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Biomedical subjects

E M Daly

Publications and source records attributed to E M Daly.

11 recordsLinked to original sources
PubMed2000

Prefrontal and medial temporal correlates of repetitive violence to self and others.

BACKGROUND: The neurobiological basis for violence in humans is poorly understood, yet violent behavior (to self or others) is associated with large social and healthcare costs in some groups of patients (e.g., the mentally retarded). The prefrontal cortex and amygdalo-hippocampal complex (AHC) are implicated in the control aggression, therefore we examined the neural integrity of these regions in violent patients with mild mental retardation and nonviolent control subjects. METHODS: We used (1)H-magnetic resonance spectroscopy (MRS) to measure 1) concentrations and ratios of N-acetyl aspartate (NAA), creatine phosphocreatine (Cr+PCr), and choline-related compounds (Cho) in prefrontal lobe of 10 violent inpatients and 8 control subjects; 2) ratios of NAA, Cr+PCr, and Cho in the AHC of 13 inpatients and 14 control subjects; and 3) frequency and severity of violence in patients. RESULTS: Compared to control subjects, violent patients had significantly (p <.05, analysis of covariance-age and IQ as confounding covariates) lower prefrontal concentrations of NAA and Cr+PCr, and a lower ratio of NAA/Cr+PCr in the AHC. Within the violent patient group, frequency of observed violence to others correlated significantly with prefrontal lobe NAA concentration (r = -0.72, p <.05). CONCLUSIONS: NAA concentration indicates neuronal density, and Cr+PCr concentration high-energy phosphate metabolism. Our findings suggest that violent patients with mild mental retardation have reduced neuronal density, and abnormal phosphate metabolism in prefrontal lobe and AHC compared to nonviolent control subjects. Further studies are needed, however, to determine if these findings are regionally specific, or generalize to other groups of violent individuals.

Adult↗
PubMed2000

Striate cortex in humans demonstrates the relationship between activation and variations in visual form.

Electrophysiologic and functional imaging studies have shown that the visual cortex produces differential responses to the presence or absence of structure within visual textures. To further define and characterize regions involved in the analysis of form, functional magnetic resonance imaging (fMRI) was used to detect changes in activation during the viewing of four levels of isodipole textures. The texture levels systematically differed in the density of visual features such as extended contours and blocks of solid color present within the images. A linear relationship between activation level and density of structure was observed in the striate cortex of human subjects. This finding suggests that a special subpopulation of striate cortical neurons participates in the ability to extract and process structural continuity within visual stimuli.

Adult↗
PubMed2000

The functional neuroanatomy of social behaviour: changes in cerebral blood flow when people with autistic disorder process facial expressions.

Although high-functioning individuals with autistic disorder (i.e. autism and Asperger syndrome) are of normal intelligence, they have life-long abnormalities in social communication and emotional behaviour. However, the biological basis of social difficulties in autism is poorly understood. Facial expressions help shape behaviour, and we investigated if high-functioning people with autistic disorder show neurobiological differences from controls when processing emotional facial expressions. We used functional MRI to investigate brain activity in nine adults with autistic disorder (mean age +/- standard deviation 37 +/- 7 years; IQ 102 +/- 15) and nine controls (27 +/- 7 years; IQ 116 +/- 10) when explicitly (consciously) and implicitly (unconsciously) processing emotional facial expressions. Subjects with autistic disorder differed significantly from controls in the activity of cerebellar, mesolimbic and temporal lobe cortical regions of the brain when processing facial expressions. Notably, they did not activate a cortical 'face area' when explicitly appraising expressions, or the left amygdala region and left cerebellum when implicitly processing emotional facial expressions. High-functioning people with autistic disorder have biological differences from controls when consciously and unconsciously processing facial emotions, and these differences are most likely to be neurodevelopmental in origin. This may account for some of the abnormalities in social behaviour associated with autism.

Adult↗
PubMed1999

High brain myo-inositol levels in the predementia phase of Alzheimer's disease in adults with Down's syndrome: a 1H MRS study.

OBJECTIVE: An extra portion of chromosome 21 in Down's syndrome leads to a dementia in later life that is phenotypically similar to Alzheimer's disease. Down's syndrome therefore represents a model for studying preclinical stages of Alzheimer's disease. Markers that have been investigated in symptomatic Alzheimer's disease are myoinositol and N-acetyl-aspartate. The authors investigated whether abnormal brain levels of myo-inositol and other metabolites occur in the preclinical stages of Alzheimer's disease associated with Down's syndrome. METHOD: The authors used 1H magnetic resonance spectroscopy (MRS) with external standards to measure absolute brain metabolite concentrations in 19 nondemented adults with Down's syndrome and 17 age- and sex-matched healthy comparison subjects. RESULTS: Concentrations of myoinositol and choline-containing compounds were significantly higher in the occipital and parietal regions of the adults with Down's syndrome than in the comparison subjects. Within the Down's syndrome group, older subjects (42-62 years, N = 11) had higher myo-inositol levels than younger subjects (28-39 years, N = 8). Older subjects in both groups had lower N-acetylaspartate levels than the respective younger subjects, although this old-young difference was not greater in the Down's syndrome group. CONCLUSIONS: The approximately 50% higher level of myo-inositol in Down's syndrome suggests a gene dose effect of the extra chromosome 21, where the human osmoregulatory sodium/myo-inositol cotransporter gene is located. The even higher myoinositol level in older adults with Down's syndrome extends to the predementia phase earlier findings of high myoinositol levels in symptomatic Alzheimer's disease.

Adult↗
PubMed1998

Volumes of medial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment (and in healthy controls).

BACKGROUND: The clinical diagnosis of Alzheimer's disease (AD) can be difficult to make in early stages of disease. Structural neuroimaging offers a potential tool in the clinical diagnosis of AD with mild cognitive impairment. Postmortem studies indicate that early neuropathology in AD occurs in medial temporal lobe limbic structures. Magnetic resonance imaging (MRI) studies that assessed these volumes in mildly impaired AD patients remain inconclusive. METHODS: Using MRI, we measured volumes of left and right hippocampus, amygdala, and anterior and posterior parahippocampal gyrus (PHG) in 13 AD patients with mild cognitive impairment, defined as > or = 20 on the Mini-Mental State Exam, and in 21 healthy age- and sex-matched controls. RESULTS: The AD patients had smaller medial temporal lobe volumes, except for the right anterior PHG. Discriminant function analysis using MRI volumes produced 94% correct group classification. CONCLUSIONS: These results show that in mildly impaired AD patients atrophy is present in medial temporal lobe structures; that MRI volumes of the anterior PHG, which contains entorhinal cortex, are reduced, but the amygdala and hippocampal volumes show greater reduction; and that discriminant function analysis using all volumes as predictors can correctly classify a high proportion of individuals.

Aged↗
PubMed1998

Cortical regions involved in visual texture perception: a fMRI study.

To determine visual areas of the human brain involved in elementary form processing, functional magnetic resonance imaging (fMRI) was used to measure regional responses to two types of achromatic textures. Healthy young adults were presented with 'random' textures which lacked spatial organization of the black and white pixels that make up the image, and 'correlated' textures in which the pixels were ordered to produce extended contours and rectangular blocks at multiple spatial scales. Relative to a fixation condition, random texture stimulation resulted in increased signal intensity primarily in the striate cortex, with slight involvement of the cuneus and middle occipital, lingual and fusiform gyri. Correlated texture stimulation also resulted in activation of these areas, yet the regional extent of this activation was significantly greater than that produced by random textures. Unlike random stimulation, correlated stimulation additionally resulted in middle temporal activation. Direct comparison of the two stimulation conditions revealed significant differences most consistently in the anterior fusiform gyrus, but also in striate, middle occipital, lingual and posterior temporal regions in subjects with robust activation patterns. While both random and correlated stimulation produced activation in similar areas of the occipital lobe, the increase in regional activation during the correlated condition suggests increased recruitment of neuronal populations occurs in response to textures containing visually salient features. This increased recruitment occurs within striate, extrastriate and temporal regions of the brain, also suggesting the presence of receptive field mechanisms in the ventral visual pathway that are sensitive to features produced by higher-order spatial correlations.

Adult↗
PubMed1997

Interactive effects of age and hypertension on volumes of brain structures.

BACKGROUND AND PURPOSE: Advanced age and hypertension have each been associated with changes in brain morphology and cognitive function. To investigate the interaction of age and hypertension with structural brain changes and neuropsychological performance in otherwise healthy patients with essential hypertension, we compared young-old (ages 56 to 69 years) and old-old (ages 70 to 84 years) hypertensive patients (n = 27) with 20 age-matched normotensive healthy control subjects, using quantitative volumetric MRI and a battery of neuropsychological tests. METHODS: Quantitative regions of interest and segmentation analyses were applied to MRI scans of brain to measure volumes of different brain structures and of cerebrospinal fluid (CSF). Severity of white matter hyperintensities (WMHs) was qualitatively rated in the MRI scans. A battery of neuropsychological tests was administered to each subject. RESULTS: The combined hypertensive group (young-old and old-old) had smaller volumes of thalamic nuclei and larger volumes of CSF in the cerebellum and temporal lobes and showed poorer performance in memory and language tests than did the control subjects. Main effects for age were significant in multiple brain regions of interest. The old-old hypertensive patients and age-matched control subjects demonstrated volume reductions in brain structures and increases in ventricular and peripheral CSF volumes compared with the younger subjects. There was a significant group x age-group interaction in temporal and occipital CSF, not related to WMH, with the old-old hypertensive patients having significantly larger CSF volumes in these regions than the young-old hypertensives and both healthy control groups. CONCLUSIONS: Hypertension exacerbates the morphological changes accompanying advanced age. Temporal and occipital regions appear most vulnerable to brain atrophy due to the interactive effects of age and hypertension.

Aged↗
PubMed1990

Physicochemical and pharmacokinetic parameters of seven lipophilic chlorambucil esters designed for brain penetration.

This report describes the physicochemical and pharmacokinetic parameters of seven chlorambucil esters, which were compared with those of chlorambucil. These esters were designed as chlorambucil prodrugs to increase the brain penetration and concentration vs time profile of chlorambucil within the CNS for potential treatment of brain tumors. They include four aliphatic esters from one to eight carbon chains in length (chlorambucil-methyl, -propyl, -hexyl, and -octyl esters) and three aromatic esters, including the phenylmethyl, phenylethyl and prednisolone ester of chlorambucil, prednimustine. The esters were lipophilic and possessed log octanol:water partition coefficients (log P values) that ranged from 4.05 to greater than 8.0. All retained alkylating activity, which was reduced compared with that of chlorambucil. In addition, all were metabolized in vivo in the rat to yield chlorambucil alone. Measurement of the in vitro rate of ester hydrolysis of the compounds to yield chlorambucil in rat plasma demonstrated that short-chain aliphatic and aromatic chlorambucil esters were rapidly broken down to their parent compound. The plasma half-lives of the compounds increased with the increasing length and complexity of their ester chain. This may have been related to an increase in the binding of the long-chain esters to plasma proteins, protecting the ester from nonspecific plasma esterases, and to a reduced affinity of plasma esterases to these esters. Pharmacokinetic analysis of chlorambucil-hexyl, -octyl, and -prednisolone esters by HPLC demonstrated that following their intravenous administration in the rat (in doses equivalent to equimolar chlorambucil, 10 mg/kg), they yielded only low concentrations of active compounds in plasma and brain. The brain:plasma ratio of these was low and similar to that of chlorambucil, and no ester demonstrated anticancer activity superior to that obtained after the administration of equimolar chlorambucil (5 mg/kg i.v., days 1-5) against brain-sequestered Walker 256 carcinosarcoma in the rat.

Alkylating Agents↗
PubMed1990

Pharmacokinetics of chlorambucil-tertiary butyl ester, a lipophilic chlorambucil derivative that achieves and maintains high concentrations in brain.

Equimolar doses of chlorambucil (10 mg/kg) and the lipophilic chlorambucil derivative, chlorambucil-tertiary butyl ester (13 mg/kg), were given i.v. to rats. Plasma and brain concentrations of chlorambucil and its active metabolites, 3,4-dehydrochlorambucil and phenylacetic mustard, as well as of chlorambucil-tertiary butyl ester were then determined by HPLC between 2 and 240 min after drug administration. Chlorambucil demonstrated a monophasic disappearance from plasma following its administration, with a half-life of 28 min. Significant amounts of phenylacetic mustard were detected after 15 min, and this agent maintained high levels of active compounds in plasma throughout the study. Only low concentrations of chlorambucil and phenylacetic mustard were detected in brain between 2 and 120 min. Following equimolar chlorambucil-tertiary butyl ester administration, it rapidly disappeared from plasma, with a half-life of approximately 2 min, and maintained low plateau concentrations between 15 and 120 min after treatment. It was not detected thereafter, although significant amounts of chlorambucil and phenylacetic mustard were detected throughout the study. Significant amounts of chlorambucil-tertiary butyl ester entered and remained within the brain, achieving a peak concentration at 15 min and disappearing thereafter with a half-life of 37 min. Low levels of chlorambucil and phenylacetic mustard were also detected. Calculated from the areas under the concentration vs time curves of total active compounds derived from chlorambucil and chlorambucil-tertiary butyl ester in brain and plasma, the brain:plasma concentration integral ratios were 0.018 and 0.68, respectively. Following equimolar doses of chlorambucil and chlorambucil-tertiary butyl ester, a 7-fold greater concentration integral was achieved by chlorambucil-tertiary butyl ester in brain at a 5-fold lower plasma concentration integral. Chlorambucil-tertiary butyl ester may be of value in the treatment of brain-sequestered tumors.

Alkylating Agents↗
PubMedDate not supplied

The clinical achievement portfolio: an outcomes-based assessment project in nursing education.

Dynamic healthcare market forces impel educators to search for innovative methods of academic assessment to measure learning outcomes. The clinical achievement portfolio is a creative and systematic tool for documenting continuous improvement of student clinical learning. The authors describe the use of the portfolio as a pilot project aimed at introducing reflective thinking and measuring clinical learning in undergraduate nursing education. Potential benefits of the clinical portfolio and implications for future research are proposed.

Attitude of Health Personnel↗