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  • AraC  (2)
  • Fungal infection  (2)
  • Autoimmune disorders  (1)
  • 1
    ISSN: 1432-1440
    Keywords: Parasitological serodiagnosis ; Specificity ; Autoimmune disorders ; Neoplasms ; HIV infection ; AIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sera from 120 patients with rheumatological disorders, neoplastic disease, infectious mononucleosis, and HIV infection, and from 30 healthy blood donors were tested for nonspecific reactivity in 13 routinely used parasite serological tests. Responses were detected in 3/30 healthy blood donors (10%) vs 25/120 patients (21%). Of 40 responses in these 28 responders most were weakly reactive, and 25 out of 40 responses were only at borderline level. Response rates were highest in patients with mononucleosis presumably due to heterophile antibodies. Only four patients had responses in at least two different serodiagnostic tests for the same parasitic infection. Response patterns indicative of a possible underlying, concurring, or superimposed parasitic infection, thus, were rare. Especially susceptible to nonspecific reactivity seemed to be immunofluorescent antibody tests for filariasis, schistosomiasis, and amebiasis. In conclusion, compared to healthy controls, false-positive serological responses seem to be more frequent in certain disease groups dependent on the test methods used. Second, the use of more than one serodiagnostic test for the same parasitic disease will substantially facilitate the identification of nonspecific reactivity. Third, for better defining the specificity of parasitological serodiagnosis, more studies should include control sera from patients with nonparasitic diseases that frequently show immunological abnormalities.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Key words Cytarabine ocfosfate ; AraC ; CLL ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cytarabine ocfosfate (YNK01) is a novel orally applicable prodrug of cytosine arabinoside. Recent pharmacokinetic studies have revealed a prolonged release of the cytotoxic agent cytosine arabinoside (araC) from hepatocytes into the systemic circulation, resulting in a half-life of approximately 24 h for araC. The specific pharmacokinetic characteristics of cytarabine ocfosfate lead to a prolonged exposure of leukemic cells to this antineoplastic agent during the 14-day cycle. The oral applicability during outpatient treatment and the sustained antineoplastic activity of araC against slowly proliferating leukemic B-cells suggest that cytarabine ocfosfate might be a useful drug in the treatment of chronic lymphocytic leukemia. Four years after diagnosis of B-CLL, a 50-year-old patient was started on cytarabine ocfosfate. Sequentially, the patient's disease had proved refractory to treatment with chlorambucil/prednisone (31 months), fludarabine (5 months), and prednimustine/mitoxantrone (3 months). These established regimens were discontinued because of increasing lymphocytosis, significant thrombocytopenia, and progressive B-symptoms. Following three cycles of cytarabine ocfosfate B-symptoms resolved, lymphadenopathy disappeared, and thrombocytopenia was significantly reduced. The patient has been free of these symptoms on a dosage of 1500 mg cytarabine ocfosfate/day (cycle of 14 days with intervals of 14–21 days) for 24 months and remains in an ongoing partial remission.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0584
    Keywords: Fungal infection ; Bone marrow transplantation ; Amphotericin B inhalations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The incidence of invasive fungal infections after bone marrow transplantation (BMT) was analyzed in 303 consecutive marrow graft recipients (allogeneicn=271, autologousn=27, syngeneicn=5). All patients received inhalations with amphotericin B (10 mg twice daily) during neutropenia. The overall incidence of invasive fungal infections within the first 120 days after transplant was 3.6% (11/303; aspergillosis: 6; yeast infection: 5). Four of the 11 cases occurred early, and seven cases were observed after neutrophil recovery and discontinuation of amphotericin B inhalation treatment. Late infection was significantly associated with the development of acute graft-versus-host disease. Four of the 11 infections (early 2/4; late: 2/7) were observed in patients with a history of previous fungal infection. Other patient and treatment characteristics were not helpful in defining potential risk factors. In particular, the incidence of invasive fungal infections did not differ between patients with more or less strict reverse isolation measures. Occasional side effects such as initial mild cough and bad taste were rare, usually disappeared during continued administration, and were in no case the reason for discontinuation of treatment. These data suggest that aerosolized amphotericin B may be a useful, convenient, and efficient prophylactic antifungal regimen in BMT.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0584
    Keywords: Key words Aspergillosis ; Fungal infection ; Acute myeloid leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Systemic aspergillosis is a well-recognized complication of chemotherapy-induced neutropenia. In this report a patient with acute myeloid leukemia is described in whom a chronic aspergillosis with systemic involvement developed after recovery from neutropenia following intensive chemotherapy and allogeneic bone marrow transplantation. The clinical features of a chronic course of systemic aspergillosis suggest a distinct clinical entity comparable to chronic systemic candidiasis.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0584
    Keywords: Key words Cytidine deaminase ; AraC ; AML ; Pharmacokinetics ; Pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The clinical effects of cytosine arabinoside (AraC) are highly dependent on schedule and dose. Many regimens administered to patients are derived from artificial model systems involving permanent leukemic cell lines. The differences in pharmacokinetics between the in vivo situation and such cell lines are largely neglected. However, cytidine deaminase activity in particular has a major impact on AraC pharmacokinetics by degrading AraC to its inactive metabolite AraU, and it has been shown to be of prognostic relevance in the treatment of acute myeloid leukemia. This study therefore investigated cytidine deaminase activities and AraC deamination in a variety of the most commonly used leukemic cell lines and fresh blasts and their impact on the results of an in vitro model system. It was found that cells from different cell lines (BLIN, CEM, HL60, K562, RAJI, REH, U937) vary greatly in cytidine deaminase activity (e.g., 1.89 nmol per min/mg in K562 versus 0.01 in BLIN cells) and degrade between 18.5 (BLIN) and 96.5% (REH) of AraC to AraU in the incubation medium. This degradation results in highly different AraC exposures for different cells (e.g., AUC of 960 ng per h/ml in REH versus 4048 ng per h/ml in BLIN cells) in spite of identical starting concentrations of the drug. Formation of AraCTP as the main cytotoxic metabolite of AraC is significantly influenced by the differences in cell type-dependent cytidine deaminase activity (e.g., 35.6 ng/107 cells in REH versus 180.2 ng/107 cells in BLIN cells). In contrast to permanent cell lines, fresh leukemic blasts and normal bone marrow mononuclear cells featured low AraC degradation in the model system.
    Type of Medium: Electronic Resource
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