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601.
Ovarian neoplasms secondary to germline BRCA mutations had been described to have a more favourable survival. There is only few data concerning the prognosis of non mutated patients presenting clinical features evocative of BRCA alterations. We retrospectively collected data from patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. Patients considered at high risk of BRCA mutation were tested for BRCA1/2 germline mutations. We described clinical, pathological and therapeutic features and compared prognosis of BRCA mutation carriers and non-mutated patients. Out of 617 ovarian cancer patients, we identified 104 patients who were considered at high risk of mutation. The 33 mutated patients were more likely to present a personal (33 vs. 10 %, p = 0.003) or a family (42 vs. 24 %, p = 0.06) history of breast/ovarian cancers. BRCA1/2 mutation carriers and wild type patients displayed similar prognosis: median progression–free survival (PFS) of 20.9 versus 37.7 months (p = 0.21); median overall survival (OS) of 151.2 versus 122.5 months (p = 0.52). Personal history of breast cancer increased both PFS [HR = 0.45 (95CI 0.25–0.81)] and OS [HR = 0.35 (95CI 0.16–0.75)]. In multivariate analysis, this parameter was an independent prognostic feature, whereas the identification of a BRCA1/2 mutation was not. In our cohort, all patients at high risk of BRCA mutation share a similar prognosis, whatever is their germline mutation status. Prognosis seems to be more influenced by clinical history than by germline mutations identification. If it is confirmed in larger and independent series, this result suggests that the hypothesis of other BRCA pathway alterations (BRCAness phenotype) deserves to be deeply explored.  相似文献   
602.
The aim of this study was to assess the effect of coronary artery bypass grafting (CABG) on myocardial perfusion and left ventricular (LV) contractile reserve in patients with reduced ejection fraction (EF). We studied 57 patients (age 59 +/- 8 years, 46 men and 11 women) with EF < or = 40% referred for CABG with dobutamine (up to 40 microg/kg/min) stress-reinjection thallium-201 single-photon emission computed tomography, and radionuclide ventriculography at rest and at low-dose dobutamine before and 3 months after CABG. An increase in resting EF > or = 5% occurred in 12 patients (group A) after CABG (EF 34% before and 46% after CABG), whereas no increase occurred in the remaining 45 patients (group B) (EF 34% before and 32% after CABG). A significant increase in EF from rest to low-dose dobutamine radionuclide ventriculography occurred before and after CABG. The magnitude of increase was more significant after than before CABG in group A (12% vs 7%) as well as in group B (13% vs 7%, both p <0.001). Patients in both groups had a significant reduction in stress, rest, and ischemic perfusion scores after CABG. However, the percentage of reduction in resting perfusion defect score was more significant in group A than in group B (60% vs 30%, respectively, p <0.01). It is concluded that CABG induces a significant improvement in resting myocardial perfusion and EF response to inotropic stimulation, even in the absence of improved EF at rest. Patients without improvement in resting EF after CABG have mild improvement in resting myocardial perfusion that may be sufficient to increase EF after CABG during inotropic stimulation, but not at rest. We describe the myocardium with these characteristics as "the reactive myocardium."  相似文献   
603.
BACKGROUND: In chronic heart failure augmented wall stress leads to increased energy demand. Supply, however, may be reduced due to coronary vasoconstriction and endothelial dysfunction. This might lead to a mismatch between demand and supply. In the present study we further explored the effect of increased demand during dobutamine stress echocardiography. METHODS AND RESULTS: Sixteen patients with idiopathic dilated cardiomyopathy (mean age 44+/-13 years, New York Heart Association class II-III, mean left ventricular ejection fraction 0.27+/-0.10) underwent dobutamine stress echocardiography (5-40 microg/min per kg bodyweight+atropine if required). Wall motion and thickening was assessed in 16 segments using a four-point scale. Eleven patients (69%) showed regions with worsening of wall motion or a biphasic response during dobutamine infusion. Of the remaining five patients one patient did not show any wall motion changes and one patient showed a partial improvement while only in three patients wall motion improvement in the whole heart was found. CONCLUSION: A majority of patients with idiopathic dilated cardiomyopathy showed decreased wall motion during increased demand, i.e. ischemia-like myocardial contractile responses during dobutamine stress echocardiography. These findings further support the concept that an energy mismatch between demand and supply might play a pathophysiological role in idiopathic dilated cardiomyopathy.  相似文献   
604.
BACKGROUND: Patients with left bundle branch block exhibit abnormal septal motion which may limit the interpretation of stress echocardiograms. This study sought to assess the diagnostic value of dobutamine-atropine stress echocardiography in left bundle branch block patients. METHODS AND RESULTS: Sixty-four left bundle branch block patients (mean age 59 years, 24 men) with suspected coronary artery disease underwent dobutamine-atropine stress echocardiography and coronary arteriography. Myocardial ischaemia was defined as new or worsening wall thickening abnormalities. Coronary artery disease was quantitatively defined as a diameter stenosis >/=50% in a major epicardial artery. Rest septal motion was normal (apart from the early systolic septal notch) in 34 patients (53%) and abnormal in 30 patients (47%). Rest septal thickening was normal in 32 patients (50%) and abnormal in 32 patients (50%). All seven patients with a QRS duration >/=160 ms and an abnormal QRS axis had abnormal rest septal motion and thickening. Inter-observer agreement for ischaemia was 88%. In all but one patient disagreement was in the septum. For the anterior and posterior circulation, respectively, sensitivity was 60% (9/15) and 67% (8/12), specificity was 94% (46/49) and 98% (51/52), and accuracy was 86% (55/64) and 92% (59/64). Sensitivity for the anterior circulation tended to be better in patients with normal rest septal thickening (83% vs 44%). CONCLUSIONS: Dobutamine-atropine stress echocardiography has excellent diagnostic specificity in left bundle branch block patients with suspected coronary artery disease. In patients with abnormal rest septal thickening, however, dobutamine-atropine stress echocardiography may lack good sensitivity for detection of coronary artery disease in the anterior circulation. Left bundle branch block patients who potentially most benefit from dobutamine-atropine stress echocardiography may initially be selected by their resting electrocardiogram.  相似文献   
605.
Array comparative genomic hybridization (aCGH) has progressively replaced conventional karyotype in the diagnostic strategy of intellectual disability (ID) and congenital malformations. This technique increases not only the diagnostic rate but also the possibility of finding unexpected variants unrelated to the indication of referral, namely incidental findings. The incidental finding of copy number variants (CNVs) located in X‐linked genes in girls addresses the crucial question of genetic counseling in the family. We report here five cases of CNVs involving the dystrophin gene detected by aCGH in girls referred for developmental delay, without any family history of dystrophinopathy. The rearrangements included three in‐frame deletions; one maternally and two paternally inherited, and two frameshift duplications: one de novo and one from undetermined inheritance. In two cases, the deletion identified in a girl was transmitted by the asymptomatic father. In the case of the maternally inherited deletion, prenatal diagnosis of dystrophinopathy was proposed for an ongoing pregnancy, whereas the cause of developmental delay in the index case remained unknown. Through these cases, we discussed the challenges of genetic counseling in the family, regarding the predictive issues for male individuals at risk for a muscular dystrophy without precise knowledge of the clinical consequences of some CNVs in the DMD gene.  相似文献   
606.
Congestive heart failure is a leading cause of mortality in developed countries. Myocardial hypertrophy resulting from hypertension often precedes heart failure. Understanding the signaling underlying cardiac hypertrophy and failure is of major interest. Here, we identified Fas receptor activation, a classical death signal causing apoptosis via activation of the caspase cascade in many cell types, as a novel pathway mediating cardiomyocyte hypertrophy in vitro and in vivo. Fas activation by Fas ligand induced a hypertrophic response in cultured cardiomyocytes, which was dependent on the inactivation of glycogen synthase kinase 3 beta (GSK3 beta) by phosphorylation. In vivo, lpr (lymphoproliferative disease) mice lacking a functional Fas receptor demonstrated rapid-onset left ventricular dilatation and failure, absence of compensatory hypertrophy, and significantly increased mortality in response to pressure overload induction that was accompanied by a failure to inhibit GSK3 beta activity. In contrast, Fas ligand was dispensable for the development of pressure overload hypertrophy in vivo. In vitro, neonatal cardiomyocytes from lpr mice showed a completely abrogated or significantly blunted hypertrophic response after stimulation with Fas ligand or angiotensin II, respectively. These findings indicate that Fas receptor signaling inhibits GSK3 beta activity in cardiomyocytes and is required for compensation of pressure overload in vivo.  相似文献   
607.
Globally, there are several critical infrastructure networks (water and gas networks) whose disruption or destruction would significantly affect the maintenance of vital societal functions, such as the health, safety, security, and social or economic well-being of people. They would also have significant local, regional, and national impacts as a result of the inability to maintain those functions, and would have similar cross-border effects. The main objective of this article is to investigate by comparative numerical studies the structural response of three types of buried pipes made of different materials, primarily steel, concrete, and high-density polyethylene, resulting from the impact of the environment through exceptional external actions, such as explosions at the surface of the land in the vicinity of the laying areas. The dynamic transient analysis of the equation of motion with the application of the explicit integration procedure was performed with the ANSYS numerical simulation program. This study allows designers to solve complex problems related to the quality of the laying ground of water networks to canals. The knowledge accumulated gives us the possibility to correctly specify the optimal economic and technical value of the ratio between the laying depth of pipes and their diameter, the importance of the radius ratio of the pipe and the thickness of its wall, and, importantly, the improvement of the quality of the foundation ground. Following the results obtained, it is estimated that the optimal economic and technical value of the ratio between the laying depth of the pipes (H) and their diameter (D) is 3, regardless of the material from which the pipe is made.  相似文献   
608.
Rearrangement and coamplification of the 8p12 and 11q13 chromosomal regions occurs in a significant proportion of breast cancers. It usually involves a complex hybrid structure in which the FGFR1 and CCND1 genes are amplified. We report here a different type of 8p12-11q13 rearrangement in the MDA-MB-175 mammary carcinoma cell line. This amplification contains the NRG1/HGL (from 8p12-21) and DOC4 (from 11q13) genes, encoding respectively a ligand for ERBB receptors and a stress-induced protein which is a mammalian ortholog of Drosophila Tenm/Odz. It has been shown previously (Wang et al, Oncogene 18: 5718-5721, 1999) that these two genes are rearranged and fused by a translocation event. This type of event was not found in 30 tumors tested that showed coamplification of the 8p12 and 11q13 regions.  相似文献   
609.
Missiaglia  E  Jacobs  B  D'  ArioG  Di  Narzo  AF  Soneson  C  Budinska  E  Popovici  V  Vecchione  L  Gerster  S  Yan  P  Roth  AD  Klingbiel  D  Bosman  F  Delorenzi  M  Tejpar  S  刘嘉 《中国肿瘤外科杂志》2014,(4):256-256
背景远端和近端结肠癌在起源,基因暴露,环境诱变及肠道菌群等方面均存在差异。然而这些差异很少被用来解释如何影响肿瘤的发生机制,特异的治疗响应及预后情况。研究系统性探索了远端与近端结肠癌的差异及这些差异的临床意义。资料与方法研究共纳入3 045例结肠癌患者的详细临床病理数据用于分析,这些患者资料均来源于PETACC3(关于结肠癌辅助化疗)临床试验。这些数据中,  相似文献   
610.
Bats are increasingly recognized as reservoirs for many different viruses that threaten public health, such as Hendravirus, Ebolavirus, Nipahvirus, and SARS- and MERS-coronavirus. To assess spillover risk, viromes of bats from different parts of the world have been investigated in the past. As opposed to most of these prior studies, which determined the bat virome at a single time point, the current work was performed to monitor changes over time. Specifically, fecal samples of three endemic Swiss bat colonies consisting of three different bat species were collected over three years and analyzed using next-generation sequencing. Furthermore, single nucleotide variants of selected DNA and RNA viruses were analyzed to investigate virus genome evolution. In total, sequences of 22 different virus families were found, of which 13 are known to infect vertebrates. Most interestingly, in a Vespertilio murinus colony, sequences from a MERS-related beta-coronavirus were consistently detected over three consecutive years, which allowed us to investigate viral genome evolution in a natural reservoir host.  相似文献   
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