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141.
Treatment of acute myocardial infarction has changed considerably during the last few years with the introduction of primary coronary angioplasty. In the acute phase risk stratification is largely based on simple clinical parameters, laboratory markers of myocardial injury and 12-lead electrocardiography. The electrocardiogram is of crucial importance especially during the first few hours after initiation of chest pain when important therapeutic decisions are made. Biochemical markers of myocardial injury are usually not elevated at that time point. Cases with inferior ST-elevation myocardial infarction from our hospital are presented to show how anatomical interpretation of ECG recorded during chest pain helps to risk stratify patients. 相似文献
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143.
BRAF and NRAS Mutations Are Frequent in Nodular Melanoma but Are not Associated with Tumor Cell Proliferation or Patient Survival 总被引:1,自引:0,他引:1
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Lars A. Akslen Sabrina Angelini† Oddbjørn Straume Ingeborg M. Bachmann ers Molven Kari Hemminki†‡ Rajiv Kumar†‡ 《Journal of general internal medicine》2005,20(5):312-317
Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) or NRAS (neuroblastoma RAS viral [V-ras] oncogene homolog) genes in cutaneous melanoma, but the relationship between these alterations and tumor cell proliferation has not been examined in human melanoma. In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%). The figures for NRAS mutations were 27% and 22%, respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but one case, and were maintained from primary tumors through their metastases. Mutations, however, were not associated with tumor cell proliferation by Ki-67 expression, tumor thickness, microvessel density, or vascular invasion, and there were no differences in patient survival. Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma. 相似文献
144.
Jannine D. Cody Courtney Sebold Patricia Heard Erika Carter Bridgette Soileau Minire Hasi-Zogaj Annice Hill David Rupert Brian Perry Louise O'Donnell Jon Gelfond Jack Lancaster Peter T. Fox Daniel E. Hale 《American journal of medical genetics. Part C, Seminars in medical genetics》2015,169(3):265-280
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Risto Raivio Doris Holmberg-Marttila Kari J Mattila 《The British journal of general practice》2014,64(627):e657-e663
Background
Continuity of care is an essential aspect of quality in general practice. This study is the first systematic follow-up of Finnish primary care patients’ assessments with regard to personal continuity of care.Aim
To ascertain whether patient-reported longitudinal personal continuity of care is related to patient characteristics and their consultation experiences, and how this had changed over the study period.Design and setting
A 15-year follow-up questionnaire survey that took place at Tampere University Hospital catchment area, Finland.Method
The survey was conducted among patients attending health centres in the Tampere University Hospital catchment area from 1998 until 2013. From a sample of 363 464 patients, a total of 157 549 responded. The responses of patients who had visited a doctor during the survey weeks (n = 97 468) were analysed. Continuity of care was assessed by asking the question: ‘When visiting the health centre, do you usually see the same doctor?’; patients could answer ‘yes’ or ‘no’.Results
Approximately half of the responders had met the same doctor when visiting the healthcare centre. Personal continuity of care decreased by 15 percentage points (from 66% to 51%) during the study years. The sense of continuity was linked to several patients’ experiences of the consultation. The most prominent factor contributing to the sense of continuity of care was having a doctor who was specifically appointed (odds ratio 7.28, 95% confidence interval = 6.65 to 7.96).Conclusion
Continuity of care was proven to enhance the experienced quality of primary care. Patients felt that continuity of care was best realised when they could consult a doctor who had been specifically appointed to them. Despite efforts of the authorities, over the past 15 years patient-reported continuity of care has declined in Finland. 相似文献148.
Lasse Pihlstrøm Aina Rengmark Kari Anne Bjørnarå Mathias Toft 《Annals of human genetics》2014,78(3):243-252
Next‐generation sequencing technologies will dominate the next phase of discoveries in human genetics, but considerable costs may still represent a limitation for studies involving large sample sets. Targeted capture of genomic regions may be combined with deep sequencing of DNA pools to efficiently screen sample cohorts for disease‐relevant mutations. We designed a 200 kb HaloPlex kit for PCR‐based capture of all coding exons in 71 genes relevant to Parkinson's disease and other neurodegenerative disorders. DNA from 387 patients with Parkinson's disease was combined into 39 pools, each representing 10 individuals, before library preparation with barcoding and Illumina sequencing. In this study, we focused the analysis on six genes implicated in Mendelian Parkinson's disease, emphasizing quality metrics and evaluation of the method, including validation of variants against individual genotyping and Sanger sequencing. Our data showed 97% sensitivity to detect a single nonreference allele in pools, rising to 100% where pools achieved sequence depth above 80x for the relevant position. Pooled sequencing detected 18 rare nonsynonymous variants, of which 17 were validated by independent methods, corresponding to a specificity of 94%. We argue that this design represents an effective and reliable approach with possible applications for both complex and Mendelian genetics. 相似文献
149.
Expression of an anti‐RNA autoantibody in a mouse model of SLE increases neutrophil and monocyte numbers as well as IFN‐I expression
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Jin‐Hwan Han Benjamin R. Umiker Anastasia A. Kazimirova Michael Fray Parimal Korgaonkar Erik Selsing Thereza Imanishi‐Kari 《European journal of immunology》2014,44(1):215-226
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of antinucleic acid autoantibodies, high levels of circulating type I interferon (IFN‐I), and an IFN‐I‐dependent elevated expression of activating FcγR. Increases in neutrophils and monocytes are often observed in clinical SLE, but how these contribute to autoantibody and IFN‐I production is poorly understood. Here, we analyzed SLE pathogenesis in 564Igi mice, an SLE‐model strain carrying gene‐targeted heavy and light chain antibody genes encoding an anti‐RNA autoantibody in a C57BL/6 background. Similar to human SLE patients, 564Igi mice produce anti‐RNA autoantibodies and expanded neutrophil and monocyte populations. These myeloid cells produced IFN‐I and exhibit increased FcγRIV expression induced via an IFN‐I autocrine loop. A direct effect of IFN‐I on 564Igi BM B cells and neutrophils was supported by their upregulation of “IFN‐I signature genes”. In addition, 564Igi developing B cells showed upregulated TLR7 resulting in IgG2a/2b class switch recombination and autoantibody production. Our results indicate that the production of anti‐RNA autoantibody is sufficient to induce an increase of BM, blood, and spleen IFN‐I‐producing neutrophils, and suggest a mechanism by which autoantibody and IFN‐I contribute to SLE by activating B lymphocytes, neutrophils, and monocyte effector cells in vivo. 相似文献
150.
Kari J Kurppa Javier Catón Peter R Morgan Ari Ristimäki Blandine Ruhin Jari Kellokoski Kristiina Heikinheimo 《The Journal of pathology》2014,232(5):492-498
Ameloblastoma is a benign but locally infiltrative odontogenic neoplasm. Although ameloblastomas rarely metastasise, recurrences together with radical surgery often result in facial deformity and significant morbidity. Development of non‐invasive therapies has been precluded by a lack of understanding of the molecular background of ameloblastoma pathogenesis. When addressing the role of ERBB receptors as potential new targets for ameloblastoma, we discovered significant EGFR over‐expression in clinical samples using real‐time RT–PCR, but observed variable sensitivity of novel primary ameloblastoma cells to EGFR‐targeted drugs in vitro. In the quest for mutations downstream of EGFR that could explain this apparent discrepancy, Sanger sequencing revealed an oncogenic BRAF V600E mutation in the cell line resistant to EGFR inhibition. Further analysis of the clinical samples by Sanger sequencing and BRAF V600E‐specific immunohistochemistry demonstrated a high frequency of BRAF V600E mutations (15 of 24 samples, 63%). These data provide novel insight into the poorly understood molecular pathogenesis of ameloblastoma and offer a rationale to test drugs targeting EGFR or mutant BRAF as novel therapies for ameloblastoma. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk 相似文献