Publication


Featured researches published by Robert B. Diasio.


Antimicrobial Agents and Chemotherapy | 1978

Evidence for Conversion of 5-Fluorocytosine to 5-Fluorouracil in Humans: Possible Factor in 5-Fluorocytosine Clinical Toxicity

Robert B. Diasio; Duane E. Lakings; John E. Bennett

A gas chromatographic-mass spectrometric method for detecting 5-fluorouracil (5-FU) in serum at concentrations as low as 10 ng/ml was used to determine to what extent 5-FU was present in the serum of patients taking oral 5-fluorocytosine (5-FC). Preliminary studies in two patients and two healthy volunteers given an initial 2-g oral dose of 5-FC demonstrated sustained serum 5-FU levels (>100 ng/ml) during the 5 h after ingestion of drug. Pharmaceutical preparations of 5-FC used in these studies were shown to be insignificantly contaminated with 5-FU (<0.03%), suggesting in vivo conversion of 5-FC to 5-FU had occurred. Serum samples from seven patients with cryptococcal meningitis treated with amphotericin B and 5-FC were examined for 5-FU. Five of these patients had experienced hematological or other toxicity attributed to 5-FC at some time during the course of therapy. Of 41 serum samples, 20 were observed to have 5-FU levels greater than 1,000 ng/ml in the range observed with cancer chemotherapeutic doses of 5-FU known to be associated with hematological toxicity. It is concluded that conversion of 5-FC to 5-FU occurs in humans and furthermore that 5-FU may account for some of the toxicity observed with 5-FC.


Antimicrobial Agents and Chemotherapy | 1978

Rapid determination of serum 5-fluorocytosine levels by high-performance liquid chromatography.

Robert B. Diasio; M E Wilburn; S Shadomy; Ana Espinel-Ingroff

A method for the rapid, quantitative determination of 5-fluorocytosine (5-FC) in serum by high-performance liquid chromatography (HPLC) has been developed. After initially ultrafiltrating the serum, a portion was injected onto a cation exchange column. 5-FC was separated by using an ammonium-phosphate buffer as the mobile phase and detected by ultraviolet absorption at 254 nm. Quantitation of 5-FC was based on the linear relationship between peak area in the chromatograms and known concentrations of 5-FC in a set of serum standards (prepared by adding from 10 to 200 micrograms of 5-FC to 1-ml aliquots of pooled human serum). This method was compared with the standard microbiological method for 5-FC. Advantages of the HPLC method include: Determination of 5-FC levels within 30 min; lack of interference from other antimicrobial drugs, particularly amphotericin B; more accurate determination of true 5-FC level, particularly at concentrations of less than 25 micrograms/ml or greater than 100 micrograms/ml; and ease with which the assay may be automated for routine use.


Cancer Research | 1984

5-Fluorouracil incorporation into DNA of CF-1 mouse bone marrow cells as a possible mechanism of toxicity

J. D. Schuetz; Hugh J. Wallace; Robert B. Diasio


Cancer Research | 1980

Metabolism and Biological Activity of 5′-Deoxy-5-Fluorouridine, a Novel Fluoropyrimidine

Armstrong Rd; Robert B. Diasio


Cancer Research | 1981

Selective Activation of 5′-Deoxy-5-fluorouridine by Tumor Cells as a Basis for an Improved Therapeutic Index

Armstrong Rd; Robert B. Diasio


Cancer Research | 1983

Decreased Immunosuppression Associated with Antitumor Activity of 5-Deoxy-5-fluorouridine Compared to 5-Fluorouracil and 5-Fluorouridine

Kevin M. Connolly; Robert B. Diasio; R. Douglas Armstrong; Alan M. Kaplan


Archive | 1981

Differential effect of allopurinol (hpp) on incorporation of 5-fluorouracil (fu) into rna of tumor and host cells isolated from cf1 mice bearing ehrlich ascites tumor (et). Abstr.

J D Schuetz; M E Wilburn; E L Jackson; Robert B. Diasio


Federation Proceedings | 1981

Characterization of 5'-deoxy-5-fluorouridine induced inhibition of tumor cell growth in vitro

R. D. Armstrong; K. M. Connolly; Robert B. Diasio


Federation Proceedings | 1983

Decreased immunosuppression associated with anti-tumor activity of 5'-dFUrd compared to 5-FUra and 5-FUrd

K. M. Connolly; Robert B. Diasio; R. D. Armstrong; A. M. Kaplan


Archive | 1982

Mechanism of fluoropyrimidine (FP) toxicity in Ehrlich ascites tumor cells (EA); Inhibition of thymidylate synthetase activity (TSA) vs. incorporation into RNA at equitoxic doses of four FP drugs

J. D. Schuetz; Hugh J. Wallace; R. Scott; Robert B. Diasio

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