84 results on '"Andreas Gschwendtner"'
Search Results
2. Diagnostik interstitieller Lungenerkrankungen – Handlungsempfehlung mit Fokus auf rheumatologische Systemerkrankungen
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Frank Reichenberger, Claudia Dechant, Sebastian Ley, Andreas Gschwendtner, Josef Benedikter, Susanna Späthling-Mestekemper, Nikolaus Kneidinger, Frank Powitz, Klaus Krüger, Matthias Wahle, and Martin Schwaiblmair
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General Medicine - Published
- 2022
3. Monitoring glacier fade out in Austrian Eastern Alps
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Andrea Fischer, Martin Stocker-Waldhuber, Lea Hartl, Kay Helfricht, Andreas Gschwendtner, Bernd Seiser, and Giulia Bertolotti
- Abstract
In the Austrian Alps, recent rapid glacier melt affected the glaciers up to the summits. Glacier disintegration, debris flows, rock falls and increased melt rates are challenging glacier monitoring. Apart from the technical and safety issues arising, the scientific question arises how long a glacier fade out can and should be observed. From a technical perspective, direct mass balance monitoring is hampered by destruction of stakes by rock fall and snow pressure mounted on the increasingly steep glacier surfaces. Glacier changes require a frequent repositioning of stakes. Deep parts of the glaciers where stakes were not mounted in the past because the area was heavily crevassed remain longer that the thinner parts where stakes were operated in past decades, for example on Jamtalferner/Silvretta. Area loss meanwhile has a significant impact on glacier wide specific mass balance, but an annual resurvey of glacier area by terrestrial photogrammetry, airborne LiDAR or UAV rises the monitoring costs and effort considerably, while the uncertainty of mapping glacier area from remote sensing images is hampered by resolution and/or debris cover. Subglacial melt in large cavities which developed during the last years so far is not quantified, but estimated from thickness loss data suggest that the contribution of basal mass loss to total mass loss can be as large as surface mass balance. Common definitions of a glacier imply ice formation from snow and firn, ice dynamics and a runoff system. For several Austrian glaciers, snow and firn cover is entirely gone. There, no new ice can form during the next decades even in case accumulation of snow would take place in future. In addition to that, flow velocities drop to From a hydrological perspective, monitoring of those glacier remnants still makes sense, as they are still part of the local hydrological system. From the perspective of hazard monitoring, glacier remnants are also worth monitoring as they are relevant for generation of debris flows and englacial/thermokarst lakes. To continue local glacier monitoring and contribute to a global database, a joint global monitoring strategy and methodology would be beneficial. For example, a definition of ‘transient glaciers’ in fade out with a specification of monitoring methods would be helpful to prolongate mass balance time series when direct measurements become impossible for the total area. That could be single stakes, geodetic methods when glacier margins are still clear, or hydrological methods.
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- 2023
4. [Diagnostics of Interstitial Lung Diseases - Practical Instructions with a Focus on Rheumatologic Systemic Diseases]
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Frank, Reichenberger, Claudia, Dechant, Sebastian, Ley, Andreas, Gschwendtner, Josef, Benedikter, Susanna, Späthling-Mestekemper, Nikolaus, Kneidinger, Frank, Powitz, Klaus, Krüger, Matthias, Wahle, and Martin, Schwaiblmair
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Arthritis, Rheumatoid ,Rheumatic Diseases ,Collagen Diseases ,Humans ,Lung Diseases, Interstitial ,Tomography, X-Ray Computed ,Lung - Abstract
Interstitial lung diseases (ILD) are etiologically heterogeneous with unknown and known causes like rheumatologic systemic diseases differing in their therapeutic and prognostic consequences. In consensus between pulmonologists, rheumatologists, radiologists, and pathologists, we developed practical instructions for ILD diagnosis in rheumatologic systemic diseases, in particular because ILD can present in early stages of rheumatic systemic diseases. ILD diagnosis is based on clinical assessment results including a detailed medical history, physical examination, focused laboratory tests, radiology with a high-resolution computed tomography, lung function, and histopathology also to differentiate it from cardiac and infection associated lung diseases. The ILD diagnosis is made in a multidisciplinary discussion leading to therapeutic and prognostic consequences. The occurrence of acute exacerbations is especially critical. They are often the causes for ILD progression and are associated with considerable mortality.
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- 2022
5. Identification of a strategic brain network underlying processing speed deficits in vascular cognitive impairment.
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Marco Duering, Mariya Gonik, Rainer Malik, Nikola Zieren, Sonia Reyes, Eric Jouvent, Dominique Hervé, Andreas Gschwendtner, Christian Opherk, Hugues Chabriat, and Martin Dichgans
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- 2013
- Full Text
- View/download PDF
6. Measurement of brain atrophy in subcortical vascular disease: A comparison of different approaches and the impact of ischaemic lesions.
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Mike O'Sullivan, Eric Jouvent, Philipp G. Saemann, Jean-François Mangin, Anand Viswanathan, Andreas Gschwendtner, Luc Bracoud, Chahin Pachai, Hugues Chabriat, and Martin Dichgans
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- 2008
- Full Text
- View/download PDF
7. Pneumothorax with Bullous Lesions as a Late Complication of Covid-19 Pneumonia: A Report on Two Clinical Cases
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Martin Schiller, Ute Huebner, Wolfgang Kick, Andreas Gschwendtner, Andreas Wunsch, and Juergen Fisahn
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medicine.medical_specialty ,Thrombotic microangiopathy ,remdesivir ,030204 cardiovascular system & hematology ,Hypoxemia ,03 medical and health sciences ,0302 clinical medicine ,Blister ,Medicine ,pneumonia ,Humans ,030212 general & internal medicine ,Diffuse alveolar damage ,Adults Clinical Communications ,emphysematous bulla ,Lung ,business.industry ,SARS-CoV-2 ,COVID-19 ,Pneumothorax ,medicine.disease ,Surgery ,respiratory tract diseases ,COVID-19 Drug Treatment ,Pneumonia ,medicine.anatomical_structure ,Viral pneumonia ,Emergency Medicine ,medicine.symptom ,business ,Complication - Abstract
Background: Coronavirus-19 disease (COVID-19) is mainly affecting the respiratory tract, causing viral pneumonia with fever, hypoxemia, and cough. Commonly observed complications include acute respiratory failure, liver or kidney injury, and cardiovascular or neurologic symptoms. In some patients, inflammatory damage results in long term complications like pulmonary fibrosis, chronic pulmonary thrombotic microangiopathy, or neurologic symptoms. The developement of spontaneous pneumothorax is reported as a rare complication mainly in consequence to mechanic ventilation in the criticall ill. Case Report: We report on two cases of COVID-19 pneumonia complicated by a spontaneous pneumothorax and bullous lesions of the lung. Bilateral giant bullae were observed in one of the cases. This complication occurred after an initial resolvement of respiratory symptoms (day 16 and day 29 after COVID-19 treatment was started). Initially, both patients had shown a rather mild course of COVID-19 pneumonia and no mechanical ventilatory support had been necessary. Why Should an Emergency Physician Be Aware of This? In both cases, COVID-19 caused alveolar damage and formation of thoracic bullae with consequent spontaneous pneumothorax as a serious complication. Emergency physicans must be aware of this complication even if the initial COVID-19 symptoms have resolved.
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- 2021
8. E-cigarette-induced lung disease: from acute to chronic
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Florian Poschenrieder, Andreas Gschwendtner, Michael Rotter, and Okka W. Hamer
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Male ,Pathology ,medicine.medical_specialty ,business.industry ,Prednisolone ,Vaping ,MEDLINE ,Anti-Inflammatory Agents ,General Medicine ,Electronic Nicotine Delivery Systems ,Middle Aged ,Flavoring Agents ,Lung disease ,X ray computed ,Cryptogenic Organizing Pneumonia ,Medicine ,Humans ,business ,Tomography, X-Ray Computed - Published
- 2020
9. Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer
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Bülent Polat, Dagmar Burchert, Werner Hohenberger, Christoph Müller-Leisse, Michael Geißler, Andreas Rosenwald, Elisabeth Rösler, Wolfgang Bank, Kay C. Willborn, Gunther Klautke, Helmut Gnann, Oliver Kölbl, Thomas Brunner, Christian Stroszczynski, Heinrich Wiesinger, Gunnar Folprecht, Ute Küchenmeister, Kirsten Papsdorf, Hagen Flach, Bernd Rosin, Matthias Schwarzbach, Guido Hildebrandt, Ursula Pession, Sanja Schmeck, Richard Viehbahn, Timo Gaiser, Michael Henke, Christof Lamberti, Robert Grützmann, Detlef Imhoff, Michael J. Eble, Peter Bronsert, Wolf O. Bechstein, Thorsten Jacobi, Bernhard Leibl, Elisabeth Germer, Claus Rödel, Wolfgang Wendt, Martin-Leo Hansmann, Jens Freiberg-Richter, Henning Schäfer, Gerhard G. Grabenbauer, Wolff Schmiegel, Peter Kappl, Harold Ortloff, Andrea Tannapfel, Nicolas Moosmann, Christiane Lange, Philipp Manegold, Vittorio Paolucci, Olaf Dirsch, Klaus Kirchhof, Michael Allgäuer, Jan Braess, Markus Zachäus, Irenäus Adamietz, Rainer Fietkau, Michael Ghadimi, Guido Woeste, Hans Jürgen Schlitt, L. Jacobasch, Ulrike Attenberger, Simon Kirste, Ulrich Halm, Godehard Lahmer, Jochen Gaedcke, Andreas Gschwendtner, Michael Flentje, Christine Volkheimer, Andreas Erbesdolber, Philipp Bruners, Jörn Sträter, Stephan Falk, Manfred Dörne, Jörg Olaf Habeck, Ulrich Stölzel, Claus-Henning Köhne, Christoph-Thomas Germer, Lutz Renziehausen, Rolf-Peter Henke, Stefan Post, Ludger Staib, Popiliu Piso, Monika Warmuth-Metz, Volker Kunzmann, Christian Wittekind, Peter Wild, Thomas Kittner, Marga Lang-Welzenbach, Tom Lüdde, Martin Eichel, Dietrich Meißner, Joachim Boese-Land, Marcel Binnebösel, Frank Griesinger, Ruth Knüchel-Clarke, Ralf-Dieter Hofheinz, Eckhardt Schneider, Giovanna Römer, Ulrich Kania, Tim Friede, Klaus Holzweißig, Thorsten Bley, Felix Steger, Stefan Krämer, Anca-Ligia Grosu, Emmanouil Fokas, Michael Pohl, Ernst Klar, Heiko Sülberg, Nils Habbe, Petra Hödl, Andre Serebrennikov, Anke Schlenska-Lange, Thomas Kuhnt, Katica Krajinovic, Ullrich Graeven, Thomas Schmidt, Stephan Sahm, Gustavo Baretton, Ulrike Ubbelohde, Kirsten Merx, Ferdinand Hofstädter, Frederik Wenz, Christian Möllecken, and Hannes Philipp Neeff
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Male ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Population ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,education ,Neoadjuvant therapy ,Neoplasm Staging ,Original Investigation ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Rectal Neoplasms ,business.industry ,Hazard ratio ,Chemoradiotherapy ,Middle Aged ,medicine.disease ,Total mesorectal excision ,Chemotherapy regimen ,Neoadjuvant Therapy ,3. Good health ,Consolidation Chemotherapy ,Oncology ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,Neoplasm Recurrence, Local ,business - Abstract
Importance Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established. Objective To report the long-term results of the secondary end points prespecified in the Randomized Phase 2 Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy (CAO/ARO/AIO-12 trial) for Locally Advanced Rectal Cancer. Design, Setting, and Participants This secondary analysis of a randomized clinical trial included 311 patients who were recruited from the accrued CAO/ARO/AIO-12 trial population from June 15, 2015, to January 31, 2018, from 18 centers in Germany. Patients with cT3-4 and/or node-positive rectal adenocarcinoma were included in the analysis. Data were analyzed from June 15, 2015, to January 31, 2018. The follow-up analysis was conducted between January 31, 2018, and November 30, 2020. Interventions Patients were randomly assigned to group A for 3 cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy), or to group B for CRT before chemotherapy. Total mesorectal excision was scheduled on day 123 after the start of total neoadjuvant therapy in both groups. Main Outcomes and Measures The end points assessed in this secondary analysis included long-term oncologic outcomes, chronic toxicity, patient-reported outcome measures for global health status (GHS) and quality of life (QoL), and the Wexner stool incontinence score. Results Of the 311 patients enrolled, 306 were evaluable, including 156 in group A (mean [SD] age, 60 [11] years; 106 men [68%]) and 150 in group B (mean [SD] age, 62 [10] years; 100 men [67%]). After a median follow-up of 43 months (range, 35-60 months), the 3-year disease-free survival was 73% in both groups (hazard ratio, 0.95; 95% CI, 0.63-1.45,P = .82); the 3-year cumulative incidence of locoregional recurrence (6% vs 5%,P = .67) and distant metastases (18% vs 16%,P = .52) were not significantly different. Chronic toxicity grade 3 to 4 occurred in 10 of 85 patients (11.8%) in group A and 8 of 66 patients (9.9%) in group B at 3 years. The GHS/QoL score decreased after total mesorectal excision but returned to pretreatment levels 1 year after randomization with no difference between the groups. Stool incontinence deteriorated 1 year after randomization in both groups and only improved slightly at 3 years, but never reached baseline levels. Conclusions and Relevance This secondary analysis of a randomized clinical trial showed that CRT followed by chemotherapy resulted in higher pathological complete response without compromising disease-free survival, toxicity, QoL, or stool incontinence and is thus proposed as the preferred total neoadjuvant therapy sequence if organ preservation is a priority. Trial Registration ClinicalTrials.gov identifier:NCT02363374
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- 2022
10. Generalized Chronic Itch as a First Sign of Malignancy Resembling Paraneoplastic Sensomotoric Neuropathy
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Andreas Gschwendtner, Ulrich Baum, M. Häberle, Minaya Beigi, and Elke Weisshaar
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Male ,medicine.medical_specialty ,Biopsy ,Dermatology ,Malignancy ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Fatal Outcome ,0302 clinical medicine ,X ray computed ,Carcinoma ,medicine ,lcsh:Dermatology ,Humans ,Paraneoplastic Polyneuropathy ,Chronic itch ,Aged ,medicine.diagnostic_test ,business.industry ,Pruritus ,General Medicine ,lcsh:RL1-803 ,medicine.disease ,Immunohistochemistry ,Carcinoma, Neuroendocrine ,030220 oncology & carcinogenesis ,Chronic Disease ,Carcinoma, Large Cell ,Neoplasms, Unknown Primary ,Neuroendocrine therapy ,Tomography, X-Ray Computed ,business ,Sign (mathematics) - Published
- 2018
11. 17q25 Locus Is Associated With White Matter Hyperintensity Volume in Ischemic Stroke, But Not With Lacunar Stroke Status
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Muhammed Saleem Khan, Emilio Ciusani, Alessandro Biffi, Helen Segal, Poneh Adib-Samii, Karen L. Furie, Myriam Fornage, Kaitlin Fitzpatrick, Hugh S. Markus, Peter M. Rothwell, Braxton D. Mitchell, Eugenio Parati, Martin Dichgans, Valerie Valant, S. J. Kittner, Benison C. Lau, Natalia S. Rost, Dale M Gamble, William J. Devan, Alexa Richie, Rainer Malik, Steve Bevan, Cathie Sudlow, Yu-Ching Cheng, Allison Kanakis, Carlos Leiva-Salinas, Silvia Lanfranconi, Joshua C. Bis, Bradford B. Worrall, Pankaj Sharma, Will Longstreth, Joanna M. Wardlaw, Thomas H. Mosley, Kerri L. Wiggins, Andreas Gschwendtner, Christopher Levi, Jonathan Rosand, Guido J. Falcone, Jane Maguire, Bruce M. Psaty, Elizabeth G. Holliday, Matthew Traylor, James F. Meschia, and Giorgio B. Boncoraglio
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Lacunar stroke ,Genotype ,Locus (genetics) ,Genome-wide association study ,Nerve Fibers, Myelinated ,Polymorphism, Single Nucleotide ,Article ,Internal medicine ,Humans ,Medicine ,cardiovascular diseases ,Aged ,Aged, 80 and over ,Advanced and Specialized Nursing ,Neurology & Neurosurgery ,medicine.diagnostic_test ,business.industry ,Case-control study ,Leukoaraiosis ,Brain ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Hyperintensity ,Stroke ,Case-Control Studies ,Stroke, Lacunar ,Ischemic stroke ,Linear Models ,Cardiology ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Chromosomes, Human, Pair 17 ,Genome-Wide Association Study - Abstract
Background and Purpose— Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke. Methods— We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke. Results— Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 ( P =0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke. Conclusions— This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction.
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- 2013
12. Education modifies the relation of vascular pathology to cognitive function: cognitive reserve in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
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Christian Opherk, Hugues Chabriat, Yvonne Mewald, Sonia Reyes, Dominique Hervé, Eric Jouvent, Nikola Zieren, Martin Dichgans, Andreas Gschwendtner, Nils Peters, and Marco Duering
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Adult ,Male ,Aging ,medicine.medical_specialty ,physiopathology [CADASIL] ,CADASIL ,physiopathology [Brain] ,Neuropsychological Tests ,Leukoencephalopathy ,Executive Function ,Cognition ,Cognitive Reserve ,Neuroimaging ,pathology [Brain] ,Memory ,psychology [CADASIL] ,Internal medicine ,medicine ,pathology [CADASIL] ,Humans ,ddc:610 ,Prospective Studies ,Effects of sleep deprivation on cognitive performance ,Aged ,Cognitive reserve ,General Neuroscience ,Neuropsychology ,Brain ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Brain size ,Cardiology ,Educational Status ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,Psychology ,Neuroscience ,Developmental Biology - Abstract
A clinical impact of cognitive reserve (CR) has been demonstrated in Alzheimer's disease, whereas its role in vascular cognitive impairment (VCI) is largely unknown. In this study, we investigated the impact of CR in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of pure VCI. A total of 247 NOTCH3 mutation carriers from a two-center study were investigated using detailed neuropsychological and neuroimaging protocols. CR was operationalized as years of formal education. Brain pathology was assessed by MRI using normalized brain volume and lacunar lesion volume as proxies. Multivariate analyses were done for each structural measure with scores of processing speed, executive function, and memory as dependent variables. Additional linear regression models were conducted with interaction terms for education × brain volume and education × lacunar lesion volume. Education had an independent impact on cognitive performance in subjects with mild and moderate degrees of brain pathology, whereas there was no significant influence of education on cognition in patients with severe MRI changes. This interaction was found for processing speed, the cognitive domain most impaired in our patients. Our findings demonstrate an interaction of education and brain pathology in regard to cognitive impairment: the effect of education seems most pronounced in early disease stages but may ultimately be overwhelmed by the pathological changes. The results extend the concept of CR to VCI.
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- 2013
13. Mikroangiopathien und Leukodystrophien als Differenzialdiagnosen
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Martin Dichgans and Andreas Gschwendtner
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Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,business - Abstract
Fur klinisch tatige Neurologen stellt die differenzialdiagnostische Einordnung von leukenzephalopathischen MRT-Veranderungen ein haufiges Problem dar, oft handelt es sich auch um Zufallsbefunde. Abgesehen von der Bildgebung, die selten spezifisch, oft aber typisch fur eine bestimmte Erkrankung ist, mussen immer auch Alter, klinische Symptome, vaskulares Risikoprofil, Geschlecht und Familienanamnese des Patienten berucksichtigt werden.
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- 2012
14. Resection of rectal carcinoids with the newly introduced endoscopic full-thickness resection device
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Helmut Neumann, Andreas Gschwendtner, Martin Grauer, and Claus Schäfer
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medicine.medical_specialty ,business.industry ,Full thickness resection device ,Rectal Neoplasms ,Dissection ,Treatment outcome ,Gastroenterology ,MEDLINE ,Carcinoid Tumor ,Colonoscopy ,Equipment Design ,Middle Aged ,Resection ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Treatment Outcome ,030220 oncology & carcinogenesis ,Intestinal Neoplasms ,Medicine ,Humans ,030211 gastroenterology & hepatology ,Female ,business - Published
- 2016
15. Hippocampal volume is an independent predictor of cognitive performance in CADASIL
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Marco Duering, Eric Jouvent, Elmar Ngo, Michael Conlon O'Sullivan, Philipp G. Saemann, Martin Dichgans, Chahin Pachai, Andreas Gschwendtner, Marie-Germaine Bousser, Anand Viswanathan, and Hugues Chabriat
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Male ,Aging ,medicine.medical_specialty ,Pathology ,Statistics as Topic ,CADASIL ,Hippocampus ,Sensitivity and Specificity ,Article ,Central nervous system disease ,Cognition ,Imaging, Three-Dimensional ,Atrophy ,Degenerative disease ,Internal medicine ,medicine ,Humans ,Dementia ,Vascular dementia ,General Neuroscience ,Reproducibility of Results ,Organ Size ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Hyperintensity ,Cardiology ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,Cognition Disorders ,Psychology ,Developmental Biology - Abstract
Recent evidence suggests that hippocampal changes are present in vascular cognitive impairment but their importance and relationship with ischaemic mechanisms remain controversial. To investigate these issues we performed MRI and cognitive assessment in a large cohort (n = 144) of patients with CADASIL, a hereditary small vessel disease and model of pure vascular cognitive impairment. Dementia status was ascribed according to DSM-IV and global cognitive function assessed with the Minimental State Examination (MMSE) and Mattis Dementia Rating Scale (MDRS). Hippocampalvolume (HV) correlated with age (r = −0.33, p < 0.001), brain volume (r = 0.39, p < 0.001) and lacunar lesion volume (r = −0.23, p = 0.008), but not white matter lesions or microhaemorrhages. HV was reduced in dementia (2272 ± 333 mm3 versus 2642 ± 349 mm3, p < 0.001) in the whole cohort and the subgroup progressing to dementia before age 60. HV correlated with MMSE (r = 0.30, p < 0.001), MDRS (r = 0.40, p < 0.001) and in a multivariate model predicted cognition independent of typical vascular lesions and whole brain atrophy. These findings strengthen the view that hippocampal atrophy is an important pathway of cognitive impairment in vascular as well as degenerative disease.
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- 2009
16. Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke
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Karen L. Furie, Thomas Meitinger, Paul D. Syme, Stephen S. Rich, Agnieszka Slowik, Mary Joan MacLeod, James F. Meschia, Mar Matarin, Martin Dichgans, S. J. Kittner, Hugh S. Markus, Braxton D. Mitchell, Anna Plourde, Bertram Müller-Myhsok, Jonathan Rosand, Erich Wichmann, Steve Bevan, Helen Ross-Adams, Andreas Gschwendtner, and John W. Cole
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Male ,medicine.medical_specialty ,Pathology ,Genotype ,Genome-wide association study ,Locus (genetics) ,Coronary Artery Disease ,Biology ,Polymorphism, Single Nucleotide ,Risk Assessment ,Article ,Coronary artery disease ,Gene Frequency ,Risk Factors ,Internal medicine ,Ethnicity ,Odds Ratio ,medicine ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,Myocardial infarction ,Stroke ,Vascular disease ,Chromosome Mapping ,Odds ratio ,medicine.disease ,Europe ,Neurology ,North America ,Cardiology ,Female ,Neurology (clinical) ,Chromosomes, Human, Pair 9 ,Risk assessment - Abstract
Recent studies have identified a major locus for risk for coronary artery disease and myocardial infarction on chromosome 9p21.3. Stroke, in particular, ischemic stroke caused by atherosclerotic disease, shares common mechanisms with myocardial infarction. We investigated whether the 9p21 region contributes to ischemic stroke risk.In an initial screen, 15 single nucleotide polymorphisms (SNPs) covering the critical genetic interval on 9p21 were genotyped in samples from Southern Germany (1,090 cases, 1,244 control subjects) and the United Kingdom (758 cases, 872 control subjects, 3 SNPs). SNPs significantly associated with ischemic stroke or individual stroke subtypes in either of the screening samples were subsequently genotyped in 2,528 additional cases and 2,189 additional control subjects from Europe and North America.Genotyping of the screening samples demonstrated associations between seven SNPs and atherosclerotic stroke (all p0.05). Analysis of the full sample confirmed associations between six SNPs and atherosclerotic stroke in multivariate analyses controlling for demographic variables, coronary artery disease, myocardial infarction, and vascular risk factors (all p0.05). The odds ratios for the lead SNP (rs1537378-C) were similar in the various subsamples with a pooled odds ratio of 1.21 (95% confidence interval, 1.07-1.37) under both fixed- and random-effects models (p = 0.002). The point estimate for the population attributable risk is 20.1% for atherosclerotic stroke.The chromosome 9p21.3 region represents a major risk locus for atherosclerotic stroke. The effect of this locus on stroke appears to be independent of its relation to coronary artery disease and other stroke risk factors. Our findings support a broad role of the 9p21 region in arterial disease.
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- 2009
17. Regulation and function of neuronal GTP-Ras in facial motor nerve regeneration
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Tsvetan Serchov, Milan Makwana, Mariya Hristova, Marion Bohatschek, Genndij Raivich, Andreas Gschwendtner, ZhiQiang Liu, Rolf Heumann, and Roger Kalla
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medicine.medical_specialty ,Time Factors ,CD3 Complex ,Neurite ,Facial motor nucleus ,Calcitonin Gene-Related Peptide ,medicine.medical_treatment ,Motor nerve ,Galanin ,Mice, Transgenic ,Biology ,Biochemistry ,Neuroprotection ,Mice ,Cellular and Molecular Neuroscience ,GTP-Binding Proteins ,Neurotrophic factors ,Internal medicine ,medicine ,Animals ,Histidine ,Extracellular Signal-Regulated MAP Kinases ,Facial Nerve Injuries ,Neurons ,Analysis of Variance ,Axotomy ,Valine ,Recovery of Function ,Nerve Regeneration ,Enzyme Activation ,Mice, Inbred C57BL ,Disease Models, Animal ,Endocrinology ,Mutation ,ras Proteins ,biology.protein ,Sciatic nerve ,Proto-Oncogene Proteins c-akt ,Neuroscience ,Neurotrophin - Abstract
Activation of Ras into the GTP-binding, 'ON' state is a key switch in the neurotrophin-mediated neuronal survival and neurite outgrowth, in vitro as well as in vivo. In the current study we explored changes in GTP-Ras levels following facial nerve injury and the ensuing regeneration and the effects of perturbing these changes in vivo using synapsin-promoter mediated neuronal expression of constitutively active Val12H-Ras (synRas). Quantification of GTP-Ras and total Ras revealed a precipitous drop in the relative GTP-Ras levels in the axotomized facial motor nucleus, to 40% of normal levels at 2 days after cut, followed by a partial recovery to 50-65% at 4-28 days. On western blots, control and axotomized nuclei from synRas mutants showed a 2.2- and 2.5-fold elevation in GTP-Ras, respectively, compared with their wild type littermate controls (p < 5%, anova, TUKEY post-hoc), with the levels in the axotomized synRas nucleus slightly but not significantly above that in the uninjured littermate control (p = 9.9%). Similar increase was also observed in the pERK but not pAKT targets of the Ras cascade. This moderate elevation of GTP-Ras strongly curtailed post-traumatic neuronal cell death (-65%), the influx of T-cells (-48%) as well as other parameters of neuroinflammatory response. Although synRas did not affect the speed of axonal regeneration or functional recovery it caused a very pronounced increase in central axonal sprouting. These current data emphasize the role of reduced active Ras, and by extension, the reduced overall level of retrograde neurotrophin signalling after axotomy, in mediating post-traumatic cell death and inflammation and in restricting the sprouting response. Moreover, the neuroprotective and central sprouting-enhancing effects of neuronal Val12H-Ras could help promote recovery in CNS injury.
- Published
- 2009
18. Genetic Variation in Soluble Epoxide Hydrolase ( EPHX2 ) Is Associated With an Increased Risk of Ischemic Stroke in White Europeans
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Stephan Ripke, Bertram Müller-Myhsok, Peter Lichtner, Thomas Meitinger, Tobias Freilinger, H-Erich Wichmann, Martin Dichgans, and Andreas Gschwendtner
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Genetic Markers ,Male ,Pathology ,medicine.medical_specialty ,Genotype ,DNA Mutational Analysis ,Single-nucleotide polymorphism ,White People ,Brain Ischemia ,Brain ischemia ,Gene Frequency ,Risk Factors ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Risk factor ,Stroke ,Allele frequency ,Aged ,Genetic testing ,Epoxide Hydrolases ,Advanced and Specialized Nursing ,Polymorphism, Genetic ,medicine.diagnostic_test ,Cerebral infarction ,business.industry ,Haplotype ,Genetic Variation ,Middle Aged ,medicine.disease ,Europe ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background and Purpose— Genetic variation in the EPHX2 gene region has been reported to influence susceptibility to ischemic stroke in blacks. We assessed the role of this gene region in white Europeans and performed analyses with regard to stroke subtypes. Methods— Twenty-six single nucleotide polymorphisms in the EPHX2 gene region were genotyped in 601 patients with ischemic stroke and 736 matched controls. Cases were subtyped according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system. Analyses were done on single markers and haplotypes using a sliding-window approach. Results— Three single nucleotide polymorphisms showed associations with an increased risk for ischemic stroke (allelic models; all P ≤0.01). One of them retained statistical significance after correction for multiple testing. Associations were observed with large-vessel stroke and stroke of undetermined etiology but not with other stroke subtypes. Conclusions— Our findings confirm and extend previous studies suggesting that genetic variation in or near the EPHX2 gene contributes to the risk of ischemic stroke. This association seems to be mediated predominantly by large-vessel disease.
- Published
- 2008
19. Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL
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M. Dichgans, Rodica Cumurciuc, Hugues Chabriat, Chahin Pachai, Andreas Gschwendtner, Markus Holtmannspötter, Michael O'Sullivan, Jean-Pierre Guichard, Anand Viswanathan, F. Buffon, and Marie-Germaine Bousser
- Subjects
Adult ,Brain Infarction ,Male ,Aging ,Pathology ,medicine.medical_specialty ,CADASIL ,Comorbidity ,Neuropsychological Tests ,Nerve Fibers, Myelinated ,Cohort Studies ,Lesion ,Leukoencephalopathy ,Disability Evaluation ,Age Distribution ,Predictive Value of Tests ,Modified Rankin Scale ,medicine ,Humans ,Prospective Studies ,cardiovascular diseases ,Aged ,Cerebral Cortex ,medicine.diagnostic_test ,Cognitive disorder ,Magnetic resonance imaging ,Cerebral Arteries ,Middle Aged ,CADASIL Syndrome ,Prognosis ,medicine.disease ,Magnetic Resonance Imaging ,Hyperintensity ,Disease Progression ,Female ,Neurology (clinical) ,medicine.symptom ,Cognition Disorders ,Psychology - Abstract
Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy caused by mutations of the Notch3 gene. The disease is characterized by T2-hyperintense lesions (subcortical white matter lesions), T1-hypointense lesions (lacunar lesions), and T2*-weighted gradient-echo (GE) lesions (cerebral microhemorrhages [CMs]) visualized on clinical MRI sequences and is considered as a model of “pure” subcortical ischemic vascular dementia. Although numerous studies have investigated the impact of white matter lesions in patients with CADASIL, the clinical importance of lacunar lesions remains unknown. Our purpose was to examine the influence of the visible MRI markers in the disease, including the load of lacunar lesions on cognitive impairment and disability in CADASIL. Methods: We collected clinical data from 147 consecutive patients enrolled in an ongoing two-center prospective cohort study. Degree of disability was assessed by modified Rankin scale and Barthel index. Degree of cognitive impairment was assessed by Mattis Dementia Rating Scale and Mini-Mental Status Examination. T1-weighted, fluid-attenuated inversion recovery, and GE images were obtained on a 1.5-T MRI. Volume and location of lacunar lesions, white matter hyperintensities (WMHs), and CMs were assessed. Results: There was a significant independent association between age, volume of lacunar lesions, and global cognitive function scales when analyzed in a multivariable model. In contrast, WMHs and CMs had no independent influence on cognitive function. Disability in this cohort was associated with volume of lacunar lesions, CMs, systolic blood pressure, and age but not with WMHs. Conclusions: Among the lesions observed on conventional MRI in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the overall lacunar lesion burden seems to have the most important impact on cognitive function and disability. These findings suggest that preventive strategies to decrease the risk of lacunar lesions as observed on MRI may reduce disease-related impairment in CADASIL. These results suggest that lacunar lesions may also play a key role in disability and cognitive impairment in more common forms of small-vessel disease.
- Published
- 2007
20. Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study
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Hugues Chabriat, Markus Holtmannspötter, Carole Boutron, Anand Viswanathan, Rodica Cumurcuic, Andreas Gschwendtner, Chahin Pachai, F. Buffon, Eric Vicaut, Martin Dichgans, Jean-Pierre Guichard, and Marie-Germaine Bousser
- Subjects
Adult ,Brain Infarction ,Male ,medicine.medical_specialty ,Hemodynamics ,Infarction ,Blood Pressure ,CADASIL ,Basal Ganglia ,Cohort Studies ,Thalamus ,Risk Factors ,Internal medicine ,Image Processing, Computer-Assisted ,medicine ,Humans ,Aged ,Cerebral Hemorrhage ,Glycated Hemoglobin ,Haemoglobin A1c ,business.industry ,Brain ,Middle Aged ,CADASIL Syndrome ,medicine.disease ,Surgery ,Blood pressure ,Hypertension ,Female ,Neurology (clinical) ,business ,Magnetic Resonance Angiography ,Brain Stem ,Cohort study - Abstract
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary arteriopathy caused by mutations of the Notch3 gene. The risk factors for cerebral microhaemorrhages (CM), their relationship to other MRI lesions in the disease and their potential clinical impact have not been previously defined. Our purpose was to examine the frequency, number and location of microhaemorrhages in a multicentre cohort study, defining predisposing factors and associated radiographic markers in CADASIL patients. We collected clinical data from 147 consecutive patients enrolled in an ongoing prospective cohort study. Degree of neurological disability and cognitive impairment were assessed by standardized scales. T(1)-weighted, FLAIR and T2*-weighted gradient-echo (GE) MRI sequences were performed. Volume and location of lacunar infarcts and white matter hyperintensity (WMH) were assessed. Number and location of CM were recorded. CM were present in 35% patients, most commonly occurring in the thalamus, brainstem and basal ganglia. The location of CM qualitatively differed from areas of lacunar infarction and WMH. There was a significant association between the presence of CM and a history of hypertension (P = 0.005), systolic blood pressure (SBP) (P = 0.014), haemoglobin A1c (HbA1c) (P = 0.004) and the volume of lacunar infarcts (P = 0.010) and WMHs (P = 0.046). The number of CM was independently associated with SBP (P = 0.005), the diagnosis of hypertension (P = 0.0004), volume of WMH (P = 0.0005) and lacunar infarcts (P = 0.004). In contrast, no association was found between blood pressure or HbA1c and the load of WMH or lacunar infarcts. The presence of CM was independently associated with increased modified Rankin scores. CM are independently associated with blood pressure and HbA1c as well as with lacunar infarct and WMH volume in CADASIL. Both the vascular risk factors and regional distribution of CM appear distinct from those associated with other MRI markers, suggesting a distinct pathological process. These lesions have a potential clinical impact in CADASIL. These findings further suggest that modulation of blood pressure and glucose levels might influence the course of the disease.
- Published
- 2006
21. Quantitative nuclear texture features analysis confirms WHO classification 2004 for lung carcinomas
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Nina Angerstein, Silvana Geleff, Andreas Gschwendtner, and Katharina Schmid
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Carcinoid Tumor ,Adenocarcinoma ,Texture (music) ,Biology ,Neuroendocrine tumors ,World Health Organization ,Pathology and Forensic Medicine ,Rosaniline Dyes ,medicine ,Carcinoma ,Humans ,Feulgen stain ,Carcinoma, Small Cell ,Aged ,Cell Nucleus ,Lung ,Middle Aged ,medicine.disease ,Chromatin ,Carcinoma, Neuroendocrine ,medicine.anatomical_structure ,Classification rule ,Carcinoma, Squamous Cell ,Carcinoma, Large Cell ,Female ,Who classification - Abstract
The purpose of this study was to discriminate the main subsets of lung carcinomas of the WHO classification of 2004 by nuclear chromatin texture feature analysis. Our collective comprised 56 typical and 19 atypical carcinoids, 37 small-cell carcinomas, 15 large-cell neuroendocrine carcinomas, 42 adenocarcinomas, and 26 squamous cell carcinomas. After Feulgen staining, cell nuclei were automatically measured using a high-resolution image analyser (CytoSavant Oncometrics, Vancouver, BC, Canada). Texture features describing the granularity and the compactness of the nuclear chromatin were extracted for calculation of classification rules, which allowed the discrimination of different tumor groups. By applying the classification rule that described the granularity of the nuclear chromatin (defined by four different parameters) small-cell and non-small-cell lung carcinoma could correctly be discriminated in 93%. No significant discrimination was possible between the different subtypes of large-cell carcinomas, including large-cell neuroendocrine carcinoma. When using compactness of chromatin (defined by four texture parameters) as a means of discrimination, carcinoids and non-small-cell lung carcinomas were correctly distinguished in 92%. No significant discrimination between neuroendocrine tumors was achieved though. Our findings are in accordance with the new WHO classification of 2004: neuroendocrine tumors of the lung are now classified according only to their mitotic counts and presence of necrosis but not by their morphology; their discrimination by the means of nuclear image analysis is not sufficient and therefore not appropriate any longer.
- Published
- 2006
22. A gene therapy induced emphysema model and the protective role of stem cells
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Leonidas Sakkas, Sofia Lampaki, Anna Papamichail, Theodora Tsiouda, Aggeliki Rapti, Paul Zarogoulidis, Konstantinos Zarogoulidis, Kosmas Tsakiridis, Antonis Papaiwannou, Despoina Sahpatzidou, Georgia Pitsiou, Ioannis Kioumis, Andreas Gschwendtner, Wolfgang Hohenforst-Schmidt, Haidong Huang, John Organtzis, Konstantinos Porpodis, Kokkona Kouzi-Koliakos, and Lutz Freitag
- Subjects
Pathology ,medicine.medical_specialty ,Chronic bronchitis ,Histology ,Genetic enhancement ,Medizin ,Stem cells ,Mesenchymal Stem Cell Transplantation ,Transfection ,Pathology and Forensic Medicine ,chemistry.chemical_compound ,Gene therapy ,Genes, Reporter ,Parenchyma ,Animals ,Humans ,Regeneration ,Medicine ,Respiratory function ,Lung ,Cells, Cultured ,Emphysema ,Mice, Inbred BALB C ,business.industry ,Research ,Regeneration (biology) ,DEAE-Dextran ,Mesenchymal Stem Cells ,General Medicine ,DDMC ,Vascular endothelial growth factor ,Disease Models, Animal ,medicine.anatomical_structure ,Pulmonary Emphysema ,chemistry ,Stem cell ,business - Abstract
Background Chronic obstructive pulmonary disease presents with two different phenotypes: chronic bronchitis and emphysema with parenchymal destruction. Decreased expression of vascular endothelial growth factor and increased endothelial cell apoptosis are considered major factors for emphysema. Stem cells have the ability of vascular regeneration and function as a repair mechanism for the damaged endothelial cells. Currently, minimally invasive interventional procedures such as placement of valves, bio-foam or coils are performed in order to improve the disturbed mechanical function in emphysema patients. However, these procedures cannot restore functional lung tissue. Additionally stem cell instillation into the parenchyma has been used in clinical studies aiming to improve overall respiratory function and quality of life. Methods In our current experiment we induced emphysema with a DDMC non-viral vector in BALBC mice and simultaneously instilled stem cells testing the hyposthesis that they might have a protective role against the development of emphysema. The mice were divided into four groups: a) control, b) 50.000 cells, c) 75.000 and d) 100.000 cells. Results Lung pathological findings revealed that all treatment groups had less damage compared to the control group. Additionally, we observed that emphysema lesions were less around vessels in an area of 10 μm. Conclusions Our findings indicate that stem cell instillation can have a regenerative role if applied upon a tissue scaffold with vessel around. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_195
- Published
- 2014
23. Diffusion Magnetic Resonance Histograms as a Surrogate Marker and Predictor of Disease Progression in CADASIL
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Hartmut Brückmann, Andreas Gschwendtner, Nils Peters, Daniel Martin, Markus Holtmannspötter, M. Dichgans, Philipp G. Sämann, Christian Opherk, and Jürgen Herzog
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,CADASIL ,Sensitivity and Specificity ,Leukoencephalopathy ,Central nervous system disease ,Predictive Value of Tests ,Risk Factors ,medicine ,Humans ,Longitudinal Studies ,Prospective Studies ,Stroke ,Advanced and Specialized Nursing ,medicine.diagnostic_test ,business.industry ,Surrogate endpoint ,Magnetic resonance imaging ,CADASIL Syndrome ,Prognosis ,medicine.disease ,Cross-Sectional Studies ,Diffusion Magnetic Resonance Imaging ,nervous system ,Sample Size ,Multivariate Analysis ,Disease Progression ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine ,Follow-Up Studies ,Diffusion MRI - Abstract
Background and Purpose— Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations in the NOTCH3 gene. MRI is sensitive in detecting preclinical involvement and changes over time. However, little is known about correlations between MRI metrics and clinical measures on a longitudinal scale. In this study, we assessed the role of quantitative MRI (T2-lesion volume and diffusion tensor imaging [DTI]–derived metrics) in monitoring and predicting disease progression. Methods— Sixty-two CADASIL subjects were followed prospectively over a period of 26.3±1.2 months. Dual-echo scans, DTI scans, and clinical scales were obtained at baseline and at follow-up. T2-lesion volumes were determined quantitatively, and histograms of mean diffusivity (MD) were produced. Results— At follow-up, T2-lesion volumes and MD histogram metrics had changed significantly (all P P Conclusions— This study establishes correlations between changes of DTI histogram metrics and clinical measures over time. DTI histograms may be used as an adjunct outcome measure in future therapeutic trials. Moreover, DTI histogram metrics predict disease progression in CADASIL.
- Published
- 2005
24. Tolerability of N-chlorotaurine in chronic rhinosinusitis applied via yamik catheter
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Thaddaeus Gotwald, Astrid Mayr, Andreas Gschwendtner, Elisabeth Appenroth, Michaela Gstöttner, Cornelia Lass-Flörl, Hannes Fischer, Andreas Neher, Markus Nagl, Hanno Ulmer, and Vladimir Kozlov
- Subjects
Adult ,Male ,Insufflation ,medicine.medical_specialty ,Taurine ,medicine.drug_class ,Therapeutic irrigation ,Catheterization ,Anti-Infective Agents ,Antiseptic ,otorhinolaryngologic diseases ,medicine ,Humans ,Sinusitis ,Therapeutic Irrigation ,business.industry ,General Medicine ,Middle Aged ,Surgery ,Catheter ,Paranasal sinuses ,medicine.anatomical_structure ,Otorhinolaryngology ,Tolerability ,Spectrophotometry ,Anesthesia ,Chronic Disease ,Cuff ,Female ,Nasal administration ,business - Abstract
Objectives: A rational approach in the treatment of chronic rhinosinusitis (CRS) is the intranasal application of antiseptic agents, due to the pathogenetic role of bacteria and fungi. N-Chlorotaurine (NCT), a mild endogenous oxidant with broad-spectrum antimicrobial activity, has been tested for the first time in CRS. Methods: This one-arm phase IIa clinical study is the first step in the clinical development of this promising substance for local therapy of CRS. The nasal and paranasal cavities of 12 patients were rinsed with 10–20 ml of 1% aqueous NCT solution, applied via a novel catheter system (YAMIK). Treatment consisted of three lavages per week for 4 weeks. Results: NCT caused neither alterations of the mucosa nor burning pain during application. Nevertheless, the insertion of the catheter, the insufflation of the posterior cuff and the overpressure inside the sinuses after infiltration led to moderate pain in some patients. Mucosal swelling decreased in all subjects, nasal breathing could be improved in nine patients and impaired olfaction in seven. Polyps did not disappear within the 1-month period of the study. Conclusions: The good tolerability and possible beneficial effects of NCT encourage its further investigation in CRS. Despite some limitations the YAMIK catheter proved to be a convenient and safe device for rinsing the nasal and paranasal sinuses. # 2005 Elsevier Ireland Ltd. All rights reserved.
- Published
- 2005
25. Valvular Disease and Myocardial Infarctions in a Patient With Behçet Disease
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A. Sandhofer, Franz Weidinger, Andreas Gschwendtner, Michael Schirmer, and Christian Wiedermann
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,Behcet disease ,business.industry ,Autopsy ,Regurgitation (circulation) ,medicine.disease ,Coronary arteries ,medicine.anatomical_structure ,Rheumatology ,Valvular disease ,Internal medicine ,Angiography ,cardiovascular system ,medicine ,Cardiology ,ST segment ,cardiovascular diseases ,Myocardial infarction ,business - Abstract
Cardiac involvement occurs in less than 5% of Behcet patients, and coincidence of regurgitation of the aortic and mitral valves and myocardial infarctions is rare. This report describes a 49-year-old Turkish man with Behcet disease (BD) of 6 years’ duration who presented with reduced left ventricular function. Both aortic and mitral valves had to be replaced. Five months later, the patient presented with non-ST segment elevation myocardial infarction. Only 1 month later, the patient was successfully resuscitated after an acute ST segment elevation inferior myocardial infarction. Coronary arteries were normal in appearance at angiography before valvular replacement and at autopsy 2 years later. This report should increase awareness of cardiac involvement in BD and its potential danger. Even in BD patients without atherothrombotic plaques, myocardial infarctions can happen. Early and adequate immunosuppressive treatment might have reduced cardiac morbidity in this patient.
- Published
- 2003
26. Longer Failure-Free Survival Interval of Epstein-Barr Virus–Associated Classical Hodgkin’s Lymphoma: A Single-Institution Study
- Author
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Andreas Gschwendtner, Alexandar Tzankov, Martina Fischhofer, Jens Krugmann, Richard Greil, Falko Fend, and Stephan Dirnhofer
- Subjects
Adult ,Male ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,medicine.medical_specialty ,Pathology ,Adolescent ,Biology ,Single Center ,medicine.disease_cause ,Polymerase Chain Reaction ,Disease-Free Survival ,Virus ,Pathology and Forensic Medicine ,Viral Matrix Proteins ,hemic and lymphatic diseases ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,RNA, Neoplasm ,Stage (cooking) ,Child ,Antigens, Viral ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hematology ,Middle Aged ,medicine.disease ,Hodgkin Disease ,Immunohistochemistry ,Epstein–Barr virus ,Lymphoma ,B symptoms ,Child, Preschool ,RNA, Viral ,Female ,medicine.symptom - Abstract
We analyzed Epstein-Barr virus association in classical Hodgkin's lymphoma from a single center in Austria with special emphasis on the latent membrane protein1 gene configuration and clinical outcome. All 119 (65 male, 54 female) patients were treated from 1974 to 1999 in the Division of Hematology and Oncology at the Department of Internal Medicine, University of Innsbruck, Austria. The mean follow-up time was 122 months (range, 3-333 mo). Epstein-Barr virus was examined by latent membrane protein1 immunohistochemistry and by in situ hybridization for Epstein-Barr virus-encoded early ribonuclein acid transcripts. For assessment of the Epstein-Barr virus subtype (A/B) and latent membrane protein1 gene configuration, the polymerase chain reaction was employed. Fifty-four reactive tonsils were used as the control population. These results as well as clinical parameters such as age, gender, tumor stage, risk factors, and B symptoms were correlated with failure-free and overall survival. Latent membrane protein1 was detected in 31/119 (26%) classical Hodgkin's lymphoma, and Epstein-Barr virus subtyping was successful in 19 of the 31 virus-infected classical Hodgkin's lymphoma cases, as well as in 28 of 54 reactive tonsils. Subtype A was observed in all classical Hodgkin's lymphoma patients and in 26/28 (93%) tonsils. The 30-base pair latent membrane protein1 gene deletion was found in only 4/31 (13%) Epstein-Barr virus-associated classical Hodgkin's lymphoma as well as in 20/54 (37%) reactive tonsils. Patients with Epstein-Barr virus-associated classical Hodgkin's lymphoma showed a significantly longer mean time to first relapse of 99 months, as compared with 49 months for the Epstein-Barr virus-negative cases (P.02), and were more frequent in those aged45 years (P.04). Epstein-Barr virus-associated classical Hodgkin's lymphoma were predominantly of the mixed-cellularity subtype and occurred more frequently in male patients, in patients with Stage III and IV, and in patients with B symptoms as well as risk factors. However, overall survival did not correlate with Epstein-Barr virus association. The 30-base pair latent membrane protein1 gene deletion had no influence on overall survival and failure-free survival time. Although the number of patients with this specific mutation was low, it further shows that an increased oncogenic potential of the latent membrane protein1 deletion variant is unlikely. This large single-center study demonstrates a low prevalence of Epstein-Barr virus positivity in classical Hodgkin's lymphoma in western Europe. In accordance with results of similar studies, the presence of Epstein-Barr virus has a beneficial effect on the length of failure-free survival despite the higher frequency of risk factors such as higher tumor stage or advanced age.
- Published
- 2003
27. Defense mechanisms of the respiratory system and aerosol production systems
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Haidong Huang, Dionysios Spyratos, Lonny Yarmus, Paul Zarogoulidis, Nevena Secen, Kaid Darwiche, Nikolaos Katsikogiannis, Konstantinos Zarogoulidis, Wolfgang Hohenforst-Schmidt, and Andreas Gschwendtner
- Subjects
medicine.medical_specialty ,Lung Neoplasms ,Respiratory System ,Medizin ,Pharmacology ,complex mixtures ,Genetic therapy ,Drug Discovery ,Administration, Inhalation ,medicine ,Humans ,Insulin ,Respiratory system ,Intensive care medicine ,Aerosolization ,Future perspective ,Respiratory Physiological Phenomena ,business.industry ,Genetic Therapy ,respiratory system ,Aerosol ,Anti-Bacterial Agents ,Clinical Practice ,Clinical trial ,business - Abstract
Aerosolized therapies have been used in everyday clinical practice for decades. Experimentation with different delivery systems have led to the creation of aerosolized insulin, antibiotics, gene therapy and chemotherapy. Several of these therapies are already clinically available while others are being investigated in active clinical trials. The main factors affecting the efficiency and safety of the aerosolized therapies are the production of the aerosol, distribution/deposition of the aerosol throughout the lung parenchyma, respiratory defense mechanisms and tissue/pharmaceutical molecule interactions. Current methods of aerosol production and distribution will be presented along with an overview of the respiratory defense mechanisms. In addition, methods of aerosol evaluation in conjunction with a future perspective of the potential development of aerosol therapies will be presented.
- Published
- 2014
28. The Determinants of Dementia After Stroke (DEDEMAS) Study: protocol and pilot data
- Author
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Marco Duering, Lisa Coloma Andrews, Andreas Gschwendtner, Martin Dichgans, Katharina Bürger, Anna Bayer-Karpinska, Axel Rominger, Christian Opherk, Vera Zietemann, and Frank A. Wollenweber
- Subjects
Male ,medicine.medical_specialty ,Amyloid ,Stroke patient ,Pilot Projects ,Neuropsychological Tests ,therapy [Dementia] ,Carotid Intima-Media Thickness ,Retina ,Cohort Studies ,Physical medicine and rehabilitation ,Fluorodeoxyglucose F18 ,Medicine ,Dementia ,Humans ,Ankle Brachial Index ,complications [Stroke] ,ddc:610 ,Stroke ,Aged ,metabolism [Amyloid] ,Neurologic Examination ,business.industry ,Waist-Hip Ratio ,medicine.disease ,Magnetic Resonance Imaging ,diagnosis [Dementia] ,pathology [Retina] ,Treatment Outcome ,Neurology ,Positron-Emission Tomography ,Physical therapy ,Poststroke dementia ,Female ,etiology [Dementia] ,business - Abstract
Rationale About 20% of stroke patients develop dementia within a few months after their event, but the determinants and mechanisms of poststroke dementia are insufficiently understood. Aims To identify and characterize the determinants of cognitive impairment poststroke. Design Observational prospective study in patients with acute stroke and no prior dementia. Six hundred subjects will be characterized by detailed interview, standardized clinical examinations, biometric measures (intima-media thickness, waist-hip ratio, and ankle-brachial index), multimodal imaging (magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography (FDG-PET), amyloid-positron emission tomography (amyloid-PET), and retinal imaging), analysis of biomarkers derived from blood and cerebrospinal fluid, and detailed cognitive testing at repeat time points. Patients will be followed for five-years with a total of five personal visits and three telephone interviews. Study Outcomes Primary end-point is the occurrence of post-stroke dementia. Secondary end-points include poststroke cognitive impairment–no dementia, stroke recurrence, and death. Predictive factors for poststroke dementia will be identified by multiple Cox proportional-hazards model. Results Baseline characteristics of the first 71 patients (study inclusion between May 2011 and August 2012) are as follows: median age, 70 years (interquartile range, 65–75); female gender, 25 (35%); median National Institutes of Health Stroke Scale at admission, 2 ( 1 – 4 ); and etiological stroke subtypes according to TOAST classification, 15% large artery disease, 18% small vessel disease, 35% cardioembolic, and 32% undetermined or multiple competing etiologies. Discussion This study will provide insights into the mechanisms of poststroke dementia and hold the potential to identify novel diagnostic markers and targets for preventive therapies. The study is registered at http://www.clinicaltrials.gov (NCT01334749) and will be extended as a multicenter study starting 2013.
- Published
- 2014
29. Interleukin-6 (IL6) and cellular response to facial nerve injury: effects on lymphocyte recruitment, early microglial activation and axonal outgrowth in IL6-deficient mice
- Author
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Roger Kalla, Andrea Koppius, Alexander Werner, ZhiQiang Liu, Leonard L. Jones, ShengLi Xu, Christian U.A. Kloss, Andreas Gschwendtner, Marion Bohatschek, Matthias Galiano, Horst Bluethmann, and Gennadij Raivich
- Subjects
Nervous system ,Microglia ,General Neuroscience ,medicine.medical_treatment ,Central nervous system ,Biology ,Nerve injury ,medicine.anatomical_structure ,Cytokine ,Immunology ,medicine ,biology.protein ,medicine.symptom ,Axotomy ,Interleukin 6 ,Neurotrophin - Abstract
Nerve injury triggers numerous changes in the injured neurons and surrounding non-neuronal cells. Of particular interest are molecular signals that play a role in the overall orchestration of this multifaceted cellular response. Here we investigated the function of interleukin-6 (IL6), a multifunctional neurotrophin and cytokine rapidly expressed in the injured nervous system, using the facial axotomy model in IL6-deficient mice and wild-type controls. Transgenic deletion of IL6 caused a massive decrease in the recruitment of CD3-positive T-lymphocytes and early microglial activation during the first 4 days after injury in the axotomized facial nucleus. This was accompanied by a more moderate reduction in peripheral regeneration at day 4, lymphocyte recruitment (day 14) and enhanced perikaryal sprouting (day 14). Motoneuron cell death, phagocytosis by microglial cells and recruitment of granulocytes and macrophages into injured peripheral nerve were not affected. In summary, IL6 lead to a variety of effects on the cellular response to neural trauma. However, the particularly strong actions on lymphocytes and microglia suggest that this cytokine plays a central role in the initiation of immune surveillance in the injured central nervous system.
- Published
- 2001
30. Microglia and the early phase of immune surveillance in the axotomized facial motor nucleus: Impaired microglial activation and lymphocyte recruitment but no effect on neuronal survival or axonal regeneration in macrophage-colony stimulating factor-defici
- Author
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ZhiQiang Liu, Cua Kloss, SL Xu, Andreas Gschwendtner, Andrea Koppius, Alexander Werner, Y Imai, S Kohsaka, JC Moller, Gennadij Raivich, and Roger Kalla
- Subjects
Glial fibrillary acidic protein ,biology ,Microglia ,Facial motor nucleus ,General Neuroscience ,Nerve injury ,Cell biology ,medicine.anatomical_structure ,Nerve growth factor ,Peripheral nerve injury ,biology.protein ,medicine ,medicine.symptom ,Neuroscience ,Cellular localization ,Astrocyte - Abstract
Activation of microglia is among the first cellular changes in the injured CNS. However, little is known about their specific contribution to secondary damage or repair processes in neighboring neurons and nonneuronal cells or to the immune surveillance of the damaged tissue. Animal models with defective microglial response such as osteopetrosis provide an approach to explore these effects. Osteopetrosis (op) is an autosomal recessive mutation with a complete deficiency of the macrophage-colony stimulating factor (MCSF; CSF-1), an important mitogen for brain microglia. In the current study we examined the effects of this MCSF deficiency on the microglial reaction and the overall cellular response to nerve injury in the mouse axotomized facial motor nucleus. In the brain, MCSF receptor immunoreactivity was found only on microglia and was strongly up-regulated following injury. MCSF deficiency led to a failure of microglia to show a normal increase in early activation markers (thrombospondin, MCSF receptor, alpha M beta 2- and alpha 5 beta 1-integrins), to spread on the surface of axotomized motoneurons, and to proliferate after injury. Early recruitment of CD3(+) T-lymphocytes to the facial nucleus 24 hours after injury was reduced by 60%. In contrast, the neuronal and astrocyte response was not affected. There was a normal increase in the neuropeptides calcitonin gene-related peptide and galanin, neuronal c-JUN, and NADPH-diaphorase and a decrease in choline acetyltransferase and acetylcholinesterase. Astrocyte glial fibrillary acidic protein immunoreactivity also showed a normal increase. There was a normal influx of macrophages and granulocytes into the injured facial nerve. Synaptic stripping, neuronal survival, and speed of axonal regeneration were also not affected. The current results show a strong, selective effect of MCSF on the early activation of microglia and, indirectly, on lymphocyte recruitment. This early phase of microglial activation appears not to be involved in the process of repair following peripheral nerve injury. However, it is important in the initiation of inflammatory changes in the brain and in the interaction with the immune system.
- Published
- 2001
31. Primary Gastrointestinal B-Cell Lymphoma - A Clinicopathological and Immunohistochemical Study of 61 Cases with an Evaluation of Prognostic Parameters
- Author
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Ulrike Berresheim, Falko Fend, Jens Krugmann, Andreas Gschwendtner, Kristine Krugmann, Stephan Dirnhofer, and Richard Greil
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Immunophenotyping ,Pathology and Forensic Medicine ,Antigens, Neoplasm ,immune system diseases ,hemic and lymphatic diseases ,Biomarkers, Tumor ,medicine ,Humans ,Fluorescent Antibody Technique, Indirect ,B-cell lymphoma ,Survival rate ,Lymph node ,Aged ,Gastrointestinal Neoplasms ,Neoplasm Staging ,Aged, 80 and over ,business.industry ,Stomach ,MALT lymphoma ,Lymphoma, B-Cell, Marginal Zone ,Cell Biology ,Middle Aged ,Prognosis ,medicine.disease ,Marginal zone ,Survival Analysis ,Lymphoma ,Survival Rate ,Ki-67 Antigen ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,Immunohistochemistry ,Female ,Tumor Suppressor Protein p53 ,business - Abstract
We hereby present a retrospective clinicopathological and immunohistochemical study of surgically resected primary gastrointestinal (GI) lymphoma with an analysis of parameters of potential prognostic relevance. From a larger series of 144 cases of primary GI lymphomas, we chose 61 cases with sufficient clinical follow-up (mean 60, range 1-219 months), classified either as extranodal marginal zone B-cell lymphoma of MALT type (MALT lymphoma) or diffuse large B-cell lymphoma (DLBCL), after having excluded other subtypes. In addition to conventional clinical and morphological parameters, the expression levels of Ki-67 (MIB-1), bcl-2 and p53 were evaluated for prognostic significance. Twenty-one (34.4%) cases were classified as pure low grade marginal zone B-cell lymphoma of MALT type, 12 (19.7%) cases as low grade MALT lymphoma with a high grade component (mixed type), and 28 (45.9%) cases as primary extranodal DLBCL. Most of the lymphomas (53/61; 86.9%) were localized in the stomach, 3 (4.9%) in the small bowel, 3 (4.9%) multifocal in both stomach and small intestine and 2 (3.3%) in the large bowel. MIB-1 expression in more than 30% of tumor cells was detected in 42 (68.6%), bcl-2 expression in 20 (32.8%) and p53 accumulation in more than 10% of neoplastic cells in 16 (26.2%) lymphomas. Both high Ki-67 expression and p53 accumulation were more prevalent in the DLBCL. 30 (49%) patients showed lymph node involvement at surgery, 14 (23%) patients suffered tumor recurrence, and 24 (38.5%) died during the follow-up period. Tumor recurrence occurred primarily in patients who had presented lymph node involvement (9/14, 64.3%). The 5-year survival rate was 66.1% for all patients. Important prognostic factors for overall survival were tumor stage (p.004) and p53 accumulation (p.05) in univariate analysis, and tumor stage in multivariate analysis (p.001). Although p53 accumulation did not reach statistical significance in our small study group, it may be both important in the transformation of low grade MALT lymphoma and an indicator for aggressive behavior in high grade tumors.
- Published
- 2001
32. DNA-ploidy analysis correlates with the histogenetic classification of thymic epithelial tumours
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Andreas Gschwendtner, Jens Krugmann, Falko Fend, Thomas Mairinger, P. J. Klingler, and Y. Hoffmann
- Subjects
medicine.medical_specialty ,Pathology ,Ploidies ,Thymoma ,medicine.diagnostic_test ,Medullary cavity ,Cytogenetics ,Thymus Neoplasms ,Biology ,medicine.disease ,Statistics, Nonparametric ,Pathology and Forensic Medicine ,Flow cytometry ,Image Processing, Computer-Assisted ,Carcinoma ,medicine ,Humans ,Image Cytometry ,Neoplasm ,Feulgen stain ,Neoplasm Recurrence, Local ,Neoplasm Staging - Abstract
The ploidy values of the epithelial component were determined in a series of thymomas and organotypic thymic carcinomas using image cytometry and the results were compared with the histological tumour subtypes according to the histogenetic classification introduced by Marino, Müller Hermelink, and Kirchner (MMHK). Forty-six cases of thymic epithelial tumours were included in the study. After reclassification according to the MMHK classification, the distribution among the subtypes was as follows: three medullary, nine mixed type, five predominantly cortical (organoid), 16 cortical thymomas, and 13 well-differentiated thymic carcinomas. Single cell preparations were made from paraffin-embedded tumour tissue and stained according to Feulgen. Ploidy analysis was performed using an automated image analysis system. In five cases, DNA cytometry could not be performed, for technical reasons. The remaining 41 cases consisted of 11 diploid and 30 non-diploid tumours. The percentage of aneuploid tumours in the different subtypes increased from medullary (0 per cent) through mixed type (44.4 per cent), predominantly cortical (75 per cent), cortical (83.3 per cent) to well-differentiated thymic carcinomas (100 per cent). DNA-ploidy determination using image cytometry correlates with the concept of the MMHK classification of thymomas.
- Published
- 1999
33. Nuclear chromatin texture analysis of nonmalignant tissue can detect adjacent prostatic adenocarcinoma
- Author
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Thomas Mairinger, Andreas Gschwendtner, and Gregor Mikuz
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Male ,Pathology ,medicine.medical_specialty ,Biopsy ,Urology ,medicine.medical_treatment ,Prostatic Hyperplasia ,Adenocarcinoma ,Sensitivity and Specificity ,Prostate cancer ,Prostate ,Image Processing, Computer-Assisted ,medicine ,Humans ,Feulgen stain ,Aged ,Retrospective Studies ,Cell Nucleus ,business.industry ,Prostatectomy ,Prostatic Neoplasms ,Middle Aged ,Hyperplasia ,medicine.disease ,Chromatin ,Fractals ,medicine.anatomical_structure ,Oncology ,Specimen collection ,Image Cytometry ,business - Abstract
BACKGROUND The aim of this study was to investigate the possibility of identifying prostatic adenocarcinoma by nuclear chromatin texture feature analysis of adjacent histologically benign-looking tissue. METHODS Two hundred and forty prostatectomy specimens were selected from the archives of the Department of Pathology, University of Innsbruck. These consisted of 67 cases of benign prostatic hyperplasia (BPH) and 173 cases of prostatic adenocarcinoma (PAC). The specimen collection was divided randomly into a training set and test set. Cytospin preparations of disaggregated cells prepared from paraffin-embedded material were stained specifically for DNA by the Feulgen method. For the cancer cases, only tissue that histologically appeared nonmalignant, from the vicinity of the lesion, was used in the sample preparation. Only normal-appearing diploid cell nuclei were analyzed from both the BPH and PAC groups. A discriminator comprised of three nuclear texture features to separate BPH from PAC cases was derived from the training set of cases, and then applied to the independent test set cases. RESULTS PAC cases were separated from BPH cases with a sensitivity of 90% and a specificity of 97% on the independent test set of cases. CONCLUSIONS This retrospective investigation demonstrates that by high-resolution image cytometry it is possible to detect the presence of prostatic adenocarcinoma with very high reliability when examining prostate samples that only contain histologically normal-looking cells. This method could become clinically relevant in identification of cancers missed by histologically negative core needle biopsies. Prostate 41:12–19, 1999. © 1999 Wiley-Liss, Inc.
- Published
- 1999
34. Quantitative assessment of bladder carcinoma by acid labile DNA assay
- Author
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Thomas Mairinger and Andreas Gschwendtner
- Subjects
Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Sensitivity and Specificity ,Bladder Urothelium ,Diagnosis, Differential ,medicine ,Carcinoma ,Humans ,Feulgen stain ,Urothelium ,Neoplasm Staging ,Carcinoma, Transitional Cell ,Urinary bladder ,Papilloma ,Receiver operating characteristic ,business.industry ,Reproducibility of Results ,Cancer ,DNA, Neoplasm ,medicine.disease ,medicine.anatomical_structure ,Transitional cell carcinoma ,Urinary Bladder Neoplasms ,Oncology ,Female ,business - Abstract
BACKGROUND Effective noninvasive methods for monitoring patients with bladder carcinoma and screening for bladder carcinoma that show better performance than the methods currently in use would be desirable for detecting urothelial carcinoma at an early, easily treatable stage. A rapidly hydrolyzed component of nuclear DNA has been described, the increase of which has been linked to malignancy. Quantitative determination of acid labile DNA has been applied successfully to detect other neoplasms. This study investigates the potential of this method to detect transitional cell carcinomas. METHODS Touch imprints of transurethral resection material from 62 cases of nonmalignant urothelium (control group including reactive changes) and 94 cases of bladder carcinoma were analyzed. The full Feulgen hydrolysis profiles of the nonmalignant and malignant urothelial cells were compared by measuring the staining density of the nuclei using digital image analysis after various hydrolysis times. Twenty cells were sampled randomly from among the cells measured for calculation of the mean optical density (MOD). The MOD of each time was used to build the hydrolysis profile of a case. RESULTS A hydrolysis time of 10 minutes was found to be the most discriminative between control and carcinoma cases. Applying a single threshold MOD value of 101 resulted in a test sensitivity of 95.7%, a specificity of 94.4%, a positive predictive value of 98.3%, a negative predictive value of 95.9%, and an area under the receiver operating characteristic curve of 0.97. CONCLUSIONS The results of this pilot study suggest that measurement of the rapidly hydrolyzed component of DNA present in the nuclei of bladder urothelium offers a highly sensitive and reliable supplement to the qualitative and subjective cytologic procedures currently in use. Cancer 1999;86:105–13. © 1999 American Cancer Society.
- Published
- 1999
35. Ploidy determination in prostatic adenocarcinoma using thin histological sections: A more sensitive way of detecting aneuploid tumor clones
- Author
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Andreas Gschwendtner and Thomas Mairinger
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Urology ,Aneuploidy ,Adenocarcinoma ,Biology ,Sensitivity and Specificity ,Prostate ,Biopsy ,medicine ,Humans ,DNA Image Cytometry ,Image Cytometry ,medicine.diagnostic_test ,Prostatic Neoplasms ,Histology ,DNA, Neoplasm ,Prognosis ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Tissue Preservation ,Cytometry - Abstract
BACKGROUND. The aim of this study was to compare the results of DNA image cytometry using single-cell preparations to measurements on thin histological slides of the same tumor block, in order to find the most sensitive way for detecting aneuploidy. METHODS. Twenty-three cases of prostatic adenocarcinoma were investigated by image cytometry to assess the DNA content of tumor cell nuclei. The histograms obtained by section measurements were corrected using the algorithms of Haroske et al. [Zentralbl Pathol 139: 407-417, 1994] and McCready and Papadimitriou [Anal Quant Cytol 5:117-123, 1983]. The basis for recalculation was an exact determination of the thickness of the sections used. RESULTS. Out of the 23 cases investigated, 10 tumors were diploid in the single-cell preparations, whereas 13 were classified as nondiploid. After tissue section measurements and mathematical correction of the histograms, five originally diploid histograms showed an additional aneuploid stem line. This was also the case in 8 of the 13 originally aneuploid cases. CONCLUSIONS. Tissue section measurements turned out to be more sensitive in detecting aneuploid tumor cell populations compared to measurements of cytospins of disintegrated tissue. As aneuploidy provides important prognostic information, this more sensitive means of ploidy determination could be of use in prostatic adenocarcinoma, and should especially be used in cases showing diploid histograms in single-cell cytometry.
- Published
- 1998
36. Primary Intestinal Non-Hodgkin's Lymphoma and Epstein-Barr Virus: High Frequency of EBV-Infection in T-cell Lymphomas of Mexican Origin
- Author
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Leticia Quintanilla-Martinez, Evelyn Gredler, Carmen Lome-Maldonado, Falko Fend, Arturo Angeles-Angeles, German Ott, Andreas Gschwendtner, and Reyes E
- Subjects
Herpesvirus 4, Human ,Cancer Research ,Pathology ,medicine.medical_specialty ,T cell ,Biology ,Lymphoma, T-Cell ,medicine.disease_cause ,Virus ,immune system diseases ,hemic and lymphatic diseases ,Intestinal Neoplasms ,medicine ,Humans ,B-cell lymphoma ,Mexico ,Hematology ,medicine.disease ,Burkitt Lymphoma ,Epstein–Barr virus ,Primary tumor ,Lymphoma ,Non-Hodgkin's lymphoma ,Tumor Virus Infections ,medicine.anatomical_structure ,Oncology ,Nasopharyngeal carcinoma ,Immunology - Abstract
Epstein-Barr virus is universally associated with endemic Burkitt's lymphoma (BL) and undifferentiated nasopharyngeal carcinoma and can be detected in a significant proportion of cases of Hodgkin's disease (HD) and peripheral T-cell lymphoma, but only rarely in sporadic B-NHL. The frequency of EBV-positivity in certain neoplasms shows important geographic variations. Both HD and sporadic BL from Latin America have shown higher rates of EBV-association than cases from Western countries. In T-NHL, the frequency of EBV-positivity is influenced by the site of the primary tumor and the phenotype of the neoplastic cells. Nasal and nasal-type T-NHL, which show a T/NK-cell phenotype with expression of CD56 are virtually always EBV-associated, whereas only a proportion of nodal, gastrointestinal and pulmonary T-NHL are EBV-infected. A recent investigation of primary intestinal lymphomas of Mexican origin demonstrated EBV-positivity in all examined cases of T-NHL and BL and a proportion of other B-NHLs. The presence of EBV was independent of the presence or absence of enteropathy. Two of 6 cases studied showed CD56 expression. The high rate of EBV-positivity independent of histologic subtype is in contrast to the low to intermediate rates of EBV-positivity found in cases of intestinal T-NHL from Western countries and indicates that geographic differences in the frequency of EBV-association of lymphoid neoplasms might also extend to a fraction of peripheral T-cell lymphomas.
- Published
- 1998
37. The legal situation of telemedicine in Austria
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Ch Markl, Andreas Gschwendtner, Thomas Mairinger, and T Netzer
- Subjects
Telemedicine ,Austria ,Political science ,Law ,Liability ,Civil law (legal system) ,Humans ,Liability, Legal ,Health Informatics ,Legislation ,Empirical legal studies - Abstract
Searches were conducted of two legal databases dealing with civil law in Austria. The searches produced 12 references relevant to telemedicine, which were obtained from a university legal library. From the literature, it can be concluded that Austrian civil regulations are sufficient to clarify the questions of liability arising in connection with the practice of telemedicine. Although no specific legislation has been enacted as yet, we would not expect such legislation to produce different results in the legal assessment of the case patterns discussed in this paper.
- Published
- 1997
38. Hydranencephaly with Renal Dysgenesis: A Coincidental Finding?
- Author
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Alfons Kreczy, Alexander Alge, Thomas Mairinger, Andreas Gschwendtner, and Elisabeth Soelder
- Subjects
Pathology ,medicine.medical_specialty ,Fetus ,Pregnancy ,business.industry ,Genetic disorder ,Obstetrics and Gynecology ,medicine.disease ,Hydranencephaly ,Reproductive Medicine ,medicine ,Gestation ,Cyst ,business ,Potter Syndrome ,Kidney disease - Abstract
We present the case of a female fetus aborted in the 20th week of gestation due to severely dysplastic kidneys, anhydramnios and hydranencephalus. The combination of these malformations is extremely rare, resulting in only 4 cases described so far. Our case is the first ever presented in a female showing polycystic-dysplastic kidneys. Multiple multinucleated neurons were a remarkable finding in the remnants of the brain. The possibility of an underlying genetic disorder is discussed, together with a brief review of the literature to date.
- Published
- 1997
39. Solitary subglottic neurofibroma: a report of an unusual manifestation
- Author
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Michaela Gstöttner, Oliver Galvan, Andreas Neher, and Andreas Gschwendtner
- Subjects
Adult ,Male ,Reoperation ,Larynx ,Glottis ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Pathology ,Biopsy ,Bronchoscopy ,medicine ,Humans ,Neurofibroma ,Neurofibromatosis ,Laryngeal Neoplasms ,Solitary neurofibroma ,Laryngoscopy ,business.industry ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,Dermatology ,The primary diagnosis ,Treatment Outcome ,medicine.anatomical_structure ,Otorhinolaryngology ,Head and neck surgery ,Laser Therapy ,Neoplasm Recurrence, Local ,business - Abstract
Neurofibromas of the larynx are extremely rare, especially in the subglottic part. Most of the patients with neurofibromas suffer from neurofibromatosis type 1 (NF1, von Recklinghausen's disease), which is characterized by cafe-au-lait spots and neurofibromas of any type. We present a case of a solitary neurofibroma in the subglottic region that relapsed 4 years after the primary diagnosis. The clinical findings, histological results and therapy are discussed.
- Published
- 2005
40. Incidental oral plasmablastic lymphoma with aberrant expression of CD4 in an elderly HIV-negative patient: how a gingival polyp can cause confusion
- Author
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Andreas Gschwendtner, Alexandar Tzankov, T Brunhuber, and Andrea Brunner
- Subjects
Mouth neoplasm ,Pathology ,medicine.medical_specialty ,Histology ,Gingival Polyp ,business.industry ,Human immunodeficiency virus (HIV) ,General Medicine ,medicine.disease ,medicine.disease_cause ,Dermatology ,Pathology and Forensic Medicine ,medicine ,medicine.symptom ,Differential diagnosis ,business ,Plasmablastic lymphoma ,Confusion - Published
- 2005
41. 2-diethylaminoethyl-dextran methyl methacrylate copolymer nonviral vector: still a long way toward the safety of aerosol gene therapy
- Author
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Wolfgang Hohenforst-Schmidt, Lutz Freitag, K. Zarogoulidis, Leslie Krauss, D Sparopoulou, Haidong Huang, Leonidas Sakkas, F J Turner, Andreas Gschwendtner, P. Zarogoulidis, and Kaid Darwiche
- Subjects
Male ,Lung Neoplasms ,Genetic enhancement ,First line ,medicine.medical_treatment ,Medizin ,Pharmacology ,Gene delivery ,Methylmethacrylate ,Virus ,Targeted therapy ,chemistry.chemical_compound ,Mice ,Random Allocation ,Administration, Inhalation ,Genetics ,medicine ,Animals ,Vector (molecular biology) ,Methyl methacrylate ,Molecular Biology ,Lung ,Emphysema ,Mice, Inbred BALB C ,business.industry ,DEAE-Dextran ,Genetic Therapy ,Virology ,Dextran ,chemistry ,Molecular Medicine ,business - Abstract
Revealing the lung tumor genome has directed the current treatment strategies toward targeted therapy. First line treatments targeting the genome of lung tumor cells have been approved and are on the market. However, they are limited by the small number of patients with the current investigated genetic mutations. Novel treatment administration modalities have been also investigated in an effort to increase the local drug deposition and disease control. In the current study, we investigated the safety of the new nonviral vector 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC; Ryujyu Science), which belongs to the 2-diethylaminoethyl-dextran family by aerosol administration. Thirty male BALBC mice, 2 month old, were included and divided into three groups. However, pathological findings indicated severe emphysema within three aerosol sessions. In addition, the CytoViva technique was applied for the first time to display the nonviral particles within the pulmonary tissue and emphysema lesions, and a spectral library of the nonviral vector was also established. Although our results in BALBC mice prevented us from further investigation of the DDMC nonviral vector as a vehicle for gene therapy, further investigation in animals with larger airways is warranted to properly evaluate the safety of the vector.
- Published
- 2013
42. Necrotizing sarcoid granulomatosis with hemoptysis: A case report and literature review
- Author
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Chong Bai, Qiang Li, Haidong Huang, Weiqiang Zheng, Chen Li, Paul Zarogoulidis, Zhi Zhu, Wolfgang Hohenforst-Schmidt, Andreas Gschwendtner, Konstantinos Zarogoulidis, and Michael Simoff
- Subjects
Vasculitis ,Adult ,Male ,Hemoptysis ,medicine.medical_specialty ,Pathology ,Histology ,Biopsy ,Medizin ,Case Report ,Necrotizing sarcoid granulomatosis ,Chest pain ,Pathology and Forensic Medicine ,Necrosis ,Sarcoidosis, Pulmonary ,Bronchoscopy ,medicine ,Humans ,Pulmonary pathology ,Granuloma ,medicine.diagnostic_test ,Thoracic Surgery, Video-Assisted ,business.industry ,Nodule (medicine) ,General Medicine ,medicine.disease ,Surgery ,Cardiothoracic surgery ,Sarcoidosis ,Radiology ,medicine.symptom ,Tomography, X-Ray Computed ,business - Abstract
Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1955868163936338 We present a case of 39-year-old male with the symptoms of fever, cough, chest pain and bloody phlegm, whose chest CT showed multiple subpleural nodules and inflammatory infiltration. Video-Assisted Thoracic Surgery ( VATS ) for right subplural nodule was performed and confirmed the diagnosis of necrotizing sarcoid granulomatosis. Prednisolone was administered and the symptoms were under control untill the occurrence of intermittent hemoptysis after 10 months. Chest CT and bronchoscope revealed the right lower lobe nodule with intraluminal necrotic tissue in the right lower lobe posterior basal segment respectively. Fatal hemoptysis happened during endobronchial biopsy by flexible bronchoscope forcep. Based on this case, we reviewed the relevant literature and discussed the clinical features, pathological changes and prognosis of the disease.
- Published
- 2013
43. Identification of a strategic brain network underlying processing speed deficits in vascular cognitive impairment
- Author
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Hugues Chabriat, Sonia Reyes, Rainer Malik, Mariya Gonik, Martin Dichgans, Eric Jouvent, Dominique Hervé, Marco Duering, Andreas Gschwendtner, Nikola Zieren, and Christian Opherk
- Subjects
Adult ,Male ,Cognitive Neuroscience ,physiopathology [CADASIL] ,CADASIL ,physiopathology [Brain] ,White matter ,Lesion ,Young Adult ,pathology [Brain] ,Neural Pathways ,medicine ,pathology [CADASIL] ,Humans ,ddc:610 ,Cognitive impairment ,Aged ,Brain network ,physiopathology [Neural Pathways] ,pathology [Neural Pathways] ,Bayesian network ,Brain ,Bayes Theorem ,Exploratory analysis ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Hyperintensity ,medicine.anatomical_structure ,Neurology ,Female ,medicine.symptom ,Psychology ,Neuroscience - Abstract
Patients with vascular cognitive impairment (VCI) commonly exhibit deficits in processing speed. This has been attributed to a disruption of frontal-subcortical neuronal circuits by ischemic lesions, but the exact mechanisms and underlying anatomical structures are poorly understood. We set out to identify a strategic brain network for processing speed by applying graph-based data-mining techniques to MRI lesion maps from patients with small vessel disease. We studied 235 patients with CADASIL, a genetic small vessel disease causing pure VCI. Using a probabilistic atlas in standard space we first determined the regional volumes of white matter hyperintensities (WMH) and lacunar lesions (LL) within major white matter tracts. Conditional dependencies between the regional lesion volumes and processing speed were then examined using Bayesian network analysis. Exploratory analysis identified a network of five imaging variables as the best determinant of processing speed. The network included LL in the left anterior thalamic radiation and the left cingulum as well as WMH in the left forceps minor, the left parahippocampal white matter and the left corticospinal tract. Together these variables explained 34% of the total variance in the processing speed score. Structural equation modeling confirmed the findings obtained from the Bayesian models. In summary, using graph-based models we identified a strategic brain network having the highest predictive value for processing speed in our cohort of patients with pure small vessel disease. Our findings confirm and extend previous results showing a role of frontal-subcortical neuronal circuits, in particular dorsolateral prefrontal and cingulate circuits, in VCI.
- Published
- 2013
44. Application of flexible bronchoscopy in inhalation lung injury
- Author
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Qiang Li, Haidong Huang, Chong Bai, Paul Zarogoulidis, Jingqing Hang, Shihui Zhu, Andreas Gschwendtner, Bing Li, Wei Zhang, Michael Simoff, Konstantinos Zarogoulidis, and Xiao-peng Yao
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,China ,Time Factors ,Histology ,Adolescent ,Medizin ,Bronchi ,Lung injury ,Severity of Illness Index ,Pathology and Forensic Medicine ,Young Adult ,Bronchoscopy ,Smoke ,medicine ,Humans ,Flexible bronchoscopy ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,Inhalation ,business.industry ,Research ,General Medicine ,Lung Injury ,Middle Aged ,Anesthesia ,Female ,business ,Burns, Inhalation - Abstract
Background As acute inhalational injury is an uncommon presentation to most institutions, a standard approach to its assessment and management, especially using flexible bronchoscopy, has not received significant attention. Methods The objective of this study is to evaluate the value of using flexible bronchoscopy as part of the evaluation and management of patients with inhalational lung injury. Twenty-three cases of inhalational lung injury were treated in our three hospitals after a fire in a residential building. The twenty cases that underwent bronchoscopy as part of their management are included in this analysis. After admission, the first bronchoscopy was conducted within 18-72 hours post inhalational injury. G2-level patients were reexamined 24 hours after the first bronchoscopy, while G1-level patients were reexamined 72 hours later. Subsequently, all patients were re-examined every 2-3 days until recovered or until only tunica mucosa bronchi congestion was identified by bronchoscopy. Results Twenty patients had airway injury diagnosed by bronchoscopy including burns to the larynx and glottis or large airways. Bronchoscopic classification of the inhalation injury was performed, identifying 12 cases of grade G1 changes and 8 cases of grade G2. The airway injury in the 12 cases of grade G1 patients demonstrated recovery in 2-8 days, in the airway injury of the 8 cases of grade G2 patients had a prolonged recovery with airway injury improving in 6-21 days averaged. The difference in recovery time between the two groups was significant (P
- Published
- 2013
45. Ischemic stroke is associated with the ABO locus: the EuroCLOT study
- Author
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Jonathan Rosand, Matthew Traylor, Sudha Seshadri, Veikko Salomaa, Robert Clarke, Anita L. DeStefano, Rodney J. Scott, Steve Bevan, Braxton D. Mitchell, Alun Evans, Philippe Amouyel, Myriam Fornage, Hugh S. Markus, Olli Saarela, Peter Wagner, Dylan Hodgkiss, Angela M. Carter, Giorgio B. Boncoraglio, Catherine Sudlow, K. L. Furie, Will Longstreth, Nicole Soranzo, Peter M. Rothwell, Jean Ferrières, John Attia, Bruce M. Psaty, Martin Dichgans, Christopher Levi, M. Arfan Ikram, Jarmo Virtamo, Gudmar Thorleifsson, Frances M K Williams, Pankaj Sharma, Martin Farrall, Kari Kuulasmaa, Per-Gunnar Wiklund, Elizabeth G. Holliday, James F. Meschia, Anna Helgadottir, Unnur Thorsteinsdottir, Michael A. Nalls, Peter J. Grant, Marco M Ferrario, Dominique Arveiler, Tim D. Spector, Andreas Gschwendtner, Eugenio Parati, Mari A. Kaunisto, Gabriela L. Surdulescu, Joshua C. Bis, Solveig Gretarsdottir, Kaisa Silander, Kari Stefansson, Thomas H. Mosely, Albert Hofman, Pirro G. Hysi, Yu-Ching Cheng, Aarno Palotie, Radiology & Nuclear Medicine, and Epidemiology
- Subjects
Male ,Neurology ,Genome-wide association study ,030204 cardiovascular system & hematology ,Bioinformatics ,Brain Ischemia ,Brain ischemia ,Coronary artery disease ,Pathogenesis ,Cohort Studies ,0302 clinical medicine ,80 and over ,genetics ,Genetics ,Aged, 80 and over ,biology ,Atrial fibrillation ,Single Nucleotide ,Middle Aged ,3. Good health ,Europe ,Stroke ,epidemiology ,Female ,Rapid Communication ,Adult ,medicine.medical_specialty ,Adolescent ,Polymorphism, Single Nucleotide ,Fibrin ,methods ,ABO Blood-Group System ,03 medical and health sciences ,Young Adult ,ABO blood group system ,medicine ,Humans ,Genetic Predisposition to Disease ,Polymorphism ,Blood Coagulation ,Aged ,epidemiology/genetics ,diagnosis/epidemiology/genetics ,genetics, Adolescent, Adult, Aged, Aged ,80 and over, Blood Coagulation ,genetics, Brain Ischemia ,diagnosis/epidemiology/genetics, Cohort Studies, Europe ,epidemiology, Female, Genetic Loci ,genetics, Genetic Predisposition to Disease ,epidemiology/genetics, Genetic Variation ,genetics, Genome-Wide Association Study ,methods, Humans, Male, Middle Aged, Polymorphism ,genetics, Stroke ,diagnosis/epidemiology/genetics, Young Adult ,Genetic Variation ,medicine.disease ,Genetic Loci ,biology.protein ,Neurology (clinical) ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
OBJECTIVE: End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy volunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype.METHODS: Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3).RESULTS: Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 × 10(-8)) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 × 10(-186)), rs10665 with FVII (p = 2.4 × 10(-47)), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 × 10(-57)) and factor VIII (p = 1.2 × 10(-36)). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88-0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). INTERPRETATION: ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype.
- Published
- 2013
46. Abstract 11: The Utility of Causative Classification System: Correlation between Causative and Phenotypic Stroke Subtypes
- Author
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Ethem Murat Arsava, Kevin Barrett, Alessandro Biffi, David Brenner, Robert Brown, Dale Gamble, Anja Grazer, Andreas Gschwendtner, Johanna Helenius, Mohammed Huq, Petra Katschnig, Michael Katsnelson, Steven Kittner, Linxin Li, Daniel L Labovitz, Shaneela Malik, James Meschia, Raid Ossi, Leema Peddareddygari, Mateusz Pucek, Kristiina Rannikmae, David Rhodes, Neha Saraf, Huma Sheikh, Eva Stoegerer, Andrew Southerland, Darren Weissman, Daniel Woo, Bradford Worrall, and Hakan Ay
- Subjects
Advanced and Specialized Nursing ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
Background: Causative Classification of Stroke (CCS) system is a novel, web-based, and fully-computerized algorithm that integrates clinical, diagnostic, and etiologic stroke characteristics in an evidence-based manner (available at http://ccs.mgh.harvard.edu ) and provides in a given patient both phenotypic subtypes where abnormal evaluation findings are simply organized in major etiologic categories and causative subtypes where abnormal evaluation findings are filtered through a decision making process to identify the most likely cause of stroke. In this study, we sought to identify the concordance between phenotypic and causative CCS subtypes in the NINDS Stroke Genetics Network (SiGN). Methods: A total of 24 adjudicators from 15 US and European sites certified in CCS retrospectively determined CCS subtypes through chart review in 7134 patients. The CCS software provided causative subtypes in 3 confidence levels as “evident”, “probable” or “possible” based on the weight of causal evidence. We estimated how often CCS classified a given major abnormal evaluation finding as the causative stroke mechanism. Results: CCS assigned 55% of patients with the phenotype of moderate-to-severe atherosclerotic stenosis into the causative category of “evident large artery atherosclerosis”. Likewise, 50% of patients with a major cardiac source (such as atrial fibrillation) were classified into “evident cardio-aortic embolism”, and 74% of those with imaging evidence of a typical lacunar infarct into “evident small artery occlusion”. In 20% to 30% of patients, phenotypic and causative categories were the same but the causative subtype was assigned with a lower level of confidence. Six to 20% of patients with a given phenotypic feature were classified into a different causative category. Failure to investigate for other subtypes in the presence of a positive test finding and the presence of multiple competing etiologies were key contributors to the observed disconcordance between phenotypic and causative subtypes. Conclusions: Our findings show that the presence of a major abnormality in stroke evaluation does not necessarily mean that it is always the cause. The ability of CCS system to discriminate between phenotypic and causative characteristics of stroke etiology provides the opportunity to refine stroke phenotypes for use in research studies.
- Published
- 2012
47. Extensive white matter hyperintensities may increase brain volume in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy
- Author
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Ophélia Godin, Martin Dichgans, Jean Guichard, Dominique Hervé, Ming Yao, Yi-Cheng Zhu, Andreas Gschwendtner, Christian Opherk, Eric Jouvent, Marco Düring, and Hugues Chabriat
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,CADASIL ,White matter ,Leukoencephalopathy ,Young Adult ,Atrophy ,Leukoencephalopathies ,pathology [Brain] ,mental disorders ,medicine ,pathology [CADASIL] ,Humans ,ddc:610 ,Prospective Studies ,metabolism [Water] ,Stroke ,Cerebral Hemorrhage ,Aged ,Advanced and Specialized Nursing ,Cerebral atrophy ,pathology [Cerebral Hemorrhage] ,business.industry ,Age Factors ,pathology [Leukoencephalopathies] ,Brain ,Water ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Hyperintensity ,pathology [Stroke, Lacunar] ,medicine.anatomical_structure ,metabolism [Brain] ,Stroke, Lacunar ,Brain size ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background and Purpose— The extent of white matter hyperintensities (WMH) is associated with cerebral atrophy in elderly people. WMH is a radiological hallmark of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), but their relationship with brain volume remains poorly understood. The association between WMH and brain volume was analyzed in a large population of patients with CADASIL. Methods— Demographic and MRI data of 278 patients recruited from a prospective cohort study were analyzed. Volumes of WMH and lacunar infarcts, number of cerebral microbleeds, and brain parenchymal fraction were measured. Multivariate analysis was used to study the impact of WMH on brain volume at baseline. Results— In univariate analyses, brain parenchymal fraction was negatively associated with age, male sex, and all MRI markers. Multiple regression modeling showed that brain parenchymal fraction was inversely related to age, number of cerebral microbleeds, and normalized volume of lacunar infarcts but positively related to normalized volume of WMH ( P P ≤0.001). Conclusion— The results of the present study suggest that extensive WMH may be associated with increase of brain volume in CADASIL. In this disorder, WMH may be related not only to loss of white matter components, but also to a global increase of water content in the cerebral tissue.
- Published
- 2012
48. Detection of Monoclonal B-Cell Populations in Decalcified, Plastic-embedded Bone Marrow Biopsies with the Polymerase Chain Reaction
- Author
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Josef Thaler, Evelyn Gredler, Falko Fend, O. Dietze, and Andreas Gschwendtner
- Subjects
Pathology ,medicine.medical_specialty ,Plastic Embedding ,Biopsy ,Molecular Sequence Data ,Population ,Biology ,Polymerase Chain Reaction ,law.invention ,Bone Marrow ,law ,medicine ,Humans ,Gene Rearrangement, B-Lymphocyte ,education ,Polyhydroxyethyl Methacrylate ,Polymerase chain reaction ,B cell ,B-Lymphocytes ,education.field_of_study ,Base Sequence ,Bone decalcification ,DNA ,General Medicine ,Gene rearrangement ,Hematologic Diseases ,Molecular biology ,Clone Cells ,medicine.anatomical_structure ,Polyclonal antibodies ,biology.protein ,Immunoglobulin heavy chain ,Bone marrow - Abstract
Polymerase chain reaction (PCR) has been employed successfully for the detection of clonal immunoglobulin gene rearrangements in paraffin-embedded clinical samples. The authors examined whether this technique can also be applied to fixed, decalcified, and plastic-embedded bone marrow biopsies. DNA extracted from 66 glycolmethacrylate-embedded trephine biopsy samples was amplified for the detection of rearranged VDJ regions of the immunoglobulin heavy chain genes using both a single-step and a semi-nested PCR technique. After exclusion of samples with inadequate DNA, clonality was confirmed in 16 (67%) of 24 cases with B cell malignancy, whereas all 11 non-B cell neoplasms, and 6 of 9 cases with normal bone marrow showed evidence of a polyclonal B cell population. Patterns indicating oligo- or monoclonality were observed in three plastic-embedded samples of normal bone marrow, although control PCR of frozen bone marrow samples obtained in parallel showed no evidence of clonality. Repeated PCR of these cases revealed inconsistent bands, probably due to the amplification of rare templates from polyclonal B cells. Decalcified, plastic-embedded bone marrow biopsies are suitable for PCR-based determination of B-cell clonality. To exclude the possibility of false-positive results, monitoring of template DNA quality and independent control amplifications are mandatory.
- Published
- 1994
49. Erratum: Ischemic stroke is associated with the ABO locus: The EuroCLOT study
- Author
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Matthew Traylor, T H Mosely, Gudmar Thorleifsson, Elizabeth G. Holliday, Catherine Sudlow, N Soranzo, O Saarela, Gabriela L. Surdulescu, Peter J. Grant, Andreas Gschwendtner, Rothwell Pmw., Pirro G. Hysi, Karen L. Furie, Angela M. Carter, J. C. Bis, James F. Meschia, Dominique Arveiler, Braxton D. Mitchell, Eugenio Parati, Jean Ferrières, M Nalls, Myriam Fornage, Unnur Thorsteinsdottir, Martin Dichgans, Christopher R Levi, Mari A. Kaunisto, Hugh S. Markus, Veikko Salomaa, Robert Clarke, Aarno Palotie, Tim D. Spector, Jarmo Virtamo, Solveig Gretarsdottir, Pankaj Sharma, Marco M Ferrario, W. T. Longstreth, Williams Fmk., Rodney J. Scott, Peter Wagner, Martin Farrall, Anna Helgadottir, Kaisa Silander, Yu-Ching Cheng, Steve Bevan, Mohammad Arfan Ikram, Sudha Seshadri, Kari Stefansson, Giorgio B. Boncoraglio, Alun Evans, Albert Hofman, Dylan Hodgkiss, P. Amouyel, Jonathan Rosand, Kari Kuulasmaa, John Attia, Bruce M. Psaty, Per-Gunner Wiklund, and Anita L. DeStefano
- Subjects
medicine.medical_specialty ,Annals ,Neurology ,business.industry ,ABO blood group system ,Internal medicine ,Ischemic stroke ,medicine ,Locus (genetics) ,Neurology (clinical) ,business ,Neuroscience - Published
- 2014
50. Adenocarcinoma of the esophagogastric junction: neoadjuvant radiochemotherapy and radical surgery : early results and toxicity
- Author
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Bernhard J. Leibl, Martin Alfrink, Andreas Gschwendtner, Wolfgang Schäfer, Gerhard G. Grabenbauer, and Stephanie Vitz
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Esophageal Neoplasms ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Adenocarcinoma ,Disease-Free Survival ,Postoperative Complications ,Gastrectomy ,Internal medicine ,Laparotomy ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Radical surgery ,Esophagus ,Neoadjuvant therapy ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Radiotherapy Dosage ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Neoadjuvant Therapy ,Surgery ,Esophagectomy ,Radiation Pneumonitis ,medicine.anatomical_structure ,Lymph Node Excision ,Lymphadenectomy ,Female ,Esophagogastric Junction ,business ,Follow-Up Studies - Abstract
To retrospectively evaluate treatment results and toxicity following a combined approach consisting of neoadjuvant radiochemotherapy and radical surgery in advanced adenocarcinoma of the esophagus and gastroesophageal junction.Between 2005 and 2009, a total of 41 consecutive patients with newly diagnosed nonmetastatic adeno-carcinoma of the esophagus and the esophagogastric junction were evaluated, of whom 23 received neoadjuvant radiochemo-therapy (RCT). A total dose of 50.4 Gy with 2 cycles of simultaneous cisplatin/5-fluorouracil (FU) or Taxol/FU-chemotherapy were applied. A radical transthoracic subtotal esophageal and proximal gastric resection through a right thoracoabdominal laparotomy with intrathoracic anastomosis was performed 6-8 weeks following RCT. This was combined with a two-field lymphadenectomy of mediastinal and abdominal lymph nodes. Standard histopathological evaluation included the application of regression grading according to Werner and Höfler. Toxicity was recorded on the basis of CTC criteria; survival curves were calculated according to Kaplan-Meier. V10, V15, and V20 data were correlated with pulmonary toxicity.Overall survival for all 23 patients was 61% at 3 years. Of the original 23 patients, 18 (78%) patients proceeded to radical surgery. Reasons for no surgery included advanced age of 79, 82, and 86 years (n = 3), severe comorbidity (n = 1), and progression during radiochemotherapy (n = 1). Surgical morbidity (grade 3-4) and mortality rates were 35% and 6%, respectively. Resurgery was necessary in 3 cases (18%). Clear resection margins were achieved in 17 of 18 patients (94%). Twelve of 18 (67%) patients initially diagnosed with T3 tumors and 3 of 3 patients with T4 tumors experienced downstaging. The ypN0 rate was 12 of 18 patients (67%). Out of a total of 18 patients, regression grading revealed10% viable cells in 8 (44%) including 3 cases (17%) with complete regression, 10-50% viable cells in 9 (50%) and50% viable cells in 1 patient. During the postoperative course or thereafter, 8 of 23 (35%) patients experienced pulmonary complications including pneumonia and/or pneumonitis. V1020% (p = 0.019), V1513% (p = 0.008), and V2010% (p = 0.008) were associated with a significant increase in the rate of pulmonary toxic effects.Neoadjuvant radiochemotherapy in patients with advanced adenocarcinoma of the esophagogastric junction followed by thoracoabdominal surgery is a feasible concept. Significant tumor regression in 44% of the patients and an ypN0 rate in 67% of the patients may favor this approach due to its high efficacy. However, to avoid toxic pulmonary effects constraints for low-dose radiation volume parameters need specific attention.
- Published
- 2010
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