Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11-16 years) developed alpha-synuclein-positive Lewy bodies in grafted neurons. Our observation has key implications for understanding Parkinson's pathogenesis by providing the first evidence, to our knowledge, that the disease can propagate from host to graft cells. However, available data suggest that the majority of grafted cells are functionally unimpaired after a decade, and recipients can still experience long-term symptomatic relief.
Synaptic dopamine release from embryonic nigral transplants has been monitored in the striatum of a patient with Parkinson's disease using [11C]-raclopride positron emission tomography to measure dopamine D2 receptor occupancy by the endogenous transmitter. In this patient, who had received a transplant in the right putamen 10 years earlier, grafts had restored both basal and drug-induced dopamine release to normal levels. This was associated with sustained, marked clinical benefit and normalized levels of dopamine storage in the grafted putamen. Despite an ongoing disease process, grafted neurons can thus continue for a decade to store and release dopamine and give rise to substantial symptomatic relief.
This paper discusses recent advances that have been made in the field of psychometrics, specifically, the application of Rasch analysis to the instrument development process. It emphasizes the importance of assessing the fundamental scaling properties of an instrument prior to consideration of traditional psychometric indicators. The paper introduces Rasch analysis and shows how it has been applied in the development of needs-based measures in order to ensure that they provide unidimensional measurement. By ensuring that scales are based on the same measurement model and that they fit the Rasch model it is possible for QoL scores to be compared across diseases by means of cocalibration and item banking.
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