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  • 11
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    Chicago : Periodicals Archive Online (PAO)
    Chicago review. 16:2 (1963:Summer) 74 
    Library Location Call Number Volume/Issue/Year Availability
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  • 12
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    Chicago : Periodicals Archive Online (PAO)
    Chicago review. 17:1 (1964) 136 
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  • 13
    ISSN: 1432-0843
    Keywords: Key words Encephalopathy ; Hepsulfam ; Acute leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Hepsulfam is a bisulfamic ester which is similar in structure to busulfan and is believed to act as a bifunctional alkylator inducing both DNA–DNA and DNA–protein crosslinks. Prior studies in patients with refractory solid tumors have identified the dose-limiting toxicity of hepsulfam to be cumulative myelosuppression resulting in prolonged leukopenia and thrombocytopenia. This phase I trial was designed to determine the maximally tolerated dose of hepsulfam administered intravenously in patients with refractory leukemias and other advanced hematologic malignancies. Hepsulfam was administered as a 30-min or 2-h intravenous infusion to 21 patients with advanced leukemia or multiple myeloma. All patients had been extensively treated and had progressive disease. Cycles were repeated every 5 weeks. Cohorts of patients were treated at 360, 480, 640, and 800 mg/m2. The dose-limiting toxicity of intravenous hepsulfam was severe encephalopathy. The single patient treated at 800 mg/m2 became comatose within 48 h and required 3 weeks for his mental status to return to baseline. There were, however, no irreversible neurological sequelae. Several patients treated at 640 mg/m2 had clinical evidence of toxic deliriums and slowing of alpha rhythm waves on electroencephalograms indicative of a gray-matter encephalopathy. When hepsulfam was infused over 30 min, patients complained of uncomfortable parasthesias, but when the drug was administered over 2 h, these acute symptoms were less common. Myelosuppression was observed in most patients. Among those patients who had some suppression of their leukemia, peripheral blood counts recovered to pretreatment levels after 3–5 weeks. Apart from CNS toxicity, non-hematologic toxicity was minimal. Pharmacokinetic studies demonstrated rapid clearance of hepsulfam so that the drug was not reliably detected in the plasma after 24 h. The recommended phase II dose of hepsulfam as a single 2-h intravenous infusion is 480 mg/m2, but this dose provided relatively little clinical benefit for patients with refractory leukemia. The dose-limiting toxicity is CNS toxicity with increasingly severe encephalopathy at doses ≥640 mg/m2. It would be reasonable to investigate further dose escalation of hepsulfam in a divided dose schedule to minimize the peak concentrations which may be related to the encephalopathy. EEG monitoring is recommended for early detection of slowing of alpha rhythm waves. Hematopoietic stem cell support will probably be required at total doses exceeding 800 mg/m2.
    Type of Medium: Electronic Resource
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  • 14
    ISSN: 1432-0843
    Keywords: Encephalopathy ; Hepsulfam ; Acute leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hepsulfam is a bisulfamic ester which is similar in structure to busulfan and is believed to act as a bifunctional alkylator inducing both DNA-DNA and DNA-protein crosslinks. Prior studies in patients with refractory solid tumors have identified the doselimiting toxicity of hepsulfam to be cumulative myelosuppression resulting in prolonged leukopenia and thrombocytopenia. This phase I trial was designed to determine the maximally tolerated dose of hepsulfam administered intravenously in patients with refractory leukemias and other advanced hematologic malignancies. Hepsulfam was administered as a 30-min or 2-h intravenous infusion to 21 patients with advanced leukemia or multiple myeloma. All patients had been extensively treated and had progressive disease. Cycles were repeated every 5 weeks. Cohorts of patients were treated at 360, 480, 640, and 800 mg/m2. The doselimiting toxicity of intravenous hepsulfam was severe encephalopathy. The single patient treated at 800 mg/m2 became comatose within 48 h and required 3 weeks for his mental status to return to baseline. There were, however, no irreversible neurological sequelae. Several patients treated at 640 mg/m2 had clinical evidence of toxic deliriums and slowing of alpha rhythm waves on electroencephalograms indicative of a gray-matter encephalopathy. When hepsulfam was infused over 30 min, patients complained of uncomfortable parasthesias, but when the drug was administered over 2 h, these acute symptoms were less common. Myelosuppression was observed in most patients. Among those patients who had some suppression of their leukemia, peripheral blood counts recovered to pretreatment levels after 3–5 weeks. Apart from CNS toxicity, non-hematologic toxicity was minimal. Pharmacokinetic studies demonstrated rapid clearance of hepsulfam so that the drug was not reliably detected in the plasma after 24 h. The recommended phase II dose of hepsulfam as a single 2-h intravenous infusion is 480 mg/m2, but this dose provided relatively little clinical benefit for patients with refractory leukemia. The dose-limiting toxicity is CNS toxicity with increasingly severe encephalopathy at doses ≥640 mg/m2. It would be reasonable to investigate further dose escalation of hepsulfam in a divided dose schedule to minimize the peak concentrations which may be related to the encephalopathy. EEG monitoring is recommended for early detection of slowing of alpha rhythm waves. Hematopoietic stem cell support will probably be required at total doses exceeding 800 mg/m2.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Biopolymers 25 (1986), S. 1685-1695 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The decrease in mobility of viscous glycol-water solvents when associated with native DNA is quantified from a study of the loss of the exciting-wavelength dependence of the phosphorescence spectrum of free and bound proflavin with increasing temperature. The data are interpreted in terms of a distribution of rate constants with an Arrhenius temperature dependence. Over the temperature range of the experiments a relative decrease of ∼ 104 in the average rate constant is observed for reorientation of the solvent when associated with DNA. The basis for this large reduction is found to derive from a large decrease in the pre-exponential factors (i.e., activation entropy) associated with the reorientation rate constants. The changes in the distribution of rate constants and the activation parameters for solvent mobility induced by DNA do not resemble the changes observed for any one of a number of small ion or molecule perturbations. The results suggest the presence of disorganized, relatively immobile solvent in association with DNA.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Biopolymers 25 (1986), S. 1673-1684 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The mobility of solvent associated with native DNA in comparison with that of the bulk solvent is monitored from the temperature-dependent red shift in the phosphorescence spectra of acridines bound to DNA and free in glycol-buffer mixtures. Over the temperature range for which the red shift occurs the phosphorescence decay changes with emission wavelength, indicating the time-dependent nature of the process. Moreover, at these temperatures, emission anisotropy measurements establish that motions of the dye itself are not involved. Correspondence between perturbations to the solvent that influence the temperature at which the red shift occurs for free acridine with those for the DNA-bound dye confirm that “bound solvent” is responsible for the spectral changes. For the DNA-bound acridines the extent of the red shift is smaller and the midpoint T1/2 of the transition is warmer. The reduction in the red shift reveals that the bound dye is less exposed to solvent and varies as 9-aminoacridine 〈 acridine orange ∼ proflavin, i.e., 9-amino-acridine is less exposed to solvent. On the other hand, the warmer T1/2 indicates that DNA-associated solvent is considerably less mobile than bulk solvent. T1/2 varies for proflavin bound to DNA, poly[d(AT)], poly[d(GC)], and poly(dG): poly(dC), and for proflavin, acridine orange, and 9-aminoacrine bound to DNA. These observations suggest that there is a heterogeneity in the mobility of DNA-associated solvent.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 17
    Unknown
    Hoboken, N.J : BiblioBytes
    Keywords: English drama., lcsh
    ISBN: 0-585-04960-2
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  • 18
    Unknown
    Champaign, Ill : Project Gutenberg
    Keywords: Cheerfulness, Poetry. ; Melancholy, Poetry. ; Didactic poetry., gsafd
    ISBN: 0-585-15074-5
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  • 19
    Unknown
    Hoboken, N.J : BiblioBytes
    Keywords: English poetry, 17th century.
    ISBN: 0-585-05300-6
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  • 20
    Unknown
    Champaign, Ill : Project Gutenberg
    Keywords: Samson, (Biblical judge), Poetry. ; Epic poetry. ; History of Biblical events, Poetry. ; Bible., N.T., Gospels, Poetry. ; English poetry., lcsh
    ISBN: 0-585-01640-2
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