British medical bulletin
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British medical bulletin · Jan 2003
ReviewMolecular and clinical classification of human prion disease.
While rare in humans, the prion diseases have become an area of intense clinical and scientific interest. The recognition that variant Creutzfeldt-Jakob disease is caused by the same prion strain as bovine spongiform encephalopathy in cattle has dramatically highlighted the need for a precise understanding of the molecular biology of human prion diseases. Detailed clinical, pathological and molecular data from a large number of human prion disease cases have shown that distinct abnormal isoforms of prion protein are associated with prion protein gene polymorphism and neuropathological phenotypes. A molecular classification of human prion diseases seems achievable through characterisation of structural differences of the infectious agent itself.
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The recent completion of a working draft of the human genome sequence promises to provide unprecedented opportunities to explore the genetic basis of individual differences in complex behaviours and vulnerability to neuropsychiatric illness. Functional neuroimaging, because of its unique ability to assay information processing at the level of brain within individuals, provides a powerful approach to such functional genomics. Recent fMRI studies have established important physiological links between functional genetic polymorphisms and robust differences in information processing within distinct brain regions and circuits that have been linked to the manifestation of various disease states such as Alzheimer's disease, schizophrenia and anxiety disorders. Importantly, all of these biological relationships have been revealed in relatively small samples of healthy volunteers and in the absence of observable differences at the level of behaviour, underscoring the power of a direct assay of brain physiology like fMRI in exploring the functional impact of genetic variation.
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Obstructed labour is an important cause of maternal deaths in communities in which undernutrition in childhood is common resulting in small pelves in women, and in which there is no easy access to functioning health facilities with the capability of carrying out operative deliveries. Obstructed labour also causes significant maternal morbidity in the short term (notably infection) and long term (notably obstetric fistulas). Fetal death from asphyxia is also common. ⋯ These seem still rather distant aspirations. In the meantime, strategies should be implemented to encourage early recognition of prolonged labour and appropriate clinical responses. The sequelae of obstructed labour can be an enormous source of human misery and the prevention of obstetric fistulas, and skilled treatment if they do occur, are important priorities in regions where obstructed labour is still common.
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While it has long been known that female fertility is impaired by oestrogen exposure, it is unclear whether environmental pollutants with weak oestrogenic effects are sufficiently potent and prevalent to have biological effects in humans. Male fertility, or sperm concentration at least, appears to have deteriorated, and there is substantial spatial variation at both national and global level, as well as a genetic component. Sperm morphology and motility are implicated too. ⋯ Weak environmental oestrogens are not responsible. Candidates include agents affecting endogenous maternal oestrogen levels, environmental anti-androgens (although these cannot explain the epidemiological findings), and dioxin and related compounds. Genetic damage should be considered as a unifying hypothesis, possibly focused on the Y-chromosome.