Valuable asset. Interview by Tim Rice.
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Biomedical subjects
Publications and source records attributed to M Stacey.
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Measurement of colony-forming ability following exposure to gamma-rays was performed on cultured skin keratinocytes and skin fibroblasts obtained from normal individuals, basal cell naevus syndrome patients (BCNS) and ataxia telangiectasia (A-T) patients. The most striking observation was the radiation resistance of 8/8 keratinocyte strains compared with fibroblasts whether from BCNS patients or normals. The single A-T keratinocyte cell strain showed the same radiosensitivity as A-T fibroblast cell strains. The differential survival of keratinocytes and fibroblasts was also observed following exposure to 254 nm UV light. The survival curves of SV40 immortalized keratinocytes and retinoblasts derived from normal individuals or BCNS patients showed large shoulder regions following exposure to gamma-rays or 254 nm UV light. An increased D37 rather than an increased D0 was therefore the feature of such curves. This contrasted with the SV40 immortalized A-T keratinocytes or fibroblasts which showed a minimal shoulder effect and an increased D0. No difference in survival was observed between BCNS and normal cells following exposure to either UV or gamma-rays.
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Two ataxia telangiectasia patients with unusual clinical and cellular features are described. Cultured fibroblasts and PHA stimulated lymphocytes from these two patients showed a smaller increase of radiosensitivity than cells from other A-T patients, as measured by colony forming ability or induced chromosome damage respectively, after exposure to ionising radiation. The response of DNA synthesis to irradiation of these cells was, however, the same as for other A-T patients. Cells from a third patient with some clinical features of A-T but with a very protracted course also showed low levels of radiation induced chromosome damage, but colony forming ability and the response of DNA synthesis after irradiation were no different from cells of normal subjects. There was, however, an increased level of translocations and unstable chromosomal rearrangements in this patient's lymphocytes.
This paper argues that two characteristics of social life impinge importantly upon medical attempts to maintain high ethical standards. The first is the tension between the role of ethics in protecting the patient and maintaining the solidarity of the profession. The second derives from the observation that the foundations of contemporary medical ethics were laid at a time of one-to-one doctor-patient relations while nowadays most doctors work in or are associated with large-scale organisations. Records cease to be the property of individual doctors, become available not only to other doctors but also to educational and social work personnel. Making records openly available to patients is suggested as the only antidote to this irreversible loss of individual practitioner control. The importance for doctors of understanding the nature of professional and bureaucratic organisations in order to deal with the hazards involved is stressed as is the responsibility of the General Medical Council to regulate medical competence as well as personal behaviour.
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In assessing some of the existing patterns and future possibilities in child health care it was found that the continuing large social class differences in morbidity and mortality may be attributed to continued poverty, both of income and therefore of diet, and also to environmental deprivation. The absence of safe places for children to play, for example, is related to the high accident rates experienced by children. Doctors admit to awareness of these social and environmental causes of unnecessary morbidity and mortality among children but have failed to address the causes directly. While the causes are outside the immediate professional provenance of doctors, it is argued that, aware as they are of this aetiology, they have a moral and professional responsibility to act collectively as a pressure group urging improvements on the relevant authorities (as they have done in the case of smoking and clean air, for example).
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The structures of the isomeric products obtained on trimethylsilylation of naturally occurring hexuronic acids and their sodium salts and lactones have been established by the application of n.m.r. (for anomeric configuration) and mass spectrometry (for ring size). The equilibria of some of the hexuronic acids in methyl sulphoxide involved a larger proportion of furanoid forms than those in water or pyridine. The proportion of furanoses was also increased by the addition of hexamethyldisilazane. Kinetic evidence indicated that two molecules of each hexuronic acid interacted autocatalytically during mutarotation.
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The free acids, sodium salts, and lactones of several hexuronic acids have been studied as their O-trimethylsilyl derivatives by gas-liquid chromatography using SE-30 and XE-60 liquid phases. Silylation was best performed in methyl sulphoxide. The equilibrium between the various forms of a hexuronic acid in methyl sulphoxide was also studied by g.l.c. following silylation. The hexamethyldisilazane used in the silylation disturbed the equilibrium attained in the solvent, but this was overcome by premixing the hexamethyldisilazane with chlorotrimethylsilane. Methyl sulphoxide and the silylating reagents gave a two-phase system in which the derivative was favourably partitioned into the upper layer. Partition coefficients and stabilities of the derivatives were measured, and a g.l.c. method for the analysis of the hexuronic acids was thereby developed. The oximes of the hexuronic acids were studied as alternative derivatives for g.l.c., and their equilibrium compositions and g.l.c. retention times are recorded.
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