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Biomedical subjects

R G Robertson

Publications and source records attributed to R G Robertson.

At least 19 recordsLinked to original sources

Rumours: constructive or corrosive.

There is an ever-greater emphasis on the maintenance of professional standards in communication among medical professionals. Much of the focus to date revolves around discourse between patients and families in the clinical arena and reflects standards developed by accrediting agencies and the government. Little has been written about the communication among professionals occurring in the administrative milieu that is largely unseen by those not engaged in the direct provision of or receipt of medical care. That rumours are a part of the interactive discourse is likely not unfamiliar to most in academia. Their potential for damage to the workplace and individuals is very real and requires recognition and in some situations, corporate action. There are options to reduce the likelihood of these kinds of communications and to manage them actively when they occur. What may result is an environment that leads to greater organisational confidence and individual productivity.

Attitude of Health Personnel↗

Spectroscopy of double-beta and inverse-beta decays from 100Mo for neutrinos.

Spectroscopic studies of two beta rays from 100Mo are shown to be of potential interest for investigating both the Majorana nu mass by neutrinoless double beta decay (0nubetabeta) and low energy solar nu's by inverse beta decay. With a multiton 100Mo detector, coincidence studies of correlated betabeta from 0nubetabeta, together with the large Q value ( Q(betabeta)), permit identification of the nu-mass term with a sensitivity of approximately 0.03 eV. Correlation studies of the inverse beta decay and the successive beta decay of 100Tc, together with the large capture rates for low energy solar nu's, make it possible to detect, in real time, individual low energy solar nu in the same detector.

Journal Article↗

Head direction cells in the primate pre-subiculum.

The function of the primate hippocampus and related structures was analysed by making recordings from the hippocampus, subiculum, presubiculum, and parahippocampal gyrus in monkeys actively walking in the laboratory. Head direction cells were found in the presubiculum. The firing rate of these cells was a function of the head direction of the monkey, with a response that was typically 10-100 times larger to the best as compared to the opposite direction. The mean half-amplitude width of the tuning of the cells was 76 degrees. The response of head direction cells in the presubiculum was not influenced by the place where the monkey was, there being the same tuning to head direction at different places in a room, and even outside the room. The response of these cells was also independent of the "spatial view" observed by the monkey, and also the position of the eyes in the head. The average information about head direction was 0.64 bits, about place was 0.10 bits, about spatial view was 0.27 bits, and about eye position was 0.04 bits. The cells maintained their tuning for periods of at least several minutes when the view details were obscured or the room was darkened. This representation of head direction could be useful together with the hippocampal spatial view cells and whole body motion cells found in primates in such spatial and memory functions as path integration.

Action Potentials↗

Spatial view cells in the primate hippocampus: effects of removal of view details.

Hippocampal function was analyzed by making recordings from hippocampal formation neurons in macaques actively walking in the laboratory. "Spatial view" cells, which respond when the monkey looks at a part of the environment were analyzed. It is shown that many of these cells retain their spatial characteristics when the view details are obscured totally by curtains and by darkness. It is shown that many of these cells respond more when the monkey is gazing toward one location in the room than toward other locations, even though none of the view details can be seen. Such cells were found in the CA1 region, the parahippocampal gyrus, and the presubiculum. Other cells stopped responding when the monkey looked toward the normally effective location in the environment if the view details were obscured. These cells were in the CA3 region of the hippocampus. The results indicate that for CA3 cells, the visual input is necessary for the normal spatial response of the neurons, and for other cells in the primate hippocampal formation, the response still depends on the monkey gazing toward that location in space when the view details are obscured. These latter cells therefore could reflect the operation of a memory system, in which the neuronal activity can be triggered by factors that probably include not only eye position command/feedback signals, but also probably vestibular and/or proprioceptive inputs. This representation of space "out there" would be an appropriate part of a primate memory system involved in memories of where in an environment an object was seen and more generally in the memory of particular events or episodes for which a spatial component normally provides part of the context.

Action Potentials↗

Information about spatial view in an ensemble of primate hippocampal cells.

Hippocampal function was analyzed by making recordings from hippocampal neurons in monkeys actively walking in the laboratory. "Spatial view" cells, which respond when the monkey looks at a part of the environment, were analyzed. To assess quantitatively the information about the spatial environment represented by these cells, we applied information theoretic techniques to their responses. The average information provided by these cells about which location the monkey was looking at was 0.32 bits, and the mean across cells of the maximum information conveyed about which location was being looked at was 1.19 bits, measured in a period of 0.5 s. There were 16 locations for this analysis, each being one-quarter of one of the walls of the room. It also was shown that the mean spontaneous rate of firing of the neurons was 0.1 spikes/s, that the mean firing rate in the center of the spatial field of the neurons was 13.2 spikes/s, and that the mean sparseness of the representation measured in a 25-ms period was 0.04 and in a 500-ms time period was 0.19. (The sparseness is approximately equivalent to the proportion of the 25- or 500-ms periods in which the neurons showed one or more spikes.) Next it was shown that the mean size of the view fields of the neurons was 0.9 of a wall. In an approach to the issue of how an ensemble of neurons might together provide more precise information about spatial location than a single neuron, it was shown that in general the neurons had different centers for their view fields. It then was shown that the information from an ensemble of these cells about where in space is being looked at increases approximately linearly with the number of cells in the ensemble. This indicates that the number of places that can be represented increases approximately exponentially with the number of cells in the population. It is concluded that there is an accurate representation of space "out there" in the primate hippocampus. This representation of space out there would be an appropriate part of a primate memory system involved in memories of where in an environment an object was seen, and more generally in the memory of particular events or episodes, for which a spatial component normally provides part of the context.

Algorithms↗

Spatial view cells in the primate hippocampus.

Hippocampal function was analysed by making recordings in rhesus monkeys actively walking in the laboratory. In a sample of 352 cells recorded in the hippocampus and parahippocampal cortex, a population of 'spatial view' cells was found to respond when the monkey looked at a part of the environment. The responses of these hippocampal neurons (i) occur to a view of space 'out there', not to the place where the monkey is, (ii) depend on where the monkey is looking, as shown by measuring eye position, (iii) do not encode head direction, and (iv) provide a spatial representation that is allocentric, i.e. in world coordinates. This representation of space 'out there' would be an appropriate part of a primate memory system involved in memories of where in an environment an object was seen, and more generally in the memory of particular events or episodes for which a spatial component normally provides part of the context.

Animals↗

Clinical and demographic variables related to "fitness to stand trial" assessments in Manitoba.

OBJECTIVE: To assess the extent to which clinical and nonclinical variables have been used by mental health professionals in Manitoba to determine fitness to stand trial. Researchers at a forensic setting in another province have suggested that demographic variables account for as much of the variance in predicting the outcome of these assessments as clinical variables. METHOD: These variables were assessed by the examination of 100 fitness assessments conducted at Winnipeg's Forensic Services unit during a 2-year period. RESULTS: Contrary to findings reported in Ontario, the variance in fitness evaluations in Manitoba was primarily accounted for by clinical rather than demographic variables. CONCLUSION: Since Manitoba's forensic clinicians were using standardized criteria that were very similar to 1992 Criminal Code revisions of fitness, the findings attest to the usefulness of these criteria.

Adult↗

Family practice residents' learning needs and beliefs about office-based psychological counseling.

BACKGROUND AND OBJECTIVES: Teaching office-based psychological counseling is an essential component of family practice training. Most counseling training has been adapted from other disciplines without adequately identifying residents' learning needs, attitudes, and beliefs about counseling. This study was designed to 1) assess family practice residents' perceived learning needs for counseling, and 2) elicit and clarify their attitudes and beliefs about counseling. METHODS: Three consecutive groups of residents anonymously recorded their questions about psychological counseling. These questions were presented to the residents in focus groups for elaboration and clarification of underlying attitudes and beliefs. A consensus panel then categorized the learning needs and identified residents' attitudes and beliefs. RESULTS: Eighty-six distinct learning need questions were identified. These items clustered into four categories: skill development, problem/patient selection, practice management, and role confusion. Focus group findings identified four major themes: the need for limits and boundaries, limited understanding of change and the therapeutic process, doubts about personal readiness, and difficulty with the integration of mind and body. CONCLUSION: These findings parallel the concerns of physicians in practice and reinforce the need to identify resident concerns about office-based counseling. Failure to identify and respond to learner concerns may limit the effectiveness of teaching efforts in this curricular area.

Attitude of Health Personnel↗

The effects of chronic continuous versus intermittent levodopa treatments on striatal and extrastriatal D1 and D2 dopamine receptors and dopamine uptake sites in the 6-hydroxydopamine lesioned rat--an autoradiographic study.

The effects of chronic 'continuous' infusion and 'intermittent' modes of levodopa/carbidopa administration on apomorphine induced circling behaviour, DA uptake sites (labelled with [3H]mazindol) and D1 and D2 DA receptor binding (labelled with [3H]SCH 23390 and [3H]sulpiride, respectively) were investigated in rats with unilateral 6-OHDA lesions of the medial forebrain bundle. The circling behaviour in response to apomorphine was greatly enhanced following chronic 'intermittent' but not 'continuous' levodopa treatments. Following the 'intermittent' regime, the lower dose of apomorphine induced a period of intense circling with delayed onset and rapid offset, than in rats given either 'continuous' infusion of levodopa or saline. The 6-OHDA lesion itself induced gross depletion of [3H]mazindol binding in all striatal subregions, NAc and OT, but not frontal cortex. [3H]Sulpiride binding in the ventrolateral striatal quadrant was increased on the denervated side and this correlated with the peak contralateral turns in response to 0.5 mg/kg apomorphine challenge. This asymmetry in striatal [3H]sulpiride binding was reduced in both groups of rats receiving levodopa. [3H]sulpiride binding in the NAc and OT and [3H]SCH 23390 binding in the striatum, NAc, OT and SNr were unaffected by DA denervation or either regime of levodopa treatments. 'Continuous' infusion and not 'intermittent' injections of levodopa reduced [3H]mazindol binding in the striatal subregions and the frontal cortex on both the denervated and intact sides. The potentiation of the behavioural response to apomorphine by chronic 'intermittent' levodopa treatment does not correspond with the levodopa induced alterations in striatal or extrastriatal DA receptors. In the same group of animals the narrowing of the duration of response to the lower dose of apomorphine may mimic the fluctuations in response to levodopa, seen clinically in long-term levodopa treated parkinsonian patients.

Animals↗

Chronic continuous and intermittent L-3,4-dihydroxyphenylalanine treatments differentially affect basal ganglia function in 6-hydroxydopamine lesioned rats--an autoradiographic study using [3H]flunitrazepam.

The effects of chronic 'continuous' and 'intermittent' L-3,4-dihydroxyphenylalanine treatments on GABA receptor function in the basal ganglia of rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle was investigated, by autoradiography with [3H]flunitrazepam. The 6-hydroxydopamine lesion itself, increased [3H]flunitrazepam binding in the substantia nigra pars reticulata (+17%, with respect to intact side) and entopeduncular nucleus (+44%), but decreased binding in the globus pallidus of the denervated hemisphere (-20%). 'Intermittent' L-3,4-dihydroxyphenylalanine treatment reduced the [3H]flunitrazepam binding changes observed in the substantia nigra pars reticulata (-13%) and entopeduncular nucleus (-4%), whereas 'continuous' infusion of the same daily dose of L-3,4-dihydroxyphenylalanine had less effect (+14%, substantia nigra pars reticulata; +26%, entopeduncular nucleus). In contrast, the [3H]flunitrazepam binding decrease in the globus pallidus of the 6-hydroxydopamine lesioned animals was unaffected by either regime of chronic L-3,4-dihydroxyphenylalanine treatment. The changes in GABA receptor function implied by these results provide further insight into the pathophysiological effects of L-3,4-dihydroxyphenylalanine treatment on basal ganglia function, following dopamine denervation. In accordance with existing electrophysiological and biochemical evidence on this subject, the main implications of these results include reduced GABA sensitivity of neurons in the entopeduncular nucleus and substantia nigra pars reticulata, following chronic 'intermittent', but not chronic 'continuous' L-3,4-dihydroxyphenylalanine treatment; this may be due to a reversal of the 6-hydroxydopamine induced decrease in the GABA-mediated neurotransmission in the striatoentopeduncular and striatonigral pathways. In contrast, the regulation of GABA receptors in the globus pallidus does not appear to be subject to modulation by chronic L-3,4-dihydroxyphenylalanine administration, suggesting that dopamine replacement in this manner does not modify the 6-hydroxydopamine induced increase in GABA-mediated neurotransmission in the stratopallidal pathway.

Animals↗

Further investigations into the pathophysiology of MPTP-induced parkinsonism in the primate: an intracerebral microdialysis study of gamma-aminobutyric acid in the lateral segment of the globus pallidus.

The technique of intracerebral microdialysis has been employed to examine the extracellular level of gamma-aminobutyric acid (GABA) within the lateral segment of the globus pallidus of two cynomolgus monkeys, before and after the induction of parkinsonism with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Microdialysis probes were acutely implanted through indwelling cannulae positioned at several sites above the lentiform nuclei in the conscious primates, and the basal and potassium (100 mM) evoked amino acid levels were monitored for 3 h. These procedures were repeated at fresh sites within the lateral globus pallidus following the induction of parkinsonism with MPTP. The levels of a number of amino acids, including Asn, Ala, Gln, Ser, and Tau were unchanged following MPTP treatment, whereas both the basal and K(+)-evoked release of GABA was consistently increased. This observation represents further corroboration of the evidence for increased GABAergic input to the lateral globus pallidus in MPTP-induced parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

The role of striatopallidal neurones utilizing gamma-aminobutyric acid in the pathophysiology of MPTP-induced parkinsonism in the primate: evidence from [3H]flunitrazepam autoradiography.

The GABA/benzodiazepine receptor complex in the basal ganglia of primates treated with the neurotoxin n-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been studied by semi-quantitative autoradiography with [3H]flunitrazepam ([3H]FNZ). Systemic treatment with MPTP produced a stable and lasting parkinsonian condition, with pronounced bradykinesia, akinesia and tremor. In the lateral segment of the globus pallidus (GPL) there was a significant reduction of [3H]FNZ binding compared with non-treated animals. There were no significant changes in the [3H]FNZ binding in the caudate nucleus, putamen and medial globus pallidus (GPM). This suggests that MPTP-treatment increases GABA release within the GPL exclusively. In view of the available evidence suggesting increased striatal output, and reduced unit activity within the GPL of the MPTP-treated primate, it seems likely that the striatal GABAergic output to the GPL is overactive in this model of Parkinson's disease. Furthermore, as there is no evidence for a change in GABA function within the GPM using this measure, the striatal neurones which innervate the GPM may be differentially affected by loss of dopamine innervation. In line with structural evidence and extrastriatal dopamine receptor distribution this suggests that the two striatopallidal systems are functionally heterogeneous. A hemi-parkinsonian primate model has also been used in this study. This model was produced by injection of MPTP directly into one carotid artery. The substantia nigra pars compacta (SNc) was destroyed on the injected side alone, and consequently the appearance of parkinsonian symptoms was confined to the contralateral side. [3H]FNZ binding in the GPL appears to be bilaterally reduced in this model, suggesting an interaction between the treated and non-treated side of the brain. In addition there is increased binding in the putamen and GPM with respect to the non-treated side of the brain. The increased [3H]FNZ binding in the GPM of the unilateral model may be due to the greater disruption of the nigropallidal and/or nigrostiatal dopamine neurones relative to the systemic model. The former would have the effect of uncoupling D1 dopamine receptors located on the terminals of striatal efferents from nigropallidal dopamine input, and as D1 dopamine receptors are implicated in the presynaptic control of GABA release from the terminals of striatal efferents, this would consequently reduce the level of GABA release in the GPM. The latter possibility would suggest that striatopallidal neurones projecting to GPM are more resistant to the effects of dopaminergic denervation than those projecting to GPL.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Induction of chorea and dystonia in parkinsonian primates.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in primates induced a parkinsonian syndrome that could be reversed by levodopa treatment. Animals quickly developed an apparent restlessness ("akathisia") of the lower limbs after as little as five doses. After 4-10 weeks of regular levodopa therapy, animals developed "peak dose" choreiform movements in the lower limbs that spread, with time, to involve the upper limbs and orofacial musculature. With further treatment (5-21 months), animals developed "peak dose" dystonia that variably involved the limbs and orofacial musculature. These conditions represent novel models of levodopa-induced chorea and dystonia in humans. They depend on the same underlying neuropathology and treatment regimen as their human counterparts. It is to be anticipated that these models of dyskinesia will be useful in determining the mechanisms underlying chorea and dystonia in humans and are ideally suited for experimental evaluation of new treatment strategies.

Animals↗

Neural mechanisms of dystonia: evidence from a 2-deoxyglucose uptake study in a primate model of dopamine agonist-induced dystonia.

The neural mechanisms that mediate dystonia were investigated in a novel experimental primate model of dopamine agonist-induced dystonia. This condition was produced by long-term (15 months) dopamine agonist therapy of a macaque monkey that had been rendered hemiparkinsonian by unilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into the right common carotid artery. The 2-deoxyglucose (2-DG) metabolic mapping technique was applied to the animal during the expression of active unilateral dystonia, and regional brain uptake of 2-DG was assessed autoradiographically. The results demonstrate that dystonia is associated with marked increases in 2-DG uptake in the constituent nuclei of the basal ganglia (caudate nucleus, putamen, medial and lateral segments of the globus pallidus) and in the subthalamic nucleus, but decreased uptake in the structures that receive output of the basal ganglia (ventral anterior/ventral lateral thalamic complex and lateral habenula). Based on these findings it is suggested that dystonia is characterized by increased activity in the putaminopallidal and pallidosubthalamic pathways, and decreased activity in the subthalamopallidal and pallidothalamic pathways.

Animals↗

Injection of excitatory amino acid antagonists into the medial pallidal segment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated primate reverses motor symptoms of parkinsonism.

Intracerebral injections of the broad spectrum excitatory amino acid antagonist kynurenic acid (50 ug) alleviated the symptoms of akinesia, tremor and rigidity in a severely parkinsonian monkey. Unilateral injection of kynurenic acid within the medial pallidal segment produced rotational behaviour away from the side of the injection, and the limbs on the contralateral side showed relief of the MPTP-induced parkinsonian symptoms. The subsequent bilateral injection of the excitatory amino acid antagonist allowed the monkey to move freely, unhindered by tremor or rigidity. In addition unilateral injections of the NMDA antagonist MK-801 (5, 25 and 50 ug) within the medial pallidum also produced dose-related rotational behaviour, with alleviation of parkinsonian symptoms in the contralateral limbs. Systemic administration of MK-801 (1 ng/kg - 1 ug/kg i.m.) was without effect.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Dyskinesia in the primate following injection of an excitatory amino acid antagonist into the medial segment of the globus pallidus.

Injection of an excitatory amino acid antagonist, kynurenic acid, into the medial segment of the globus pallidus of the conscious monkey elicited dyskinesia of the contralateral limbs. In most respects the dyskinesia was indistinguishable from the disorder that is produced by ablation of the subthalamic nucleus, or injection of a GABA antagonist into the subthalamic nucleus. Injections of kynurenic acid into the lateral segment of the globus pallidus, by contrast, did not provoke dyskinesia. The effect of kynurenic acid is attributed to the blockade of neurotransmission from the subthalamic nucleus to the medial pallidal segment, and the results suggest that the neurotransmitter utilised by this pathway is an excitatory amino acid.

Animals↗