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Biomedical subjects

T G Merrett

Publications and source records attributed to T G Merrett.

At least 19 recordsLinked to original sources

House dust mite sensitivity: interaction of genetics and allergen dosage.

Pairwise analysis of siblings from 21 families showed that house dust mite (HDM) sensitive children were exposed to higher concentrations of Der p I allergen in their mattress (P = 0.005) and bedding (P = 0.04), but not bedroom floor (P = 0.33), than their atopic sibling who was not sensitive to HDM antigens. There was no difference in the exposure to HDM numbers/100 mg of dust in the mattress (P = 0.61) or bedroom floors (P = 0.09). In contrast, pairwise analysis of siblings from 15 families showed that HDM sensitive children were not exposed to significantly different concentrations of Der p I in the mattress (P = 0.96), bedding (P = 0.11) or bedroom floor (P = 0.70) nor HDM numbers/100 mg of dust in the mattress (P = 0.12) and bedroom floor (P = 0.98) than their non-atopic siblings. These findings were identical when absolute allergen load was compared in these pairs. Genetic linkage studies in these families suggest the tendency to atopic IgE responses is conferred by a putative atopy locus on chromosome 11q. These results together suggest that differences in allergen levels in beds, among siblings with a comparable genetic tendency to atopy, play a significant role in determining the development of HDM allergy.

Allergens

Effectiveness of an acaricide in management of house dust mite allergy.

The effects of treating the environment of 25 dust mite-allergic patients with an acaracide are reported. Remarkable symptomatic improvements in asthma, eczema, or rhinitis were observed. Many patients could reduce or stop medication, and these benefits have persisted for up to a year after using Acarosan once only. Relapse of symptoms following exposure to untreated dusty environments was observed on many occasions confirming that the improvements were due to removal of the mite allergen.

Adolescent

Environmental factors and symptoms in infants at high risk of allergy.

STUDY OBJECTIVE: To identify environmental determinants of six symptoms associated with allergic disease in infancy. DESIGN: Infants were participants in a prospective randomised controlled trial of feeding practices in families with a history of atopy. SETTING: Infants were recruited in two maternity hospitals in S Wales and followed up in the community for 1 year. PARTICIPANTS: Mothers of 519 infants agreed to participate, but 36 were excluded (mainly for moving home or failing to attend for follow-up), leaving 483 in the study (253 male, 230 female). Infants were followed up and examined for evidence of allergic disease at 3, 6, and 12 months. MEASUREMENTS AND MAIN RESULTS: At each examination, mothers were questioned about episodes of illness in the infant, and the data presented relate to (reported and observed) eczema and nasal discharge, and (reported) wheeze, prolonged colds, diarrhoea and vomiting. Mothers kept a diary with details of feeding for the first 6 months. All homes were visited by a nurse who took samples of dust for dust mite antigen analysis. Extensive socio-demographic data were collected. None of the factors studied showed a convincing relationship with eczema. In a multiple logistic regression analysis breast feeding appeared to protect against wheeze, nasal discharge, colds, vomiting and diarrhoea. Having more siblings increased the likelihood of prolonged colds, and (together with overcrowding) of wheeze and nasal discharge. Maternal smoking and low social class were associated with wheeze, and house dust antigen with prolonged colds. Respiratory symptoms were associated with some aspects of housing but these could not be distinguished clearly from other social factors. Babies born in Autumn were at increased risk of wheeze, vomiting and diarrhoea. CONCLUSIONS: Environmental factors play an important part in determining risk of symptoms in potentially atopic babies. These factors are in principle open to manipulation.

Allergens

Prevalence of atopy is unrelated to presence of inflammatory bowel disease.

The prevalence of atopy (assessed by prick testing and serum IgE measurement), and of symptoms associated with atopy, has been defined in 122 patients with inflammatory bowel disease (IBD) and 103 age-matched controls. History analysis for atopic symptoms, and serum IgE levels, showed no differences between controls and IBD patients, or IBD subgroups (Crohn's disease, ulcerative colitis, ulcerative proctitis). Both in controls and in IBD patients, the prevalence of positive skin tests was higher in young people (aged less than 30) than in others; taking account of age distribution within the groups, there were no differences between controls and IBD patients, or subgroups, in the prevalence of positive skin tests. Our finding do not support the hypothesis that reaginic hypersensitivity plays a significant role in the pathogenesis of IBD.

Adolescent

Infant feeding and allergy.

The effect of withholding cows' milk was examined in 487 infants at high risk of allergic disease. Before birth they were randomly allocated either to a control group, most of whom received cows' milk preparations, or to an intervention group, who were offered a soya based substitute. Eczema and wheezing occurred to a similar extent in the two groups during the first year of life, although napkin rash, diarrhoea, and oral thrush were commoner in the intervention group, especially during the first three months. Breast feeding for any length of time was associated with a reduced incidence of wheezing and diarrhoea.

Animals

Clinical, histological and immunological studies in 50 patients with bullous pemphigoid.

Fifty patients with bullous pemphigoid were investigated over periods of up to 7 years. Sequential studies of circulating basement membrane zone (BMZ) antibody titres revealed two groups of patients: 44% had a high initial titre (greater than 1:160) and 56% had a low initial titre (less than 1:160). Subjects with titres greater than 1:160 continued to have high titres, whereas in those with lower titres the BMZ antibodies usually became undetectable after 4 months. The BMZ antibody titres were of no prognostic value. High titres remained high even in patients who were in remission and off treatment, and in these subjects, there was no evidence of a change in the IgG subclass. The initial BMZ IgG antibody titres showed a highly significant correlation with total serum IgE concentrations. A significant correlation also existed between total serum IgE and IgG4 concentrations, although not between the serum IgE and the peripheral blood eosinophil count. No anti-BMZ antibody of IgE class was found, nor specific IgE against inhalants and foods identified, and the significance of the high total serum IgE remains unexplained. The majority of those followed for more than 2 years were able to stop their steroid therapy without further blistering: this confirms that pemphigoid tends to be a self-limiting disease. Nine patients had a recent history of malignant disease, and this is no more than would be expected for this age group of patients: however, 3 patients presented with pemphigoid and figurate erythema and all died of neoplastic disease, suggesting that such patients should be investigated thoroughly for neoplasia.

Adult

Infant feeding and allergy: 12-month prospective study of 500 babies born into allergic families.

This investigation studied 487 babies for symptoms of allergic disease during their first year of life. Because of their positive family histories all the babies are at high risk of becoming allergic. The babies were randomly divided such that cows' milk was deliberately withheld from one group; infants in this group were fed with a soya substitute where required. No benefit resulted from withholding cows' milk, indeed symptoms were more usually associated with this group. Breast feeding, even for a short period, was clearly associated with a lower incidence of wheeze, prolonged colds, diarrhoea, and vomiting. It seemed that the duration of breast feeding was less important than whether or not the child had been breast-fed at all. Wheezing was both more common among boys than girls (P less than .05) and if the mother was a smoker. Other environmental features related to wheezing were social class, month of birth, lack of breast feeding, exposure to dampness, mould and coal fires, but not to domestic pets nor to the numbers of mites found in bedding and carpets. Mite exposure was, however, associated with prolonged colds. Eczema was the only allergic symptom not positively associated with any environmental factor; moreover, it was neither associated with a lack of breast feeding nor with inclusion of cows' milk in the diet. Eczema was associated with the incidence of positive skin prick tests and IgE antibodies to egg white. IgE and IgG4 antibodies were estimated at birth (mothers' and cord bloods) and 3 and 12 months later.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Phadiatop--a novel IgE antibody screening test.

The Phadiatop test, which is based on a multi-allergen allergosorbent, proved to be a test that is simple to perform in the laboratory and produces reliable results. When compared with the more conventional RAST atopy screening test for grass, mite and IgE antibodies it produced similar results, except in those rare instances of patients who were RAST-positive only for moulds where the Phadiatop test was decidedly superior. The Phadiatop test disc contains only inhalant allergens and so it could not be used for screening infants and very young children whose IgE response, if any, is probably limited to foods.

Evaluation Studies as Topic

IgE antibodies to foods are not a feature of cystic fibrosis.

It has been suggested that patients with cystic fibrosis have abnormal immune responses to foods. We have measured IgE antibodies to inhalants and foods (by RAST) in 105 patients with cystic fibrosis aged between 8 months and 28 years. Serum IgE was elevated (greater than 180 kU/l) in 21 patients. In 43, IgE antibodies were detected in serum. The majority of positive results were with house-dust mite, grass pollen or Aspergillus. Only four of the patients had a positive RAST to a food--one to milk, one to wheat and two to egg. On the basis of high serum IgE or positive RAST results, 44.8 per cent of the patients were atopic and the frequency of atopy was age-related, being higher in patients aged 4 years or more. However, the presence of food antibodies was unrelated to age. This study confirms the high prevalence of atopy in patients with cystic fibrosis but unequivocally demonstrates that the presence of IgE antibodies to foods in their serum is rare.

Adolescent

Food-allergic asthma in general practice.

A survey was undertaken to assess the importance of food allergy in asthma. Seventy-two asthmatics aged 15-60 years were identified in a general practice and compared with 72 controls matched for age and sex. A diagnostic procedure involving dietary elimination and challenge was carried out on those who thought food exacerbated their symptoms, together with those with concurrent eczema, positive skin tests to food or positive food IgE-RAST. The asthmatics more frequently had positive skin tests of IgE-RAST to food than the controls, but these tests proved to be rather non-specific in identifying provoking foods. One patient was found to be allergic to wheat and his clinical condition improved when wheat was removed from his diet. Two patients seemed to respond to other foodstuffs, but the effects were small, the foods (honey and peppermint) unimportant, and the patients' symptoms appeared to be largely due to other factors. Most cases of alleged food-induced asthma could not be confirmed by challenge testing. This survey suggests that some degree of provocation by food (excluding drink) affects at least 4 per cent of adult asthmatics, although in some of these patients it plays an unimportant part in the disease.

Adolescent

Immunologic studies in allergen-induced late-phase asthmatic reactions.

We have measured plasma histamine, serum neutrophil chemotactic activity (NCA) and complement (C3 and C4) over a 24-hour period in patients experiencing either early- and late-phase (dual) or single early asthmatic reactions to inhaled allergens. There was a significant biphasic elevation in plasma histamine, which paralleled the fall in forced expiratory volume in 1 sec in 10 patients with dual responses, whereas in seven subjects with single early reactions, only a single early increase in histamine concentrations was observed. In general, in the individual subjects, the changes in plasma histamine paralleled both the elevations in serum NCA and the decreases in forced expiratory volume in 1 sec. By gel filtration on Sephacryl S-400, anion exchange chromatography on DEAE Sephacel, and chromatofocusing with Polybuffer Exchanger 94, the major NCA of both the early and the late reactions was associated with proteins having an estimated molecular size of 600,000 daltons, an elution from DEAE Sephacel at 0.15M to 0.30M of NaCl (pH 8.1), and a pI of approximately 6.5. There were no appreciable changes in serum C3 and C4 up to 24 hr after challenge in subjects with late-phase responses. The patterns of asthmatic response were not related to either the total or allergen-specific serum IgE or IgG4 concentrations. These results support the view that mediators of hypersensitivity participate in late-phase as well as early asthmatic reactions.

Adolescent

Immediate hypersensitivity, IgE and asthma.

Twenty-one asthmatic and twenty-two non-asthmatic children and nine asthmatic adults from two different rural areas of Tanzania, and eight asthmatic children from Dar-es-Salaam were surveyed by questionnaires, skin testing and the measurement of serum IgE. Asthma was significantly commoner in female rural children (four males, fifteen females). The rural asthmatic children apparently had less skin reactivity (in seven of nine tests) and lower specific (in two of four tests) and total serum IgE than age-, sex- and village-matched controls. This pattern of asthma in rural children in the tropics represents a different type of asthma from that found in temperate zones. In contrast, the adult rural asthmatics and the urban children seemed to have the pattern of increased skin reactivity and serum IgE found in asthmatic patients from temperate climates.

Asthma

Total and specific IgG4 antibody levels in atopic eczema.

Total IgG4 and IgG4 antibody levels specific for 10 allergens (three inhaled and seven ingested) were measured by radioimmunoassay of sera taken from three groups of adult patients: (1) 32 cases of atopic eczema, (2) 28 cases of respiratory allergy and (3) 156 normal volunteers. In all three groups IgG4 antibody activity was mainly directed against common foods, and generally the group with atopic eczema had higher total and specific IgG4 levels than the cases of respiratory allergy, who in turn had higher titres than the normal group. There was within each group a tendency for men to have more total IgG4 than women and the difference was statistically significant among the normals. There was evidence of an IgG4 restricted response in atopic eczema because despite the group's elevated total IgG4 its total IgG4 remained within normal limits. Furthermore specific IgG4 was correlated with the corresponding specific IgE level in five of the 10 allergens examined. These results are generally consistent with the view that IgG4 levels are raised in cases of atopic eczema due to prolonged exposure to an allergen which initiated an IgE response.

Adolescent

Food intolerance: a community survey.

1. A questionnaire inquiring about food intolerance was sent to a random sample of the electorate in a small South Wales town. Replies were received from 170 men and 305 women, the response rates being 87 and 93% respectively. 2. Adverse effects of some food were reported by 19% of men and 26% of women, or 14 and 18% respectively if minor digestive symptoms are excluded. Certain foods were thought to cause non-abdominal symptoms by 4% of men and 10% of women, and vomiting, diarrhoea or abdominal pain by 11% of men and 10% of women. 3. Plasma IgE was measured in a random subset of ninety-nine women and found to be significantly lower in those with major symptoms than in the rest. This suggests that allergy is probably not a common cause of food intolerance.

Female