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Biomedical subjects

D J Dick

Publications and source records attributed to D J Dick.

At least 37 records · Page 2Linked to original sources
PubMed1994

Mechanically induced changes in action potential duration and left ventricular segment length in acute regional ischaemia in the in situ porcine heart.

OBJECTIVE: The electrophysiological events accompanying early ischaemia are important. The aim of this study was to investigate mechano-electric feedback in acute regional myocardial ischaemia in the intact heart in situ by measuring the change in action potential duration in response to increased ventricular loading imposed by transient aortic occlusion. METHODS: 11 landrace pigs were anaesthetised and their hearts exposed. A pneumatically operated blood pressure clamp was placed around the aorta. Monophasic action potentials and an index of segment motion were recorded from the epicardium in and around the ischaemic area produced by a snare placed around a coronary artery. Ventricular and systemic arterial pressures were measured. An initial aortic clamp was performed during which control recordings were taken. The coronary artery was then tied and the aorta clamped for 5-10 s every 5 min for the duration of the 30 min tie. Recordings were taken from the ischaemic area and non-ischaemic areas. RESULTS: Aortic clamp before ischaemia increased intraventricular diastolic and systolic pressure and reduced action potential duration in all the areas studied (p < 0.001). During acute regional myocardial ischaemia aortic clamping resulted in significantly more shortening of the action potential in the ischaemic area after 10 min of ischaemia than in the control area (5 ms v 10 ms, p = 0.008). Over the following 20 min the degree of shortening decreased. The greater shortening at 10 min could not be attributed to changes in the end diastolic segment length or peak ventricular pressure and could thus represent a change in the expression of mechano-electric feedback by ischaemic myocardium rather than a change in loading conditions. CONCLUSIONS: During the first 30 min following a coronary artery occlusion mechano-electric feedback in the ischaemic myocardium varies with time.

Action Potentials↗
PubMed1994

Regional electromechanical alternans in anesthetized pig hearts: modulation by mechanoelectric feedback.

Electrical and mechanical alternans have often been found to coexist. However, the factors controlling their interdependence are not known. In this study we measure regional electrical and mechanical activity during mechanical alternans to investigate this relationship. Mechanical alternans was induced by rapid atrial pacing in 18 anesthetized, open-chest pigs. Regional segmental contraction and monophasic action potential were measured in three areas of left ventricle using epicardial tripodal strain gauges and suction electrodes. Electrical alternans always accompanied pulsus alternans. The phase of electrical alternans was not related to any measure of regional mechanical activity but did show a constant discordant relation to peak ventricular pressure. This suggested that mechanically dependent changes in action potential duration (mechanoelectric feedback) may be important in modulation electrical alternans. In support of this, pulsus alternans simulated by clamping the proximal aorta on alternate beats was associated with electrical alternans comparable to that produced with rapid atrial pacing. Mechanoelectric feedback modulates regional electrophysiology in the intact heart and may be important in the generation of electrical alternans.

Anesthesia, General↗
PubMed1993

Characterisation of regional myocardial dynamics during mechanical alternans in heart of anaesthetised pig.

OBJECTIVE: The aim was to investigate the behaviour of regional myocardium during mechanical alternans in a multidirectional manner. METHODS: Mechanical alternans was induced in 12 anaesthetised open chested pigs by rapid atrial pacing. In contrast to previous studies, regional mechanical activity was simultaneously assessed at up to three different sites on the left ventricle using epicardial measuring devices able to provide multidirectional information on segment motion. Pressure-length loops were plotted to assess different patterns of segmental motion. The integral of pressure and length was calculated to obtain a regional work index for each beat. RESULTS: Pressure-length loops revealed profound abnormalities in segment motion and work index during regional mechanical alternans. Myocardial segments either performed alternate amounts of positive work on each beat or alternate amounts of positive and negative work on each beat. Alternating segments contracted out of phase with each other and were occasionally stretched during systole. CONCLUSIONS: The spatio-temporal heterogeneity of regional mechanical behaviour is greatly increased during mechanical alternans.

Anesthesia, General↗
PubMed1989

Visuospatial working memory in Parkinson's disease.

Visuospatial impairment is frequently reported in Parkinson's disease but the psychological mechanisms which subserve the impaired abilities and the way in which breakdown of the mechanisms leads to performance deficits have not been precisely delineated. This paper reports experimental investigations designed to test the hypothesis that the locus of the impairment is the visuospatial subsystem of working memory. Subjects were a group of sixteen patients with Parkinson's disease of mild to moderate severity and a matched control group. They performed complex visuospatial and verbal memory tasks. The Parkinsonian group were significantly slower than the control group when performing the visuospatial task. They were not significantly slower and made no more errors than the control group on the verbal task. The findings are compatible with the hypothesis that the visuospatial subsystem of working memory is impaired in Parkinson's disease. It is demonstrated that the impairment is not the result of a reduction in the capacity of this subsystem but is due to difficulty in utilising information stored in the subsystem to perform complex visuospatial tasks.

Aged↗
PubMed1988

Neuronal anti-nuclear antibody in paraneoplastic sensory neuronopathy.

Sera from 3 patients with a paraneoplastic sensory neuronopathy and small cell carcinoma of the lung were found to contain an IgG directed against neuronal nuclei and the nuclei of cells in adrenal medulla. Plasma from one of these patients was injected into laboratory mice for 100 days but passive transfer of the syndrome could not be effected. Plasma did not affect the viability of the dorsal root ganglia cells in tissue culture but did appear to bind to their nuclei. The role of this antibody remains uncertain.

Aged↗
PubMed1988

Cytochrome oxidase deficiency: immunological studies of skeletal muscle mitochondrial fractions.

We report a 2-year-old girl who presented with delayed development, weakness and persistent vomiting. She had a demyelinating peripheral neuropathy. The activity of cytochrome oxidase in skeletal muscle from the patient was 10% of controls. Immunochemical studies using antibodies to holo-cytochrome oxidase and the individual subunits showed a low concentration of all detectable subunits.

Child, Preschool↗
PubMed1988

Muscarinic cholinergic receptor subtypes in hippocampus in human cognitive disorders.

Total muscarinic receptor levels, the levels of the subtypes exhibiting high and low affinity for pirenzepine, and the high- and low-affinity agonist states of the receptor were investigated in hippocampal tissue obtained at autopsy from mentally normal individuals and the following pathological groups: Alzheimer's disease, Parkinson's disease, Down's syndrome, alcoholic dementia, Huntington's chorea, and motor-neurone disease. A moderate decrease in the density of both high-affinity pirenzepine and high-affinity agonist subtypes was found in Alzheimer's disease, whereas a trend towards an increase in the overall muscarinic receptor density was apparent in the parkinsonian patients without dementia, mainly due to an increase in the low-affinity agonist state; the differences between the Alzheimer's disease and nondemented parkinsonian cases were highly significant. As previously reported, the levels of both choline acetyltransferase and acetylcholinesterase were markedly reduced in both Alzheimer's disease and Parkinson's disease--with a greater loss of both enzymes in the demented subgroup of parkinsonian patients. Activities of the cholinergic enzymes were also extensively reduced in Down's syndrome, accompanied by a loss of high-affinity pirenzepine binding. There were no significant receptor or enzyme alterations in the other groups studied. These observations suggest that in the human brain, extensive degeneration of cholinergic axons to the hippocampus, as indicated by a loss of cholinergic enzymes, is not necessarily accompanied by extensive muscarinic receptor abnormalities (as might be expected if a major subpopulation were presynaptic). Moreover, the opposite changes in muscarinic binding in Parkinson's and Alzheimer's diseases may be related to the greater severity of dementia in the latter disease.

Acetylcholinesterase↗
PubMed1987

Nicotinic receptor abnormalities in Alzheimer's and Parkinson's diseases.

The status of cholinergic receptors in dementia is related to the question of potential cholinergic therapy. Whilst muscarinic receptor binding is generally reported to be normal or near normal, findings are reported which indicate substantial reductions of hippocampal nicotinic (high affinity nicotine) binding (occurring in conjunction with decreased choline acetyltransferase) in both Alzheimer's and Parkinson's but not Huntington's disease. A further indication that nicotinic receptor function may be abnormal in Alzheimer's disease is the extensive loss of an endogenous compound, detected for the first time in human brain, which inhibits normal nicotinic binding. Both receptor binding and the inhibitor are also substantially decreased with increasing age in the normal hippocampus.

Adult↗
PubMed1987

Reaction times and attention in Parkinson's disease.

Ten patients with Parkinson's disease performed a simple reaction time task in which, on hearing a tone, they pressed a button with the left thumb. In the first experiment tones sometimes occurred unannounced and at other times were preceded (by between 0 and 3200 ms) by a warning signal. The second experiment was identical to the first except that the subject had simultaneously to perform a simple continuous task with his right hand. Patients had slower reaction times than controls under all circumstances. In general, however, the effect of a warning signal and the effect of a second task were the same for both groups. In the control group the effect of a warning signal depended on whether or not a second task was being performed. Specifically, the advantage of a warning signal for reaction time was lost after long intervals (greater than 200 ms) when a second task was being performed. Parkinson's disease patients lost this advantage even when they were not performing a second task. Animal studies have suggested that dopamine deficiency results in an increase in neural "noise" in the basal ganglia. The behavioural consequences of this may be that Parkinson's disease patients always perform as if they were carrying out another task at the same time. In contrast, their ability to benefit from a warning signal and to allocate attentional resources are unimpaired.

Adult↗
PubMed1987

Cryptococcal choroidoretinitis and immunodeficiency.

A 30 year old man with Hodgkin's disease, clinically in remission, presented with blurred vision in one eye due to a choroiditis. He developed headaches 10 days after commencing oral steroids and was subsequently found to have cryptococcal meningitis. The meningitis and choroiditis resolved on antifungal medication. This is the first case of cryptococcal choroiditis recorded in the United Kingdom.

Adult↗
PubMed1986

A trial of flunarizine in the treatment of Duchenne muscular dystrophy.

Twenty-seven boys with Duchenne muscular dystrophy (DMD) entered a double-blind controlled trial of treatment with the calcium antagonist flunarizine. They were matched for age and disability. At monthly intervals, muscle power, functional ability, locomotor score, contractures, and forced vital capacity were measured by a team not involved in clinical care. Over a period of 1 year, flunarizine in a dose of up to 0.25 mg/kg/day had no effect on the clinical course of the disease.

Adolescent↗
PubMed1986

Cerebellar structure and function in the murine mutant "jolting".

The morphology of the cerebellar cortex of the murine mutant "jolting" and its phenotypically normal littermate was studied. The general organisation of the cerebellum of normal mice was similar in all respects to that described for other vertebrate species. In "jolting" mice aged 4 months or more there was a marked loss of Purkinje cells and spheroids were present on Purkinje cell axons. An ultrastructural examination showed that the spheroids contained randomly orientated neurofilaments, degenerating mitochondria and autophagic vacuoles. The abnormalities in the cerebellum appeared confined to the Purkinje cells. Extracellular recordings were made of the electrical activity of the cerebellar cortex of anaesthetised mice. In the cerebellar cortex of "jolting" animals, Purkinje cells generated little spontaneous activity, but complex discharges resulting from climbing fibre inputs were indistinguishable from normal. The abnormal electrical activity of Purkinje cells in "jolting" mice could be seen in animals as young as 3 weeks. It was concluded that the "jolting" mouse suffers from a cerebellar ataxia.

Action Potentials↗
PubMed1986

Solitary extranodal lymphoma of sciatic nerve.

A solitary extranodal malignant lymphoma (non-Hodgkin's lymphoma, centrocytic type) of the sciatic nerve is described in a 64-year-old woman. Whereas previous reports of peripheral nervous system lymphoma have described multifocal lesions and generally an association with systemic lymphomas, in this case the lymphoma was confined to a segment of a peripheral nerve and was not associated with systemic lymphoma. The clinical presentation was a progressive weakness and sensory disturbance in the right leg. Clinical and electrophysiological examination indicated a lesion in the sciatic nerve, and computerised tomography of the right thigh revealed an enlarged distal segment of the sciatic nerve. On surgical exploration, a fusiform tumour of the sciatic nerve was resected. Pathological examination, including immunohistology and electron microscopy revealed a malignant lymphoma. An unusual histological feature was the presence in the tumour and infiltrated nerve of an extracellular eosinophilic non-amyloid material, similar to that occasionally seen in nodal lymphomas. The patient showed no evidence of lymphoma at other sites at the presentation and this has been confirmed at a 9-month review.

Female↗
PubMed1986

Cholinergic receptors in cognitive disorders.

Cholinergic receptors (muscarinic subtypes M1 and M2, and putative nicotinic binding) have been examined in the hippocampus obtained at autopsy from a variety of patients with cognitive disorders (Alzheimer's, Parkinson's, and Huntington's diseases, Down's Syndrome and alcoholic dementia) and compared with neurologically normal controls and cases of Motor Neuron disease. In all of the disorders associated with a pre-synaptic cortical cholinergic deficit reflected by an extensive loss of choline acetyltransferase (Alzheimer's disease, Parkinson's disease and Down's Syndrome) there was a substantial reduction in the binding of (3H) nicotine to the nicotinic receptor. By contrast reductions in both muscarinic subtypes (M1 and M2) were apparent to only a moderate extent in Alzheimer's disease, whereas in Parkinson's disease binding was significantly increased (apparently not in relation to anti-cholinergic drug treatment) in the non-demented but not demented cases. A further abnormality detected in Alzheimer's disease but not the other disorders investigated was a decrease in an endogenous inhibitor of nicotinic binding, the identity of which is as yet unknown but which may be a candidate for a possible endogenous modulator of the nicotinic receptor. These observations suggest that in Alzheimer's disease not only muscarinic but also nicotinic receptor function should be considered in relation both to future therapeutic strategies and, in the search for a clinical marker which might be of diagnostic value, to potential probes of the cortical cholinergic system.

Cognition Disorders↗
PubMed1986

Valproate causes metabolic disturbance in normal man.

Valproate is an important anticonvulsant which is rarely associated with fatal hepatotoxicity. Previous experiments have shown that valproate inhibits several metabolic processes in isolated rat hepatocytes and when administered to starved rats causes a fall in the blood concentrations of glucose and ketone bodies. Since these changes may be related to the hepatotoxicity, the effect of valproate administration on intermediary metabolism in man was studied. One gram of valproate given orally to fasted normal humans caused a 78% fall in the concentration of 3-hydroxybutyrate and a 60% fall in total ketones. Also the concentrations of lactate, pyruvate, alanine and glycerol increased after valproate administration. Similar changes were observed after intravenous administration of 400 mg of valproate. Valproate clearly has a significant effect on intermediary metabolism in the liver and this is probably related to the mechanism of the hepatotoxicity.

Acetoacetates↗