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Biomedical subjects

E Scott

Publications and source records attributed to E Scott.

At least 37 records · Page 2Linked to original sources
PubMed1997

Subcortical hyperintensities on magnetic resonance imaging in patients with severe depression--a longitudinal evaluation.

In a longitudinal evaluation of 37 patients with severe depression who had undergone brain magnetic resonance imaging (MRI) 6 months-2 years (mean 14.1 months) previously, the degree of residual dysfunction was predicted by the extent of subcortical white matter hyperintensities (WMHS, p < .01), longer time elapsed since the MRI scan (p < .05), older age (p < .05), and older age at onset of affective disorder (p < .05). Ten (27%) patients developed "probable" dementia syndromes of the vascular type, with such syndromes being predicted by WMHS (p < .01) and older age of onset of affective disorder (p < .05). Institutionalization of patients was predicted largely by the combination of chronic depression, progressive cognitive decline, and advanced age. The study supports the notion that a subgroup of patients with late-onset depressive disorders, without a family history of depression, and with risk factors to cerebrovascular disease, have extensive WMHS on MRI, and that such structural brain changes predispose to chronic depression and progressive cognitive decline.

Adult↗
PubMed1997

Utilising molecular biological and histopathological techniques to study the dopaminergic system in patients with melancholia.

OBJECTIVE: To describe the rationale for investigating the dopaminergic system in patients with melancholia by applying molecular biological (notably, in situ hybridisation) and histopathological techniques in postmortem brain tissue. METHOD: Relevant advances in the functional neuroanatomy of frontostriatal circuits, as well as insights from clinical neuroimaging studies in primary and secondary depressive disorders, are presented. These are integrated with developments in the pharmacological and molecular characteristics of dopamine receptor subtypes and recognition of their selective anatomical distribution. RESULTS: Converging data from the basic and clinical neurosciences suggest that the pathophysiology of depressive disorders characterised by psychomotor phenomena, such as melancholia, may involve dysregulation of dopaminergic mechanisms within complex frontostriatal circuits. CONCLUSIONS: The key feature of in situ hybridisation is its capacity to test for variations in the functional components of designated biochemical systems within highly specific anatomical regions. We utilise this approach, in combination with relevant histopathological techniques, to test the structural and functional integrity of the dopaminergic system within key fronto-striatal circuits in patients who had exhibited psychomotor phenomena. The same approach can also be used to study the integrity of other relevant biochemical systems, such as the serotoninergic and noradrenergic systems, in patients with other mood disorders.

Brain Mapping↗
PubMed1997

Analgesics: a comparison of therapeutic knowledge and inter-professional liaison between general practitioners and community pharmacists.

The aim of this study was to ascertain general practitioners' (GPs') and pharmacists' knowledge of analgesics, to establish professional opinion on their use, and to assess the extent of pharmacist input into the prescribing of analgesics. Pharmacists displayed a better knowledge of analgesics than their colleagues in general practice, but had little input into the prescribing decisions made by GPs. Pharmacists' knowledge is not being put to best use in contributing to the preparation of practice formularies, and links between these two health professional groups need to be developed further.

Analgesics↗
PubMed1996

Trinucleotide repeat expansion in the FRAXE locus is not common among institutionalized individuals with non-specific developmental disabilities.

Expansion of a polymorphic GCC-repeat at the FRAXE locus has been associated with expression of chromosome fragility at this site and cognitive impairment in some individuals previously testing negative for CGG-repeat expansion in the fragile X mental retardation-1 (FMR1) gene. To determine the frequency of FRAXE triplet repeat expansion among persons with developmental disability, 396 individuals from two institutions were studied, all of whom were negative for FMR1 repeat expansion. Clinically, there was a wide range of mental impairment, with the majority (61.1%) being severely to profoundly affected. The distribution of FRAXE GCC-repeat numbers in the study population was 5-38: 28 (5.6%) with 10-14 repeats; 366 (73.8%) with 15-19 repeats; 74 (14.9%) with 20-24 repeats; 20 (4.0%) with 25-29 repeats; and 5 (1.0%) with 30-38 repeats, with no individuals demonstrating repeat expansion. One profoundly retarded male was found to have a deletion of about 40 bp. Southern blots of HindIII-digested DNAs from individuals with > or = 26 repeats all showed normal patterns. These results suggest that FRAXE GCC-repeat expansion is not a common cause of developmental disability in institutionalized persons with mild to profound mental retardation.

Adult↗
PubMed1996

A molecular mechanism of integrin regulation from bone cells stimulated by orthodontic forces.

The purpose of this paper is to discuss a molecular mechanism in the signal transduction pathways of the regulation of integrin genes taking place in bones cells as a result of orthodontic or mechanical stimulation. Human osteosarcoma (HOS) TE-85 cells were cultured in Dulbecco's modified Eagle's medium (DMEM)/F-12 and grown to confluency in Flexercell type I dishes and orthodontic forces were applied to the cells via an intermittent strain of 3 cycles/minute using the Flexercell Strain Unite System for periods of 15 and 30 minutes, 2 and 24 hours and 3 days. Antibodies against beta 1 and alpha v integrins were immunolocalized in strained and unstrained cultures. Total RNA was extracted and cDNA probes were used to measure at various mRNA expression of beta 1 (1.2 kb) and alpha v (1.1 kb) integrins. A cDNA probe for cyclophylin (750 b) was used for controls of gene expression. Results showed that mechanical stimulation caused a reorganization of integrin distribution in comparison with non-stimulated controls. mRNA for beta 1 expression showed a marked increase at 30 minutes and 3 days, while mRNA levels for alpha v did not change with strain. The selective expression of integrins mRNA is indicative of a specific gene regulation by mechanical stimulation in the cells studied.

Bone Remodeling↗
PubMed1996

Interest among occupational therapy managers in measuring workload for case costing.

OBJECTIVES: Interest in costing health care delivery on an individual case basis has increased in recent years as concern with overall health care costs has heightened. Costing exercises have been largely oriented around medical classification systems. Measures to incorporate the contributions of allied health activities such as occupational therapy are relatively recent. The objective of this study was to examine the attitudes and opinions of senior occupational therapy managers toward workload measurement on the basis of case mix. METHOD: A survey was sent to all 198 senior occupational therapy managers in accredited Canadian facilities, which was completed by 182 respondents for a response rate of 92%. The questionnaire asked about workload measurement system(s) currently used, satisfaction with the system(s), and needs and expectations of workload systems in general. RESULTS: The majority of respondents were using a time recording workload measurement system and expressed relatively low levels of satisfaction with it. Current systems were unable to provide costing data, which respondents ranked as very important for themselves as managers. The majority of respondents believed that it would be useful or very useful to be able to cost occupational therapy services by a diagnostic grouping system and to establish standard protocols per diagnosis, standard times per procedure per institution, and standard times per procedure for the profession. CONCLUSION: There is support for developing or expanding current methods of measuring workload. Senior occupational therapy managers would like to be able to predict their workload prospectively, a step that will accommodate the move toward case costing and program management.

Attitude of Health Personnel↗
PubMed1995

Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression.

In 39 hospital inpatients with severe primary depressive disorders, we evaluated the relationships between subcortical hyperintensities on magnetic resonance imaging (MRI) and clinical features, neuropsychological impairment and response to standard therapies. Both white matter and gray nuclei lesions were associated with older age and the absence of a family history of affective disorder. White matter hyperintensities were also associated with onset of first affective episode after the age of 50 years and impaired psychomotor speed. Most importantly, the severity of white matter hyperintensities predicted a poorer response to treatment (r = -0.44, p < .01). Negative correlations of the same order were detected in those (n = 20) who received electroconvulsive therapy (r = -0.42, p = .06) and those (n = 19) who received pharmacotherapy alone (r = -.49, p < .05). This study provides preliminary evidence supporting the clinical and prognostic significance of extensive white matter hyperintensities in patients with severe depression.

Activities of Daily Living↗
PubMed1995

Early events in the invasion of the human nail plate by Trichophyton mentagrophytes.

A new in vitro model for the study of nail invasion by dermatophyte fungi was developed. The dermatophyte Trichophyton mentagrophytes, and fragments of finger-nails and toe-nails were used. Arthroconidia were inoculated on the ventral surface of the nails. After 6 h, adherence and germination of arthroconidia was observed. By 16 h, small germ tubes with side branches were evident. At about 24 h, micro-colonies had become established. At 48 h, a mycelium had formed, and at about 72 h most of the nail fragment was covered with fungal growth. Nail penetration occurred from the ventral surface through the intercellular spaces, and with longer incubation all three layers were invaded by arthroconidia growing through channels. Nail invasion occurred in the absence of added nutrients. Dermatophyte fungi appeared to invade the nail by a combination of mechanical and chemical factors. The model provides a substrate to study the pharmacokinetics and bioavailability of new antifungal agents in situ.

Humans↗
PubMed1995

Patient information leaflets on over-the-counter (OTC) medicines: the manufacturer's perspective.

A survey was undertaken to assess the views of the manufacturers of over-the-counter (OTC) products about (i) the value of patient information leaflets (PILs), (ii) the recent European Community directive relating to PILs and (iii) the procedures which are in place for producing and testing PILs. Although approximately half (15/31) of the respondents (response rate 31/58) thought that PILs were more important for OTC than prescription only medicines, this view was not unanimous. A majority (18/28) thought that the new EC directive would provide too much information to patients although only a small number (2/27) thought that the regulations were unnecessary. Indication for the product was thought to be the most important information for the immediate outer packaging. Only about one-third (35%) of patients are thought to read PILs, in contrast to the majority who read the outer packaging. A wide variety of departments contribute to preparing PILs. The marketing department had a major input particularly with respect to layout and testing of leaflets. On the whole the design and production of PILs involves considerable effort but their testing appears less structured and thorough.

Drug Information Services↗
PubMed1995

The response to thrombin of human neutrophils: evidence for two novel receptors.

Human alpha-thrombin was a chemoattractant for human neutrophils yielding a maximal response of similar magnitude to that observed with formyl-Met-Leu-Phe. The observed chemotaxis was not due to stimulation of the proteolytically activated thrombin receptor since: (1) this receptor was not detected by flow cytometry; (2) the inactive thrombin mutant Ser195-->Ala elicited a chemotactic response indistinguishable from that caused by wild-type thrombin; (3) antibodies to the cleavage site of the proteolytically activated receptor did not affect thrombin-induced chemotaxis; (4) a thrombin receptor activating peptide (TRAP) failed to stimulate chemotaxis. These data indicate the existence of a thrombin receptor for neutrophil chemotaxis which is not activated by proteolysis. In addition, although wild-type and ser195-->Ala thrombin did not cause an increase in intracellular Ca2+, a Ca2+ response to TRAP was observed with neutrophils from some donors. The TRAP-induced increase in Ca2+ was reproducible, dose dependent and specific. The use of alanine-substituted peptides demonstrated that the Ca2+ response was due to TRAP stimulation of a receptor other than the proteolytically activated thrombin receptor. Thus, it is necessary to re-evaluate the assumption made in previous studies that responses to TRAP are mediated by the proteolytically activated thrombin receptor.

Adult↗
PubMed1994

Differential effects of serum on lipopolysaccharide receptor-directed macrophage activation for nitric oxide production.

In this manuscript, the effects of fetal bovine serum (FBS) on activation of mouse macrophages through the p73 lipopolysaccharide (LPS) receptor have been evaluated. In confirmation of earlier published studies, FBS will significantly potentiate the ability of LPS to activate macrophages to produce nitric oxide (NO). Evidence that this potentiating effect of FBS is mediated primarily by an interaction with LPS is provided by data showing that the stimulating effects of a hamster IgM monoclonal antibody to the p73 LPS receptor are significantly suppressed under identical conditions of FBS addition. The presence of FBS enhances both the kinetics of LPS-induced NO production and delays the induction of MAb5D3-induced NO production. The data establish that the ability of FBS to reduce MAb5D3-initiated NO production can only be manifest during the first 4-6 h following activation with antibody. Similarly, the ability of polymyxin B (which does not affect MAb5D3 activity) to inhibit LPS-dependent macrophage activation is also only effective during the first 4-6 h of stimulation, suggesting a parallel kinetic profile in the activation of the inducible NO synthase by these related activators. These studies provide data which suggest a dual role for serum factors in LPS-dependent macrophage activation, a direct effect of FBS on LPS which potentiates its immunostimulatory activity, and a secondary down-regulation effect which is manifest at the level of the macrophage.

Animals↗
PubMed1994

Interleukin-1 beta induces differential gene expression in aortic smooth muscle cells.

PURPOSE: Abdominal aortic aneurysms are characterized by an accelerated turnover of extracellular matrix proteins and by an inflammatory infiltrate that releases the cytokines interleukin-1 beta and tumor necrosis factor-alpha. We examined the gene expression of human aneurysmal aortic smooth muscle cells and normal aortic smooth muscle cells after treatment with interleukin-1 beta and tumor necrosis factor-alpha by measuring the changes in smooth muscle cell collagen, elastin, collagenase, and tissue inhibitor of metalloproteinase messenger ribonucleic acid levels in response to these cytokines. METHODS: Biopsy of aneurysmal aorta (n = 6) and donor normal aorta (n = 3) was obtained at operation. Medial smooth muscle cells were cultured, passaged (P2 to P4), and incubated with 0, 10, 100, or 1000 pg/ml interleukin-1 beta, tumor necrosis factor-alpha, or platelet-derived growth factor for 24 hours. Total ribonucleic acid was harvested. Percentage changes in messenger ribonucleic acid from control levels for type I and type III procollagen, elastin, collagenase, 72 kDa type IV collagenase, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 were measured by Northern hybridization. Analyses were performed with analysis of variance (p < 0.05). All comparisons between aneurysmal aortic smooth muscle cells and normal aortic smooth muscle cells represent comparisons between one aneurysmal aorta and one normal aorta. RESULTS: Added interleukin-1 beta resulted in significant, dose-dependent increases in the collagenase messenger ribonucleic acid level at all concentrations tested in both aneurysmal aorta and normal aorta. The increase in the collagenase messenger ribonucleic acid level ranged from a minimum increase of 123% for 10 pg/ml interleukin-1 beta in aneurysmal aortic smooth muscle cells to a maximum of 450% for 1000 pg/ml interleukin-1 beta in normal aortic smooth muscle cells. Interleukin-1 beta caused a significant decrease in the steady-state messenger ribonucleic acid levels for type 1 procollagen in both aneurysmal and normal aorta. The greatest reduction in type 1 procollagen messenger ribonucleic acid levels occurred at 100 pg/ml interleukin-1 beta in both aneurysmal aortic smooth muscle cells (-39%) and normal aortic smooth muscle cells (-48%). The only observed qualitative difference between aneurysmal aortic smooth muscle cells and normal aortic smooth muscle cells was the change in tissue inhibitor of metalloproteinase-1 messenger ribonucleic acid levels in response to added interleukin-1 beta. In aneurysmal aortic smooth muscle cells interleukin-1 beta at 1000 pg/ml significantly increased messenger ribonucleic acid levels by 82%, whereas levels of tissue inhibitor of metalloproteinase-1 messenger ribonucleic acid in normal aortic smooth muscle cells did not change in response to added interleukin-1 beta. Interleukin-1 beta did not alter messenger ribonucleic acid levels for type III procollagen, elastin, type IV collagenase, or tissue inhibitor of metalloproteinase-2 in aneurysmal aorta or normal aorta. When tumor necrosis factor-alpha or platelet-derived growth factor were added, this did not significantly change aneurysmal aortic smooth muscle cells messenger ribonucleic acid levels for collagenase, type IV collagenase, tissue inhibitor of metalloproteinase-1, tissue inhibitor of metalloproteinase-2, and type I and type III procollagen. CONCLUSIONS: These findings suggest that interleukin-1 beta, through its effect on smooth muscle cell collagenase and collagen gene expression, mediates the increased matrix turnover observed in aneurysms. Macrophages may induce changes in aortic smooth muscle cell gene expression in a paracrine manner that could lead to aneurysm formation.

Aged↗
PubMed1994

Responding to workload measurement needs.

Workload measurement is a way of capturing and recording the time and/or activities of personnel in the performance of their health care duties. The traditional focus of workload systems in occupational therapy has been on resource allocation, activity tracking and long range planning. The systems are not organized to link with other institutional, financial and management tools to identify and cost client and programme resource use. The position taken in this paper is that occupational therapy workload measurement systems must be expanded to meet these new managerial responsibilities. Occupational therapists must be able to prospectively predict their workload to accommodate the move towards case costing and programme management. The paper also provides information from a national survey which indicates that there is support from the field for this position.

Canada↗