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R McIvor

Publications and source records attributed to R McIvor.

4 recordsLinked to original sources
PubMed1999

Methotrexate resistance conferred by transplantation of drug-resistant transgenic marrow cells fractionated bycounterflow elutriation.

Introduction of genes conferring drug resistance into hematopoietic cells may allow for improved chemotherapy by protection of normally drug-sensitive cells from the toxic side-effects of antitumor agents. We recently reported that transplantation of murine marrow transgenic for drug-resistant dihydrofolate reductase (DHFR) protected mice from lethal doses of methotrexate (MTX), demonstrating the feasibility of imparting drug resistance to recipients of marrow expressing drug-resistant DHFR activity. In order to optimize this strategy it is necessary to identify the hematopoietic cell populations which mediate drug resistance. For this purpose, we separated committed progenitor populations from primitive hematopoietic cells in DHFR transgenic marrow by counterflow elutriation (CE). As expected, supplementation with a fraction containing committed progenitors afforded protection from MTX-induced aplasia observed early after transplantion in animals administered MTX. In contrast, supplementation with a fraction containing primitive hematopoietic cells depleted of committed progenitors failed to provide immediate protection from early aplasia, but instead contributed to drug resistance 4 to 5 weeks after transplantation. The presence of primitive hematopoietic progenitors in both fractions was evident from Southern hybridization analysis for donor transgenic cells 2 months post-transplant. We conclude that protection from aplasia associated with MTX administration immediately after transplantation requires expression of drug-resistant DHFR activity in more differentiated, committed hematopoietic cells, while primitive DHFR transgenic progenitors contribute to long-term drug resistance. These results help to define the appropriate target cells for improved chemotherapy by protection of hematopoietic cells through the introduction of new genes conferring drug resistance.

Animals↗
PubMed1998

The community treatment order: clinical and ethical issues.

OBJECTIVE: In the light of recent legislation, this paper reviews the implementation of the Community Treatment Order (CTO) in terms of clinical efficacy and ethical issues involved in its use. The debate surrounding the introduction of CTOs in other countries is explored. METHOD: A Medline search was conducted and references of recent articles followed up, with attention to Australian, New Zealand and international trends. A review of relevant legislation and government reports was conducted. RESULTS: There has been limited debate in the Australian and New Zealand literature concerning the operation of CTOs. Despite their increasing and widespread use, there is a paucity of research on the efficacy of CTOs. Concerns about their negative effects on civil liberties have been stressed in the United Kingdom and American literature. CONCLUSIONS: If the continued use of CTO is to be justified, both clinically and from the civil liberties perspective, controlled research needs to be carried out to identify whether CTOs are more effective than comprehensive assertive community outreach programs in reducing relapse rates and hospitalisation, and increasing compliance. Clinical guidelines concerning who is most likely to respond to such orders need to be developed. Alternatives to the CTO are explored, and future directions in research are outlined.

Australia↗
PubMedDate not supplied

Pharmacotherapy of post-traumatic stress disorder with a novel psychotropic.

This was a multicenter, randomized, double-blind, parallel trial conducted in outpatients in three countries. Following screening and placebo washout, patients received brofaromine (a combined MAO-A inhibitor/5-HT transport inhibitor) or placebo in a flexible dosing design. Based upon the CAPS, a standardized post-traumatic stress disorder (PTSD) interview, findings from a cohort involving both subchronic and chronic traumatic stress marginally favored brofaromine over placebo; however, not to a statistically significant degree. With a more conservation definition of the syndrome, employing a primary cohort of patients with PTSD of one year or greater duration, brofaromine significantly reduced PTSD symptoms in comparison with placebo. In all analyses a substantial proportion of patients in both drug and placebo groups remained symptomatic throughout. Findings were supported by an analysis of secondary measures. Brofaromine may be of benefit in the therapy of PTSD.

Adult↗