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131.
132.
Lewis Landsberg MD Louis J. Aronne MD Lawrence J. Beilin MB BS MD MA Valerie Burke MD Leon I. Igel MD Donald Lloyd‐Jones MD ScM James Sowers MD 《Obesity (Silver Spring, Md.)》2013,21(1):8-24
In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and The American Society of Hypertension agreed to jointly sponsor a position paper on obesity‐related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced‐based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients. Obesity (2012) 相似文献
133.
The molecular mechanism of hepcidin-mediated ferroportin down-regulation 总被引:13,自引:0,他引:13 下载免费PDF全文
De Domenico I Ward DM Langelier C Vaughn MB Nemeth E Sundquist WI Ganz T Musci G Kaplan J 《Molecular biology of the cell》2007,18(7):2569-2578
Ferroportin (Fpn) is the only known iron exporter in vertebrates. Hepcidin, a peptide secreted by the liver in response to iron or inflammation, binds to Fpn, inducing its internalization and degradation. We show that after binding of hepcidin, Fpn is tyrosine phosphorylated at the plasma membrane. Mutants of human Fpn that do not get internalized or that are internalized slowly show either absent or impaired phosphorylation. We identify adjacent tyrosines as the phosphorylation sites and show that mutation of both tyrosines prevents hepcidin-mediated Fpn internalization. Once internalized, Fpn is dephosphorylated and subsequently ubiquitinated. An inability to ubiquitinate Fpn does not prevent hepcidin-induced internalization, but it inhibits the degradation of Fpn. Ubiquitinated Fpn is trafficked through the multivesicular body pathway en route to degradation in the late endosome/lysosome. Depletion of proteins involved in multivesicular body trafficking (Endosome Sorting Complex Required for Transport proteins), by small-interfering RNA, reduces the trafficking of Fpn-green fluorescent to the lysosome. 相似文献
134.
Karen?ConnorEmail author Eric?Cheng Hilary?C.?Siebens Martin?L.?Lee Brian?S.?Mittman David?A.?Ganz Barbara?Vickrey 《BMC neurology》2015,15(1):258
Background
Parkinson’s disease, the second most common neurodegenerative disease, is diagnostically defined by motor impairments, but also includes often under-recognized impairments in cognition, mood, sleep, and the autonomic nervous system. These problems can severely affect individuals’ quality of life. In our prior research, we have developed indicators to measure the quality of care delivered to patients with Parkinson’s disease, and we identified gaps in delivering evidence-based treatments for this population. Effective strategies to close these gaps are needed to improve patient quality of life.Methods/design
Building on prior research we developed a multi-faceted proactive implementation program called Care Coordination for Health Promotion and Activities in Parkinson’s Disease (CHAPS). To be eligible, patients had to have at least two visits with a primary diagnosis of idiopathic Parkinson’s disease (ICD-9 code: 332.0) at one of five Veterans Affairs Medical Centers in the southwestern United States from 2010 to 2014. The program consists of telephone assessments, evidence-based protocols, and tools to enhance patient self-management, care planning, and coordination of care across providers, including an electronic database to support and track coordination of care. Our mixed-methods study employs a randomized, controlled trial design to test whether the CHAPS intervention improves performance in 38 quality measures among an analytic sample of 346 patients. The 38 quality measures are categorized into overarching areas of communication, education, and continuity; regulatory reporting; diagnosis; periodic assessment; medication use; management of motor and non-motor symptoms; use of non-pharmacological approaches and therapies; palliative care; and health maintenance. Secondary outcomes are patient health-related quality of life, self-efficacy, and perceptions of care quality. We are also evaluating the extent of the CHAPS Program implementation and measuring program costs and impacts on health services utilization, in order to perform a analysis of the CHAPS program from the perspective of the Veterans Health Administration (VA). Outcomes are assessed by interviewer-administered surveys collected at baseline and at 6, 12, and 18 months, and by medical record chart abstractions. Analyses will be intention-to-treat.Discussion
The CHAPS Program is poised for dissemination within the VA National Parkinson’s Disease Research, Education, and Clinical Center Consortium if demonstrated efficacious.Trial Registration
ClinicalTrials.gov NCT01532986; registered on January 13, 2012.135.
Stephen W. Waldo Daniel A. Brenner James M. McCabe Mark Dela Cruz Brian Long Venkata A. Narla Joseph Park Ameya Kulkarni Elizabeth Sinclair Stephen Y. Chan Suzaynn F. Schick Namita Malik Peter Ganz Priscilla Y. Hsue 《PloS one》2015,10(2)
ObjectiveThe endothelium is a key mediator of vascular homeostasis and cardiovascular health. Molecular research on the human endothelium may provide insight into the mechanisms underlying cardiovascular disease. Prior methodology used to isolate human endothelial cells has suffered from poor yields and contamination with other cell types. We thus sought to develop a minimally invasive technique to obtain endothelial cells derived from human subjects with higher yields and purity.MethodsNine healthy volunteers underwent endothelial cell harvesting from antecubital veins using guidewires. Fluorescence-activated cell sorting (FACS) was subsequently used to purify endothelial cells from contaminating cells using endothelial surface markers (CD34 / CD105 / CD146) with the concomitant absence of leukocyte and platelet specific markers (CD11b / CD45). Endothelial lineage in the purified cell population was confirmed by expression of endothelial specific genes and microRNA using quantitative polymerase chain reaction (PCR).ResultsA median of 4,212 (IQR: 2161 – 6583) endothelial cells were isolated from each subject. Quantitative PCR demonstrated higher expression of von Willebrand Factor (vWF, P<0.001), nitric oxide synthase 3 (NOS3, P<0.001) and vascular cell adhesion molecule 1 (VCAM-1, P<0.003) in the endothelial population compared to similarly isolated leukocytes. Similarly, the level of endothelial specific microRNA-126 was higher in the purified endothelial cells (P<0.001).ConclusionThis state-of-the-art technique isolates human endothelial cells for molecular analysis in higher purity and greater numbers than previously possible. This approach will expedite research on the molecular mechanisms of human cardiovascular disease, elucidating its pathophysiology and potential therapeutic targets. 相似文献
136.
Background
The study aimed to investigate the pharmacokinetics of intravenous ciprofloxacin and the adequacy of 400 mg every 12 hours in critically ill Intensive Care Unit (ICU) patients on continuous veno-venous haemodiafiltration (CVVHDF) with particular reference to the effect of achieved flow rates on drug clearance.Methods
This was an open prospective study conducted in the intensive care unit and research unit of a university teaching hospital. The study population was seven critically ill patients with sepsis requiring CVVHDF. Blood and ultrafiltrate samples were collected and assayed for ciprofloxacin by High Performance Liquid Chromatography (HPLC) to calculate the model independent pharmacokinetic parameters; total body clearance (TBC), half-life (t1/2) and volume of distribution (Vd). CVVHDF was performed at prescribed dialysate rates of 1 or 2 L/hr and ultrafiltration rate of 2 L/hr. The blood flow rate was 200 ml/min, achieved using a Gambro blood pump and Hospal AN69HF haemofilter.Results
Seventeen profiles were obtained. CVVHDF resulted in a median ciprofloxacin t1/2 of 13.8 (range 5.15-39.4) hr, median TBC of 9.90 (range 3.10-13.2) L/hr, a median Vdss of 125 (range 79.5-554) L, a CVVHDF clearance of 2.47+/-0.29 L/hr and a clearance of creatinine (Clcr) of 2.66+/-0.25 L/hr. Thus CVVHDF, at an average flow rate of ~3.5 L/hr, was responsible for removing 26% of ciprofloxacin cleared. At the dose rate of 400 mg every 12 hr, the median estimated Cpmax/MIC and AUC0-24/MIC ratios were 10.3 and 161 respectively (for a MIC of 0.5 mg/L) and exceed the proposed criteria of >10 for Cpmax/MIC and > 100 for AUC0-24/MIC. There was a suggestion towards increased ciprofloxacin clearance by CVVHDF with increasing effluent flow rate.Conclusions
Given the growing microbial resistance to ciprofloxacin our results suggest that a dose rate of 400 mg every 12 hr, may be necessary to achieve the desired pharmacokinetic - pharmacodynamic (PK-PD) goals in patients on CVVHDF, however an extended interval may be required if there is concomitant hepatic impairment. A correlation between ciprofloxacin clearance due to CVVHDF and creatinine clearance by the filter was observed (r2 = 0.76), providing a useful clinical surrogate marker for ciprofloxacin clearance within the range studied.Trial Registration
Current Controlled Trials ISRCTN52722850 相似文献137.
138.
AE Clarke S Bernatsky KH Costenbader MB Urowitz DD Gladman PR Fortin M Petri S Manzi DA Isenberg A Rahman D Wallace C Gordon C Peschken MA Dooley EM Ginzler C Aranow SM Edworthy O Nived S Jacobsen G Ruiz-Irastorza E Yelin SG Barr L Criswell G Sturfelt L Dreyer I Blanco L Gottesman CH Feldman R Ramsey-Goldman 《Arthritis research & therapy》2012,14(Z3):A16
139.
140.
Eliana Alves Liliana Costa Carla MB Carvalho Jo?o PC Tomé Maria A Faustino Maria GPMS Neves Augusto C Tomé José AS Cavaleiro ?ngela Cunha Adelaide Almeida 《BMC microbiology》2009,9(1):70