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Biomedical subjects

R G Brown

Publications and source records attributed to R G Brown.

At least 19 recordsLinked to original sources

The anatomy of melancholia--focal abnormalities of cerebral blood flow in major depression.

Using positron emission tomography (PET) and 15Oxygen, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P less than 0.05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P less than 0.05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder.

Adult

Simple and choice reaction time and the use of advance information for motor preparation in Parkinson's disease.

The effects of different types of advance information (warning signal, temporal cue, movement parameter cue), presented at different intervals before an imperative stimulus on reaction time (RT) were examined. Sixteen patients with Parkinson's disease and 16 age-matched normal controls performed a simple reaction time (SRT) task, an uncued, two partially cued (cueing of direction of movement or hand) and a fully cued visual four choice reaction time (CRT) tasks. An S1-S2 paradigm was used, where a warning signal/precue (S1) preceded the imperative signal (S2) by 0 (uncued and unwarned conditions), 200 ms, 800 ms, 1600 ms or 3200 ms. When the unwarned SRT and uncued CRT conditions were compared, the patients were slower than the controls in both conditions, with the group differences being larger for the CRT than the SRT task. Both patients and controls benefited from a warning signal presented before the imperative stimulus (S2), especially when it occurred 200 ms prior to S2. Advance information about the parameters of the required response was used by both patients and controls to preprogramme responses before the onset of S2. In both groups, RTs were generally faster for longer S1-S2 intervals. With an S1-S2 interval of 3200 ms, advance information about two movement parameters was 'fully' used by the patients to preprogramme responses such that their fully cued CRT was reduced to the level of SRT. In the controls, this process was complete by 800 ms. The most parsimonious explanation of the pattern of results across the SRT, fully cued CRT and uncued CRT conditions would be in terms of a slowness in response initiation in Parkinson's disease, which is a stage of processing common to all RT conditions. Deficits at one or more of the stages of processing unique to CRT are, however, necessary to explain the differentially greater slowness of uncued CRT in Parkinson's disease.

Aged

The effect of withdrawal of dopaminergic medication on simple and choice reaction time and the use of advance information in Parkinson's disease.

Eight patients with Parkinson's disease performed simple reaction time (SRT), uncued, partially and fully cued four choice (CRT) tasks. They were tested on two occasions; on their normal dose of dopaminergic medication and following withdrawal of such medication for an average of 14.4 hours. Disability as rated on the Webster scale was greater in the drug reduced state. Although RTs were generally slower when tested in the drug reduced state than when on medication, few differences emerged. Withdrawal of dopaminergic medication had no effect on unwarned SRT and unwarned and uncued CRT performance. Both on and off medication, the patients benefited from a warning signal presented before the imperative stimulus. In both medication states, the speeding up of RT was greatest with a warning signal presented 200 ms before S2. When the imperative stimulus was unwarned, the temporal predictability of its occurrence speeded RT more when on medication than when off. Advance movement parameter information was used by patients to pre-programme responses both on and off medication. In both medication states, the fully cued CRT was the same as SRT only with the 3200 ms S1-S2 interval. Medication state had no effect on movement time or the number of errors. It is suggested that slowness in motor readiness and motor programming may not be specific to striatal dopamine deficiency but rather a nonspecific concomitant of brain damage.

Adult

Effect of practice on performance of a skilled motor task in patients with Parkinson's disease.

Parkinson's disease leads to a breakdown in the execution of highly practised, skilled movements such as walking and handwriting. The improved execution of skilled movements with practice can be understood as a process of schema learning, the determining of the relevant parameters of the specific movement. The ability of patients with Parkinson's disease and age matched normal control subjects to improve their performance, with practice, on a skilled motor task, doing up buttons, was assessed. The task was assessed on its own and with simultaneous foot tapping. Both groups showed an initial improvement in the task on its own and deterioration in performance when buttoning with foot tapping. The amount of interference, however, decreased with practice, particularly in the patients with a 2 Hz tapping rate. The results suggest that patients with Parkinson's disease are capable of schema learning but require more practice than control subjects to achieve comparable levels of performance. This may be a reflection of the fundamental motor dysfunction of the disease rather than a specific learning deficit.

Adult

Regional cerebral blood flow abnormalities in depressed patients with cognitive impairment.

Depression with cognitive impairment, so called depressive pseudodementia, is commonly mistaken for a neurodegenerative dementia. Using positron emission tomography (PET) derived measures of regional cerebral blood flow (rCBF) a cohort of 33 patients with major depression was studied. Ten patients displayed significant and reversible cognitive impairment. The patterns of rCBF of these patients were compared with a cohort of equally depressed non-cognitively impaired depressed patients. In the depressed cognitively impaired patients a profile of rCBF abnormalities was identified consisting of decreases in the left anterior medial prefrontal cortex and increases in the cerebellar vermis. These changes were additional to those seen in depression alone and are distinct from those described in neurodegenerative dementia. The cognitive impairment seen in a proportion of depressed patients would seem to be associated with dysfunction of neural systems distinct from those implicated in depression alone or the neurodegenerative dementias.

Bipolar Disorder

Cognitive function in Parkinson's disease: from description to theory.

From the large body of empirical evidence on cognitive function in Parkinson's disease, a number of attempts have been made to describe the characteristics of the deficits and the conditions under which they are observed. This review considers descriptions limited to specific domains of cognition such as visuospatial function, memory and 'frontal' function, and more general descriptions relating to 'set-shifting', sequencing, temporal ordering and recency discrimination, the locus of cognitive control and bradyphrenia. Later in the paper an attempt is made to provide some theoretical framework for the various descriptions. Two theories are discussed representing contrasting, but complementary approaches. The first is a 'psychological' theory in which the concept of depleted processing resources is suggested as a possible mechanism to explain the observable deficits. The second is a neurobiological model that attempts to integrate information from diverse sources to provide a model for the neuroanatomical and neurochemical substrate that may underlie some of the behavioural deficits.

Caudate Nucleus

Alaskan malamute chondrodysplasia--VIII. Incorporation of [14C]glucosamine and [3H]serine in hepatic metal-binding proteins of Canis familaris.

1. Hepatic proteins isolated from control kennel dogs bound small quantities of zinc and iron and the peptide fraction contained neither metal. 2. Zince loading of kennel dogs stimulated an hepatic uptake of five times more zinc and three times more iron than an equivalent copper load. The increase in metal concentration was noted in the 10,000 dalton protein. 3. Both the 12,000 and 10,000 dalton proteins isolated from kennel dogs contained more binding sites specific for zinc than for either copper or iron. All three proteins isolated from Alaskan Malamutes showed a smaller affinity for zinc than copper or iron. 4. Both copper and zinc loading stimulated an uptake of [14C]glucosamine and [3H]serine from the peptide fraction of control kennel dogs into the 10,000 dalton protein.

Animals

Alaskan malamute chondrodysplasia--VII. Isolation and characterization of copper, zinc and iron binding proteins in Canis familiaris.

1. Three low molecular weight (12,000, 10,000 and 7,000) metal binding proteins have been isolated from the livers of normal and chondrodysplastic Alaskan Malamutes. 2. Comparison studies between kennel (mixed breed) dogs and both adult and immature Alaskan Malamutes suggested that the disturbance in trace mineral metabolism found in the Malamutes is almost entirely reflected in the 12,000 mol. wt species. 3. The major copper-inducible protein (10,000 mol. wt) observed in kennel dogs was not found to be inducible in Malamutes and contained constant ratios of both copper and zinc to protein in metal binding proteins isolated from the livers of both normal and dwarf Malamutes. 4. The copper and zinc found in the UM2 concentrates (mol. wt greater than 2000) of immature Malamutes showed very little affinity to the proteins and these metals were found chiefly in a peptide fraction which apparently serves as a reservoir from which the storage proteins obtain the metals that they bind. 5. Regression analysis indicated a statistically significant correlation between both copper and zinc concentrations and the carbohydrate concentration in the proteins investigated.

Amino Acids

Postfeeding radioimmunoassay artefact in heparinized pig plasma: studies with intestinal calcium-binding protein.

Samples of pig blood were taken in relation to feeding and assayed for intestinal CaBP by radioimmunoassay. When heparinized plasma was assayed by a double-antibody technique, significant postprandial increases of plasma immunoreactivity between twofold and 10-fold were noted. These apparent feeding responses were seen only with heparinized plasma and not with EDTA plasma, ACD plasma, or serum. Nor were such responses seen when heparinized plasma was assayed with talc or charcoal methods for phase seperation. The height of the artefactual response in immunoreactivity following feeding was related to the amount of carrier serum added during the incubation with second antibody and with the duration of this incubation. The artefact was seen in the presence of 0.01M EDTA. These results demonstrate a striking postfeeding radioimmunoassay artefact localized to the second-antibody precipitation step. The artefact can easily be avoided by several methodological changes. Such an artefact could conceivably affect other double-antibody radioimmunoassays of hormones or other substances. Caution is advised when double-antibody radioimmunoassays are used to assay samples taken in relation to feeding.

Animals

The transverse lumbosacral back flap.

The transverse lumbosacral back flap is presented as a good one to use for coverage of sacral defects. Its reliability appears to be due to an axial pattern of its proximal portion, and to an uninterrupted subdermal vascular plexus across the midline of the back (supplying the terminal portion). A retrospective analysis of its use in 20 patients, over the last 3 years, suggests that when it is designed properly it can be most useful in the management of sacral pressure sores.

Adolescent

Alaskan Malamute chondrodysplasia. V. Decreased gut zinc absorption.

Experiements were conducted to determine if zinc absorption was impaired in Alaskan Malamutes which had a genetic chondrodysplasia or dwarfism. When the uptake of an oral dose of 65Zn from the gut in blood was measured in whole dogs it was found that the chondrodysplastic animals absorbed only 25 per cent the amount absorbed by their controls. In vitro studies suggested that 65Zn was initially bound to a protein fraction in all cases but it was later released to a non-protein fraction in the case of normal dogs. This transfer did not occur in the case of the chondrodysplastic dog and it suggests that the transfer of zinc from a protein to a non-protein fraction in the mucosal cell may be the missing step in the dog with chondrodysplasia.

Animals