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991.
Gattermann N Finelli C Della Porta M Fenaux P Stadler M Guerci-Bresler A Schmid M Taylor K Vassilieff D Habr D Marcellari A Roubert B Rose C 《Haematologica》2012,97(9):1364-1371
Background
Reductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on there reductions/improvements have been limited to case reports and small studies.Design and Methods
To explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients’ Iron Chelation with Exjade® (EPIC) study using International Working Group 2006 criteria.Results
Two-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders.Conclusions
This analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes. 相似文献992.
Hirsch P Tang R Marzac C Perrot JY Fava F Bernard C Jeziorowska D Marie JP Legrand O 《Haematologica》2012,97(2):241-245
ATP-binding cassette transporter (and specially P-glycoprotein) activity is a well known prognostic factor in acute myeloid leukemia, but when compared to other molecular markers its prognostic value has not been well studied. Here we study relationships between this activity, fms-like tyro-sine kinase 3(FLT3/ITD), nucleophosmin(NPM1), CAAT-enhancer binding protein alpha(CEBPα), and brain and acute leukemia cytoplasmic protein (BAALC), in 111 patients with normal cytogenetics who underwent the same treatment, and evaluate its prognostic impact. Independent factors for survival were age (P=0.0126), ATP-binding cassette transporter activity (P=0.018) and duplications in the fms-like tyrosine kinase 3 (P=0.0273). In the 66 patients without fms-like tyrosine kinase 3 duplication and without nucleophosmin mutation, independent prognostic factors for complete remission achievement and survival were age and ATP-binding cassette transporter activity. In conclusion, ATP-binding cassette transporter activity remains an independent prognostic factor, and could assist treatment decisions in patients with no nucleophosmin mutation and no fms-like tyrosine kinase 3 duplication. 相似文献
993.
994.
995.
Jennifer G. Goldman Reena A. Ghode Bichun Ouyang Bryan Bernard Christopher G. Goetz Glenn T. Stebbins 《Parkinsonism & related disorders》2013,19(9):806-811
BackgroundDaytime and nighttime sleep disturbances and cognitive impairment occur frequently in Parkinson's disease (PD), but little is known about the interdependence of these non-motor complications. Thus, we examined the relationships among excessive daytime sleepiness, nighttime sleep quality and cognitive impairment in PD, including severity and specific cognitive deficits.MethodsNinety-three PD patients underwent clinical and neuropsychological evaluations including the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Patients were classified as having normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD) using recently proposed Movement Disorder Society PD-MCI and PDD criteria. Relationships between the sleep and cognitive measures and PD cognitive groups were examined.ResultsThe PD cohort included PD-NC (n = 28), PD-MCI (n = 40), and PDD (n = 25) patients. ESS scores, as a measure of daytime sleepiness, were significantly worse (p = 0.005) in cognitively impaired PD patients, particularly PDD patients. ESS scores correlated significantly with Mini-Mental State Examination scores and also with cognitive domain scores for attention/working memory, executive function, memory, and visuospatial function. In contrast, PSQI scores, as a measure of nighttime sleep quality, neither differed among cognitive groups nor correlated with any cognitive measures.ConclusionsDaytime sleepiness in PD, but not nighttime sleep problems, is associated with cognitive impairment in PD, especially in the setting of dementia, and attention/working memory, executive function, memory, and visuospatial deficits. The presence of nighttime sleep problems is pervasive across the PD cognitive spectrum, from normal cognition to dementia, and is not independently associated with cognitive impairment or deficits in cognitive domains. 相似文献
996.
997.
Gleicy K. Barcelos Yannick Tholance Sebastien Grousson Bernard Renaud Armand Perret-Liaudet Frederic Dailler Luc Zimmer 《Neurocritical care》2013,18(2):234-244
Purpose
The aim of this study was to determine if the measurement of blood biomarkers of glucose cerebral metabolism, performed with retrograde jugular catheter, could predict the outcome of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients.Methods
This study was conducted in 68 poor-grade aSAH patients. A total of 4,024 blood samples obtained from jugular and radial catheters were analyzed for glucose, lactate, and oxygen content every 8 h for 10 ± 0.5 days. Metabolic ratio (MR) and lactate–oxygen index (LOI) were obtained by ratios using arterio-jugular differences. Functional outcome was evaluated at 12 months with the Glasgow Outcome Scale.Results
Outcome was unfavorable in 40 patients. In this group of patients, the MR was significantly lower (p < 0.0001) and the LOI was significantly higher (p = 0.0001) than in the group with favorable outcome. The MR cutoff value, below which the patients are likely to have an unfavorable outcome, was determined to be 3.35. More interestingly, the data obtained in this study demonstrated that the patients achieving an unfavorable outcome were distinguished from those with a favorable outcome by having at least three events of MR inferior to 3.35 (sensitivity = 90 %, specificity = 82.1 %). Moreover, in patients who developed cerebral vasospasm, we observed a significant decrease in the MR.Conclusion
Our data provide additional support to the view that the MR is a reliable marker for predicting the outcome of poor-grade aSAH patients. Prospective studies are needed to confirm its value in multimodal monitoring. 相似文献998.
Laura A. Smith Callahan Erin P. Childers Sharon L. Bernard Scott D. Weiner Matthew L. Becker 《Acta biomaterialia》2013,9(7):7420-7428
New systematic approaches are necessary to determine and optimize the chemical and mechanical scaffold properties for hyaline cartilage generation using the limited cell numbers obtained from primary human sources. Peptide functionalized hydrogels possessing continuous variations in physico-chemical properties are an efficient three-dimensional platform for studying several properties simultaneously. Herein, we describe a polyethylene glycol dimethacrylate (PEGDM) hydrogel system possessing a gradient of arginine–glycine–aspartic acid peptide (RGD) concentrations from 0 mM to 10 mM. The system is used to correlate primary human osteoarthritic chondrocyte proliferation, phenotype maintenance and extracellular matrix (ECM) production to the gradient hydrogel properties. Cell number and chondrogenic phenotype (CD14:CD90 ratios) were found to decline in regions with higher RGD concentrations, while regions with lower RGD concentrations maintained cell number and phenotype. Over three weeks of culture, hydrogel regions containing lower RGD concentrations experience an increase in ECM content compared to regions with higher RGD concentrations. Variations in actin amounts and vinculin organization were observed within the RGD concentration gradients that contribute to the differences in chondrogenic phenotype maintenance and ECM expression. 相似文献
999.
Kim Freriks Henri J.L.M. Timmers Romana T. Netea-Maier Catharina C.M. Beerendonk Barto J. Otten Janiëlle A.E.M. van Alfen-van der Velden Maaike A.F. Traas Hanneke Mieloo Guillaume W.H.J.F.L. van de Zande Lies H. Hoefsloot Ad R.M.M. Hermus Dominique F.C.M. Smeets 《European journal of medical genetics》2013,56(9):497-501
Turner syndrome (TS) is the result of (partial) X chromosome monosomy. In general, the diagnosis is based on karyotyping of 30 blood lymphocytes. This technique, however, does not rule out tissue mosaicism or low grade mosaicism in the blood. Because of the associated risk of gonadoblastoma, mosaicism is especially important in case this involves a Y chromosome. We investigated different approaches to improve the detection of mosaicisms in 162 adult women with TS (mean age 29.9 ± 10.3). Standard karyotyping identified 75 patients (46.3%) with a non-mosaic monosomy 45,X. Of these 75 patients, 63 underwent additional investigations including FISH on buccal cells with X- and Y-specific probes and PCR-Y on blood. FISH analysis of buccal cells revealed a mosaicism in 19 of the 63 patients (30.2%). In five patients the additional cell lines contained a (derivative) Y chromosome. With sensitive real-time PCR we confirmed the presence of this Y chromosome in blood in three of the five cases. Although Y chromosome material was established in ovarian tissue in two patients, no gonadoblastoma was found. Our results confirm the notion that TS patients with 45,X on conventional karyotyping often have tissue specific mosaicisms, some of which include a Y chromosome. Although further investigations are needed to estimate the risk of gonadoblastoma in patients with Y chromosome material in buccal cells, we conclude that FISH or real-time PCR on buccal cells should be considered in TS patients with 45,X on standard karyotyping. 相似文献
1000.
Maarten J. Van Den Bossche Mojca Strazisar Sophia Cammaerts Anthony M. Liekens Geert Vandeweyer Veerle Depreeuw Maria Mattheijssens An‐Sofie Lenaerts Sonia De Zutter Peter De Rijk Bernard Sabbe Jurgen Del‐Favero 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2013,162(3):273-282
Over the last years, genome‐wide studies consistently showed an increased burden of rare copy number variants (CNVs) in schizophrenia patients, supporting the “common disease, rare variant” hypothesis in at least a subset of patients. We hypothesize that in families with a high burden of disease, and thus probably a high genetic load influencing disease susceptibility, rare CNVs might be involved in the etiology of schizophrenia. We performed a genome‐wide CNV analysis in the index patients of eight families with multiple schizophrenia affected members, and consecutively performed a detailed family analysis for the most relevant CNVs. One index patient showed a DRD5 containing duplication. A second index patient presented with an NRXN1 containing deletion and two adjacent duplications containing MYT1L and SNTG2. Detailed analysis in the subsequent families showed segregation of the identified CNVs. With this study we show the importance of screening high burden families for rare CNVs, which will not only broaden our knowledge concerning the molecular genetic mechanisms involved in schizophrenia but also allow the use of the obtained genetic data to provide better clinical care to these families in general and to non‐symptomatic causal CNV carriers in particular. © 2013 Wiley Periodicals, Inc. 相似文献