ABSTRACT
BACKGROUND: Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. METHODS: We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis. RESULTS: Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies. CONCLUSIONS: Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.
Subject(s)
Genetic Association Studies , Hypersensitivity/genetics , Respiratory Sounds/genetics , Allergens/immunology , Asia , Asthma/genetics , Child , DNA-Binding Proteins/genetics , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics , Ecuador , Eczema/genetics , Europe , Gene Frequency/genetics , Guanine Nucleotide Exchange Factors/genetics , Humans , Hypersensitivity/blood , Hypersensitivity/immunology , Immunoglobulin E/blood , Immunoglobulin E/immunology , Interleukin-13/genetics , Interleukin-4 Receptor alpha Subunit/genetics , Linkage Disequilibrium/genetics , Lipopolysaccharide Receptors/genetics , New Zealand , Polymorphism, Single Nucleotide/genetics , Proteinase Inhibitory Proteins, Secretory/genetics , Receptors, IgE/genetics , Respiratory Sounds/immunology , Rhinitis, Allergic, Perennial/genetics , Rhinitis, Allergic, Seasonal/genetics , Serine Peptidase Inhibitor Kazal-Type 5 , Skin Tests , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/genetics , Toll-Like Receptor 9/genetics , Transcription Factors/genetics , Transforming Growth Factor beta1/genetics , Tumor Necrosis Factor-alpha/geneticsABSTRACT
OBJECTIVE: This study aimed to evaluate the adverse effects of extensively hydrolyzed milk formula on growth in infants and toddlers. METHODS: Prospectively, 45 infants and toddlers with a positive history of cow's milk allergy confirmed by positive skin prick test and high IgE levels for either alpha-lactalbumin, beta-lactoglobulin, or casein and positive single-blind food challenge received extensively hydrolyzed milk formulas for 1 year. Sex-normalized percentiles of heights and weights of infants and toddlers before their enrollment in the study were compared to those at the end of the study. The contribution of breastfeeding, early use of bottle feeding and intake of adapted or special milk formulas, and history of bronchitis and atopic dermatitis on toddlers' growth were also evaluated by multivariate analysis. RESULTS: Similar percentiles of the children's weight and height were observed at the beginning of the study and 1 year later. According to the multivariate analysis, sex, breastfeeding, early bottle feeding, ingestion of adapted or special milk formulas, atopic dermatitis, and bronchitis were not correlated with either the children's weight or height at diagnosis of the allergy or at 1 year of follow-up (P > .10). Weights and heights were not different between toddlers who had atopic dermatitis or bronchitis during the study period and those who did not. CONCLUSIONS: Growth of infants and toddlers with cow's milk allergy was not affected by the intake of extensively hydrolyzed milk for 1 year. Atopic dermatitis and bronchitis did not appear to have any deleterious effect on these children's growth.
Subject(s)
Bronchitis/immunology , Dermatitis/immunology , Infant Formula/chemistry , Milk/immunology , Animals , Body Height , Breast Feeding , Bronchitis/blood , Caseins/metabolism , Dermatitis/blood , Female , Follow-Up Studies , Humans , Immunity, Innate/immunology , Immunoglobulin E/blood , Immunoglobulin E/immunology , Infant , Lactoglobulins/blood , Lactoglobulins/immunology , Male , Milk/adverse effects , Prospective Studies , Single-Blind MethodSubject(s)
Bezoars/diagnostic imaging , Duodenum , Stomach , Adult , Bezoars/surgery , Duodenum/diagnostic imaging , Endoscopy , Female , Humans , Radiography , Stomach/diagnostic imagingSubject(s)
Hypersensitivity , Adolescent , Child , Dermatitis, Atopic/diagnosis , Dermatitis, Contact/diagnosis , Diagnosis, Differential , Food Hypersensitivity/diagnosis , Humans , Hypersensitivity/diagnosis , Hypersensitivity/therapy , Respiratory Hypersensitivity/diagnosis , Rhinitis, Allergic, Perennial/diagnosis , Rhinitis, Allergic, Seasonal/diagnosisABSTRACT
Se plantea que desde su descubrimiento por Howell y Mc Loan, en 1916, la heparina, sustancia anticoagulante utilizada en la terapéutica humana, ha sido aislada mediante diferentes procedimientos a partir de tejidos animales, tales como el pulmón y la mucosa intestinal de los ganados vacuno y porcino. Se describe un procedimiento industrial para la obtención de heparina sódica a partir de mucosa intestinal, basado en los principios descritos por Barlow en 1964 (uso de las sales cuaternarias de amonio como precipitantes) y por Sumik en 1969 (utilización de enzimas proteolíticas). Para su procedimiento, la mucosa previamente tratada, se digiere en condiciones de pH, temperatura y concentraciones de enzimas adecuadas, aislado el principio activo mediante precipitación selectiva(AU)