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41.
Long QT syndrome and Brugada syndrome are potentially fatal inherited arrhythmogenic diseases. Thanks to the contribution of molecular genetics, the genetic bases, pathogenesis, and genotype-phenotype correlation of both diseases have been progressively unveiled and shown to have an extremely high degree of genetic heterogeneity. The clinical manifestation of the diseases is also highly variable. Symptomatic patients experience ventricular tachyarrhythmias which may lead to recurrent syncope and/or sudden cardiac death. In long QT syndrome patients with syncope, therapy with beta-blockers has proven effective. When, despite beta-blocker treatment, arrhythmia-related symptoms continue to occur, an implantable cardioverter defibrillator is indicated. Such a device should also be implanted in resuscitated patients. In symptomatic patients with Brugada syndrome, the implantable cardioverter defibrillator is the only life-saving option. In asymptomatic patients with a Brugada ECG pattern, risk stratification has become of utmost importance in order to discover which patients really need definitive treatment. 相似文献
42.
The objective of the study was to identify commonalities among the International Classification of Functioning, Disability
and Health (ICF) Core Sets of osteoarthritis (OA), osteoporosis (OP), low back pain (LBP), rheumatoid arthritis (RA) and chronic
widespread pain (CWP). The aim is to identify relevant categories for the development of a tentative ICF Core Set for musculoskeletal
and pain conditions. The ICF categories common to the five musculoskeletal and pain conditions in the Brief and Comprehensive
ICF Core Sets were identified in three steps. In a first step, the commonalities across the Brief and Comprehensive ICF Core
Sets for these conditions were examined. In a second and third step, we analysed the increase in commonalities when iteratively
excluding one or two of the five conditions. In the first step, 29 common categories out of the total number of 120 categories
were identified across the Comprehensive ICF Core Sets of all musculoskeletal and pain conditions, primarily in the component
activities and participation. In the second and third step, we found that the exclusion of CWP across the Comprehensive ICF
Core Sets increased the commonalities of the remaining four musculoskeletal conditions in a maximum of ten additional categories.
The Brief ICF Core Sets of all musculoskeletal and pain conditions contain four common categories out of a total number of
62 categories. The iterative exclusion of a singular condition did not significantly increase the commonalities in the remaining.
Based on our analysis, it seems possible to develop a tentative Comprehensive ICF Core Set across a number of musculoskeletal
conditions including LBP, OA, OP and RA. However, the profile of functioning in people with CWP differs considerably and should
not be further considered for a common ICF Core Set. 相似文献
43.
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45.
Toller IM Neelsen KJ Steger M Hartung ML Hottiger MO Stucki M Kalali B Gerhard M Sartori AA Lopes M Müller A 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(36):14944-14949
The bacterial pathogen Helicobacter pylori chronically infects the human gastric mucosa and is the leading risk factor for the development of gastric cancer. The molecular mechanisms of H. pylori-associated gastric carcinogenesis remain ill defined. In this study, we examined the possibility that H. pylori directly compromises the genomic integrity of its host cells. We provide evidence that the infection introduces DNA double-strand breaks (DSBs) in primary and transformed murine and human epithelial and mesenchymal cells. The induction of DSBs depends on the direct contact of live bacteria with mammalian cells. The infection-associated DNA damage is evident upon separation of nuclear DNA by pulse field gel electrophoresis and by high-magnification microscopy of metaphase chromosomes. Bacterial adhesion (e.g., via blood group antigen-binding adhesin) is required to induce DSBs; in contrast, the H. pylori virulence factors vacuolating cytotoxin A, γ-glutamyl transpeptidase, and the cytotoxin-associated gene (Cag) pathogenicity island are dispensable for DSB induction. The DNA discontinuities trigger a damage-signaling and repair response involving the sequential ataxia telangiectasia mutated (ATM)-dependent recruitment of repair factors--p53-binding protein (53BP1) and mediator of DNA damage checkpoint protein 1 (MDC1)--and histone H2A variant X (H2AX) phosphorylation. Although most breaks are repaired efficiently upon termination of the infection, we observe that prolonged active infection leads to saturation of cellular repair capabilities. In summary, we conclude that DNA damage followed by potentially imprecise repair is consistent with the carcinogenic properties of H. pylori and with its mutagenic properties in vitro and in vivo and may contribute to the genetic instability and frequent chromosomal aberrations that are a hallmark of gastric cancer. 相似文献
46.
"What to measure" refers to domains stable over time. "How to measure" is constantly evolving. Lacking a common terminology and common underlying conceptual model of functioning and disability, what and how to measure have been described differently in the various OMERACT Core Sets. With the approval of the International Classification of Functioning, Disability and Health (ICF) by the World Health Assembly in 2001, we now have a universally conceptual model that integrates the biomedical and societal model of functioning and disability. The so-called ICF Core Sets can be used as a basis for the further specification of OMERACT domains addressing aspects of functioning. In line with the successful approach taken by OMERACT, it is suggested to comprehensively specify the domain "function" when defining "what should be measured," and only then to recommend how to measure or which health status measure to use. We recommend comparing the specifications of domains addressing aspects of functioning of OMERACT Core Sets already established with the ICF Core Sets, and examine whether the ICF Core Sets may be useful for the further specification of these domains. 相似文献
47.
Trans-differentiation of prostatic stromal cells leads to decreased glycoprotein hormone alpha production 总被引:1,自引:0,他引:1
Rumpold H Mascher K Untergasser G Plas E Hermann M Berger P 《The Journal of clinical endocrinology and metabolism》2002,87(11):5297-5303
Age-related development of benign prostatic hyperplasia is an important health issue in developed countries. The histopathogenetic hallmark of this disease is the increase in relative and absolute numbers of smooth muscle cells (SMC). Glycoprotein hormone alpha-subunit (GPHalpha) is expressed in the human prostate, and, because of its structural similarities to other cystine knot growth factors, it has been considered to have growth regulatory functions of its own. Primary cell cultures allowing for selective cultivation of prostatic epithelial cells, fibroblasts, and SMC were established. Directed trans-differentiation and cellular homogeneity was pursued by confocal scanning laser microscopy with cell type-specific markers. GPHalpha production by these cells was assessed by immunofluorimetric assays. Its predominant source was young fibroblasts, whereas replicative senescent fibroblasts, SMC, and control fibroblasts from foreskin did not produce significant amounts. Functionally, GPHalpha reduced growth of stromal cells at concentrations of 10 and 100 nmol/liter as shown by cell viability assays. It is concluded that histogenetic reorganization over the adult lifetime, guided by endocrine factors like steroid hormones together with senescence of fibroblasts, leads to a decreased production of growth inhibitors, such as GPHalpha, favoring proliferation and the development of benign prostatic hyperplasia. 相似文献
48.
Stamm TA Cieza A Coenen M Machold KP Nell VP Smolen JS Stucki G 《Arthritis and rheumatism》2005,53(3):431-439
OBJECTIVE: To validate the International Classification of Functioning, Disability and Health (ICF) Comprehensive Core Set for Rheumatoid Arthritis (RA) from the patient perspective. METHODS: Patients with RA were interviewed about their problems in daily functioning. Interviews were tape recorded and transcribed verbatim. Interview texts were divided into meaning units. The concepts contained in these meaning units were linked to the ICF according to 10 established linking rules. Of the transcribed data, 15% were analyzed and linked by a second health professional. The degree of agreement was calculated using the kappa statistic. RESULTS: Twenty-one patients were interviewed. Two hundred twenty different concepts contained in 367 meaning units were identified in the qualitative analysis of the interviews and linked to 109 second-level ICF categories. Of the 76 second-level categories from the ICF RA Core Set, 63 (83%) were also found in the interviews. Twenty-five second-level categories, which are not part of the current ICF RA Core Set, were identified in the interviews. The result of the kappa statistic for agreement was 0.62 (95% boot-strapped confidence interval 0.59-0.66). CONCLUSION: The validity of the ICF RA Core Set was supported by the perspective of individual patients. However, some additional issues raised in this study but not covered in the current ICF RA Core Set need to be investigated. 相似文献
49.
The international classification of functioning, disability and health (ICF) has been developed by the World Health Organization (WHO) to describe health and handicaps in more detail in order to allow better classification and registration. The ICF comprises the disease, structure, functioning, activity and participation as well as corresponding factors related to the individual and the environment. By this means an integrated concept and assessment of biologic, individual and social aspects of health is attained. The ICF represents an essential addition to the international classification of diagnoses (ICD) and procedures (OPS). The ICF consists of two interelated parts. The first part that describes functioning and disability contains two components: one related to the body (functioning and structure) and one related to activity and participation. The second part describes the context factors (related to the environment and the individual). Body functions are the physical and mental functions of the organism. Body structures are the anatomically defined parts of the body. Activity describes how a task is solved or how an action can be performed and participation is the way in which an individual is involved in the environment and society. The ICF categories make the classification of all aspects of functioning and health in individuals easier and independent of diseases or specific assessment instruments. However, since there are more than 1,400 categories, the ICF cannot be used in daily practice in this form. Therefore, attempts are made to identify those parts of the ICF that are relevant for specific patients, situations and disease states or activities. These are the so-called ICF core sets. This article attempts to give an overview on the ICF, to provide an insight into recent work on the ICF related to musculoskeletal and rheumatic diseases and, finally, to describe how an ICF core set for patients with acute arthritis was made possible by means of a successful multicenter cooperative effort. 相似文献
50.