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S Dische

Publications and source records attributed to S Dische.

149 records · Page 9Linked to original sources
PubMedDate not supplied

Desmethylmisonidazole (Ro 05-9963): clinical pharmacokinetics after multiple oral administration.

The O-demethylated metabolite of misonidazole, Ro 05-9963, has been administered orally, prior to irradiation, to over 50 patients with malignant disease in order to assess the effectiveness of this compound as a hypoxic cell radiosensitizer. This paper reports the pharmacokinetic data observed in those patients who received multiple doses to a total of 12 gm-2. The mean time and magnitude of the peak plasma concentration was determined together with the plasma profile and half-life at the start and finish of each regime of 6, 20, 25 or so fractions. Half-life was independent of drug dose while peak plasma levels rose with increasing amount of drug given. The importance of urinary clearance for this polar drug is indicated by the figure of approximately 50% of administered dose excreted by this route over 24 hours, compared to less than 25% for misonidazole. It was also illustrated by the increased half-life shown by one patient who suffered renal failure during treatment. Peak plasma concentration appeared to be slightly later and were more variable than in the more ideal conditions of the normal volunteer study. In addition, this study confirmed the latter study's findings that absorption is rapid following oral administration of Ro 05-9963, yielding peak plasma levels nearly as high as those seen with misonidazole. Administration in capsules rather than aqueous solution lead to slower absorption, but the peak level did not change.

Administration, Oral↗
PubMedDate not supplied

Skin rashes associated with the administration of the 2-nitroimidazole, misonidazole.

Misonidazole, a 2-nitroimidazole, is receiving extensive trial as a radiosensitizing drug in the treatment of patients with malignant disease. Drug sensitivity rashes have been observed and the collected cases from three centers are reported. Of a total of 380 patients there were five (1.3%) instances of definite rash and ten (2.6%) instances of observed rash. These figures are compared with the incidence of sensitivity rashes with other drugs in the nitroimidazole group.

Adult↗
PubMedDate not supplied

Bcl-2 expression correlates with favourable outcome in head and neck cancer treated by accelerated radiotherapy.

The aim of this study was to investigate bcl-2 expression in head and neck cancer patients and to investigate its correlation with biological and clinical characteristics and outcome of accelerated radiotherapy. A series of 93 patients with squamous cell carcinoma of the head and neck who had been uniformly treated with continuous hyperfractionated accelerated radiation treatment (CHART) were investigated. These patients had also been injected with bromodeoxyuridine (BrdUrd) to measure cell kinetic parameters using flow cytometry (FCM) and their p53 protein status had also previously been described. Bcl-2 expression was assessed using immunohistochemistry. Sixteen of the 93 (17.2%) patients stained positively for bcl-2 proto-oncogene. The percentage of positive tumour cells within the specimens was highly variable, ranging from a few percent to complete positivity. Bcl-2 positivity was correlated with improved local control (p > 0.0016) and survival (p > 0.012) in comparison with non-expressing tumours. There was no correlation between bcl-2 expression and histological grade, T stage or site but overexpressors were almost exclusively node negative. The significance of bcl-2 was reduced when node negative tumours were analysed alone. There was no correlation of bcl-2 with p53 expression but there was a trend for overexpression to be associated with diploidy and rapidly proliferating tumours. These data suggest that bcl-2 expression in head and neck cancer is not associated with disease progression.

Cell Division↗