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  • 1
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Multiple Sklerose ; TNF-α-Antagonisten ; Lenercept ; Infliximab ; Linomid ; Deoxyspergualin ; Sulfasalazin ; Il-10 ; TGF-β2 ; IVIg ; Orale Toleranz ; Extrakorporale Photopherese ; Cladribin ; APL ; Altered peptide ligands ; Keywords Multiple sclerosis ; TNF α-antagonist ; Linomide ; Deoxyspergualine ; Sulfasalazine ; IL-10 ; TGF-β2 ; IVIg ; Oral tolerance ; Extracorporeal photopheresis ; Cladribine ; APL ; Altered peptide ligands
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Recent immunobiological findings together with advances in biotechnology, ameliorations in clinical trial design, and MRI developments have led to a variety of therapeutical approaches in multiple sclerosis (MS). However, in contrast to successfully introduced new treatments, a number of therapeutical failures exist as well: despite impressive data from animal models, convincing concepts, and promising phase I/II studies, some investigated drugs and strategies showed no positive effects in clinical trials, or trials had to be terminated because of unexpected side effects. This article provides an overview of clinical studies that have failed or been abandoned for other reasons. Tumor necrosis factor (TNF) α-antagonists which have led to negative effects in two studies (Lenercept, Infliximab) are discussed in detail. These results raise critical questions concerning the hypothetical pathogenesis of MS lesions and the value of MRI in the assessment of clinically relevant therapeutic drug effects. In addition to a description of the immunobiological background, studies on the immunosuppressive agents linomide, deoxyspergualin, sulfasalazine and cladribine, trials for the cytokines interleukin-10 and TGF-β2, the studies on remyelination by intravenous immunoglobulins (IVIg), oral tolerance, and extracorporeal photopheresis are discussed.
    Notes: Zusammenfassung Neue immunbiologische Erkenntnisse haben zusammen mit Fortschritten in der Biotechnologie, Verbesserungen im Design von Medikamentenstudien und Entwicklung der Kernspintomographie zu einer Vielfalt prüfbarer Therapieansätze bei der multiplen Sklerose geführt. Neben erfolgreichen immunmodulatorischen Therapien gibt es jedoch einige Fehlschläge: Trotz eindrucksvoller tierexperimenteller Daten, überzeugender Konzepte oder gar Erfolg versprechender Phase-I/II-Studien erbrachten die untersuchten Medikamente letztendlich keine positive Wirkung oder zeigten unerwartete schwere Nebenwirkungen. Dieser Artikel gibt eine aktuelle Zusammenstellung von Therapiestudien, die fehlgeschlagen sind oder aus anderen Gründen abgebrochen wurden. Im Zentrum steht die Blockierung des TNF-α, die in 2 Studien (Lenercept, Infliximab) sogar zu negativen Effekten geführt hatte. Diese Resultate werfen kritische Fragen bezüglich Läsionspathogenese und Wertigkeit der Kernspintomographie in der Beurteilung klinischer Therapieeffekte auf. Außerdem werden die Studien für die immunsuppressiven Agenzien Linomid, Deoxyspergualin, Sulfasalazin und Cladribin, für die Zytokine Interleukin-10 und TGF-β2, die Studien zur Remyelinisierung durch intravenöse Immunglobuline (IVIg), zur oralen Toleranzinduktion und zur extrakorporalen Photopherese diskutiert.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Interferon beta-1b ; Multiple-Sklerose-Therapie ; Sekundär chronisch progrediente multiple Sklerose ; Key words Interferon beta-1b ; Multiple sclerosis therapy ; Secondary progressive multiple sclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Several phase III studies have proven that the beta-interferons have positive effects on the number and severity of acute exacerbations of relapsing remitting multiple sclerosis. Recently the first study on the effectiveness of interferon beta-1b in secondary progressive multiple sclerosis was published. In a multicenter, double-blind, randomized, placebo-controlled study 718 patients with secondary progressive multiple sclerosis and an expanded disability status scale (EDSS) value between 3.0 and 6.5 were treated with either 8 Mio. interferon beta-1b or placebo subcutaneously every second day for two to three years. The primary study end-point was the time until confirmed progression of the disease as signified by a one point increase of the EDSS value (for initial EDSS values between 3.0 and 5.5) or 0.5 point increase when the initial EDSS value was between 6.0 and 6.5. After two years an interim analysis showed a highly significant difference in delay of disease progression by nine to twelve months for the treatment group (p=0.0008). This means that interferon beta-1b is the first recombinant beta-interferon to be shown effective in the treatment of secondary progressive multiple sclerosis.
    Notes: Zusammenfassung Bei der schubförmigen multiplen Sklerose ist der positive Einfluß der Betainterferone auf die Häufigkeit und Schwere der Schübe durch mehrere Phase-III-Studien überzeugend belegt. Vor kurzem wurde die erste große Studie zur Wirksamkeit von Interferon beta-1b bei sekundär chronisch progredientem Krankheitsverlauf publiziert. In einer multizentrischen, doppelblinden, randomisierten, placebokontrollierten Studie wurden insgesamt 718 Patienten mit sekundär chronisch progredienter multipler Sklerose und einem EDSS (“expanded disability status scale”) zwischen 3,0 und 6,5 Punkten mit entweder 8 Mio. IE Interferon beta-1b oder Placebo jeden zweiten Tag subkutan behandelt und über zwei bis drei Jahre beobachtet. Primärer Studienendpunkt war die Zeit bis zum Erreichen einer anhaltenden Krankheitsprogression im Sinne einer EDSS Verschlechterung um einen Punkt (bei einem Ausgangs EDSS von 3,0–5,5) bzw. 0,5 Punkten bei einem Ausgangs EDSS von 6,0–6,5 Punkten. Bereits bei der im Protokoll vorgesehenen 2-Jahres-Zwischenauswertung bestand ein hochsignifikanter Unterschied zugunsten der behandelten Gruppe (p=0.0008) im Sinne einer Verzögerung der Progression um neun bis zwölf Monate nach zwei bis drei Behandlungsjahren. Somit ist Interferon beta-1b das erste bei sekundär chronisch progredienter multipler Sklerose als wirksam belegte rekombinante Betainterferon.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1459
    Keywords: Multiple sclerosis ; HTLV-I ; Polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary DNAs from peripheral blood mononuclear cells (PBMCs) of 21 patients with multiple sclerosis (MS), 1 patient with tropical spastic paraparesis (TSP) as well as DNAs from brain and spinal cord of 5 MS cases and 3 controls were examined for human T-cell lymphotropic virus (HTLV)-related sequences by polymerase chain reaction. The primers used were derived from the HTLV-I gag, env and tax genes. Amplified products were separated on agarose gels, blotted onto nylon membranes and hybridized to specific radiolabelled oligonucleotides. The sensitivity of amplification and hybridization was one copy of target DNA in 105 cellular genomes. None of the specimens was positive for HTLV-I sequences except the TSP probe. These negative data are all the more significant because brain material from MS patients was used in these studies. Our studies thus fail to support speculations that HTLV-I is involved in the aetiology of multiple sclerosis.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0165-1781
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0165-1781
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1920
    Keywords: Multiple sclerosis ; Magnetic resonance imaging ; Brain ; Gadolinium ; Database
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The unique sensitivity of magnetic resonance imaging (MRI) in detecting disease activity in multiple sclerosis (MS) and the objective nature of the information obtained suggest that MRI will be a useful and reliable way of monitoring treatment trials. There is a need to develop an appropriate database which would provide a standardised means of assessment, not only of MRI, but also of essential clinical information. As part of the program of Concerted Action in Multiple Sclerosis, funded by the Commission of the European Community (CEC), we have developed a database for recording serial brain MRI results. The database consists of core, entry and follow-up sections. Both entry and follow-up parts are subdivided into clinical, MR system and MRI data. We expect that the use of this database will maximise efficiency of MRI monitoring in MS treatment trials, particularly in multicentre studies.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1920
    Keywords: Magnetic resonance imaging ; Quantification ; Multiple sclerosis ; Treatment ; Evaluation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Magnetic resonance scans of 74 patients with multiple sclerosis participating in a controlled trial were compared 6 months before and at the end of a 24–32 months-treatment period with either Cyclosporin A (n=31) or Azathioprine (n=43). Both qualitative rating and computation of lesion volume showed deterioration in more than 40% of the patients, while by clinical criteria only 10–30% were worse. No significant difference was noted when the two treatment groups were compared. If careful repositioning and standardized image parameters are used, MRI is an indispensable tool for the objective determination of disease progression in MS although it cannot replace clinical examination.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1459
    Keywords: Multiple sclerosis ; Human retroviruses ; HIV ; HTLV-I ; Virus-specific antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A total of 135 sera and 18 cerebrospinal fluid (CSF) samples from patients with multiple sclerosis (MS) were screened for antibodies to human T-cell lymphotropic virus type I(HTLV-I) and human immunodeficiency virus (HIV) by ELISA tests. None of the sera or CSF reacted with HIV antigens. Only 3 out of 135 MS sera but no MS CSF showed increased reactions in the ELISA test for HTLV-I. However, these positive reactions were classified as non-specific by immunoprecipitation. Thus no serological evidence for infection with HIV, HTLV-I, or a related retrovirus was found in the MS patients.
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  • 10
    ISSN: 1432-1459
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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