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51.
Monoaminergic activities in Lewy Body dementia: Relation to hallucinosis and extrapyramidal features
E. K. Perry E. Marshall P. Thompson I. G. McKeith D. Collerton A. F. Fairbairn I. N. Ferrier D. Irving R. H. Perry 《Journal of neural transmission (Vienna, Austria : 1996)》1993,6(3):167-177
Summary Serotonergic (5-HT) and dopaminergic activities have been examined in Lewy Body Dementia (LBD) and compared with Parkinson's disease (PD) and Alzheimer's disease (AD). In the neocortex the LBD subgroup experiencing hallucinations was distinguised from the other categories by an increase in the 5HIAA:5HT ratio measured in frontal cortex and by the serotonergic (5-HIAA or 5-HIAA:5-HT): cholinergic (choline acetyltransferase) ratio in frontal and temporal cortex. In the neostriatum (caudate nucleus), loss of dopamine and increased HVA: dopamine ratio correlated with the reduction in substantia nigra neurons in LBD but not PD, despite the greater loss of neurones and dopamine and the higher dopamine turnover ratio in PD. LBD patients experiencing severe Parkinsonism as a result of neuroleptic treatment tended to have lower neuron counts, in combination with higher turnover ratios, than the remainder. Qualitative differences between LBD and PD included decreased cortical 5-HT turnover in PD compared with the increase in LBD. There were no significant changes in any parameter in AD, with the exception of a reduction in temporal cortex 5HIAA. The results suggest that although the neurochemical pathology of LBD and PD involves similar systems, the nature of the derangements differs sufficiently between the diseases to account for differences in symptomatology. 相似文献
52.
Mark Domken Robert Bothwell Ian McKeith 《International journal of geriatric psychiatry》1995,10(1):41-46
Data were collected on inpatients admitted to one psychogeriatric unit in the Newcastle upon Tyne area, in the first 6 months of 1985, 1988 and 1991—a period which saw substantial reductions in the number of long-term elderly care bed numbers in the statutory sector. Admissions to the unit increased by almost 50% over the 6 years while mean length of stay decreased from 12.4 to 9.4 weeks. Between 1988 and 1991 discharges into private sector care increased considerably with no evidence that this group differed in any way from those patients discharged into statutory care in terms of level of dependency or presence of behavioural problems. Patients with high dependency needs or behaviour problems which were difficult to manage tended to stay in hospital for much longer periods, possibly indicating a shortfall of suitable long-stay facilities for this patient group. 相似文献
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Motor subtype and cognitive decline in Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies 总被引:3,自引:0,他引:3
Burn DJ Rowan EN Allan LM Molloy S O'Brien JT McKeith IG 《Journal of neurology, neurosurgery, and psychiatry》2006,77(5):585-589
BACKGROUND: A previous cross sectional study found over-representation of a postural instability gait difficulty (PIGD) motor subtype in Parkinson's disease patients with dementia (PDD) and dementia with Lewy bodies (DLB), compared with Parkinson's disease (PD). AIMS: (1) To examine rates of cognitive and motor decline over two years in PD (n=40), PDD (n=42) and DLB (n=41) subjects, compared with age matched controls (n=41), (2) to record whether motor phenotypes of PD, PDD, and DLB subjects changed during the study, (3) to find out if cognitive and motor decline in PD was associated with baseline motor subtype, and (4) to report the incidence of dementia in PD patients in relation to baseline motor subtype. RESULTS: Most of PDD and DLB participants were PIGD subtype at baseline assessment. In the non-demented PD group, tremor dominant (TD) and PIGD subtypes were more evenly represented. Cognitive decline over two years was greater in PDD and DLB groups (mean decline in MMSE -4.5 and -3.9, respectively), compared with PD (-0.2) and controls (-0.3). There was an association between PIGD subtype and increased rate of cognitive decline within the PD group. Of 40 PD patients, 25% of the 16 PIGD subtype developed dementia over two years, compared with none of the 18 TD or six indeterminate phenotype cases (chi2=6.7, Fisher's exact test p<0.05). CONCLUSION: A PIGD motor subtype is associated with a faster rate of cognitive decline in PD and may be considered a risk factor for incident dementia in PD. 相似文献
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IG Azcárate P Marín-García N Camacho S Pérez-Benavente A Puyet A Diez L Ribas de Pouplana JM Bautista 《British journal of pharmacology》2013,169(3):645-658
Background and Purpose
Blood-stage Plasmodium parasites cause morbidity and mortality from malaria. Parasite resistance to drugs makes development of new chemotherapies an urgency. Aminoacyl-tRNA synthetases have been validated as antimalarial drug targets. We explored long-term effects of borrelidin and mupirocin in lethal P. yoelii murine malaria.Experimental Approach
Long-term (up to 340 days) immunological responses to borrelidin or mupirocin were measured after an initial 4 day suppressive test. Prophylaxis and cure were evaluated and the inhibitory effect on the parasites analysed.Key Results
Borrelidin protected against lethal malaria at 0.25 mg·kg−1·day−1. Antimalarial activity of borrelidin correlated with accumulation of trophozoites in peripheral blood. All infected mice treated with borrelidin survived and subsequently developed immunity protecting them from re-infection on further challenges, 75 and 340 days after the initial infection. This long-term immunity in borrelidin-treated mice resulted in negligible parasitaemia after re-infections and marked increases in total serum levels of antiparasite IgGs with augmented avidity. Long-term memory IgGs mainly reacted against high and low molecular weight parasite antigens. Immunofluorescence microscopy showed that circulating IgGs bound predominantly to late intracellular stage parasites, mainly schizonts.Conclusions and Implications
Low borrelidin doses protected mice from lethal malaria infections and induced protective immune responses after treatment. Development of combination therapies with borrelidin and selective modifications of the borrelidin molecule to specifically inhibit plasmodial threonyl tRNA synthetase should improve therapeutic strategies for malaria. 相似文献58.
A B Singleton A M Gibson I G McKeith C A Ballard R H Perry P G Ince J A Edwardson C M Morris 《Neuroreport》1999,10(7):1507-1510
Dementia with Lewy bodies (DLB) is the second most common cause of dementia in the elderly after Alzheimer's disease (AD). The apolipoprotein E gene (APOE) is a major risk factor, but can only account for approximately 50% of AD cases. Whole genome scanning in late-onset AD families has suggested that a locus on chromosome 12 may contribute significantly to disease development. Recently the alpha2-macroglobulin gene (A2M) on chromosome 12 has been suggested as a candidate locus for AD. We therefore determined the influence of two polymorphisms in A2M, a pentanucleotide deletion 5' to the bait domain exon, and a valine to isoleucine polymorphism in the thiolester site of the protein, in AD and DLB cohorts. No evidence was observed for an association between the thiolester or deletion polymorphisms and AD or DLB alone or when accounting for the APOE epsilon4 allele. We did, however, identify a non-significant excess of deletion homozygotes in the AD and DLB groups. This genotype accounted for 4% of disease cases but was absent in the control population. Given that the A2M deletion polymorphism is non-functional, the chromosome 12 AD/DLB locus may be situated elsewhere and not with these A2M polymorphisms. 相似文献
59.
M. P. Walker G. A. Ayre C. H. Ashton V. R. Marsh K. Wesnes E. K. Perry J. T. O'Brien I. G. McKeith C. G. Ballard 《Human psychopharmacology》1999,14(7):483-489
Fluctuating levels of consciousness (FC) are a key feature in neurodegenerative dementias, yet clinical identification is poor, hindering accurate diagnosis. One hundred and nineteen patients (32 Dementia with Lewy Bodies (DLB), 57 Alzheimer's disease (AD) and 30 controls) with clinical scores of FC were assessed using an attentional task. Cortical arousal was assessed in 25 of these patients using electroencephalography. Over 90 s both variability in attention (p<0·0001) and fluctuations in electrocortical activity (p<0·0001) correlated with clinical FC scores, and with each other (p<0·0001). Variability in attention and electrocortical arousal are accurate FC markers and can assist differential diagnosis of AD and DLB. Previous work has underestimated the intensity and hence impact of FC in dementia. Copyright © 1999 John Wiley & Sons, Ltd. 相似文献
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