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Biomedical subjects

D A Thomas

Publications and source records attributed to D A Thomas.

112 records · Page 7Linked to original sources
PubMedDate not supplied

Secondary leukemia after treatment with paclitaxel and carboplatin in a patient with recurrent ovarian cancer.

The occurrence of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) has been reported after treatment with cytotoxic alkylating agent-based chemotherapy for solid tumors. We report a patient with metastatic ovarian carcinoma treated with carboplatin and paclitaxel, who developed secondary acute erythroid leukemia. The overall survival of patients with stage III and IV ovarian cancer has increased in the past decade. Monitoring of the long-term outcome of paclitaxel- and platinum-based regimens is warranted, particularly with regard to monitoring the development of secondary MDS and/or AML. The incidence and outcome of secondary leukemia in the setting of active ovarian carcinoma is reviewed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Pulmonary effects of chronic exposure to liposome aerosols in mice.

Administering liposome-encapsulated drugs by aerosols could be a feasible way of targeting drugs to the lung, specifically to pulmonary alveolar macrophages (AM). In the mouse model, we characterized uptake of carboxyfluorescein- (CF-) labeled liposomes by AM in vivo after acute inhalation of liposome aerosols, and the effects of chronic exposure to liposome aerosols on lung histology and AM function. Mice were placed in a nose-only exposure module and exposed to liposome or saline aerosols for 1 h per day, 5 days per week, for 4 weeks. Five mice of both the experimental and control groups were removed weekly and their lungs examined. Liposomes were made from hydrogenated soy phosphatidylcholine (HSPC) at 50 mg/mL. In vivo uptake of liposomes by AM was documented by fluorescence microscopy and flow cytometry of bronchoalveolar lavage (BAL). A consistent amount of 1-3 micrograms of lipid inhaled per dosing per mouse was estimated from fluorescence measurements. Addition of Triton X-100 to BAL caused a significant increase in fluorescence intensity, indicating that liposomes remained intact in the lung for a period of time. The chronic inhalation study showed no histologic changes of the lung or untoward effects on the general health or survival of animals. AM phagocytic function, intracellular killing, and fatty acid composition were not affected. Transmission electron microscopy and morphometry (computerized image analysis) of AM likewise showed no alterations as a result of the treatment. It was concluded that AM uptake of liposomes delivered by aerosol was operant in vivo. This finding validates the concept of alveolar macrophage-directed delivery of liposome-encapsulated agents to the lung via inhalation. It was also concluded that chronic liposome aerosol inhalation in mice produced no untoward effects on survival, histopathology, and macrophage function. These data confirm and extend prior findings regarding the functional and morphologic interactions of liposomes with AM in vitro (Gonzalez-Rothi et al., Exp. Lung Res. 17:687-705, 1991).

Administration, Intranasal↗