Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
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In the diseased brain, upon activation microglia express binding sites for synthetic ligands designed to recognize the 18-kDa translocator protein TP-18, which is part of the so-called peripheral benzodiazepine receptor complex. PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide], the prototype synthetic ligand, has been widely used for the functional characterization of TP-18. Its cellular source in activated microglia has been established using high-resolution, single-cell autoradiography with the R-enantiomer [3H](R)-PK11195. ⋯ Thus, a profile of active disease emerges that matches some of the typical distribution patterns known from structural neuroimaging techniques, but additionally shows involvement of brain regions linked through neural pathways. In the context of cell-based in vivo neuropathology, the image data are thus best interpreted in the context of the emerging cellular understanding of brain disease or damage, rather than the definitions of clinical diagnosis. One important observation, borne out by experiment, is the long latency with which activated microglia or increased PK11195 retention appear to gradually emerge and remain in distal areas secondarily affected by disease, supporting speculations that the presence of activated microglia is an important corollary of brain plasticity.
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Medical care of patients with dementia often occurs within a physician-patient relationship whose features differ from relationships with patients without dementia. Many basic assumptions of the physician-patient relationship may not completely hold true, and certain aspects of the patient role may be shared by others besides the patient. For example, the entire premise of consent to the patient role may be inapplicable to patients who lack insight into their illness. ⋯ This can lead to viewing patients as collections of symptoms rather than as humans suffering with illnesses and burdens. The fact that certain medical interventions, such as treatment of neuropsychiatric disturbances that do not trouble the patient, may appear to be initiated for the primary purpose of alleviating caregiver emotional stress also affects the physician-patient relationship. The present review examines how this relationship may be altered and presents a framework within which these alterations can be considered.