BACKGROUND: Increasing evidence suggests that patterns of T-cell immunity to inhalant allergens in genetically diverse human populations are more heterogeneous than previously assumed, and that covert differences in expression patterns might underlie variations in airway disease phenotypes. We tested this proposition in a community sample of children. METHODS: We analysed data from 172 individuals who had been recruited antenatally to a longitudinal birth cohort study. Of the 194 birth cohort participants, data from the 147 probands (age range 8.6-13.5 years) who consented to blood collection were included along with data from 25 consenting siblings (mean age 11 years [range 7.4-17.4]). We ascertained clinical phenotypes related to asthma and allergy. We measured T-cell responses to allergens and mitogens, together with blood eosinophils and IgE/IgG antibodies, and assessed associations between these indices and clinical phenotypes. FINDINGS: Atopy was associated with allergen-specific T-helper (Th)2 responses dominated by interleukin 4, interleukin 5, interleukin 9, interleukin 13, whereas interleukin 10, tumour necrosis factor alpha, and interferon gamma responses were common to both atopics and non-atopics. The wheal size from skin prick with allergen was positively associated with in-vitro interleukin 5 and interferon gamma responses, and negatively associated with interleukin 10. Asthma, especially in atopics, was strongly associated with eosinophilia/interleukin 5, and bronchial hyper-responsiveness (BHR) was associated with eosinophilia plus polyclonal interferon gamma production. BHR in non-atopics was associated with elevated allergen-specific and polyclonal interleukin 10 production. INTERPRETATION: Parallel immunological and clinical profiling of children identified distinctive immune response patterns related to asthma and wheeze compared with BHR, in atopics non-atopics. Immunological hyper-responsiveness, including within the Th1 cytokine compartment, is identified as a hallmark of BHR. RELEVANCE TO PRACTICE: These findings highlight the heterogeneity of immune response patterns in asthmatic children, including those with seemingly homogeneous Th2-driven atopic asthma. Further elucidation of the covert relationships between wheezing phenotypes and underlying immunophenotypes in this age group will potentially lead to more effective treatments for what is an unexpectedly heterogeneous collection of disease subtypes.

Adolescent↗

PubMedDate not supplied

Lifestyle related risk factors for poor health in residential settings for people with intellectual disabilities.

Little information is available on the prevalence and determinants of lifestyle related risk factors for poor health (obesity, poor diet, physical inactivity, smoking and alcohol abuse) among people with intellectual disabilities. This study reports the prevalence of these risk factors for 500 people with intellectual disabilities living in different forms of residential provision in the UK. Variables which predict the presence of these risk factors are also identified. While levels of smoking and alcohol abuse were low, the prevalence of poor diet, obesity in women and physical inactivity was high. Analyses of predictors of risk factors present a mixed pattern with regard to participant and service characteristics, with greater ability and less restrictive residential settings being associated with poor diet, smoking and obesity, but physical inactivity being associated with lower ability and more restrictive settings. It is argued that increasing levels of moderate or vigorous physical activity among people with intellectual disabilities would be the single most effective way of improving the health of people with intellectual disabilities.

Adult↗

PubMedDate not supplied

Morphine and etorphine: XIV. Detection by ELISA in equine urine.

We have raised antibodies to morphine and etorphine and developed one-step enzyme-linked immunosorbent assays (ELISA) for these drugs as part of a panel of post race tests for drugs in racing horses. These tests are simple, can be completed in 2 h, and can be read by visual inspection. The morphine ELISA has an I50 for morphine of about 1.5 ng/mL, while the etorphine ELISA has an I50 for etorphine of 250 pg/mL. Cross-reactivity studies show that the antimorphine antibody cross-reacts well with levorphanol, hydromorphone, and oxycodone, while the anti-etorphine antibody showed no cross-reactivity with buprenorphine, diprenorphine, oxymorphone, morphine, or thebaine. The morphine test readily detected parent morphine or its metabolites in equine urine for at least 8 h after administration of 50 mg/horse, while a 0.1 micrograms/kg dose of etorphine was detectable for up to 48 h post dosing. For each test the background activity in post-race urines was equal to or less than the I50 for the standard curves, making them useful equine forensic tests. Each of these tests has detected "positives" in post race urine samples and as such these tests are capable of substantially improving the speed and efficacy of both pre-race and post-race testing for morphine, etorphine, and their congeners in racing horses.

Animals↗

PubMedDate not supplied

Health problems in children with Down's syndrome.

The health problems of 117 children with Down's syndrome were identified through a questionnaire to their mothers, as part of a wider study of the process of adaptation among families in the Manchester Down's Syndrome Cohort. At the time of the present study, the children were all of school age: mean age 9 years 2 months, range 6 to 14 years. Results from the current study are compared with that from earlier studies involving these children. Vision and hearing problems and respiratory infections were identified as the most common health problems, affecting a large percentage of the children. While a high proportion had been hospitalized and had undergone operations, the proportion of children who had missed more than 4 weeks of schooling in the previous 12 months was not high compared to the general child population. Equally, the numbers who had suffered accidents did not appear unduly high. Poor child health was found to be associated with a higher level of behaviour problems and increasing maternal stress over time. The need for health screening to continue during this period of childhood is identified.

Adolescent↗

PubMedDate not supplied

Social life of school children with Down's syndrome.

Frequency of participation in organized activities and informal play contacts with other children were investigated for a group of 118 children with Down's syndrome. Measures were based on mothers' reports. As part of a study of child and family functioning, a wide range of child, parent and family variables was measured and the relationships of these to the extent of the children's social contacts were investigated in multivariable analyses. Family variables of social class, parental education, marital relationship, and achievement and recreational orientation were found to be significantly related to the measures of the child's social life. In addition, children at the lower end of the IQ range in this sample were likely to have fewer informal play contacts. These results point to the influence of the family in stimulating and maintaining the children's social activities.

Adolescent↗

PubMedDate not supplied

Service needs of families of children with severe physical disability.

Service contacts, perceived helpfulness of services and needs for help were investigated in a sample of 107 families of young children with severe physical disability. Many families were in contact with a multiplicity of different services and overall frequency of contact was high. Despite this, there was evidence of considerable unmet need, particularly in the provision of information to families. Families with the highest levels of unmet need were likely to have experienced high levels of strain from life events and to have children with mental retardation as well as physical disability, fathers in those families were more likely to be unemployed and mothers were more likely to use passive optimism in coping with child problems. The findings indicate the importance of services which are easily accessible to parents, the provision of information to parents about such services, the co-ordination of services through a 'link' person and the accurate and individual assessment of family needs.

Adaptation, Psychological↗

PubMedDate not supplied

Investigating deep phylogenetic relationships among cyanobacteria and plastids by small subunit rRNA sequence analysis.

Small subunit rRNA sequence data were generated for 27 strains of cyanobacteria and incorporated into a phylogenetic analysis of 1,377 aligned sequence positions from a diverse sampling of 53 cyanobacteria and 10 photosynthetic plastids. Tree inference was carried out using a maximum likelihood method with correction for site-to-site variation in evolutionary rate. Confidence in the inferred phylogenetic relationships was determined by construction of a majority-rule consensus tree based on alternative topologies not considered to be statistically significantly different from the optimal tree. The results are in agreement with earlier studies in the assignment of individual taxa to specific sequence groups. Several relationships not previously noted among sequence groups are indicated, whereas other relationships previously supported are contradicted. All plastids cluster as a strongly supported monophyletic group arising near the root of the cyanobacterial line of descent.

Cyanobacteria↗

PubMedDate not supplied

Two distinct truncated apolipoprotein B species in a kindred with hypobetalipoproteinemia.

Two novel, distinct truncated forms of apolipoprotein B (apo B) designated as apo B-90 and apo B-40 were found in five members of a kindred with hypobetalipoproteinemia. Sodium dodecyl sulfate gels and immunoblots of plasma or low density lipoprotein (LDL) (d = 1.019 to 1.063 g/ml) of the affected members demonstrated the presence of one or both of the truncated apo B bands. Employing four monoclonal anti-LDL antibodies with defined regional specificities, we demonstrated that amino terminal epitopes of the truncated apo Bs were intact, but that 10% and 60%, respectively, of the carboxyl terminal regions were absent. Thrombin digestion of apo B-90 generated an abnormally small T2 fragment, confirming that approximately 550 amino acids had been deleted from the carboxyl terminus of apo B-100. Restriction fragment length polymorphism analysis and variable number of tandem repeat typing of the 3' flanking hypervariable region of the apo B gene made it possible to distinguish all four parental alleles and therefore to follow the inheritance of the apo B variants through the family. This pedigree analysis confirmed the inheritance of the apo B-90 and apo B-40 identified by monoclonal antibody binding studies. Siblings heterozygous for apo B-90 or apo B-40 exhibited greater than 65% lower concentrations of apo B-90 or apo B-40 relative to apo B-100 and had 5th percentile LDL cholesterol concentrations. Compound heterozygotes (apo B-90/apo B-40) had the lowest LDL levels, and their LDL particles were small in size.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMedDate not supplied

A good reputation draws a crowd.

Explore the source record for details and available documents.

Audiovisual Aids↗

PubMedDate not supplied

Quality-adjusted life years: cost-effective medical decision-making.

It is well-documented that the resources available to meet the healthcare needs of Americans are limited. Consequently, it is inevitable that limits will have to be set regarding how much can be spent. While such a proposal is obviously controversial, limits are already in place in many areas of healthcare. The problem is determining how to allocate healthcare dollars in order to get the most benefit.

Culture↗

PubMedDate not supplied

The effectiveness of services for people with learning disabilities.

The government white paper The New NHS has placed emphasis on service effectiveness and expects it to be measured. Clinical governance is expected to provide robust internal mechanisms for this. A National Institute for Clinical Effectiveness will provide a lead on clinical and cost-effectiveness and a Commission for Health Improvement oversee the quality of clinical services (Department of Health, 1997). Signposts for Success (NHS Executive, 1998) sets out good practice guidance for commissioners and providers of health services for people with learning disabilities. This states that its aim is to deliver 'person-centred services, equality of access, support to use services and social inclusion', person-centred services being defined as those that put 'service users' wishes and needs at the centre'. This article looks at how one trust is trying to meet these requirements following this guidance.

Benchmarking↗

PubMedDate not supplied

I am a nurse in theatre and would like to set up a practice development group.

Explore the source record for details and available documents.

Humans↗