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  • Articles: DFG German National Licenses  (3)
  • 2000-2004  (3)
  • Breast  (1)
  • Drug resistance  (1)
  • Elderly subjects  (1)
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  • Articles: DFG German National Licenses  (3)
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  • 1
    ISSN: 1432-1335
    Keywords: Key words DNA repair ; Resistance modifier ; Drug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Modulation of DNA repair represents one strategy to overcome cellular drug resistance to alkylating agents and platinum compounds. The effects of different known DNA repair modulators such as O 6-benzylguanine (6 μg/ml), fludarabine (25 ng/ml), aphidicolin (8.5 ng/ml), pentoxifylline (1.4 μg/ml) and methoxamine (12.4 μg/ml) on the cytotoxicity of mafosfamide, chlorambucil, 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), cisplatin and carboplatin were tested in human lung cancer cell lines. Methods: Chemosensitivity of the human adenocarcinoma cell line MOR/P and the cisplatin-resistant subline MOR/CPR as well as the large-cell lung cancer cell line L23/P and its cisplatin-resistant counterpart L23/CPR were evaluated by the MTT colorimetric assay. Results: O 6-benzylguanine, an inhibitor of O 6-alkylguanine-DNA alkyltransferase, significantly sensitised MOR/P and MOR/CPR cells to the cytotoxic effect of BCNU. Fludarabine, methoxamine and aphidicolin did not change the chemosensitivity of the parental and cisplatin-resistant cell lines to any cytotoxic drug tested. Interestingly, O 6-benzylguanine enhanced the chemoresistance of parental and cisplatin-resistant cell lines to platinum compounds. Also, pentoxifylline increased resistance of the MOR cell lines to mafosfamide. Conclusions: Modulation of DNA repair elicits not only chemosensitisation but may also enhance cellular resistance to DNA-affine drugs.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1084
    Keywords: Key words: Papilloma ; Breast ; MRM ; Galactography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The aim of this study was evaluation of MRI alone and in combination with mammography and galactography in the diagnosis of intraductal papillomas. From 1994 to 1998, a total of 48 women presenting with pathologic mammary secretion underwent galactography and magnetic resonance mammography (MRM). Thirty-five patients aged 16–71 years (average age 46 years) subsequently underwent surgery or diagnostic puncture and the histologic findings were compared with the results of the radiologic examination. Histology revealed papillomas in 16 cases. In 6 of these patients, there was associated malignant degeneration. Malignancy without associated papilloma was observed in 3 cases. Galactography displayed a sensitivity of 94 % and a specificity of 79 % with five false-positive findings and one false-negative finding in the recognition of intraductal papillomas. Malignant processes were detected by mammography/galactography in only one instance. Magnetic resonance mammography visualized pathologic contrast medium uptake in 8 of 9 cases of malignant disease (sensitivity 89 %). One patient with in situ ductal carcinoma escaped detection with MRM. Papillomas showed no or below-the-threshold-lying contrast uptakes with no specific sign suggestive of papilloma. Galactography in combination with mammography remains the primary diagnostic procedure in cases of pathologic mammary secretion or suspected papilloma. The addition of MRI permits exclusion of malignant disease with a high degree of certainty; thus, expectant management in individual cases with negative findings appears justified.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Key words Polysomnography ; Elderly subjects ; Zopiclone ; Temazepam ; Cognitive psychomotor performance ; Memory ; GABA-A/BDZ receptor ; REM density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The increased prevalence of sleep disturbance in old age is accompanied by a higher prescription rate of hypnotics, predominantly benzodiazepines in the elderly. In young volunteers zopiclone exerts a beneficial effect on sleep continuity without suppression of SWS and REM sleep; psychomotor performance and vigilance seemed to be less impaired than under classical benzoediazepines. Objective: The present study investigates the effects of zopiclone on sleep EEG and cognitive performance in comparison to temazepam and placebo in the elderly population. Methods: Single oral doses of zopiclone (7.5 mg), temazepam (20 mg) and placebo were administered in a randomized double-blind, completely counterbalanced cross-over design to 12 healthy elderly men and women (65.9+3.6 years, range 60–70 years). On each of the 3 study nights a sleep EEG was registered from 10 p.m. to 6.30 a.m. and cognitive performance tests were applied at 8 p.m., 2 a.m. (when subjects were awake for 30 min), 7 a.m. and 9 a.m. Results: After zopiclone treatment, sleep continuity had significantly improved and sleep stage 4 was increased compared to temazepam and placebo. In addition, both active substances significantly reduced REM density. Neither active compound substantially altered psychomotor and memory performance. Conclusions: Zopiclone and temazepam can be considered as effective hypnotics in elderly subjects when administered in that dosage. The superiority of zopiclone on sleep architecture may be related to a more specific action of zopiclone at the GABA-A benzodiazepine receptor complex. The suppression of REM density by both compounds and their subtle effects on cognition may reflect a GABAergic mediated reduction of cholinergic neurotransmission.
    Type of Medium: Electronic Resource
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