British medical bulletin
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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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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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Current evidence suggests that the overall load of infectious agents, including respiratory viruses, encountered early in life is an important factor influencing maturation of the immune system from a type 2 bias at birth towards predominantly type 1 responses, thus avoiding atopic diseases. The 'hygiene hypothesis' proposes that the relatively sterile environment present in industrialised Western countries has contributed to the recent epidemic of asthma and atopy. Whether specific infections are of greater or lesser protective value is an important question if strategies are to be derived to mimic the beneficial effects of childhood infection whilst avoiding morbidity and potential mortality of the natural pathogens. ⋯ Viruses are detected in up to 85% of such episodes. Rhinovirus is common in all age groups; respiratory syncytial virus (RSV) is most important in infants and young children. Knowledge of the immunopathogenetic mechanisms of virus infection in the asthmatic airway will lead to the development of new treatments for virus-induced asthma.
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Radiotherapy has an established role in the treatment of rectal cancer. In primary resectable cancer, numerous randomised trials have shown that particularly pre-operative, and to some extent also postoperative, radiotherapy substantially reduces the risk of local failure. This is seen also with total mesorectal excision. ⋯ In non-resectable cancer, radiotherapy may cause down-staging, allow surgery, and may cure some patients. Whether radiochemotherapy is more efficient has yet to be firmly established. The role of pre-operative radio(chemo)therapy to permit more sphincter-preserving procedures with adequate long-term function is not defined.
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There is currently intense research activity aimed at the development of new delivery systems for vaccines. The goal is to identify optimal methods for presenting target antigens to the immune system in a manner that will elicit immune responses appropriate for protection against, or treatment of, a specific disease. ⋯ This article will review three categories of delivery systems: (i) adjuvants and formulations; (ii) antigen vectors, including live attenuated micro-organisms and synthetic vectors; and (iii) novel devices for vaccine administration. The review will be restricted to late stage developments in the field of human vaccination.