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K R Mitchell

Publications and source records attributed to K R Mitchell.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of Ha-ras mutational spectra of N-methyldibenzo[c,g]carbazole and 7H-dibenzo[c,g]carbazole-induced mouse skin tumors.

Carcinogenic N-heterocyclic aromatic hydrocarbons are formed during the incomplete combustion of fossil fuels as well as cigarette smoke. N-Methyldibenzo[c,g]carbazole (NMeDBC) and 7H-dibenzo[c,g]carbazole (DBC) are members of this group. DBC induces mouse skin and liver tumors, whereas NMeDBC induces only mouse skin tumors. The objective of this study was to elucidate the mechanism of action of these compounds in skin by assessing the Ha-ras mutational spectra induced by a two-stage initiation-promotion protocol. NMeDBC (200 nmol) or DBC (200 nmol) was applied to the back skin of 24 female Hsd:ICR(Br) mice (12 per group) once. 12-O-tetradecanoylphorbol-13-acetate (TPA) (2 microg) was then applied twice weekly for 28 wk. Tumors were screened for Ha-ras mutations using enriched polymerase chain reaction and mutations defined by dideoxy sequencing. In DBC animals 58% produced papillomas, of which 71% had codon 61 mutations, 4% had codon 12 mutations, 4% had codon 13 mutations, and 21% had no Ha-ras mutations. In NMeDBC animals 92% produced papillomas, of which 73% had codon 61 mutations and 27% had no Ha-ras mutations. All of the codon 61 mutations, from both NMeDBC and DBC, were CAA-->CTA transversions. The DBC-induced tumors with the codon 12 mutation had a GGA-->GAA transition, and the codon 13 mutation was a GGC-->GTC transversion. These results suggest that NMeDBC is a more potent tumor inducer than DBC, but the resulting H-ras mutations in each group were predominantly in codon 61, and, therefore, mutation induction in skin by each chemical appears to proceed by a similar mechanism.

Animals↗
PubMed1999

Frequent Ha-ras mutations in murine skin and liver tumors induced by 7H-dibenzo[c,g]carbazole.

7H-dibenzo[c,g]carbazole (DBC) is a potent liver and skin carcinogen when topically applied to the back skin of mice. This compound is found in complex mixtures produced during incomplete combustion of fossil fuels as well as in wood and tobacco smoke. The objective of this study was to elucidate the mechanism of action of this compound by assessing the Ha-ras mutational spectra of skin and liver tumors induced in a mouse model system. Low doses (50 nmol) and high doses (100 nmol) of DBC were applied topically to the backs of Hsd:ICR(Br) mice twice weekly. No treatment and solvent application were used as controls. After the mice were killed, the skin and liver tumors were removed, DNA was isolated, and tumor DNA was screened for Ha-ras codon 12, 13, and 61 mutations by using an enriched polymerase chain reaction method. Mutations were confirmed by reverse cyclic dideoxy sequencing. No mutations were found in codons 12 and 13 of DBC-induced tumors, whereas one acetone-control tumor had a codon 13 mutation. Sixty-seven percent of skin tumors and 45% of liver tumors induced by high doses of DBC and 67% of skin tumors induced by low doses of DBC contained codon 61 mutations, whereas liver tumors induced by low doses of DBC did not. The codon 61 mutations were exclusively A:T-->T:A transversions within the second base (CAA-->CTA). These results indicate that DBC is a unique polycyclic aromatic hydrocarbon in that it induces both skin and liver tumors upon topical application and that the mutational spectra are the same in tumors from two target organs, skin and liver, yet different from tumors from a third target organ, lung.

Animals↗
PubMed1996

The legislation of active voluntary euthanasia in Australia: will the slippery slope prove fatal?

At 2.00 am on the morning of May 24, 1995 the Northern Territory Legislative Assembly Australia passed the Rights of the Terminally Ill Act by the narrow margin of 15 votes to 10. The act permits a terminally ill patient of sound mind and over the age of 18 years, and who is either in pain or suffering, or distress, to request a medical practitioner to assist the patient to terminate his or her life. Thus, Australia can lay claim to being the first country in the world to legalise voluntary active euthanasia. The Northern Territory's act has prompted Australia-wide community reaction, particularly in South Australia, Tasmania and the Australian Capital Territory where proposals to legalise euthanasia have already been defeated on the floor of parliament. In New South Wales (NSW) the AIDS Council of NSW has prepared draft euthanasia legislation to be introduced into the Upper House as a Private Member's Bill some time in 1996. In this paper, we focus on a brief description of events as they occurred and on the arguments for and against the legalisation of euthanasia which have appeared in the media.

Adult↗
PubMed1995

Ethical reasoning and decision-making in the clinical setting: assessing the process.

Clinical ethical reasoning and analysis are skills as central to good patient care as the efficient application of biomedical knowledge to diagnosis and prognosis. However, experience in teaching clinical ethics to senior medical students has indicated that simply trying to 'apply' the knowledge learnt about ethical theories, principles, concepts and rules in the clinical setting does not ensure ethical competence in clinical decision-making. In 1992, we developed and piloted a three-session programme that focused on a more systematic approach to the way students identified and attempted to manage ethical issues in their clinical practice. This programme was modified and improved in 1993 and further expanded in 1994. Our experience suggests that many students are now better able to bridge what has been called the 'gap' between the possession of ethical knowledge and its actual use in clinical decision-making. The remaining problem was assessment. How do you assess clinical ethical reasoning and decision-making? In the preclinical years of medical education, knowledge-based assessment tools, like the modified essay question (MEQ), provide a means for assessing the sensitivity of students to ethical issues. However, such tools permit neither an appraisal of how students actually make clinical ethical decisions, nor which factors students perceive as important in making an actual clinical decision. In order to make this type of appraisal, we developed a format for a written case report that facilitated our assessing the process as well as the end-product, the decision.(ABSTRACT TRUNCATED AT 250 WORDS)

Australia↗
PubMed1995

Teaching clinical ethics as a professional skill: bridging the gap between knowledge about ethics and its use in clinical practice.

Ethical reasoning and decision-making may be thought of as 'professional skills', and in this sense are as relevant to efficient clinical practice as the biomedical and clinical sciences are to the diagnosis of a patient's problem. Despite this, however, undergraduate medical programmes in ethics tend to focus on the teaching of bioethical theories, concepts and/or prominent ethical issues such as IVF and euthanasia, rather than the use of such ethics knowledge (theories, principles, concepts, rules) to clinical practice. Not surprisingly, many students and clinicians experience considerable difficulty in using what they know about ethics to help them make competent ethical decisions in their day-to-day clinical practice. This paper describes the development of a seminar programme for teaching senior medical students a more systematic approach to ethical reasoning and analysis and clinical decision-making.

Curriculum↗
PubMed1995

'These sorts of people don't do very well': race and allocation of health care resources.

Recent literature has highlighted issues of racial discrimination in medicine. In order to explore the sometimes subtle influence of racial determinants in decisions about resource allocation, we present the case of a 53-year-old Australian Aboriginal woman with end-stage renal failure. The epidemiology of renal failure in the Australian Aboriginal population and amongst other indigenous peoples is discussed. We show that the use of utilitarian outcome criteria for resource allocation may embody subtle racial discrimination where consideration is not given to issues of justice, race, culture and gender. It is only where the processes by which resources are allocated are transparent, clearly defined and based upon consultation with individual patients that issues and justice are likely to be adequately addressed.

Americas↗
PubMed1994

Guidelines for no-CPR orders.

A no-CPR decision is not synonymous with abandonment and does not, of itself, rescind the obligations of the health care team to provide the highest quality care. Rather, a no-CPR order is best seen as one element of a comprehensive and dynamic management plan which should be reviewed and changed as the patient's medical condition warrants. A no-CPR order, therefore, offers an opportunity to rethink the goals of therapy in the light of discussions with the critically ill patient and his or her family.

Australia↗
PubMed1993

Medical futility, treatment withdrawal and the persistent vegetative state.

Why do we persist in the relentless pursuit of artificial nourishment and other treatments to maintain a permanently unconscious existence? In facing the future, if not the present world-wide reality of a huge number of persistent vegetative state (PVS) patients, will they be treated because of our ethical commitment to their humanity, or because of an ethical paralysis in the face of biotechnical progress? The PVS patient is cut off from the normal patterns of human connection and communication, with a life unlike other forms of human existence. Why the struggle to justify ending a life which, it is said, has suffered an irreversible loss of the content of consciousness? Elsewhere, the authors have addressed the ethical controversies and confusion engendered by ambiguous terminology, misuse of medical facts and the differing interpretations of what constitutes 'effective' treatment: in particular, the issue of whether in fact artificial nutrition and hydration is a medical treatment, or simply part of the obligatory care owed to all patients, permanently unconscious or not. In this paper, we intend to argue that recent analyses of medical futility, its meaning and ethical implications, despite an absence of public consensus, permit some tentative re-evaluation of our ethical obligations to the PVS patient.

Coma↗
PubMed1993

Assessing the clinical ethical competence of undergraduate medical students.

At the University of Newcastle, health law and ethics is taught and assessed in each year of the five-year curriculum. However, the critical question for assessment remains: 'Does teaching ethics have a measurable effect on the clinical activity of medical students who have had such courses?' Those responsible for teaching confront this question each year they sit down to construct their assessment tools. Should they assess what the student knows? Should they assess the student's moral reasoning, that is, what decisions the student makes, and, how these decisions are justified, or should they assess what the student actually does when dealing with patients in the clinical setting, and how he or she does it? From 1982 to 1991, assessment at Newcastle was primarily aimed at determining the quality of the students' ethics knowledge base. This paper describes the strengths and limitations of a purely knowledge-based method of evaluation and why in 1992, we are now attempting to redefine and assess, what we call 'clinical ethical competence' in terms of how students actually apply this knowledge base in a controlled clinical context.

Australia↗
PubMed1992

Teaching bioethics to medical students: the Newcastle experience.

Over the past two decades in the USA, bioethics has become an accepted component of medical education, whereas in Australia, 10 years or even less would encompass the history of most existing programmes. Given the legendary conservatism of medical schools in Australia and the intractability of the medical curriculum, this is still a remarkable achievement. But does the teaching of bioethics change the thinking and/or decision-making behaviour of medical students or practitioners exposed to such courses? Those involved know only too well how difficult such courses are to design and evaluate since the connection between ethics education and practice is not known and may never be demonstrated to the satisfaction of critics. Critics not only seek answers to the questions of whether the teaching of bioethics makes a difference, which is a fair question, but they also seek answers to the question of whether bioethics should be taught in medical schools. Can bioethics be taught? Whose bioethics is being taught? What does the trained bioethicist contribute? Some of these questions arise from misunderstanding and some reflect the still too dominant view in medical schools which divides disciplines into those which provide 'practical skills', and those which contribute only theoretical and therefore peripheral knowledge. The authors will address these questions in the light of their experience at Newcastle, Australia, where the Faculty of Medicine has been teaching bioethics for over a decade.

Attitude of Health Personnel↗
PubMed1986

Satisfaction of patients with medical student's clinical skills.

A patient satisfaction-dissatisfaction rating scale was developed to measure patients' perceptions of the attitudes and communication skills of medical students. An 11-item questionnaire was completed by trained patients following an end-of-year clinical assessment of the first- and third-year students of a five-year training program. The patients rated 80 percent of the first-year students and 90 percent of the third-year students as acceptable as future doctors. The patients showed a statistically significant preference for the third-year students (p less than 0.05). To assess the reliability over time of patient reactions, two consecutive third-year student groups were compared, and no significant differences in patient satisfaction-dissatisfaction were apparent. The patients tended to perceive female students as more satisfactory than male students. A weak positive correlation between faculty assessments of students and those of the patients was observed. These results suggest that patients are capable of detecting small general improvements in students' attitudes and general manner across years of training and that the patients' ratings are reliable over time.

Australia↗