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排序方式: 共有873条查询结果,搜索用时 31 毫秒
161.
A Hirsch F Windhausen JG Tijssen AJ Oude Ophuis WJ van der Giessen PM van der Zee JH Cornel FW Verheugt RJ de Winter 《European heart journal》2009,30(6):645-654
AIMS: In several observational studies, revascularization is associated with substantial reduction in mortality in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS). This has strengthened the belief that routine early angiography would lead to a reduction in mortality. We investigated the association between actual in-hospital revascularization and long-term outcome in patients with nSTE-ACS included in the ICTUS trial. METHODS AND RESULTS: The study population of the present analysis consists of ICTUS participants who were discharged alive after initial hospitalization. The ICTUS trial was a randomized, controlled trial in which 1200 patients were randomized to an early invasive or selective invasive strategy. The endpoints were death from hospital discharge until 4 year follow-up and death or spontaneous myocardial infarction (MI) until 3 years. Among 1189 patients discharged alive, 691 (58%) underwent revascularization during initial hospitalization. In multivariable Cox regression analyses, in-hospital revascularization was independently associated with a reduction in 4 year mortality and 3 year event rate of death or spontaneous MI: hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.37-0.96] and 0.46 (95% CI 0.31-0.68). However, when intention-to-treat analysis was performed, no differences in cumulative event rates were observed between the early invasive and selective invasive strategies: HR 1.10 (95% CI 0.70-1.74) for death and 1.27 (95% CI 0.88-1.85) for death or spontaneous MI. CONCLUSION: The ICTUS trial did not show that an early invasive strategy resulted in a better outcome than a selective invasive strategy in patients with nSTE-ACS. However, similar to retrospective analyses from observational studies, actual revascularization was associated with lower mortality and fewer MI. Whether an early invasive strategy leads to a better outcome than a selective invasive strategy cannot be inferred from the observation that revascularized patients have a better prognosis in non-randomized studies. 相似文献
162.
MJ Hatfield L Tsurkan JL Hyatt X Yu CC Edwards LD Hicks RM Wadkins PM Potter 《British journal of pharmacology》2010,160(8):1916-1928
Background and purpose:
Carboxylesterases (CEs) metabolize a wide range of xenobiotic substrates including heroin, cocaine, meperidine and the anticancer agent CPT-11. In this study, we have purified to homogeneity human liver and intestinal CEs and compared their ability with hydrolyse heroin, cocaine and CPT-11.Experimental approach:
The hydrolysis of heroin and cocaine by recombinant human CEs was evaluated and the kinetic parameters determined. In addition, microsomal samples prepared from these tissues were subjected to chromatographic separation, and substrate hydrolysis and amounts of different CEs were determined.Key results:
In contrast to previous reports, cocaine was not hydrolysed by the human liver CE, hCE1 (CES1), either as highly active recombinant protein or as CEs isolated from human liver or intestinal extracts. These results correlated well with computer-assisted molecular modelling studies that suggested that hydrolysis of cocaine by hCE1 (CES1), would be unlikely to occur. However, cocaine, heroin and CPT-11 were all substrates for the intestinal CE, hiCE (CES2), as determined using both the recombinant protein and the tissue fractions. Again, these data were in agreement with the modelling results.Conclusions and implications:
These results indicate that the human liver CE is unlikely to play a role in the metabolism of cocaine and that hydrolysis of this substrate by this class of enzymes is via the human intestinal protein hiCE (CES2). In addition, because no enzyme inhibition is observed at high cocaine concentrations, potentially this route of hydrolysis is important in individuals who overdose on this agent. 相似文献163.
LN Barlow-Mosha DS Bagenda PK Mudiope MC Mubiru LM Butler MG Fowler PM Musoke 《African health sciences》2012,12(3):249-258
Background
Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs.Objective
To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment.Methods
Clinical, immunologic, and virologic outcomes of HIV-infected ART-naïve children aged six months to 12 years, were evaluated up to 96 weeks post-ART initiation.Results
From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7–13.9) and 348,846copies/mL (IQR 160,941–681,313) respectively at baseline. Using Kaplan-Meir estimates, 75% of children had undetectable viral loads (<400copies/mL) at 96weeks of ART. Children with a baseline CD4 cell percent >15% were 3 times more likely to achieve viral load <400copies/mL than those with baseline CD4 cell percent <5% after adjusting for baseline age {aHR = 3.03 (1.10–8.32), p=0.03}; no difference was found among those with CD4 cell percent >5–14.9% and <5%.Conclusion
Treatment with generic adult FDC for HIV-infected Ugandan children led to sustained clinical, immunologic and virologic response during 96 weeks of ART. Early initiation of ART is key to achieving virological success. 相似文献164.
Bergman JE Janssen N van der Sloot AM de Walle HE Schoots J Rendtorff ND Tranebjaerg L Hoefsloot LH van Ravenswaaij-Arts CM Hofstra RM 《Human mutation》2012,33(8):1251-1260
CHARGE syndrome is characterized by the variable occurrence of multisensory impairment, congenital anomalies, and developmental delay, and is caused by heterozygous mutations in the CHD7 gene. Correct interpretation of CHD7 variants is essential for genetic counseling. This is particularly difficult for missense variants because most variants in the CHD7 gene are private and a functional assay is not yet available. We have therefore developed a novel classification system to predict the pathogenic effects of CHD7 missense variants that can be used in a diagnostic setting. Our classification system combines the results from two computational algorithms (PolyPhen-2 and Align-GVGD) and the prediction of a newly developed structural model of the chromo- and helicase domains of CHD7 with segregation and phenotypic data. The combination of different variables will lead to a more confident prediction of pathogenicity than was previously possible. We have used our system to classify 145 CHD7 missense variants. Our data show that pathogenic missense mutations are mainly present in the middle of the CHD7 gene, whereas benign variants are mainly clustered in the 5' and 3' regions. Finally, we show that CHD7 missense mutations are, in general, associated with a milder phenotype than truncating mutations. 相似文献
165.
MR Danzig RA Ghandour P Chang AA Wagner PM Pierorazio ME Allaf JM McKiernan 《Urologic oncology》2017,35(3):116
Purpose
We compared renal function outcomes among patients in the surveillance and intervention arms of the DISSRM registry.Materials and methods
Patients were grouped into chronic kidney disease stages by estimated glomerular filtration rate range. Cases were considered up staged if a more advanced chronic kidney disease stage was entered during followup. Chronic kidney disease up staging-free survival was compared among groups using Kaplan-Meier analysis and paired comparisons log rank tests. Multivariate Cox regression identified independent predictors of chronic kidney disease up staging-free survival.Results
A total of 162 patients met the study inclusion criteria, with 68 in the surveillance arm, 65 undergoing partial nephrectomy, 15 undergoing radical nephrectomy, and 14 undergoing cryoablation. Median tumor size was 2.2 cm. Mean estimated glomerular filtration rate change was significantly larger for radical nephrectomy vs. surveillance (?9.2 vs. ?0.5 ml/min/1.73 m2) and for radical vs. partial nephrectomy (?9.2 vs. ?1.9 ml/min/1.73 m2) (P = 0.001). No other groups differed significantly. On Kaplan-Meier analysis, patients undergoing radical nephrectomy had significantly worse chronic kidney disease up staging-free survival vs. those treated with partial nephrectomy (P = 0.029), surveillance (P = 0.007), and cryoablation (P = 0.019). No other groups differed significantly. On multivariate analysis, radical nephrectomy independently predicted poor chronic kidney disease up staging-free survival (odds ratio vs. surveillance 30.6, P = 0.001). Neither partial nephrectomy (P = 0.985) nor cryoablation (P = 0.976) predicted poor chronic kidney disease up staging-free survival relative to surveillance.Conclusions
Patients in the surveillance arm had superior estimated glomerular filtration rate preservation compared to those in the radical nephrectomy but not the partial nephrectomy arm. In certain patients with small renal masses, surveillance and partial nephrectomy may offer comparable renal functional outcomes. This could be partly attributable to a modest estimated glomerular filtration rate decrease associated with surveillance itself. A thorough understanding of the renal functional impacts of treatment modalities is critical in the management of small renal masses. 相似文献166.
Effect of subconjunctival glucose on retinal ganglion cell survival in experimental retinal ischaemia and contrast sensitivity in human glaucoma 下载免费PDF全文
167.
J.J.J. de Sonnaville D. van der Feltz van der Sloot L. Ernst D. Wijkel R.J. Heine 《Diabetic medicine》1996,13(5):482-486
The purpose of the study was to assess the reliability of mydriatic 60° fundus photography in a retinopathy screening programme for Type 2 diabetic patients in a primary health care setting. In 323 eligible consecutive Type 2 diabetic patients above 40 years of age, attending a regional shared care diabetes project, mydriatic wide angle fundus photography was compared with standardized fundoscopy in dilated pupils as the recommended test for the detection of diabetic retinopathy. Fundus photography included two black and white transparencies per eye visualizing the central and nasal retinal field. Fundoscopy findings and pictures were scored according to modified Wisconsin criteria. Fundoscopy revealed in 95/646 eyes (14.7 %) some degree of diabetic retinopathy. Sensitivity and specificity of fundus photography (omitting ungradable transparencies) were 97 % for the diagnosis of any diabetic retinopathy (DRP). All patients with moderate and severe DRP (Wisconsin grade 3 and worse) according to fundoscopy were detected by fundus photography. In conclusion, mydriatic wide angle 60° fundus photography, making two pictures per eye, can be applied effectively and reliably in the detection of diabetic retinopathy in patients with Type 2 diabetes. 相似文献
168.
European consensus on the concepts and measurement of the pathophysiological neuromuscular responses to passive muscle stretch 下载免费PDF全文
J. C. van den Noort E. Aertbeliën M. Bonikowski S. M. Braendvik E. W. Broström A. I. Buizer J. H. Burridge A. van Campenhout B. Dan J. F. Fleuren S. Grunt F. Heinen H. L. Horemans C. Jansen A. Kranzl B. K. Krautwurst M. van der Krogt S. Lerma Lara C. M. Lidbeck J.‐P. Lin I. Martinez C. Meskers D. Metaxiotis G. Molenaers D. A. Patikas O. Rémy‐Néris K. Roeleveld A. P. Shortland J. Sikkens L. Sloot R. J. Vermeulen C. Wimmer A. S. Schröder S. Schless J. G. Becher K. Desloovere J. Harlaar 《European journal of neurology》2017,24(7):981-e38
169.
Background: Several inflammatory biomarkers are implicated in the pathogenesis of periodontitis including interleukin-1β (IL-1β) and C-reactive protein (CRP). This study investigated the presence of these factors in gingival crevicular fluid (GCF) and their relationship to clinical and social determinants of periodontitis in the Australian population.
Methods: Equal numbers of periodontitis cases and non-cases were sampled during oral epidemiologic examination in the National Survey of Adult Oral Health. GCF was sampled from four sites where probing pocket depth (PPD) and recession were recorded. From these, IL-1β and CRP were quantified by ELISA and the log amount of GCF IL-1β (pg) per person and the proportion of adults with detectable CRP was computed.
Results: Periodontitis cases (n = 511) had significantly higher levels of IL-1β and CRP than non-cases (n = 562). PPD, clinical attachment loss, plaque and gingivitis indices were positively associated with elevated levels of both biomarkers. Levels of both were positively associated with age, low socio-economic position and non-Australian birth.
Conclusions: The presence of IL-1β and CRP in GCF are associated with periodontal disease parameters within the Australian population. The levels of both biomarkers are influenced by age, education and eligibility for public dental care. 相似文献
Methods: Equal numbers of periodontitis cases and non-cases were sampled during oral epidemiologic examination in the National Survey of Adult Oral Health. GCF was sampled from four sites where probing pocket depth (PPD) and recession were recorded. From these, IL-1β and CRP were quantified by ELISA and the log amount of GCF IL-1β (pg) per person and the proportion of adults with detectable CRP was computed.
Results: Periodontitis cases (n = 511) had significantly higher levels of IL-1β and CRP than non-cases (n = 562). PPD, clinical attachment loss, plaque and gingivitis indices were positively associated with elevated levels of both biomarkers. Levels of both were positively associated with age, low socio-economic position and non-Australian birth.
Conclusions: The presence of IL-1β and CRP in GCF are associated with periodontal disease parameters within the Australian population. The levels of both biomarkers are influenced by age, education and eligibility for public dental care. 相似文献
170.
Andrew D Beggs Enric Domingo Megan McGregor Mikael Presz Elaine Johnstone Rachel Midgley David Kerr Dahmane Oukrif Marco Novelli Muti Abulafi Shirley V Hodgson Wakkas Fadhil Mohammad Ilyas Ian PM Tomlinson 《Oncotarget》2012,3(11):1348-1355
Repair of double strand DNA breaks (DSBs) is pivotal in maintaining normal cell division and disruption of this system has been shown to be a key factor in carcinogenesis. Loss of expression of the DSB repair proteins have previously been shown to be associated with poorer survival in colorectal cancer. We wished to ascertain the relationship of altered expression of the DSB repair proteins γ-H2AX (gamma-H2AX), ATM and Ku70 with biological and clinico-pathological features of colorectal cancer. 908 tumours from the VICTOR clinical trial of stage II/III colorectal cancer were analysed for expression of γ-H2AX, ATM and Ku70 using immunohistochemistry. Expression levels were correlated with CIN and with disease-free survival, correcting for microsatellite instability, BRAF/KRAS mutation status, Dukes stage, chemo/radiotherapy, age, gender and tumour location. Down-regulated Ku70 expression was associated with chromosomal instability (p=0.029) in colorectal cancer. Reduced ATM expression was an independent marker of poor disease-free survival (HR=1.67, 95% CI 1.11-2.50, p=0.015). For Ku70, further studies are required to investigate the potential relationship of non-homologous end joining with chromosomal instability. Loss of ATM expression might serve as a biomarker of poor prognosis in colorectal cancer. 相似文献