A pediatric randomized, controlled trial of German cockroach subcutaneous immunotherapy.

BACKGROUND: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children. OBJECTIVE: To determine if nasal allergen challenge (NAC) responses to cockroach allergen would improve following one year of SCIT. METHODS: Urban children with asthma, that were cockroach-sensitized and reactive on NAC, participated in a yearlong randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean total nasal symptoms scores (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test (SPT) wheal size, serum allergen-specific antibody production and T-cell responses to cockroach allergen were assessed. RESULTS: Changes in mean NAC TNSS did not differ between SCIT-assigned (n=28) versus placebo-assigned (n=29) participants (p=0.63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum specific IgE (sIgE) decreased to a similar extent in both groups, while decreased cockroach SPT wheal size was greater among SCIT participants (p=0.04). A 200-fold increase in cockroach sIgG4 was observed among subjects receiving SCIT (p<0.001) but was unchanged in the placebo group. T-cell interleukin-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (p=0.002), while no effect was observed for interleukin-10 or interferon-gamma. CONCLUSION: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum sIgG4 production and down-modulation of allergen stimulated T-cell responses.

IgE, but not IgG4, antibodies to Ara h 2 distinguish peanut allergy from asymptomatic peanut sensitization.

BACKGROUND: There are no available clinical tests that can accurately predict peanut allergy (PA) and/or anaphylaxis. This study is aimed at evaluating whether the component-resolved diagnostic (CRD) IgE and IgG4 tests can (i) distinguish PA from asymptomatic peanut sensitization (PS) and (ii) differentiate anaphylactic from nonanaphylactic PA. METHODS: This study included 20 nonatopic controls, 58 asymptomatically peanut-sensitized children, 55 nonanaphylactic, and 53 anaphylactic PA cases from the Chicago Food Allergy Study. IgE and IgG4 to 103 allergens were measured using the ImmunoCAP ISAC technology and were compared among each group of children. The random forest test was applied to estimate each allergen's ability to predict PA and/or peanut anaphylaxis. RESULTS: Peanut allergy cases (with or without anaphylaxis) had significantly higher IgE reactivity to Ara h 1-3 (peanut allergens) and Gly m 5-6 (soy allergens) than asymptomatically sensitized children (P < 0.00001). Similar but more modest relationships were found for IgG4 to Ara h 2 (P < 0.01). IgE to Ara h 2 was the major contributor to accurate discrimination between PA and asymptomatic sensitization. With an optimal cutoff point of 0.65 ISU-E, it conferred 99.1% sensitivity, 98.3% specificity, and a 1.2% misclassification rate in the prediction of PA, which represented a higher discriminative accuracy than IgE to whole peanut extract (P = 0.008). However, none of the IgE and/or IgG4 tests could significantly differentiate peanut anaphylaxis from nonanaphylactic PA. CONCLUSIONS: IgE to Ara h 2 can efficiently differentiate clinical PA from asymptomatic PS, which may represent a major step forward in the diagnosis of PA.

African ancestry, early life exposures, and respiratory morbidity in early childhood.

BACKGROUND: Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. OBJECTIVE: To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. METHODS: We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. RESULTS: Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02-1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19-1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14-1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05-1.34) and European ancestry (OR: 0.84, 95% CI: 0.74-0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (OR(whites) : 0.31, 95% CI: 0.09-1.14; OR(hispanic) : 0.47, 95% CI: 0.20-1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. CONCLUSIONS AND CLINICAL RELEVANCE: In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to evaluate wheezing disparities and a proxy for differentially distributed genetic and early life risk factors associated with childhood recurrent wheezing.

Gene-vitamin D interactions on food sensitization: a prospective birth cohort study.

BACKGROUND: It has been hypothesized that vitamin D deficiency (VDD) contributes to the development of food sensitization (FS) and then food allergy. However, the epidemiological evidence is conflicting. We aim to examine whether cord blood VDD is associated with FS and whether such association can be modified by genetic variants in a prospective birth cohort. METHODS: This study included 649 children who were enrolled at birth and followed from birth onward at the Boston Medical Center. We defined VDD as cord blood 25(OH)D < 11 ng/ml, and FS as specific IgE ≥ 0.35 kUA/l to any of eight common food allergens in early childhood. We genotyped potentially functional single-nucleotide polymorphisms (SNPs) in 11 genes known to be involved in regulating IgE and 25(OH)D concentrations. Logistic regressions were used to test the effects of VDD on FS individually and jointly with SNPs. RESULTS: Among the 649 children, 44% had VDD and 37% had FS. When examined alone, VDD was not associated with FS. When examined jointly with SNPs, a significant interaction between IL4 gene polymorphism (rs2243250) and VDD (p(interaction) = 0.003, p(FDR) = 0.10) was found: VDD increased the risk of FS among children carrying CC/CT genotypes (OR = 1.79, 95%CI: 1.15-2.77). Similar but weaker interactions were observed for SNPs in MS4A2 (rs512555), FCER1G (rs2070901), and CYP24A1 (rs2762934). When all four SNPs were simultaneously considered, a strong gene-VDD interaction was evident (p(interaction) = 9 × 10(-6) ). CONCLUSIONS: Our data demonstrate that VDD may increase the risk of FS among individuals with certain genotypes, providing evidence of gene-vitamin D interaction on FS.

Association between short sleep duration and the risk of sensitization to food and aero allergens in rural Chinese adolescents.

BACKGROUND: Both long and short sleep duration have been associated with obesity, cardiovascular disease, and diabetes. However, there have been no previous studies investigating the potential relationship between altered sleep duration and allergen sensitization. OBJECTIVE: To explore the association between sleep duration and sensitization to food and aeroallergens. METHODS: This study includes 1534 rural Chinese adolescent twins aged 12-21 years who completed standard sleep questionnaires and skin prick tests (SPTs) to nine food and five aeroallergens. Total sleep time was defined as the interval from bedtime to wake-up time minus sleep latency. Sensitization was defined as having at least one positive SPT. RESULTS: Compared with individuals with the highest (third) tertile of sleep duration, those who slept less were more likely to be sensitized to any food allergen with odds ratios (ORs) of 1.9 [95% confidence interval (CI): 1.3-2.7] and 1.4 (95% CI: 1.0-1.9) for the first and second tertiles (trend test P(trend)=3×10(-4)), respectively. The corresponding ORs for sensitization to any aeroallergen were 1.5 (95% CI: 1.1-2.0) and 1.3 (95% CI: 1.0-1.7) (P(trend)=8×10(-3)). These associations were independent of percent body fat. In addition, we observed a significant dose-response association between the number of positive SPTs and percentage of shortest sleep duration (first tertile) (P(trend)=1×10(-3)). CONCLUSIONS AND CLINICAL RELEVANCE: In this sample of relatively lean rural Chinese adolescents, we found that short sleep duration was associated with increasing risk of sensitization to food and aeroallergens, independent of percent body fat. Longitudinal studies are needed to further determine the temporal and causal relationships. If short sleep duration indeed is one of the risk factors for allergic sensitization, the global burden of allergic diseases could be dramatically reduced by providing appropriate guidance on sleep duration for youth.

Allergen-specific IgE as a biomarker of exposure plus sensitization in inner-city adolescents with asthma.

BACKGROUND: Relationships among allergen-specific IgE levels, allergen exposure and asthma severity are poorly understood since sensitization has previously been evaluated as a dichotomous, rather than continuous characteristic. METHODS: Five hundred and forty-six inner-city adolescents enrolled in the Asthma Control Evaluation study underwent exhaled nitric oxide (FE(NO)) measurement, lung function testing, and completion of a questionnaire. Allergen-specific IgE levels and blood eosinophils were quantified. Dust samples were collected from the participants' bedrooms for quantification of allergen concentrations. Participants were followed for 12 months and clinical outcomes were tracked. RESULTS: Among sensitized participants, allergen-specific IgE levels were correlated with the corresponding settled dust allergen levels for cockroach, dust mite, and mouse (r = 0.38, 0.34, 0.19, respectively; P < 0.0001 for cockroach and dust mite and P = 0.03 for mouse), but not cat (r = -0.02, P = 0.71). Higher cockroach-, mite-, mouse-, and cat-specific IgE levels were associated with higher FE(NO) concentrations, poorer lung function, and higher blood eosinophils. Higher cat, dust mite, and mouse allergen-specific IgE levels were also associated with an increasing risk of exacerbations or hospitalization. CONCLUSIONS: Allergen-specific IgE levels were correlated with allergen exposure among sensitized participants, except for cat. Allergen-specific IgE levels were also associated with more severe asthma across a range of clinical and biologic markers. Adjusting for exposure did not provide additional predictive value, suggesting that higher allergen-specific IgE levels may be indicative of both higher exposure and a greater degree of sensitization, which in turn may result in greater asthma severity.

Genetic and environmental contributions to allergen sensitization in a Chinese twin study.

BACKGROUND: Allergic disease is on the rise worldwide. Effective prevention of allergic disease requires comprehensive understanding of the factors that contribute to its intermediate phenotypes, such as sensitization to common allergens. OBJECTIVE: To estimate the degree of genetic and environmental contributions to sensitization to food and aeroallergens. METHODS: Sensitization was defined as a positive skin prick test to an allergen. We calculated the zygosity-specific concordance rates and odds ratios (ORs) for sensitization to food and aeroallergens in 826 Chinese twin pairs [472 monozygotic (MZ) and 354 dizygotic (DZ)] aged 12-28 years. We also applied structural equation modelling procedures to estimate genetic and environmental influences on sensitization. RESULTS: The concordance rates and risk of sensitization in one twin given the presence vs. the absence of sensitization in the other twin were higher in MZ twins than those in DZ twins. However, a large number of MZ twins were discordant in sensitization to common allergens. These observations suggest both genetic and environmental factors influence sensitization. Consistently, the estimated heritability and individual environmental components of the liability to sensitization ranged from 0.51 to 0.68 and 0.32 to 0.49, respectively, based on the best-fitted structural equation model. We also observed high phenotypic correlations between sensitization to two aeroallergens (cockroach and dust mite: 0.83) and two food allergens (peanut and shellfish: 0.58), but only moderate correlations for the pairs between sensitization to a food and an aeroallergen (0.31-0.46). The shared genetic and environmental factors between paired sensitizations contribute to the observed correlations. CONCLUSION: We demonstrated that sensitization to common food and aeroallergens were influenced by both genetic and environmental factors. Moreover, we found that paired allergen sensitizations might share some common sets of genes and environmental factors. This study underscores the need to further delineate unique and/or pleiotropic genetic and environmental factors for allergen sensitization.

Food allergy is associated with an increased risk of asthma.

BACKGROUND: The atopic march is well documented, but the interrelationship of food allergy (FA) and asthma is not well understood. OBJECTIVE: The aim of this study was to examine the strength of the association and temporal relationships between FA and asthma. METHODS: This analysis included 271 children >or=6 years (older group) and 296 children <6 years (younger group) from a family-based FA cohort in Chicago, IL. Asthma was determined by parental report of physician diagnosis. FA status was determined based on the type and timing of clinical symptoms after ingestion of a specific food, and results of prick skin test (Multi-Test II) and allergen-specific IgE (Phadia ImmunoCAP). Analyses were carried out using logistic regression accounting for important covariates and auto-correlations among siblings. Kaplan-Meier curves were used to compare the time to onset of asthma with the FA status. RESULTS: Symptomatic FA was associated with asthma in both older [odds ratio (OR)=4.9, 95% confidence interval (CI): 2.5-9.5] and younger children (OR=5.3, 95% CI: 1.7-16.2). The association was stronger among children with multiple or severe food allergies, especially in older children. Children with FA developed asthma earlier and at higher prevalence than children without FA (Cox proportional hazard ratio=3.7, 95% CI: 2.2-6.3 for children >or=6 years, and hazard ratio=3.3, 95% CI: 1.1-10 for children <6 years of age). No associations were seen between asymptomatic food sensitization and asthma. CONCLUSIONS: Independent of markers of atopy such as aeroallergen sensitization and family history of asthma, there was a significant association between FA and asthma. This association was even stronger in subjects with multiple food allergies or severe FA.

Familial aggregation of food allergy and sensitization to food allergens: a family-based study.

BACKGROUND: The increasing prevalence of food allergy (FA) is a growing clinical and public health problem. The contribution of genetic factors to FA remains largely unknown. OBJECTIVE: This study examined the pattern of familial aggregation and the degree to which genetic factors contribute to FA and sensitization to food allergens. METHODS: This study included 581 nuclear families (2,004 subjects) as part of an ongoing FA study in Chicago, IL, USA. FA was defined by a set of criteria including timing, clinical symptoms obtained via standardized questionnaire interview and corroborative specific IgE cut-offs for > or =95% positive predictive value (PPV) for food allergens measured by Phadia ImmunoCAP. Familial aggregation of FA as well as sensitization to food allergens was examined using generalized estimating equation (GEE) models, with adjustment for important covariates including age, gender, ethnicity and birth order. Heritability was estimated for food-specific IgE measurements. RESULTS: FA in the index child was a significant and independent predictor of FA in other siblings (OR=2.6, 95% CI: 1.2-5.6, P=0.01). There were significant and positive associations among family members (father-offspring, mother-offspring, index-other siblings) for total IgE and specific IgE to all the nine major food allergens tested in this sample (sesame, peanut, wheat, milk, egg white, soy, walnut, shrimp and cod fish). The estimated heritability of food-specific IgE ranged from 0.15 to 0.35 and was statistically significant for all the nine tested food allergens. CONCLUSION: This family-based study demonstrates strong familial aggregation of FA and sensitization to food allergens, especially, among siblings. The heritability estimates indicate that food-specific IgE is likely influenced by both genetic and environmental factors. Together, this study provides strong evidence that both host genetic susceptibility and environmental factors determine the complex trait of IgE-mediated FA.

Biological potency of German cockroach allergen extracts determined in an inner city population.

BACKGROUND: Cockroach allergy is an important cause of inner city asthma. To perform valid studies on the diagnosis and treatment of cockroach allergy, biological potencies of test extracts need to be established, and a surrogate in vitro test for biological potency should be chosen. METHODS: Sixty-two cockroach-allergic adult subjects were recruited for quantitative skin testing with three commercial German cockroach extracts. The intradermal D50 values were determined using linear interpolation, and the biologic potencies were determined from D50 data. The extracts were also analysed for relative potency, using a competition ELISA, and for specific allergen content, using a two-site ELISA. RESULTS: Estimates of each extract's D50 were analysable in 48-55 subjects, with D50s between 10.3 and 11.8. All three extracts were bioequivalent using pre-set criteria. The biological potencies of the extracts were 1738-8570 bioequivalent allergy units (BAU)/mL (geometric mean=3300), and these relative potencies were similar to those estimated by competition ELISA and specific allergen content. IgE against cockroach allergens were detected in sera from 34 subjects with analysable D50s, and 17 subjects had IgE directed against specific cockroach allergens. Although the presence of anti-Bla g 5 correlated with the subjects' skin test responses for 2/3 extracts, no single allergen was immunodominant. Antibody responses among the subjects were heterogeneous. CONCLUSIONS: Although commercial cockroach extracts are relatively low in potency, immunotherapeutic doses should be achievable. Biological potency may be estimated using D50 testing, a combination of specific allergen determinations, or by an overall potency assay such as the competition ELISA. CAPSULE SUMMARY: The biological potency of three German cockroach allergen extracts, determined in an inner city population, was 1738-8570 BAU/mL. No one allergen was immunodominant, and surrogate in vitro testing methods were examined.

Allergy evaluation and immunotherapy.

Up to 10% of children and adolescents in the United States may have asthma and up to 40% may be affected by allergic rhinitis. Most people know that asthma is a serious disease, but "hay fever" is often mistakenly considered trivial. However, hay fever symptoms can significantly influence a patient's quality of life, causing fatigue, headache, and even cognitive impairment. Both asthma and allergic rhinitis can result in lost sleep, many missed school days, and the inability to participate in sports and other recreational activities in which young people engage. An appropriate diagnosis is the first step toward improving quality of life for these young patients. This article reviews diagnostic procedures for allergic disease, and-because compliance is frequently an issue with school-aged patients-it also reviews current thinking on allergen immunotherapy, a treatment that provides effective long-term control in appropriately selected patients.

Asthma medications and how to use them.

Aerosolized medications for the treatment of asthma are now considered to be the delivery system of choice. Despite their popularity, traditional pressurized metered dose inhalers are associated with a variety of drawbacks. This article reviews the aerosolized drug delivery systems currently available, along with their advantages and disadvantages. Patient technique in the use of these agents is addressed. Special considerations in children and the elderly are discussed, with specific recommendations tailored to these age groups, followed by practical suggestions for general inhaler use.

[Chrome, nickel and manganese in stainless steel cooking utensils and legal regulations]. / Krom, nikal i mangan u posudu od nehrdajuceg celika i zakonski propisi.

Assaying chromium nickel and manganese for specific migrations with a 4%-acetic acid under specific time and temperature related conditions is an obligatory part of the hygienic safety surveillance. Routine surveillance of a larger number of imported cooking utensils has shown the specific migrations to be more or less above the maximum allowances for chromium and/or nickel, and less frequently so for manganese. Further tests with repeated extraction, however, revealed that the levels of all three metals in most of the unfit samples were within the allowed limits. With respect to our findings, and to a longer period of use of the cooking utensils, amendments to the current regulations demanding obligatory testing after repeated extraction seem justified.

Do latex precautions in children with myelodysplasia reduce intraoperative allergic reactions?

Children with myelodysplasia have an increased incidence of latex allergy, which can lead to severe intraoperative allergic reactions. Despite widespread recommendations to avoid intraoperative latex exposure, little evidence exists to support the efficacy of this practice. We examined the incidence of intraoperative allergic reactions in children with myelodysplasia who underwent 1,025 operations in a 36-month period before and after institution of a standardized latex-avoidance protocol. Risk factors for an intraoperative reaction were found to be a history of latex allergy (p = 0.001) and surgery performed before institution of the latex-avoidance protocol (p = 0.01). The estimate of increased risk for allergic reaction was 3.09 times higher in cases performed without latex avoidance. Recognized violation of the protocol after its institution led to severe allergic reactions in three patients. Our experience suggests that a latex-avoidance protocol reduces intraoperative allergic reactions in children with myelodysplasia. Development of severe allergic reactions with violation of the protocol reinforces the importance of vigilance on the part of all operating room personnel in its implementation.

Lead poisoning associated with the use of Ayurvedic metal-mineral tonics.

OBJECTIVE: The aim of this study was to confirm the connection between lead poisoning and the use of traditional Ayurvedic metal mineral tonics. METHODS: The study group comprised 29 subjects (26 adults and three children) who had previously taken Ayurvedic metal mineral tonics. All subjects were tested for lead absorption by blood lead, erythrocyte delta-aminolevulinic acid dehydratase activity and erythrocyte protoporphyrin. RESULTS: Eighteen samples of Ayurvedic preparations were obtained from 15 subjects and analyzed for lead content. Five adult subjects with established lead poisoning received chelation therapy. In Ayurvedic preparations a wide range of lead content was found (0.9-72,990 micrograms Pb/g; 0.35-29,900 micrograms Pb/capsule or tablet). The blood lead, erythrocyte delta-aminolevulinic acid dehydratase and erythrocyte protoporphyrin of the subjects, grouped according to the remedies used, correlated with the lead content in the preparations (p < 0.001). Chelation therapy was successful in normalization of laboratory findings and clinical recovery. CONCLUSION: Ayurvedic metal-mineral tonics are again identified as a potential source of high lead. The import of such tonics should be strictly controlled.

A follow-up study in a lead smelter community following the introduction of an effective pollution control system.

A follow-up study using biological and environmental monitoring was performed in a lead smelter community to assess the health risk of inhabitants and to establish how long it takes after the introduction of an effective emission control system to declare a lead-contaminated area safe for normal living. In specific population groups (mothers and children) biological indicators of lead exposure and lead effect on hemoglobin synthesis were determined 2 years before and 11 consecutive years after the installation of bag filters. At the same time lead was monitored in the airborne and deposited particulates, in household dust and in soil. The results clearly show that the process of normalization is rather slow. The difference in blood lead and erythrocyte delta-aminolevulinic acid dehydratase between the exposed and control groups, even 12 years after bag filters installation, was still remarkable. It appears that soil, contaminated with lead from past exposure, is a major source of increased lead absorption in a population for many years.

A competitive kinin receptor antagonist, [DArg0, Hyp3, DPhe7]-bradykinin, does not affect the response to nasal provocation with bradykinin.

1. In two double-blind, placebo controlled studies, we tested the effects of intranasal administration of 500 micrograms of a competitive kinin receptor antagonist, [DArg0, Hyp3, DPhe7]-bradykinin (NPC 567), on the response to nasal provocation with 20 micrograms of bradykinin. Nasal lavage was performed before and after provocation, and subjects recorded symptom scores. Lavages were assayed for albumin and TAME-esterase activity (indicators of vascular permeability). 2. In our initial study, 12 subjects received NPC 567 or placebo 5 min before bradykinin. After placebo, bradykinin challenge resulted in values (mean +/- s.e. mean) for albumin, TAME-esterase activity and total symptom scores of 275 +/- 51 micrograms ml-1, 32.1 +/- 7.2 counts min-1 x 10(-3), and 1.8 +/- 0.5, respectively. After NPC 567, bradykinin challenge resulted in values of 317 +/- 99 micrograms ml-1, 31.4 +/- 6.9 counts min-1 x 10(-3), and 2.6 +/- 0.4 for these parameters. No significant difference was observed between placebo and drug treatment for any parameter. 3. To evaluate if the lack of drug effect was due to its enzymatic degradation prior to bradykinin administration, a second study was performed in which NPC 567 was coadministered with bradykinin (n = 8). After placebo-bradykinin challenge, values of 168 +/- 42 micrograms ml-1, 11.3 +/- 4.0 counts min-1 x 10(-3), and 2.8 +/- 0.6 were recorded for albumin, TAME-esterase activity, and symptom scores, respectively, while following NPC 567-bradykinin challenge, these values were 174 +/- 51 micrograms ml-1, 12.3 +/- 4.1 counts min-1 x 10(-3), and 3.1 +/- 0.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary calcium and blood lead levels in women.

Nutritional factors are known to influence metabolism and toxicity of several metals in animal experiments, but relevant human data are scarce and inconclusive. In this work, we tested the hypothesis that dietary calcium influences lead metabolism in humans. Blood lead concentrations were used as indicators of lead exposure and metabolism. Two groups of peasant women living in similar conditions in two different regions in Yugoslavia (100 in each) were chosen as subjects for this purpose. In region A, the dietary calcium intake was about 940 mg, and in region B about two times lower, i.e., 450 mg/day. The average blood lead concentration was significantly lower in women from region A (69 micrograms/L) than from region B (83 micrograms/L). Our results support the assumption that adequate calcium intake might be one of the preventive measures for decreasing lead absorption. This new evidence, sought for some time by nutritionists and toxicologists, needs further international confirmation.

Pharmacology of nasal provocation with bradykinin: studies of tachyphylaxis, cyclooxygenase inhibition, alpha-adrenergic stimulation, and receptor subtype.

We have evaluated mechanisms by which nasal provocation with bradykinin may induce symptoms of rhinitis. Repeated nasal challenges with 100 micrograms of bradykinin led to reproducible increases in symptoms and in vascular permeability. Premedication with aspirin did not alter bradykinin-induced responses. Topical application of the alpha-adrenergic agonist oxymetazoline significantly reduced bradykinin-induced subjective nasal congestion scores, but did not lead to a significant decrease in total symptoms or in vascular permeability. Finally, the B1 kinin receptor agonist des-Arg9-bradykinin (1 mg) was totally ineffective in inducing symptoms or increasing vascular permeability. Thus, nasal provocation with bradykinin leads to induction of symptoms and increased vascular permeability, presumably via stimulation of B2 kinin receptors, and is not dependent on prostanoid generation.