Biomedical subjects
C D May
Publications and source records attributed to C D May.
Studies of hypersensitivity reactions to foods in infants and children.
In order to extend previous investigations of adverse reactions to foods performed at this institution, 68 children, aged 5 mo to 15 yr, were studied. All subjects reported a history of adverse reaction to ingestion of one or more of the 14 foods under study. Sixteen of 43 subjects, 3 yr of age or older, had 22 adverse reactions during 94 food challenges with one or more of the 14 foods. All reactions confirmed were to peanut or other nuts, milk, egg, and soy. Skin testing with 1:20 weight/volume concentrations of food extracts applied by the puncture technique produced a net wheal reaction 3 mm or greater in all subjects 3 yr of age or older in whom double-blind food challenges confirmed the history of adverse reaction. Thirteen of 25 children less than 3 yr of age manifested adverse reactions during 49 food challenges. Skin testing by puncture technique produced a net wheal 3 mm or greater in 9 children less than 3 yr of age in whom food challenge elicited a clinical response within 2 hr. One of 4 subjects less than 3 yr of age in whom the adverse reaction occurred more than 4 hr after food challenge exhibited a wheal to puncture skin test of 3 mm or greater. These studies suggest that at present double-blind food challenge is an indispensible tool for the unequivocal evaluation of adverse reactions to foods.
Appraisal of skin tests with food extracts for diagnosis of food hypersensitivity.
Seventy-six children aged 5 months to 15 years who exhibited a net weal of 3.0 mm or greater to a puncture skin test with one or more of fourteen foods were subjected to double-blind food challenge. Confirmed reactions to double-blind food challenge were found to occur only with peanut, milk, egg and soybean. Puncture skin tests with 1:20 w/v concentration of food extracts identified all subjects who exhibited an adverse reaction during the double-blind food challenge. Performance of intradermal skin tests did not identify any additional subjects who reacted clinically to double-blind food challenge.
A modern clinical approach to food hypersensitivity.
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Proper use of skin tests with food extracts in diagnosis of hypersensitivity to food in children.
This study was undertaken to determine the proper use of skin tests with food extracts in diagnosis of hypersensitivity to food in children. Cutaneous reactions evoked by graded amounts of food extracts were compared with results of double-blind food challenge and in vitro release of histamine from leucocytes. A 3 mm or greater weal reaction in skin tests by puncture technique using food extracts of 1:20 w/v concentration was found to indicate the degree of hypersensitivity likely to be associated with clinically significant hypersensitivity reactions to food. Proper use of this simple technique will facilitate accurate diagnosis of food hypersensitivity in children by identifying the group among whom all positive reactions to food challenges will be found. Nevertheless, double-blind food challenge is essential to establish a diagnosis of symptomatic hypersensitivity to food.
A study of serum antibodies to isolated milk proteins and ovalbumin in infants and children.
Serum antibodies to cow milk proteins and ovalbumin were measured quantitatively. Food hypersensitivity of the immediate type was determined to be present or absent by skin tests and double-blind food challenges. Elevated levels of antibodies to milk proteins in sera characteristic of infants fed cow milk were found to decline with age, so that sera from children who were 6 to 15 years of age (inclusive), not hypersensitive to food, had significantly lower levels than the infants. In contrast, sera from age-matched children, who were shown to have hypersensitivity to some food, were found to have levels of antibodies to milk proteins as elevated as in infancy. Hypersensitivity was not necessarily to milk but often to some other food. This persistence of greater antibody production to milk throughout childhood in those hypersensitive to some food indicates a fundamental difference from those without hypersensitivity to food, either in permeability, in immunological reactivity of the gut or in development of immunological unresponsiveness. Implications for pathogenesis of clinical disorders are discussed.
High spontaneous release of histamine in vitro from leukocytes of persons hypersensitive to food.
In vitro studies of antigenic release of histamine from peripheral leukocytes (basophils) have been done in more than 600 allergic children. Ordinarily only about 5% to 10% of the histamine content of leukocytes will leak out or be released "spontaneously" during incubation of suspensions in vitro, without the addition of antigen. A small percentage of children were found to have leukocytes that released 25% to 100% of the histamine content spontaneously during incubation. The significance of this was not apparent until recently, when studies were concentrated on children suspected of hypersensitivity reactions to foods, among whom a much greater prevalence of spontaneous histamine release from leukocytes was encountered. Of children proved by a double-blind food challenge to react with manifestations of immediate hypersensitivity, 100% had leukocytes that consistently released over 25% (usually between 50% and 100%) of the histamine content spontaneously without the addition of antigen. Such high spontaneous histamine release appears to be characteristic of persons with clinical evidence of hypersensitivity to food.
Objective clinical and laboratory studies of immediate hypersensitivity reactions to foods in asthmatic children.
Clinical and laboratory observations were made with 38 children afflicted with chronic severe asthma (reversible obstructive airway disease) in which hypersensitivity to food was incriminated in the histories. Symptoms were evoked in double-blind food challenges in only 11/38 children and 14/70 challenges, and were characteristic of immediate-type hypersensitivity and were chiefly gastrointestinal, even though asthma was the common presenting complaint. There were no delayed reactions. Peanut was responsible for 8 reactions, egg for 5, and cow's milk for 1. The feature that most successfully identified those having positive reactions in challenges was a significant wheal reaction in a skin test by puncture technique using a verified extract of 1:20 W/V concentration. No subject with clinically significant, symptomatic hypersensitivity to food had a negative puncture test, and puncture tests were positive in only 10/56 instances of negative reactions in food challenges. Laboratory observations included release of histamine and enzymes from leukocytes and the levels of neutrophil enzymes in serum before and after food provocation tests. While these determinations were of interest with respect to the immunochemical basis of reactions to foods, they did not prove useful for practical clinical diagnosis. The outstanding laboratory findings was the occurrence of "spontaneous" release of 25% to 100% of the histamine from leukocytes in all cases proved clinically hypersensitive by food challenges, which suggests that this may be an indicator of immediate-type hypersensitivity to food. From the findings in the study, a general approach to food hypersensitivity was developed in which the immunologic components coupled with quantitative concentration-response relationships serve to render comprehensible the distinction between asymptomatic (immunologic) hypersensitivity and symptomatic (clinical) hypersensitivity.
Lack of interference in skin tests by histamine in food extracts.
Because histamine occurs naturally in some food products, quantitative analysis of the histamine content of extracts of food used for skin testing seemed desirable to determine its effect in the production of positive reactions. Up to 200 nanograms of histamine per milliliter were found in some food extracts. When the extracts are diluted to 1:100 and 1:1000 W/V for skin testing the amount of histamine which would be injected in a intradermal skin test is one-thousandth of the amount required to produce a significant wheal. Therefore the histamine content of the foods analyzed is too small to be of practical concern and not enough to give nonspecific wheal reactions in intradermal tests using extracts of 1/1000 or 1/100 W/V concentrations. Nonspecific reactions in skin tests are probably most often due to use of food extracts of unnecessarily high concentration.
Food allergy: a commentary.
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Treatment of allergic disorders with injections of allergen extracts.
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