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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 23 (1989), S. 63-67 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The role of chemotherapy in the treatment of retinoblastoma (RB) is unsatisfactory and clinical research is severely limited. A xenograft model for testing chemotherapeutic and other atents has been developed by the heterotransplantation of human RB cells into the anterior chamber of the nude mouse eye. A grading system for visually monitored tumor growth was designed to allow serial observations and documentation of the response to therapy in the model. This method of monitoring compared favorably with histopathologic, photographic, or other criteria in the reproducible, sequential evaluation of tumor status. Six chemotherapeutic agents [vincristine (VCR), doxorubicin (DOX), actinomycin D (ACT-D), dimethyltriazeno-imidazole carboxamide (DTIC), cyclosphosphamide (CMP), and diaziquone (AZQ)] were then tested in the model against a patient-derived xenograft line. Results were expressed as the delay in tumor progression judged by serial grading. CPM produced a consistent response in all treated tumors, as did DTIC to a lesser, more variable extent. In 3 of 10 tumors treated with CPM and in 1 of 18 treated with DTIC, complete responses were maintained for at least 20 weeks. VCR, DOX, and ACT-D were ineffective, producing patterns of tumor progression no different from those in the control group. AZQ was most effective, producing responses far exceeding those of conventional agents. The model allows quantitative documentation of the response to therapy in heterotransplanted human RB. Further testing of new agents and combinations is warranted. AZQ may be active against RB.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1437-7780
    Keywords: therapeutic drug monitoring ; pharmacokinetics ; teicoplanin ; glycopeptide ; clinical trials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty-five published clinical studies were reviewed in which teicoplanin serum concentrations were determined. A variety of assay methods were used, including bioassay, solid phase enzyme receptor assay, HPLC and immunoassay, and in some studies, more than 1 methodology was used. Fourteen studies gave sufficient data on the method of assay, timing of assays relative to dosage or during therapy, and route of administration of teicoplanin to be included in a detailed pharmacokinetic analysis. Since a wide range of dosing regimens were employed, the studies were grouped in order to facilitate analysis according to the teicoplanin maintenance dose, either 200 mg, 400 mg or 6 mg/kg/day. Six studies used a dose of 200 mg/day and although the mean trough concentrations varied by as much as 3-fold, they did not exceed 10 mg/L in the first 7 days of therapy. Six studies used a 400 mg/day maintenance dose and the mean trough concentrations varied from 4 to 11 mg/L on days 1–2, to 9 to 17 mg/L on days 6–7 of therapy. In 5 of these studies, the mean trough concentration was less than 10 mg/L for the first 48 hours of treatment. In 2 studies where a dose of 6 mg/kg/day was used, the mean concentrations did not exceed 10 mg/L until day 7, while in the other study they were greater than 10 mg/L beginning on day 1. A retrospective analysis of 58 clinical cases reported in the literature, 42 of whom had staphylococcal infections, indicated that serum concentrations and teicoplanin concentration/MIC ratios were related to clinical cure particularly for patients with staphylococcal infections. Trough concentrations of greater than 10 mg/L were related to favorable outcomes when all 58 patients were analyzed and trough concentrations of greater than 20 mg/L were related to cure for those who had staphylococcal infections. While retrospective in nature, this review indicates that there is considerable variation in teicoplanin pharmacokinetics in the different patient groups, only some of which is related to differences in dosing, timing of blood collection for assay or assay methodology. In addition, these data suggest that pharmacokinetic parameters such as trough and postdose teicoplanin concentrations, and phamracodynamic factors such as serum concentration MIC ratios may be related to clinical outcome with teicoplanin therapy.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-0832
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Various antisera raised either to antigens ofCandida albicans or to sub-lethal infections of blastospores (convalescent sera) were tested for their efficacy in diagnosing systemic disease in artifically infected animals. Globulin from convalescent serum, when conjugated with alkaline phosphatase and used in enzyme-linked immunosorbent assays (ELISA), was the only antiserum type which detected circulatingCandida-related antigen in the serum of infected animals. Conjugates made from anti-mannan, anti-blastospore or antimycelial globulin did not detect antigen. Mannan did not appear to be related to an antigen produced in sera of experimentally infected mice. The significance of these results in the diagnosis of systemic candidosis is discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Young children with malignant brain tumours have particularly poor survival and manifest severe sequelae of radiation therapy. A multi-institutional pilot study of post-operative primary chemotherapy for children under 3 years with primitive neuroectodermal tumours (PNET) or ependymoma was initiated in 1987. The chemotherapy protocol comprised earboplatin, vincristine and the “eight drugs in 1 day” regimen. Radiation was recommended only if tumour progression or recurrence was documented. A total of 14 patients between 5 and 36 months of age were enrolled. Seven had supratentorial tumours (PNET, pinealoblastoma, intracranial retinoblastoma) with multiple predictors of adverse outcome. Four of these responded to initial chemotherapy but subsequently progressed and all had died by 16 months from diagnosis. The seven patients with infratentorial tumours (three medulloblastomas, four ependymomas) had more favourable predictors of outcome: no meningeal dissemination and gross macroscopic resection in six of the seven cases. One patient progressed rapidly and died within 5 months. The other six are alive at 37–57 months from diagnosis. Four are in continuous complete remission at 57, 51, 41 and 37 months, respectively from the time of their tumour resection. One is described as having stable disease with a persistent radiographic lesion at 41 months from diagnosis. One has relapsed on two occasions and is the only surviving patient to have been irradiated. Intelligence scores for the six long-term survivors have thus for remained within the normal range. It is suggested that some infants with standard-risk ependymoma and, possibly, medulloblastoma may be cured without radiation therapy.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7373
    Keywords: brain ; tumor ; xenograft ; chemotherapy ; cyclophosphamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Chemotherapy for brain tumors remains unsatisfactory. Despite increasing participation in clinical trials, there is a clear need for pre-clinical models. Heterotransplantation of surgical specimens directly into the anterior chamber of the nude mouse eye has been demonstrated to produce evaluable xenografts. Drug access in this model is considered to mimic the blood-brain barrier. Five clinical specimens in 3 children with primitive neuroectodermal tumor/medulloblastoma were the sources of 293 intraocular xenografts (5 cohorts by source). Each tumor-bearing mouse received 1 of 5 drugs or normal saline, by intraperitoneal injection, weekly for 5 weeks. Response was monitored for up to 22 weeks, using a staging system which estimates the proportion of the anterior chamber filled by tumor. Results were analysed both as response rates (shrinkage in excess of 50%) at the conclusion of the treatment course and as time to tumor progression by the life table method. Comparison of response rates within cohorts by source of xenografts (exact chi-square test for overall and 2-sided Fisher's exact test for paired comparisons) indicated cyclophosphamide to be the most effective single agent. In logrank analyses cyclophosphamide achieved significantly longer delays to progression than all other drugs in one cohort and longer delays than all but diaziquone in 2 other cohorts. The intraocular xenograft model is a clinically relevant system for the study of therapeutic agents in brain tumors. The effectiveness of intensive dosage cyclophosphamide in a model dependent on access across the blood-aqueous barrier is important and consistent with recent clinical data.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-0832
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Candida albicans strain 22114 was avirulent for mice compared with strain 19321 in that, administered intravenously, 106 blastospores of 22114 failed to kill whereas 106 blastospores of 19321 produced 100% mortality. Cortisone treatment rendered mice susceptible to killing by 22114. Chitin assay showed that cortisone stimulated the growth of both strains in the mouse kidney. Growth of 19321 was increased up to five-fold and 22114 up to forty-fold. The strains may have differential susceptibility to cortisone-sensitive host defences which control fungal growth in vivo.
    Type of Medium: Electronic Resource
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