Robert N. Hamburger

Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: A randomized study

The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally randomized, controlled trial of infants of atopic parents. The diet of the prophylactic-treated group (N = 103) included (1) maternal avoidance of cows milk, egg, and peanut during the third trimester of pregnancy and lactation and (2) infant use of casein hydrolysate (Nutramigen) for supplementation or weaning, and avoidance of solid foods for 6 months; cows milk, corn, soy, citrus, and wheat, for 12 months; and egg, peanut, and fish, for 24 months. In the control group (N = 185), mothers had unrestricted diets, and infants followed American Academy of Pediatrics feeding guidelines. The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated (16.2%) compared to the control (27.1%) group (p = 0.039), resulting from reduced food-associated atopic dermatitis, urticaria and/or gastrointestinal disease by 12 months (5.1% versus 16.4%; p = 0.007), and any positive food skin test by 24 months (16.5% versus 29.4%; p = 0.019), caused primarily by fewer positive milk skin tests (1% versus 12.4%; p = 0.001). The prevalences of allergic rhinitis, asthma, and inhalant skin tests were unaffected. Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months. Thus, reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life.

Genetic and environmental factors affecting the development of atopy through age 4 in children of atopic parents: a prospective randomized study of food allergen avoidance

The effect of food allergen avoidance, as well as other environmental and genetic factors, on the development of atopy were determined in this follow‐up report of a prospective randomized controlled study of 288 infants of atopic parents, in which 78% were available for evaluation at age 4 years. The prophylactictreated group consisted of mothers who avoided cow milk. egg. and peanut during the last trimester of pregnancy and lactation and of infants who avoided cow milk until 1 year (casein hydrolysate supplementation prior to 1 year) and egg, peanut, and fish until after 2 years. The control group consisted of maternal/infant pairs who followed standard feeding practices. The cumulative prevalence of food allergy and food sensitization remained lower in the prophylactic treated group from 1 to 4 years of age. However, the period (current) prevalence of food allergy in both study groups was similar (about 5%) at 3 and 4 years. Such findings suggest that period prevalence may represent the more appropriate measure to assess the impact of intervention measures on the development of atopic disease at older ages. Prophylactic‐treated children evidenced lower levels of IgG beta lacloglobulin (BLG) at 4 months and I and 2 years (p < 0.0001) and lower IgG ovalbumen/ovomucoid (OVA) levels only at 2 years (p < 0.001). Both groups evidenced similar prevalences of asthma, allergic rhinitis, and positive inhalant skin tests from birth to 4 years. Children with food allergy evidenced higher 4 year cumulative prevalences of allergic rhinitis and asthma (p < 0.05). Risk factors for atopic disease by age 4 years were shown by multivariate analysis (p < 0.05) to include (1) unrestricted diet and elevated cord blood IgE with food allergy, (2) male gender and lower paternal level of education with asthma, and (3) non‐caucasian ethnicity and spring/summer birth with atopic dermatitis and allergic rhinitis. Serum IgE levels were not significantly different between groups at 3 and 4 years, despite their being a trend towards lower serum IgE levels in the prophylactic‐treated group at 4 months (p < 0.07). In the control group, formula feeding prior to 4 months was associated with higher 4 month serum IgE levels (p < 0.05). Stepwise linear regression revealed that serum IgE variability from birth to 4 years was influenced by male gender, non‐caucasian ethnicity, maternal and paternal serum IgE levels, 4 month IgG BLG levels, positive food and inhalant skin tests, and the development of atopic dermatitis, food allergy, asthma, and allergic rhinitis. These findings demonstrate the strength of genetic factors and their modulation by dietary and envi‐ronmental influences in the development of atopy and reveal that the reduction in food allergy in infancy by maternal/infant food allergen avoidance fails to affect respiratory allergy development from birth to 4 years.

Genetics of IgE and allergy: Serum IgE levels in twins

Abstract Serum IgE levels are an important risk factor in allergic disease resulting from immediate-type hypersensitivity. IgE levels of middle-aged male monozygous twins (54 pairs) and dizygous twins (39 pairs) were measured and a significant genetic effect on IgE levels was observed (H = 0.592). A significant genetic effect was also noted in twin children (H = 0.789). The statistical relationship between IgE levels and atopic disease, as well as aspects of the methods of analysis of twin data, is discussed.

Anaphylaxis-like reactions to corticosteroid therapy.

Abstract This is a report of a 17-year-old male patient with a history of reactions characterized by the precipitous onset of urticaria, angioedema, and increased bronchospasm following therapy for status asthmaticus with either Solu-Medrol or Solu-Cortef. Intravenous challenge with 40 mg. of Solu-Medrol and methylprednisolone sodium succinate and oral challenge with 40 mg. of methylprednisolone produced dramatic confirmation of his history within 2, 11, and 35 minutes, respectively. Intravenous challenge with 4 mg. of Solu-Medrol and methylprednisolone sodium succinate, and oral challenges with 40 mg. of prednisolone and prednisone and 6 mg. of dexamethasone produced no adverse reactions. Direct skin testing revealed positive immediate reactions to pure methylprednisolone and hydrocortisone, whereas on passive transfer these reactions were negative for 4 and 48 hours. Negative skin test reactions were obtained to Solu-Medrol, methylprednisolone sodium succinate, methylprednisolone sodium acetate, prednisolone, prednisone, triamcinolone, dexamethasone, Solu-Cortef, hyrocortisone sodium succinate, and cortisone actate. Serial measurements during two intravenous challenges which produced anaphylaxis revealed no significant changes in 6 components of the complement system, fibrinogen, or the presence of split products.

Standardization and stability of immunoglobulin E (IgE)

Abstract World Health Organization Reference Standard 68·341 for immunoglobulin E (IgE) was found to contain 2.42 ng. per unit relative to purified myeloma IgE. IgE is relatively stable under various conditions of storage and processing.

Serum IgE in patients with minimal-change nephrotic syndrome

Serum levels of IgE were studied in 53 children; 17 children had minimal-change nephrotic syndrome, 9 had probable MCNS, and 27 had other renal diseases. These studies showed higher levels of IgE in patients with MCNS and probable MCNS than in the renal control subjects or in the general population. Patients with MCNS who received therapy with cyclophosphamide had lower levels of IgE than those who did not.

Ige and cardiovascular disease: Results from a population-based study

Because previous reports have suggested that IgE-mediated events may lead to both platelet activation and arterial spasm, a population-based study of 262 men and 315 women, aged 38 to 82, was conducted to investigate the association of serum IgE levels with myocardial infarction, stroke, and noninvasively diagnosed large-vessel peripheral arterial disease. In men with previous myocardial infarction, previous stroke, or current large-vessel peripheral arterial disease, geometric mean serum IgE levels were increased 119 percent, 164 percent, and 78 percent, respectively. These associations were statistically significant (p less than 0.05). Because IgE was positively or inversely correlated with several traditional cardiovascular disease risk factors, logistic regression was used to evaluate the independent association of IgE with any cardiovascular disease (myocardial infarction, stroke, or large-vessel peripheral arterial disease). In a model including age, cigarette smoking, fasting plasma glucose level, diastolic blood pressure, and low-density lipoprotein cholesterol level as covariates, IgE was positively and independently associated with any cardiovascular disease (p = 0.03). Similar evaluations in women revealed no correlation between IgE and cardiovascular disease by either univariate or multivariable analysis. These data indicate that IgE may be an independent marker for cardiovascular disease in men, and thus suggest IgE-mediated events may play a role in the pathogenesis of cardiovascular disease.

Cellular immunity and the hypothalamic-pituitary axis in major affective disorder: A preliminary study

To assess cellular immune status and the hypothalamic-pituitary axis in patients with major depression, we examined peripheral blood mononuclear cells and measured the plasma levels of four neurohormones. Eleven patients with major depression had increased % of T4 lymphocytes and decreased concanavalin (Con A) stimulated T lymphocyte proliferation when compared with 11 age-, sex-, and race-matched control subjects. Percent of total lymphocytes labeled as all T lymphocytes, all B lymphocytes, and natural killer cells did not differ in the two groups, nor did mitogen-induced interleukin-2 production. These findings support theories of interaction between depression and immune cell function.

Severe Cow's Milk Induced Colitis In an Exclusively Breast-fed Neonate Case Report and Clinical Review of Cow's Milk Allergy

Cows milk induced eosinophilic colitis presenting in the first week of life has been reported, but is very rare. The authors describe a 4-day-old female infant who presented with profuse rectal bleeding resulting in a hematocrit fall from 38% to 30% within 8 hr after hospital admission. Sigmoidoscopy revealed colonic mucosa that was red, edematous, and friable, with punctate hemorrhages. Rectal biopsy showed marked eosinophilic infiltration with multifocal hemorrhage. Further history indicated that while the infant had been exclusively breast-fed since birth, the nursing mother had been drinking 4-5 glasses of cows milk per day since delivery. Prick puncture skin testing of the infant was positive for cows milk protein. A serum radioallergosorbent test (RAST) for cows milk protein was positive. The infants serum IgE was 1.5 IU/ml. Rectal bleeding resolved when the patient was given a casein hydrolysate formula (Nutramigen, Mead Johnson Nutrition, Evansville, IN), and endoscopy one week later showed improvement, with only scattered areas of erythema, and no friability. We conclude that since the infant was exclusively breast-fed, the milk protein must have passed into the breast milk antigenically intact. Prenatal sensitization probably occurred. Cows milk induced allergic colitis should be considered in the differential diagnosis of colitis in breast-fed neonates.

Mitogen-stimulated lymphocyte proliferation and pituitary hormones in major depression ☆

To assess cellular immune status and the hypothalamic-pituitary (HP) axis in patients with major depression, we examined peripheral blood mononuclear cells (PBMC) and measured the plasma levels of cortisol, adrenocorticotropin hormone (ACTH), growth hormone (GH), and prolactin (PRL). Twenty patients with major depression were compared with 20 control subjects matched for age, sex, and race. The dose-response curves for concanavalin-A (Con-A) and phytohemagglutinin (PHA) stimulation were not significantly different between the two groups. The patients had decreased Con-A-stimulated T-lymphocyte proliferation when compared to the control subjects, but only at the lowest suboptimal concentration of Con-A. None of the four concentrations of PHA-stimulated proliferation were different between the two groups, neither was PHA-induced interleukin-2 production. Within the patient group only, plasma prolactin (PRL) correlated significantly with stimulated lymphocyte proliferation using two optimal concentrations of PHA and one optimal concentration of Con-A, when the proliferation was expressed using the stimulation index.