Hwang, A E*
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Common variants in the region of the UMOD gene, which encodes uromodulin (Tamm-Horsfall protein), associate with chronic kidney disease (CKD) and estimated GFR (eGFR). Whether uromodulin levels associate with UMOD variants or with the risk for developing CKD is unknown. We conducted an age- and gender-matched case-control study (n = 200) of incident CKD (eGFR <60 ml/min per 1.73 m(2)) within the Framingham Heart Study (FHS). Baseline urinary uromodulin concentrations were related to case-control status 9.9 yr later and to genotype at rs4293393. As a replication set, we tested the genotype association with uromodulin concentration in the Atherosclerosis Risk in Communities (ARIC) Study (n = 42). Geometric means of uromodulin concentrations were 51% higher in case than in control subjects (P = 0.016). The adjusted odds ratio of CKD per 1-SD higher concentration of uromodulin was 1.72 (95% confidence interval 1.07 to 2.77; P = 0.03) after accounting for CKD risk factors and baseline eGFR. We observed lower urinary uromodulin concentrations per each copy of the C allele at rs4293393 in both cohorts. In summary, elevated uromodulin concentrations precede the onset of CKD and associate with a common polymorphism in the UMOD region.
- MeSH
- chronická nemoc MeSH
- cystická onemocnění ledvin genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- genotyp MeSH
- hodnoty glomerulární filtrace fyziologie MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- molekulární motory genetika MeSH
- mukoproteiny genetika moč MeSH
- nemoci ledvin genetika moč patofyziologie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- těžké řetězce myosinu genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
OBJECTIVES: This study investigated the characteristics, evaluation, prognostic impact, and treatment of coronary artery disease (CAD) in patients with heart failure and preserved ejection fraction (HFpEF). BACKGROUND: CAD is common in patients with HFpEF, but it remains unclear how CAD should be categorized, evaluated for, and treated in HFpEF. METHODS: Clinical, hemodynamic, echocardiographic, treatment, and outcome characteristics were examined in consecutive patients with previous HFpEF hospitalizations who underwent coronary angiography. RESULTS: Of the 376 HFpEF patients examined, 255 (68%) had angiographically-proven CAD. Compared with HFpEF patients without CAD, patients with CAD were more likely to be men, to have CAD risk factors, and to be treated with anti-ischemic medications. However, symptoms of angina and heart failure were similar in patients with and without CAD, as were measures of cardiovascular structure, function, and hemodynamics. Compared with patients without CAD, HFpEF patients with CAD displayed greater deterioration in ejection fraction and increased mortality, independent of other predictors (hazard ratio: 1.71, 95% confidence interval: 1.03 to 2.98; p = 0.04). Complete revascularization was associated with less deterioration in ejection fraction and lower mortality compared with patients who were not completely revascularized, independent of other predictors (hazard ratio: 0.56, 95% confidence interval: 0.33 to 0.93; p = 0.03). CONCLUSIONS: CAD is common in patients with HFpEF and is associated with increased mortality and greater deterioration in ventricular function. Revascularization may be associated with preservation of cardiac function and improved outcomes in patients with CAD. Given the paucity of effective treatments for HFpEF, prospective trials are urgently needed to determine the optimal evaluation and management of CAD in HFpEF.
- MeSH
- časové faktory MeSH
- echokardiografie MeSH
- funkce levé komory srdeční fyziologie MeSH
- koronární angiografie MeSH
- lidé MeSH
- míra přežití trendy MeSH
- následné studie MeSH
- nemoci koronárních tepen komplikace radiografie chirurgie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- revaskularizace myokardu metody MeSH
- senioři MeSH
- srdeční selhání komplikace diagnóza mortalita MeSH
- tepový objem * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Minnesota MeSH
Many hospitals and medical clinics have been using a wearable sensor in its health care system because the wearable sensor, which is able to measure the patients' biometric information, has been developed to analyze their patients remotely. The measured information is saved to a server in a medical center, and the server keeps the medical information, which also involves personal information, on a cloud system. The server and network devices are used by connecting each other, and sensitive medical records are dealt with remotely. However, these days, the attackers, who try to attack the server or the network systems, are increasing. In addition, the server and the network system have a weak protection and security policy against the attackers. In this paper, it is suggested that security compliance of medical contents should be followed to improve the level of security. As a result, the medical contents are kept safely.
- MeSH
- algoritmy MeSH
- ambulantní monitorování přístrojové vybavení MeSH
- biometrie MeSH
- chorobopisy MeSH
- cloud computing * MeSH
- důvěrnost informací MeSH
- elektronické zdravotní záznamy MeSH
- internet MeSH
- lékařská informatika přístrojové vybavení MeSH
- lidé MeSH
- poskytování zdravotní péče MeSH
- programovací jazyk MeSH
- sběr dat MeSH
- ukládání a vyhledávání informací metody MeSH
- zabezpečení počítačových systémů * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIM: Right heart function is not well characterized in patients with heart failure and preserved ejection fraction (HFpEF). The goal of this study was to examine the haemodynamic, clinical, and prognostic correlates of right ventricular dysfunction (RVD) in HFpEF. METHODS AND RESULTS: Heart failure and preserved ejection fraction patients (n = 96) and controls (n = 46) underwent right heart catheterization, echocardiographic assessment, and follow-up. Right and left heart filling pressures, pulmonary artery (PA) pressures, and right-sided chamber dimensions were higher in HFpEF compared with controls, while left ventricular size and EF were similar. Right ventricular dysfunction (defined by RV fractional area change, FAC <35%) was present in 33% of HFpEF patients and was associated with more severe symptoms and greater comorbidity burden. Right ventricular function was impaired in HFpEF compared with controls using both load-dependent (FAC: 40 ± 10 vs. 53 ± 7%, P < 0.0001) and load-independent indices (FAC adjusted to PA pressure, P = 0.003), with enhanced afterload-sensitivity compared with controls (steeper FAC vs. PA pressure relationship). In addition to haemodynamic load, RVD in HFpEF was associated with male sex, atrial fibrillation, coronary disease, and greater ventricular interdependence. Over a median follow-up of 529 days (IQR: 143-1066), 31% of HFpEF patients died. In Cox analysis, RVD was the strongest predictor of death (HR: 2.4, 95% CI: 1.6-2.6; P < 0.0001). CONCLUSION: Right heart dysfunction is common in HFpEF and is caused by both RV contractile impairment and afterload mismatch from pulmonary hypertension. Right ventricular dysfunction in HFpEF develops with increasing PA pressures, atrial fibrillation, male sex, and left ventricular dysfunction, and may represent a novel therapeutic target.
- MeSH
- dysfunkce pravé srdeční komory komplikace mortalita patofyziologie MeSH
- fibrilace síní komplikace mortalita patofyziologie MeSH
- hemodynamika fyziologie MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- sexuální faktory MeSH
- srdeční selhání komplikace mortalita patofyziologie MeSH
- studie případů a kontrol MeSH
- tepový objem fyziologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- audiometrie metody MeSH
- dospělí MeSH
- hluk na pracovišti škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- nedoslýchavost z hluku * diagnóza epidemiologie etiologie MeSH
- programy Healthy People MeSH
- průzkumy a dotazníky využití MeSH
- statistika jako téma MeSH
- zemědělství * pracovní síly MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Geografické názvy
- Spojené státy americké MeSH
Complex II of the respiratory chain (RC) recently emerged as a prominent regulator of cell death. In both cancer cells as well as neurodegenerative diseases, mutations in subunits have been found along with other genetic alterations indirectly affecting this complex. Anticancer compounds were developed that target complex II and cause cell death in a tumor-specific way. Our mechanistic understanding of how complex II is activated for cell death induction has recently been made clearer in recent studies, the results of which are covered in this review. This protein assembly is specifically activated for cell death via the dissociation of its SDHA and SDHB subunits from the membrane-anchoring proteins through pH change or mitochondrial Ca(2+) influx. The SDH activity contained in the SDHA/SDHB subcomplex remains intact and then generates, in an uncontrolled fashion, excessive amounts of reactive oxygen species (ROS) for cell death. Future studies on this mitochondrial complex will further elucidate it as a target for cancer treatments and reveal its role as a nexus for many diverse stimuli in cell death signaling.
- MeSH
- buněčná smrt fyziologie MeSH
- elektronový transportní řetězec fyziologie MeSH
- energetický metabolismus fyziologie MeSH
- mitochondrie fyziologie MeSH
- regulace genové exprese fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
AIM: Activating mutations in the epidermal growth factor receptor (EGFR) are predominantly detected in pulmonary adenocarcinoma and have been reported in small cell lung cancer (SCLC) for decades. This retrospective single-center study aimed to determine the frequency and types of EGFR mutations in SCLC in Taiwan. METHODS: This study comprises a consecutive cohort of 161 patients histologically diagnosed with SCLC between January 1992 and August 2014 at the Department of Pathology in Keelung Chang Gung Memorial Hospital, Taiwan. Archived formalin-fixed paraffin-embedded sections from 71 patients were eligible for molecular analysis. EGFR mutation analysis was performed using a fully-automated IdyllaTM EGFR Mutation Test and confirmed a comparable result through Qiagen Therascreen® EGFR RGQ PCR. In addition, EGFR gene copy number was assessed in EGFR-mutated tumors by fluorescence in situ hybridization (FISH). RESULTS: Mutational status of the EGFR gene was successfully analyzed in 63 specimens by both IdyllaTM and Qiagen platforms. Both methods detected L858R point mutation in exon 21 in an 81-year-old female and a 47-year-old male non-smoker. Both tumors show no concurrent EGFR gene amplification. The overall agreement between results obtained with the IdyllaTM EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR was 100% Conclusions. Our results showed that EGFR mutation is a rare mutation type in a consecutive series of de novo SCLC. Furthermore, the performance of IdyllaTM EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR on archived paraffin sections of limited quantities is available with the high agreement of results.
- MeSH
- erbB receptory genetika MeSH
- formaldehyd MeSH
- hybridizace in situ fluorescenční MeSH
- lidé MeSH
- malobuněčný karcinom plic * genetika MeSH
- mutace MeSH
- mutační analýza DNA metody MeSH
- nádory plic * diagnóza MeSH
- nemalobuněčný karcinom plic * diagnóza MeSH
- parafín MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
BACKGROUND: Left atrial (LA) structure and function are altered in most heart failure (HF) patients, but there may be fundamental differences in LA properties between HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). METHODS AND RESULTS: One hundred ninety-eight HF patients (51% HFpEF, New York Heart Association 3.1±0.7) and 40 HF-free controls underwent catheterization, echocardiography, and follow-up. Compared with controls, HF patients had larger and more dysfunctional left atria. At identical mean LA pressure (20 versus 20 mm Hg; P=0.9), HFrEF patients had larger LA volumes (LA volume index 50 versus 41 mL/m(2); P<0.001), whereas HFpEF patients had higher LA peak pressures, lower LA minimal pressures, higher LA stiffness (0.79 versus 0.48 mm Hg/mL; P<0.001), greater LA pulsatility (19 versus 13 mm Hg; P<0.001), and higher wall stress variations. Despite smaller LA volumes, better function, and less mitral regurgitation, HFpEF patients had more atrial fibrillation (42 versus 26%; P=0.02). LA dysfunction was associated with increased pulmonary vascular resistance and right ventricular dysfunction in both HF phenotypes. After a median follow-up of 350 days, 31 HFpEF and 28 HFrEF patients died. LA function (total LA EF) was associated with lower mortality in HFpEF (hazard ratio 0.43; 95% confidence interval, 0.2-0.9; P<0.05), but not in HFrEF. CONCLUSIONS: HFrEF is characterized by greater eccentric LA remodeling, whereas HFpEF by increased LA stiffness, which might contribute to greater atrial fibrillation burden. LA function is associated with pulmonary vascular disease and right HF in both HF phenotypes, but is associated with outcome more closely in HFpEF, supporting efforts to improve LA function in this cohort.
- MeSH
- cévní rezistence fyziologie MeSH
- dysfunkce pravé srdeční komory patofyziologie MeSH
- fenotyp MeSH
- lidé středního věku MeSH
- lidé MeSH
- prognóza MeSH
- remodelace síní fyziologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- srdce - funkce levé síně fyziologie MeSH
- srdeční selhání patofyziologie MeSH
- tepový objem fyziologie MeSH
- tuhost cévní stěny fyziologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH