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排序方式: 共有173条查询结果,搜索用时 296 毫秒
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Kang H. Zheng Sotirios Tsimikas Tania Pawade Jeffrey Kroon William S.A. Jenkins Mhairi K. Doris Audrey C. White Nyanza K.L.M. Timmers Jesper Hjortnaes Maximillian A. Rogers Elena Aikawa Benoit J. Arsenault Joseph L. Witztum David E. Newby Marlys L. Koschinsky Zahi A. Fayad Erik S.G. Stroes S. Matthijs Boekholdt Marc R. Dweck 《Journal of the American College of Cardiology》2019,73(17):2150-2162
Background
Lipoprotein(a) [Lp(a)], a major carrier of oxidized phospholipids (OxPL), is associated with an increased incidence of aortic stenosis (AS). However, it remains unclear whether elevated Lp(a) and OxPL drive disease progression and are therefore targets for therapeutic intervention.Objectives
This study investigated whether Lp(a) and OxPL on apolipoprotein B-100 (OxPL-apoB) levels are associated with disease activity, disease progression, and clinical events in AS patients, along with the mechanisms underlying any associations.Methods
This study combined 2 prospective cohorts and measured Lp(a) and OxPL-apoB levels in patients with AS (Vmax >2.0 m/s), who underwent baseline 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), repeat computed tomography calcium scoring, and repeat echocardiography. In vitro studies investigated the effects of Lp(a) and OxPL on valvular interstitial cells.Results
Overall, 145 patients were studied (68% men; age 70.3 ± 9.9 years). On baseline positron emission tomography, patients in the top Lp(a) tertile had increased valve calcification activity compared with those in lower tertiles (n = 79; 18F-NaF tissue-to-background ratio of the most diseased segment: 2.16 vs. 1.97; p = 0.043). During follow-up, patients in the top Lp(a) tertile had increased progression of valvular computed tomography calcium score (n = 51; 309 AU/year [interquartile range: 142 to 483 AU/year] vs. 93 AU/year [interquartile range: 56 to 296 AU/year; p = 0.015), faster hemodynamic progression on echocardiography (n = 129; 0.23 ± 0.20 m/s/year vs. 0.14 ± 0.20 m/s/year] p = 0.019), and increased risk for aortic valve replacement and death (n = 145; hazard ratio: 1.87; 95% CI: 1.13 to 3.08; p = 0.014), compared with lower tertiles. Similar results were noted with OxPL-apoB. In vitro, Lp(a) induced osteogenic differentiation of valvular interstitial cells, mediated by OxPL and inhibited with the E06 monoclonal antibody against OxPL.Conclusions
In patients with AS, Lp(a) and OxPL drive valve calcification and disease progression. These findings suggest lowering Lp(a) or inactivating OxPL may slow AS progression and provide a rationale for clinical trials to test this hypothesis. 相似文献3.
In animal experiments arrhythmias induced by cardiac glycosides which prove fatal if untreated can be terminated by administration of glycoside-specific antibodies. Immunotherapy with digoxin-specific antibody fragments had hitherto only been employed on one occasion, namely in a person who had taken a massive overdose of digoxin with suicidal intent and who had failed to respond to symptomatic treatment. The present paper describes the use of F(ab')2 fragments of digoxin-specific antibodies in a female patient with lanatoside C intoxication to treat the associated life-threatening cardiac arrhythmia. The arrhythmia was rapidly terminated and normal sinus rhythm was restored. Treatment with the heterologous antibodies did not cause any side-effects. 相似文献
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Nastassja Köhn Johannes Maubach Rene Warschkow Catherine Tsai Daniel P. Nussbaum Daniel Candinas Beat Gloor Bruno M. Schmied Dan G. Blazer Mathias Worni 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2018,20(11):1073-1081
Background
Current consensus guidelines suggest that gallbladder cancer (GBC) patients with resected T1a disease can be observed while patients with T1b or greater lesions should undergo lymphadenectomy (LNE). The primary aim of this study was to critically explore the impact of LNE in early-stage GBC on overall survival (OS) on a population-based level.Method
The 2004–2014 National Cancer Database was reviewed to identify non-metastatic GBC patients with T1a, T1b, or T2 disease and grouped whether a dedicated LNE was performed. OS and relative survival were assessed using Cox proportional hazard regression analyses before and after propensity score adjustments.Results
4015 patients were included, 246 (6%) had T1a, 654 (16%) T1b, and 3115 (78%) T2 GBC. The rate of positive lymph nodes was 13%, 12%, and 40% for T1a, T1b, and T2 tumors, respectively. Even after propensity score adjustment, no OS benefit was found if LNE was performed for T1a disease (HR:0.63, 95%CI:0.35–1.13) while OS was improved for T1b (HR:0.65, 95%CI:0.49–0.87) and T2 tumors (HR:0.65, 95%CI:0.57–0.73).Conclusion
Despite a higher rate of nodal positivity among patients with T1a disease compared to previous reports, there was no impact on survival and current treatment guidelines appear appropriate for the management of T1a disease. 相似文献6.
Megan Banky Ross A. Clark Benjamin F. Mentiplay John H. Olver Michelle B. Kahn Gavin Williams 《Archives of physical medicine and rehabilitation》2019,100(8):1482-1491
ObjectiveTo investigate whether a three-dimensional (3-D) camera (Microsoft Kinect) and a smartphone can be used to accurately quantify the joint angular velocity and range of motion (ROM) compared to a criterion-standard 3-D motion analysis system during a lower limb spasticity assessment.DesignObservational, criterion-standard comparison study.SettingLarge rehabilitation center.ParticipantsA convenience sample of 35 controls, 35 patients with a neurologic condition, and 34 rehabilitation professionals (physiotherapists and rehabilitation doctors) participated (N=104).InterventionsNot applicable.Main Outcome MeasuresThe Modified Tardieu Scale was used to assess spasticity of the quadriceps, hamstrings, soleus, and gastrocnemius. Data for each trial were collected concurrently using the criterion-standard Optitrack 3-D motion analysis (3DMA) system, Microsoft Kinect, and a smartphone. Each healthy control participant was assessed by 1 health professional and each patient with a neurological condition was assessed by 3 health professionals. Spearman correlation coefficient and intraclass correlation coefficient with 95% confidence intervals were used to report the strength of the relationships investigated.ResultsThe smartphone and Microsoft Kinect demonstrated excellent concurrent validity with the 3DMA system. Overall, 74.8% of the relationships investigated demonstrated a very strong (≥0.80) correlation across all of the testing parameters. The Microsoft Kinect was superior to the smartphone for measuring joint start and end angle, the smartphone was superior for measuring joint angular velocity, and the 2 systems were comparable for measuring total joint ROM.ConclusionsThese findings provide preliminary evidence that user-friendly, low-cost technologies can be used to facilitate accurate measurements of joint angular velocity and angles during a lower limb spasticity assessment in a clinical setting. 相似文献
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The portacaval and splenocaval shunt in the normal rat. A morphometric and functional reevaluation 总被引:2,自引:0,他引:2
Consequences of a portacaval and a distal splenocaval shunt on the liver were examined in normal male rats with measurements of the fractional clearance of ICG, of aminopyrine demethylation and of the hepatic ultrastructure with morphometric techniques. Twenty days after a portacaval shunt liver weight/100 g body weight was 30% smaller than in sham-operated controls. The most pronounced reduction of 50% occurred with surface area of the RER, whereas hepatocyte volumes, SER-surface area, mitochondria and peroxisomes were reduced between 30 and 40% hepatogenic lysosomes and non-hepatocytes/100 g b.wt. remained unchanged. The loss of liver mass is therefore compatible with the hypothesis, that it is the consequence of a decrease in synthetic and an increase in catabolic processes. The rate of elimination of ICG from plasma was proportional to the liver weight (r = 0,79, n = 20) and 14C-exhalation derived from [14C]aminopyrine was correlated with the surface of the SER (r = 0.72, n = 20), confirming that the morphometrically observed changes are functionally relevant. The lack of morphological and functional sequelae following distal splenocaval shunt suggests that blood drained by the splenic vein is not essential for the integrity of the liver in rats. 相似文献
9.
We investigated whether endothelin-2/vasoactive intestinal contractor (ET-2/VIC) gene expression, upregulated by hypoxia in cancer cells, was associated with differentiation in neuronal cells. RT-PCR analysis, morphological observations, and immunostaining revealed that CoCl2, a hypoxic mimetic agent, at 200 microM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced neurite outgrowth in PC-12 rat pheochromocytoma cells. These effects induced by 200 microM CoCl2 were completely inhibited by the antioxidant N-acetyl cysteine at 20 mM. In addition, CoCl2 increased the level of intracellular reactive oxygen species (ROS) at an early stage. Furthermore, interleukin (IL)-6 gene expression was upregulated upon the differentiation induced by CoCl2. These results suggest that expression of ET-2/VIC and ET-1 mediated by ROS may be associated with neuronal differentiation through the regulation of IL-6. When the cells were treated with 500 microM CoCl2 for 24 hr, however, ET-2/VIC gene expression disappeared, IL-6 gene expression was downregulated, and necrosis was subsequently induced in the PC-12 cells. 相似文献
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