Quantitative magnetic resonance imaging (MRI) was used to assess global and regional cerebral volumes in patients with a clinical diagnosis of subcortical vascular dementia (VD) and Alzheimer's ...disease (AD). Whole brain volume, cerebrospinal fluid volume, volumes of the temporal, frontal and parietal lobes, the cerebellum and the amygdala-hippocampus complex were determined using a personal computer-based software. Seventeen patients with VD, 22 patients with AD and 13 healthy controls were included. Analysis of covariance using age as covariate demonstrated significant mean differences between controls and dementia groups with respect to all morphological parameters. However, apart from the volume of the cerebellum no significant volumetric differences were found between VD and AD. These results indicate that MRI-based volumetry allows differentiation between AD or VD from normal controls and that measurement of cerebellar volume may be of use to separate vascular and degenerative dementia. However, since the distribution of cerebral atrophy in both dementia groups is very similar, it is suggested that the atrophic changes are not specific to the underlying cause but rather reflect the selective vulnerability of neuronal structures.
To examine the association of insulin and sympathetic nervous system activity with blood pressure elevation in a cross-sectional study of 752 nondiabetic male participants of the Normative Aging ...Study, aged 43-90 years.
Testing included a physical examination, medical history, fasting and post-carbohydrate insulin and glucose levels determinations, an anthropometric examination, and 24 h urine collection for catecholamine level determination. Total obesity was represented by body mass index, central obesity by the abdomen circumference:hip circumference ratio, and sympathetic nervous system activity by 24 h urinary excretion of norepinephrine.
Systolic and diastolic blood pressure (SBP and DBP, respectively) were positively related to body mass index, abdomen:hip ratio, norepinephrine excretion, and insulin levels in univariate analyses. The relationship between insulin level and SBP and DBP persisted after adjustment for body mass index, abdomen:hip ratio, norepinephrine, age, smoking, physical activity level, and antihypertensive medication use. The norepinephrine level was related to SBP and DBP after adjustment for insulin level, age, smoking, physical activity level, and antihypertensive medication use, and these relationships remained marginally significant after further adjustment for body mass index and abdomen:hip ratio. In contrast, neither body mass index nor abdomen:hip ratio were related to blood pressure after adjustment for insulin level. Among participants in the lowest tertiles both of insulin and of norepinephrine levels, 10% were hypertensive, compared with 35% in the highest tertiles of these variables. In a multiple logistic regression model, insulin level, norepinephrine level, and an interaction term for insulin level with norepinephrine excretion were independent predictors of hypertension.
The results suggest that insulin level and sympathetic nervous system activity are associated with hypertension among middle-aged and elderly men.
Pathological and biochemical studies indicate that beta-amyloid (betaA4) deposition is a hallmark in the pathogenesis of Alzheimer's disease (AD). Neuroimaging studies demonstrate that the respective ...cerebral changes primarily strike the temporal lobe and the amygdala-hippocampus complex and may be reliably assessed using quantitative magnetic resonance imaging (MRI). Therefore one may expect that reduced betaA4-levels are significantly correlated with measures of the temporal lobe rather than global cerebral atrophy in AD patients. To test this hypothesis in a clinical study, cerebrospinal fluid concentrations of total betaA4 and its major C-terminal variations betaA4 1-40 and betaA4 1-42 were compared with cerebral changes as assessed by quantitative magnetic resonance imaging (MRI). Significantly (P< 0.05) reduced betaA4 1-40 and betaA4 1-42 levels were found in the AD patients (17 female; six male; AD/NINCDS-ADRDA-criteria) in comparison to the patients with major depression (seven female; two male; DSM-III-R). Within the AD group, betaA4 and betaA4 1-42 levels were significantly correlated with the volume of the temporal lobes (r= 0.46 and r= 0.48, respectively) but none of the other volumetric measures. These findings indicate that changes in cerebral betaA4 levels contribute to temporal lobe atrophy in AD and support the possibility that betaA4 is central to the etiology of AD.
Establishing the diagnosis in patients with clinical signs and symptoms suggesting primary degenerative disease with marked frontal lobe involvement is difficult. Neuroimaging methods, in particular ...positron emission tomography (PET) with the tracer 18fluoro-2-deoxyglucose (FDG) and cerebrospinal fluid (CSF) examination of beta-amyloid and tau-protein levels may give additional information. We report five patients with clinical and radiological features of degenerative dementia with predominantly frontal involvement and one patient with primary progressive aphasia Diagnostic work-up included computed tomography (CT), magnetic resonance imaging (MRI), PET and tau-protein and beta-amyloid level determination in CSF. While neuropsychological performance varied among patients, CT and MRI demonstrated persistently frontal lobe involvement. PET revealed corresponding changes with frontal hypometabolism, but in addition, four patients (among them two with no corresponding temporal changes in CT or MRI) showed a decreased glucose uptake in the temporal cortices. CSF samples from five patients revealed elevated beta-amyloid 1-42 and tau levels in three and two patients, respectively. Reduced beta-amyloid 1-40 was found in two patients. We conclude that occurrence of clinical symptoms of frontotemporal dementia is accompanied by frontal hypometabolism regardless of additional clinical findings. The value of determination of beta-amyloid and tau protein levels remains to be determined.
Deferred prosecutions and the independent monitor Robinson, James K; Urofsky, Philip E; Pantel, Christopher R
International journal of disclosure and governance,
12/2005, Letnik:
2, Številka:
4
Journal Article
Recenzirano
In response to today's wave of corporate investigations and prosecutions, prosecutors have sought to require significant changes in corporate culture, compliance and controls and, as importantly, to ...monitor those changes for a reasonable time. The result is the corporate deferred prosecution agreement and its adjunct, the Independent Monitor. This paper first will review the development of deferred prosecution agreements and the factors which may determine which companies receive such treatment; secondly, it will analyse the Independent Monitor's role, both the common terms of reference and certain unique terms relevant to specific cases; and thirdly, it will suggest the outlines of an Independent Monitor's workplan. PUBLICATION ABSTRACT
In humans, growth hormone receptor (GHR) transcripts exist in two isoforms differing by the retention (GHRfl) or exclusion (GHRd3) of exon 3, whereas in mice GHRfl is solely expressed. This ...species-specific expression pattern is believed to result from an alternative splice event that, on the basis of conflicting data obtained in humans, has been considered to be tissue-, developmentally, and/or individual-specific. To decipher the molecular basis of this unusual trait, we isolated a 6.8-kilobase fragment spanning exon 3 from individuals expressing GHRfl. Sequence analysis revealed the existence of two 99% identical retroelements flanking this exon. Unexpectedly, individuals expressing GHRd3 displayed a 2.7-kilobase deletion involving exon 3, which most likely results from an ancestral homologous recombination between the two retroelements. The lineage of these retroelements during primate evolution revealed the species specificity of the GHRd3 allele. These findings led us to propose a model underlying the existence of the sole GHRfl allele in most species. Such a retrovirus-mediated alternative splice mimicry, which clears up several as yet unexplained phenomena (i.e. the above-mentioned expression data, the Mendelian inheritance of GHR expression patterns, and the deletion of nonconsecutive exons in growth hormone resistant patients), represents a novel physiological mechanism accounting for protein diversity between and within species.
We used the Heaviness of Smoking Index, a subset of the Fagerstrom Test for Nicotine Dependence, to classify 608 cigarette smokers planning a cessation attempt as low or high in nicotine dependence. ...Subjects within each level of dependence were then randomly assigned to placebo, 2-mg, or 4-mg nicotine gum treatment. Subjects were also provided brief (5–10 min per visit) behavioral counseling during a 1-year period of follow-up. At 1 year post-cessation, quit rates were 11.2, 19.5, and 18.4% for low-dependence smokers receiving placebo, 2-mg, and 4-mg gum, respectively (plinear trend=0.20). For high-dependence smokers, quit rates at 1 year were 6.1, 15.7, and 20.7% for the placebo, 2-mg, and 4-mg gum conditions, respectively (plinear trend=0.002). The interaction of nicotine-gum dose and dependence group was not significant (p=0.42), nor did the 2-mg and 4-mg doses differ significantly in effectiveness, though both 2-mg and 4-mg gum were significantly more effective than placebo gum. We also found a significant dose-related effect for nicotine gum to moderate post-cessation heart-rate decline. Other variables related to abstinence at 1 year post-cessation were a longer period of abstinence on a prior quit attempt, being married, higher education level, and having a non-smoking spouse or significant other. Results indicate that nicotine gum is a significant aid to smoking cessation, more than doubling the odds of successful cessation compared to the odds for placebo-gum users. The 4-mg dose provided a non-significant increase in cessation rates for high-dependence smokers. Smoking history and demographic variables also have a significant impact on the outcome of a quit-smoking attempt.
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