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  • 1
    ISSN: 1432-0584
    Keywords: malignes Melanom ; hochdosiertes Mustargen (HN2) ; autologe Knochenmarkstransplantation ; Malignant melanoma ; High-dose nitrogen mustard (HN2) ; Autologous bone marrow transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In a Phase I trial patients with advanced malignant melanoma were treated with high-dose nitrogen mustard (HN2) and autologous bone marrow transplantation. Three patients were entered into the protocol. After procurement of 1.1–5.5×105 committed stem cells (CFU-C) per kg body wt, 33 mg/m2 of HN2 was administered i.v. as a bolus. Forty-eight hours later the noncryopreserved bone marrow was reinfused i.v. Side effects consisted of nausea, vomiting, anorexia, alopecia, phlebitis, hepatotoxicity, and neurotoxicity. Cardiotoxicity and hypocalcemia were encountered as unanticipated side effects not described so far by using lower dosages of HN2. Granulocytopenia of less than 1.0×109/l and thrombocytopenia of less than 50.0×109/l lasted for a mean of 10 and 8 days, respectively. Measureable disease present in two of three patients did not respond to the dose of HN2 used in this protocol. This study shows that hematologic recovery was shorter than previously reported in studies using HN2 without autologous bone marrow transplantation. The nonhematologic side effects of this dose of HN2, however, were severe and preclude the use of higher doses.
    Notes: Zusammenfassung Wir berichten über eine Phase-I-Studie, in der drei Patienten mit fortgeschrittenem malignem Melanom mit Mustargen (HN2) in hoher Dosierung und autologer Knochenmarkstransplantation behandelt wurden. Nach der Entnahme von 1,1–5,5×105 determinierten Stammzellen (CFU-C) pro Kilogramm Körpergewicht wurden 33 mg/m2 HN2 i.v. injiziert. Achtundvierzig Stunden später wurde das Knochenmark transfundiert. Die Nebenwirkungen bestanden aus Erbrechen, übelkeit, Appetitlosigkeit, Haarausfall, Venenentzündung, Leber- und Nerventoxizität. Beeinträchtigung der Herzfunktion und Hypokalzämie waren unerwartete Nebenwirkungen, die bisher bei der üblichen Dosierung von HN2 nicht beschrieben worden sind. Granulopenie von weniger als 1,0×109/l dauerte 10 Tage, Thrombopenie von weniger als 50,0×109/l 8 Tage. Die me\baren Metastasen von zwei Patienten sprachen auf die Behandlung nicht an. Diese Studie zeigt anhand eines historischen Vergleichs, da\ die Erholung der Knochenmarksfunktion durch die Verwendung von autologem Knochenmark beschleunigt wurde, da\ aber die schweren, nichthämologischen Nebenwirkungen eine weitere Dosissteigerung von HN2 ausschlie\en.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Self-Infusion ; Primates ; Secobarbital ; Chlordiazepoxide ; Choice Procedure ; Preference ; Multiple Addiction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Monkeys were exposed to a 24 h continuous experimental procedure which provided a periodic forced choice between the self-infusion of secobarbital versus saline. Preference for secobarbital over saline was readily obtained using choice trials programmed approximately every 2 h at a dose of 9 mg/kg of secobarbital per infusion. Preference for self-infusion of chlordiazepoxide over saline was obtained using choice trials every 3 h, and a dose on the order of 1 mg/kg per infusion. In a subsequent experiment, two of the animals addicted to chlordiazepoxide were given a choice every 3 h between an infusion of chlordiazepoxide or secobarbital. Following a period of intake of both drugs, a gradual shift in preference from chlordiazepoxide to secobarbital was observed over a period of some 60 days. In general, this preference procedure provides a flexible technique with several dependent measures for single or multiple drug addiction studies.
    Type of Medium: Electronic Resource
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