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  • 1
    ISSN: 1432-1440
    Keywords: Immunoglobulin-containing cells ; Cerebrospinal fluid ; Immunocytochemistry ; Inflammatory diseases ; HIV-encephalitis ; Multiple sclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An immunocytochemical technique allowing repeated use of antisera is applied to identify immunoglobulin-containing cells (ICC) of the IgG, IgA, and IgM class in the cerebrospinal fluid (CSF) of 298 patients with various neurological disorders. The demonstration of ICC in the CSF is highly indicative of an inflammatory disease (p〈0.0001; Chi-square test). In the group of noninflammatory disorders ICC are only found in three cases of lymphomas, two dysgerminomas, and one glioblastoma. ICC of all classes are seen in acute viral and bacterial infections of the CNS including tick-borne meningopolyneuritis Bannwarth. IgG-positive ICC predominate in chronic inflammatory disorders like multiple sclerosis and HIV encephalitis. In HIV-positive patients IgA-or IgM-positive cells are strongly indicative of an opportunistic infection of the brain. Persistent high levels of ICC in three patients with bacterial meningitis are associated with a fatal outcome.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 187 (1992), S. 51-57 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 187 (1992), S. 51-57 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1433-0407
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Tumor-necrosis factor ; Genetic polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor necrosis factor-α (TNFα) is a pluripotent proinflammatory cytokine and is thought to play an important role in the inflammatory process of multiple sclerosis (MS). A G→A transition in the TNFα promotor at position –308 (TNF2 allele) has been shown to be associated with increased TNFα production. This study was designed to detect wether the TNF2 allele is associated with disease progression in MS. We examined the TNFα–308 polymorphism with an allelic discrimination PCR to detect the G→A transition in the genomic DNA of 283 MS patients from Germany and in 72 patients with amyotrophic lateral sclerosis (ALS) and 66 with stroke from the same genetic background who served as controls. Disease severity was defined by the progression index (PI) and by progression to the important clinical landmarks of Extended Disability Status Score (EDSS) 3.5 and 6. In addition, we evaluated the TNFα mRNA expression in whole blood with quantitative PCR. No differences were found between the presence of the TNF2 allele in MS, ALS, or stroke patients. Among the MS patients the TNF2 allele was not associated with a certain disease course. No association was found between the accumulation of neurological deficits and progression to clinical landmarks. Although MS patients with the TNF2 allele tended to progress more rapidly from EDSS 3.5 to EDSS 6 this difference was nonsignificant (P = 0.2). Nevertheless, we observed significantly higher TNFα mRNA expression in blood cells of stable patients carrying the TNF2-allele in comparison to the group with the wild type (P = 0.024). To examine the effect of genetic background we examined the DNA of 60 MS patients and 20 healthy controls in a Cypriot population of Greek origin. There was a significantly lower frequency of the TNF2 allele in the Cyprus population than in Germans (P = 0.01). No significant differences were found between the frequencies of the TNF2 allele in Cypriot MS patients and controls. Although the TNF2 allele is associated with higher TNFα mRNA baseline levels, our data indicate that this allele appears not to contribute to MS susceptibility or severity. In addition our data demonstrate that the TNFα–308 polymorphism is segregated differentially in two European populations of different genetic origin.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Der Internist 40 (1999), S. 119-125 
    ISSN: 1432-1289
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Die Behandlung der Multiplen Sklerose hat durch die Einführung von Interferonen in der letzten Zeit eine interessante und erfolgreiche Bereicherung erfahren. Mit den neuen, rekombinanten Beta-Interferon Präparaten ist die Therapie der schubförmigen multiplen Sklerose deutlich verbessert worden. Alle drei großen Therapie-Studien (Betaferon®/Schering, Avonex™/ Biogen und Rebif®/Serono) haben übereinstimmend gezeigt, daß dieses immunmodulatorische Therapiekonzept in der klinischen Anwendung sinnvoll ist. Der folgende Beitrag will den aktuellen Stand der Studienergebnisse berichten und die vermuteten Wirkmechanismen in das pathogenetische Modell dieser häufigsten chronisch entzündlichen Erkrankung (Tabelle 1) des zentralen Nervensystems einordnen. Die Arbeit liefert wichtige Fakten und Hinweise zur Indikationsstellung und Handhabung. Da es zwischen der Inneren Medizin und der Neurologie enge Berührungspunkte gibt, und auch die Therapie mit Interferonen natürlich in der Inneren Medizin große Bedeutung erlangt hat, ist eine Darstellung dieses modernen und eindrucksvollen Themas für den Leserkreis von Der Internist durchaus von übergeordneten Interesse.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Multiple Sklerose ; Therapie ; Immunsuppression ; Eskalierende Immuntherapie ; Mitoxantron ; Key words Multiple sclerosis ; Treatment ; Immunosuppression ; Rescue therapy ; Mitoxantrone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Mitoxantrone is an anthracenedione antineoplastic agent that has recently been shown to be effective in ameliorating disease activity in multiple sclerosis (MS) as indicated by clinical and MRI data. However, the role of mitoxantrone in escalating treatment of patients with frequent and severe relapses and with rapid progression of disability is less clear. In this retrospective analysis we report on 15 patients with severe relapsing-remitting (9 patients) and secondary progressive MS with superimposed exacerbations (6 patients) treated openlabeled with mitoxantrone in our Clinical Research Group from July 1994 to October 1998. Eleven of these patients (73%) were treated with azathioprine, interferon-beta-1b or cyclophosphamide before. The patients received mitoxantrone over a period of at least 12 months (19±6 months) with a single dose of 10 mg/m2 monthly for the first three months. Thereafter, infusions were repeated every 3 months (total dose 141 mg±45 mg). The annual relapse rate could be significantly reduced from 3,0±1,5 in the year before therapy to 0,5±0,5 during therapy. Nine patients (60%) were stabilised, while four patients (27%) showed an improvement of disability. The treatment was well tolerated with only minor side effects. These results although retrospectively obtained confirm previous trials showing that mitoxantrone may be useful in MS patients with frequent and severe exacerbations and/or a rapidly progressive course of the disease who have had other immunomodulatory medication.
    Notes: Zusammenfassung Schwer verlaufende Formen der multiplen Sklerose (MS) mit mehreren Schüben pro Jahr und inkompletter Remission oder mit rasch progredientem Verlauf und drohendem Verlust der Gehfähigkeit erfordern den Einsatz intensiver immuntherapeutischer Maßnahmen. Die Wirksamkeit von Mitoxantron bei der MS konnte in kontrollierten Studien nachgewiesen werden, doch besteht nach wie vor Unklarheit über den Stellenwert dieser Substanz im Rahmen einer eskalierenden MS-Therapie. Im Zeitraum von Juli 1994 bis Oktober 1998 wurden in der Klinischen Forschungsgruppe für Multiple Sklerose und Neuroimmunologie von etwa 1300 Patienten/Jahr 50 Patienten mit schwerem schubförmigem oder sekundär chronisch-progredientem Verlauf und überlagerten Schüben mit Mitoxantron behandelt. Fünfzehn dieser Patienten (9 Patienten mit schubförmigem und 6 Patienten mit sekundär chronisch-progredientem Verlauf) mit einer Therapiedauer von mindestens 12 Monaten wurden retrospektiv analysiert. Elf dieser Patienten (73%) hatten eine immunsuppressive Vorbehandlung mit Azathioprin, Interferon-beta-1b bzw. Cyclophosphamid. Über einen mittleren Zeitraum von 19±6 Monaten wurde Mitoxantron in einer Dosierung von 10 mg/m2 Körperoberfläche zunächst in vierwöchentlichen, dann in dreimonatlichen Abständen (mittlere Gesamtdosis 141±45 mg) gegeben. Unter dieser Therapie konnte die jährliche Schubrate signifikant von 3,0±1,5 im Jahr vor Therapiebeginn auf 0,5±0,5 Schübe/Jahr unter Therapie gesenkt werden. Neun (60%) der Patienten waren gemessen an der EDSS stabil, 4 (27%) verbesserten sich unter der Behandlung. Die Therapie wurde bis auf leichtere Nebenwirkungen, vorwiegend Übelkeit und Erbrechen, im allgemeinen gut vertragen. Diese Therapiebeobachtungen entsprechen dem in kontrollierten prospektiven Studien beobachteten positiven Effekt von Mitoxantron. Diese Behandlungsform kann im Sinne einer eskalierenden Immuntherapie bei schwer verlaufender MS und nach Versagen anderer immunmodulatorischer Maßnahmen erfolgreich eingesetzt werden.
    Type of Medium: Electronic Resource
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