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A Bennie

Publications and source records attributed to A Bennie.

8 recordsLinked to original sources

Impaired spatial learning in aged rats is associated with loss of p75-positive neurons in the basal forebrain.

We investigated age-related changes in the number and size of neurons positive for the p75 neurotrophin receptor in the cholinergic basal forebrain of female Dark Agouti rats. Since the integrity of these neurons is known to be closely associated with performance in tests of spatial learning ability, we also investigated the incidence of age-related spatial learning impairments, using the Barnes maze. Spatial learning impairments occurred with increasing frequency with age. No rats showed impairment at six months, but 50% were impaired at 14 months and 71% at 26 months. There was no correlation between age and decreased number of p75-positive neurons in the rostral basal forebrain, which consists of the medial septum and vertical limb of the diagonal band of Broca. In the caudal basal forebrain, which consists of the horizontal limb and the nucleus of Meynert, there was a 13% reduction in the number of p75-positive neurons at 17 months compared to six months, and a 30% reduction at 26 months. There was a strong correlation between the presence of spatial learning impairment and a reduction in the number of p75-positive neurons. This correlation was most evident in the rostral basal forebrain, but was also present in the caudal basal forebrain. In the rostral basal forebrain, all learning impaired rats had fewer p75-positive neurons than the average number in unimpaired rats. A close correspondence between the presence of p75 and choline acetyltransferase was evident in basal forebrain neurons of learning-impaired and unimpaired rats. Gross pathological changes to the morphology of p75-positive neurons were relatively frequent in learning-impaired rats. These changes consisted of hypertrophy, appearance of vacuoles, and marginalisation of the cytoplasm. The results indicate the susceptibility of p75-positive neurons to degenerative changes with aging, and show that the loss of these neurons in the basal forebrain was strongly correlated with impairment in spatial learning.

Age Factors↗

Enlarged cholinergic forebrain neurons and improved spatial learning in p75 knockout mice.

The p75 low affinity neurotrophin receptor (p75) can induce apoptosis in various neuronal and glial cell types. Because p75 is expressed in the cholinergic neurons of the basal forebrain, p75 knockout mice may be expected to show an increased number of neurons in this region. Previous studies, however, have produced conflicting results, suggesting that genetic background and choice of control mice are critical. To try to clarify the conflicting results from previous reports, we undertook a further study of the basal forebrain in p75 knockout mice, paying particular attention to the use of genetically valid controls. The genetic backgrounds of p75 knockout and control mice used in this study were identical at 95% of loci. There was a small decrease in the number of cholinergic basal forebrain neurons in p75 knockout mice at four months of age compared with controls. This difference was no longer apparent at 15 months due to a reduction in numbers in control mice between the ages of 4 and 15 months. Cholinergic cell size in the basal forebrain was markedly increased in p75 knockout mice compared with controls. Spatial learning performance was consistently better in p75 knockout mice than in controls, and did not show any deterioration with age. The results indicate that p75 exerts a negative influence on the size of cholinergic forebrain neurons, but little effect on neuronal numbers. The markedly better spatial learning suggests that the function, as well as the size, of cholinergic neurons is negatively modulated by p75.

Aging↗

Downregulation of the p75 neurotrophin receptor in tissue culture and in vivo, using beta-cyclodextrin-adamantane-oligonucleotide conjugates.

Formation of complexes with beta-cyclodextrin derivatives via adamantyl groups was found to enhance the uptake and antisense efficacy of phosphorothioate oligos targeted to the p75 neurotrophin receptor in neuronally differentiated PC12 cells. After a 2-week course of systemic administration to mice (by intraperitoneal injection), there was evidence of a pronounced uptake of these oligos by the dorsal root ganglia (DRG), as well as by liver and kidney. There was no uptake by the brain. Consistent with uptake of antisense oligos by the DRG, systemic administration resulted in marked and consistent downregulation of p75 in DRG neurons. These results indicate that cyclodextrin-adamantane-oligo conjugates have great potential as agents to downregulate target genes in neurons, particularly in vivo in the peripheral nervous system.

Adamantane↗

Falls: a coordinated strategy.

Falls are a common and serious health problem. Responses to the problem should address the individual, the individual's environment, the system of health or residential care used by the individual, and the local community. This article describes a response to the issue of falls in Ryde Hospital and its surrounding community. This response has multiple components which include patient and staff education and interventions with people who have fallen. These initiatives have been developed without additional resources and incorporated into existing systems of care provision.

Accidental Falls↗

Health outcomes as an organisation-wide quality initiative.

Since the burgeoning of the 'health outcomes' movement there has been an ever-increasing body of literature on health outcomes policy debates, directions, frameworks and tools for implementing health outcome-directed initiatives. There is a significant gap in the literature, however, in regard to translating a comprehensive health outcomes policy into practice at a local level. This paper addresses that gap. It describes the local implementation of a comprehensive health outcomes approach which works across the continuum of care. It identifies those organisation-wide structures and processes that support successful progress, thereby providing a useful guide to other organisations wishing to institutionalise the health outcomes approach.

Community Networks↗

The inter rater reliability of the original and of the modified Ashworth scale for the assessment of spasticity in patients with spinal cord injury.

Thirty patients with spinal cord injury (SCI) were randomly selected to participate in this study which evaluated the inter rater reliability of the original and of the modified Ashworth scale for the assessment of spasticity in the lower limbs. A doctor and a physiotherapist rated the muscle tone of hip adductors, hip extensors, hip flexors and ankle plantarflexors according to the original and to the modified Ashworth scale. The results were analyzed using a Cohen's Kappa statistical test and showed varying levels of reliability for different muscle groups and limbs. Kappa values ranged between 0.21 and 0.61 (mean 0.37). The original scale was slightly more reliable than was the modified scale. However, this difference was not significant (P > 0.05), and was not consistent between the two limbs and between different muscle groups. It was concluded that the Ashworth scale is of limited use in the assessment of spasticity in the lower limb of patients with SCI. Further work is required to establish a standardised speed of muscle stretching during the test, or to find more appropriate grades and descriptions of spasticity for this patient group. The effects of training of the raters in the use of the scales also warrants further investigation.

Adolescent↗

Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe.

In a study of the pathogenesis and clinical features of megaloblastic anaemia in southern Africa, we evaluated 144 consecutive Zimbabwean patients with megaloblastic haemopoiesis. Vitamin B12 deficiency was diagnosed in 86.1% of patients and was usually due to pernicious anaemia; isolated folate deficiency accounted for only 5.5% of cases. Anaemia was present in 95.8% of patients; the haemoglobin (Hb) was < or = 6 g/dl in 63.9%. Neurological dysfunction was noted in 70.2% of vitamin B12-deficient patients and was most striking in those with Hb values > 6 g/dl. Serum levels of methylmalonic acid, homocysteine, or both, were increased in 98.5% of patients. Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe and, contrary to textbook statements, is often due to pernicious anaemia. Isolated folate deficiency is less common. As reported in industrialized countries 75 years ago, anaemia is almost always present and often severe. Neurological dysfunction due to vitamin B12 deficiency is most prominent in patients with mild to moderate anaemia.

Anemia, Megaloblastic↗