Paediatrics (RCH) - Research Publications
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ItemBivariate variance-component analysis, with application to systolic blood pressure and total cholesterol levels in the Framingham Heart Study(BIOMED CENTRAL LTD, 2003-12-31)BACKGROUND: The correlations between systolic blood pressure (SBP) and total cholesterol levels (CHOL) might result from genetic or environmental factors that determine variation in the phenotypes and are shared by family members. Based on 330 nuclear families in the Framingham Heart Study, we used a multivariate normal model, implemented in the software FISHER, to estimate genetic and shared environmental components of variation and genetic and shared environmental correlation between the phenotypes. The natural logarithm of the phenotypes measured at the last visit in both Cohort 1 and 2 was used in the analyses. The antihypertensive treatment effect was corrected before adjustment of the systolic blood pressure for age, sex, and cohort. RESULTS: The univariate correlation coefficient was statistically significant for sibling pairs and parent-offspring pairs, but not significant for spouse pairs. In the bivariate analysis, the cross-trait correlation coefficients were not statistically significant for all relative pairs. The shared environmental correlation was statistically significant, but the genetic correlation was not significant. CONCLUSION: There is no significant evidence for a close genetic correlation between systolic blood pressure and total cholesterol levels. However, some shared environmental factors may determine the variation of both phenotypes.
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ItemA J-protein is an essential subunit of the presequence translocase-associated protein import motor of mitochondria(ROCKEFELLER UNIV PRESS, 2003-11-24)Transport of preproteins into the mitochondrial matrix is mediated by the presequence translocase-associated motor (PAM). Three essential subunits of the motor are known: mitochondrial Hsp70 (mtHsp70); the peripheral membrane protein Tim44; and the nucleotide exchange factor Mge1. We have identified the fourth essential subunit of the PAM, an essential inner membrane protein of 18 kD with a J-domain that stimulates the ATPase activity of mtHsp70. The novel J-protein (encoded by PAM18/YLR008c/TIM14) is required for the interaction of mtHsp70 with Tim44 and protein translocation into the matrix. We conclude that the reaction cycle of the PAM of mitochondria involves an essential J-protein.
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ItemNo Preview AvailableThe PIRO concept: P is for predisposition(BIOMED CENTRAL LTD, 2003-06-01)
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ItemDirect signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1(ROCKEFELLER UNIV PRESS, 2003-09-15)Bone morphogenetic proteins (BMPs) regulate multiple cellular processes, including cell differentiation and migration. Their signals are transduced by the kinase receptors BMPR-I and BMPR-II, leading to Smad transcription factor activation via BMPR-I. LIM kinase (LIMK) 1 is a key regulator of actin dynamics as it phosphorylates and inactivates cofilin, an actin depolymerizing factor. During a search for LIMK1-interacting proteins, we isolated clones encompassing the tail region of BMPR-II. Although the BMPR-II tail is not involved in BMP signaling via Smad proteins, mutations truncating this domain are present in patients with primary pulmonary hypertension (PPH). Further analysis revealed that the interaction between LIMK1 and BMPR-II inhibited LIMK1's ability to phosphorylate cofilin, which could then be alleviated by addition of BMP4. A BMPR-II mutant containing the smallest COOH-terminal truncation described in PPH failed to bind or inhibit LIMK1. This study identifies the first function of the BMPR-II tail domain and suggests that the deregulation of actin dynamics may contribute to the etiology of PPH.
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ItemPoor potential coverage for 7-valent pneumococcal conjugate vaccine, Malawi(CENTER DISEASE CONTROL, 2003-06-01)Streptococcus pneumoniae infections can be prevented by using new conjugate vaccines, but these vaccines have limited serogroup coverage. We report the first serogrouping data from carried and invasive isolates obtained from children and adults in Malawi. The 7-valent vaccine would cover 41% of invasive isolates from children and 25% from adults. A 9-valent vaccine, including types 1 and 5, would cover 66% of invasive isolates from children and 55% from adults.
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ItemLog odds of carrying an Ancestral Mutation in BRCA1 or BRCA2 for a defined personal and family history in an Ashkenazi Jewish woman (LAMBDA)(BIOMED CENTRAL LTD, 2003-01-01)INTRODUCTION: Ancestral mutations in BRCA1 and BRCA2 are common in people of Ashkenazi Jewish descent and are associated with a substantially increased risk of breast and ovarian cancer. Women considering mutation testing usually have several personal and family cancer characteristics, so predicting mutation status from one factor alone could be misleading. The aim of this study was to develop a simple algorithm to estimate the probability that an Ashkenazi Jewish woman carries an ancestral mutation, based on multiple predictive factors. METHODS: We studied Ashkenazi Jewish women with a personal or family history of breast or ovarian cancer and living in Melbourne or Sydney, Australia, or with a previous diagnosis of breast or ovarian cancer and living in the UK. DNA samples were tested for the germline mutations 185delAG and 5382insC in BRCA1, and 6174delT in BRCA2. Logistic regression was used to identify, and to estimate the predictive strength of, major determinants. RESULTS: A mutation was detected in 64 of 424 women. An algorithm was developed by combining our findings with those from similar analyses of a large study of unaffected Jewish women in Washington. Starting with a baseline score, a multiple of 0.5 (based on the logistic regression estimates) is added for each predictive feature. The sum is the estimated log odds ratio that a woman is a carrier, and is converted to a probability by using a table. There was good internal consistency. CONCLUSIONS: This simple algorithm might be useful in the clinical and genetic counselling setting. Comparison and validation in other settings should be sought.
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ItemAdolescent chronic illness: A qualitative study of psychosocial adjustment(ACAD MEDICINE SINGAPORE, 2003-01-01)INTRODUCTION: The purpose of this study was to investigate the psychosocial issues facing young people living with a chronic medical condition. MATERIALS AND METHODS: Subjects were young people with a range of medical conditions who were on a waiting list to participate in the Chronic Illness Peer Support programme at the Centre for Adolescent Health, Royal Children's Hospital, Melbourne, Australia. Young people agreed to in-depth interviews which were taped and transcribed. Thematic analysis was undertaken by two researchers working independently. RESULTS: Thirty-five young people were interviewed. Thematic analysis revealed five broad themes: control (in control, under control, out of control); emotional reactions (happiness, frustration, anger, sadness, anxiety); acceptance (of illness, of others, of self); coping strategies, and; a search for meaning. The importance of social connections was emphasised. While illustrating the difficulties of managing a chronic medical condition during adolescence, a generally positive message emerges about these young people. CONCLUSIONS: Many young people with chronic illness appear relatively resilient in the face of the adjustment challenges presented by their illness. Interventions that allow a young person to explore meaning, build self-esteem, and acceptance through positive social connections are likely to improve adjustment outcomes in this group.
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ItemGeneral anaesthesia or conscious sedation for painful procedures in childhood cancer: the family's perspective(BRITISH MED JOURNAL PUBL GROUP, 2003-03-01)BACKGROUND: Until recently, midazolam sedation was routinely used in our institution for bone marrow aspirates and lumbar punctures in children with cancer. It has been perceived by many doctors and nurses as being well tolerated by children and their families. AIM: To compare the efficacy of inhalational general anaesthesia and midazolam sedation for these procedures. METHODS: A total of 96 children with neoplastic disorders, who received either inhalational general anaesthesia with sevoflurane, nitrous oxide, and oxygen (GA) or sedation with oral or nasal midazolam (SED) as part of their routine preparation for procedures were studied. The experiences of these children were examined during their current procedure and during their first ever procedure. Main outcome measures were the degree of physical restraint used on the child, and the levels of distress and pain experienced by the child during the current procedure and during the first procedure. The family's preference for future procedures was also determined. RESULTS: During 102 procedures under GA, restraint was needed on four occasions (4%) when the anaesthetic mask was first applied, minimal pain was reported, and children were reported as distressed about 25% of the time. During 80 SED procedures, restraint was required in 94%, firm restraint was required in 66%, the child could not be restrained in 14%, median pain score was 6 (scale 0 (no pain) to 6 (maximum pain)), and 90% of the parents reported distress in their child. Ninety per cent of families wanted GA for future procedures. Many families reported dissatisfaction with the sedation regime and raised concerns about the restraint used on their child. CONCLUSIONS: This general anaesthetic regime minimised the need for restraint and was associated with low levels of pain and distress. The sedation regime, by contrast, was much less effective. There was a significant disparity between the perceptions of health professionals and those of families with respect to how children coped with painful procedures.
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ItemFamily risk factors for cannabis use: a population-based survey of Australian secondary school students(CARFAX PUBLISHING, 2003-06-01)The objective of this study was to investigate relationships between adolescent cannabis use and indices of parent - child attachment, family functioning and parent attitudes to drugs and delinquency. A total of 2848 year 9 and 2363 year 11 students participated in the Victorian Adolescent Health and Well-Being Survey (1999). The study was a school-based random sample of 535 metropolitan and rural, government and non-government secondary schools throughout Victoria, Australia. Cannabis use was defined as 'any' and 'weekly' use in the last 30 days. Multivariate logistic regression was used to identify independent associations between cannabis use and parent - child attachment, family functioning and parent attitudes to drugs and delinquency. Cannabis use in year 9 was associated with permissive parent attitudes to drugs and delinquency (any use: adjusted odds ratio (OR) = 8.1; weekly use: adjusted OR = 7.6), and was particularly sensitive to small changes in the quality of the parent - child relationship with risk increasing threefold for those describing their attachment as 'good' compared with 'very good' (any use: adjusted OR = 2.8, weekly use adjusted OR = 2.9). A similar, but more moderate pattern association was evident in year 11. After adjusting for other family and background factors, poor family functioning showed minimal association with level of cannabis use at both year levels. Results suggest that intervention efforts might sensibly target strengthening parent - children relationships and promoting less permissive parent attitudes to drug use.
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ItemAdolescent resilience: a concept analysis(ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2003-02-01)There is need for greater clarity around the concept of resilience as it relates to the period of adolescence. Literature on resilience published between 1990 and 2000 and relevant to adolescents aged between 12- and 18-years of age was reviewed with the aim of examining the various uses of the term, and commenting on how specific ways of conceptualizing of resilience may help develop new research agendas in the field. By bringing together ideas on resilience from a variety of research and clinical perspectives, the purpose of the review is to explicate core elements of resilience in more precise ways, in the hope that greater conceptual clarity will lead to a range of tailored interventions that benefit young people.