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Lambrou GI Papadimitriou L Chrousos GP Vlahopoulos SA 《Molecular and cellular endocrinology》2012,351(2):142-151
Twenty years ago a proteasome inhibitor was suggested as therapy for glucocorticoid-resistant multiple myeloma, a disease that involves terminally differentiated B cells. Since then, research has proven that it has utility on a number of tumors resistant to chemotherapy. Hematologic malignancy, however, often involves lesser differentiated cells, which have a high potential to modulate their intrinsic machinery and thereby activate alternative rescue pathways. A corresponding multiplicity of therapies is not always practical. One approach to conditions with heterogeneous physiology is to identify key biochemical mediators, thereby reducing the number of treatment targets. Results from several ongoing studies indicate convergence of genomically diverse signal pathways to a limited number of key downstream regulators of apoptosis. Convergence of pathways can be exploited to address the problem of genetic heterogeneity in acute leukemia: this would mean treating multiple molecular aberrations with fewer drugs and enhanced therapeutic benefit. 相似文献
83.
Kalleas C Anagnostopoulos K Sinopoulou K Delaki E Margaritis D Bourikas G Tsatalas C Kortsaris A Tentes I 《Hemoglobin》2012,36(1):64-72
A decade of screening (years 2000 to 2010) for hemoglobinopathies in 3,931 patients was performed at the General Hospital of Poligiros, Halkidiki, Northern Greece. Among the patients examined, 10.8% heterozygotes for β-thalassemia (β-thal) were found, as well as 4.1% with sickle cell disease and 1.2% with double β-thal/Hb S [β6(A3)Glu→Val] heterozygosity. Iron deficiency was observed in 23.4%. The geographical distribution in the region revealed a substantial incidence of hemoglobinopathies even in mountainous areas. This pattern did not follow the typical distribution according to the malaria hypothesis, as incidence did not dovetail with swamp locations recorded in the past. The HBB gene mutations for 85 patients were also analyzed. Most prevalent in Halkidiki, Northern Greece, was the codon 39 (C>T) mutation (27.1%) followed by the IVS-I-110 (G>A) mutation (22.4%); this was in direct contrast to the current distribution of the same mutations seen in the rest of Greece (Greek National Genetic Database, GNGD). This frequency inversion was statistically significant, with the difference from the GNGD being 20.6% for the IVS-I-110 mutation (p <0.0005) and 7.6% for the codon 39 mutation (p = 0.0238). The history of Halkidiki, denoting a clear example of geographical isolation from the rest of the country, may possibly account for a potentially diverse genetical identity of the disease in this region. 相似文献
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Evangelia Liouta Theodosis Kalamatianos Faidon Liakos George Stranjalis 《Neurocase》2013,19(2):211-215
Subdural fluid collections (SFC) are characteristic complications of shunting for idiopathic normal pressure hydrocephalus (iNPH). This report presents two shunted iNPH patients with clinically silent postoperative SFC, detected after abnormal neuropsychological findings. These cases highlight the value of neuropsychological assessment in the routine postoperative assessment of iNPH. 相似文献
86.
Andreas Roposch MD MSc FRCS Liang Q. Liu MBBS PhD Evangelia Protopapa MSc 《Clinical orthopaedics and related research》2013,471(6):1946-1954
Background
Wide variation exists in reported prevalence estimates and management standards of developmental dysplasia of the hip (DDH). Discrepancies in diagnosticians’ opinions may explain some of this variation.Questions/purposes
We sought to determine (1) the consistency with which pediatric orthopaedic surgeons rate the importance of diagnostic criteria for DDH, and (2) whether there were geographic differences in how the diagnostic criteria were rated by surgeons.Methods
One hundred ninety-seven of 220 members of the European Paediatric Orthopaedic Society and 100 of 148 members of the British Society of Children’s Orthopaedic Surgery treating children with DDH participated in this cross-sectional study across 35 countries (15 regions). Each rated 37 items in four domains that specialists previously had identified as the most important features associated with DDH in early infancy. We determined consistency using the intraclass correlation coefficient (ICC; two-way random-effects model) interpreted as poor (0–0.40), acceptable (0.41–0.74), or good (≥ 0.75).Results
Poor consistency among surgeons was found in rating the 37 diagnostic criteria (ICC, 0.33; 95% CI, 0.24–0.45). Consistency was poor for three domains (patient characteristics/history: ICC, 0.29; 95% CI, 0.16–0.58; ultrasound: ICC, 0.26; 95% CI, 0.14–0.52; radiography: ICC, 0.34; 95% CI, 0.12–0.95) and acceptable for one (clinical examination: ICC, 0.50; 95% CI, 0.33–0.73). Surgeons in particular regions appeared to have a concept of DDH diagnosis that distinguished them from specialists of other regions; consistency in eight regions was greater (ICC ≥ 0.40) than consistency among all 15 regions.Conclusions
The consistency of specialists in rating diagnostic criteria for DDH was lower than expected, and there was considerable geographic variation in terms of how specialists assigned importance ratings of the diagnostic criteria; these findings are somewhat counterintuitive, given the frequency with which this condition is diagnosed. These inconsistencies could explain, partly, the widely differing prevalence estimates and management standards of DDH. 相似文献87.
Constantine Dimitrakakis Flora Zagouri Alexandra Tsigginou Spyros Marinopoulos Theodoros N. Sergentanis Antonis Keramopoulos George C. Zografos Konstantina Ampela Dimosthenis Mpaltas Christos Papadimitriou Meletios-Athanassios Dimopoulos Aris Antsaklis 《Breast care (Basel, Switzerland)》2013,8(3):203-207
Zusammenfassung
Hintergrund: Die Auswirkungen einer Schwangerschaft auf die Prognose des Mammakarzinoms werden in der Literatur kontrovers diskutiert. Wir haben eine gepaarte Fall-Fall-Studie konzipiert, in der schwangerschaftsasso-ziierte Mammakarzinom (SAM)-Fälle entsprechend ihres Stadiums, Alters und Jahr der Diagnosestellung mit Mammakarzinom-Patientinnen gepaart wurden. Patientinnen und Methoden: 39 aufeinanderfolgende SAM-Fälle wurden mit 39 prämenopausalen Fällen von Brust-krebs gepaart. Univariate und multivariate Überlebens-analysen mit Anpassung an Stadium, Grad, Östrogen-rezeptorstatus und Alter zum Zeitpunkt der Diagnose wurden durchgeführt. Ergebnisse: Hinsichtlich des Gesamtüberlebens deutete die univariate Analyse auf ein längeres Gesamtüberleben für nicht-SAM-Fälle vs. SAM-Fälle hin. Gleichzeitig war ein fortgeschritteneres Stadium ein Prädiktor für ein kürzeres Überleben. Die multivariate Analyse bestätigte die unabhängige ver-schlechternde Auswirkung einer Schwangerschaft. Inter-essanterweise ergab eine genestete Post-hoc-Analyse der SAM-Fälle Hinweise auf ein kürzeres Gesamtüberleben für das dritte Trimester. Die oben erwähnten Ergebnisse für das Gesamtüberleben konnten desweiteren bei der Untersuchung des rezidivfreien Überlebens reproduziert werden. Schlussfolgerung: Mit ihrem gepaarten Fall-Fall-Design deutet die vorliegende Studie darauf hin, dass Schwangerschaft ein schlechter Prognosefaktor beim Mammakarzinom ist. 相似文献88.
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