Author
Ulrich Bogdahn
Other affiliations: Hoffmann-La Roche, Volkswagen Foundation, University of Bern ...read more
Bio: Ulrich Bogdahn is an academic researcher from University of Regensburg. The author has contributed to research in topics: Neural stem cell & Neurogenesis. The author has an hindex of 67, co-authored 344 publications receiving 32279 citations. Previous affiliations of Ulrich Bogdahn include Hoffmann-La Roche & Volkswagen Foundation.
Topics: Neural stem cell, Neurogenesis, Glioma, Progenitor cell, Stroke
Papers published on a yearly basis
Papers
More filters
••
TL;DR: Together, the investigated combination is tolerable and feasible and neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data.
Abstract: Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for. In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx™, PEG-Dox) and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m2 daily during radiotherapy (60 Gy) and 150-200 mg/m2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression. The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12) was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison. Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data clinicaltrials.gov NCT00944801.
86 citations
••
TL;DR: It is suggested that mutant huntingtin alters the hippocampal microenvironment thus resulting in an impaired neurogenesis, and this adverse microenvironment impeded neuro genesis upregulation such as induced by physical exercise.
83 citations
••
TL;DR: Data show that in patients with severe neurological manifestations of late Lyme disease, not only Bb‐specific T‐cell lines but also T cells reactive to central or peripheral nervous system autoantigens can be found.
Abstract: In 3 patients with Lyme radiculomyelitis, cellular immune reactions of cerebrospinal fluid (CSF) lymphocytes were analyzed. Phenotypic analysis of CSF cells demonstrated that the majority were T cells (CD3+) of the helper/inducer subset (CD4+). These T cells were directly expanded from the CSF by limiting dilution. A total of 505 T-cell lines were tested for Borrelia burgdorferi (Bb)-specific proliferation and also partly tested for reactivity to a panel of central and peripheral nervous system antigens. Proliferative assays revealed 33 of them to be Bb specific, 16 to be specific for myelin basic protein, 16 to be specific for peripheral myelin, 1 to be specific for cardiolipin, and 2 to be specific for galactocerebrosides. The antigen-specific proliferation was restricted by autologous human leukocyte antigen (HLA) class II molecules. The majority of CSF-derived T-cell lines stained positively for CD3, CD4, and HLA class II antigens and negatively for CD8 (cytotoxic/suppressor subset). One T-cell line provided help for the production of specific IgG by autologous B cells and secreted gamma-interferon upon stimulation with Bb antigen in the presence of autologous antigen-presenting cells. These data show that in patients with severe neurological manifestations of late Lyme disease, not only Bb-specific T-cell lines but also T cells reactive to central or peripheral nervous system autoantigens can be found.
81 citations
••
TL;DR: Severe dysphagia requiring FGT is common in patients with stroke referred for neurorehabilitation and functional outcome measurements (FIM, FCM) including the cognitive function (attention, concentration etc.) could play an important role for prediction of swallowing regeneration and survival in neurore rehabilitation.
Abstract: Dysphagia is estimated to
occur in up to 50% of the stroke
neurorehabilitation population.
Those patients with severe neurogenic
oropharyngeal dysphagia
(NOD) may receive feeding
gastrostomy tubes (FGT) if noninvasive
therapies prove ineffective
in eliminating aspiration or sustaining
adequate nutritional intake.
Our aim was to quantify the recovery
of swallowing function, and to
identify variables predictive of
survival after dysphagic stroke
requiring FGT placement. We identified consecutive stroke
patients with severe dysphagic
stroke requiring FGT placement admitted
to a rehabilitation hospital
between May 1998 and October
2001. The medical records were reviewed,
and demographic, clinical,
videofluoroscopic (VSS) and neuroimaging
information were
abstracted. A follow–up telephone
interview was performed to determine
whether the FGT was still in
use, had been removed,or if the patient
had died. State death certificate
records were reviewed to ascertain
date of death for subjects who
had expired by the time of follow–up.
Univariate and multivariate
analyses were performed. 11.6 % (77/664) of stroke patients
admitted during the study period
had severe dysphagic stroke with
FGT insertion. Follow–up was
available for 66 (85.7 %) of these
individuals at a mean of two years
after acute stroke. On follow–up
64% (42/66) of the patients were
alive and 45 % had had the FGT
removed and resumed oral diets.
On univariate analysis patients who
were alive at the time of follow–up
had received FGT feeding for a
shorter period of time (p < 0.0003),
showed no signs of aspiration on
the Clinical Assessment of Feeding
& Swallowing (CAFS,p < 0.020) and
on the Videofluoroscopic Swallowing
Study (VSS, 0.001), had a better
discharge FIM–Score (Functional
Independence Measure) for eating
(p < 0.0002) and cognitive function
(p < 0.002) as well as better discharge
FCM–Score (Functional
Communication Measure) for
swallowing (p < 0.0001). On multivariate
analysis we developed a
model consisting of FGT removal at
discharge from the rehabilitation
hospital (p < 0.011) and non–aspiration
during VSS (p < 0.040) that
was significantly associated with
longer survival time during follow–up. Severe dysphagia
requiring FGT is common in patients
with stroke referred for neurorehabilitation.
Patients who had a
FGT in place at the time of discharge
from the stroke rehabilitation
unit or aspirated during VSS
were substantially more likely to
have died by the time of follow–up
compared to those who had had the
FGT removed and had no signs of
aspiration on VSS. However functional
outcome measurements
(FIM, FCM) including the cognitive
function (attention, concentration
etc.) could play an important role
for prediction of swallowing regeneration
and survival in neurorehabilitation.
These findings may have
practical utility in guiding physicians
and speech language pathologists
when advising patients and
families about prognosis in stroke
survivors with severe dysphagia.
79 citations
••
TL;DR: It is concluded that cerebellar lesions affect remote cortical regions that are part of a putative cortico-cerebellar network.
79 citations
Cited by
More filters
••
9,362 citations
••
TL;DR: These guidelines supersede the prior 2007 guidelines and 2009 updates and support the overarching concept of stroke systems of care and detail aspects of stroke care from patient recognition; emergency medical services activation, transport, and triage; through the initial hours in the emergency department and stroke unit.
Abstract: Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...
7,214 citations
••
01 Jan 2018
TL;DR: The 3rd edition of the International Classification of Headache Disorders (ICHD-3) may be reproduced freely for scientific, educational or clinical uses by institutions, societies or individuals if the Society’s permission is granted.
Abstract: The 3rd edition of the International Classification of Headache Disorders (ICHD-3) may be reproduced freely for scientific, educational or clinical uses by institutions, societies or individuals. Otherwise, copyright belongs exclusively to the International Headache Society. Reproduction of any part or parts in any manner for commercial uses requires the Society’s permission, which will be granted on payment of a fee. Please contact the publisher at the address below. International Headache Society 2013–2018. Applications for copyright permissions should be submitted to Sage Publications Ltd, 1 Oliver’s Yard, 55 City Road, London EC1Y 1SP, United Kingdom (tel: þ44 (0) 207 324 8500; fax: þ44 (0) 207 324 8600; permissions@sagepub.co.uk) (www.uk.sagepub.com). Translations
6,269 citations
••
University Hospital of Lausanne1, University of Toronto2, Erasmus University Rotterdam3, University Medical Center Utrecht4, Queen's University5, European Organisation for Research and Treatment of Cancer6, University of Western Ontario7, Medical University of Vienna8, French Institute of Health and Medical Research9, National Institutes of Health10, University of Tübingen11, University of Calgary12
TL;DR: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up, and a benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years.
Abstract: BACKGROUND: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. METHODS: Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. FINDINGS: Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. INTERPRETATION: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. FUNDING: EORTC, NCIC, Nelia and Amadeo Barletta Foundation, Schering-Plough.
6,161 citations
••
TL;DR: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylation of theMGMT promoter did notHave such a benefit and were assigned to only radiotherapy.
Abstract: background Epigenetic silencing of the MGMT (O 6 -methylguanine–DNA methyltransferase) DNArepair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. methods We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. results The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P<0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups. conclusions Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.
6,018 citations