193 research outputs found
Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab
No full textObjectiveTo examine the association between peripheral blood lymphocyte pharmacodynamics and autoimmune adverse events (AEs) or return of disease activity in alemtuzumab-treated patients with relapsing-remitting MS.MethodsPatients received 2 alemtuzumab courses (12 mg/d IV; 5 days at baseline, 3 days 12 months later) in the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis studies (NCT00530348 and NCT00548405) and could then receive as-needed alemtuzumab or other disease-modifying therapy in a 4-year extension (NCT00930553). Lymphocytes were phenotyped quarterly over 2 years using fluorescence-activated cell sorting. Pharmacodynamic assessments included counts of total lymphocytes, CD3(+) T cells, CD4(+)/CD8(+) T cells (total/naive/memory/regulatory [T-reg]), and CD19(+) B cells (total/immature/mature/memory) and ratios of CD19(+) (total/immature/mature/memory) to T-reg (CD4(+)/CD8(+)) counts. Assessed autoimmune AEs included immune thrombocytopenia, nephropathies, and thyroid events. Efficacy assessments included relapses, 6-month confirmed disability worsening (CDW), and MRI disease activity.ResultsLymphocyte repopulation patterns, including ratios between distinct lymphocyte subsets (e.g., CD19(+) to T-reg cell count ratios), showed no significant differences over 2 years in patients developing/not developing autoimmune AEs, relapses, CDW, or MRI activity through 6 years following alemtuzumab. Lymphocyte kinetics were also unrelated to multiple autoimmune AEs or extreme clinical phenotypes.ConclusionsRepopulation kinetics of the evaluated peripheral lymphocyte subsets did not predict autoimmune AE occurrence or disease activity, including return of disease activity after 2 alemtuzumab courses. Further study is needed to investigate potential antigen-level markers of treatment response.This study was supported by Sanofi and Bayer HealthCare Pharmaceuticals. Prof. H. Wiendl was supported by the Deutsche Forschungsgemeinschaft (DFG) Grant CRC128 Project A09, and the Kompetenznetz Multiple Sklerose (Competence Network for Multiple Sclerosis) funded by the Federal Ministry of Education and Research (FKZ 01GI1308B 01GI0907).Wiendl, H (corresponding author), Univ Munster, Munster, Germany.
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sj-docx-1-msj-10.1177_13524585211044479 – Supplemental material for Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study
No full textSupplemental material, sj-docx-1-msj-10.1177_13524585211044479 for Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study by Amit Bar-Or, Heinz Wiendl, Xavier Montalban, Enrique Alvarez, Maria Davydovskaya, Silvia R Delgado, Evgeniy P Evdoshenko, Natasa Giedraitiene, Katrin Gross-Paju, Sulev Haldre, Craig E Herrman, Guillermo Izquierdo, Guntis Karelis, Fritz Leutmezer, Miroslav Mares, Jose E Meca-Lallana, Dalia Mickeviciene, Jacqueline Nicholas, Derrick S Robertson, Denis V Sazonov, Kenneth Sharlin, Bharathy Sundaram, Natalia Totolyan, Marta Vachova, Martin Valis, Morten Bagger, Dieter A Häring, Inga Ludwig, Roman Willi, Martin Zalesak, Wendy Su, Martin Merschhemke and Edward J Fox in Multiple Sclerosis Journal</p
LB82 Effect of Ofatumumab on Serum Immunoglobulin Levels and Infection Risk in Relapsing Multiple Sclerosis Patients from the Phase 3 ASCLEPIOS I and II Trials
No full textFil: Correale, Jorge. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.Fil: de Seze, Jérôme. University Hospital of Strasbourg; Francia.Fil: Bar-Or, Amit. University of Pennsylvania. Perelman School of Medicine. Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology; Estados Unidos.Fil: Cross, Anne H. Washington University School of Medicine; Estados Unidos.Fil: Kappos, Ludwig. University Hospital and University of Basel. Departments of Medicine, Clinical Research,
Biomedicine and Biomedical Engineering. Neurologic Clinic and Policlinic; Suiza.Fil: Selmaj, Krzysztof. Center for Neurology; Polonia.Fil: Wiendl, Heinz. University of Muenster; Alemania.Fil: Kerloeguen, Cecile. Novartis Pharma AG; Suiza.Fil: Goodyear, Alexandra. Novartis Pharmaceuticals Corporation; Estados Unidos.Fil: Pingili, Ratnakar. Novartis Pharmaceuticals Corporation; Estados Unidos.Fil: Sullivan, Roseanne. Novartis Pharmaceuticals Corporation; Estados Unidos.Fil: Gupta, Ayan Das. Novartis Healthcare; India.Fil: Jehl, Valentine. Novartis Pharma AG; Suiza.Fil: Häring, Dieter A. Novartis Pharma AG; Suiza.Fil: Merschhemke, Martin. Novartis Pharma AG; Suiza.Fil: Hauser, Stephen L. University of California. UCSF Weill Institute for Neurosciences. Department of Neurology; Estados Unidos
Bernard Horst - The connections between life and work
No full textThis thesis focuses on Bernard Horst, who is introduced, based on the historical background of the period in which he lived as well as literary reviews and the interpretation of his selected novels. The thesis aims to provide a complex overview of findings about this writer and should also - using overviews of the history of the Czech literature and literary dictionaries - partially answer the following question: In what light can the personality of a marginal author address a contemporary reader, through which perspective can this author be seen and, most importantly, how this author can be discussed using the wider literary context
The probing of the Czech poetry of the 90. years of the 20. century
No full textThis thesis examines the poetry of poets who officially entered the Czech literary scene in 1990s - after The Velvet Revolution. That was a period of time when Czech literary life changed completely. The thesis focuses on the artists born during the 1960s and the early 1970s - Petr Borkovec, Martin Langer, Pavel Kolmačka and Petr Hruška. The thesis concentrates on the analysis of their first two individual collections published between 1990-1998. What is important is the fact that the authors are not negatively influenced by the cultural politics from the communism era. First, the thesis outlines the events on the Czech literary scene after the revolution. Then it offers a view of the individual poets' works. This part also presents the critical reflection of the period, while the main focus is on the interpretation of poetic works. Through analytical reading this thesis follows the fundamental motive constants and it also reflects other important components of the early authorial poetics. The aim is to point out the tendencies in young Czech poetry at the time of sudden multiplicity of possibilities and to prove or disprove the presence of traditional poetics. Keywords: Czech poetry, 1990, poetic debut, Petr Borkovec, Martin Langer, Pavel Kolmačka, Petr Hrušk
The Existential Poetry and Jiří Orten
No full textThe work is divided into two chapters. In the first one the World's and Czech poets (chosen on the basis of Orten's list of reading) are analyzed. Those authors could be understood as impersonators or predecessors of the existential tendencies and it's provable Orten knew their works well (i.a. Rilke, Rimbaud, Akhmatova, Mácha, Weiner, Halas, Holan, Zahradníček, Bonn and Daniel). The second and more voluminous chapter consists of the motives' and topics' analysis of Orten's literary work, focused mainly on the poetry and less on the other literary genres - notes, letters, prose. The most of his poems and notes is based on the factual life experience and their ethos is founded on both existential and Christian moral philosophy. There's also an influence of some other intellectual tendencies and artistic styles like folk literature, romanticism, impressionism, less intensively expressionism, naturalism, psychoanalysis, surrealism and naturism. To get the coherent interpretation of Orten's work it's necessary to reflect (beside the existential motives) the pathos of the intimate traumatic relationship to the father, the girl(friend)s and the unborn child as well as the deeply Christian understanding of reality (connected with the biblical /The Old Testament/ dialogical relation to the God, the..
Analysis of Viktor Dyk's early short stories
No full textPráce se zabývá vybranými ranými povídkami Viktora Dyka. V první části analyzujeme dvě povídky "mimetičtějšího" rázu, tzn. úžeji se vztahující ke skutečnosti a řadící se v tomto ohledu k ne primárně uměleckým žánrům Dykovy tvorby. Charakterizujeme na tomto materiálu základní rozlišení postav svědek vs. idealista. Naznačujeme zde také spoje s možnými předlohami některých vedlejších postav a analogii s tvorbou Viktora Dyka jakožto literárního kritika. Ve druhé části jsou předmětem naší analýzy povídky méně "mimetické". Zaměřujeme se především na novou náplň, kterou se postavy, na něž zde dosud lze aplikovat zmiňované rozlišení, odlišují od postav z první dvojice povídek. V závěru pak ještě na dramatu Veliký mág dokládáme, že se protiklad "mimetičnost" vs. "nemimetičnost" neprojevuje jenom v Dykových raných povídkách, ale i později a jinde.The thesis deals with several selected early short stories by Viktor Dyk. In the first part, we analyse two short stories with a greater "mimetic" character, i.e. stories with narrower relation to reality and, in that sense, belonging to the genres of Dyk's work that are not primarily artistic. Based on this material, we characterize the elementary distinction between two types of characters: observers and idealists. We also outline an analogy with Dyk's literary criticism and connection between some side characters and their possible models. In the second part, less "mimetic" short stories become the subject of our analysis. We concentrate mainly on the new meaning by which the above-mentioned types of characters differ from their predecessors from the first pair of analysed stories. Finally, in the conclusion, we show that the opposition between "mimetic" and "non- mimetic" manifests itself not only in Dyk's early short stories, but even later in his other works, such as the drama Veliký mág.Department of Czech and Comparative LiteratureÚstav české literatury a komparatistikyFilozofická fakultaFaculty of Art
Analysis of Viktor Dyk's early short stories
No full textThe thesis deals with several selected early short stories by Viktor Dyk. In the first part, we analyse two short stories with a greater "mimetic" character, i.e. stories with narrower relation to reality and, in that sense, belonging to the genres of Dyk's work that are not primarily artistic. Based on this material, we characterize the elementary distinction between two types of characters: observers and idealists. We also outline an analogy with Dyk's literary criticism and connection between some side characters and their possible models. In the second part, less "mimetic" short stories become the subject of our analysis. We concentrate mainly on the new meaning by which the above-mentioned types of characters differ from their predecessors from the first pair of analysed stories. Finally, in the conclusion, we show that the opposition between "mimetic" and "non- mimetic" manifests itself not only in Dyk's early short stories, but even later in his other works, such as the drama Veliký mág
Karel Poláček, a prose writer, in a contemporary reflection of his novel Men in Offside.
No full textKarel Poláček, a prose writer, in a contemporary reflection of his novel Men in Offside is a bachelor thesis which is talking about Karel Poláček in context of his prose writings but this thesis is mostly focused on his literary output Men in Offside which was published in 1931. The first part of this thesis is about a prose writings of this author, second part is talking about the novel Men in Offside and the third major part is focused on contemporary literature criticism to this novel. The aim of this thesis is to introduce this author who wrote Men in Offside and who pictured lives of the football fans in the thirties of the twenty century. It should show the contemporary reaction on this novel. Powered by TCPDF (www.tcpdf.org
Characters and stories of Prague's underworld as reflected in late 19th and early 20th century fiction
No full textThe diploma thesis deals with various genres which, at the turn of the century, depicted life of the Prague offscourings, i.e. socially excluded and frequently humiliated inhabitants of Prague. The main objective is to give a characteristic of a homeless character, the man on the street, also known as the "Prague vagabond", a character which regularly appears in literature of the period. The thesis discusses several specific Prague vagabonds whom it subsequently compares to the literary type of vagabond (the author used Daniela Hodrová's theoretical findings about the literary type) and shows the impact the city environment has on him. Besides that, the author follows the way the city itself is described as the vagabond of Prague is closely connected with and to a large extent determined by his home city. Primarily, the thesis works with fiction (although a few plays are included as well) and aims to focus on authors of the period who are not widely known today, e.g. R. J. Kronbauer, K. L. Kukla, V. Plaček, F. L. Šmíd, and J. Hais Týnecký. Keywords Prague, Prague offscourings, vagabond, beggar, social issues, literary character, environmen
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