Reproducibility of linear cardiac output measurement by Doppler ultrasound alone

Inclusion of a pig aorta in an artificial circulation with pulsed blood flow allowed correlation of minute distance, measured in the aorta by Doppler ultrasound, and absolute blood flow, measured by timed blood-volume collection. The correlation coefficient was 0.99 with a standard error of prediction that was 5.4% of the minute distance predicted at a standard flow rate of 5 litres per minute. The horizontal distance between 95% confidence limits for a single prediction expressed as a percentage of 5 litres per minute was 33%, and this corresponded to the range of flow rates of 1.65 litres per minute that could give rise to the same measurement. In 142 patients duplicate measurements of minute distance were made with repositioning of the ultrasound transducer between recordings. The mean difference between paired readings, expressed as a percentage of the average (SD) of each pair was 5.4 (4.7)%. Thus, the non-invasive measurement of linear cardiac output by Doppler ultrasound is similarly reproducible in vitro and in vivo and compares favourably with the measurement of volumetric cardiac output by thermodilution.     

A case‐control study of Parkinson's disease and tobacco use: Gene‐tobacco interactions

A case‐control study of genetic, environmental, and occupational risk factors for Parkinson's disease (PD) was carried out in five European countries (Italy, Malta, Romania, Scotland, and Sweden) to explore the possible contribution of interactions among host and environmental factors in sporadic PD. Whereas smoking habits confirmed its negative association with PD, a possible modulatory role of genetic polymorphisms was investigated to obtain further mechanistic insights. We recruited 767 cases of PD and 1989 age‐matched and gender‐matched controls. Participants completed an interviewer‐administered questionnaire including the history of smoking habits. The polymorphisms of genes involved either in metabolism of compounds contained in tobacco smoke (CYP2D6, CYP1B1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, SOD2, EPHX and NAT2) or in dopaminergic neurotransmission (MAOA, MAOB, DAT1 and DRD2) were characterized by PCR based methods on genomic DNA. We found evidence of statistically significant gene‐tobacco interaction for GSTM1, NAT2, and GSTP1, the negative association between tobacco smoking and PD being significantly enhanced in subjects expressing GSTM1‐1 activity, in NAT2 fast acetylators, and in those with the GSTP1*B*C haplotype. Owing to the retrospective design of the study, these results require confirmation. © 2010 Movement Disorder Society     

Novel PCR-based diagnostic tools for Charcot-Marie-Tooth type 1A and hereditary neuropathy with liability to pressure palsies.

The majority of cases of Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are the result of DNA duplications and deletions respectively of a 1.5 Mb region on 17p11.2. The region contains the peripheral myelin protein 22 gene (PMP-22) and is flanked by homologous proximal and distal CMT1A-REP elements. The majority of duplications and deletions arise during meiotic recombination following misalignment and unequal crossing-over between the proximal and distal CMT1A-REP elements. The cross-over breakpoints are most frequently located within a 1.7 Kb hotspot of recombination and produce novel duplication or deletion junctional CMT1A-REPs with unique restriction patterns. Here we describe the use of PCR based tests, which amplify a 3.6 Kb region including the 1.7 Kb hotspot from specific CMT1A-REPs, for the rapid diagnosis of CMT1A and HNPP patients. In an analysis of 96 CMT1A and 30 HNPP patients, duplication and deletion events were detected in all samples with cross-over breakpoints known to be within the region amplified by PCR.     

The Experience of Self‐Management in Adolescent Women with Spina Bifida

It is essential for youth with chronic health conditions like spina bifida (SB) to develop self‐management skills to combat vulnerability, achieve self‐sufficiency, and transition to adulthood. The purpose of this qualitative study was to describe the experience of self‐management in 31 adolescent women with SB. Three themes emerged from this study: (1) opportunities to engage in self‐management activities—knowledge, skills, and aspirations; (2) dance of individuation—parental impact on self‐management; and (3) advocacy within self‐management—confronting discrimination and stigma. The findings indicate that assessment and interventions to enhance self‐management in adolescent women with SB are critical for supporting the range of condition‐related and life skills needed for a transition to adulthood and independent living.     

Candida albicans mannan- and protein-induced humoral, cellular and cytokine responses in atopic dermatitis patients

BACKGROUND: The cytokine observed most often in atopic dermatitis (AD) is IL-4, but a role for IL-5 and IFN-gamma in the late and delayed phase reactions has been suggested. In AD with head, neck and shoulder distribution, hypersensitivity to saprophytic yeasts is an important pathogenetic factor. The yeast allergens include both the mannan polysaccharides and the proteins. Mannans are major cross-reacting allergens likely to be involved in the pathogenesis of AD. OBJECTIVE: To characterize the humoral, lymphoproliferative and cytokine (IL-2, 4, 5 and IFN-gamma) responses of peripheral blood mononuclear cells (PBMCs) induced by Candida albicans mannan and protein antigens in AD. METHODS: Fifteen AD patients and seven healthy controls were included. Ficoll-isolated PBMCs were stimulated by PHA and laboratory-generated mannan and protein extracts of C. albicans. Lymphocyte proliferation was measured and cytokine production was studied by ELISA. The antigen-specific IgG and IgE antibodies were analysed by ELISA and nitrocellulose RAST. RESULTS: In AD mannan (P < 0.005) and protein (P < 0.002), specific IgE levels were higher than in healthy controls. Both mannan and protein-specific lymphoproliferations (both: P < 0.02) were higher in AD than in healthy controls. Mannan, but not protein, induced long lasting IL-2 and IL-4 productions from 24 h lasting up to 66-96 h and IL-5 and IFN-gamma productions with elevated levels at 66 and 96 h. The mannan-induced IL-2 (P = 0.015) and IFN-gamma (P < 0.005) were increased in AD as compared with healthy controls. Significant correlations were seen between the protein-induced proliferation responses and both serum total IgE (r = 0.59, P < 0.01) and protein-specific IgE (r = 0.65, P < 0.005). The mannan-induced IL-2 responses correlated with the specific IgE (r = 0.62, P < 0.01) and proliferation (r = 0.51, P < 0.02) and S-IgE level (r = 0.71, P < 0. 002). Mannan-induced IL-4 and IFN-gamma productions also correlated (r = 0.43, P < 0.05). CONCLUSIONS: C. albicans mannan induced elevated IL-2 and IFN-gamma responses in AD patients. The correlations of the cytokine responses with mannan-induced IgE and proliferation responses suggest that C. albicans mannan induced TH1 type cytokine responses are involved in AD.     

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project: An open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728]

Background

Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification [8] has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine.

Methods/design

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

     

‘It's their blood not mine’: Who's responsible for (not) telling relatives about genetic risk?

With advances in the ‘new genetics’, an increasing number of people will have access to genetic information and predictive or susceptibility testing. Genetic knowledge has implications for individuals themselves, as well as other family members. In general, health professionals encourage people to pass on genetic risk information to their relatives. However, the disclosure of such information is not always straightforward and, consequently, some people may not be aware of their risk. If risk information is actively withheld, genetic counsellors may need to determine whether they have a duty to pass this on, particularly when preventive action can be taken. To date, little research has explored the barriers and facilitators in family communication about genetic risk. This paper draws on empirical data from a qualitative study exploring communication in families with late-onset familial disease. Interviews were conducted with participants who received genetic counselling for risk of Huntington's disease and hereditary breast or ovarian cancer. Participants' experiences of who was responsible for (not) telling relatives in their families is studied. A number of themes were identified. These were: (1) ‘whose place is it to tell’, (2) the gendering of disclosure, and (3) who is ‘family’. The implications of these findings are considered.     

父母的母语与儿童预防性医疗行为的差异有关

目的:研究父母的母语为非英语的婴儿比父母的母语为英语的婴儿是否更不易接受推荐的预防性医疗行为。研究设计:笔者对1999年1月1日至2000年9月30日期间在华盛顿州出生的所有38793例参加医疗救助的1岁婴儿进行回顾性组群研究。主要因素为自己报告的父母的母语。笔者使用多参数回