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Biomedical subjects

M Grossman

Publications and source records attributed to M Grossman.

At least 19 recordsLinked to original sources

Trying to tell a tale: discourse impairments in progressive aphasia and frontotemporal dementia.

OBJECTIVE: To assess discourse in patients with frontotemporal dementia (FTD). METHODS: The authors asked patients with progressive nonfluent aphasia (PNFA), patients with semantic dementia (SemD), and nonaphasic patients with a disorder of social comportment and executive functioning (SOC/EXEC) to narrate the story of a wordless children's picture book. RESULTS: The authors found significant discourse impairments in all three groups of patients. Moreover, there were qualitatively important differences between the groups. Patients with PNFA had the sparsest output, producing narratives with the fewest words per minute. Patients with SemD had difficulty retrieving words needed to tell their narratives. Though not aphasic, patients with SOC/EXEC had profound difficulty organizing their narratives, and they could not effectively express the point of the story. This deficit correlated with poor performance on a measure of executive resources requiring an organized mental search. In addition, a correlation of narrative organization with cortical atrophy in patients with SOC/EXEC was significant in right frontal and anterior temporal brain regions. CONCLUSIONS: Impaired day-to-day communication in nonaphasic frontotemporal dementia patients with a disorder of social comportment and executive functioning is due in part to a striking deficit in discourse organization associated with right frontotemporal disease. Difficulty with discourse in progressive aphasia is due largely to the language impairments of these patients.

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Cognitive functioning in sporadic amyotrophic lateral sclerosis: a six month longitudinal study.

OBJECTIVE: To observe changes in cognition over six months in subjects with recently diagnosed sporadic amyotrophic lateral sclerosis (ALS). METHODS: The study used a between-group and within-group longitudinal design. Nineteen ALS subjects and eight matched caregivers were recruited to participate in baseline neuropsychological assessments that were repeated six months later. Between group comparisons for these variables were undertaken at baseline and six months later. Within group/across time comparisons for these variables were carried out for both groups. Individual analyses for the neuropsychological variables using z scores were done for the ALS subjects using their baseline performance as the basis for comparison with their six month performance. RESULTS: The between-group and within-group comparisons did not show significant differences in cognitive function over time. In individual analyses, however, seven of 19 ALS subjects (36.84%) developed abnormal neuropsychological performance over six months. CONCLUSIONS: Early in the disease course, over one third of the ALS subjects developed cognitive deficits over six months. These findings support the hypothesis that cognitive deficits in ALS become more prominent over time.

Aged↗

Comparison of family histories in FTLD subtypes and related tauopathies.

Pedigrees from 269 patients with frontotemporal lobar degeneration (FTLD), including frontotemporal dementia (FTD), FTD with ALS (FTD/ALS), progressive nonfluent aphasia, semantic dementia (SD), corticobasal degeneration, and progressive supranuclear palsy were analyzed to determine the degree of heritability of these disorders. FTD/ALS was the most and SD the least heritable subtype. FTLD syndromes appear to have different etiologies and recurrence risks.

Adult↗

A longitudinal study of sentence comprehension difficulty in primary progressive aphasia.

CONTEXT: Patients with primary progressive aphasia have sentence comprehension difficulty, but the longitudinal course of this deficit has not been investigated. OBJECTIVE: To determine how grammatical, single word meaning, and working memory factors contribute to longitudinal decline of sentence comprehension in primary progressive aphasia. We hypothesised partially distinct patterns of sentence comprehension difficulty in subgroups of patients with progressive non-fluent aphasia (PNFA) and semantic dementia (SD). DESIGN: Cohort. SETTING: Institutional out patient referral centre. PATIENTS: PNFA (n = 14), SD (n = 10). MAIN OUTCOME MEASURE: Sentence comprehension accuracy. RESULTS: PNFA patients were significantly impaired at understanding grammatically complex sentences when first seen, and this was more evident than impairment of their comprehension of grammatically simple sentences (p<0.05). Comprehension of grammatically complex sentences correlated with their working memory deficit at presentation (p<0.05). PNFA patients showed modest decline over time in grammatical comprehension. In SD, comprehension of grammatically complex sentences was not more impaired than comprehension of grammatically simple sentences when first seen, but these patients demonstrated a significant longitudinal decline in understanding grammatically complex sentences (p<0.05). Cox regression analyses showed that a deficit in single word meaning contributes to the progressive impairment for grammatically complex sentences in SD (p<0.05), but working memory does not contribute to longitudinal decline in PNFA. CONCLUSION: Patients with PNFA and SD have sentence comprehension difficulty, but distinct factors contribute to this impairment during the course of their disease.

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Metacognitive deficits in frontotemporal dementia.

OBJECTIVES: To investigate whether metacognitive impairments in self-awareness and self-monitoring occur in patients with frontotemporal dementia (FTD), particularly among those with prominent social and dysexecutive impairments. METHODS: Patients diagnosed with FTD were divided by clinical subtype (social-dysexecutive (n = 12) aphasic (n = 15), and constituent subgroups of progressive non-fluent aphasia and semantic dementia) and compared with subjects with probable Alzheimer's disease (AD, n = 11) and age-matched healthy controls (n = 11). All subjects completed comprehensive behavioural ratings scales, which were compared with caregiver ratings. Subjects also rated their test performances in verbal associative fluency, word list learning, and memory task with comparisons made between actual and judged performance levels. RESULTS: The FTD sample as a whole showed significantly less behavioural self-awareness and self-knowledge than the AD and healthy control samples. FTD patients with prominent social and dysexecutive impairments demonstrated the most extensive loss of self-awareness and self-knowledge, significantly overrating themselves in multiple social, emotional, and cognitive domains, and failing to acknowledge that any behavioural change had occurred in most areas. The remaining clinical samples showed select and minimal discrepancies. All clinical groups were significantly unaware of their apathy levels. Most FTD patients judged episodic cognitive test performance adequately, with partial difficulties observed in the socially impaired and progressive non-fluent aphasia subgroups. CONCLUSIONS: FTD patients, particularly those with prominent social and dysexecutive impairments, exhibit profound metacognitive anosognosia that may represent a loss of self-awareness, self-monitoring, and self-knowledge, likely related to significant prefrontal pathophysiology. Other FTD clinical groups and AD patients showed less pervasive and more select metacognitive deficiencies.

Adult↗

Clinical and neuropathologic variation in neuronal intermediate filament inclusion disease.

BACKGROUND: Recently described neuronal intermediate filament inclusion disease (NIFID) shows considerable clinical heterogeneity. OBJECTIVE: To assess the spectrum of the clinical and neuropathological features in 10 NIFID cases. METHODS: Retrospective chart and comprehensive neuropathological review of these NIFID cases was conducted. RESULTS: The mean age at onset was 40.8 (range 23 to 56) years, mean disease duration was 4.5 (range 2.7 to 13) years, and mean age at death was 45.3 (range 28 to 61) years. The most common presenting symptoms were behavioral and personality changes in 7 of 10 cases and, less often, memory loss, cognitive impairment, language deficits, and motor weakness. Extrapyramidal features were present in 8 of 10 patients. Language impairment, perseveration, executive dysfunction, hyperreflexia, and primitive reflexes were frequent signs, whereas a minority had buccofacial apraxia, supranuclear ophthalmoplegia, upper motor neuron disease (MND), and limb dystonia. Frontotemporal and caudate atrophy were common. Histologic changes were extensive in many cortical areas, deep gray matter, cerebellum, and spinal cord. The hallmark lesions of NIFID were unique neuronal IF inclusions detected most robustly by antibodies to neurofilament triplet proteins and alpha-internexin. CONCLUSION: NIFID is a neuropathologically distinct, clinically heterogeneous variant of frontotemporal dementia (FTD) that may include parkinsonism or MND. Neuronal IF inclusions are the neuropathological signatures of NIFID that distinguish it from all other FTD variants including FTD with MND and FTD tauopathies.

Adult↗

Dissociation of numbers and objects in corticobasal degeneration and semantic dementia.

BACKGROUND: Semantic memory is thought to consist of category-specific representations of knowledge that may be selectively compromised in patients with neurodegenerative diseases, but this has been difficult to demonstrate reliably across object categories. METHODS: The authors evaluated performance on several simple measures requiring number representations (including addition and magnitude judgments of single digits), and on a task that requires object representations (an object naming task) in patients with corticobasal degeneration (CBD; n = 13) and semantic dementia (SD; n = 15). They also examined regional cortical atrophy using voxel-based morphometric analyses of high resolution structural MRI in subgroups of five CBD patients and three SD patients. RESULTS: CBD patients were consistently more impaired on simple addition and magnitude judgment tasks requiring number representations compared to object representations. Impaired performance with numbers in CBD was associated with cortical atrophy in right parietal cortex. By comparison, SD patients demonstrated a greater impairment on a naming task requiring object representations relative to their performance on measures involving number representations. This was associated with left anterior temporal cortical atrophy. CONCLUSION: The cognitive and neuroanatomic dissociations between CBD and SD are consistent with the hypothesis that number and object representations constitute distinct domains in semantic memory, and these domains appear to be associated with distinct neural substrates.

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[The nursing labour market in Canada (1985-1999)].

This literature review analysed both published and unpublished scientific and professional studies on the nursing labour market in Canada within the period of 1985 to 1999. The goal was to conduct a situational analysis utilising statistical data and canvassing all concerned parties to extract their points of view. The analysis revealed significant cyclical variations in the evolution of the workforce, particularly with respect to auxiliary nurses, such as the perceived existence of major problems in recruiting new professionals in the field and retaining existing professionals in their organisations, the lack of homogeneity in educational training programmes, and the co-existence of several operational structures for organising nursing care, of which there is a lack of evaluation on their effectiveness. The results of the literature review identify the necessity to further develop the knowledge base on such a relevant dimension of the nursing labour market.

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Grammatical and resource components of sentence processing in Parkinson's disease: an fMRI study.

BACKGROUND: Sentence comprehension requires linguistic processing as well as cognitive resources such as working memory (WM) and information-processing speed (IPS). The authors hypothesize that sentence comprehension difficulty in patients with mild PD is due to degradation of the large-scale neural network that supports cognitive resources during sentence processing. OBJECTIVE: To understand the neural basis for sentence comprehension difficulty in PD. METHOD: Regional brain activity with blood oxygenation level-dependent fMRI was monitored while seven PD patients and nine healthy seniors answered a simple probe about written sentences that vary in their grammatical and cognitive resource properties. RESULTS: Healthy seniors recruited posterolateral temporal and ventral inferior frontal regions of the left hemisphere, brain regions associated with grammatical processing that were also activated by PD patients. Healthy seniors also recruited left dorsal inferior frontal, right posterolateral temporal, and striatal regions that are associated with cognitive resources during sentence processing. Direct contrasts showed that striatal, anteromedial prefrontal, and right temporal regions are recruited to a significantly lesser degree in PD, but these patients have increased activation of right inferior frontal and left posterolateral temporal-parietal areas during sentence comprehension. CONCLUSION: These findings associate impaired sentence comprehension in PD with interruption of a large-scale network important for cognitive resources during sentence processing. These results also imply compensatory up-regulation of cortical activity that allows patients with mild PD to maintain sentence comprehension accuracy.

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A model for failure of a chicken embryo to survive incubation.

Proper assessment of factors contributing to failure of an egg to hatch, i.e., infertility and embryonic mortality, is important in poultry production. A model consisting of the sum of two cumulative logistic distributions was proposed previously to describe the distribution for time of mortality during incubation; model parameters, including probabilities of infertility and mortality, were estimated by the method of least squares. The objective of this paper was to improve the previous model and method of estimation by evaluating alternative distributions and methods; we propose four recommendations. First, probabilities of infertility and mortality should be estimated as observed proportions rather than as model parameters. Second, parameters of the distribution for time of mortality should be estimated using a diphasic Weibull distribution rather than a diphasic logistic distribution. Third, parameters of the distribution for time of mortality should be estimated using noncumulative proportions rather than cumulative proportions. Fourth, parameters of the distribution for time of mortality should be estimated by maximum likelihood rather than by least squares. The minimum Hellinger distance, however, is a good alternative to maximum likelihood to estimate distribution parameters if the distribution of mortality is not known exactly or if the data contain outliers.

Animals↗

Modeling extended lactation curves of dairy cattle: a biological basis for the multiphasic approach.

Objectives of this study are to describe the biological basis for multiphasic milk production and to propose a new empirical model for the lactation curve. To illustrate this model, we used data on 3573 first-lactation Holsteins having lactations of various lengths (285, 345, 405, 465, and 525 d) and with various days open (45, 105, 165, 225, and 285 d). The model describes an increasing first phase of milk yield and a series of decreasing phases of yield. The increasing phase, described by an increasing logistic function of time, is associated with increase in number of active mammary gland cells and increase in yield per cell. The decreasing phases, described by three decreasing logistic functions of time, are associated with decreases in cell number due to apoptosis and in yield per cell due to pregnancy. The new model is [equation: see text] where yDIM is milk yield at each day in milk (DIM), a1 is upper level for the increasing first phase, and p2, p3, and p4 = (1 - p2 - p3) are proportions of a1 for the decreasing second, third, and fourth phases; b's are proportional to duration of each phase; and c's are time of maximum increase or decrease. Nonlinear regression was used to fit average milk yield for each of nine datasets, four with 180 d carried calf and five with 240 d carried calf. Average results indicated that for the first phase, upper level of milk yield was about 22 kg. Duration was about 120 d, centered on time of maximum increase, which was about 11 d before calving. For the second phase (first phase of apoptosis), decrease in yield was relatively large (about 20%) and duration was relatively long (about 375 d). Time of maximum decrease was about 107 d after calving. For the third phase (pregnancy), decrease in yield was relatively small (about 6%) and duration was relatively short (about 200 d). Time of maximum decrease was about 300 d after calving. For each additional day open, time of maximum decrease increased about 1 d. For the fourth phase (second phase of apoptosis), decrease in yield was relatively large (about 74%) and duration was relatively long (about 765 d). Duration for the lactation length of 525 d was exceptionally long. Time of maximum decrease was about 382 d after calving. For each additional day of lactation, duration increased about 5.4 d and day of maximum decrease increased about 0.82 d. We believe that it is possible to model empirically standard and extended lactation curves of dairy cows, based on biological theory and predicated on the multiphasic approach. Further research to understand better the biology of extended lactations, using the proposed multiphasic model, should use planned extended lactations that are at least 525 d in milk and have at least 240 d carried calf.

Animals↗

Analysis of tau haplotypes in Pick's disease.

Pick's disease (PiD) is characterized by the deposition of tau protein as three-repeat tau Pick bodies, whereas progressive supranuclear palsy (PSP) involves the deposition of four-repeat tau neurofibrillary tangles. PSP is associated with the tau H1 haplotype. The authors investigated a possible association between PiD and the tau H1 or H2 haplotype. There was no difference between the tau H2 haplotype or H2H2 genotype frequency in PiD cases and control subjects. No tau mutations were identified in pathologically typical cases of PiD, with antibody 12-E8-negative Pick bodies.

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Influence of storage days on the distribution for time of embryonic mortality during incubation.

Breakout analysis of 11,254 chicken eggs that failed to hatch was used to assess the influence of storage days on the distribution for time of embryonic mortality during incubation and on reproductive efficiency. Eggs were collected over 30 d, stored from 2 through 18 d, and incubated in two hatches. For each storage day within hatch, proportions of embryonic mortality during each of the 21 d of incubation, among embryos that did not survive incubation, were fitted by a diphasic Weibull distribution. Multivariate analysis was used to assess the influence of hatch and storage days within hatch on parameters of the distribution and on two measures of reproductive efficiency, proportions of embryonic mortality during incubation among all eggs incubated P(mort) and among fertile eggs incubated P(mort/fert), and to obtain partial correlation coefficients. Storage days influenced the distribution for time of embryonic mortality in each hatch, but the effect was different for each hatch. As the number of storage days increased, P(mort) and P(mort/fert) increased. Partial correlations showed that P(mort) and P(mort/fert) decreased as the proportion of embryos that died during the first phase decreased and as duration of the second phase increased. The shape of the distribution for time of mortality during incubation influenced reproductive efficiency. Factors that influence the shape of this distribution, other than hatch and storage days within hatch, should be studied to increase reproductive efficiency in the poultry industry.

Animals↗

Dopamine supports sentence comprehension in Parkinson's Disease.

OBJECTIVE: To determine the role of dopamine in the executive resource component of sentence comprehension. METHODS: We studied sentence-picture matching in 20 right-handed, non-demented, native English speakers with mild Parkinson's disease (PD) when 'on' and 'off' their levodopa, taking into account disease duration to control for endogenous dopamine metabolism. We also administered a verbal working memory measure that does not involve specific grammatical manipulations. RESULTS: PD patients 'off' levodopa demonstrated a significant discrepancy in their comprehension of grammatically complex sentences compared to grammatically simpler sentences that was not evident when PD patients were 'on' levodopa. An error analysis demonstrated that impaired comprehension of grammatically complex sentences when 'off' levodopa was associated with poorer performance on foils requiring working memory resources. Performance on an independent measure of verbal working memory correlated only with comprehension of grammatically complex sentences during levodopa supplementation, but working memory according to this measure did not differ during 'on' and 'off' states. CONCLUSION: Dopamine supports the executive resources contributing to sentence comprehension in PD.

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Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick's Disease.

An international group of clinical and basic scientists participated in the Frontotemporal Dementia and Pick's Disease Criteria Conference at the National Institutes of Health in Bethesda, Md, on July 7, 2000, to reassess clinical and neuropathological criteria for the diagnosis of frontotemporal dementia (FTD). Previous criteria for FTD have primarily been designed for research purposes. The goal of this meeting was to propose guidelines that would enable clinicians (particularly neurologists, psychiatrists, and neuropsychologists) to recognize patients with FTD and, if appropriate, to expedite their referral to a diagnostic center. In addition, recommendations for the neuropathological criteria of FTD were reviewed, relative to classical neuropathology and modern molecular biology.

Adult↗

Frequency of tau gene mutations in familial and sporadic cases of non-Alzheimer dementia.

BACKGROUND: Mutations in the tau gene have been reported in families with frontotemporal dementia (FTD) linked to chromosome 17. It remains uncertain how commonly such mutations are found in patients with FTD or non-Alzheimer dementia with or without a positive family history. OBJECTIVE: To determine the frequency of tau mutations in patients with non-Alzheimer dementia. PATIENTS AND METHODS: One hundred one patients with non-Alzheimer, nonvascular dementia, most thought to have FTD. Of these, 57 had a positive family history of dementia. Neuropathologic findings were available in 32. The tau gene was sequenced for all exons including flanking intronic DNA, portions of the 3' and 5' untranslated regions, and at least 146 base pairs in the intron following exon 10. RESULTS: Overall, the frequency of the tau mutations was low, being 5.9% (6/101) in the entire group. No mutations were found in the 44 sporadic cases. However, 6 (10.5%) of the 57 familial cases and 4 (33%) of the 12 familial cases with tau pathologic findings had mutations in the tau gene. The most common mutation was P301L. CONCLUSIONS: We conclude that tau mutations are uncommon in a neurology referral population with non-Alzheimer dementia, even in those with a clinical diagnosis of FTD. However, a positive family history and/or tau pathologic findings increase the likelihood of a tau mutation. There must be other genetic and nongenetic causes of FTD and non-Alzheimer dementia, similar to the etiologic heterogeneity present in Alzheimer disease.

Chromosomes, Human, Pair 17↗