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Biomedical subjects

C Goddard

Publications and source records attributed to C Goddard.

88 records · Page 5Linked to original sources
PubMed1981

Studies on the mechanism of secretion of corticosteroids by the isolated perfused adrenal of the rat.

A technique for the perfusion of the rat adrenal cortex is described. With tissue culture Medium 199 the preparation was responsive in terms of steroid production of both ACTH and K+ ions. Production of corticosterone and 18-hydroxydeoxycorticosterone (18-hydroxy-DOC) was stimulated by ACTH when it was administered at rates between 5 uu.'/min and 5 mu./min. Increasing the K+ ion concentration of the perfusate from 3.6 to 5.4 and 8.9 mmol/l stimulated the production of aldosterone, 18-hydroxycorticosterone and deoxycorticosterone, although not of corticosterone or 18-hydroxy-DOC. This preparation has been used to study further the mechanism of secretion of corticosterone and 18-hydroxy-DOC. Thus, production of these two steroids was measured at different perfusion flows, varying between 0.1 and 0.6ml/min, with different levels of ACTH stimulation. Corticosterone production was significantly (P less than 0.001) increased by increasing flows both under control conditions and with ACTH was administered at constant rates of 50 uu./min or 1 mu./min. Production of 18-hydroxy-DOC was not affected by flow either under control conditions or with 50 uu. ACTH/min. However, when ACTH was administered at 1 mu./min. 18-hydroxy-DOC production was also significantly (P less than 0.001) increased by flow. The results are consistent with those obtained in previous in-vitro studies and have been interpreted as suggesting that the main mechanism of corticosterone secretion is simple diffusion. In contrast, 18-hydroxy-DOC secretion, at least at sub-maximal levels of stimulation, appears to require a more complex process.

18-Hydroxydesoxycorticosterone↗
PubMedDate not supplied

Phase I clinical trial of mitozolomide.

Mitozolomide (NSC-353451; CCRG 81010; M and B 39565) is a novel potential anticancer agent that was selected for phase I study on the basis of broad spectrum activity in mouse tumors. Initially, mitozolomide was given iv as a short infusion to 37 patients in doses ranging from 8 to 153 mg/m2. Nausea and vomiting was dose-related but was not severe. The dose-limiting toxic effect was thrombocytopenia at doses greater than 115 mg/m2, and recovery from the thrombocytopenia was delayed up to 8 weeks. Partial responses were seen in two patients with adenocarcinoma of the ovary. The pharmacokinetics of mitozolomide showed that the half-life of the intact drug in the plasma was between 1 and 1.3 hours. The area under the curve was proportional to the dose administered. Mitozolomide is well-absorbed; therefore, future studies are recommended using a single-dose schedule orally or iv. In the phase I study reported here, a dose of 115 mg/m2 appeared to be safe, but additional studies have shown that when given orally to an older population, most patients experienced thrombocytopenia less than 50,000 cells/mm3. The recommended dose using current data is 90 mg/m2 iv or orally.

Administration, Oral↗