5) oral challenges documented asthmatic responses 15 to 30 min after ingestion of K2S2O5. Laboratory investigations failed to demonstrate specific reaginic antibody recognition of K2S2O5 in these patients. Furthermore, their peripheral basophils did not release histamine during in vitro challenges with K2S2O5. It seems likely that additional asthmatic subjects have such sensitivities but are currently assumed to have "food allergies." Such individuals can be suspected of having this sensitivity by history, and oral K2S2O5 challenges can identify asthmatics who are sensitive.
187 citations
TL;DR: It was demonstrated that bridging of receptor molecules by divalent antireceptor antibody or its F(ab’), fragments induced Histamine release without participation of IgE, while the binding of Fab’ monomer fragments with the receptor was not sufficient for triggering histamine release.
Abstract: It has been established that mast cells and basophil granulocytes bear specific receptors for IgElP4 and that the reaction of cell-bound IgE molecules, either by multivalent antigen or with divalent anti-IgE antibody, induces release of a variety of chemical mediators from the cells.j* 6 With respect to the mechanisms of mediator release, it has been suggested that polymerization of cell-bound IgE molecules may activate membrane-associated enzymes that in turn initiate the process of histamine release.iq 8 In order to analyze initial triggering events on the mast cells for IgE-mediated histamine release, I prepared antibodies against IgE receptors on rat mast cells (anti-RBL).” Analysis of the antibody preparation revealed that the major antibodies in the preparation are directed toward the binding sites for IgE in the receptor molecules.‘O Using this antireceptor antibody (anti-RBL), it was demonstrated that bridging of receptor molecules by divalent antireceptor antibody or its F(ab’), fragments induced histamine release without participation of IgE, while the binding of Fab’ monomer fragments with the receptor was not sufficient for triggering histamine release. However, when receptor-bound Fab’ monomer was bridged with divalent antirabbit y-globulin (anti-RGG), mast cells were triggered. This situation is similar to anti-IgEinduced histamine release in which receptor-bound IgE molecules are bridged by anti-IgE (Fig. 1). From
172 citations
TL;DR: A characteristic pattern of symptomatic presentation and a paucity of the in vivo and in vitro findings associated with IgE-mediated nasal disease distinguishes this homogeneous disorder from perennial allergic rhinitis.
Abstract: Fifty-two patients with perennial nasal symptoms of sneezing paroxysms, profuse watery rhinorrhea, and pruritus of the nasopharyngeal mucosa in an "on-again-off-again" symptomatic pattern have been clinically and immunologically characterized. Historically, age at onset of symptoms showed equal distribution from the first through the fifth decades, and the duration of symptoms at diagnosis ranged from 3 mo to 40 yr (mean 9 yr). Trigger factors associated by the 52 patients with the acute onset of nasal symptoms were none or unknown in 22 (42%), weather changes in 16 (31%), odors in eight (15%), and noxious or irritating substances in six (12%). No patients had a history or physical examination consistent with nasal polyposis, bronchial asthma, current sinusitis, nor otitis media. Fifty percent had a negative family history for either chronic rhinitis or bronchial asthma. Nasal secretion smears revealed marked eosinophilia during symptomatic periods. Intradermal skin tests were negative in 49 patients. Serum radioallergosorbent test (RAST) confirmed immediate hypersensitivity skin tests in two of the three patients with positive skin tests. Mean total eosinophil count was 218/mm3. Quantitative immunoglobulins were normal in all patients. Mean serum IgE was 74 IU/ml. Methacholine bronchial challenge was negative in 37 of 37 patients tested. An open aspirin challenge was negative in 13 of 13 patients tested. Spontaneously collected nasal secretions or 0.9% saline nasal washes were analyzed for percent eosinophils, total protein, IgG, IgA, IgE, and RAST to six perennial aeroallergens in 31 of the 52 patients. Neither elevated total IgE nor evidence of specific IgE was found in the study patients' nasal secretions. This report describes 52 patients with symptoms similar to those seen in perennial allergic rhinitis. A characteristic pattern of symptomatic presentation and a paucity of the in vivo and in vitro findings associated with IgE-mediated nasal disease distinguishes this homogeneous disorder from perennial allergic rhinitis.
157 citations
TL;DR: It is concluded that the clinical and immunologic responses to venom immunotherapy are dose dependent and are more reliably complete at the recommended maintenance dose of 100 micrograms of each venom than at a dose of 50micrograms.
Abstract: The clinical and immunologic efficacy of venom immunotherapy up to 50 micrograms maintenance doses (half the recommended dose) was examined in 23 patients with anaphylactic sensitivity to insect stings and is compared with that in two groups of patients treated with the full 100-micrograms recommended dose. Four of the 19 patients challenged with insect stings had mild systemic reactions not requiring treatment. This 79% clinical efficacy is significantly less than the 96% to 100% success achieved with treatment to full 100-micrograms maintenance doses. The venom-specific IgG antibody response to the 50-micrograms dose reached a level significantly lower than observed with 100 micrograms doses. We conclude that the clinical and immunologic responses to venom immunotherapy are dose dependent and are more reliably complete at the recommended maintenance dose of 100 micrograms of each venom than at a dose of 50 micrograms.
133 citations
TL;DR: There is a loss of circulating suppressor-cytoxic T cells in the majority of patients with active atopic dermatitis, compared to healthy controls and controls with other skin diseases or respiratory allergic disease.
Abstract: Peripheral blood lymphocytes from 22 patients with atopic dermatitis, 17 age-matched healthy controls, 10 patients with other skin diseases, and 14 patients with either asthma or allergic rhinitis were characterized by reactivity with monoclonal antibodies to the surface antigens of helper-inducer (T4) and suppressor-cytotoxic (T8) T cell subsets and to a common T cell antigen (T3). In contrast to healthy controls and controls with other skin diseases or respiratory allergic disease, patients with atopic dermatitis had a reduced percentage of T3-positive (T3+) cells (p 0.05). A selective increase in the ratio of T4+ cells over T8+ cells was observed in 17 of 22 patients with atopic dermatitis but not in any of the controls. Thus there is a loss of circulating suppressor-cytotoxic T cells in the majority of patients with active atopic dermatitis.
TL;DR: It is postulated that propranolol potentiated anaphylaxis in these patients by inhibition of adenylate cyclase, resulting in lowered intracellular cyclic AMP and a lowered threshold of mediator release.
Abstract: Anaphylaxis to known allergens occurred in two patients under treatment for hypertension with propranolol. The clinical course of both cases was similar. Bradycardia associated with an undetectable blood pressure, unusual severity, and sluggish response to treatment were major common factors in which blockade of the beta-adrenergic system may have had a role. Propranolol, a beta-adrenergic antagonist that acts competitively by blocking the adenylate cyclase receptor on efferent cells, is well recognized to cause increased airways resistance in some asthmatic and normal subjects. It is postulated that propranolol potentiated anaphylaxis in these patients by inhibition of adenylate cyclase, resulting in lowered intracellular cyclic AMP and a lowered threshold of mediator release. The bradycardia during profound hypotension is attributed to an unopposed cholinergic action caused by blunting of the normal endogenous beta-adrenergic response by propranolol.
TL;DR: The major contributor to this age--skin test relationship was the level of total serum IgE that was highest in young people and decreased progressively with age, which contributed to the age-related prevalence of allergen skin-test reactions.
Abstract: Allergen skin reactivity to 14 common local antigens was studied in a community population sample. Differences in the prevalence of positive reactions were related to both the specific antigen itself and the age of the subjects. For most allergens, peak prevalence occurred in the 20- to 34-yr age group, falling thereafter with increasing age. The frequency distribution of reactions revealed a bimodal curve, peaks occurring among nonreactors and those with eight positive reactions out of the 14 tests that were applied. The major contributor to this age-skin test relationship was the level of total serum IgE that was highest in young people and decreased progressively with age. Histamine skin reactions, which were smallest in younger subjects compared with all three older age groups, also contributed to the age-related prevalence of allergen skin-test reactions.
TL;DR: All subjects manifested dose-related increases in pulse rate, pulse pressure, skin temperature, cutaneous flush, and headache; only one subject (an asthmatic) developed a significant reduction in peak expiratory flow rate.
Abstract: The dose-related effects of histamine on selected cardiovascular and pulmonary responses in 10 normal control and six mild allergic asthmatic subjects were investigated. Histamine was infused in sequentially increasing concentrations of 0.05, 0.1, 0.25, 0.5, and 1.0 μ/kg/min. The infusions were repeated after pretreatment with the H- I receptor antagonist hydroxyzine and/or the H-2 receptor antagonist cimetidine. All subjects manifested dose-related increases in pulse rate, pulse pressure, skin temperature, cutaneous flush, and headache; only one subject (an asthmatic) developed a significant reduction in peak expiratory flow rate. The decrease in peak expiratory flora rate in this subject was markedly attenuated by hydroxyzine pretreatment. The asthmatic subjects required somewhat larger concentrations of histamine (p
TL;DR: Ten peanut-sensitive patients were enrolled in a double-blind crossover trial to determine whether ingestion of peanut oil can induce adverse reactions in such individuals, and peanut oil ingestion does not pose a risk to peanut- sensitive individuals.
Abstract: Ten peanut-sensitive patients were enrolled in a double-blind crossover trial to determine whether ingestion of peanut oil can induce adverse reactions in such individuals. All patients had experienced prior allergic reactions to peanut ingestion, including any of the following: generalized urticaria, angioedema, abdominal cramps, vomiting, diarrhea, bronchospasm, or shock. All patients had elevated levels of serum IgE antibodies to both crude peanut extract and the purified peanut allergen, Peanut-I, by RAST assay; binding values ranged from 2 to 26 times that of negative control serum. All patients demonstrated negative puncture skin tests to both peanut oil and olive oil (control). At 30-min intervals, patients ingested 1, 2, and 5 m/ of either oil contained in 1 m/ capsules while under constant observation. These quantities exceed the maximum estimated dose of peanut oil that would occur in single meals. Patients returned 2 wk later for ingestion challenge with the remaining oil. No untoward reactions were observed with either peanut oil or olive oil. Peanut oil ingestion does not pose a risk to peanut-sensitive individuals.
TL;DR: There is no evidence that any type of therapy, including hyposensitization therapy, will directly influence prognosis, and the dictum that most children "outgrow" their asthma is incorrect.
Abstract: There is no evidence that any type of therapy, including hyposensitization therapy, will directly influence prognosis. The long-term prognosis of childhood asthma is less optimistic than previously believed. Approximately 30% of the patients who become symptom-free in adolescence relapse and become symptomatic in early adulthood. Blair's recent 20-yr follow-up report on 267 childhood asthmatics revealed that only 50% had become almost or completely symptom-free. Moreover, there is evidence that 60% of those who become symptom-free still demonstrate bronchial hyperreactivity and are liable to wheeze again if challenged with an appropriate stimuli. Therefore, the dictum that most children "outgrow" their asthma is incorrect and a more likely explanation is that most childhood asthmatics "outgrow" their pediatricians.
TL;DR: It is confirmed that oral theophylline at therapeutic serum levels inhibits LESP and induces gastroesophageal reflux (GER) measured by acid reflux tests in most normal adults.
Abstract: In a randomized, double-blind manner, 15 normal adults were given a single oral loading dose of anhydrous theophylline (6.5 +/- 0.9 mg/kg) and nine normal adults were given placebo. All subjects were tested for serum theophylline levels, acid reflux (using intraesophageal pH probe), and lower esophageal sphincter pressure (LESP) at 1.5, 4, and 8 hr after treatment. Of subjects with negative baseline acid reflux tests, eight of 13 (61.5%) given theophylline developed positive acid reflux tests compared with none of eight subjects given placebo. One of nine (11%) placebo subjects reported heartburn compared with 11 of 15 (73%) subjects given theophylline. The maximum mean percent change in LESP from baseline was +5.62 +/- 28.8% in the placebo group and -25.01 +/- 23.7% in the theophylline group (p = 0.01) at 4 hr after treatment. While only two of nine (22%) adults given placebo had at least a 14% reduction in LESP following treatment, all of the 15 subjects sustained a minimum of 14% relaxation in LESP. This study confirms that oral theophylline at therapeutic serum levels inhibits LESP and induces gastroesophageal reflux (GER) measured by acid reflux tests in most normal adults.
TL;DR: Extracts of 19 different peanut products and peanut oil were tested for their allergenicity by the radioallergosorbent test inhibition assay, suggesting that these products are not allergenic.
Abstract: Extracts of 19 different peanut products and peanut oil were tested for their allergenicity by the radioallergosorbent test inhibition assay using a crude peanut extract from raw peanuts as the standard for comparison. Seventeen of the extracts were able to competitively inhibit the binding of serum IgE from peanut-sensitive patients with the solid-phase raw peanut extract. Peanut oil and the extract from hydrolyzed peanut protein did not inhibit binding, which suggests that these products are not allergenic. The peanut hull flour extract showed a slight ability to inhibit binding, suggesting that this product contains minor amounts of the peanut allergen.
TL;DR: Measurement of bronchial responsiveness to histamine is a useful adjunct to history in determining the severity of asthma in an individual and should be considered as an objective way of grading subjects according to severity of Asthma in a clinical study.
Abstract: Seventy-eight children who had a history of asthma were studied while they were symptom-free. There was a highly significant correlation between the dose of aerosolized histamine that produced a decrease in FEV1 of 20% and each of the features in the history that indicated severity of asthma. The correlation was strengthened by the combination of these features into a weighted asthma history score. None of the subjects with mildly increased bronchial reactivity had a history score of severe asthma, and none with markedly increased bronchial reactivity had mild asthma. There was also a highly significant correlation between histamine dose and the results of spirometric tests for airway obstruction. However, the correlation between asthma history score and provocative histamine dose was highly significant even in the 21 subjects who were apparently free of airway obstruction at the time of testing. Furthermore, the correlation between asthma history score and histamine dose was stronger than that between asthma score and any spirometric test, indicating that the histamine test more accurately assessed the overall severity of the asthma. Measurement of bronchial responsiveness to histamine is a useful adjunct to history in determining the severity of asthma in an individual and should be considered as an objective way of grading subjects according to severity of asthma in a clinical study.
TL;DR: The epithelium is made up of eight different cells with the ciliated cell, the microvillar or brush cell, and the goblet cells being the predominant cells forming the surface as mentioned in this paper.
Abstract: The airways epithelium is made up of eight different cells with the ciliated cell, the microvillar or brush cell, and the goblet cells being the predominant cells forming the surface. These cells are joined by epithelial tight junctions and covered by a layer of mucus. The epithelium also contains an abundance of nerve fibres which are more concentrated in the extrathoracic airways. These irritant receptors or rapidly adapting stretch receptors run circumferentially around the surface cells and respond to a wide variety of stimuli including gases, smoke, dust, aerosols and antigens. While mast cells can be found in the airways lumen and in the epithelium, the greatest number are located in the submucosa. The epithelial surface barrier is normally quite impermeable to material that lands on it. However, a wide variety of injuries can induce inflammatory reactions and change the mucosal permeability to allow more easy access to the irritant receptors in the epithelia and mast cells in the submucosa. Injury by cigarette smoke induces an inflammatory reaction which causes an increase in mucosal permeability which returns to control values within a six-hour period. Maximal mucosal permeability is associated with the exudative phase of the inflammatory reaction where there is an increase in airways edema. By the time the polymorphonuclear leukocytes migrate to the mucosal surface, the permeability has returned to normal. These minimal inflammatory injuries are also associated with an increased cell turnover which may be responsible for the thickening of the basement membrane in chronic inflammatory states such as asthma.
TL;DR: Higher doses of stanozolol (4 mg/day), which caused greater immunochemical responses, were unnecessary for control of clinical disease and were unjustified for chronic therapy because of more frequent side effects.
Abstract: Stanozolol, an inexpensive anabolic steroid with a 30:1 anabolic:androgenic ratio, was administered to 12 male and 15 female patients with biochemically proven hereditary angioedema over a 2-yr period to obtain a systematic assessment of the relationship between drug dosage and clinical response, incidence of side effects, and amelioration of complement abnormalities. All 27 patients attained the minimal effective dose, ranging from 0.5 to 2 mg daily, which controlled the frequency and intensity of symptoms with minimal side effects. At daily maintenance doses of 2, 1, and 0.5 mg the frequencies of attacks per weeks of therapy were 1/14.6, 1/7.2, and 1/8.2 wk, respectively. Side effects with maintenance therapy included menstrual abnormalities and virilization in four females and elevation of serum creatinine phosphokinase (CPK) in five males. In six patients on maintenance doses of stanozolol, serum levels of testosterone, free thyroxin (T4), and thyroxin binding globulin (TBG) (four males), and of estradiol, progesterone, T4, and TBG (two females) were normal. Slightly low serum levels of progesterone and TBG were found in two females who had normal menstrual cycles. Statistically significant elevations above pretherapy levels of serum inhibitor to the activated first component of complement function and C4 protein and function occurred when patients were on maintenance therapy, but these measurements remained below the lower limit of normal range. Higher doses of stanozolol (4 mg/day), which caused greater immunochemical responses, were unnecessary for control of clinical disease and were unjustified for chronic therapy because of more frequent side effects.
TL;DR: A immunochemical method of assay of aeroallergens based on capture of airborne pollen, fungal spores, and amorphous particles on fiberglass sheets with a high-volume air sampler successfully extracted allergen from the sheets.
Abstract: Because particulate aeroallergens may exist in amorphous form as well as in pollen grains and fungal spores and because symptoms of allergic diseases presumably correlate with the total amount of allergen exposure, an immunochemical method of assay of aeroallergens would be useful. We report such a method based on (1) capture of airborne pollen, fungal spores, and amorphous particles 0.3 μm in diameter on fiberglass sheets with a high-volume air sampler; (2) elution of the sheets with buffered saline; and (3) analysis of eluate allergen content by radioallergosorbent test (RAST) inhibition assays. In preliminary indoor experiments we applied various quantities of short ragweed (SRW) pollen or dry Alternaria powder to the sheets while airflow was maintained at 1.19 m3/min. We compared techniques for extraction of allergen from the sheets, including homogenization, cutting and soaking, and descending elution of sheets. Although all three methods successfully extracted allergen from the sheets, an 8-hr descending elution procedure was optimal from the standpoint of yield and convenience. Eluates from filters exposed to as little as 4 mg of SRW pollen or Alternaria powder produced satisfactory RAST inhibition curves. When the sampler was operated outdoors continuously we could measure the atmospheric allergenic activity for both Alternaria and SRW from July to September. This allergenic activity was highly correlated with the traditional morphologic counts of airborne ragweed pollen and Alternaria spores.
TL;DR: It is suggested that humoral immunologic abnormalities are not directly responsible for the lung changes in silicosis and cannot be used as "guides" to predict severity or progression of disease.
Abstract: Serum specimens from 53 patients with silicosis were examined for the presence of antinuclear antibodies (ANA), rheumatoid factor (RF), immunoglobulins, and immune complexes. These humoral immunologic parameters were compared with radiographic changes and pulmonary function studies. A significant percentage of patients had an increased prevalence of ANA, RF, and immunoglobulin elevation (IgG, IgA). Immune complexes determined by the Raji-cell assay were detected in 31% of the patients. However, there was no significant correlation between any humoral immunologic abnormality and radiographic changes or declines in pulmonary function tests. These findings suggest that humoral immunologic abnormalities are not directly responsible for the lung changes in silicosis and cannot be used as "guides" to predict severity or progression of disease.
TL;DR: It is suggested the replacement of intravenous hydrocortisone sodium succinate with dexamethasone in the treatment of such a population of patients with intrinsic asthma and aspirin sensitivity.
Abstract: Eleven patients with intrinsic asthma and aspirin sensitivity were challenged with intravenous hydrocortisone sodium succinate (Solu-Cortef; the Upjohn Co., Kalamazoo, Mich.). Three patients showed definite evidence of bronchospasm, which was easily reversed by subcutaneous administration of epinephrine. Evidence is presented which suggests that this reaction was not caused by other constituents of the preparation but rather was caused by Solu-Cortef alone. No atopy was demonstrated in the group as a whole, and the reaction observed was probably nonallergic in nature. We suggest the replacement of intravenous hydrocortisone sodium succinate with dexamethasone in the treatment of such a population.
TL;DR: Patients being administered theophylline appear to be at added risk for the development of toxicity when erythromycin is added to the therapeutic regimen.
Abstract: The effect of erythromycin base on theophylline kinetics was studied in eight informed, nonsmoking, adult males who received a 15-min infusion of theophylline (aminophylline) 5 mg/kg, prior to (control) and after (experimental) a 7-day course of 1 gm daily ervthromycin base (E-Mycin). Each subject acted as his own control. Multiple serum samples were collected for 24 hr after each dose and were analyzed for theophylline by high-pressure liquid chromatography. The mean ± SD pharmacokinetic parameters for each phase of study were as follows: apparent volume of distribution (L/kg) 0.45 ± 0.05 (control), 0.41 ± 0.05 (experimental); clearance (ml · min/kg) 0.83 ± 0.17 (control), 0.60 ± 0.11 (experimental). elimination half-life (hr) 6.65 ± 1.88 (control), 8.10 ± 1.58 (experimental). Erythromycin significantly affected the elimination half-life and clearance of theophylline (p 0.05). Therefore patients being administered theophylline appear to be at added risk for the development of toxicity when erythromycin is added to the therapeutic regimen.
TL;DR: The possibility of genetic influences on susceptibility to mouse allergy were suggested by a negative association between the incidence of HLA-DRW6 and positive prick-test responses to urinary proteins from C57BL and BALB/c mice among the 54 subjects who were exposed to mice and tested for DR locus antigens.
Abstract: Symptomatic and immunologic responses to allergens from laboratory mice were studied in a research institute. Subjects who had been exposed to mice and 50 unexposed subjects were studied by questionnaire and by prick tests with seven prevalent aeroallergens and allergens from mouse urine and pelts. Of the 121 exposed subjects, 39 (32.2%) had respiratory, ocular, or cutaneous symptoms after exposure to mice; occurrence of these symptoms correlated with positive skin tests to purified mouse urinary proteins (MUP) and pelt allergens from CBA/H mice. Serum levels of IgG antibodies correlated with the frequency of mouse exposure. In subjects with seasonal allergic rhinitis, nasal symptoms from exposure to mice, positive prick tests to MUP, and IgE antibodies to MUP were significantly more prevalent. The possibility of genetic influences on susceptibility to mouse allergy were also suggested by a negative association between the incidence of HLA-DRW6 and positive prick-test responses to urinary proteins from C57BL and BALB/c mice among the 54 subjects who were exposed to mice and tested for DR locus antigens (p = 0.05). However, no significant differences in any of the loci studied could be shown in subjects with and without nasal symptoms from exposure to mice.
TL;DR: The results indicate that some patients with the exercise-induced anaphylactic syndrome are unusual examples of severe cholinergic urticaria, and the utility of a regular exercise program as part of the management of some Patients with cholera requires further investigation.
Abstract: Two patients presented with a history of exercise-induced hypotension associated with severe pruritus and either generalized urticaria or facial angioedema. Each patient was exercised under controlled conditions with use of a bicycle ergometer exerciser (900 KPM/min) for 20 to 30 min at 23 C. Each patient complained of generalized pruritus and then erupted in lesions typical of cholinergic urticaria. In one patient the lesions became confluent about the face and were followed by eyelid edema, lip swelling, and transient hypotension. Plasma histamine levels were elevated in each patient and reached a maximal level between 20 and 25 min. Neither patient had a change in forced expiratory volume in one second during the episode and detailed pulmonary function testing in one patient revealed no change in airway resistance, specific Conductance, forced expiratory vital capacity, or forced expiratory flow rates. One patient had a positive methacholine chloride (Mecholyl) skin test with satellite lesions, and the second patiem was skin-test negative. The skin test-positive patient, who was not hypotensioe when initially challenged, was strenuously exercised for 15 min/day. Progressively less severe reactions were seen associated with diminished histamine release, and the patient is now on a dailv exercise program, symptoms in the second patient are controlled with hydroxazine. Our results indicate that some patients with the exercise-induced anaphylactic syndrome are unusual examples of severe cholinergic urticaria. Furthermore, the utility q1 a regular exercise program as part of the management of some patients with cholinergic urticaria requires, further investigation.
TL;DR: The hydroxyzine-cimetidine combination was favored by 11 of 19 (58%) patients, in addition to producing the lowest symptom scores and the greatest histamine-48/80 wheal suppression, and support the efficacy of combination H1 and H2 antihistamines in the management of some patients with difficult chronic urticaria.
Abstract: Nineteen patients with chronic idiopathic urticaria (duration 2 to 192 mo) referred to our clinic as therapeutic failures were treated sequentially with five regimens. These were administered orally in a double-blind random sequence and included hydroxyzine pamoate (25 mg q.i.d.) plus one of the following: (1) placebo, (2) terbutaline (2.5 mg q.i.d.), (3) cyproheptadine (4 mg q.i.d.), (4) chlorpheniramine (4 mg q.i.d.), and (5) cimetidine (300 mg q.i.d.). Therapeutic response was assessed by patient's subjective choice, symptom diary scores, and suppression of wheal response to intradermal injections of histamine and compound 48/80. At least 35% improvement was noted in all patients with an average optimal response of 70%. The hydroxyzine-cimetidine combination was favored by 11 of 19 (58%) patients, in addition to producing the lowest symptom scores and the greatest histamine-48/80 wheal suppression. These results support the efficacy of combination H 1 and H 2 antihistamines in the management of some patients with difficult chronic urticaria.
TL;DR: The authors found that exposure of normal cells to low (10−6)M concentrations of histamine, isoproterenol, or prostaglandin E desensitized the cells to subsequent stimulatory concentrations of any of the agonists.
Abstract: Studies of mononuclear leukocytes from patients with atopic dermatitis showed depressed cyclic AMP (cAMP) responses after exposure to isoproterenol, histamine, and prostaglandin E1. Because plasma and tissue histamine levels are elevated in atopic dermatitis, we questioned whether histamine or other mediators might be responsible for cAMP abnormalities. We found that exposure of normal cells to low (10(-6)M) concentrations of histamine, isoproterenol, or prostaglandin E desensitized the cells to subsequent stimulatory concentrations of any of the agonists. This heterologous desensitization occurred within 15 min and persisted for days, with gradual recovery of cAMP responses roughly paralleling those of cells from patients with atopic dermatitis. These findings provide a possible explanation for Szentivanyi's beta adrenergic blockade theory and the depressed leukocyte cAMP response to multiple agonists in atopy.