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Established risk factors cannot explain all the variance in coronary heart disease (CHD). Immunoglobin E (IgE), a mediator of allergy, can affect platelets and arterial smooth muscle. We previously demonstrated a cross-sectional association between IgE and cardiovascular disease (CVD) in men. The present study evaluated this relationship prospectively in 278 men and 343 women followed for a mean of 8.9 years. There was an association between IgE and coronary disease in men, but not in women. There was no association for CVD, stroke, or all-cause mortality. The age-adjusted relative risk (RR) for coronary mortality in men with baseline IgE > or = 200 kU/L was 1.66 (p < or = 0.66), but for nonfatal myocardial infarction (MI) it was 6.46 (p < or = 0.01). This association was independent of smoking and other risk factors, and unrelated to allergy. Thus, elevated IgE was a strong independent prospective risk factor for nonfatal, but not fatal, MI in men.

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A new FDA-cleared product has been introduced for screening suspected allergic patients using a small blood sample. The QUIDEL Allergen Screens (AS) are simple to use dipstick tests that measure allergen-specific IgE to ten of the most important regional allergens. We compared the results obtained by prick-puncture skin testing (ST) to those obtained with the AS on 103 patients with allergic symptoms. Of the 103 patients studied, there were 67 with positive skin tests, and 57 of those were positive by AS and ten were AS negative. Of the 36 with negative skin tests, 2 were positive by AS and 34 were AS negative. Compared with ST, the AS results gave a sensitivity of 85% and a specificity of 94% for identifying the allergic patient. Of the ten patients positive by ST but negative by AS, five were ST positive at the 1+ level; the other five were repeatedly negative by AS and confirmed negative by RAST. On an allergen basis, the ST and AS methods showed an 85% agreement. A subset of 24 patients from the foregoing group was studied for total IgE and allergen-specific IgE with products from both Pharmacia (P) and QUIDEL (Q). In this group of patients, skin test results gave seven patients negative and 18 patients positive to one or more allergens. While the overall Total IgE results were higher for ST patients, the Total IgE results alone did not effectively discriminate between ST-positive and ST-negative patients. The allergen-specific, however, results by both methods showed excellent agreement with the ST results.(ABSTRACT TRUNCATED AT 250 WORDS)

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Age-adjusted geometric mean IgE levels in 621 older subjects were higher in men (26.3 kU/L) than in women (19.1 kU/L), and decreased with age. The higher levels in men were largely a result of a strong positive association with cigarette smoking. Among allergic conditions, a personal history of asthma was associated with the highest IgE levels. In multiple linear regression models in men, cigarette smoking was the single strongest correlate of IgE levels, while a personal history of allergy was the strongest correlate in women. Our results suggest important nonallergic as well as allergic determinants of IgE levels in populations.

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Cow's 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 cow's milk per day since delivery. Prick puncture skin testing of the infant was positive for cow's milk protein. A serum radioallergosorbent test (RAST) for cow's milk protein was positive. The infant's 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. Cow's milk induced allergic colitis should be considered in the differential diagnosis of colitis in breast-fed neonates.

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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 cow's 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; cow's 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.

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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.

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Cow's milk allergy in the first year of life is one of the most common problems faced by pediatricians. Both over and under diagnosis is seen. Cow's milk allergy, which is IgE-mediated should be differentiated from milk intolerance due to lactase deficiency or other causes. Cow's milk allergy may effect the gastrointestinal tract, respiratory tract, skin or blood. Anaphylaxis may occur. Diagnosis is made primarily on clinical grounds but skin tests and/or RAST are of value. Elimination and subsequent challenge confirms the diagnosis but challenge is not always necessary. Challenge should not be performed if there is evidence of anaphylaxis. Avoidance is the mainstay of treatment and breastfeeding is the optimal choice. Since antigenically intact cow's milk protein can pass into the breast milk, the mother should avoid excessive intake of milk products herself while breast feeding. Alternatives to breast milk such as soy formulas or hydrolysed casein or whey formulas may be used. Twenty-five percent of milk-sensitive infants are also allergic to soy protein. Hydrolysed casein formulas are more hypoallergenic but are expensive and less palatable. Hydrolysed whey formula, which is comparable in expense to soy formulas but is less allergenic, may prove of value in the management of the milk-allergic infant as well as for prophylaxis in infants from susceptible parents. Parents of infants born to families with bilateral atopic histories may be able to prevent milk allergy by using dietary manipulations which include decreased prenatal maternal milk intake and while breast feeding as well as careful avoidance of milk products in the infant's diet during the first year of life.

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To explore changes in immune cell status with changes in the hypothalamic-pituitary (HP) axis in 20 patients with major depression as compared with 20 age-, sex-, and race-matched control subjects, we examined peripheral blood mononuclear cells (PBMC) for total T-cells (T3), total B-cells (B1), two T-cell subsets (T4 and T8), and natural killer cells (NKH1), and we measured the plasma level of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin (PRL). The ratio of T4/T8 was increased in the patients. Within the group of control subjects only, increasing age correlated significantly with decreasing plasma PRL. Within the group of patients only, GH positively correlated significantly with T8 and NKH1, as did PRL with NKH1. No between-groups difference was found for T3, B1, T4, T8, NKH1, cortisol, ACTH, GH, or PRL.

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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.

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1. To assess the effect of age on cellular immune status and the HP axis in patients with major depression, we examined peripheral blood mononuclear cells (PBMC) and measured the plasma level of four neurohormones. 2. In 36 subjects, decreasing T lymphocyte response to con A covaried with age. Percent of lymphocytes labeled as T8 lymphocytes tended to decrease and T4/T8 ratio tended to increase with increasing age. 3. Hamilton and Beck scores were significantly different between the two sex and race matched groups of 18 depressed patients and 18 control subjects, and plasma prolactin was significantly higher in depressed subjects. 4. Increasing age correlated with decreasing T lymphocyte response to con A in the combined group of all subjects, and in the control group, but not in the patient group. 5. Hamilton and Beck scores correlated inversely with T lymphocytes response in the combined group of all subjects. 6. Differences in mitogen responsiveness between patient and control groups were not found, having been obscured by the effect of age. 7. These findings indicate the need to age match subjects when studying the interaction between depression and immune cell function.

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Over the past 7 years we have enrolled several hundred families in a study of the prophylaxis of atopic allergy. Initially, control and study patients were at different institutions, but more recently a true double-blind random assignment to control or study group has been instituted. Nevertheless, all of the infants from these highly atopic families can be utilized to obtain the data reported; that is, the rate of change of IgE levels, the appearance of food sensitization (food-specific IgE), the signs and symptoms of atopic allergy diseases and the changes in cow's milk-specific IgG antibody during the first 2 years of life. Some aspects of the first three of these parameters have been presented in the eight references to this paper, but only preliminary data on the use of IgG anti-cow's milk antibody as a measure of compliance has been available. In this paper an analysis is presented of the various patterns of IgG antibody levels in the first 60 infants of the over 200 who have been studied to date. Both the age of onset and the subsequent changes in the foregoing immunologic measurements provide fundamental data with which to measure the success rate of any prophylactic or therapeutic regimen and may improve our capacity to predict the future course of infants and children with a strong familial tendency to allergy.

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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.

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