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Biomedical subjects

W J Casey

Publications and source records attributed to W J Casey.

13 recordsLinked to original sources

Is renal revascularization in diabetic patients worthwhile?

PURPOSE: This retrospective review describes surgical management of atherosclerotic renovascular disease (RVD) in hypertensive adults with diabetes mellitus. METHODS: From July 1987 through July 1995, 54 consecutive hypertensive diabetics (mean 213/103 mm Hg; mean medications three drugs) requiring either insulin (16 patients) or oral hypoglycemic therapy (38 patients) had operative repair of atherosclerotic RVD. Renal dysfunction (serum creatinine [SCr] > or = 1.3 mg/dl) was present in 82% of patients (mean SCr 2.4 mg/dl). Associations between blood pressure and renal function response to operation and preoperative parameters were examined. Clinical characteristics, response to operation, and dialysis-free survival were compared with those of 291 nondiabetic patients. RESULTS: Four (7.4%) operative deaths occurred. Among 50 survivors blood pressure response was considered cured or improved in 72% and unchanged in 28%. Of 42 patients with renal dysfunction 40% had improved function including three patients removed from dialysis. No preoperative parameter examined demonstrated a significant association with blood pressure or renal function response. During follow-up 10 additional patient deaths occurred, and eight patients progressed to dialysis dependence. Time to death or dialysis was associated with preoperative estimates of glomerular filtration (p = 0.03) and the change in estimates of glomerular filtration after operation (p = 0.01). Compared with 291 nondiabetics, the diabetic group had no statistical difference in improved function response (40% vs 51%, p = 0.21); however, diabetics had a significantly lower rate of beneficial blood pressure response (72% vs 89%, p = 0.01) and an increased risk of dialysis or death during follow-up (p = 0.02). By multivariate analysis independent predictors of time to death or dialysis included the presence of diabetes mellitus, patient age, history of congestive heart failure, and increased serum creatinine. CONCLUSIONS: Most of the selected diabetic patients had a beneficial blood pressure response after undergoing operative repair of atherosclerotic RVD, albeit at a lower rate compared with nondiabetics. In diabetics poor renal function before and after operation was associated with progression to dialysis and death. Improved renal function after operation was associated with improved survival; however, function response to renal revascularization was difficult to predict.

Aged

Quantitation of drug sensitivity by human metastatic melanoma colony-forming units.

We measured the effect of 6 standard (Adriamycin, BCNU, DTIC, melphalan, vinblastine, actinomycin D) and 3 Phase II agents (cis-platinum, vindesine, AMSA) on melanoma colony-forming units (CFU) in soft agar from biopsies of 50 patients with metastatic melanoma. Melanoma CFU demonstrated marked heterogeneity in chemosensitivity to these 9 drugs. Reduction in survival of CFU below 38% at one-tenth the pharmacologically achievable 1h concentration (our operational definition of chemosensitivity) was obtained in only 19% of 200 in vitro trials, and was usually the same whether or not patients had been exposed to prior chemotherapy, suggesting that melanoma CFU are inherently resistant to presently available chemotherapeutic drugs. The soft-agar assay was 86% accurate (25/29 cases) in identifying drugs to which the tumour was resistant in vivo, and 63% accurate (12/19 trials) in identifying drugs to which the tumour was clinically sensitive, counting mixed responses as responses. In contrast, if mixed responses were classified as progressive disease, the accuracy of identification of sensitivity fell to 42% (8/19 trials). These investigations furnish a quantitative description of the chemosensitivity of human metastatic melanoma CFU. Additionally, these studies serve as a useful step towards the development of an in vitro chemosensitivity test for human melanoma, and provide an operational quantitative basis for further exploration of in vitro-directed therapy in metastatic neoplasms.

Antineoplastic Agents

In vitro clonal assay for human metastatic melanoma cells.

An in vitro assay for clonogenic tumor cells was applied to human metastatic melanomas. Melanoma colony formation was observed in 22 of 33 samples obtained from a variety of involved tissues. The melanocytic tumor origin of colonies was established by serial observations by inverted light microscopy, staining of fixed colonies for melanin, and cytological and karyotypic analysis of cells within colonies. Two morphologically distinct types of colonies were identified, one consisting of light large cells and the second of dark small cells. Investigations of factors which modulate growth and differentiation of clonogenic melanoma cells may provide a clearer understanding of this neoplasm.

Cells, Cultured

Nonhuman primate restraint device for ocular drug studies.

A restraining device for nonhuman primates was designed which effectively prevented the animal from touching the eyes and thereby transferring a topically applied drug from 1 eye to the other. This permitted use of 1 eye of the same animal as a reliable control for observation of pharmacologic effects. The design permitted self-feeding by the animal. It did not produce chafing or pressure sores and resulted in no psychologic depression. The device has been used successfully for a 5-mo period.

Animals