The early nephrotoxic effect of the antitumor drug adriamycin (ADR) is suggested to be related to the generation of oxygen free radicals. Therefore the O2-dependence and the influence of free radical scavengers were studied in the model of the isolated perfused single glomerulus of Myxine glutinosa and by histochemical demonstration of the glomerular ATP-ase. In Myxine, the glomerular ATP-ase activity was decreased after injection of ADR (5 mg/kg, i.v.). Both ADR-treated Myxine and controls were exposed for 48 h to an artificial atmosphere of 20% O2/80% N2 or 80% O2/20% N2, respectively. After 10 days a significant decrease of the hydraulic conductivity (k) was measured in the experimental group exposed to 80% O2 (k-values expressed as nl/s.mm Hg.mm2: controls (7): 0.059 +/- 0.017; ADR (7): 0.033 +/- 0.026). The reduction of k following the administration of ADR (20 mg/kg) could be prevented by the sulphydryl donor N-acetylcysteine (NAC). The sieving coefficient for albumin (phi) was significantly increased in ADR-treated animals, showing no O2-dependence (phi x 10(-2): controls (7) 1.3 +/- 0.2; ADR 20% O2 (8): 8.1 +/- 9.6; ADR 80% O2 (7): 6.9 +/- 6.7). phi was not affected by NAC. The lipid peroxide levels in liver, kidney and heart of Myxine increased after the administration of ADR, peaking by day 2 to 5. The circulation disorders of ADR-treated Myxine were not due to an accumulation of the drug in the heart, but rather to a lack of the intracellular antioxidant glutathione. It is concluded that the early nephrotoxic effect of ADR, as reflected by a decreased glomerular ATP-ase activity, is mediated by free radical formation. Oxidative stress on membrane compounds seems to reduce the water permeability of the glomerular barrier, while the ADR-induced sieving defect may be due to oxygen independent pathological mechanisms.
Percutaneous placement of Dacron-covered stents is a safe and effective procedure for salvage of a dialysis fistula. First results are promising, with a tendency to prolongation of the time interval between reinterventions.
The purpose of this study was to investigate whether the four-fold magnification mammography (direct magnification, DIMA) technique would perform better than conventional 1.5-fold magnification mammography in the differentiation of breast microcalcifications into benign and malignant. Fifty patients with non-palpable microcalcifications detected by mammography were examined immediately prior to surgical biopsy using both a conventional (1.5-fold) and the DIMA (fourfold) magnification mammography techniques. The microcalcifications were classified by five experienced radiologists using morphological criteria. A receiver operating characteristics curve (ROC) analysis of the sensitivity and specificity of both techniques in assessing malignancy was then carried out. The DIMA mammography technique was slightly but non-significantly superior to the conventional method in detecting malignancy (p > 0.05). Coarse granular and pleomorphic calcifications were detected more frequently with the DIMA technique. Coarse calcifications were significantly more frequently associated with histologically benign findings, whereas fine granular calcifications were significantly more likely to be malignant lesions. Assessment of malignancy associated with microcalcifications using morphological criteria is not significantly improved by mammography techniques with higher magnification.
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