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Biomedical subjects

C S Hosking

Publications and source records attributed to C S Hosking.

At least 19 recordsLinked to original sources

Challenge confirmation of late-onset reactions to extensively hydrolyzed formulas in infants with multiple food protein intolerance.

BACKGROUND: Many infants with cow's milk protein intolerance have adverse reactions to soy, casein and whey hydrolysate formula and to other foods. The recent development of Neocate, a hypoallergenic, nutritionally complete infant formula composed of individual amino acids and other nutrients, has enabled these infants to be stabilized. OBJECTIVE: We observed the effect of food challenges in infants with reported hypersensitivity to hypoallergenic formulas. METHODS: Eighteen infants (median age, 7 1/2 months) were given Neocate formula for 2 months and then underwent a 7-day double-blind placebo-controlled challenge with the formula previously best tolerated. RESULTS: In 12 of the 18 infants irritability, vomiting, diarrhea, and/or eczema flares developed during the formula challenge. In two patients symptoms developed immediately, but in the remainder adverse reactions evolved within 7 days (range, 4 to 7 days). Adverse reactions were to soy formula (six patients), whey hydrolysate (two), and casein hydrolysate (four). When infants were 12 months of age, parents reported adverse reactions after the ingestion of other low allergen foods (median, six; from a panel of 10 such foods). CONCLUSION: A group of infants with late-onset adverse reactions to soy, extensively hydrolyzed casein, and whey formulas and to other foods has been identified. Neocate formula proved to be an effective substitute formula for these patients.

Amino Acids

A major continuous allergenic epitope of bovine beta-lactoglobulin recognized by human IgE binding.

Hexapeptides of sequential overlapping sequences of beta-lactoglobulin (BLG) were used to probe serum from children with immediate-type cow milk allergy for IgE binding to continuous epitopes of BLG in an enhanced enzyme-linked immunosorbent assay (ELISA). Six regions of IgE binding were identified on the BLG molecule and these were synthesized as dodecapeptides. Inhibition of IgE binding to whole BLG was used to confirm the BLG-specific binding of IgE to each of the synthesized peptides. One of the peptides, peptide 4, showed inhibition in an IgE anti-BLG radioimmunoassay to all 16 sera tested. The patterns of inhibition with the native BLG molecule and peptide 4 were significantly correlated (P = 0.005), suggesting that this peptide contains a major continuous IgE binding epitope of BLG.

Allergens

Cow milk allergy within the spectrum of atopic disorders.

In order to examine the relationship between cow milk allergy (CMA) and atopic disorders in childhood, a consecutive group of 42 infants with IgE mediated CMA was followed for at least 2 years. The incidence of sensitization to common food and inhalant antigens and the development of eczema, asthma, and food allergies was examined for the cohort and compared between patients whose CMA remitted and those with persistent disease. In this cohort the prevalence of eczema was 57%, asthma 69%, egg allergy 67%, peanut allergy 55%, and 83% of infants demonstrated positive skin-prick tests to three or more allergens. At the end of the study CMA had remitted in 13 patients (median age 44 months) whereas in 29 patients it persisted (median age 44 months). Although there was no significant difference in the incidence of eczema or asthma during the study between these two patient groups, the incidence of allergy to egg and peanut butter was significantly greater for children with persistent CMA. Consistent with our hypothesis that children with persistent CMA have a more severe dysregulation of IgE synthesis than those whose disease remits, patients with persistent CMA had a significantly higher incidence of and level of skin sensitivity to inhalant and other dietary allergens. Sensitization to the inhalant allergens Dermatophagoides pteronyssinus, cat dander and rye grass was frequently seen in early infancy and increased during the study period. Thus, children with IgE mediated CMA frequently generate IgE responses to multiple dietary and inhalant allergens in infancy and early childhood and develop immediate hypersensitivity to other foods as well as clinical eczema, and asthma.

Allergens

Lymphocyte production of gamma-interferon as a test for non-tuberculous mycobacterial lymphadenitis in childhood.

Infection with Mycobacterium avium, M. intracellulare and M. scrofulaceum (MAIS) organisms in normal children may result in cervical lymphadenopathy. There is a poor response to anti-tuberculous therapy and surgical excision of infected nodes is necessary. The diagnosis therefore requires consideration in children with cervical lymphadenopathy. A simple in vitro assay is described which may be useful for diagnosis prior to excision. Whole blood is cultured with M. avium purified protein derivative. After 24 h the plasma is removed and the concentration of gamma interferon (IFN-gamma) quantified by a radioimmunometric assay. In a prospective study of 38 children with neck lesions, 16 showed MAIS organisms isolated from cultures of excised tissue. The level of IFN-gamma produced by peripheral blood lymphocytes from children in the MAIS group was significantly greater when compared with children having operations for neck lesions that were not due to MAIS organisms (P < 0.001).

Adolescent

Natural history of cows' milk allergy in children: immunological outcome over 2 years.

In this investigation 98 children (median age 24 months) with cows' milk allergy (CMA) were studied over a median period of 2 years to see whether acquisition of clinical tolerance to cows' milk was associated with the changes in levels of IgG and IgE anti-cows' milk antibodies, and skin test reactivity to a cows' milk extract. Two groups of CMA patients were examined. The first were IgE sensitized and responded rapidly to small volumes of cows' milk with urticaria, and/or exacerbations of eczema, and/or wheeze, and/or vomiting (n = 69). The second, a late reacting group (n = 29) demonstrated coughing, diarrhoea, eczematoid rashes, and/or a combination of these which developed more than 20 hr after commencing normal volumes of cows' milk. Significant immunological changes were confined to the 69 IgE sensitized immediate-reacting-group of patients. Of these, there were 15 children who achieved clinical tolerance to cows' milk and they showed a significant fall in the levels of skin test reactivity to cows' milk over the study period (P < 0.01). In addition, these 15 children had lower serum IgE antibodies to cows' milk proteins both at the outset and the final follow-up compared with the 54 patients whose CMA persisted. No consistent change in the IgG antibody responses to cows' milk proteins was seen in either group of patients over the study period. The findings suggest patients with immediate type hypersensitivity to cows' milk proteins whose disease persists for more than 2 years have a more severe dysregulation of IgE synthesis to cows' milk proteins from the outset.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Gamma-interferon production in cow milk allergy.

The aim of this study was to develop an assay to assist in the diagnosis of delayed onset of adverse responses to cow milk in children, by measurement of gamma-interferon (GIFN) produced in vitro in response to beta-lactoglobulin-stimulated blood mononuclear cells. Diagnostic procedures identified 75 children with immediate reactions who had high total IgE and IgE-isotype responses to cow milk, 17 children who developed reactions after 24 h and had low total IgE and low IgE-isotype response to cow milk, and 59 milk-tolerant children. GIFN production was less in children with immediate reactions compared to those with late reactions (P < 0.009), or milk-tolerant children (P = 0.022). The results of this study suggest enhanced T-cell reactivity may be involved in the immuno-pathogenesis of non-immediate cow milk allergy, but GIFN production was not a clinically useful diagnostic test.

Age Factors

Charting infant distress: an aid to defining colic.

The value of a 24-hour distress diary, previously validated against a voice-activated audiotape record, was investigated in 30 infants with colic and 30 control infants. The infants with colic had significantly more distress behavior (300.0 minutes vs 102.5 minutes; p < 0.001), although overlap of duration of distress was noted. On the basis of a clinical definition of colic--total distress lasting 180 minutes in a 24-hour period--the diary had a sensitivity of 77% and a specificity of 87%. The sensitivity of the chart was confirmed in a separate study of another 90 infants with colic.

Child Behavior

Childhood asthma: clinical and immunological changes over a decade.

A group of 26 Australian asthmatic children with laboratory-proven bronchial hyper-reactivity to the allergens of rye grass pollen and/or the house dust mite has been studied over a 9-year period. Clinical symptoms and drug scores were used to evaluate the severity of the patients' asthma and, wherever possible, blood samples were obtained before, during and after the rye grass pollen seasons. The cumulative symptom and drug scores for the 20 patients with bronchial hyper-reactivity to rye grass pollen extract tended to increase during and fall after each pollen season but the peaks were of decreasing amplitude over the 9 years. Since a proportion of these patients underwent hyposensitization to rye grass during year 1, longitudinal comparisons were made between year 2 and year 9. Comparing the individuals at the same three seasonal time-points revealed significantly lower drug scores in year 9 compared with year 2, and in parallel with this, significantly lower total IgE, IgE anti-rye and IgG anti-rye antibodies at all three assessment points. In the 14 patients with bronchial hyper-reactivity to house dust mite the severity of the asthma and the median levels of IgE and IgG mite specific antibodies all decreased over the study period. Despite the progressive improvement in asthma and diminishing immune responses to both rye grass and house mite in the patients, no immunological feature could be identified that correlated significantly with clinical outcome.

Adolescent

Bovine milk, including pasteurised milk, contains antibodies directed against allergens of clinical importance to man.

Pasteurised and raw bovine milk and bovine colostrum samples were assayed by enzyme-linked immunoassay for the presence of antibodies directed against a selection of allergens of importance in human atopic disease. Samples were tested for the presence of antibodies directed against or cross-reacting with ryegrass pollen, house dust mites, Aspergillus mould and wheat proteins. Antibodies of each specificity were detected in every sample tested, including all samples of commercial pasteurised milk. The results are discussed with reference to a hypothesis that dietary xenogeneic antibodies may play a role in the emergence of some human atopic disease, and the recent demonstration that oral immunisation with xenogeneic antibodies may lead to the production of anti-immunoglobulin antibodies including anti-idiotypic antibodies.

Allergens

[Promotive effects of thymus peptide on mitogen-induced child thymocyte proliferation].

This paper reports a cytocentrifugation study of the morphological changes of mitogen-induced proliferating child thymocytes stimulated by thymus peptides. The proliferation response of child thymocytes to PHA was far more significant than those to ConA and PWN. This differs from the more pronounced effect of ConA on thymocyte proliferation in mice. In vitro, child thymocytes did not respond to thymus peptide without mitogen-induction. However, when thymus peptide was added to thymocyte culture with PHA, ConA, or PWN, proliferation responses were significantly enhanced, being most marked in the PHA-induced cell culture. The mechanism of the enhancing effect of thymus peptide on mitogen-induced human thymocytes is discussed.

Drug Synergism

Oral immunization with xenogeneic antibodies stimulates the production of systemic and mucosal anti-idiotypic antibodies.

The humoral and mucosal immune responses to oral immunization with xenogeneic antibodies were studied using an animal model in which female rabbits were fed daily doses of the MOPC-315 murine IgA antibody, and were mated during the course of the feeding programme. Serum and colostrum samples were assayed for the presence of anti-idiotypic antibodies by ELISA assay, before and after depletion of anti-IgA antibodies, by affinity chromatography using another murine IgA idiotype. It was shown that all animals responded to exposure to the MOPC-315 idiotype with the production of serum anti-murine immunoglobulin antibodies and that four of six animals produced serum anti-idiotypic antibodies. That the immune response included antibodies directed against the antigen-binding site was confirmed by competition ELISA assay. Mucosal IgG and IgA anti-immunoglobulin antibodies were present in milk from all antibody-fed rabbits tested, and IgA anti-idiotypic antibodies were detectable in the colostrum of one rabbit. The results provide some support for the hypothesis that human exposure to xenogeneic antibodies, most commonly bovine milk immunoglobulins, may provoke the production of anti-idiotypic antibodies, and that such exposure may lead to disturbances of immune regulation.

Administration, Oral

Natural history of cow milk allergy: clinical outcome.

Of an initial cohort of 100 children with challenge-proven cow milk allergy, 97 were reviewed after 5 years to determine the effect of prolonged cow milk avoidance on clinical features, the reported frequency of adverse reactions to other foods, and the reported emergence of other atopic disorders. The mean age at diagnosis was 16 months, and at final follow-up 99 months. Cow milk tolerance by challenge was demonstrated in 28% of patients by 2 years of age, 56% by 4 years, and 78% by 6 years. Only 25% of children were allergic to cow milk alone; parents reported associated adverse reactions to many other foods, including egg (58%), soy milk (47%), and peanut (34%). Exclusion of cow milk from the diet of infants and young children with cow milk allergy did not prevent the subsequent development of atopic disorders. At final follow-up, 40% of patients reportedly had asthma, 21% atopic eczema, and 43% allergic rhinitis. It is unclear whether independent mechanisms control the development of cow milk allergy and other atopic conditions.

Animals

Antibodies to polyclonal IgA, IgA1, and IgA2 and isotype-specific immune complexes in IgA nephropathy.

The concentrations of serum IgG and IgM antibodies to polyclonal IgA (IgAp), IgA1, and IgA2 were determined by enzyme immunoassay in 31 patients with IgA nephropathy and 30 healthy controls. Patients with IgA nephropathy had significantly raised concentrations of serum IgA compared to controls (Mann-Whitney U test, P = 0.001) and increased concentrations of conglutinin-binding IgA immune complexes (P = 0.024). No differences in the median concentrations of IgG and IgM anti-IgA antibodies were found between the patients and the controls. In serum samples from healthy controls there was a significant positive correlation between IgM anti-IgAp and IgA immune complex concentrations (P = 0.05), which contrasted with the finding of an inverse correlation between IgM anti-IgAp and IgA immune complex concentrations in patients with IgA nephropathy (P less than 0.05). In addition, the concentrations of conglutinin binding IgM immune complexes in serum were found to correlate with the concentration of IgM anti-IgAp (0.010 less than P less than 0.025), IgM anti-IgA1, and IgM anti-IgA2 (P much less than 0.005 for both) in patients with IgA nephropathy but not in controls. IgM anti-IgA antibodies may be important in augmenting the clearance of IgA immune complexes from the serum of patients with IgA nephropathy.

Adolescent

Recovery from milk allergy in early childhood: antibody studies.

We assessed the relationships of clinical symptoms and serum antibody levels during follow-up of 47 patients, aged 3 to 66 months, who were shown by formal milk challenge to have cow milk allergy. Three groups of patients were identified. Group 1 patients (n = 15) were sensitized to IgE and responded rapidly to small volumes of milk with urticaria, an exacerbation of eczema, wheeze, or vomiting. In the second group (n = 24), symptoms of milk enteropathy (vomiting and diarrhea) developed between 1 and 20 hours after milk ingestion. In the group 3 patients (n = 8), coughing, diarrhea, eczematoid rashes, or a combination of these developed more than 20 hours after normal volumes of milk were given. Serum levels of IgG, IgA, IgM, and IgE and of milk-specific anti-cow milk antibodies of these isotypes were measured initially and then at a median follow-up time of 16 months (range 6 to 39 months). In this investigation, changes in these immunologic measures during the study period were related to whether or not clinical tolerance to cow milk was achieved. At follow-up, six patients from group 1, ten from group 2, and two from group 3 were milk tolerant. No consistent change in any of the immunologic measurements was associated with remission of the disease. These findings raise the question of whether acquisition of clinical tolerance to cow milk in cow milk allergy can be attributed solely to immunologic events.

Animals