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ASPIRIN INTOLERANCE
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untoward neurological sequelae were proved to be due to the vaccine.4O Vaccination can be adopted in Britain with confidence that it will reduce the hazards from measles and confer longlasting immunity. Measles vaccine is a freeze-dried product and therefore relatively stable, but after reconstitution with the diluent provided by the manufacturer it should be used immediately. The vaccine is not normally recommended until the second year of life, because small amounts of maternal antibody inhibit the growth of vaccine virus. The disease is, however, more severe in infancy, and for special high-risk infants (for example, those with malnutrition or heart, respiratory, or 40.
Nader, P. R., Warren, R. J. Pediatrics, Springfield, 1968, 41, 997.
Annotations ASPIRIN INTOLERANCE
THE incidence of untoward effects from ingestion of aspirin is remarkably low. Of its ill-effects, intoxication and gastrointestinal bleeding have received most attention; but hypersensitivity reactions to small quantities are not uncommon, and relatively little is known about their
Idiosyncrasy to aspirin usually presents as skin rashes and signs of anaphylaxis. Asthma, angioneurotic cedema, and laryngeal spasm may be life-threatening; cross-sensitivity with related substances is uncommon. Cooke1 found no reaction from salicylic acid, benzoic acid, antipyrine, sodium acetate, and methyl salicylate in aspirin-sensitive patients; and in a study of 182 similar patients Samter and Beershave found no untoward reactions after administration of sodium salicylate, salicylic-acid esters, choline salicylate, thioaspirin, and N-acetyl-p-aminophenol. Apparently, therefore, intolerance to aspirin is not an intolerance to salicylates. The incidence of penicillin and sulphonamide sensitivity was not higher than expected in a normal population, but Samter and Beers found that indomethacin and tartrazine caused symptoms in the skin and respiratory tract of these patients, and that morphine and codeine produced startling and severe reactions in a few of them. Indomethacin, like aspirin, is a minor analgesic; while tartrazine, or hydrazine-yellow, is a colouring-matter in various foodstuffs. Another interesting feature of aspirin hypersensitivity is its association with other conditions. Prickman and Buchstein3 studied 62 patients and found sinusitis in 4, hay-fever in 11, vasomotor rhinitis and nasal polyps in 21, asthma in 43, migraine in 6, and urticaria or angioneurotic oedema in 10. Samter and Beers found similar associations in their 182 patients. In the second or third decade of life an intermittent vasomotor rhinitis commonly developed in patients of each sex, with profuse watery secretions eventually followed by chronic nasal blockade and loss of intermittency. As swelling of the nasal mucous membranes continued, nasal and paranasal polyps developed. 92 of the 182 patients, in fact, had nasal polyps, which tended to be bilateral and responded poorly to treatment; 68 patients had had multiple polypectomies, some as often as once a month.
nature.
1. Cooke, R. A. J. Am. med. Ass. 1919, 73, 759. 2. Samter, M., Beers, R. F. Ann. intern. Med. 1968, 68, 975. 3. Prickman, L. E., Buchstein, H. F. J. Am. med. Ass. 1937, 108,
445.
other chronic disease) it may well be advisable to give vaccine at six months and to repeat the dose at one year, at least until the general incidence of the disease is reduced to a negligible sum. When they appear, reactions to the vaccine usually come between the seventh and tenth day after immunisation and last for one or two days. When vaccinating children with or disease neurological family history of convulsions, y-globulin should be given at the same time as the vaccine but into another site. y-globulin of potency suitable for this purpose is to be made available by the Public Health Laboratory Service. The only definite contraindication to measles vaccination is in children with leuksemia or other malignant disease. Bronchial asthma in these aspirin-sensitive patients tended to appear in middle-age and sometimes followed nasal polypectomy. In its early stages it is readily reversed by bronchodilators, and responds to smaller doses of corticosteroids than are required for control of immunologically induced bronchial asthma of comparable severity. Nasal polyposis and bronchial asthma continue whether or not aspirin is ingested; and indeed the first aspirin-induced reaction may not occur until respiratory manifestations of the disease have been present for years. It seems unlikely that aspirin hypersensitivity is a manifestation of an atopic state, because, although a significant number of patients studied by Samter and Beers had a family history of atopy, less than 3% showed unequivocal evidence of the condition. Aspirin hypersensitivity is different in several respects, therefore, from other forms of allergic manifestation. Samter and Beers suggest that non-immunological mechanisms are responsible, and point out that the substances which induce aspirin-like symptoms in hypersensitive patients have one characteristic in commonnamely, that they are strong minor analgesics. There is considerable evidence that " pain " receptors are chemoreceptors4 and that bradykinin and related peptides are the mediators which stimulate them. It is also known 4 that aspirin and similar analgesic compounds antagonise the effects of bradykinin peripherally; and this may be at least partly responsible for their analgesic action. Possibly, as Samter and Beers suggest, in the aspirin-hypersensitivity state there is increased responsiveness of chemoreceptors in the nasal and bronchial mucous membranes to a variety of these peptides and their therapeutic antagonists. The most important practical feature of this condition is that it cannot be predicted by skin tests but only by the clinical history; and patients with a warning history must be strongly enjoined not to take aspirin in any of its many forms. CANCER IN CATS AND DOGS
SPONTANEOUS cancers in the dog and cat, domestic animals that face many of the hazards of men’s lives as well as those of their own, have often been recorded 5 6; but not much is known about the total impact of cancer on these animals. Attempts at estimates have been based on attendance at veterinary clinics, on studies of impounded 4.
5. 6.
Lim, R. K. S. Proceedings of the 3rd International Pharmacological Meeting, Sao Paulo, 1966; vol. IX. Oxford, 1968. Mulligan, R. M. Neoplasms of the Dog. Baltimore, 1949. Ann. N.Y. Acad. Sci. 1963, 108, 619.
untoward neurological sequelae were proved to be due to the vaccine.4O Vaccination can be adopted in Britain with confidence that it will reduce the hazards from measles and confer longlasting immunity. Measles vaccine is a freeze-dried product and therefore relatively stable, but after reconstitution with the diluent provided by the manufacturer it should be used immediately. The vaccine is not normally recommended until the second year of life, because small amounts of maternal antibody inhibit the growth of vaccine virus. The disease is, however, more severe in infancy, and for special high-risk infants (for example, those with malnutrition or heart, respiratory, or 40.
Nader, P. R., Warren, R. J. Pediatrics, Springfield, 1968, 41, 997.
Annotations ASPIRIN INTOLERANCE
THE incidence of untoward effects from ingestion of aspirin is remarkably low. Of its ill-effects, intoxication and gastrointestinal bleeding have received most attention; but hypersensitivity reactions to small quantities are not uncommon, and relatively little is known about their
Idiosyncrasy to aspirin usually presents as skin rashes and signs of anaphylaxis. Asthma, angioneurotic cedema, and laryngeal spasm may be life-threatening; cross-sensitivity with related substances is uncommon. Cooke1 found no reaction from salicylic acid, benzoic acid, antipyrine, sodium acetate, and methyl salicylate in aspirin-sensitive patients; and in a study of 182 similar patients Samter and Beershave found no untoward reactions after administration of sodium salicylate, salicylic-acid esters, choline salicylate, thioaspirin, and N-acetyl-p-aminophenol. Apparently, therefore, intolerance to aspirin is not an intolerance to salicylates. The incidence of penicillin and sulphonamide sensitivity was not higher than expected in a normal population, but Samter and Beers found that indomethacin and tartrazine caused symptoms in the skin and respiratory tract of these patients, and that morphine and codeine produced startling and severe reactions in a few of them. Indomethacin, like aspirin, is a minor analgesic; while tartrazine, or hydrazine-yellow, is a colouring-matter in various foodstuffs. Another interesting feature of aspirin hypersensitivity is its association with other conditions. Prickman and Buchstein3 studied 62 patients and found sinusitis in 4, hay-fever in 11, vasomotor rhinitis and nasal polyps in 21, asthma in 43, migraine in 6, and urticaria or angioneurotic oedema in 10. Samter and Beers found similar associations in their 182 patients. In the second or third decade of life an intermittent vasomotor rhinitis commonly developed in patients of each sex, with profuse watery secretions eventually followed by chronic nasal blockade and loss of intermittency. As swelling of the nasal mucous membranes continued, nasal and paranasal polyps developed. 92 of the 182 patients, in fact, had nasal polyps, which tended to be bilateral and responded poorly to treatment; 68 patients had had multiple polypectomies, some as often as once a month.
nature.
1. Cooke, R. A. J. Am. med. Ass. 1919, 73, 759. 2. Samter, M., Beers, R. F. Ann. intern. Med. 1968, 68, 975. 3. Prickman, L. E., Buchstein, H. F. J. Am. med. Ass. 1937, 108,
445.
other chronic disease) it may well be advisable to give vaccine at six months and to repeat the dose at one year, at least until the general incidence of the disease is reduced to a negligible sum. When they appear, reactions to the vaccine usually come between the seventh and tenth day after immunisation and last for one or two days. When vaccinating children with or disease neurological family history of convulsions, y-globulin should be given at the same time as the vaccine but into another site. y-globulin of potency suitable for this purpose is to be made available by the Public Health Laboratory Service. The only definite contraindication to measles vaccination is in children with leuksemia or other malignant disease. Bronchial asthma in these aspirin-sensitive patients tended to appear in middle-age and sometimes followed nasal polypectomy. In its early stages it is readily reversed by bronchodilators, and responds to smaller doses of corticosteroids than are required for control of immunologically induced bronchial asthma of comparable severity. Nasal polyposis and bronchial asthma continue whether or not aspirin is ingested; and indeed the first aspirin-induced reaction may not occur until respiratory manifestations of the disease have been present for years. It seems unlikely that aspirin hypersensitivity is a manifestation of an atopic state, because, although a significant number of patients studied by Samter and Beers had a family history of atopy, less than 3% showed unequivocal evidence of the condition. Aspirin hypersensitivity is different in several respects, therefore, from other forms of allergic manifestation. Samter and Beers suggest that non-immunological mechanisms are responsible, and point out that the substances which induce aspirin-like symptoms in hypersensitive patients have one characteristic in commonnamely, that they are strong minor analgesics. There is considerable evidence that " pain " receptors are chemoreceptors4 and that bradykinin and related peptides are the mediators which stimulate them. It is also known 4 that aspirin and similar analgesic compounds antagonise the effects of bradykinin peripherally; and this may be at least partly responsible for their analgesic action. Possibly, as Samter and Beers suggest, in the aspirin-hypersensitivity state there is increased responsiveness of chemoreceptors in the nasal and bronchial mucous membranes to a variety of these peptides and their therapeutic antagonists. The most important practical feature of this condition is that it cannot be predicted by skin tests but only by the clinical history; and patients with a warning history must be strongly enjoined not to take aspirin in any of its many forms. CANCER IN CATS AND DOGS
SPONTANEOUS cancers in the dog and cat, domestic animals that face many of the hazards of men’s lives as well as those of their own, have often been recorded 5 6; but not much is known about the total impact of cancer on these animals. Attempts at estimates have been based on attendance at veterinary clinics, on studies of impounded 4.
5. 6.
Lim, R. K. S. Proceedings of the 3rd International Pharmacological Meeting, Sao Paulo, 1966; vol. IX. Oxford, 1968. Mulligan, R. M. Neoplasms of the Dog. Baltimore, 1949. Ann. N.Y. Acad. Sci. 1963, 108, 619.