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Biomedical subjects

L Amaducci

Publications and source records attributed to L Amaducci.

At least 73 records · Page 4Linked to original sources

Cross-national interrater agreement on the clinical diagnostic criteria for dementia. WHO-PRA Age-Associated Dementia Working Group, WHO-Program for Research on Aging, Health of Elderly Program.

We assessed the interobserver agreement on the clinical diagnosis of dementia syndrome and dementia subtypes as part of a cross-national project on the prevalence of dementia. Fourteen clinicians from the participating countries (Canada, Chile, Malta, Nigeria, Spain, and the United States) independently assessed the diagnosis of 51 patients whose clinical information was in standard records written in English. We used the DSM-III-R and ICD-10 criteria for dementia syndrome, the NINCDS-ADRDA criteria for Alzheimer's disease (AD), and the ICD-10 criteria for other dementing diseases, and measured interobserver agreement. We found comparable levels of agreement on the diagnosis of dementia using the DSM-III-R (kappa = 0.67) as well as the ICD-10 criteria (kappa = 0.69). Cognitive impairment without dementia was a major source of disagreement (kappa = 0.10). The kappa values were 0.58 for probable AD, 0.12 for possible AD, and rose to 0.72 when the two categories were merged. The interrater reproducibility of the diagnosis of vascular dementia was 0.66 in terms of kappa index; the diagnoses of other dementing disorders as a whole reached a kappa value of 0.40. This study suggests that clinicians from different cultures and medical traditions can use the DSM-III-R and the ICD-10 criteria for dementia effectively and thus reliably identify dementia cases in cross-national research. The interrater agreement on the diagnosis of dementia might be improved if clear-cut guidelines in the definition of cognitive impairment are provided. To improve the reliability of AD diagnosis in epidemiologic studies, we suggest that the NINCDS-ADRDA "probable" and "possible" categories be merged.

Aged↗

Relation between MRI features and dementia in cerebrovascular disease patients with leukoaraiosis: a longitudinal study.

We examined selective MRI features (localization and degree of white matter abnormalities, cortical and subcortical atrophy) in relation to cognitive decline in patients with cerebrovascular disease (CVD) and leukoaraiosis (LA). We enrolled 6 female and 18 male CVD patients (mean age 66.2 +/- 6.6 years) whose Magnetic Resonance Images (MRI) revealed LA and who displayed a history of stroke or TIA; none showed signs of cortical infarcts or normal pressure hydrocephalus. Two blind raters independently scored MRI scans with a high level of agreement. All patients underwent extensive clinico-neuropsychological assessment upon admission to the study and 19 were followed for an average of 48 +/- 7.6 months. Twelve patients were initially classified as non-demented and 12 as demented. Three years later, one in the former group had become demented and mental impairment had worsened for 6 patients in the latter group; these 7 subjects were labeled as "decliners". Ventricular indexes were significantly higher in the demented group and correlated with severity of mental impairment, while the degree of LA was similar in demented and non-demented subjects. Neither white matter lesions nor sulcal and ventricular enlargement differed statistically between decliners and non-decliners.

Aged↗

Cerebral soluble ubiquitin is increased in patients with Alzheimer's disease.

A study concerning the amount of soluble ubiquitin in different cortical and subcortical regions of brains from patients with Alzheimer's disease compared to the amount in normal brains is presented. Several samples from 9 brain regions were processed and analyzed by liquid chromatography. In almost all the investigated cerebral regions the soluble ubiquitin content was significantly higher in pathologic tissue than in normal tissue. The primary structure of ubiquitin isolated from brain tissue affected by Alzheimer's degenerative processes was determined and resulted to be identical to normal human ubiquitin. These findings, together with the detection of polyubiquitinated proteins in paired helical filaments of neurofibrillary tangles described by several authors, suggest that an impairment of the process of intracellular, ubiquitin-dependent proteolysis might play an important role in the pathogenesis of this neurodegenerative disease. On the other hand, the expression of the correct polypeptide sequence in brain with Alzheimer's disease seems to exclude a mutation of the polyubiquitin gene as a cause of these alterations.

Adult↗

Effect of phosphatidylserine on free radical susceptibility in human diploid fibroblasts.

We studied the effect of phosphatidylserine (PdtSER) on oxygen metabolite toxicity in skin fibroblast cell lines from apparently normal subjects. Fibroblast damage was produced by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by xanthine-oxidase (Xo). In order to quantify cell damage, we measured lactate dehydrogenase (LDH) activity in culture medium and cell viability in fibroblast cultures, with and without preincubation for 4 days with PdtSER 13 microM, after Xo incubation. We found a significant increase of LDH activity in culture medium of cells without preincubation with PdtSER. No significant increase of LDH activity was observed in the same cell lines after preincubation with PdtSER.

Acetaldehyde↗

Induction of experimental autoimmune encephalomyelitis in rats and immune response to myelin basic protein in lipid-bound form.

Encephalitogenic activity of myelin basic protein (MBP) isolated in a form retaining binding to all myelin lipids was tested in Lewis rats. Immunization with this new stable lipid-bound and native-like preparation (LB-MBP), induced experimental autoimmune encephalomyelitis (EAE) as intensively as the classical lipid free MBP (LF-MBP). During the course of the disease, high affinity specific response to LB-MBP and high frequency of LB-MBP specific precursors was observed in peripheral lymphoid organs, indicating that the disease occurred in presence of anti LB-MBP specific T-cell responsivity. Short term lines, generated from lymphocytes collected at the onset of the disease from LB-MBP immunized rats, showed a strong dose-dependent response to LB-MBP, but not to LF-MBP. The present data indicate that in rat, LB-MBP maintains encephalitogenic activity and induces expansion of a specific T-cell population. These data suggest also that LB-MBP is a new autoantigen that may be relevant in human diseases.

Animals↗

Cerebrospinal fluid proteins in patients with leucoaraiosis: possible abnormalities in blood-brain barrier function.

Some CSF protein abnormalities have been proposed as a possible marker for vascular dementia. We studied the CSF protein levels and albumin ratio in 21 patients (mean age 64.04 +/- 7.5) with progressive bilateral motor impairment, and a CT picture of leucoaraiosis. Seven of these patients also presented with dementia. Twenty-seven Alzheimer's disease patients (mean age 59.59 +/- 5.30) without leucoaraiosis were taken as controls. We also evaluated the correlations of the albumin ratio values with the diagnosis of dementia, the severity of cognitive impairment, the degree of cerebral atrophy and presence of infarcts on CT, and the abnormalities in CSF circulation, found on isotopic cisternography, in the leucoaraiosis group. After controlling for age and sex, the patients with leucoaraiosis showed greater CSF albumin levels (0.27 g/l +/- 0.11 vs. 0.21 g/l +/- 0.06; covariance analysis P = 0.066), CSF IgG values (4.68 mg/100 ml +/- 1.45 vs. 2.85 mg/100 ml +/- 1.03; covariance analysis P < 0.001), and a higher albumin ratio (0.0078 +/- 0.0027 vs. 0.0058 +/- 0.0019; covariance analysis P = 0.013) than those with Alzheimer's disease. The variations of these parameters were not apparently related to the presence of dementia in the leucoaraiosis group. A significantly higher albumin ratio was observed in patients with a slowed CSF circulation compared to those with normal CSF circulation (0.0086 +/- 0.0028 vs. 0.0059 +/- 0.0019; covariance analysis P = 0.05). We conclude that, independently from the presence of dementia, patients with leucoaraiosis have CSF abnormalities consistent with functional blood-brain barrier alterations.

Aged↗

Antibodies specific for the lipid-bound form of myelin basic protein during experimental autoimmune encephalomyelitis.

On the hypothesis that myelin basic protein isolated with surrounding lipids may constitute an autoantigen in demyelinating diseases, we studied the antibody response to the lipid-free and lipid-bound form of myelin basic protein during the course of experimental autoimmune encephalomyelitis induced in rats with either form of protein. Immunization with the lipid-bound form of myelin basic protein induced high titres of antibodies directed to the protein, accompanied by no antibodies to cerebroside 30 days after immunization. Antibodies specifically directed to the lipid-bound form of myelin basic protein were revealed after removal of antibodies recognizing the delipidated myelin basic protein. Anti lipid-bound myelin basic protein antibodies could already be detected at day 10 post-immunization, reaching a maximum at day 20 post-immunization. Demonstrations of antibodies entirely specific for the lipid-bound form of myelin basic protein suggests that this molecule may present epitopes not to be found in its already extensively studied primary structure, possibly the result of conformational changes following lipid binding.

Animals↗

Stimulation of glycolytic key enzymes in cerebral cortex by insulin.

In adult male Wistar rats, a test was conducted to find whether or not insulin, administered intracerebroventricularly, would stimulate the activities of the glycolytic key enzymes hexokinase and phosphofructokinase in brain tissue as in non-neuronal tissue. The data clearly demonstrated an increase in these enzyme activities in cerebral cortex by approximately 20% after 80 mU insulin, whereas the increase in the hippocampus was just short of statistical significance. It is concluded that insulin controls glycolytic flux in the brain, and the suggestion that any perturbation in insulin signal transduction has severe impacts on brain glucose metabolism seems justified.

Animals↗

Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial Alzheimer's disease.

The c-FOS gene product, a putative transacting transcriptional regulator of the amyloid precursor protein (APP) gene, is a candidate locus for the familial Alzheimer's disease (FAD) mutation on chromosome 14 (FAD14). In light of this functional relationship, we investigated the nucleotide sequence and segregation of c-FOS and the nucleotide sequence of the 5' APP promoter. Single-stranded conformational polymorphisms (SSCPs) in the c-FOS gene revealed that c-FOS closely cosegregates with the FAD14 gene but does not show allelic association with FAD. A conservative third-position T-->C mutation was demonstrated in exon 2 (codon 84) of c-FOS, and a C-->G substitution was detected at -209 bp in the 5' promoter of APP. Neither were unique to FAD and are unlikely to be pathogenic or secondary modifiers of the FAD phenotype. We conclude that the c-FOS open reading frame is probably not the site of the FAD14 locus, but we cannot exclude the existence of modifier loci on chromosome 21.

Adult↗

Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.

Criteria for the diagnosis of vascular dementia (VaD) that are reliable, valid, and readily applicable in a variety of settings are urgently needed for both clinical and research purposes. To address this need, the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), resulting in research criteria for the diagnosis of VaD. Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features. These criteria are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible). They await testing and validation and will be revised as more information becomes available.

Brain↗

Long-term safety of azathioprine therapy in multiple sclerosis.

We compared the frequency of malignancies in 207 multiple sclerosis patients (mean age 35.75 years, SD 10.60) who took 2.0 mg/kg azathioprine daily (mean duration 4.16 years; SD 2.38) and in 247 nontreated patients (mean age 35.44 years; SD 11.94). Five malignancies were diagnosed in the azathioprine group compared with seven in the control group. The age-adjusted occurrence rate was 3.62/1,000 person-years (95% CI, 1.17 to 8.43) in the treated and 4.24/1,000 person-years (95% CI, 1.70 to 8.73) in the nontreated group; the age-adjusted relative risk of developing a tumor was 0.85.

Adenocarcinoma↗

Survey of Italian neurological output in the three years 1989-1991.

On the wave of the furore over the haphazard approach to academic promotion in Italy and the role of published work in it, our analysis clears the role of the neurological publications in the three years 1989-1991. The data analysis, carried out by consulting on-line data bank and comparing the Italian production with that one of two sampled countries (France and Germany), shows that in the field of clinical neuroscience, this criticism is not in order.

Data Collection↗

Free radical injury in skin cultured fibroblasts from Alzheimer's disease patients.

Oxygen radical production is postulated to be a major cause of cell damage in aging. We have studied the response to toxic oxygen metabolites of fibroblast cell lines derived from skin biopsies of patients with familial and sporadic Alzheimer's disease compared with those derived from normal controls. Fibroblasts were damaged by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by 50 mU of xanthine-oxidase. To quantify cell damage we measured lactate dehydrogenase activity in the culture medium and cell viability in fibroblast cultures from four normal subjects, five FAD, and four AD patients after 2 hours of Xo incubation. We found a significant increase of LDH activity in FAD vs. controls and also in AD vs. controls, suggesting that AD cells are more susceptible to oxygen radical damage than are normal controls.

Alzheimer Disease↗

Alzheimer skin fibroblasts show increased susceptibility to free radicals.

We have studied the response to toxic oxygen metabolites of fibroblasts derived from skin biopsies of 5 patients with familial (FAD) and 4 with sporadic (AD) Alzheimer's disease compared with those derived from 4 normal controls. Fibroblasts were damaged by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by 50 munits of xanthine-oxidase (Xo). To quantify cell damage we measured lactate dehydrogenase (LDH) activity in the culture medium and cell viability in fibroblast cultures. We found a significant increase in LDH activity in the FAD vs. controls and also in the AD vs. controls.

Acetaldehyde↗

Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14.

Familial Alzheimer's disease (FAD) has been shown to be genetically heterogeneous, with a very small proportion of early onset pedigrees being associated with mutations in the amyloid precursor protein (APP) gene on chromosome 21, and some late onset pedigrees showing associations with markers on chromosome 19. We now provide evidence for a major early onset FAD locus on the long arm of chromosome 14 near the markers D14S43 and D14S53 (multipoint lod score z = 23.4) and suggest that the inheritance of FAD may be more complex than had initially been suspected.

Aged↗