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  • 1
    Keywords: POOR-PROGNOSIS ; BRAIN-TUMORS ; CHILDHOOD MEDULLOBLASTOMA ; RISK STRATIFICATION ; outcome prediction ; TP53 MUTATIONS ; PATHWAY ACTIVATION ; MOLECULAR SUBGROUPS ; NEUROTROPHIN RECEPTOR TRKC ; MYCN AMPLIFICATION
    Abstract: Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.
    Type of Publication: Journal article published
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  • 2
    ISSN: 0168-9002
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters A 164 (1992), S. 374-378 
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Experimental Gerontology 17 (1982), S. 387-397 
    ISSN: 0531-5565
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 114 (1973), S. 175-190 
    ISSN: 1432-1076
    Keywords: NBT test ; Bacterial infections ; Hemophilia A ; Endotoxin (effect on granulocytes)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wird über Untersuchungen mit dem leicht modifizierten cytochemischen NBT-Test von Gifford u. Malawista berichtet. Bei 51 Kindern und 11 Erwachsenen fand sich ein Normalbereich von 33±12% Formazanzellen. Unabhängig vom Geburtsgewicht hatten 22 reife Neugeborene und 37 Frühgeborene anfänglich erhöhte Werte, die innerhalb der ersten 2 Lebenswochen zur Erwachsenennorm abfielen. Bei 38 von 48 Kindern mit bakteriellen Infektionen und 1 Fall von Candida-Sepsis fiel der Test pathologisch aus, während Kinder mit Virusinfektionen, Tbc und Kollagenosen normale Werte hatten. Bei der Meningokokken-Sepsis wurde der Test erst nach 24–36 Std positiv. Dabei reagierten die Liquorzellen nicht eher als die Blutgranulocyten. Erhöhte Werte fanden sich auch bei den meisten Patienten mit Hämophilie A, nicht aber bei Patienten mit Blutungen aus anderer Ursache. In vitro konnte die NBT-Reduktion durch Einwirkung von bakteriellem Endotoxin in Phase I des Testes stimuliert werden. Steroide hatten in vitro keinen Einfluß auf die Formazanzellbildung.
    Notes: Abstract The cytochemical NBT test of Gifford and Malawista was slightly modified. In 51 healthy children and in 11 adults we found 33±12% formazan cells. Irrespective of weight, 22 mature newborns and 37 premature infants initially had increased formazan cell counts, decreasing to adult levels within the first 2 weeks of life. The NBT test was abnormal in 38 out of 48 children with bacterial infections and in 1 infant with candida-septicemia, but normal in children with viral diseases, tuberculosis or collagen diseases. In meningococcal septicemia the test became positive only after 24–36 hrs, cerebrospinal fluid cells not reacting in advance to blood granulocytes. In most cases of hemophilia A NBT reduction was increased, but not in patients with bleeding of different etiology. Bacterial endotoxin stimulated NBT reduction by action in phase I of the test. Steroids in vitro did not depress the formazan cell count.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of thiamine pyrophosphatase (TPPase) activity in the acinar cells of the rat sublingual gland has been studied at various stages of the secretory cycle following stimulated secretion. The rats were stimulated to secrete by an intraperitoneal injection of isoproterenol and pilocarpine. In non-stimulated glands, TPPase activity is detected mainly in 3–4 cisternae at the inner concave side of the Golgi complex and in some adjacent condensing vacuoles as in other cells. In the acinar cells 1 to 2 h after stimulation, however, reaction product for the same enzyme activity is detected in the cisternae at the outer aspect, as well as the inner aspect, of the Golgi complex and even in the cisternae of the endoplasmic reticulum (ER). About 4 h after stimulation, TPPase activity becomes concentrated in 3–4 disternae at the inner concave side of the Golgi complex as in the acinar cells under non-stimulated conditions. Morphological observations of the acinar cells 1 to 2 h after the stimulation have indicated that the reorganization of the Golgi complex and ER is a major event which occurs at this stage. It is possible that this cellular event is related to the occurrence of TPPase activity in those sites which normally show negative reaction in non-stimulated state.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1433-0350
    Keywords: Key words Hydrocephalus ; Endoscopic III ventriculostomy ; Outcome ; MRI ; Cine-MRI ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to analyze the surgical outcome according to clinical characteristics and to evaluate the correlation between clinical improvement and neuroimaging changes, we retrospectively reviewed 32 children who had undergone endoscopic III ventriculostomy (ETV) from February 1994 to May 1998. There were 15 boys and 17 girls, with a mean age of 5.2 years (range: 1 month to 13 years). The etiology of the hydrocephalus was primary aqueductal stenosis in 18 patients, secondary aqueductal stenosis caused by tumors in 5, IV ventricle outlet obstruction in 5, and hydrocephalus associated with meningomyelocele in 4. The mean duration of follow-up was 19.4 months (range 1–50 months). Overall, surgical outcome was regarded as good in 21 of 29 patients. Surgical outcome was poor in patients younger than 1 year (P〈0.05). Neuroimaging 1 month after ETV showed a decrease in ventricular size in 11 of the 16 patients with good surgical outcomes. Five showed minimal changes only. In patients with good outcomes, ventricular size tended to decrease as time passed. Resolution of periventricular edema, flow void in the III ventricle on T2-weighted axial images, and cine-MR imaging were sensitive indicators of good outcome. We suggest that ETV be considered as a primary treatment option in patients older than 1 year of age with noncommunicating hydrocephalus. In addition, time factors should be taken into consideration when surgical outcome is judged. Changes in ventricular size could not predict surgical outcome completely in themselves. Therefore, a comprehensive postoperative assessment should be made with the help of T2-weighted MRI and cine-MRI.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-5195
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé. A cause de l’idée selon laquelle la thrombose veineuse profonde post-opéraloire est rare parmi les patients asiatiques, la tromboprophylaxie pour les patients opérés est inhabituelle. Nous avons accompli une étude, comparant la prophylaxie au moyen d’héparine de bas poids moléculaire en utilisant du calcium nadroparine (Fraxiparine Sanofi France) et la non-prophylaxie sur 100 patients subissant un remplacement total de la hanche. Les patients ont subi une vénographie bilatérale avant l’opération et 10 jours après. Huit patients (16%) ont développé une thrombose veineuse dans le groupe de contrôle, contre 1 (2%) dans le groupe traité (p = 0.015, 95% CI 0.02 – 0.67). Trois embolies pulmonaires sont survenues dans le groupe de contrôle et 1 dans le groupe traité (p = 0.27 95% CI 0.04 – 2.44) aucune n’étant fatale. La perte de sang intra-opératoire et post-opératoire n’a pas varié de manière significative entre les deux groupes. Notre étude démontre que l’incidence de la thrombose veineuse profonde post-opératoire chez les patients asiatiques est notable bien qu’elle soit moindre que dans les pays occidentaux et confirme la sûreté et l’efficacité du calcium nadroparine pour la prévenir aprés un remplacement total de la hanche.
    Notes: Summary. Because of the belief that post-operative deep vein thrombosis (DVT) is rare in Asian patients, thromboprophylaxis is not usually prescribed for surgical patients. This study reports an open multi-centre controlled study of the use of a low molecular weight heparin, nadroparin calcium (Fraxoparine Sanofi France), as opposed to no prophylaxis in 100 patients undergoing uncemented total hip replacement. The patients had bilateral venography performed preoperatively and 10 days after operation. Eight patients (16%) developed DVT in the control group of 50 patients and 1 (2%) in the treatment group, also of 50 patients. Pulmonary embolus occurred in 1 patient in the treatment group and in 3 in the control group. Intraoperative and postoperative blood loss did not differ significantly between the two groups. Our study suggests that the incidence of DVT in Asian patients, though somewhat less than in their Western counterparts, is still considerable. It confirms the safety and efficacy of nadroparin calcium in preventing post-operative DVT in patients undergoing elective total hip replacement.
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  • 9
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract On the basis of mutational analysis, the genes for phosphonate uptake and degradation in Escherichia coli were shown to be organized in a 10.9-kb operon of 14 genes (named phnC to phnP) and induced by phosphate (Pi) starvation [Metcalf and Wanner (1993) J Bacteriol 175: 3430–3442]. The repression of phosphonate utilization by Pi has hindered both the biochemical characterization of the carbon-phosphorus (C-P) lyase activity and the development of improved methods for phosphonate biodegradation in biotechnology. We have cloned the genes phnG to phnP (associated with C-P lyase activity) with the lac promoter to provide expression of C-P lyase in the presence of Pi. A number of strains lacking portions of the phn operon have been constructed. In vivo complementation of the strains, in which phnC to phnP (including both Pn transport and catalysis genes) or phnH to phnP (including only catalysis genes) was deleted, with plasmids carrying various fragments of the phn operon revealed that the expression of phnC-phnP gene products is essential to restore growth on minimal medium with phosphonate as the sole phosphorus source, while phnG-phnM gene products are required for C-P lyase activity as assessed by in vivo methane production from methylphosphonic acid. The minimum size of the DNA required for the whole-cell C-P lyase activity has been determined to be a 5.8-kb fragment, encompassing the phnG to phnM genes. Therefore, there is no requirement for the phnCDE-encoded phosphonate transport system, suggesting that cleavage of the C-P bond may occur on the outer surface of the inner membrane of E. coli cells, releasing the carbon moiety into the periplasm. These data are in agreement with the observation that phosphonates cannot serve as the carbon source for E.␣coli growth.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1365-2842
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: summary  The aim of this study was to quantify the extent of abutment screw loosening and thus understand the role of frictional and wear factors in abutment screw loosening by using a cyclic loading device to compare Diamond Like Carbon (DLC)-coated and non-coated implants. The properties of DLC films, including hardness, wear resistance, chemical stability, and biocompatibility, are similar to those of real diamond materials. In this study, a 1-μm thick DLC film served to protect and lubricate a layer of commercially-pure titanium affixed to the top of a dental implant (external hexagon-shaped implant). A cyclic loading force was then applied to the top of the prosthetic portion of the implants in order to determine the difference in looseness of the titanium abutment screw between ten DLC-coated implants and ten non-coated implants. The abutment screw loosening tests were performed with 100 N of force at a frequency of 20 Hz. Data indicate that implants with a DLC coating are more resistant to an applied force (P = 0·002) than are those without the coating. We hope these results will be useful for preventing implant abutment screw loosening.
    Type of Medium: Electronic Resource
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