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  • 1
    Electronic Resource
    Electronic Resource
    Renal and hepatic toxicity after high-dose 7-hydroxymethotrexate in the rat (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 119-124 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To examine directly the hepatic and renal toxicity of 7-hydroxymethotrexate (7-OH-MTX) without interference of the parent compound methotrexate (MTX), we purified and gave 100 mg/kg 7-OH-MTX to rats, a dose resulting in serum levels of 7-OH-MTX comparable with those achieved in the clinic after the administration of high-dose MTX (HD-MTX). After only 5 h, the 7-OH-MTX-treated rats demonstrated 2.6-fold increases in serum creatinine values and 2-fold elevations in serum aspartate aminotransferase (ASAT) levels as compared with the controls. Morphologic evidence of toxicity, however, was apparent only in the kidneys. Intraluminal cellular debris containing membranous material and deteriorated organelles was seen, but no precipitate of the delivered drug. The peak serum concentration of 7-OH was up to 939 μM, and concentrations of 7-OH-MTX declined triphasically, showing at1/2α value of 2.45 min, at1/2β value of 30.5 min, and a terminal half-life (t1/2γ) of 240 min. The total clearance value was 14.5 ml min−1 kg, and the postdistributional volume of distribution (Vβ) was 5070 ml/kg. Our results may indicate a direct toxic effect of 7-OH-MTX on kidney and liver cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685928
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    A morphometrical analysis of dysplasia in small adenomas of the large instestine (1987)
    Springer
    Virchows Archiv 410 (1987), S. 119-124 
    Details
    ISSN: 1432-2307
    Keywords: Morphometry ; Adenomas ; Large intestine ; Dysplasia ; Normal mucosa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a morphometrical study of 40 colorectal adenomas less than 10 mm in diameter and of 10 specimens of normal mucosa, it was found that nuclear size, perimeter and shape-factor of the epithelial cells were significantly different in neoplastic when compared with normal tissues. The same was found for the volume fraction of stroma, gland spaces, goblet and non-goblet epithelium, for the gland diameter, nuclear stratification height and stratification index, but not for the epithelial height nor the total volume fraction of the epithelium. In a multivariate analysis, stratification index and nuclear size of the epithelial cells contributed most significantly to determination of the histological grade of dysplasia in adenomas. By the combination of these two morphometric variables 75% of all adenomas could be correctly allocated to the grade of dysplasia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00713515
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Natural history of adenomas (1991)
    Springer
    World journal of surgery 15 (1991), S. 3-6 
    Details
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé A partir de 55 ans, on voit se développer chez un tiers de la population un ou plusieurs adénomes colorectaux. Dans les 10 ans à venir, 3 à 5% de ces patients adénomateux deviendront cancereux. Le taux plutôt bas de passage de l'adénome au cancer signifie que la plupart des individus ayant des adénomes n'auront jamais de cancer colorectal. Il faut élargir nos connaissances pour prévoir le devenir de chaque patient adénomateux. On y parviendra probablement grâce au progrès constant dans la technologie des gènes et grâce aux grandes études prospectives de suivi des patients à adénome.
    Abstract: Resumen Una tercera parte de los individuos mayores de 55 años poseen adenomas Únicos o mÚltiples de la región colorrectal. En el curso del siguiente decenio, 3–5% de las personas con adenomas tienen la probabilidad de desarrollar un carcinoma. La relativamente baja tasa de conversión del adenoma benigno a neoplasia maligna indica que la mayoría de aquellas que tienen un adenoma jamás habrán de desarrollar carcinoma colorrectal. Se requiere mayores conocimientos para lograr predecir la evolución final del paciente con adenoma. Tales conocimientos probablemente serán obtenidos mediante el progreso en la tecnología genética y a través de amplios estudios prospectivos de seguimiento de los pacientes con adenomas.
    Notes: Abstract One-third of individuals over the age of 55 years have single or multiple colorectal adenomas. During a subsequent period of 10 years, 3–5% of adenoma-bearing individuals will probably develop a carcinoma. The rather low conversion rate from benign to malignant disease indicates that most individuals with adenomas will never develop colorectal carcinoma. More knowledge is required to predict the outcome of the individual adenoma in a given patient. This will probably be obtained by increasing progress within gene technology and through large prospective follow-up studies of adenoma-bearing patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01658952
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Renal and hepatic toxicity after high-dose 7-hydroxymethotrexate in the rat (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 119-124 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. To examine directly the hepatic and renal toxicity of 7-hydroxymethotrexate (7-OH-MTX) without interference of the parent compound methotrexate (MTX), we purified and gave 100 mg/kg 7-OH-MTX to rats, a dose resulting in serum levels of 7-OH-MTX comparable with those achieved in the clinic after the administration of high-dose MTX (HD-MTX). After only 5 h, the 7-OH-MTX-treated rats demonstrated 2.6-fold increases in serum creatinine values and 2-fold elevations in serum aspartate aminotransferase (ASAT) levels as compared with the controls. Morphologic evidence of toxicity, however, was apparent only in the kidneys. Intraluminal cellular debris containing membranous material and deteriorated organelles was seen, but no precipitate of the delivered drug. The peak serum concentration of 7-OH was up to 939 μM, and concentrations of 7-OH-MTX declined triphasically, showing a t 1/2α value of 2.45 min, a t 1/2β value of 30.5 min, and a terminal half-life (t 1/2γ) of 240 min. The total clearance value was 14.5 ml min–1 kg, and the postdistributional volume of distribution (Vβ) was 5070 ml/kg. Our results may indicate a direct toxic effect of 7-OH-MTX on kidney and liver cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685928
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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