Association of airway cathepsin B and S with inflammation in cystic fibrosis.

Irreversible tissue damage within the cystic fibrosis (CF) lung is mediated by proteolytic enzymes during an inflammatory response. Serine proteinases, in particular neutrophil elastase (NE), have been implicated however, members of the cysteine proteinase family may also be involved. The aim of this study was to determine cathepsin B and S levels in cystic fibrosis (CF) sputum and to assess any relationship to recognized markers of inflammation such as sputum NE, interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-a), urine TNF receptor 1 (TNFr1), plasma IL-6, and serum C-reactive protein (CRP). Proteinase activities were measured in the sputum of 36 clinically stable CF patients using spectrophotometric and fluorogenic assays. Immunoblots were also used to confirm enzyme activity data. All other parameters were measured by ELISA. Patients had a mean age of 27.2 (8.2) years, FEV. of 1.6 (0.79) L and BMI of 20.7 (2.8). Both cathepsin B and S activities were detected in all samples, with mean concentrations of 18.0 (13.5)?µg/ml and 1.6 (0.88)?µg/ml, respectively and were found to correlate not only with each other but with NE, TNF-a and IL-8 (in all cases .?<?0.05). Airway cathepsin B further correlated with circulatory IL-6 and CRP however, no relationship for either cathepsin was observed with urine TNFr1. This data indicates that cathepsin B and S may have important roles in the pathophysiology of CF lung disease and could have potential as markers of inflammation in future studies. Pediatr. Pulmonol. 2010; 45:860–868.

Atopy, home environment and the risk of childhood-onset type 1 diabetes: a population-based case-control study

Background: The marked increases in the incidence of type 1 diabetes in recent decades strongly suggest the role of environmental influences. These environmental influences remain largely unknown.

Explicit argumentation as a supervisory tool for decision making in child protection cases involving human rights issues

This paper addresses the problems often faced by social workers and their supervisors in decision making where human rights considerations and child protection concerns collide. High profile court cases in the United Kingdom and Europe have consistently called for social workers to convey more clarity when justifying their reasons for interfering with human rights in child protection cases. The themes emerging from these case law decisions imply that social workers need to be better at giving reasons and evidence in more explicit ways to support any actions they propose which cause interference with Convention Rights. Toulmin (1958, 1985) offers a structured approach to argumentation which may have relevance to the supervision of child protection cases when social workers and managers are required to balance these human rights considerations. One of the key challenges in this balancing act is the need for decision makers to feel confident that any interventions resulting in the interference of human rights are both justified and proportionate. Toulmin’s work has already been shown to have relevance for assisting social workers navigate pathways through cases involving competing ethical and moral demands (Osmo and Landau, 2001) and more recently to human rights and decision making in child protection (Duffy et al, 2006). Toulmin’s model takes the practitioner through a series of stages where any argument or proposed recommendation (claim) is subjected to intense critical analysis involving exposition of its strengths and weaknesses. The author therefore proposes that explicit argumentation (Osmo and Landau, 2001) may help supervisors and practitioners towards safer and more confident decision making in child protection cases involving the interference of the human rights of children and parents. In addition to highlighting the broader context of human rights currently permeating child protection decision making, the paper will include case material to practically demonstrate the application of Toulmin’s model of argumentation to the supervision context. In this way the paper adopts a strong practice approach in helping to assist practitioners with the problems and dilemmas they may come up against in decision making in complex cases.

Effect of genotype on changes in intelligence quotient after dietary relaxation in phenylketonuria and hyperphenylalaninaemia

Background-Associations between genotype and intellectual outcome in patients with phenylketonuria are complicated because intelligence is influenced by many variables, including environmental factors and other genetic determinants. Intellectual changes with age, both on and after relaxation of diet, vary within the patient population. This study aims to determine whether a significant association exists between genotype and change in intelligence after relaxation of diet.

Safeguarding children and public health: midwives' responsibilities

Using a healthy settings framework, this study aims to compare and contrast how midwives working in either hospital or community settings are currently responding to the co-occurrence of domestic and child abuse; their perceived role and willingness to identify abuse; record keeping; reporting of suspected or definite cases of child abuse; and training received. Methods: A survey questionnaire was sent to 861 hospital and community midwives throughout Northern Ireland, which resulted in 488 midwives completing the questionnaire, a 57% response rate. Comparisons were made using descriptive statistics and cross-tabulation and the questionnaire was validated using exploratory factor analysis. Results: Community midwives reported receiving more training on domestic and child abuse. Although a high percentage of both hospital and community midwives acknowledged a link between domestic and child abuse, it was the community midwives who encountered more suspected and definite (p

Peanut allergy and allergic airways inflammation.

Asthma is a major risk cofactor for anaphylactic deaths in children with peanut allergy. Peanut allergy is generally thought to be a lifelong condition, but some children outgrow their coexistent asthma. It has recently been shown that children who have ‘outgrown’ their asthma symptoms may have ongoing eosinophilic airways inflammation. The need for regular inhaled corticosteroid treatment in peanut allergic children and adolescents who have outgrown their asthma is however unclear. The aims of our study were to look at fractional exhaled nitric oxide levels (FeNO), as a non-invasive marker of eosinophilic airways inflammation, in peanut allergic children and assess whether children with outgrown asthma had elevated levels. Children with peanut allergy were recruited at two pediatric allergy clinics in Belfast, UK. Exhaled nitric oxide levels (FeNO) were measured using the Niox Mino in all children. Of the 101 peanut allergic children who consented for enrolment in the study, 94 were successfully able to use the NIOX Mino. Age range was 4–15 yr (median 10 yr); 61% were boys. Thirty (32%) had never wheezed, 37 (39%) had current treated asthma, 20 (21%) had at least 1 wheezing episode within the last year but were not taking any regular asthma medication (wheeze no treatment), and 7 (7%) had outgrown asthma. All children with outgrown asthma had elevated levels of FeNO (>35 ppb), and 75% of children defined as ‘wheeze no treatment’ had elevated FeNO levels (>35 ppb). Outgrown asthma and children defined as ‘wheeze no treatment’ had higher levels of FeNO than those with no history of wheeze or current treated asthma (p = 0.003). In children with peanut allergy, we found that those who had outgrown asthma had elevated FeNO levels in keeping with ongoing eosinophilic airways inflammation.

The extent and nature of family alcohol and drug use: Findings from the Belfast Youth Development Study

Using data from an ongoing longitudinal study of adolescent drug use, this study examines the proportion of teenagers living with parents who are problem alcohol or drug users. Around two percent of parents report high levels of problem drinking and one per cent report problem drug use. If a broader definition of hazardous drinking is used, the proportion of teenagers exposed increases to over 15 per cent. When substance use is examined at a family level (taking account of alcohol and drug use amongst dependent children in addition to that of parents), the proportion of families experiencing some form of substance use is considerable. These findings add further support to the call for increased recognition of the needs of dependent children within adult treatment services when working with parents. Likewise, the reduction of harm to children as a result of parent substance use should be an increasingly important priority for family support services. This is likely to be achieved through the closer integration of addiction and family services.

Tuberous sclerosis complex: clinical features, diagnosis, and prevalence within Northern Ireland

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 and TSC2 genes on chromosomes 9 and 16 respectively. Diagnosis is based on clinical features but can be difficult as a result of variable phenotypic expression. With the advantage of mutation analysis in making a diagnosis of TSC, and improved identification of the associated clinical features, there have been few new data on its prevalence and on the proportion of cases due to new mutations. We have performed a retrospective epidemiological study on the prevalence of TSC, the clinical features attributed to it, and the availability of mutational analysis. We identified 73 known patients with TSC (5 deceased): 39 were female and 34 male. Ages ranged from 10 months to 69 years, with a mean age of 27 years 11 months (SD 16y 10mo). The point prevalence of TSC in our study was estimated at I out of 24 956 on the prevalence day (30 April 2004). The majority of patients (42.5%) were diagnosed at less than 15 months of age; 25% were not given a diagnosis on first developing symptoms. In all, 93.2% had epilepsy and 71.2% had a learning disability.* A mutation was identified in 95.8% of those tested (26% TSC1 and 74% TSC2). TSC2 mutations were correlated with a more severe phenotype. The new mutation rate was calculated at 64%. We conclude that the prevalence of TSC is higher than previously calculated. We recommend that all children with epilepsy be assessed for features of TSC. Larger studies will be required to assess the prevalence of mutations in each gene, and genotype-phenotype correlation.

Mosaic monosomy 14: clinical features and recognizable facies

A 1-year-old child with clinical features of monosomy 14 is reported. She has dysmorphic facial features including ocular colobomata, dolichocephaly and microcephaly, retinal pigmentation, severe seizures, fair curly hair and tapering fingers. There was severe mental retardation. This is the first reported case of severe mosaic monosomy 14, with up to 30% mosaicism. A recognizable facial gestalt is present in children with 14q deletions or partial monosomy 14, as well as susceptibility to infection, feeding difficulties, seizures and retinal pigmentation. (C) 2004 Lippincott Williams Wilkins.

An Irish three-generation family of Cornelia de Lange syndrome displaying autosomal dominant inheritance

The existence of familial de Lange syndrome has been documented in sibs and in parent-child families, but the inheritance pattern continues to be the cause of much debate. We describe a classically affected neonate with de Lange syndrome, an affected mother and probably affected maternal grandmother. These cases show evidence for a dominantly inherited syndrome with a de Lange phenotype.

Hereditary ataxias and paediatric neurology: new movers and shakers enter the field

Over 25 autosomal dominant and autosomal recessive spinocerebellar ataxias have been isolated over the last decade. The recognition of paediatric ataxia phenotypes and, in addition, other movement disorders including hereditary choreiform and parkinsonian syndromes, has improved our knowledge of these diseases. Advances in molecular genetics has allowed fuller delineation and better recognition of these diseases. (C) 2003 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.