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Biomedical subjects

E Egan

Publications and source records attributed to E Egan.

28 records · Page 2Linked to original sources
PubMed1984

Effects of 1-beta-D-arabinofuranosylcytosine incorporation on eukaryotic DNA template function.

1-beta-D-Arabinofuranosylcytosine (ara-C) incorporates into DNA, and the extent of this incorporation correlates significantly with inhibition of DNA synthesis. The incorporated ara-C residue provides a poor primer terminus for further chain elongation. There is a highly significant relationship between formation of (ara-C) DNA and loss of clonogenic survival. The present studies confirm that incorporation of ara-C into DNA, and not the competitive inhibition of DNA polymerase, is responsible for inducing lethal cellular events. The results also demonstrate that the incorporated ara-C residue is not excised from the DNA strand. Furthermore, the presistence of ara-C residues in DNA inhibits recovery of DNA synthesis following exposure to drug. The relative DNA chain-terminating effect of ara-C provides several mechanisms of action that explain internucleotide and chain terminus positioning of ara-C residues, reinitiation of previously replicated DNA segments, and DNA strand or chromosomal breaks. The precise mechanism of action is dependent upon dose scheduling of this drug.

Animals↗
PubMed1983

A phase I-II study of combination therapy with thymidine and cytosine arabinoside.

Twenty-one patients with leukemia and lymphoma refractory to conventional therapy were treated with thymidine (dThd) at a dose of 75 g/m2/day for 48 h by continuous intravenous (IV) infusion, followed by cytosine arabinoside (ara-C) on an escalating dose schedule of 25-625 mg/m2/day for 48 h by continuous IV infusion. Toxicity included somnolence (1 patient), mucositis (2 patients), and myelosuppression (19 patients). One patient died prior to completion of therapy. Because of the patient population studied (mainly consisting of patients with leukemia refractory to conventional therapy) and the prevalence of myelosuppression prior to therapy, a median toxic dose was not evaluable. Therapeutic responses included a partial remission in a patient with acute myelogenous leukemia (AML) refractory to ara-C. An additional six patients with acute leukemia refractory to ara-C transiently cleared their peripheral blood of blasts, and a decrease in circulating blasts was noted in two other patients. Biochemical studies conducted on the peripheral blasts of two patients confirmed an enhancement by dThd of the incorporation of ara-C into the DNA of circulating blasts.

Adolescent↗
PubMed1982

5-Fluorouracil incorporation in DNA of human breast carcinoma cells.

We have demonstrated previously the presence of 5-fluorouracil (FUra) residues in L1210 DNA. These findings have been extended to the MCF-7 human breast carcinoma cell line. Cesium sulfate gradient centrifugation has been used to separate the MCF-7 RNA and DNA fractions. Alkali and RNase digests have also been used to remove any possible RNA contaminating the DNA fraction. The purified DNA has been analyzed by high-pressure liquid chromatography following digestion to nucleotides and nucleosides. The results demonstrate that FUra residues are detectable in the DNA of these human breast carcinoma cells following exposure to either FUra of 5-fluorodeoxyuridine. Further, the extend of FUra incorporation in both MCF-7 RNA and DNA is similar with either fluorinated pyrimidine. We also demonstrate that the FUra incorporation in DNA from this human cell line can be enhanced by concurrent incubation with thymidine.

Breast Neoplasms↗
PubMedDate not supplied

Primary care anticoagulant management using near patient testing.

BACKGROUND: Indications for anticoagulant treatment are increasing and new approaches to anticoagulant services require a shift from hospital to primary care. AIM: To pragmatically test the validity and effectiveness of primary care anticoagulant management using near patient testing. METHODS: Twelve CoaguCheck monitors were supplied to 16 rural practices that had previously provided supervision of anticoagulant therapy. Practices were required to record data for eligible patients from September 1998 to April 1999 and to forward one blood sample per week to the regional hospital laboratory for parallel testing. RESULTS: Nine practices returned data on 122 patients. Indications for anticoagulation Included atrial fibrillation (n = 56), valve replacement (n = 12) and deep venous thrombosis or pulmonary embolus (n=12). Regression of the mean of 185 paired readings against their difference confirmed the validity of the CoaguCheck monitor (r2 = 0.00 [95% CI -0.38 to 0.38]). There were 692 International Normalised Ratio (INR) tests performed representing an average of 5.7 tests per patient. The desired therapeutic range was provided for 609 (88%) of these tests; 294 (48.3%) were within the desired therapeutic range. Results differed significantly between practices. CONCLUSIONS: This study confirmed the validity of anticoagulant management using the CoaguCheck monitor in primary care.

Anticoagulants↗