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R Ashcroft

Publications and source records attributed to R Ashcroft.

At least 19 recordsLinked to original sources
PubMed2004

Differential effects of intra-midbrain raphe and systemic 8-OH-DPAT on VTA self-stimulation thresholds in rats.

RATIONALE: Intra-median raphe nucleus (MRN) administration of the 5-HT(1A) receptor agonist 8-OH-DPAT decreases lateral hypothalamic self-stimulation thresholds and is reported to have biphasic effects following systemic administration. These experiments attempted to extend the previous findings to mesolimbic pathway self-stimulation at ventral tegmental area (VTA) electrodes. OBJECTIVES: This study was conducted to provide comparative data for systemic and intra-dorsal raphe nucleus (DRN) and intra-MRN effects of 8-OH-DPAT on VTA self-stimulation. METHODS: Male Sprague-Dawley rats with VTA electrodes were trained to respond for electrical stimulation. Systemic and intra-midbrain raphe 8-OH-DPAT effects on rate-frequency thresholds were measured. Systemic administration of WAY 100635 was used to confirm 5-HT(1A) receptor mediation of 8-OH-DPAT effects. RESULTS: 8-OH-DPAT (0.003-0.3 mg kg(-1) SC) increased rate-frequency thresholds and decreased maximal response rates. WAY 100635 alone (0.0125-0.1 mg kg(-1) SC) did not alter these measures. Intra-DRN and intra-MRN 8-OH-DPAT (5.0 microg) decreased rate-frequency thresholds without altering maximal response rates. Intra-DRN 8-OH-DPAT (0.1-5.0 microg) induced a slight decrease and intra-MRN 8-OH-DPAT a slight increase in locomotor activity. WAY 100635 (0.1 mg kg(-1)) blocked effects of 8-OH-DPAT on VTA self-stimulation. CONCLUSION: These results confirm threshold-decreasing effects of intra-MRN 8-OH-DPAT and extend this to the DRN and to VTA thresholds. Monophasic dose dependent increases in VTA thresholds following systemic 8-OH-DPAT are not equivalent to reports for hypothalamic self-stimulation. Differences between studies may be attributable to stimulation site and/or differences in threshold measurement procedures. Effects of WAY 100635 in this study indicate 5-HT(1A) receptor mediation of these 8-OH-DPAT effects.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2003

Bach to the future: response to: Extending preimplantation genetic diagnosis: medical and non-medical uses.

Professor Robertson sketches an elegant framework for policy evaluation and regulation of the use of preimplantation genetic diagnosis for various medical, medical related, and non-medical purposes. In criticism of his position, I argue that the distinction between policy and ethics upon which his argument relies is highly unstable, and the approach taken to ethical evaluation of particular parental interests leaves open many issues which the policy approach would hope to exclude. In conclusion I argue that while his position ultimately fails, the onus is on his critics to come up with a viable and satisfying alternative.

Attitude to Health↗
PubMed2001

Are antipsychotic drugs the right treatment for challenging behaviour in learning disability?: The place of a randomised trial.

People with learning disability sometimes display challenging behaviour. This can be managed by use of antipsychotic medication or behavioural therapy or both. There is no solid evidence, however, that these therapies are safe and effective. A randomised controlled trial of antipsychotic medication has been proposed to deliver such evidence. However, this presents difficult issues in the ethics of research with learning disabled people. In particular, is a trial the most efficient and fairest way to evaluate practice in this area? This paper reviews the clinical situation, gives the rationale for the trial, and analyses the ethical arguments for and against such a trial.

Antipsychotic Agents↗
PubMed2000

The ethics of reusing archived tissue for research.

Pathologists have been establishing archives of human organs and tissue for research use for many years now. Controversy has arisen recently over these collections, particularly with regard to the right of patients or relatives to consent to removal and retention of tissue, genetic research using stored tissue samples, and commercial exploitation of tissue collections and genetic material. This paper discusses the ethics of reusing existing archives of tissue. New archives are established under much more stringent conditions than in the past. What rules should apply to existing archives? Guidelines to regulate such use are useful, but face serious difficulties in balancing the variety of public and private interests relating to tissue banking. Consent cannot be obtained retrospectively, but public trust can be established by open acknowledgement of the evolution of ethical standards and strict adherence to current best practice. Guidelines and standards vary from country to country, but ethical principles should not. The implications of this view for pathologists worldwide are discussed.

Ethics, Medical↗
PubMed2000

International research ethics.

This article provides a critical overview of the most important issues pertaining to the ongoing debate on international research ethics. It critically describes three problems of continuing concern: 1) the question of whether the distinction between therapeutic and non-therapeutic research should be upheld; 2) the questions of whether currently demanded best proven diagnostic and therapeutic methods of treatment for all research subjects is feasible both in developed and in developing countries, and whether it should be upheld; 3) the questions of who owns international research ethics guidelines and regulatory frameworks and, how decisions about changes to such international guidelines can possibly be achieved, given that it seems to be the case that genuine disagreement about issues of content is possible and likely.

AIDS Vaccines↗
PubMed2000

The decision making process regarding the withdrawal or withholding of potential life-saving treatments in a children's hospital.

OBJECTIVES: To investigate the factors considered by staff, and the practicalities involved in the decision making process regarding the withdrawal or withholding of potential life-sustaining treatment in a children's hospital. To compare our current practice with that recommended by the Royal College of Paediatrics and Child Health (RCPCH) guidelines, published in 1997. DESIGN: A prospective, observational study using self-reported questionnaires. SETTING: Tertiary paediatric hospital. PATIENTS AND PARTICIPANTS: Consecutive patients identified during a six-month period, about whom a formal discussion took place between medical staff, nursing staff and family regarding the withholding or withdrawal of potentially life-sustaining treatments. The primary physician and primary nurse involved in the discussion were identified. METHOD: Two questionnaires completed independently by the primary physician and nurse. RESULTS: Twenty-two patients were identified (median age 1 year; range 1 day-34 years). In 20 cases treatment was withdrawn or withheld, in two cases treatment was continued. Nursing staff considered family wishes and family perceptions of patient suffering as significantly more important factors in decision making than medical staff, who considered prognostic factors as most important. In only two cases were the patient's expressed wishes apparently available. In most cases staff considered the patient's best interests were served and the process would not be enhanced by the involvement of an independent ethics committee. The exceptions were those cases in which treatment was continued following disagreement between parties. CONCLUSIONS: Our current practice is consistent with that recommended by the RCPCH. The contribution of the patient, provision of staff counselling and general practitioner (GP) involvement were identified as areas for improvement.

Child↗
PubMed1986

Immunohistochemical identification of proliferating cells in organ culture using bromodeoxyuridine and a monoclonal antibody.

The ability to measure cell proliferation is important in the study of cancer biology. The usual technique for quantitating proliferating cells in tissue explant and organ culture by detection of [3H]-thymidine incorporation into DNA by autoradiography is tedious and time-consuming. We have developed a technique for identification and quantitation of bromodeoxyuridine (an analogue of thymidine) in cultured tissue explants. Fetal mouse colon explants were exposed in vitro to bromodeoxyuridine (BUdR) or [3H]-thymidine for 3 to 72 hr and then for various periods to unlabeled thymidine. The tissues were stained with a monoclonal anti-bromodeoxyuridine antibody and in parallel [3H]-thymidine incorporation was detected by autoradiography. Incorporation of BUdR was measured by quantitating the amount of pigment deposited over nuclei after immunohistochemical staining, using an optical data digitizer. It was found that both techniques identified proliferating cells. Dividing cells were present both in crypts and in the surrounding stroma in Day 14 fetal mouse colon cultures. The immunohistochemical technique was more rapid and less cumbersome than autoradiography.

Animals↗
PubMed1982

Autoantibodies to fibroblasts in scleroderma.

Sera from 33 patients with scleroderma were examined for immunofluorescent reactivity with viable or acetone-fixed fibroblasts. All 33 sera reacted with the cell surface membranes of viable fibroblasts. 23 of 33 sera (70%) also reacted with nuclei of acetone-fixed fibroblasts. The commonest nuclear staining pattern was homogeneous (46%) followed by nucleolar (36%) and speckled (23%). 70% showed more than 1 staining pattern in the same serum. Antibody titres of homogeneous and nucleolar staining patterns (1:8 to 1:1024) were generally higher than those of the speckled pattern (1:8 to 1:256). No change in pattern or titre was noted in sera from 4 patients over a 10-12 month period. Antibody in sera with homogeneous or nucleolar staining patterns belonged to one or more of the 3 major antibody classes, IgG, IgM or IgA while antibody in sera with a speckled nuclear pattern belonged to the IgM class only. No correlation was found between the pattern of anti-nuclear reactivity and visceral involvement.

Adult↗