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  • 1
    ISSN: 1569-8041
    Keywords: breast cancer ; cardiotoxicity ; cyclophosphamide ; epirubicin ; high dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To prospectively evaluate the long term cardiac effects of high-dose epirubicin and cyclophosphamide given to women with early stage, poor prognosis breast cancer. Patients and methods: Women with stage 2 breast cancer and 10+ nodes or 4+ nodes and estrogen receptor negative tumor, or stage 3 breast cancer received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 gm/m2 with peripheral blood progenitor cell and filgrastim support. Treatment was given every 28 days (n = 79) or 21 days (n = 20). Fifty patients received radiotherapy to the chest wall or breast, 25 of to the left side. Patients were assessed clinically regularly during chemotherapy and at least three times yearly after completion of treatment. Cardiac left ventricular ejection fraction (LVEF) was assessed by radionuclide scan before therapy, after each cycle of chemotherapy, three months and six months after completion of chemotherapy, and yearly thereafter until relapse. Results: Ninety-nine women were treated, and 92 completed all three cycles of chemotherapy. The median age was 43 years (range 24 to 60 years). All patients were included in this analysis. The median relapse-free survival was 39 months (11 to 68 months). There was a significant fall in LVEF during chemotherapy. In general, there was no further deterioration in cardiac function from the third month after cessation of treatment, however there was substantial variation between individuals. 35 patients had at least one LVEF measure less than normal (〈50%), but the LVEF returned to normal in 20 of these with further follow-up. Cardiac dysfunction was not increased in women who received radiotherapy and was not different between cohorts given chemotherapy every three or every four weeks. One patient died of acute myocardial necrosis following the third cycle of chemotherapy. Two patients developed clinical evidence of cardiac failure, and another had radiological signs but was asymptomatic. One woman died of progressive cardiac failure, one recovered clinically but also developed recurrent breast cancer, while the third recovered after commencement of medical therapy. Conclusions: During follow-up after high-dose epirubicin and cyclophosphamide as delivered in this study, the LVEF fell to below normal in approximately one third of patients. However, in over half of these patients the LVEF subsequently recovered to the normal range, and the incidence of clinically evident chronic cardiac failure was low. Further follow-up is required to assess the long- term safety. A randomized comparison with standard-dose anthracycline-based chemotherapy is needed to determine whether this regimen is associated with an increased risk of clinical cardiac toxicity.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Plant and soil 66 (1982), S. 81-89 
    ISSN: 1573-5036
    Keywords: Extractable organic matter ; N availability index ; Organic matter ; Organic N ; Soil storage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The effect was studied of storage temperature on the index of available soil N wich uses U.V. absorbance of a 0.01M NaHCO3 extract as an indicator. The U.V. absorbance was found to increase at a non-linear rate for four soils stored at temperatures of 50, 75, and 150°C. The change in extract absorbance due to extended soil storage at each of these temperatures was positively correlated to the percent organic matter, percent N, C/N value and concentration of humic substances in soils, but not to the extract absorbance prior to soil storage. These findings were not consistent with room temperature storage data which showed a linear increase in extract absorbance with soil storage time. The change in absorbance for the room temperature case was not related to any of the soil parameters mentioned above. Analysis of a soil stored at 105°C showed an increase in ninhydrin-detectable N, protein N and Kjeldahl N of the NaHCO3 extract, while the apparent molecular weight distribution of extracted organic matter (as determined by gel filtration) showed only a slight change. As a comparison to the NaHCO3 extract, a boiling CaCl2 extract of the same soil was also analyzed; and the absorbance at 260 nm was found to increase in a curvilinear fashion with starage time at 75°C but to less of an extent than was noted with the NaHCO3 extract. Nitrogen availability indexes based on the U.V. absorbance of these extracts, particularly those utilizing the NaHCO3 extract, would be significantly affected by soil storage at elevated temperatures.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Plant and soil 64 (1982), S. 331-341 
    ISSN: 1573-5036
    Keywords: Humic substances ; Molecular weight distribution ; N availability index ; Ninhydrindetectable N ; Relative N uptake ; Soil proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Two soil extracts used for chemical indexes for N availability, 0.01M NaHCO3 and boiling 0.01M CaCl2, were analyzed in effort to learn more about the nature of the extracted organic matter (O.M.). The two extracts appeared to remove different fractions of the soil O.M. A study of five soils showed that the C/N value of the NaHCO3 extract (following decarbonation) was significantly higher than that of the total soil O.M.; while the C/N value in the boiling CaCl2 extract was not significantly different from that in the soil O.M. There was also significant variation in C/N values among soils for the boiling CaCl2 extract. The extracts of three soils were analyzed for apparent molecular weight distribution using gel filtration and the results compared to those for base-extracted humic substances. Almost all the molecules in the extracts had apparent molecular weights less than 21,000 daltons while 21 to 47% of the humic substances from the same soils (extracted with 0.5M NaOH) had molecular weights greater than 21,000 daltons. In the boiling CaCl2 extract, 78 to 87% of the humic substances had apparent molecular weights less than 1,000 daltons, whereas with the NaHCO3 extract, 42 to 83% of the humic substances were in the 1,000 to 21,000 dalton range. Forty-three to 92% of the N extracted by the NaHCO3 was in protein form, and 8 to 30% was ninhydrin-detectable. In the boiling CaCl2 extract 25 to 30% of the extracted N was ninhydrin-detectable. For the same 10 soils, ninhydrin-detectable N values of the boiling CaCl2 extract appeared closely related to greenhouse and field relative N uptake, while the ninhydrin-detectable N values of the NaHCO3 extract appeared unrelated to both. The protein N and protein in plus ninhydrin-detectable N values of the NaHCO3 extract were closely related to greenhouse relative N uptake only. The results of this study indicated that specific fractions of the soil O.M. were being extracted by the two solutions and that significant differences existed in the chemical nature of the two extracts.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1569-8041
    Keywords: cyclophosphamide ; dose-escalation ; epirubicin ; filgrastim ; G-CSF ; non-Hodgkin's lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: To define a maximum tolerated dose (MTD) for the combination of epirubicin and cyclophosphamide with filgrastim (r-met-HuG-CSF) in patients with advanced solid tumors and non-Hodgkin's lymphoma (NHL). Patients and methods: Thirty-five patients with advanced solid tumors were enrolled in stages I and II. Twenty-one patients were treated in stage I in sequential cohorts of at least three patients at increasing dosage levels of cyclophosphamide and epirubicin, for up to six cycles every 21 days. At the completion of stage I, a MTD for epirubicin was established. Fourteen patients were treated in stage II, in cohorts of three or more. The epirubicin dose remained constant at the MTD dosage from stage I. Cyclophosphamide was further dose-escalated to establish its MTD. Twenty-one patients with previously untreated non-Hodgkin's lymphoma were treated in stage III with the MTD established in the prior stages. Results: The MTD in stage I was epirubicin 150 mg/m2 and cyclophosphamide 1500 mg/m2 with cumulative neutropenia as the dose-limiting toxicity (DLT). Cumulative thrombocytopenia prevented further dose-escalation of cyclophosphamide in stage II. The stage III regimen consisted of six, 21-day cycles of epirubicin 150 mg/m2, cyclophosphamide 1500 mg/m2, vincristine 2 mg, and prednisolone 100 mg for five days with filgrastim support. Nineteen of twenty-one patients (90%) completed six cycles of treatment, eight (38%) without dose reduction. Common toxicity criteria (CTC) grade 4 neutropenia (neutrophil nadir 〈0.5 × 109/l) was documented in 85 of 118 cycles (72%). Neutropenic fever was documented in 17 of 21 patients (81%) on at least one occasion. Severe thrombocytopenia (〈25 × 109/l) was seen in fourteen of 118 cycles (12%) and increased with cycle number. There was no significant non-hematological toxicity. Conclusion: Significant dose-escalation of epirubicin and cyclophosphamide was possible with filgrastim support. The MTD achieved was approximately double that of standard-dose therapy. This study forms the basis of an ongoing randomized study evaluating dose-intensification in intermediate grade NHL.
    Type of Medium: Electronic Resource
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