PET measurement of cardiac and nigrostriatal denervation in Parkinsonian syndromes.

Scintigraphic imaging with (123)I-metaiodobenzylguanidine ((123)I-MIBG) has demonstrated extensive losses of cardiac sympathetic neurons in idiopathic Parkinson's disease (IPD). In contrast, normal cardiac innervation has been observed in (123)I-MIBG studies of multiple-system atrophy (MSA) and progressive supranuclear palsy (PSP). Consequently, it has been hypothesized that cardiac denervation can be used to differentiate IPD from MSA and PSP. We sought to test this hypothesis by mapping the distribution of cardiac sympathetic neurons in patients with IPD, MSA, and PSP by using PET and (11)C-meta-hydroxyephedrine ((11)C-HED). Also, the relationship between cardiac denervation and nigrostriatal denervation was investigated by measuring striatal presynaptic monoaminergic nerve density with PET and (11)C-dihydrotetrabenazine ((11)C-DTBZ). METHODS: (11)C-HED and (11)C-DTBZ scans were obtained for patients with IPD (n = 9), MSA (n = 10), and PSP (n = 8) and for age-matched control subjects (n = 10). Global and regional measurements of (11)C-HED retention were obtained to assess the extent of cardiac sympathetic denervation. (11)C-DTBZ binding was measured in the caudate nucleus, anterior putamen, and posterior putamen. RESULTS: As expected, extensive cardiac denervation was observed in several of the patients with IPD. However, substantial cardiac denervation was also seen in some patients with MSA and PSP. (11)C-DTBZ studies demonstrated striatal denervation in all patients with IPD and in most patients with MSA and PSP. No correlation was found between cardiac (11)C-HED retention and striatal (11)C-DTBZ binding. CONCLUSION: Cardiac sympathetic denervation was found to occur not only in IPD but also in other movement disorders, such as MSA and PSP. This finding implies that scintigraphic detection of cardiac sympathetic denervation cannot be used independently to discriminate IPD from other movement disorders, such as MSA and PSP. Cardiac sympathetic denervation was not correlated with striatal denervation, suggesting that the pathophysiologic processes underlying cardiac denervation and striatal denervation occur independently in patients with parkinsonian syndromes. These findings provide novel information about central and peripheral denervation in patients with neurodegenerative disorders.     

Neuropsychological predictors of self-neglect in cognitively impaired older people who live alone.

OBJECTIVE: The authors examined the accuracy of certain neuropsychological tests in the prediction of harm resulting from self-neglect in cognitively impaired seniors who lived alone. METHODS: The study included 130 participants, aged 65 and older, who scored less than 131 on the Dementia Rating Scale. Neuropsychological tests were administered at baseline, resulting in eight predictive scores. Informants and primary care physicians provided information about harm that occurred to the participants during the 18-month prospective follow up. An incident was defined as harmful if it occurred as the result of self-neglect or disorientation and resulted in physical injury or property loss or damage and required emergency interventions. Proportional hazard regression analysis was conducted to examine the predictive relationship between the eight neuropsychological tests and time to incident harm with age, sex, education, the Charlson Comorbidity Index, and the Mini-Mental State Examination included in the model as covariates. RESULTS: Twenty-seven participants experienced harm during the 18-month follow-up period. A proportional hazards model indicated that three neuropsychological tests, which measured recognition memory, executive functioning, and conceptualization, were independent risk factors for harm. CONCLUSIONS: These findings provide insight into why harm occurred in these cognitively impaired elders who lived alone. They also support the ecologic validity of these tests and suggest directions for the development of intervention strategies for harm prevention.     

Natural killer cell activity and autologous mixed lymphocyte response of splenic,mesenteric lymph node,and colonic lymphocytes during DMH-induced colon carcinogenesis in the rat

Twoin vitro models of immune surveillance were used to examine the immune status of the gut-associated lymphoid tissue, mesenteric lymph nodes, and spleen during the early stages of 1,2-dimethylhydrazine (DMN)-induced colon tumorigenesis. DMH-and vehicletreated Fischer rats were sacrificed at one of three time points; one week, two months, or five months after cessation of treatment. Colonic, lymph node, and splenic natural killer cell cytolytic activity toward YAC-1 tumor targets and T-cell response to autologous la-induced balstogenesis were measured at each time point. We found little change in natural killer cell activity or T-cell proliferation induced by autologous Ia gene products at these time periods.This investigation was supported in part by grant CA26917 from the National Cancer Institute, Department of Health and Human Services.