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Biomedical subjects

M Albert

Publications and source records attributed to M Albert.

At least 19 recordsLinked to original sources
PubMed1997

The course of psychopathologic features in mild to moderate Alzheimer disease.

BACKGROUND: The onset and course of the psychopathologic features of Alzheimer disease have not been established in prospective, longitudinal studies. METHODS: Two hundred thirty-five patients with early, probable Alzheimer disease were recruited at 3 sites and observed naturalistically for up to 5 years. At 6-month intervals, the Columbia University Scale for Psychopathology in Alzheimer's Disease was administered. Markov analyses were used to predict the probability of a specific symptom developing or being maintained at the next visit. For each symptom category, the maximum frequency of occurrence at 4 consecutive points (duration, 2 years) was calculated. RESULTS: Misidentification, wandering or agitation, and physical aggression increased during follow-up. At any visit, the likelihood of a new symptom developing was greatest for behavioral disturbance, intermediate for paranoid delusions and hallucinations, and least for depressed mood with vegetative features. Wandering or agitation occurred at 3 or more of 4 consecutive visits (duration, 2 years) in the majority of patients, paranoid delusions and hallucinations were intermediate in their degree of persistence, and depressed mood with vegetative signs rarely persisted. CONCLUSIONS: Behavioral disturbance, particularly agitation, is common and persistent in patients with Alzheimer disease. Psychotic symptoms are less common and show moderate persistence over time. Depressed mood with vegetative signs is uncommon and rarely persists. These findings suggest leads about the optimal treatment duration for specific subtypes of psychopathologic features.

Aged↗
PubMed1997

The absence of an apolipoprotein epsilon4 allele is associated with a more aggressive form of Alzheimer's disease.

We investigated the relationship between APOE genotype and rate of disease progression and survival in 99 patients with probable Alzheimer's disease (AD) who were followed biannually for up to 6 years. Patients were stratified into two groups, those with and without at least one APOE epsilon4 allele. The rate of decline in modified Mini-Mental State Examination scores was slower, the presence of extrapyramidal signs was decreased, and the development of myoclonus occurred later among patients with APOE epsilon4 alleles compared with patients with other genotypes. Compared with patients without an APOE epsilon4 allele, the risk of mortality was also decreased in patients with at least one epsilon4 allele (RR = 0.38; CI = 0.17-0.84, p < 0.02). Because the decline in mental ability as well as the development of myoclonus and extrapyramidal signs are consistent manifestations of disease progression, our results imply that APOE epsilon4 is associated with a less aggressive form of AD.

Age of Onset↗
PubMed1997

Participation in clinical trials and long-term outcomes in Alzheimer's disease.

The objective of this study was to determine whether participation in clinical trials affects long-term outcomes in Alzheimer's disease (AD). Participation in clinical trials for persons with dementia is often justified on the grounds that patients benefit from the medical oversight typical of trials, even when experimental agents do not demonstrate short-term benefits. This claim has not been rigorously assessed. Of 215 community-resident subjects enrolled in a prospective study of outcomes in AD, 101 participated in randomized clinical trials (RCTs) during the first 2 years of follow-up. These subjects were compared with subjects who met eligibility requirements for RCTs but did not participate (N = 57) and with subjects who were ineligible (N = 57), over a total of 3.5 years of follow-up. Survival analyses assessed risk of death, nursing home placement, and incident functional deficit end points, adjusting for baseline differences. Subjects who participated in RCTs were younger and more highly educated. Mortality, risk of hospitalization, number of medical examinations conducted by study physicians, and onset of severe functional deficit did not differ between the groups, but risk of nursing home admission was significantly lower among RCT participants compared with eligible nonparticipants and ineligible subjects (16.8% versus 36.8% and 31.6%, respectively [p = 0.01]). The difference in risk of nursing home placement may represent a long-term, drug-related benefit to patients, a selection effect (caregivers of patients who participate in RCTs differ from caregivers of patients who do not), or a positive effect on caregivers (greater contact with a medical service may be associated with better care-giving outcomes). Further research is required to assess these effects.

Aged↗
PubMed1997

Hepatic ultrasonographic findings in experimental carbon tetrachloride intoxication of the dog.

An experimental study was undertaken in dogs with carbon tetrachloride (CCl4) intoxication to describe and follow the changes in the ultrasound appearance of the liver. Characteristic ultrasound features (enlarged liver, increased echogenicity with fine, tightly-packed echoes, and loss of echogenicity of the portal vein walls) were seen from day 2 of the experiment, culminating between days 2 and 7. Subsequently the liver gradually and almost completely regained its normal ultrasound appearance. Ultrasonographic findings corresponded to the severity of the clinicopathological parameters, and changed parallel with the results of liver biopsies. Histology of the biopsy samples revealed acute centrolobular lipid accumulation with necrobiosis and necrosis in the hepatocytes in the first stage of the disease. In the second stage, a secondary reparatory-inflammatory process and reparation in the interstitial tissue were seen. In some dogs, ill-defined hyperechoic foci were observed within the liver during the regenerative phase. Hepatic ultrasonography seems to be a reliable and relatively sensitive method for monitoring liver dystrophy with necrobiosis and lipid accumulation and to follow the course of steatosis in clinical cases. Ultrasound-guided biopsy can further improve the diagnostic accuracy of ultrasonography in liver dystrophy.

Alanine Transaminase↗
PubMed1996

Modeling the influence of extrapyramidal signs on the progression of Alzheimer disease.

OBJECTIVE: To determine how the advent of extrapyramidal signs influences the progression of Alzheimer disease as measured by standard clinical measures. DESIGN: We applied growth curve models to prospective data to characterize patients' cognitive and functional changes over time. To detect changes in disease course related to extrapyramidal signs, their onset was treated as a time-dependent covariate. SETTING: Three research medical centers. PARTICIPANTS: Patients (n = 217) with probable Alzheimer disease. INTERVENTION: Patients were followed up semiannually for 5 years. MAIN OUTCOME MEASURES: Scores on the modified Mini-Mental State Examination and measures of basic and instrumental activities of daily living from the Blessed Dementia Rating Scale. RESULTS: For basic and instrumental activities of daily living, disease course was more rapid once extrapyramidal signs developed. Decline in the modified Mini-Mental State Examination score was greater at the time the signs developed, but not at subsequent visits. CONCLUSIONS: The point at which extrapyramidal signs emerge is associated with measurable acceleration in the progression of Alzheimer disease. This may in part explain why extrapyramidal signs are associated with a poorer prognosis. The differential influence of extrapyramidal signs on cognitive and functional measures suggests that the pathological changes underlying these disease features may vary.

Aged↗
PubMed1996

Comparison of receiver operating characteristic curves on the basis of optimal operating points.

RATIONALE AND OBJECTIVES: We developed a method of comparing receiver operating characteristic (ROC) curves on the basis of the utilities associated with their optimal operating points (OOPs). METHODS: OOPs were computed for paired ROC curves on the basis of isocost lines in ROC space with slopes ranging from 0.1 to 3.0. For each pair of OOPs corresponding to a single isocost slope, the difference in costs and the variance of this difference was computed. A sensitivity analysis was thus obtained for the difference between the two curves over a range of isocost slopes. Three published data sets were evaluated using this technique, as well as by comparisons of areas under the curves and of true-positive fractions at fixed false-positive fractions. RESULTS: The OOPs of paired ROC curves often occur at different false-positive fractions. Comparisons of ROC curves on the basis of OOPs may provide results that differ from comparisons of curves at a fixed false-positive fraction. CONCLUSION: ROC curves may be compared on the basis of utilities associated with their OOPs. This comparison of the optimal performance of two diagnostic tests may differ from conventional statistical comparisons.

Costs and Cost Analysis↗
PubMed1996

Self-efficacy beliefs and change in cognitive performance: MacArthur Studies of Successful Aging.

Data from a cohort of relatively high functioning, older men and women were used to test the hypothesis that stronger self-efficacy beliefs predict better maintenance of cognitive performance. Structural equation modeling revealed that stronger baseline instrumental efficacy beliefs predicted better verbal memory performance at follow-up among men but not among women, controlling for baseline verbal memory score and sociodemographic and health status characteristics. For both men and women there were no significant associations between either type of self-efficacy beliefs and measures of nonverbal memory, abstraction, or spatial ability. Consistent with previous research showing relationship between baseline cognitive performance and change in self-efficacy beliefs, better abstraction ability was also predictive of increase in instrumental efficacy beliefs among the men.

Age Factors↗
PubMed1996

Application of a growth curve approach to modeling the progression of Alzheimer's disease.

BACKGROUND: Studies using clinical measures to track AD progression often assume linear declines over the entire course of the disease, which may not be justified. The objective of this study was to model change in measures of the clinical severity of Alzheimer's disease (AD) over time. METHODS: We developed a method to apply growth curve models to prospective data and characterize AD patients' functional change over time. Data from the modified Mini-Mental State Examination (mMMSE) and measures of basic and instrumental ADL, administered semiannually for up to 5 years to 236 patients with probable AD, were modeled. RESULTS: The rate of decline in mMMS scores per 6-month interval gradually increased as scores dropped from the maximum of 57 to 20. The rate of decline then decreased as scores approached 0, resulting in an inverse "S" curve. The rate of increase in instrumental ADL scores per interval attenuated as the scores increased, while that for basic ADL scores across intervals was constant. CONCLUSIONS: Differences in the pattern of progression of the three measures is in part a function of their psychometric properties. The progression curves may also reflect content-specific features of the instruments. Superimposition of the modeled decline in these three content areas suggests a hypothetical model of the relative timing of cognitive and functional changes in AD.

Activities of Daily Living↗
PubMed1996

Quality of life in patients with Alzheimer's disease as reported by patient proxies.

OBJECTIVE: To measure behaviors indicative of quality of life (QOL) in patients with Alzheimer's disease and to examine correlates of patient QOL. DESIGN: Cross-sectional investigation. SETTING: Multi-center study. PARTICIPANTS: Sample of 130 diagnosed patients. PRINCIPAL OUTCOME MEASURES: Proxy ratings of (1) the frequency, opportunity, and enjoyment of 15 non-ADL activities potentially within the capacity of a demented person, and (2) the frequency of a series of positive and negative affects, evident in clearly demarcated facial and bodily expressions. RESULTS: QOL ratings were reliably elicited. Family and institutional caregivers differed only in reports of opportunity for patient activity. Frequency of activities declined with increasing severity of dementia. The frequency of negative affects increased and positive affects declined with increasing severity of dementia, but correlations were weak. High QOL, defined by frequent activity and positive affect, was evident in a quarter of the sample. In multivariate models, functional and cognitive status independently predicted QOL among community-resident older adults; only absence of antipsychotics was related to QOL among older people in nursing homes. Patient education, a marker of premorbid state, independently predicted some activity patterns. CONCLUSIONS: Although the subjective world of the demented patient is not directly accessible, readily observable behaviors offer a basis for assessing QOL.

Affect↗
PubMed1996

Cyclin B (p56cdc13) localization in the yeast Schizosaccharomyces pombe: an ultrastructural and immunocytochemical study.

The eucaryote cell cycle is driven by a set of cyclin dependent kinases (CDKs) associated to cyclins, which confer not only the activity but also the substrate specificity and the proper localization of the kinase activity. In the fission yeast Schizosaccharomyces pombe, only one cyclin, the product of the cdc13 gene (p56cdc13), is required to be associated with p34cdc2, to control the complete cell cycle. Earlier studies have localized this complex mainly in the nucleus and its periphery. Using new improved electron microscopy (EM) technologies, based on high pressure freezing fixation, we refined previous studies, evidencing cytoplasmic localization of p56cdc13, in addition to the nuclear localization previously observed. Further immunofluorescence studies, performed on aldehydically fixed cells, confirmed our EM results, emphasizing the major cytoplasmic localization of p56cdc13 in interphase cells and the relocalization towards the nucleus in mitotic cells, suggesting that the S pombe cyclin B localization is cell cycle-regulated.

Cyclins↗
PubMed1995

Clinical correlates of Alzheimer's disease with and without silent radiographic abnormalities.

OBJECTIVE: To determine whether patients with Alzheimer's disease (AD) who do not have historical or clinical evidence of stroke but who do have computed tomographic or magnetic resonance imaging evidence of noncortical lesions smaller than 2 cm or periventricular "caps" differ from other patients with AD. METHODS: The computed tomographic or magnetic resonance imaging scans of 158 patients meeting criteria of the National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable AD were reviewed by one neuroradiologist. Two measures of disease severity--the Modified Mini-Mental State examination and the Blessed Dementia Rating Scale (Part I)--were subjected to two-way analysis of variance with scan type (computed tomography or magnetic resonance imaging) and lesion number as between-group factors and age and disease duration as covariates. RESULTS: No relationship was seen between lesion number or periventricular caps and disease severity. CONCLUSION: In this cross-sectional analysis using these clinical measures, patients with AD who have well-defined radiographic abnormalities cannot be differentiated from patients with AD who do not have them.

Adult↗
PubMed1995

A standardized technique for establishing onset and duration of symptoms of Alzheimer's disease.

OBJECTIVES: To develop an informant-based semistructured interview to determine the onset and duration of symptoms of Alzheimer's disease, and to use this instrument with informants to characterize a cohort of mildly impaired patients with Alzheimer's disease. DESIGN: In study 1, interrater and interinformant reliability was examined for the date of onset and the order of appearance for specific symptoms that were elicited by the semistructured onset interview. In study 2, the instrument was used to characterize disease onset in a cohort of patients with Alzheimer's disease who were participating in a large multicenter study. SUBJECTS: Informants of patients with Alzheimer's disease. RESULTS: In study 1, interrater reliability for duration of illness was excellent (intraclass correlation coefficient = .99, P < .001), and interinformant reliability was good (intraclass correlation coefficient = .86, P < .001). Agreement for the presence of a given symptom was highest for those that were most commonly reported (eg, memory and performance difficulty). In study 2, 89% of the cohort had memory problems, and 63.9% had performance difficulties as the first or second symptom. Depression and language problems were less commonly reported. Psychosis and behavioral disturbances were rarely reported as the first problem. CONCLUSION: This instrument provides a reliable procedure for standardizing the estimation of duration of illness based on retrospective report.

Aged↗
PubMed1995

Complex study of the physiological role of cadmium. III. Cadmium loading trials on broiler chickens.

Cadmium (Cd) loading trials were conducted on a total of 110 (3 x 10 and 4 x 20) broiler chickens prereared for 21 days. The control chickens received no cadmium, while chickens in the six treatment groups were given different doses of Cd as an aqueous solution of CdSO4 administered either into the crop or mixed in the feed. The chickens were kept in a climatized animal house and treated usually for 3-5 weeks (maximum 68 days), with the exception of group Cd-75 chickens which were treated up to 239 days of age. The chickens' health status, body mass and feed consumption were monitored throughout the trial. On days 14-20 and on day 42 of the trial 2 chickens per group, then at the end of trial a total of 25 chickens were killed in anaesthesia. These birds, together with chickens that died or were killed during the trial, were subjected to detailed gross pathological examination. From 11 organs (kidney, liver, spleen, testicle, brain, myocardium, skeletal muscle, lungs, digestive tract, pancreas, tubular bones) of these chickens samples were taken for assay for a total of 16 elements, as well as for light and electron microscopic examination. With the exception of groups Cd-30 and Cd-600, no abnormal clinical signs were observed in the first two weeks of the trial. Chickens of group Cd-30 died before day 8-12 of the trial among signs of complete anorexia, rapid emaciation, huddling and diarrhoea, while chickens of group Cd-600 died before day 28, showing similar clinical signs. The body mass of chickens fed a Cd-supplemented diet either remained constant or decreased substantially, in a degree proportional to the Cd load. The only exception was group Cd-2.5, in which the average body mass of birds at the end of week 8 slightly exceeded that of the controls. Four out of the 10 cockerel chicks fed a diet containing 75 ppm Cd up to 239 days of age died of intercurrent diseases; the remaining six grew well and reached a body mass of 3.8-4.3 kg. Feed conversion efficiency was satisfactory in the control group and in group Cd-2.5 (2.1 and 2.4 kg, respectively) and could not be evaluated in a realistic manner in the other groups. At necropsy, the cockerel chicks of groups Cd-30 and Cd-600 showed severe emaciation, liver and kidney degeneration, myocardial hypertrophy and cardiac dilatation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Complex study of the physiological role of cadmium. II. Effect of cadmium load on the cadmium content of eggs.

The possibility of "cadmium (Cd) contamination" of eggs and the dynamics of Cd accumulation were studied. A total of 40 (4 x 10) Japanese quails weighing 155-200 g, being at the middle phase of egg production and kept on batteries in a climatized animal house were used. The birds were fed a standard quail layer diet and drank tap-water ad libitum. With the exception of the control group (Cd-0), the diet of the other three groups was supplemented with Cd sulphate homogeneously mixed in the diet so that it contained 75 mg (Cd-75), 150 mg (Cd-150) and 300 mg (Cd-300) per kg. During the 37-day feeding trial the quails' behaviour, health status and daily egg production were monitored and the birds were weighed weekly. The egg production of the experimental groups, particularly of those exposed to a high Cd load, rapidly decreased: at the highest Cd load (300 ppm) egg production completely ceased at days 10-11 of the trial. The total Cd content of the eggs rose already from the 3rd day of the feeding trial and by day 10 it reached a value of 0.777 mg/kg dry matter in the eggs of quails of group Cd-75. This was about five times the value measured in the control quails' eggs (0.165 mg/kg dry matter). The Cd content of the egg-white and egg-yolk (maximum values: 0.212 and 0.107 mg/kg dry matter) also increased to about 2 or 3 times that measured in the control eggs. The Cd content of eggs reached the peak in the 2nd week of the feeding trial, then started to decrease, and in the 3rd and 4th weeks not even the eggs laid by quails exposed to a high Cd load contained more Cd than about twice the concentration measured in the controls' eggs. The elucidation of this hitherto not studied process requires further investigations. The phenomenon may be due to a lack of the protein necessary for Cd transport and to the impairment of Cd absorption and of the excretory activity of the oviduct. The higher Cd concentrations measured in the egg were accompanied by markedly elevated Fe, K and S values. In the egg samples collected in the 4th week a substantial reduction in Ca and P concentration was observed. As regards the mineral elements measured in the egg-shell, a significant negative correlation was established between the concentration of Cd and those of Zn, Mg and Ca.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Balanced activation of coagulation and fibrinolysis after a 2-h triathlon.

To examine whether exercise-induced thrombin formation is accompanied by increased in vivo plasmin formation, we measured molecular markers and neoantigens of the hemostatic system in 10 male subjects (mean 29 yr. range 19-38) before, immediately after, and 2, 8, and 21 h after a triathlon lasting 128-163 min. Thrombin-antithrombin (TAT) complexes, fibrinopeptide A (FPA), and tissue plasminogen activator (t-PA) antigen were maximally increased immediately after exercise and decreased thereafter rapidly. Prothrombin fragment 1 + 2 (PTF1 + 2), fibrin degradation products (FbDP) and plasmin-antiplasmin (PAP) complexes rose to a similar extent 0 and 2 h after exercise decreased thereafter. The maximal levels of PTF1 + 2, TAT, FPA, and FbDP were 1.5-, 2.1-, 1.8-, and 1.9-fold above baseline, respectively. This investigation shows that strenuous prolonged exercise leads to a moderate activation of blood coagulation resulting in thrombin and fibrin formation which is accompanied by a greatly enhanced plasmin generation. It is concluded that the hemostatic of healthy individuals is well kept in balance when stimulated by prolonged strenuous exercise.

Adult↗
PubMed1994

Serotonin and NADPH-diaphorase in the dorsal raphe nucleus of the adult rat.

NADPH-diaphorase histochemistry, employed as a marker for nitric oxide synthase (NOS), was combined with serotonin (5-HT) immunofluorescence to investigate the relationship between NOS and 5-HT in the rat dorsal raphe nucleus. Many NADPH-diaphorase labelled cells and varicose axons were observed in the nucleus. Coexistence between NADPH-diaphorase and 5-HT occurs in cells of the dorsomedial and ventromedial subgroups but not in the lateral subgroups. Coexistence was not observed in axons, but NADPH-diaphorase labelled axons contact 5-HT/NADPH-diaphorase containing cell bodies. These findings have implications for the role of nitric oxide in 5-HT pathways and for the mechanism of action of 5-HT neurotoxins.

Amino Acid Oxidoreductases↗
PubMed1994

Comparison of neurologic changes in 'successfully aging' persons vs the total aging population.

OBJECTIVE: To determine age-related changes in neurologic function in the general population. DESIGN: To administer a neurologic examination to participants in such a way that it is possible to calculate the proportion of elderly persons in the population with each abnormal finding and the proportion of persons with each finding but without evidence of the medical and neurologic diseases likely to produce neurologic abnormalities (eg, stroke and diabetes). SETTING: Individuals were selected from a community-dwelling population. PARTICIPANTS: A stratified random sample of 467 persons aged 65 years and older were evaluated. RESULTS: Many neurologic abnormalities are increasingly common with advancing age and are present in a substantial portion of the elderly population. The prevalence of abnormal neurologic findings not attributable to disease, however, is substantially lower, typically one half to one third the total prevalence. Moreover, the increase with age in the prevalence of abnormal neurologic findings not attributable to major disease varies substantially among the different measures. CONCLUSIONS: Primitive reflexes and measures of gait show statistically significant increases with age in multiple measurement domains, suggesting a selective age-related vulnerability.

Aged↗