Biomedical subjects

M Albert

Publications and source records attributed to M Albert.

At least 19 recordsLinked to original sources

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

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

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↗

PubMed1994

Comparison of the precision of two standardized co-ordinate systems for the quantitation of brain anatomy: preliminary results.

We assessed reproducible definition of two standardized co-ordinate systems for intersubject analysis of brain images. The baselines in the two co-ordinate systems were a modification of the canthomeatal (mCM) line and the anterior-posterior commissural (AC-PC) line. Axial spin-echo MR images of four subjects at 1.5T were used. Operator error was computed from the replicate analyses of two operators. The mCM line was determined by the lens of the eye and the internal auditory canal, and the AC-PC line was determined by the intersection of AC and PC with the interhemispheric fissure. Reproducibility of the mCM markers (SD = 0.59 mm) did not differ significantly from that of the AC-PC line (SD = 0.68 mm). The measurement error of the angle of the baseline (delta alpha), however, was more than 7 times as large for the AC-PC line as for the mCM line. An additional error affecting the rostrocaudal rotation of the co-ordinate systems, attributable to the distance between the anatomic markers, was 2.1 and 3.6 degrees (3 mm and 5 mm slice thickness) for the mCM co-ordinate system and 8.2 and 11.0 degrees (3 mm and 5 mm slice thickness) for the AC-PC system. The AC-PC line based co-ordinate system is therefore, less reproducible than the mCM line based system. This could be improved if a combination of axial and sagittal images were used for the definition of the AC-PC line.

Brain↗

PubMed1994

Plasma homovanillic acid and performance on motor and cognitive tasks in community-dwelling elderly: MacArthur studies of successful aging.

To investigate the dopaminergic correlates of the aging-related motor and cognitive deficits, the dopamine metabolite homovanillic acid (HVA) in plasma was studied in a community-dwelling elderly cohort (n = 141). The results showed that hand-signature time (HST), a measure of bradykinesia, correlated negatively with plasma HVA (r = -0.24, p < .007). Similarities task performance showed a trend-level positive correlation with plasma HVA (r = 0.15, p = .08). Because plasma HVA is derived from several sources including central dopaminergic neurons and both central and peripheral noradrenergic neurons, the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in plasma was also measured to indirectly estimate the relationships, with HVA originating from noradrenergic metabolism. Plasma MHPG significantly correlated with similarities scores (r = 0.34, p < .001) but not with HST. The results suggested that the association of HVA with prolonged HST may be related to central dopamine metabolism, but its association with similarities scores may be due to noradrenergic metabolism. The results raise the possibility that prolonged HST may be an indicator of preclinical brain dopamine loss in the elderly.

Aged↗

PubMed1994

Predicting changes in physical performance in a high-functioning elderly cohort: MacArthur studies of successful aging.

BACKGROUND: Performance-based measures of physical performance were examined for an older cohort of relatively high-functioning men and women. Relationships between baseline physical performance and sociodemographic and health status characteristics were also examined. Three-year pattern changes in performance are described, and sociodemographic and health status predictors of change are investigated. METHODS: A cohort of relatively high-functioning men and women, aged 70-79, was identified in 1988 by subsampling from three community-based studies on the basis of physical and cognitive function. Baseline in-home assessments included tests of physical performance and measurement of sociodemographic characteristics and health status. A summary measure of physical performance was developed from tests of balance, gait, lower body strength and coordination, and manual dexterity. In-home assessments were repeated at follow-up in 1991. RESULTS: Better physical performance at baseline was more common among males, Whites, those reporting higher income and education, and those with fewer chronic conditions. In linear regression models, declines in performance were predicted by older age, lower income, higher education, relative weight and blood pressure, lower peak expiratory flow, prevalent diabetes and incident health conditions and hospitalizations during follow-up. Improvements in performance were also observed; the only significant association was with race (i.e., being Black). CONCLUSIONS: Declines in physical performance within a high-functioning cohort are predictable from sociodemographic and health status characteristics. The patterns of both decline and improvement in performance observed in this cohort suggest that older age is not uniformly associated with declines, indicating the potential for effective interventions to promote more successful aging.

Activities of Daily Living↗

PubMed1994

Assessing patient dependence in Alzheimer's disease.

BACKGROUND: While cognitive and functional deficits are the hallmark of Alzheimer's disease (AD), loss of social function (and the dependence this implies) is also critical, especially in early stages of disease. Little attention has been directed to this facet of dementing disease. We describe a scale for assessing dependency in AD and present a baseline profile of dependency in a cohort of AD patients. METHODS: In a study of the predictors of the course of AD, 233 patients in early stages of disease (modified MMS > or = 30) were assessed. Psychometric properties of the dependence scale were established. To validate the scale, dependence scores at baseline were correlated with a series of measures assessing cognition and function. The course of dependency over 18 months of follow-up was also analyzed. RESULTS: The scale shows adequate reliability (test-retest, intraclass correlation). Dependence stage was related to other measures of disease severity. Scalogram analysis shows that the dependence scale is consistent with the course of functional loss established for dementing disease. Prospective data indicate sensitivity of the scale to disease progression. CONCLUSION: Dependency is a distinct, measurable component of dementing disease and should be considered an important outcome in studies of AD.

Activities of Daily Living↗

PubMed1994

Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer's disease: prospective analyses from the Predictors Study.

OBJECTIVE: To examine whether either extrapyramidal signs or psychotic features are associated with more rapid progression of Alzheimer's disease. BACKGROUND: It has been unclear whether extrapyramidal signs and psychosis are predictors of faster course or are simply late signs. METHODS: Two hundred thirty-six patients with mild Alzheimer's disease were recruited in three cities and followed semiannually. RESULTS: Using Cox proportional hazards models that adjusted for age, sex, disease severity, and estimated duration of illness at study entry, the presence of extrapyramidal signs at entry was associated with higher relative risk (RR) of reaching moderate cognitive (RR = 2.35, 95% CI = 1.12 to 4.92) or functional (RR = 2.31, 95% CI = 1.37 to 3.90) severity, nursing home entry (RR = 2.51, 95% CI = 1.32 to 4.76), or death (RR = 3.04, 95% CI = 1.31 to 7.05). Psychosis predicted only the functional end point (RR = 1.85, 95% CI = 1.18 to 2.90). Using regression models, modified Mini-Mental State scores declined 1.30 points (95% CI = 0.16 to 2.44) per 6-month interval, more among patients with than those without extrapyramidal signs; patients with psychosis declined 1.15 (95% CI = 0.52 to 1.77) more mMMS points per interval. CONCLUSIONS: This study confirms extrapyramidal signs and psychosis as robust predictors of disease end points and rapid progression in Alzheimer's disease.

Age Factors↗

PubMed1994

Age at onset of Alzheimer's disease: relation to pattern of cognitive dysfunction and rate of decline.

We examined the pattern of cognitive impairment and rate of cognitive and functional decline as a function of age at symptom onset in 127 patients with probable Alzheimer's disease (AD). At baseline, early-onset (before age 65) and late-onset groups were mildly and comparably impaired on the modified Mini-Mental State Examination (mMMS) and the Blessed Dementia Rating Scale-Part 1 (BDRS). Repeated-measures analysis of variance revealed significantly more rapid decline in early-onset subjects over a 2-year follow-up period. Multivariate linear regression analyses indicated that age at symptom onset strongly predicted rate of decline on the mMMS and the BDRS, even after controlling for symptom duration, gender, family history of dementia, and baseline mMMS and BDRS scores. Early- and late-onset AD subjects also differed in terms of pattern of performance on the mMMS. Early-onset subjects scored significantly lower than late-onset subjects on attentional items of the mMMS at baseline and follow-up. Conversely, late-onset subjects scored significantly lower than early-onset subjects on memory and naming items at baseline, and the two groups were comparable on these tasks at follow-up. Results provide longitudinal evidence of more rapid cognitive and functional decline in subjects with early-onset AD and suggest that early-onset AD may be characterized by predominant impairment of attentional skills.

Age of Onset↗

PubMed1994

Biochemical and physiological effects of long-term sublethal T-2 toxin feeding in rabbits.

Effects of 4-7-week feeding of naturally contaminated wheat grains containing 0.284 mg T-2 toxin/kg were investigated on the health, certain serum biochemical parameters and reproductive status of sexually mature, virgin female rabbits. Three of the ten contaminated animals died before the end of the experiment (acute, fibrinous-purulent peritonitis and pneumonia). Hepatic damages are suggested by significant serum alanine aminotransferase and slight aspartate aminotransferase, gamma-glutamyl transferase, malate dehydrogenase activity increases, as well as by cholinesterase activity decrease as compared to control animals. The damage of kidney function is indicated by significantly higher creatinine level, as compared to the control. The T-2 toxin feeding also impaired ovarian functions, reflecting by unaltered progesteron concentration, macro- and microscopical pictures after GnRH-stimulation.

Animals↗

PubMed1994

Effects of long-term aluminum exposure on certain serum constituents in broiler chickens.

The aim of this work was to study the effects of 35 days exposure to aluminium on certain serum biochemical quantities in chickens. Broiler chicks (TETRA-726 hybrid, male) were kept in a climate-controlled stall with feed and water ad libitum, from day 1 of age, for 7 weeks. From the beginning of the third week aluminium was added to the diet as aluminium chloride. Treatments included supplemental aluminium content of 0, 200, 1000 and 3000 mg/kg ration. At the end of the experiment, blood samples were taken from the v. ulnaris. The treated groups showed significantly elevated alkaline phosphatase activities, as well as increased cholesterol concentrations and decreased triacylglycerol concentrations, and these changes were dose-dependent. The concentration of uric acid was significantly higher in the group receiving 1000 mg/kg ration, but significantly lower in the group receiving 3000 mg/kg ration, compared with the controls. In the treated groups, the concentration of glucose, as well as the activities of cholinesterase, aspartate aminotransferase, gamma-glutamyl transferase and creatine kinase were similar in the controls and treated animals. High levels of alkaline phosphatase are due to increased osteoblastic activity, provoked by the disturbance of bone formation, caused in turn by aluminium. Alterations in serum uric acid may be connected with metabolic disturbances (e.g. renal function, cation--anion balance etc.). Neither hepatic nor muscle damage was found.

Aluminum Chloride↗