Universitatskliniken Bonn

Bonn, Germany

Universitatskliniken Bonn

Bonn, Germany

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Wirz S.,Abteilung fur Anasthesie | Nadstawek J.,Universitatskliniken Bonn | Kuhn K.U.,Universitatsklinikum des Saarlandes | Vater S.,Universitatskliniken Bonn | And 2 more authors.
Schmerz | Year: 2010

Aim: The authors conducted an open-label investigation examining the effects of modafinil in reducing fatigue in patients with cancer, undergoing cancer treatment, and receiving opioid therapy. Methods: After approval by the local Ethics Committee and informed consent cancer patients who reported fatigue - defined as persistent tiredness interfering with usual functioning - were enrolled in the study. Once daily, patients received 100 mg open-label modafinil. The Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and a visual analogue scale (VAS, 0-10) were performed at baseline (t1), day 7 (t2), and day 28 (t3). Further assessment comprised the d2 Test of Attention (d2), the Hamilton Depression Scale (HAMD), the Eastern Cooperative Oncology Group-Score (ECOG), side effects, and patients' satisfaction with modafinil treatment. Results: Of the 37 patients who were enrolled, 29 completed all assessments in the study. Modafinil had a significant effect on the FSS (t1 44.612.2, t2 3912.4, t3 35.313.8 (p=0.015), on the VAS (t1 63.1), t2 4.52.8, t3 3.72.8 (p=0.005), and an insignificant effect on d2 parameters of neurophysiological functioning and ESS. No differences were seen for ECOG and patients' satisfaction. No severe adverse effects were detected. Conclusion: Modafinil improved alertness and cognitive skills in patients receiving cancer pain treatment by enhancing vigilance and cognitive performance. Although confirmation of this preliminary result is needed, these findings suggest that modafinil may improve quality of life in this patient population. However, in Germany the use of modafinil for fatigue is off-label and careful assessment of fatigue is needed prior to treatment. Randomized controlled trials are needed to confirm this evidence. © 2010 Springer-Verlag.


Dobbins S.E.,Institute of Cancer Research | Broderick P.,Institute of Cancer Research | Melin B.,Umeå University | Feychting M.,Karolinska Institutet | And 25 more authors.
Nature Genetics | Year: 2011

To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P combined = 1.88 ×10-14). This finding advances our understanding of the genetic basis of meningioma development. © 2011 Nature America, Inc. All rights reserved.


Simon M.,Universitatskliniken Bonn | Hosking F.J.,Institute of Cancer Research | Marie Y.,University Pierre and Marie Curie | Gousias K.,Universitatskliniken Bonn | And 17 more authors.
Clinical Cancer Research | Year: 2010

Purpose: Genome-wide association studies have recently identified single-nucleotide polymorphisms (SNP) in five loci at 5p15.33 (rs2736100, TERT), 8q24.21 (rs4295627, CCDC26), 9p21.3 (rs4977756, CDKN2A/CDKN2B), 20q13.33 (rs6010620, RTEL1), and 11q23.3 (rs498872, PHLDB1) to be associated with glioma risk. Because gliomas are heterogeneous in histology, molecular alterations, and clinical behavior, we have investigated these polymorphisms for potential correlations with tumor histology and patient survival. Experimental Design: We studied the relationship between SNPs and glioma subtype in two large patient cohorts from France and Germany, totaling 1,577 patients, as well as the relationship between SNP genotype and overall survival. Results: In both cohorts, the frequencies of rs2736100 and rs6010620 risk genotypes were highly correlated with high-grade disease (P < 0.001), whereas rs4295627 and rs498872 risk genotypes were inversely related to tumor grade (P < 0.001). These data show that genetic variations at these loci have subtype-specific effects on the risk of developing glioma. In contrast, the rs4977756 genotype was not correlated with tumor grade, consistent with the causal variant having a generic influence on glioma development. None of the five SNPs was associated with prognosis independent of tumor grade. Conclusions: Our findings provide novel insight into etiologic pathways in the different glioma subtypes. ©2010 AACR.


Kandenwein J.A.,Universitatskliniken Bonn | Park-Simon T.-W.,Klinik fur Frauenheilkunde und Geburtshilfe | Schramm J.,Universitatskliniken Bonn | Simon M.,Universitatskliniken Bonn
Journal of Neuro-Oncology | Year: 2011

The extent of resection and the intrinsic biological aggressiveness of the tumor have been repeatedly identified as the primary determinants of meningioma recurrence. Invasive growth limits the resectability of meningiomas. Tumor invasion is mediated by matrix metalloproteases and their inhibitors such as uPA and PAI-1. In some cancers uPA expression is controlled in part by promoter methylation. In the work reported in this paper we investigated the role of uPA/PAI-1 expression and methylation of the uPA promoter in meningiomas. Sixty-five tumor tissue samples (WHO grade I: 26, grade II: 27, grade III: 12) from 58 patients were analyzed for uPA and PAI-1 protein content using a commercially available ELISA kit. For uPA promoter methylation analysis, a 365-bp promoter fragment was amplified by PCR after bisulfite treatment and subjected to a methylation-sensitive restriction digest with AciI. Pertinent clinical data were retrieved from the patients' charts. uPA and PAI-1 protein expression correlated significantly with WHO grade (uPA: P < 0.033, PAI-1: P < 0.001). High (>6 ng/ml = median) PAI-1 levels were seen more frequently in tumors with brain invasion (P = 0.006) and proved a significant predictor of the patients' prognosis (Kaplan-Meier estimates of progression-free survival: P = 0.004). Increased methylation of the uPA promoter was found to correlate significantly with lower levels of uPA expression. Our data suggest PAI-1 (and possibly to a lesser degree uPA) as potential prognostic markers in meningiomas. uPA expression in meningiomas might, in part, be controlled by promoter methylation. © 2010 Springer Science+Business Media, LLC.


Kurzwelly D.,Universitatskliniken Bonn | Herrlinger U.,Universitatskliniken Bonn | Simon M.,Universitatskliniken Bonn
Advances and technical standards in neurosurgery | Year: 2010

Seizures complicate the clinical course of > 80% of patients with low-grade gliomas. Patients with some tumor variants almost always have epilepsy. Diffuse low-grade gliomas (LGG) are believed to cause epilepsy through partial deafferentiation of nearby brain cortex (denervation hypersensitivity). Glioneural tumors may interfere with local neurotransmitter levels and are sometimes associated with structural abnormalities of the brain which may produce seizures. The severity of tumor associated epilepsy varies considerably between patients. Some cases may present with a first seizure. Others suffer from long-standing pharmacoresistant epilepsy. Seizure control rates of > 70-80% can be expected after complete tumor resections. Patients with drug-resistant epilepsy require a comprehensive preoperative epileptological work-up which may include the placement of subdural (and intraparenchymal) electrodes or intraoperative electrocorticography (ECoG) for the delineation of extratumoral seizure foci. Partial and subtotal tumor resections are helpful in selected cases, i.e. for gliomas involving the insula. In one series, 40% of patients presented for surgery with uncontrolled seizures, i.e. medical therapy alone often fails to control tumor-related epilepsy. Use of the newer (second generation) non-enzyme inducing antiepileptic drugs (non-EIAED) is encouraged since they seem to have lesser interactions with other medications (e.g. chemotherapy). Chemotherapy and irradiation may have some minor beneficial effects on the patients' seizure disorder. Overall 60-70% of patients may experience recurrent epilepsy during long-term follow-up. Recurrent seizures (not infrequently heralding tumor recurrence) after surgery continue to pose significant clinical problems.


Gebel J.,Universitatskliniken Bonn | Jacobshagen A.,Universitatskliniken Bonn | Koch S.,Universitatskliniken Bonn | Exner M.,Universitatskliniken Bonn
Hygiene + Medizin | Year: 2015

Background: For the manual pre-cleaning of endoscopes, enzymatic cleaners as well as disinfectant cleaners may be used. However, it has been reported that products containing peracetic acid have protein-fixation - properties. The objective of this study was to verify these observations. Materials and Method: Instead of endoscopes we used process challenge devices. Test 1 consisted of manual pre-cleaning, test 2 consisted of manual pre-cleaning and an additional cleaning process in an automated washer-disinfector. The following products were tested in the manual pre-cleaning: product A, a disinfectant cleaner based on peracetic acid, and product B, an enzymatic cleaning agent. Glutaraldehyde with known protein-fixation properties was used a reference substance. The tests were performed corresponding to the Guideline for the Validation of Automated Cleaning and Disinfection Procedures for Reprocessing Thermolabile Endoscopes (version 22 August 2011) compiled by DGSV, AKI, DEGEA, DGVS and AK EDG as well as to DIN EN ISO 15883-5:2005, Annex I - Test soils and methods for demonstrating cleaning efficacy. Results: Protein determination after using the enzymatic cleaner or the disinfectant cleaner based on peracetic acid showed that after manual pre-cleaning as well as after manual and subsequent automated reprocessing in a washer-disinfector the protein load on the challenge devices was reduced up to the detection limit and no protein residues were demonstrated with Amido Black. After manual pre-cleaning of the challenge devices with glutaraldehyde, fixation of the test soil was clearly detectable. Conclusions: Based on our test results we found that neither the disinfectant cleaner based on peracetic acid nor the enzymatic cleaner showed protein-fixation properties.


Kandenwein J.A.,Universitatskliniken Bonn | Bostroem A.,Universitatskliniken Bonn | Feuss M.,Universitatskliniken Bonn | Pietsch T.,Universitatskliniken Bonn | Simon M.,Universitatskliniken Bonn
Acta Neurochirurgica | Year: 2011

Background: Intracranial subependymomas are rare, slow-growing and usually non-invasive tumors. The aim of this study was to analyze our experience with the surgical treatment of intracranial subependymomas. Methods: Between 1991 and 2007, 11 patients with intracranial subependymomas had surgery in our institution. Mean age of the patients was 54.4 years (ranging from 40 to 85 years). Results: Tumors were located in the fourth ventricle in seven patients and in the lateral ventricle in four patients. Most patients presented with symptoms related to intracranial hypertension and/or cerebellar signs and symptoms (headache: eight patients; dizziness: six patients; nausea: six patients; gait ataxia: four patients), one patient with cognitive decline and flattened affect, and one patient with a hemiparesis. Six patients presented with hydrocephalus, but only one needed a permanent cerebrospinal fluid (CSF) shunt. Complete removal of the tumor was possible in eight cases. Following surgery, only one patient experienced a permanent drop of his Karnofsky Performance Index (from 70 to 60). Median follow-up was 37 months. There were no true recurrences during follow-up. A second surgery was required 7 years after the first operation for progression of an incompletely resected tumor. Conclusions: Removal of symptomatic subependymomas can be performed safely. Prognosis is excellent after a complete resection. The potential for a surgical cure, low surgical complication rates and the risk of undertreatment of a more aggressive tumor together may justify surgery for asymptomatic lesions © 2011 Springer-Verlag.


Fischer N.,Universitatskliniken Bonn | Fisang C.,Universitatskliniken Bonn | Hirner A.,Universitatskliniken Bonn | Muller S.C.,Universitatskliniken Bonn
Chirurg | Year: 2011

Intrathoracic kidneys are rare and are often only diagnosed incidentally. The literature on intrathoracic kidneys in children and adults is reviewed and discussed, focusing on diagnostic procedures and surgical therapy. Additionally, the case of a 35-year-old woman with a relapse of a left-sided intrathoracic kidney after pregnancy is reported. Diagnostic procedures and the surgical management are discussed. © 2010 Springer-Verlag.


PubMed | Universitatskliniken Bonn
Type: Journal Article | Journal: Journal of neuro-oncology | Year: 2011

The extent of resection and the intrinsic biological aggressiveness of the tumor have been repeatedly identified as the primary determinants of meningioma recurrence. Invasive growth limits the resectability of meningiomas. Tumor invasion is mediated by matrix metalloproteases and their inhibitors such as uPA and PAI-1. In some cancers uPA expression is controlled in part by promoter methylation. In the work reported in this paper we investigated the role of uPA/PAI-1 expression and methylation of the uPA promoter in meningiomas. Sixty-five tumor tissue samples (WHO grade I: 26, grade II: 27, grade III: 12) from 58 patients were analyzed for uPA and PAI-1 protein content using a commercially available ELISA kit. For uPA promoter methylation analysis, a 365-bp promoter fragment was amplified by PCR after bisulfite treatment and subjected to a methylation-sensitive restriction digest with AciI. Pertinent clinical data were retrieved from the patients charts. uPA and PAI-1 protein expression correlated significantly with WHO grade (uPA: P < 0.033, PAI-1: P < 0.001). High (>6 ng/ml = median) PAI-1 levels were seen more frequently in tumors with brain invasion (P = 0.006) and proved a significant predictor of the patients prognosis (Kaplan-Meier estimates of progression-free survival: P = 0.004). Increased methylation of the uPA promoter was found to correlate significantly with lower levels of uPA expression. Our data suggest PAI-1 (and possibly to a lesser degree uPA) as potential prognostic markers in meningiomas. uPA expression in meningiomas might, in part, be controlled by promoter methylation.


PubMed | Universitatskliniken Bonn
Type: Case Reports | Journal: Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen | Year: 2011

Intrathoracic kidneys are rare and are often only diagnosed incidentally. The literature on intrathoracic kidneys in children and adults is reviewed and discussed, focusing on diagnostic procedures and surgical therapy. Additionally, the case of a 35-year-old woman with a relapse of a left-sided intrathoracic kidney after pregnancy is reported. Diagnostic procedures and the surgical management are discussed.

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