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Administration of radiographic contrast media in high-risk patients
12 Abstracts
J. ALLERGY CLIN. IMMUNOL. MARCH 1982
direct histamine liberation rather than being mediated by IgE. The authors believe that these reactions to no-carbon paper are real and are not due to atmospheric conditions in the plant or to mass hysteria. Since other observations have shown some connection between inhalation of the vapors from the solvent used in the manufacturing of no-carbon transfer paper and neurologic symptoms in office workers, it would be simple to make this correlation in relation to dermatitis. However, there is as yet insufficient evidence to implicate this material.
D.S.
Incidence of atopy in rheumatic disease Peskett S, Platts-Mills T, Ansell B, Stearnes G: J Rheumatol 8:321, 1981. Pages 321-324 This study was designed to assess whether patients with juvenile chronic arthritis (JCA) or rheumatoid arthritis (RA) have a normal incidence of specific responses to an inhalant allergen. In addition, the authors searched for evidence of involvement of IgE antibodies in these diseases. Forty patients with JCA, ages 2 to 27 yr, and 40 normal adult controls were studied. A personal and family history of atopy was taken, and all patients were prick tested with five common allergen extracts: grass pollen, house dust, Dermatophagoides pteronyssinus, mixed molds, and either cat or dog dander. Serum IgG and IgE antibodies to the group I protein of rye grass pollen were measured by antigen binding radioimmunoassay (RIA), and total serum IgE was measured by a double-antibody inhibition RIA. Sera were obtained from 66 patients with adult RA. Six of the JCA patients showed positive skin tests to grass pollen; five of these had clear histories of seasonal hay fever, as well as appropriate levels of pollen-specific IgG and IgE. Four of the JCA patients also had positive skin tests to the house dust mite. Only nine of the sera from patients with adult RA contained significant levels of antigen-specific IgG, whereas only one of these nine had antigen-specific IgE antibodies. This incidence of IgG antibodies (14%) was lower than that in the JCA group and much lower than the incidence in the adult controls. The total IgE levels in the adult RA group were also lower than those of the normal controls. These results do not suggest that children with JCA respond abnormally to inhalant allergens. The results for patients with adult RA suggest that these patients may have poor ability to recognize and respond to inhalant allergens. None of the results suggests that IgE or IgG reaginic antibodies are involved in these diseases.
A.J.C.
Schizophrenia, celiac disease and antibodies to food McGuffin P, Gardiner P, Swinburne L: Biol Psychiatry 16:281, 1981. There is some evidence from both epidemiologic and clinical sources suggesting an association between sensitiv-
ity to ingested cereals and the production of schizophrenic symptoms. It has been reported by others that cereal- and milk-free diets promote recovery from schizophrenia. A causal link between gluten sensitivity and celiac disease is well established, and the presence of dietary antibodies in the sera of the majority of cases are known to occur. If schizophrenia and celiac disease share a common etiologic factor, serologic similarities may be apparent. In this study, the authors used a tanned red-cell technique to detect the presence of antibodies to milk, egg white, and gluten in the serum of schizophrenic patients. Thirty-one patients with schizophrenia, 29 patients with affective disorders, and 30 healthy controls were studied. Serum dietary antibodies were measured by a tanned red-cell agglutination test. Tanned red cells were coated with whole cow's milk, egg white, and gluten extract, and the titers for each antibody in the three groups of subjects were compared. The distribution of food antibody titers in schizophrenic and affectivedisorder patients, as well as controls, were shown not to be significantly different. None of the patients had a positive personal or family history of food allergy, celiac disease, chronic diarrhea, or malabsorption. The authors admit that their sample cells were small but did not exclude the possibility that gluten exercises a pathogenic effect by cell-mediated immune mechanisms rather than via humoral antibodies. It is also pointed out that there are two other nonimmunologicmechanisms by which gluten may produce a deleterious effect in schizophrenia. Gluten may be a source of a neuroactive peptide that induces exacerbation of symptoms, or it may interfere with the efficacy of antischizophrenic drugs.
A.J.C.
Administration of radiographic contrast media in high-risk patients Greenberger P, Patterson R, Kelly J, Stevenson D, Simon R, Lieberman P: Invest Radiol 15(6 Suppl.):40, 1980. Approximately 2% of all patients receiving radiographic contrast media (RCM) develop anaphylactoid reactions (ARs). Some of these reactions are of the immediate type and are clinically similar to IgE-mediated hypersensitivity reactions, presenting as urticaria, angioedema, bronchospasm, hypotension, or rhinitis. Although the RCM reactions have been attributed to histamine release, no definite evidence has ever been established for the pathophysiologic mechanism of these reactions. Thirty percent of patients who had experienced an AR to RCM at some time in the past have had a recurrence after subsequent exposure to RCM. This figure does not even include patients who have had the more severe type of reactions. A previous investigation reported that RCM AR patients who had previously experienced severe reactions were well protected by pretreatment with steroids beginning 18 hr before the repeat procedure. In another study it was found that in 42 high-risk patients, pretreatment with diphenhy-
VOLUME 63 NUMBER 3
Abstracts
13
Pharmacology, physiology, and pathology
sured after challenge of these strips with C5a, acetylcholine, histamine, and serotonin, and the C5a-induced contraction was expressed as a percentage of the maximal response obtained with acetylcholine. Repeat exposure to C5a diminished the contractility of the strip, whereas washing the tissue after initial exposure did not affect the duration of contraction. This C5a response was not influenced by diphenhydramine, an inhibitor of the HI receptor, but this drug did delay the compound 48/80-induced smoothmuscle contraction. Further, metamide, an inhibitor of the H2 receptor, also failed to inhibit C5a-induced smoothmuscle contraction, as did atropine and phentolamine, which inhibits c~-adrenergic receptors. Since C5a is capable of releasing histamine from guinea pig mast cells, the failure of diphenhydramine and metamide to block the C5ainduced muscle contraction indicates that this action is independent of histamine release from the tissue. This finding may b e extrapolated to the bronchospasm observed in human asthma. D.S.
Bronchoconstriction produced in man by leukotrienes C and D Holroyde MC, Altounyan REC, Cole M, Dixon M, Elliott EV: Lancet 2:8236, 1981.
Intermittent positive pressure breathing administration of terbutaline: a dose response study
dramine effectively protected all but 11.9% of the group. To investigate the problem further, a group of patients of high risk for RCM AR was pretreated with a combined prednisone and diphenhydramine protocol. Three doses of 50 mg of prednisone each were given orally every 6 hr, with the final dose given 1 hr prior to the RCM administration; 50 mg of diphenhydramine were given intramuscularly simultaneously with RCM. Of the 168 patients in the study group, two developed generalized urticaria of short duration and nine had other types of mild systemic reactions. No serious reactions were encountered. In spite of these excellent though not perfect results, the authors warn that it is essential that adequate resuscitation equipment and trained personnel be available whenever RCM is administered. H.J.F.
The effects of inhaling leukotrienes (LT) C and D (LTC and LTD) were assessed in two healthy, non-smoking, non-atopic adults. LTC and LTD, freshly prepared, were inhaled via nebulizer, with subsequent interval measurement of forced expiratory volume (FEV) and partial expiratory flow-volume curves. The subjects responded with an equal degree of bronchoconstriction to LTC and LTD and with resultant cough after inhalation. Disodium cromoglycate administered before LT nebulization failed to block the LT-induced bronchial hyperreactivity. The SRS-A inhibitors FPL-55712 and FPL 59257 modified the bronchial response to LT when inhaled before challenge, especially by eliminating the LT-induced cough. The authors determined that LT inhalation did not have a noticeable effect on FEV but did reduce expiratory flow at low lung volumes. The peripheral rather than the central airways are therefore implicated as the site of reactivity to LT inhalational challenge. D.S.
C5a induced tracheal contraction: a histamine independent mechanism Regal JF, Eastman AY, Picketing RJ: J Immunol 124:2876, 1980. C5a (anaphylatoxin) causes contraction of smooth muscle isolated from guinea pig trachea independent of the contraction induced by histamine. The authors prepared partially purified C5a from yeast-activated guinea pig serum for testing on strips of guinea pig tracheal smooth muscle maintained in a tissue bath. Isometric contractions were mea-
Trautlein J J, Serra R: Ann Allergy 47:76, 1981. Terbutaline, a selective beta-2 sympathomimetic amine, administered orally or by subcutaneous injection, has been demonstrated to be a useful adjunct in the treatment of acute and chronic asthma. This study investigated the airway responses to terbutaline administered via intermittent positive pressure breathing (IPPB) therapy. The study group comprised eight patients (ages 49 to 70 yr) with chronic obstructive pulmonary disease (five with bronchial asthma, two with chronic obstructive lung disease, and one with emphysema), who had previously demonstrated a reversible airway component of at least 15%. Prior to the study period, all patients bad routine electrocardiogram, blood and urine studies, and baseline pulmonary function tests (FVC, FEV~, FEF25-~, and PEFR) performed after abstaining from all bronchodilators for 12 hr. Terbutaline sulfate was then administered in incremental doses by inhalation via a Monaghan M-510 IPPB apparatus until pulmonary function measurements plateaued or a 15beat increase in heart rate was observed. After the inhalation of 0.5 mg of terbutaline, all pulmonary function measurements were significantly improved over baseline values; at 1.0 mg of terbutaline, further increases in FVC, FEV1, and FEF25-7~ were minimal but were significantly greater for PEFR. A cumulative dose of 3.0 mg was administered to only two patients. After nebulization of terbutaline, mean baseline systolic blood pressm'e (121.3) increased significantly to 131.8 at 0.5 mg and to 135.5 at 1.0 mg; there were no significant differences in heart rate or diastolic blood pressure at either dose, nor were there any complaints of palpitation or fine motor tremor. The authors conclude that terbutaline administered by a
J. ALLERGY CLIN. IMMUNOL. MARCH 1982
direct histamine liberation rather than being mediated by IgE. The authors believe that these reactions to no-carbon paper are real and are not due to atmospheric conditions in the plant or to mass hysteria. Since other observations have shown some connection between inhalation of the vapors from the solvent used in the manufacturing of no-carbon transfer paper and neurologic symptoms in office workers, it would be simple to make this correlation in relation to dermatitis. However, there is as yet insufficient evidence to implicate this material.
D.S.
Incidence of atopy in rheumatic disease Peskett S, Platts-Mills T, Ansell B, Stearnes G: J Rheumatol 8:321, 1981. Pages 321-324 This study was designed to assess whether patients with juvenile chronic arthritis (JCA) or rheumatoid arthritis (RA) have a normal incidence of specific responses to an inhalant allergen. In addition, the authors searched for evidence of involvement of IgE antibodies in these diseases. Forty patients with JCA, ages 2 to 27 yr, and 40 normal adult controls were studied. A personal and family history of atopy was taken, and all patients were prick tested with five common allergen extracts: grass pollen, house dust, Dermatophagoides pteronyssinus, mixed molds, and either cat or dog dander. Serum IgG and IgE antibodies to the group I protein of rye grass pollen were measured by antigen binding radioimmunoassay (RIA), and total serum IgE was measured by a double-antibody inhibition RIA. Sera were obtained from 66 patients with adult RA. Six of the JCA patients showed positive skin tests to grass pollen; five of these had clear histories of seasonal hay fever, as well as appropriate levels of pollen-specific IgG and IgE. Four of the JCA patients also had positive skin tests to the house dust mite. Only nine of the sera from patients with adult RA contained significant levels of antigen-specific IgG, whereas only one of these nine had antigen-specific IgE antibodies. This incidence of IgG antibodies (14%) was lower than that in the JCA group and much lower than the incidence in the adult controls. The total IgE levels in the adult RA group were also lower than those of the normal controls. These results do not suggest that children with JCA respond abnormally to inhalant allergens. The results for patients with adult RA suggest that these patients may have poor ability to recognize and respond to inhalant allergens. None of the results suggests that IgE or IgG reaginic antibodies are involved in these diseases.
A.J.C.
Schizophrenia, celiac disease and antibodies to food McGuffin P, Gardiner P, Swinburne L: Biol Psychiatry 16:281, 1981. There is some evidence from both epidemiologic and clinical sources suggesting an association between sensitiv-
ity to ingested cereals and the production of schizophrenic symptoms. It has been reported by others that cereal- and milk-free diets promote recovery from schizophrenia. A causal link between gluten sensitivity and celiac disease is well established, and the presence of dietary antibodies in the sera of the majority of cases are known to occur. If schizophrenia and celiac disease share a common etiologic factor, serologic similarities may be apparent. In this study, the authors used a tanned red-cell technique to detect the presence of antibodies to milk, egg white, and gluten in the serum of schizophrenic patients. Thirty-one patients with schizophrenia, 29 patients with affective disorders, and 30 healthy controls were studied. Serum dietary antibodies were measured by a tanned red-cell agglutination test. Tanned red cells were coated with whole cow's milk, egg white, and gluten extract, and the titers for each antibody in the three groups of subjects were compared. The distribution of food antibody titers in schizophrenic and affectivedisorder patients, as well as controls, were shown not to be significantly different. None of the patients had a positive personal or family history of food allergy, celiac disease, chronic diarrhea, or malabsorption. The authors admit that their sample cells were small but did not exclude the possibility that gluten exercises a pathogenic effect by cell-mediated immune mechanisms rather than via humoral antibodies. It is also pointed out that there are two other nonimmunologicmechanisms by which gluten may produce a deleterious effect in schizophrenia. Gluten may be a source of a neuroactive peptide that induces exacerbation of symptoms, or it may interfere with the efficacy of antischizophrenic drugs.
A.J.C.
Administration of radiographic contrast media in high-risk patients Greenberger P, Patterson R, Kelly J, Stevenson D, Simon R, Lieberman P: Invest Radiol 15(6 Suppl.):40, 1980. Approximately 2% of all patients receiving radiographic contrast media (RCM) develop anaphylactoid reactions (ARs). Some of these reactions are of the immediate type and are clinically similar to IgE-mediated hypersensitivity reactions, presenting as urticaria, angioedema, bronchospasm, hypotension, or rhinitis. Although the RCM reactions have been attributed to histamine release, no definite evidence has ever been established for the pathophysiologic mechanism of these reactions. Thirty percent of patients who had experienced an AR to RCM at some time in the past have had a recurrence after subsequent exposure to RCM. This figure does not even include patients who have had the more severe type of reactions. A previous investigation reported that RCM AR patients who had previously experienced severe reactions were well protected by pretreatment with steroids beginning 18 hr before the repeat procedure. In another study it was found that in 42 high-risk patients, pretreatment with diphenhy-
VOLUME 63 NUMBER 3
Abstracts
13
Pharmacology, physiology, and pathology
sured after challenge of these strips with C5a, acetylcholine, histamine, and serotonin, and the C5a-induced contraction was expressed as a percentage of the maximal response obtained with acetylcholine. Repeat exposure to C5a diminished the contractility of the strip, whereas washing the tissue after initial exposure did not affect the duration of contraction. This C5a response was not influenced by diphenhydramine, an inhibitor of the HI receptor, but this drug did delay the compound 48/80-induced smoothmuscle contraction. Further, metamide, an inhibitor of the H2 receptor, also failed to inhibit C5a-induced smoothmuscle contraction, as did atropine and phentolamine, which inhibits c~-adrenergic receptors. Since C5a is capable of releasing histamine from guinea pig mast cells, the failure of diphenhydramine and metamide to block the C5ainduced muscle contraction indicates that this action is independent of histamine release from the tissue. This finding may b e extrapolated to the bronchospasm observed in human asthma. D.S.
Bronchoconstriction produced in man by leukotrienes C and D Holroyde MC, Altounyan REC, Cole M, Dixon M, Elliott EV: Lancet 2:8236, 1981.
Intermittent positive pressure breathing administration of terbutaline: a dose response study
dramine effectively protected all but 11.9% of the group. To investigate the problem further, a group of patients of high risk for RCM AR was pretreated with a combined prednisone and diphenhydramine protocol. Three doses of 50 mg of prednisone each were given orally every 6 hr, with the final dose given 1 hr prior to the RCM administration; 50 mg of diphenhydramine were given intramuscularly simultaneously with RCM. Of the 168 patients in the study group, two developed generalized urticaria of short duration and nine had other types of mild systemic reactions. No serious reactions were encountered. In spite of these excellent though not perfect results, the authors warn that it is essential that adequate resuscitation equipment and trained personnel be available whenever RCM is administered. H.J.F.
The effects of inhaling leukotrienes (LT) C and D (LTC and LTD) were assessed in two healthy, non-smoking, non-atopic adults. LTC and LTD, freshly prepared, were inhaled via nebulizer, with subsequent interval measurement of forced expiratory volume (FEV) and partial expiratory flow-volume curves. The subjects responded with an equal degree of bronchoconstriction to LTC and LTD and with resultant cough after inhalation. Disodium cromoglycate administered before LT nebulization failed to block the LT-induced bronchial hyperreactivity. The SRS-A inhibitors FPL-55712 and FPL 59257 modified the bronchial response to LT when inhaled before challenge, especially by eliminating the LT-induced cough. The authors determined that LT inhalation did not have a noticeable effect on FEV but did reduce expiratory flow at low lung volumes. The peripheral rather than the central airways are therefore implicated as the site of reactivity to LT inhalational challenge. D.S.
C5a induced tracheal contraction: a histamine independent mechanism Regal JF, Eastman AY, Picketing RJ: J Immunol 124:2876, 1980. C5a (anaphylatoxin) causes contraction of smooth muscle isolated from guinea pig trachea independent of the contraction induced by histamine. The authors prepared partially purified C5a from yeast-activated guinea pig serum for testing on strips of guinea pig tracheal smooth muscle maintained in a tissue bath. Isometric contractions were mea-
Trautlein J J, Serra R: Ann Allergy 47:76, 1981. Terbutaline, a selective beta-2 sympathomimetic amine, administered orally or by subcutaneous injection, has been demonstrated to be a useful adjunct in the treatment of acute and chronic asthma. This study investigated the airway responses to terbutaline administered via intermittent positive pressure breathing (IPPB) therapy. The study group comprised eight patients (ages 49 to 70 yr) with chronic obstructive pulmonary disease (five with bronchial asthma, two with chronic obstructive lung disease, and one with emphysema), who had previously demonstrated a reversible airway component of at least 15%. Prior to the study period, all patients bad routine electrocardiogram, blood and urine studies, and baseline pulmonary function tests (FVC, FEV~, FEF25-~, and PEFR) performed after abstaining from all bronchodilators for 12 hr. Terbutaline sulfate was then administered in incremental doses by inhalation via a Monaghan M-510 IPPB apparatus until pulmonary function measurements plateaued or a 15beat increase in heart rate was observed. After the inhalation of 0.5 mg of terbutaline, all pulmonary function measurements were significantly improved over baseline values; at 1.0 mg of terbutaline, further increases in FVC, FEV1, and FEF25-7~ were minimal but were significantly greater for PEFR. A cumulative dose of 3.0 mg was administered to only two patients. After nebulization of terbutaline, mean baseline systolic blood pressm'e (121.3) increased significantly to 131.8 at 0.5 mg and to 135.5 at 1.0 mg; there were no significant differences in heart rate or diastolic blood pressure at either dose, nor were there any complaints of palpitation or fine motor tremor. The authors conclude that terbutaline administered by a