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Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
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Local demineralization as a model for bone strength reductions in lytic transcortical metastatic lesions. 总被引:1,自引:0,他引:1
The structural consequences of bone density changes associated with lytic metastatic lesions were investigated using an experimental model of regular, lytic metastatic lesions in bone. Circular holes were drilled in the mid-diaphyseal cortex of paired adult canine femora. The region around the defect was demineralized in one bone of each pair with 0.8 N HCl. Specimens were tested to failure in four-point bending. Defect size was determined from conventional planar radiographs as the maximum apparent defect diameter divided by the periosteal diameter. Demineralization resulted in irregular defect geometries, which increased the maximum defect dimension 33% to 57% with respect to the original drill hole diameter. Demineralization resulted in additional strength reductions beyond those expected from the original drill hole alone. Despite the irregular demineralization patterns observed, strength reductions were in close agreement with those predicted from data for regular, nondemineralized holes (r2 = 0.93). The results demonstrate that irregular diaphyseal defect borders may not require more complex fracture risk predictors than can be determined from analytic and experimental studies of regular defect geometries. Our results also demonstrate that errors of over 100% can occur when measuring diaphyseal defect size from radiographs that are not optimally aligned with respect to the defect. 相似文献
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Leslee J. Shaw Romalisa Miranda-Peats Piotr Slomka John Friedman Sean W. Hayes Daniel S. Berman Gary V. Heller Marcin Dada William E. Boden Paul Casperson Robert A. O’Rourke Ronald Schwartz William S. Weintraub David J. Maron Spencer King Koon Teo Pamela Hartigan 《Journal of nuclear cardiology》2006,13(5):685-698
Background Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after
intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical
outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial.
Methods and Results The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical
therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been
designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia
at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship
between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate
the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization
patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic
intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive
risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization
in reducing patients’ ischemic burdens.
Conclusions The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology.
We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based
management of patients with stable coronary disease.
The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research
and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained
from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data
Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon;
and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional
funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research
from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging. 相似文献
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J. Hayes T. Shatari P. Toozs-Hobson† K. Busby S. Pretlove† S. Radley M. Keighley 《Colorectal disease》2007,9(4):332-336
OBJECTIVE: The outcome of immediate repair of obstetric third-degree tears is poorly documented. Immediate repair may give better functional results than delayed repair because scarring is reduced. This aim of this prospective study was to examine the early outcome of immediate repair of third-degree tears. METHOD: A total of 121 women who had immediate repair of obstetric third-degree tears underwent interview, anal ultrasonography and anorectal physiology. RESULTS: At review, 79 (65%) were completely asymptomatic (score = 0), 23 (19%), had minor flatus incontinence or mild urgency causing no compromise to their quality of life (score 1-4), and 19 (16%) had clinically embarrassing faecal incontinence (score 5-24). Thirty-nine (32%) had an intact internal anal sphincter (IAS) and external anal sphincter (EAS) (i.e. a successful repair), eight (7%) had a defect in the IAS alone but the EAS was intact (i.e. a successful repair but a residual IAS defect), 43 (35%) had a residual defect in the EAS alone (IAS intact) and 31 (26%) had a persistent defect in the IAS and EAS. Residual defects in either or both of the sphincters were associated with a significantly higher incidence of abnormal resting and squeeze anal pressures. Anal manometry had no correlation with symptoms. The highest proportion of severe incontinence was in those with an IAS defect alone (37%) and when there was a residual IAS and EAS defect (24%). Only 2 of 39 (5%) with an intact IAS and EAS had severe incontinence and only 8 of 43 (18%) with a residual EAS defect alone had severe faecal incontinence. CONCLUSION: These results indicate a good outcome following immediate repair of third-degree obstetric tears and emphasize the role of the IAS in providing continence. 相似文献
9.
John L Hayes 《American journal of orthodontics and dentofacial orthopedics》2005,128(5):557-8; author reply 558
10.
TF Leung WC Tsoi CK Li KW Chik MMK Shing PMP Yuen 《Acta paediatrica (Oslo, Norway : 1992)》1998,87(6):705-777
We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients. 相似文献