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51.
Kemp Z Carvajal-Carmona L Spain S Barclay E Gorman M Martin L Jaeger E Brooks N Bishop DT Thomas H Tomlinson I Papaemmanuil E Webb E Sellick GS Wood W Evans G Lucassen A Maher ER Houlston RS;ColoRectal tumour Gene Identification 《Human molecular genetics》2006,15(19):2903-2910
To identify a novel susceptibility gene for colorectal cancer (CRC), we conducted a genome-wide linkage analysis of 69 pedigrees segregating colorectal neoplasia in which involvement of known loci had been excluded, using a high-density single nucleotide polymorphism (SNP) array containing 10,204 markers. Multipoint linkage analyses were undertaken using both non-parametric (model-free) and parametric (model-based) methods. After the removal of SNPs in strong linkage disequilibrium, we obtained a maximum non-parametric linkage statistic of 3.40 (P=0.0003) at chromosomal region 3q21-q24. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a dominant model (HLOD=3.10, genome-wide P=0.038) with 62% of families linked to the locus. We provide evidence for a novel CRC susceptibility gene. Further studies are needed to confirm this localization and to evaluate the contribution of this locus to disease incidence. 相似文献
52.
Anke J E de Veer Barbara Stringer Berno van Meijel Anneke L Francke 《BMC palliative care》2018,17(1):119
Background
People experiencing homelessness often encounter progressive incurable somatic diseases in combination with psychiatric and psychosocial problems, and many need palliative care at the end of their lives. Little is known about how palliative care for this group can be started in good time and provided optimally. The objective of this paper is to give insight into the extent people experiencing homelessness have access to good palliative care.Methods
Qualitative in-depth interviews were held to reconstruct the cases of 19 people experiencing homelessness in the Netherlands. Eight cases concerned persons being in the palliative phase (using the surprise question) and the other 11 cases concerned persons recently died after a period of ill health due to somatic illness. We used purposive sampling until data saturation was reached. The total number of interviews was 52. All interviews were transcribed verbatim and analysed inductively.Results
Three key themes were: ‘late access’, ‘capricious trajectory’ and ‘complex care’. The first key theme refers to the often delayed start of palliative care, because of the difficulties in recognizing the need for palliative care, the ambivalence of people experiencing homelessness about accepting palliative care, and the lack of facilities with specific expertise in palliative care for them. The second key theme refers to the illness trajectory, which is often capricious because of the challenging behaviour of people experiencing homelessness, an unpredictable disease process and a system not being able to accommodate or meet their needs. The third key theme refers to the complexity of their care with regard to pain and symptom control, psychosocial and spiritual aspects, and the social network.Conclusions
The care for in the palliative phase does not satisfy the core requirements of palliative care since there are bottlenecks regarding timely identification, the social network, and the assessment and management of physical symptoms and psychosocial and spiritual care needs. Education in palliative care of outreach professionals, training staff in shelters in the provision of palliative care, and building a network of palliative care specialists for people experiencing homelessness.53.
Nienke Bekkema Anke J.E. de Veer Annemieke M.A. Wagemans Cees M.P.M. Hertogh Anneke L. Francke 《Patient education and counseling》2014
Objective
This paper explores the personal beliefs and specific considerations of professionals regarding decisions about potentially burdensome medical interventions in the end-of-life care for people with intellectual disabilities (ID).Methods
A survey questionnaire covering decision making about potentially burdensome medical interventions was sent to nationally representative samples of 294 ID care staff-members, 273 ID physicians and 1000 GPs.Results
Professionals predominantly believed that considerations about quality of life are most important. Quality of life and wellbeing were also frequently considered in both decisions to start/continue an intervention and decisions to forgo/withdraw an intervention. Seventy percent believed that people with ID should always be informed about interventions, and 61% would respect a refusal by the person. The family's wishes were explicitly considered more often than the wishes of the person with ID.Conclusion
Although respondents agree that the quality of life is highly important, the wishes of people with ID (especially of those with severe/profound ID) were often not considered in decisions about potentially burdensome medical interventions.Practice implications
To enhance the active involvement of people with ID in decision making we recommend that professionals integrate collaborative principles in decision making and make use of pictorial and easy reading resources. 相似文献54.
Beijing and Haarlem genotypes are overrepresented among children with drug-resistant tuberculosis in the Western Cape Province of South Africa 下载免费PDF全文
Marais BJ Victor TC Hesseling AC Barnard M Jordaan A Brittle W Reuter H Beyers N van Helden PD Warren RM Schaaf HS 《Journal of clinical microbiology》2006,44(10):3539-3543
Drug resistance among children with culture-confirmed tuberculosis (TB) provides an accurate measure of transmitted drug resistance within the community. We describe the genotype diversity in children with culture-confirmed TB and investigate the relationship between genotype and drug resistance. A prospective study was conducted from March 2003 through August 2005 at Tygerberg Children's Hospital, in the Western Cape Province of South Africa. All children (<13 years of age) diagnosed with culture-confirmed TB were included. Genotype analysis and phenotypic drug susceptibility testing were performed on the first culture-positive isolate from each patient. Mutation analysis was performed on all drug-resistant isolates. Spoligotyping was successfully performed on isolates from 391/399 (98%) children diagnosed with culture-confirmed TB. Drug susceptibility testing was also performed on 391 isolates; 49 (12.5%) were resistant to isoniazid, and 20 (5.1%) of these were resistant to both isoniazid and rifampin. Beijing was the most common genotype family, identified in 130/391 (33.2%) cases, followed by LAM in 114/391 (29.2%) cases. The presence of both Beijing and Haarlem genotype families was significantly associated with drug resistance (26/49 [53.1%] versus 113/342 [33.0%]; odds ratio, 1.7; 95% confidence interval, 1.0 to 2.9). The high prevalence of Beijing and LAM in children with culture-confirmed TB reflects considerable transmission of these genotype families within the community. The overrepresentation of Beijing and Haarlem genotype families in children with drug-resistant TB demonstrates their contribution to transmitted drug resistance and their potential importance in the emergent drug-resistant TB epidemic. 相似文献
55.
Nellist M van den Heuvel D Schluep D Exalto C Goedbloed M Maat-Kievit A van Essen T van Spaendonck-Zwarts K Jansen F Helderman P Bartalini G Vierimaa O Penttinen M van den Ende J van den Ouweland A Halley D 《European journal of human genetics : EJHG》2009,17(3):319-328
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of hamartomas in a variety of organs and tissues. The disease is caused by mutations in either the TSC1 gene on chromosome 9q34 or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, interact to form a protein complex that inhibits signal transduction to the downstream effectors of the mammalian target of rapamycin (mTOR). Here we investigate the effects of putative TSC1 missense mutations identified in individuals with signs and/or symptoms of TSC on TSC1-TSC2 complex formation and mTOR signalling. We show that specific amino-acid substitutions close to the N-terminal of TSC1 reduce steady-state levels of TSC1, resulting in the activation of mTOR signalling and leading to the symptoms of TSC. 相似文献
56.
Ans M W van den Ouweland Peter Elfferich Bernard A Zonnenberg Willem F Arts Tjitske Kleefstra Mark D Nellist Jose M Millan Caroline Withagen-Hermans Anneke J A Maat-Kievit Dicky J J Halley 《European journal of human genetics : EJHG》2011,19(2):157-163
Tuberous sclerosis complex (TSC), an autosomal dominant disorder, is a multisystem disease with manifestations in the central nervous system, kidneys, skin and/or heart. Most TSC patients carry a pathogenic mutation in either TSC1 or TSC2. All types of mutations, including large rearrangements, nonsense, missense and frameshift mutations, have been identified in both genes, although large rearrangements in TSC1 are scarce. In this study, we describe the identification and characterisation of eight large rearrangements in TSC1 using multiplex ligation-dependent probe amplification (MLPA) in a cohort of 327 patients, in whom no pathogenic mutation was identified after sequence analysis of both TSC1 and TSC2 and MLPA analysis of TSC2. In four families, deletions only affecting the non-coding exon 1 were identified. In one case, loss of TSC1 mRNA expression from the affected allele indicated that exon 1 deletions are inactivating mutations. Although the number of TSC patients with large rearrangements of TSC1 is small, these patients tend to have a somewhat milder phenotype compared with the group of patients with small TSC1 mutations. 相似文献
57.
Raquel Dávila Fajardo Rob van Os Marrije R. Buist Lon Uitterhoeve Anneke M. Westermann Gemma G. Kenter Coen R.N. Rasch Lukas J.A. Stalpers 《Gynecologic oncology》2014
Objective
The aim of this study is to investigate the impact of treatment policy changes in cervical cancer patients treated with adjuvant (chemo) radiotherapy.Methods
Between 1970 and 2007, 292 patients received adjuvant radiotherapy after a radical hysterectomy with pelvic lymphadenectomy for early stage cervical carcinoma. All patients received pelvic radiotherapy (40 Gy–46 Gy in 1.8 Gy–2 Gy/fraction). Vaginal vault brachytherapy boost (10–14 Gy) was increasingly used for patients with high-risk factors, and since 1993 systematically applied in patients with at least 2 of the 3 risk factors: adenocarcinoma, nodal involvement and parametrial invasion. Cisplatin-based chemotherapy was introduced in this group of patients from 2000.Results
The 5-year cumulative risk of local recurrence (CRLR) was 13% (95%CI 9%–17%), resulting in an overall 5-year survival (OS) of 78% (95%CI 83%–73%). Since 1970, the OR for the 5-year locoregional recurrence risk (LRR) decreased from 2.5 to 1.15 (linear-OR = − 0.02/year). The OR for the 5-year mortality risk reduced from 2.2 in 1970 to 1.0 in 2007 (linear-OR = − 0.03/year). The largest risk reductions were observed before 1990 with a minor rise after 2002. The risk of severe late toxicity reduced from 1.8% to 1.5% (linear-OR = − 0.03/year). The addition of concomitant adjuvant chemotherapy since 2000 may have benefited a subgroup of patients with squamous cell carcinoma, but not the patients with adenocarcinoma, and after introduction of chemotherapy the risk of severe late toxicity tripled from 2% to 7%.Conclusion
Since 1970, tumour recurrence risk and mortality have decreased, as radiation dose increased. The potential benefit of concomitant adjuvant chemotherapy could not be demonstrated in this nonrandomized study. 相似文献58.
Patriek Mistiaen Andre Ament Anneke L Francke Wilco Achterberg Ruud Halfens Janneke Huizinga Henri Post 《BMC health services research》2010,10(1):226
Background
Many devices are in use to prevent pressure ulcers, but from most little is known about their effects and costs. One such preventive device is the Australian Medical Sheepskin that has been proven effective in three randomized trials. In this study the costs and savings from the use of the Australian Medical Sheepskin were investigated from the perspective of a nursing home. 相似文献59.
Phenotypically resembling myeloid derived suppressor cells are increased in children with HIV and exposed/infected with Mycobacterium tuberculosis 下载免费PDF全文
Nelita Du Plessis Ruschca Jacobs Andrea Gutschmidt Zhuo Fang Paul D. van Helden Manfred B. Lutz Anneke C. Hesseling Gerhard Walzl 《European journal of immunology》2017,47(1):107-118
Increased disease susceptibility during early life has been linked to immune immaturity, regulatory T‐cell/TH2 immune biasing and hyporesponsiveness. The contribution of myeloid derived suppressor cells (MDSCs) remains uninvestigated. Here, we assessed peripheral MDSC in HIV‐infected and ‐uninfected children with tuberculosis (TB) disease before, during and after TB treatment, along with matched household contacts (HHCs), HIV‐exposed, ‐infected and ‐uninfected children without recent TB exposure. Serum analytes and enzymes associated with MDSC accumulation/activation/function were measured by colorimetric‐ and fluorescence arrays. Peripheral frequencies of cells phenotypically resembling MDSCs were significantly increased in HIV‐exposed uninfected (HEU) and M.tb‐infected children, but peaked in children with TB disease and remained high following treatment. MDSC in HIV‐infected (HI) children were similar to unexposed uninfected controls; however, HAART‐mediated MDSC restoration to control levels could not be disregarded. Increased MDSC frequencies in HHC coincided with enhanced indoleamine‐pyrrole‐2,3‐dioxygenase (IDO), whereas increased MDSC in TB cases were linked to heightened IDO and arginase‐1. Increased MDSC were paralleled by reduced plasma IP‐10 and thrombospondin‐2 levels in HEU and significantly increased plasma IL‐6 in HI HHC. Current investigations into MDSC‐targeted treatment strategies, together with functional analyses of MDSCs, could endorse these cells as novel innate immune regulatory mechanism of infant HIV/TB susceptibility. 相似文献
60.
Ormrod D Spencer CM 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》1999,11(6):431-438
black triangle Levosalbutamol is a chirally pure beta(2)-adrenoceptor agonist developed from racemic salbutamol. black triangle The therapeutically inactive (S)-enantiomer in racemic salbutamol may be associated with increased airway hyperreactivity in patients with asthma. Levosalbutamol aims to provide equivalent control of symptoms to salbutamol but without this potential unfavourable effect. black triangle The pharmacodynamic and pharmacokinetic profiles of levosalbutamol were similar to those of racemic salbutamol and no additional effects were reported. Levosalbutamol was bronchoprotective following a methacholine challenge. black triangle A large clinical study demonstrated that inhaled levosalbutamol, 0.625mg or 1.25mg 3 times daily, provided effective relief from the symptoms of asthma. Levosalbutamol 0.625mg was at least as effective as racemic salbutamol 2.5mg. black triangle Levosalbutamol was well tolerated in clinical trials and the risk/benefit ratio was reported to be superior to that of racemic salbutamol. 相似文献