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Biomedical subjects

J A Edwardson

Publications and source records attributed to J A Edwardson.

At least 73 records · Page 4Linked to original sources
PubMed1990

Prevalence rates of dementia in an ageing population: are low rates due to the use of insensitive instruments?

The varying prevalence rates of dementia reported in elderly populations may be partly due to the use of different diagnostic measures. In a recent study in which diagnosis was based on the CAPE, a 12-item questionnaire, the prevalence rate for severe cognitive impairment for the age group 75 years or over was lower than previously reported. In the present study, the performance of the CAPE was examined in an elderly general-practice sample with a higher than usual risk of dementia. The study diagnosis was based on a combination of the diagnosis made by the computer program AGECAT and a clinical diagnosis made by the interviewing psychiatrist. Forty-five per cent of patients with definite or probable dementia, as defined, and 100% of those with possible dementia had scores above the cut-point on the CAPE. The sensitivity of the CAPE was low compared with that of other rating scales. It is concluded that the low reported rate with the CAPE is probably due to only the more severe cases being identified. For comparative purposes it is important to know the level of dementia that the instruments used are detecting.

Aged↗
PubMed1990

Reduced gastrointestinal absorption of calcium in dementia.

Several reports have suggested that the neurodegenerative change in Alzheimer-type dementia (ATD) may be related to alterations in calcium homoeostasis. The absorption of radiocalcium (45Ca) in 26 ATD subjects and 11 patients with multi-infarct dementia (MID) was compared to 24 normal age- and sex-matched controls. The absorption of radiocalcium was significantly lower in both ATD and MID when compared to controls. The reduced 45Ca absorption in ATD occurred in the presence of normal plasma concentrations of PTH and vitamin D metabolites and the serum concentrations of calcium and aluminium were in the normal range. The data suggest that the reduced uptake of radioactive calcium observed in ATD is a non-specific derangement.

Aged↗
PubMed1990

Gallium-67 as a potential marker for aluminium transport in rat brain: implications for Alzheimer's disease.

Evidence of a link between aluminium and Alzheimer's disease, parkinsonism-dementia of Guam, and dialysis encephalopathy raises questions regarding the role of this element in the pathogenesis of these conditions. Therefore, we have investigated the use of gallium-67 (67Ga) as a marker for brain uptake of aluminium. The binding of 67Ga to plasma proteins has been studied, and the blood-brain barrier permeability and autoradiographic distribution of this isotope in rat brain determined in vivo. The autoradiographic distribution of 125I-Fe-transferrin receptors in rat brain has also been determined in vitro. Results show that 67Ga was bound to plasma transferrin, entered the brain with a blood-brain barrier permeability of 2.48 x 10(-6) ml/min/g, and showed a marked regional distribution that was very similar to that of 125I-Fe-transferrin receptors. Our data suggest that the vulnerability of the hippocampus, amygdala, and cerebral cortex in conditions such as those mentioned above may be partly due to an increased uptake and deposition of aluminium in these regions by the iron transport system.

Aluminum↗
PubMed1989

Geographical relation between Alzheimer's disease and aluminum in drinking water.

In a survey of eighty-eight county districts within England and Wales, rates of Alzheimer's disease in people under the age of 70 years were estimated from the records of the computerised tomographic (CT) scanning units that served these districts. Rates were adjusted to compensate for differences in distance from the nearest CT scanning unit and for differences in the size of the population served by the units. Aluminium concentrations in water over the past 10 years were obtained from water authorities and water companies. The risk of Alzheimer's disease was 1.5 times higher in districts where the mean aluminium concentration exceeded 0.11 mg/l than in districts where concentrations were less than 0.01 mg/l. There was no evidence of a relation between other causes of dementia, or epilepsy, and aluminium concentrations in water.

Adult↗
PubMed1989

Comparison of the regional distribution of transferrin receptors and aluminium in the forebrain of chronic renal dialysis patients.

Recent studies have emphasised the potential neurotoxicity of aluminium in dialysis encephalopathy and it has also been suggested that this element may have a role in the pathogenesis of Alzheimer's disease. Aluminium is known to be transported by the iron transport protein transferrin. In this study using receptor autoradiography we have demonstrated the presence of transferrin binding sites in the human forebrain and shown a pattern similar to that found in other species. Imaging secondary ion mass spectrometry has demonstrated the distribution of aluminium-containing cell-like profiles in the brains of chronic renal dialysis patients who have raised levels of brain aluminium (greater than 4 micrograms/g dry weight) and even in dialysis patients where the gross level of aluminium was within the normal range. The density of these profiles corresponded to the regions of high transferrin receptor density. In contrast, the distribution of iron in the brain showed an inverse correlation with transferrin receptor density with highest iron levels present in the globus pallidus, an area of low transferrin receptor density. These results suggest that the regional distribution of neuropathological changes seen in dialysis encephalopathy patients and also Alzheimer's disease may reflect the distribution of transferrin receptors. The discrepancy between iron distribution and transferrin receptor distribution suggests that further, as yet uncharacterized mechanisms, govern the distribution of brain iron.

Adult↗
PubMed1989

[D-TRP11]-neurotensin, unlike alpha-flupenthixol, may not block amphetamine-induced hyperactivity in rats.

Recent reports have suggested that neurotensin (NT) and some of its analogues resemble neuroleptics, for example alpha-flupenthixol (FLU), in their ability to suppress locomotor activity. The results obtained support this conclusion, but only if total photocell counts (the "traditional" index) are considered. An improved method of measuring activity--where subjects have to interrupt photocell beams in sequence before a ("conditional") count is registered--suggested, in direct contrast to the total counts index, that the stable analogue of neurotensin [D-Trp11]-neurotensin (DTNT) increased activity slightly (Sahgal and Keith, 1986). The present report is on the effects of DTNT (0-8 microgram/rat, i.c.v.) and FLU (0-1 mg/kg, i.p.) on hyperactivity induced by D-amphetamine (1.5 mg/kg, i.p.). The usual total counts index of activity suggested that FLU and DTNT blocked the increase. On the other hand, conditional count data suggested that only FLU was effective. Both measures indicated that FLU and amphetamine, administered separately, suppressed and enhanced activity, respectively. In contrast, DTNT at these doses had no significant effect on the conditional counts but markedly suppressed total counts. Subsequent observation of DTNT-treated rats placed in small open fields, suggested that the peptide induced marked circling (ambulatory) behaviour, at the cost of other behavioural categories, especially rearing and grooming. It is argued that (a) DTNT may not resemble neuroleptics in its effects on motor behaviour and (b) conditional activity counts, and also measures relating to brief interruptions of photocell beams, can provide useful additional information concerning motor activity.

Amphetamine↗
PubMed1988

Cortisol, ACTH, and dexamethasone concentrations in a psychogeriatric population.

Cortisol and adrenocorticotrophic hormone (ACTH) were measured at 2 time points before the administration of 1 mg of dexamethasone (day 1) and 1 time point on the following day (day 2). Thirteen severely depressed elderly patients, 15 patients with Alzheimer-type dementia (ATD), and 16 normal controls were studied. Cortisol was markedly elevated in depressed patients compared with the other subjects in day 1 samples. Following dexamethasone, both the depressed and ATD patients showed a similar elevation of cortisol compared with controls. ACTH concentrations were not significantly different between the groups before dexamethasone, but were significantly higher in both depressed and ATD patients after dexamethasone. More depressed patients than ATD patients exhibited hypersecretion of ACTH after dexamethasone. This implies that ACTH is less responsive to glucocorticoid feedback in elderly depressed patients, which may be a factor in causing hypercortisolemia.

Adrenocorticotropic Hormone↗
PubMed1988

Amino acid neurotransmitter levels in gliomas and their relationship to the incidence of epilepsy.

The cause of epilepsy due to gliomas is not known. Explanations that is due to mass effect, infiltration and site of the tumour appear insufficient. We have investigated the possibility that epilepsy due to gliomas is caused by interference with normal GABA and glutamate uptake and metabolism in the surrounding cortex. Analysis of human glioma biopsy specimens for the amino acid neurotransmitters and glutamine has shown that gliomas associated with epilepsy have a higher concentration of glutamine. This may be of importance since an elevated concentration of glutamine has been shown to be associated with the onset and severity of cobalt-induced epilepsy.

Amino Acids↗
PubMed1988

A multiple timepoint study of N-terminal pro-opiomelanocortin in depression using a two-site recognition immunoradiometric assay.

N-pro-opiomelanocortin (N-POMC) is secreted from the same precursor as ACTH and beta-endorphin. Elevated plasma ACTH and beta-endorphin/beta-lipotrophin concentrations have been reported in depression, however there have been no previous studies of N-POMC. Twenty-five patients with major depression and 18 control subjects were studied at five timepoints to examine diurnal rhythm and the effect of a dexamethasone suppression test. N-POMC was measured using a newly developed two-site recognition immunoradiometric assay (IRMA). This demonstrated advantages of sensitivity, specificity and simplicity compared with existing radioimmunoassays. N-POMC exhibited a pattern of diurnal rhythm and suppression in response to dexamethasone as described for other POMC derived peptides. Depressed subjects had higher levels of N-POMC at 0900 h post-dexamethasone than did control subjects. In conclusion, the results of this study are consistent with a hypothesis of cosecretion of POMC-derived peptides. N-POMC has a similar pattern of abnormal concentrations to ACTH and beta-endorphin/beta-lipotrophin in depression. This constitutes probable evidence of POMC-derived peptide resistance to glucocorticoid feedback in this condition.

Adult↗
PubMed1987

Raised thyrotrophin-releasing hormone, pyroglutamylamino peptidase, and proline endopeptidase are present in the spinal cord of wobbler mice but not in human motor neurone disease.

The Wobbler mouse (wr) is a mutant that exhibits loss of anterior horn cells in the spinal cord and brainstem and subsequent muscle wasting, particularly of the forelimbs and neck. The wr mice, 2-3 months of age, were found to have increased levels of immunoreactive-thyrotrophin-releasing hormone (ir-TRH) in the spinal cord and pons and medulla, but not in other CNS areas. This increase was observed in dorsal and ventral cord and at cervical, thoracic, and lumbar levels and was confirmed by HPLC to be authentic TRH. The levels of immunoreactive-somatostatin, -neurotensin, and -substance P were not raised in the CNS of wr mice. The activities of two peptidases capable of degrading TRH, pyroglutamylaminopeptidase (PGAP, EC 3.4.11.8) and proline endopeptidase (PEP, EC 3.4.21.26), and the level of 5-hydroxyindoleacetic acid were also raised in the spinal cord of 2-3-month-old wr mice although the activities of alanine aminopeptidase and lactate dehydrogenase and the level of 5-hydroxytryptamine were not. Increased spinal cord levels of ir-TRH and PGAP and PEP activities were not observed in the 1-month-old wr mice. In addition, a pilot study using spinal cord obtained at autopsy from three patients with motor neurone disease and 12 control subjects indicated no increase in spinal cord ir-TRH, PGAP, or PEP in human motor neurone disease.

Aminopeptidases↗
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↗
PubMed1986

Aluminosilicates and senile plaque formation in Alzheimer's disease.

Aluminium and silicon were found to be colocalised in the central region of senile plaque cores in studies with energy dispersive X-ray microanalysis. The distribution of these elements was similar in cores isolated from the cerebral cortex of patients with senile dementia of the Alzheimer type and in cores studied in situ from tissue sections from the cerebral cortex of presenile and senile patients with Alzheimer's disease, and elderly, mentally normal patients. High-resolution solid-state nuclear magnetic resonance techniques showed aluminium and silicon to be present as aluminosilicates. The presence of aluminosilicates at the centre of senile plaque cores contrasts with the distribution of other inorganic constituents and suggests that they may be involved in the initiation or early stages of senile plaque formation.

Aged↗
PubMed1986

Aluminosilicates and the ageing brain: implications for the pathogenesis of Alzheimer's disease.

Senile plaques are a neuropathological feature of the ageing brain and consist of abnormal neuritic and glial processes surrounding an extracellular core of material with fibrillary ultrastructure. Present at low densities in the cerebral cortex of most aged individuals, they occur in large numbers in Alzheimer's disease, the major form of senile dementia. Energy-dispersive X-ray microprobe analysis of isolated cores and plaques in situ from patients with Alzheimer's disease or Down's syndrome and from normal controls has shown co-localization of high concentrations of aluminium (4-19%) and silicon (6-24%) at the centre of the core. The presence of these elements as aluminosilicates has been confirmed using solid-state 27Al nuclear magnetic resonance. These findings provide a link with the other major neuropathological feature of Alzheimer's disease, the neurofibrillary tangle-bearing neurons, where high intracellular levels of Al and Si have also been reported. The focal deposition of these elements may be an early and essential factor in the pathogenesis of Alzheimer-type changes, reflecting an increased exposure to aluminium.

Aged↗
PubMed1986

Histidyl-proline, a rapidly degraded metabolite of thyrotropin releasing hormone, has behavioural activity.

The effects of intracerebroventricular (ICV) administration of histidyl-proline (His-Pro; 0, 1, 10 and 100 micrograms/rat), a rapidly degraded metabolite of thyrotropin releasing hormone (TRH), were assessed using three behavioural paradigms. Locomotor activity was significantly increased over 30, but not 90, min following administration of the highest dose. This stimulatory effect was more apparent when naive rats were tested in an open field without any prior exposure to the apparatus; the effect was attenuated on a second exposure. His-Pro treated subjects also tended to prefer the area near the walls of the apparatus. The effects of the dipeptide on visual perception were studied, using a two-choice task. A low but not high (10, versus 100 micrograms/rat) dose of His-Pro increased response switching, but did not affect response repetition, latencies or percent correct performance. The results indicate that His-Pro can alter behaviour by affecting motor output, as well as emotional processes.

Animals↗
PubMed1986

Molecular forms of somatostatin, substance P and neurotensin in fresh human cerebral cortex.

The molecular forms of somatostatin, substance P and neurotensin in fresh normal human cerebral cortex have been investigated using high performance liquid chromatography and radioimmunoassay. For each peptide most of the immunoreactivity measured corresponds to a single molecular form co-eluting with the authentic peptide. Small differences in the minor peaks of somatostatin and substance P immunoreactivity are seen when compared to the results of similar studies on post mortem human brain. A substantial difference in the molecular forms of neurotensin was seen which suggests that degradation of this peptide may occur post mortem.

Adult↗