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In 1998, FIGO (International Federation of Gynecologists and Obstetricians) required a change from clinical to surgical staging in early endometrial cancer. This staging requirement raised numerous controversies around the importance of determining nodal status and its impact on outcomes. A diversity of opinions exists as to the actual benefits and toxicities associated with surgical staging which includes lymph node sampling, ranging from those whose opinion is that staging is required for all patients even when the a priori risk of nodal involvement is extremely low through to those who consider that staging is unnecessary in any patient. While knowledge of the presence or absence of extra uterine sites of disease may change treatment approaches and direct different treatment interventions in some patients, the impact of those changes on survival is much less clear. This paper examines recommendations for surgical staging in various subgroups of patients with clinically early endometrial cancer and the impact on survival and toxicity of the various approaches and the subsequent use of adjuvant irradiation and/or chemotherapy. 相似文献
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AndrewJ. Stott Michel C. Maillard Vahri Beaumont David Allcock Omar Aziz Alexander H. Borchers Wesley Blackaby Perla Breccia Gillian Creighton-Gutteridge Alan F. Haughan Rebecca E. Jarvis Christopher A. Luckhurst Kim L. Matthews George McAllister Scott Pollack Elizabeth Saville-Stones Amanda J. Van de Poël Huw D. Vater Julie Vann Rachel Williams Dawn Yates Ignacio Muoz-Sanjun Celia Dominguez 《ACS medicinal chemistry letters》2021,12(3):380
Using an iterative structure–activity relationship driven approach, we identified a CNS-penetrant 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO, 12) with a pharmacokinetic profile suitable for probing class IIa histone deacetylase (HDAC) inhibition in vivo. Given the lack of understanding of endogenous class IIa HDAC substrates, we developed a surrogate readout to measure compound effects in vivo, by exploiting the >100-fold selectivity compound 12 exhibits over class I/IIb HDACs. We achieved adequate brain exposure with compound 12 in mice to estimate a class I/IIb deacetylation EC50, using class I substrate H4K12 acetylation and global acetylation levels as a pharmacodynamic readout. We observed excellent correlation between the compound 12 in vivo pharmacodynamic response and in vitro class I/IIb cellular activity. Applying the same relationship to class IIa HDAC inhibition, we estimated the compound 12 dose required to inhibit class IIa HDAC activity, for use in preclinical models of Huntington’s disease. 相似文献
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The most common indication for an echocardiogram is for the assessment of left ventricular (LV) function and, in the evaluation of cardiomyopathy (CM), this becomes even more important. However, conventional echocardiographic measures of ventricular function are insensitive at detecting subtle perturbations in contractility. In patients with CM, the ability to detect abnormalities early in the course of the disease to establish a diagnosis can be critical and often may influence specific treatments administered as well as establish important prognostic information. Technologic advances in echocardiographic imaging during the last decade now allow for the measurement of LV strain and strain rate (SR) imaging. Strain and SR imaging allow for a more precise characterization of the mechanics of myocardial contraction and relaxation (deformation imaging) and emerging data are establishing the use of these techniques in a variety of different cardiomyopathic conditions. After establishing a common understanding of strain imaging as well as defining the methods by which these measures can be incorporated into an echocardiographic examination, we will review the accumulating information illustrating the great promise that this imaging modality has in the care of patients with CM. This review will focus on the role of strain and SR imaging in CM. 相似文献
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Blood donors are routinely screened for hepatitis C virus infection. Some individuals have weak or restricted virus-specific antibody responses, and are classed as indeterminate. Such donors are almost always negative for viral RNA in blood. We postulated that previous transient virus exposure might account for some of these cases. With sensitive ex-vivo analyses of T-cell responses, we identified virus-specific responses in 15 of 30 indeterminate blood donors tested, compared with none in controls (p=0.0013). Additionally, these responses were typically focused on core-derived peptides. These findings suggest previous exposure to the virus in many indeterminate blood donors. 相似文献
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Red-cell GSH regeneration and glutathione reductase activity in G6PD variants in the Ferrara area 总被引:2,自引:0,他引:2
Barbara B. Anderson Gianni Carandina Marco Lucci Gillian M. Perry† Calogero Vullo 《British journal of haematology》1987,67(4):459-466
Summary. Red-cell studies were carried out on three groups of G6PD-deficient subjects with different G6PD variants from the Ferrara area of Northern Italy. Red-cell GSH and activities of G6PD, glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured. A method was developed to measure red-cell GSH regeneration after oxidation of endogenous GSH in whole blood by diamide and only this clearly distinguished the variants from each other and from normal. Regeneration by 1 h was lowest in the Mediterranean variant, 0–10.2% in contrast to 93–98% in normal. A predisposition to a haemolytic crisis after ingestion of fava beans was not clearcut, but subjects appeared to be at risk if GSH regeneration at 1 h was less than 30% of the endogenous level, and red-cell FAD+ was very high indicated by high in vitro GR activity and inhibition by added FAD+ .
It is suggested that the most informative tests in G6PD deficiency are measurements of GSH regeneration in intact red cells plus GR activity and/or red-cell flavin compounds. 相似文献
It is suggested that the most informative tests in G6PD deficiency are measurements of GSH regeneration in intact red cells plus GR activity and/or red-cell flavin compounds. 相似文献