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  • Digitale Medien  (5)
  • renal failure  (3)
  • DNA ploidy  (2)
  • 1
    ISSN: 1432-2307
    Schlagwort(e): Key words Subclonal expansion ; DNA ploidy ; Colorectal carcinoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  DNA heterogeneity of colorectal carcinomas has been investigated by flow cytometry; most studies have focused on the clinical usefulness of DNA ploidy analysis. Since cancers consist of predominant subclones with proliferative advantage due to clonal expansion, we attempted to analyse the clonal expansion of colorectal carcinomas within a tumour by measuring DNA ploidy. The DNA ploidy and heterogeneity of multiple fresh samples obtained from 164 colorectal adenocarcinomas were analysed by flow cytometry. Each tumour was divided into an average of six specimens, which were analysed separately. For 146 of the tumours (89%) at least one DNA aneuploid population was found within the cancer tissue examined. DNA multiploidy was detected in 26 cases (17.8%) among the cancers with aneuploidy. Based on the DNA index (DI), hypertriploid aneuploidy (1.7〈DI〈1.8) was found most frequently in the aneuploid colorectal cancers examined. DNA ploidy heterogeneity was seen in 75 (51.4%) of the DNA aneuploid tumours. There were only 3 cases with more than three subclones including a diploid line. The present results indicate that colorectal carcinomas consist of a few dominant subclones and have a DNA content (hypertriploid aneuploid) that confers a proliferative advantage.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-2307
    Schlagwort(e): Gastric cancer ; p53 immunostaining ; Gland isolation method ; DNA ploidy ; Flow cytometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The expression of p53 was studied immunohistochemically in combination with the DNA ploidy pattern by gland isolation in 97 alcohol-fixed gastric lesions. A polyclonal antibody, CM-1, was applied to the paraffin-embedded sections in this study. Overexpression of the p53 protein was found in 73.2% of 41 well or moderately differentiated gastric carcinomas and 52.2% of 23 cases with poor differentiation (P〈0.05). Immunoreactivity of p53 was also detected in isolated cancerous glands. No p53 immunoreactivity was detected in benign gastric lesions including adenomas, hyperplastic polyps and regions of intestinal metaplasia. In addition, flow cytometric DNA analysis was performed on isolated glandular epithelium adjacent to the portions used for immunostaining. DNA aneuploidy (DA) was detected in 85.7% of the well or moderately differentiated carcinomas and 42.9% of those with poor differentiation (P〈0.05). There was a positive correlation between DA, p53 positivity and the presence of regional lymph node metastasis, but not with other clinicopathological variables. In spite of the limited applicability of this method to poorly differentiated gastric cancer, we found that immunostaining and flow cytometry in combination with the gland isolation method facilitates analysis of gastric carcinogenesis.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-1041
    Schlagwort(e): famotidine ; renal failure ; H2-receptor antagonist ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of a new, potent H2-receptor antagonist, famotidine, 20 mg i.v. was studied in 7 subjects with normal renal function and in 24 patients with varying degrees of renal impairment. The volume of distribution at steady state was 1.14 l/kg in normal subjects and was not altered in renal failure. The half-life of elimination was 2.59 h in normal subjects and was unchanged in mild renal failure (creatinine clearance, CLCR 90–60 ml/min/1.48 m2) but was increased to 4.72 h in moderate renal failure (CLCR 60–30 ml/min/1.48 m2), and to 12.07 h in severe renal failure (CLCR below 30 ml/min/1.48 m2). The cumulative urinary excretion and renal clearance of famotidine were correspondingly reduced in patients with impaired kidney function. In normal subjects and in patients with mild to moderate renal failure, about 70% of famotidine was excreted through the kidney, mainly by tubular secretion. In patients with a CLCR above 60 ml/min/1.48 m2 the normal daily dose of famotidine can be employed, but in those with a CLCR between 60 and 30 ml/min/1.48 m2 the dose should be reduced by half, and in patients with a CLCR below 30 ml/min/1.48 m2 a reduction by three quarters of the normal dose is recommended.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    ISSN: 1432-1041
    Schlagwort(e): TZU-0460 ; renal failure ; H2-receptor antagonist ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied pharmacokinetics of a new H2-receptor antagonist, TZU-0460, in patients with varying degrees of renal impairment. The apparent volume of distribution at steady-state was 1.70 l/kg, and the plasma protein binding of TZU-0460 or its active metabolite, desacetyl TZU-0460 was less than 10% in normal subjects. These variables were not altered with renal impairment. Sixty percent of TZU-0460 given orally was excreted via the kidney, mainly by tubular secretion. The half-time of elimination was 3.94 h in normal subjects, and was prolonged to 12.13 h in severe renal failure (creatinine clearance below 30 ml/min/1.48 m2). Dosage adjustment of TZU-0460 is necessary in renal failure.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    ISSN: 1432-1041
    Schlagwort(e): SUN 1165 ; renal failure ; antiarrhythmic agent ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 1 · kg−1, the absorption rate constant was 2.2 h−1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml · min−1 · 1.48 m−2). Dosage adjustment of SUN 1165 is necessary in renal failure.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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