Neurochirurgische Universitatsklinik

Bonn, Germany

Neurochirurgische Universitatsklinik

Bonn, Germany
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Hopkins P.M.,St James's Hospital | Ruffert H.,University of Leipzig | Snoeck M.M.,Canisius Wilhelmina Ziekenhuis | Girard T.,University of Basel | And 19 more authors.
British Journal of Anaesthesia | Year: 2015

It is 30 yr since the British Journal of Anaesthesia published the first consensus protocol for the laboratory diagnosis of malignant hyperthermia susceptibility from the European Malignant Hyperthermia Group. This has subsequently been used in more than 10 000 individuals worldwide to inform use of anaesthetic drugs in these patients with increased risk of developing malignant hyperthermia during general anaesthesia, representing an early and successful example of stratified medicine. In 2001, our group also published a guideline for the use of DNA-based screening of malignant hyperthermia susceptibility. We now present an updated and complete guideline for the diagnostic pathway for patients potentially at increased risk of developing malignant hyperthermia. We introduce the new guideline with a narrative commentary that describes its development, the changes to previously published protocols and guidelines, and new sections, including recommendations for patient referral criteria and clinical interpretation of laboratory findings. © 2015 The Author 2015.

Sanson M.,University Pierre and Marie Curie | Hosking F.J.,Institute of Cancer Research | Shete S.,University of Texas M. D. Anderson Cancer Center | Zelenika D.,French Atomic Energy Commission | And 42 more authors.
Human Molecular Genetics | Year: 2011

While gliomas are the most common primary brain tumors, their etiology is largely unknown. To identify novel risk loci for glioma, we conducted genome-wide association (GWA) analysis of two case-control series from France and Germany (2269 cases and 2500 controls). Pooling these data with previously reported UK and US GWA studies provided data on 4147 glioma cases and 7435 controls genotyped for 424 460 common tagging single-nucleotide polymorphisms. Using these data, we demonstrate two statistically inde- pendent associations between glioma and rs11979158 and rs2252586, at 7p11.2 which encompasses the EGFR gene (population-corrected statistics, Pc = 7.72 × 10-8 and 2.09 × 10-8, respectively). Both associ- ations were independent of tumor subtype, and were independent of EGFR amplification, p16INK4a deletion and IDH1 mutation status in tumors; compatible with driver effects of the variants on glioma development. These findings show that variation in 7p11.2 is a determinant of inherited glioma risk. © The Author 2011. Published by Oxford University Press. All rights reserved.

Enciso-Mora V.,Institute of Cancer Research | Hosking F.J.,Institute of Cancer Research | Di Stefano A.L.,University Pierre and Marie Curie | Zelenika D.,French Atomic Energy Commission | And 32 more authors.
British Journal of Cancer | Year: 2013

Background:Most of the heritable risk of glioma is presently unaccounted for by mutations in known genes. In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developing glioma.Methods:To comprehensively evaluate the impact of variation in TP53 on risk, we analysed 23 tagSNPs and imputed 2377 unobserved genotypes in four series totaling 4147 glioma cases and 7435 controls.Results:The strongest validated association signal was shown by the imputed single-nucleotide polymorphism (SNP) rs78378222 (P=6.86 × 10-24, minor allele frequency ∼0.013). Confirmatory genotyping confirmed the high quality of the imputation. The association between rs78378222 and risk was seen for both glioblastoma multiforme (GBM) and non-GBM tumours. We comprehensively examined the relationship between rs78378222 and overall survival in two of the case series totaling 1699 individuals. Despite employing statistical tests sensitive to the detection of differences in early survival, no association was shown.Conclusion:Our data provided strong validation of rs78378222 as a risk factor for glioma but do not support the tenet that the polymorphism being a clinically useful prognostic marker. Acquired TP53 inactivation is a common feature of glioma. As rs78378222 changes the polyadenylation signal of TP53 leading to impaired 3′-end processing of TP53 mRNA, the SNP has strong plausibility for being directly functional contributing to the aetiological basis of glioma. © 2013 Cancer Research UK. All rights reserved.

Spinal cord stimulation is nowadays an established therapy for various neuropathic and vasculopathic pain syndromes after more conservative measures have failed. However, 40 years ago, only 5 years after the first worldwide implantation in the US, this therapy was promoted in Germany. In 1972, the first devices were implanted in the Departments of Neurosurgery at the Universities Hannover and Freiburg. These pioneering efforts and the establishment of the therapy are intimately associated with three names: Jörg-Ulrich Krainick, Uwe Thoden, and Wolfhard Winkelmüller. Nowadays about 1700 spinal cord stimulation systems are implanted annually in Germany. The development of spinal cord stimulation from the beginnings up to now taking into special consideration the early years in Germany are presented. © Deutsche Schmerzgesellschaft e.V. Published by Springer-Verlag Berlin Heidelberg - all rights reserved 2013.

Gousias K.,University of Bonn | Gousias K.,Neurochirurgische Universitatsklinik | Schramm J.,University of Bonn | Simon M.,University of Bonn
Acta Neurochirurgica | Year: 2014

Background: Any correlation between the extent of resection and the prognosis of patients with supratentorial infiltrative low-grade gliomas may well be related to biased treatment allocation. Patients with an intrinsically better prognosis may undergo more aggressive resections, and better survival may then be falsely attributed to the surgery rather than the biology of the disease. The present study investigates the potential impact of this type of treatment bias on survival in a series of patients with low-grade gliomas treated at the authors' institution. Methods: We conducted a retrospective study of 148 patients with low-grade gliomas undergoing primary treatment at our institution from 1996-2011. Potential prognostic factors were studied in order to identify treatment bias and to adjust survival analyses accordingly. Results: Eloquence of tumor location proved the most powerful predictor of the extent of resection, i.e., the principal source of treatment bias. Univariate as well as multivariate Cox regression analyses identified the extent of resection and the presence of a preoperative neurodeficit as the most important predictors of overall survival, tumor recurrence and malignant progression. After stratification for eloquence of tumor location in order to correct for treatment bias, Kaplan-Meier estimates showed a consistent association between the degree of resection and improved survival. Conclusion: Treatment bias was not responsible for the correlation between extent of resection and survival observed in the present series. Our data seem to provide further support for a strategy of maximum safe resections for low-grade gliomas. © 2013 Springer-Verlag Wien.

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