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71.
Mouse white adipose tissue‐derived mesenchymal stem cells gain pericentral and periportal hepatocyte features after differentiation in vitro,which are preserved in vivo after hepatic transplantation
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Ingo Helbig Marielle E M Swinkels Emmelien Aten Almuth Caliebe Ruben van 't Slot Rainer Boor Sarah von Spiczak Hiltrud Muhle Johanna A J?hn Ellen van Binsbergen Onno van Nieuwenhuizen Floor E Jansen Kees P J Braun Gerrit-Jan de Haan Niels Tommerup Ulrich Stephani Helle Hjalgrim Martin Poot Dick Lindhout Eva H Brilstra Rikke S M?ller Bobby PC Koeleman 《European journal of human genetics : EJHG》2014,22(7):896-901
A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies. 相似文献
74.
Pawel Buczkowicz Ute Bartels Eric Bouffet Oren Becher Cynthia Hawkins 《Acta neuropathologica》2014,128(4):573-581
Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumour-related death in children. In the majority of cases diagnosis is based on clinical and MRI findings, resulting in the scarcity of pre-treatment specimens available to study. Our group has developed an autopsy-based protocol to investigate the histologic and biologic spectrum of DIPG. This has also allowed us to investigate the terminal pattern of disease and gain a better understanding of what challenges we are facing in treating DIPG. Here, we review 72 DIPG cases with well documented clinical history and molecular data and describe the pathological features of this disease in relation to clinical and genetic features. Fifty-three of the samples were autopsy material (7 pre-treatment) and 19 were pre-treatment biopsy/surgical specimens. Upon histological review, 62 patients had high-grade astrocytomas (18 WHO grade III and 44 WHO grade IV patients), 8 had WHO grade II astrocytomas, and 2 had features of primitive neuroectodermal tumour (PNET). K27M-H3 mutations were exclusively found in tumours with WHO grade II–IV astrocytoma histology. K27M-H3.1 and ACVR1 mutations as well as ALT phenotype were only found in WHO grade III–IV astrocytomas, while PIK3CA mutations and PDGFRA gains/amplifications were found in WHO grade II–IV astrocytomas. Approximately 1/3 of DIPG patients had leptomeningeal spread of their tumour. Further, diffuse invasion of the brainstem, spinal cord and thalamus was common with some cases showing spread as distant as the frontal lobes. These findings suggest that focal radiation may be inadequate for some of these patients. Importantly, we show that clinically classic DIPGs represent a diverse histologic spectrum, including multiple cases which would fit WHO criteria of grade II astrocytoma which nevertheless behave clinically as high-grade astrocytomas and harbour the histone K27M-H3.3 mutation. This suggests that the current WHO astrocytoma grading scheme may not appropriately predict outcome for paediatric brainstem gliomas. 相似文献
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Ronald H. M. A. Bartels Hieronymus Boogaarts Gert Westert 《Acta neurochirurgica》2013,155(6):1057-1067
Background
Regularly, patients are not involved in development of evaluative tools. Investigators define outcomes according to their interests. These can be different with those of the patients. Therefore, it may be difficult for patients to choose between treatment options, because the outcomes’ measurements may not reflect their problems in daily life. Most ideally, patients are involved from the beginning in the development of an outcome measurement tool. In this study, a new concept was demonstrated in which a questionnaire was developed in collaboration with patients to evaluate the quality of surgical care of a frequently encountered entity (carpal tunnel syndrome) that is meaningful for and understandable by patients.Methods
Through a patient participatory research in an academic hospital, 50 consecutive patients who recently underwent surgical decompression of carpal tunnel syndrome were asked to optimize a questionnaire. An existing questionnaire was sent to the patients with the request to grade the relevance of each question. They were also offered the possibility to add questions from their point of view.Results
All questions were found relevant. Finally, the questionnaire was modified by adding one question proposed by the patients. They wanted to include a question that would evaluate the effect of the treatment. Therefore, a question was introduced to evaluate the effect of the surgery on the symptoms and signs with a six-item Likert scale varying from severely worsened to free of signs and symptoms. Finally, the EQ-5D-5 L was added as a measure of quality of life.Conclusions
The participation of patients is essential but until now not usual when a tool for evaluating the success of a treatment is developed. Information that is meaningful for patients but not obligate for researchers can easily be missed in the classical development of outcome measurement tools. This information will be crucial when future patients try to understand the findings of research in order to make an appropriate decision between eventual treatment options. 相似文献78.
A. Thelen C. Benckert H.‐M. Tautenhahn H.‐M. Hau M. Bartels J. Linnemann J. Bertolini M. Moche C. Wittekind S. Jonas 《The British journal of surgery》2013,100(1):130-137
Background:
Data on liver resection for hepatocellular carcinoma (HCC) without cirrhosis are sparse. The present study was conducted to evaluate the indications and results of liver resection for HCC with regard to safety and efficacy.Methods:
Data for patients who had liver resection for HCC without cirrhosis between January 1996 and March 2011 were retrieved retrospectively using a prospective database containing information on all patients who underwent hepatectomy for HCC. Patient and tumour characteristics were analysed for influence on overall and disease‐free survival to identify prognostic factors by univariable and multivariable analysis.Results:
The 1‐, 3‐ and 5‐year overall survival rates after resection with curative intent for HCC without cirrhosis were 84, 66 and 50 per cent respectively. Disease‐free survival rates were 69, 53 and 42 per cent respectively. The 90‐day mortality rate was 4·5 per cent (5 of 110 patients). Surgical radicality and growth pattern of the tumour were independent prognostic factors for overall survival. Disease‐free survival after resection with curative intent was independently affected by growth pattern and by the number and size of tumour nodules.Conclusion:
Liver resection for HCC without cirrhosis carries a low perioperative risk and excellent long‐term outcome if radical resection is achieved. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. 相似文献79.
Snijders D Schoorl M Schoorl M Bartels PC van der Werf TS Boersma WG 《European Journal of Internal Medicine》2012,23(5):436-441
BackgroundD-dimer levels are in several studies elevated in patients with CAP. In this study we assess the use of D-dimer levels and its association with severity assessment and clinical outcome in patients hospitalised with community-acquired pneumonia.MethodsIn a subset of randomised trial patients with community-acquired pneumonia serial D-dimer levels was analysed. CURB-65 scores were calculated at admission.ResultsA total of 147 patients were included. D-dimer levels at admission were higher in patients with severe CAP (2166 ± 1258 versus1630 ± 1197 μg/l, p = 0.03), with clinical failure at day 30 (2228 ± 1512 versus 1594 ± 1078 μg/l, p = 0.02) and with early failure (2499 ± 1817 μg/l versus 1669 ± 1121 μg/l, p = 0.01). Non-survivors had higher D-dimer levels (3025 ± 2105 versus 1680 ± 1128 μg/l, p = 0.05). None of the 16 patients with D-dimer levels < 500 μg/l died. In multivariate analysis D-dimer levels were not associated with clinical outcome. D-dimer levels have poor accuracy for predicting clinical outcome at day 30 (AUC 0.62, 95% CI 0.51–0.73) or 30 day mortality (AUC 0.71 (95% CI 0.51–0.91)). Addition of D-dimer levels to CURB-65 did not increase accuracy. No differences were observed in serial D-dimer levels between patients with clinical success or failure at day 30.ConclusionD-dimer levels are elevated in patients with CAP. Significantly higher D-dimer levels are found in patients with clinical failure and with severe CAP. D-dimer levels as single biomarker or as addition to the CURB-65 have no added value for predicting clinical outcome or mortality. D-dimer levels < 500 μg/l may identify candidates at low risk for complications. 相似文献
80.
Geels LM Bartels M van Beijsterveldt TC Willemsen G van der Aa N Boomsma DI Vink JM 《Addiction (Abingdon, England)》2012,107(3):518-527
Aims To determine the effect of age, sex and cohort on the prevalence and genetic architecture of adolescent alcohol use (AAU). Design Survey study in participants registered with the Netherlands Twin Register. Setting Twins from the general population. Participants Two cohorts (data collected in 1993 and 2005–08) of twins aged 13–15, 16–17 and 18–21 years. In 1993 and 2005–08 a total of 3269 and 8207 twins, respectively, took part. Measurements Survey data on initiation and frequency of alcohol use and quantity of alcohol consumed. Findings The prevalence of alcohol initiation increased between 1993 and 2005–08 for both males and females. The largest difference was for girls observed at ages 13–15, where the prevalence increased from 59.5% to 72.4%. We also found increases in prevalence across cohorts for quantity of alcohol consumed and non‐significant increases for frequency of alcohol use. From age 16 onwards, boys drank more frequently and larger quantities than girls. Genetic model fitting revealed that the genetic architecture of AAU did not differ between birth cohorts, nor were there differences between boys and girls. Genetic factors explained between 21% and 55% of individual differences in alcohol measures throughout adolescence. Shared environment explained between 17% and 64% of variance in alcohol use, across different age groups and alcohol measures. Conclusions In the Netherlands, the prevalence of alcohol initiation, frequency and quantity has increased in adolescents over a 15‐year period, but there are no changes in the genetic architecture of adolescent alcohol use. 相似文献