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71.
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72.
Dr. Jonathan A. Leighton M.D. Miguel A. Valdovinos M.D. John H. Pemberton M.D. Doris M. Rath R.N. Michael Camilleri M.D. 《Diseases of the colon and rectum》1993,36(2):182-185
Our aim was to characterize the clinical spectrum of anorectal dysfunction among eight patients with progressive systemic sclerosis (PSS) who presented with altered bowel movements with or without fecal incontinence. The anorectum was assessed by physical examination, proctosigmoidoscopy, and anorectal manometry. There was concomitant involvement of the other regions of the digestive tract in all patients as determined by barium studies, endoscopy, or manometry: eight esophageal, three gastric, four small bowel, and two colonic. Seven patients had fecal incontinence, and four also had second-degree complete rectal prolapse. Abnormal anorectal function, particularly abnormal anal sphincter resting pressures, were detected in all patients; anal sphincter pressures were lower in those with rectal prolapse. Rectal capacity and wall compliance were impaired in seven of seven patients. Successful surgical correction of prolapse in three patients resulted in restoration of incontinence for six months and seven years in two of the three patients. We conclude that rectal dysfunction and weakness of the anal sphincters are important factors contributing, respectively, to altered bowel movements and fecal incontinence in patients with gastrointestinal involvement by PSS. Rectal prolapse worsens anal sphincter dysfunction and should be sought routinely as it is a treatable factor aggravating fecal incontinence in patients with PSS.This work was presented in part at the Annual Meeting of the American Gastroenterological Association, May 1992, and appears in abstract form in Gastroenterology 1992;102:A473.Supported in part by the General Clinical Research Center Grant 00585 from the National Institutes of Health. 相似文献
73.
Jerraco L. Johnson Benjamin Miedema Brooke Converse Doris Hill Alice M. Buchanan Claire Bridges J. Megan Irwin Mary E. Rudisill Melissa Pangelinan 《Journal of developmental and physical disabilities》2018,30(3):427-437
The aim of this study was to compare the influence of two different instructional climates on the accumulation of moderate-to-vigorous physical activity (MVPA) during a fully-inclusive adapted recreational physical activity program. A total of 32 children (18 typically-developing (TD), and 14 with developmental disabilities (DD) ranging in ages from 5 to 9 years, participated in six, 60-min adapted recreational sessions. Of those six sessions, three incorporated an autonomy-supportive climate (high autonomy), and three incorporated direct instruction (low autonomy). MVPA was measured using accelerometers. A repeated measures ANOVA was conducted to determine significant differences in MVPA between group (TD/DD), climate (autonomy/direct), and a group x climate interaction. Significant group and climate main effects were observed (p?=?0.002 and 0.014, respectively). However, there was not a significant group x climate interaction (p?=?0.313). These results suggest that although the group of children with disabilities spent less time in MVPA compared to their typically-developing peers, all participants spent more time in MVPA for the autonomy-supportive climate compared to the low-autonomous climate. This study is the first to quantitatively assess the efficacy of a fully-inclusive autonomy-supportive climate on physical activity levels in children with and without developmental disabilities. 相似文献
74.
Niels?Egholm?PedersenEmail author Lars?Simon?Rasmussen John?Asger?Petersen Thomas?Alexander?Gerds Doris??stergaard Anne?Lippert 《Journal of clinical monitoring and computing》2018,32(1):109-116
The national early warning score (NEWS) is recommended to detect deterioration in hospitalised patients. In 2013, a NEWS-based system was introduced in a hospital service with over 250,000 annual admissions, generating large amounts of NEWS data. The quality of such data has not been described. We critically assessed NEWS data recorded over 12 months. This observational study included NEWS records from adult inpatients hospitalized in the Capital Region of Denmark during 2014. Physiological variables and the use of supplementary oxygen (NEWS variables) were recorded. We identified implausible records and assessed the distributions of NEWS variable values. Of 2,835,331 NEWS records, 271,103 (10%) were incomplete with one or more variable missing and 0.2% of records containing implausible values. Digit preferences were identified for respiratory rate, supplementation oxygen flow, pulse rate, and systolic blood pressure. There was an accumulation of pulse rate records below 91 beats per minute. Among complete NEWS records, 64% had NEWS?≥?1; 29% had NEWS?≥?3; and 8% had NEWS?≥?6. In a large set of NEWS data, 10% of the records were incomplete. In a system where data were manually entered into an electronic medical record, digit preferences and the accumulation of pulse rate records below 91 beats per minute, which is the limit for NEWS point generation, showed that staff practice influenced the recorded values. This indicates a potential limitation of transferability of research results obtained in such systems to fully automated systems. 相似文献
75.
76.
Dyslipidaemia is an important risk factor for the development of chronic kidney disease (CKD) and cardiovascular disease (CVD). CKD generates an atherogenic lipid profile, characterised by high triglycerides, low high-density lipoprotein (HDL) cholesterol and accumulation of small dense low-density lipoprotein (LDL) particles, comparable to that in the metabolic syndrome. These changes are due specifically to the effects of CKD on key enzymes, transfer proteins and receptors involved in lipid metabolism. Dyslipidaemia is further compounded by dialysis, immunosuppressive drugs, and concomitant diseases such as diabetes mellitus. Post hoc analyses from large intervention trials suggest the benefit of statins in patients with early CKD, but prospective clinical trials in haemodialysis (HD) and renal transplant recipients have not conclusively shown improvements in hard cardiovascular end-points. The lack of efficacy of statins in late-stage CKD could be a consequence of other disease processes, such as calcific arteriopathy and insulin resistance, which are not modified by lipid-lowering agents. Despite uncertainty and pending the results of ongoing statin trials such as Study of Heart and Renal Protection (SHARP) and AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events), major international guidelines continue to support statin therapy in CKD and renal transplant patients to reduce cardiovascular risk burden. Because of increased risk of toxicity, particularly myopathy, statins and other lipid-regulating agents should be used cautiously in CKD and renal transplant recipients. 相似文献
77.
Summary Data from single injection studies on 23 normal subjects led to development of an intravenous primed — constant infusion test. The plasma glucose response to this test was determined in 48 normal and 24 diabetic subjects. Variation in plasma glucose concentration at equilibrium was minimal in normal and marked in diabetic subjects — assessed by the difference between maximum and minimum glucose concentration over the final 25 min of a 50 min infusion. This parameter was used successfully in predicting the course of 16 pregnant women with clinical suspicion of prediabetes unresolved by oral glucose tolerance tests.Submitted as part fulfillment of the requirements for Doctor of Medicine, Monash University, Melbourne, 1967. 相似文献
78.
79.
Arnold M. Katz Michihiko Tada Doris I. Repke Jo-Anna M. Iorio M.A. Kirchberger 《Journal of molecular and cellular cardiology》1974,6(1):73-78
Cardiac microsomes prepared by two different methods were compared in terms of Ca-binding and Ca-uptake, believed to represent markers for fragmented sarcoplasmic reticulum, and the (Na+ + K+)-activated ATPase activity considered to be a marker for the plasma membrane. Microsomes prepared in dilute buffer (H2O-microsomes) contain two to four times the activity of sarcoplasmic reticulum markers when compared to microsomes prepared in 10% sucrose (suc-microsomes). Conversely, the plasma membrane marker was present in greater amounts in the suc-microsomes. Basal, epinephrine-stimulated and NaF-stimulated adenylate cyclase activities were slightly higher in H2O-microsomes, as was the degree of stimulation by the β-adrenergic agonist. These findings provide evidence that both β-receptor and adenylate cyclase activities may be present in the heart's sarcoplasmic reticulum, as well as in the sarcolemma. 相似文献