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Bassem R. Haddad Lei Gu Tuomas Mirtti Ayush Dagvadorj Paraskevi Vogiatzi David T. Hoang Renu Bajaj Benjamin Leiby Elyse Ellsworth Shauna Blackmon Christian Ruiz Mark Curtis Paolo Fortina Adam Ertel Chengbao Liu Hallgeir Rui Tapio Visakorpi Lukas Bubendorf Marja T. Nevalainen 《The American journal of pathology》2013,182(6):2264-2275
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Maciej Tomaszewski James Eales Matthew Denniff Stephen Myers Guat Siew Chew Christopher P. Nelson Paraskevi Christofidou Aishwarya Desai Cara Büsst Lukasz Wojnar Katarzyna Musialik Jacek Jozwiak Radoslaw Debiec Anna F. Dominiczak Gerjan Navis Wiek H. van Gilst Pim van der Harst Nilesh J. Samani Stephen Harrap Pawel Bogdanski Ewa Zukowska-Szczechowska Fadi J. Charchar 《Journal of the American Society of Nephrology : JASN》2015,26(12):3151-3160
The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10−5) and diastolic BP (P=7.61×10−3) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10−3). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP. 相似文献
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Development of mitral stenosis after single mitraclip insertion for severe mitral regurgitation 下载免费PDF全文
James Cockburn MD MRCP Paraskevi Fragkou MBBS David Hildick‐Smith MD MRCP 《Catheterization and cardiovascular interventions》2014,83(2):297-302
We report the first case of mitral stenosis following Mitra‐Clip insertion in a patient with symptomatic NYHA IV heart failure, secondary to severe mitral regurgitation (MR). A 79‐year‐old female with a history of prior aortic valve replacement underwent percutaneous mitral valve (MV) repair. A single clip was advanced coaxially down onto the MV under TOE guidance, with the anterior and posterior leaflets clipped together between A2 and P2. TOE confirmed a significant reduction in MR (grade 4 to grade 1). Despite initial symptomatic relief, she represented 3 months later with similar symptoms. Repeat TOE confirmed a well positioned Mitra‐Clip with mild residual MR. However, the possibility of significant mitral stenosis was raised due to the presence of significant turbulence through the bi‐orifice valve, with a peak gradient of 25 mm Hg. In addition there was evidence of severe functional tricuspid valve (TV) regurgitation with elevated pulmonary artery pressures (PAP 90 mm Hg), confirmed on subsequent right heart catheterization. After repeated heart team discussions and a failure of optimal medical therapy, and despite a logistic EuroScore of 35.5, minimally invasive surgical replacement of the MV and simultaneous TV repair was undertaken via a right thoracotomy. Despite procedural success and initial good postoperative response, the patient died subsequently from a combination of hospital‐acquired pneumonia and significant gastrointestinal bleeding (post operative day 35). Mitra‐Clip is a promising novel approach to MV repair. The establishment of further clinical and echocardiographic based selection criteria will help identify the correct patients for this treatment. © 2013 Wiley Periodicals, Inc. 相似文献
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Irini Flouri Theodora E. Markatseli Paraskevi V. Voulgari Kyriaki A. Boki Ioannis Papadopoulos Loukas Settas Dimitrios Zisopoulos Fotini N. Skopouli Alexios Iliopoulos George K. Bertsias Pierre Geborek Alexandros A. Drosos Dimitrios T. Boumpas Prodromos Sidiropoulos 《Seminars in arthritis and rheumatism》2014
Objective
To compare effectiveness, drug survival, and safety between infliximab, adalimumab, and etanercept, in a nationwide cohort of rheumatoid arthritis (RA) patients.Methods
This study is a prospective cohort study of 1208 active RA patients. Effectiveness, drug survival, and serious adverse events during entire follow-up (median 2.9 years) were monitored.Results
EULAR and CDAI responses were comparable between the three agents (EULAR good/moderate responses at 12 months ranged 76–79%). At 12 months, 15–23% achieved remission. For adalimumab and etanercept, adjusted hazard rate (HR) for EULAR/ACR remission (reference: infliximab) was 2.7 and 2.1 (95% confidence interval was 1.7–4.1 and 1.3–3.4, respectively); males (HR 1.6; 1.1–2.4), use of glucocorticoids (HR 2.0; 1.3–3.0), and swollen joint count >7 (HR 0.36; 0.24–0.55) were independent predictors. Five-year drug survival was 31%, 43%, and 49% for infliximab, adalimumab, and etanercept, respectively (p = 0.010). Infliximab was associated with significantly more withdrawals due to adverse events. Disease activity, CRP, and use of glucocorticoids predicted efficacy-related drug survival; age, use of methotrexate, and prior DMARDs failures predicted safety-related survival. Risk for serious infections was lower with adalimumab (odds ratio [OR] 0.62; 0.38–1.00) or etanercept (OR 0.39; 0.21–0.72) than infliximab, independent of the effects of age (OR 1.65; 1.37–2.00 per 10 years), tender joint count >10 (OR 1.86; 1.21–2.86), and glucocorticoids >35 mg/week (OR 1.83; 1.12–2.99).Conclusions
Response rates were comparable among anti-TNF agents. Overall, 5-year drug survival was below 50%, with infliximab demonstrating increased safety-related discontinuations. Remission rates are low in clinical practice. Strategies to increase effectiveness and long-term survival of anti-TNF agents in RA are needed. 相似文献27.
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Charchar FJ Bloomer LD Barnes TA Cowley MJ Nelson CP Wang Y Denniff M Debiec R Christofidou P Nankervis S Dominiczak AF Bani-Mustafa A Balmforth AJ Hall AS Erdmann J Cambien F Deloukas P Hengstenberg C Packard C Schunkert H Ouwehand WH Ford I Goodall AH Jobling MA Samani NJ Tomaszewski M 《Lancet》2012,379(9819):915-922
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