Search PubMed⌕ Search

Biomedical subjects

C Spencer

Publications and source records attributed to C Spencer.

At least 37 records · Page 2Linked to original sources

Children and the city: a summary of recent environmental psychology research.

The environmental psychology literature is reviewed as it focuses on children's needs and experiences of towns and cities. Children are, we argue, the unacknowledged outsiders in the planning and management of urban areas; yet their enjoyment of and contribution to these areas is ignored at our peril. We discuss the importance of place attachment in the child's developing personal identity; and the rich affordances of towns and cities for the child's well-being and development, alongside an assessment of the evidence about the social and physical dangers that are more frequently stressed in popular discussions: these range from strangers and street crime, to traffic and pollution. Other related topics reviewed include: children's favourite places and their role in the child's self-regulation; the role of exploration of the local area as part of the child's widening social and cognitive world; gender differences in patterns of exploration, and whether these might be changing; and examples of children's involvement at more than a token level in the planning of their communities. The role of children as consumers in the local economy, and their use of public places, malls and plazas, has often been discussed as if they were inevitably socially problematic, and that their presence inevitably led to conflicts with adult users: yet we argue for a view of cityscapes which bring the different strands of society together. We conclude by discussing those Continental European city designs which foster the participation of children in the city's social life.

Child↗

Home or hospital for stroke rehabilitation? results of a randomized controlled trial : I: health outcomes at 6 months.

BACKGROUND AND PURPOSE: We wished to examine the effectiveness of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke. METHODS: This was a randomized, controlled trial comparing early hospital discharge and home-based rehabilitation with usual inpatient rehabilitation and follow-up care. The trial was carried out in 2 affiliated teaching hospitals in Adelaide, South Australia. Participants were 86 patients with acute stroke (mean age, 75 years) who were admitted to hospital and required rehabilitation. Forty-two patients received early hospital discharge and home-based rehabilitation (median duration, 5 weeks), and 44 patients continued with conventional rehabilitation care after randomization. The primary end point was self-reported general health status (SF-36) at 6 months after randomization. A variety of secondary outcome measures were also assessed. RESULTS: Overall, clinical outcomes for patients did not differ significantly between the groups at 6 months after randomization, but the total duration of hospital stay in the experimental group was significantly reduced (15 versus 30 days; P<0.001). Caregivers among the home-based rehabilitation group had significantly lower mental health SF-36 scores (mean difference, 7 points). CONCLUSIONS: A policy of early hospital discharge and home-based rehabilitation for patients with stroke can reduce the use of hospital rehabilitation beds without compromising clinical patient outcomes. However, there is a potential risk of poorer mental health on the part of caregivers. The choice of this management strategy may therefore depend on convenience and costs but also on further evaluations of the impact of stroke on caregivers.

Aged↗

Home or hospital for stroke Rehabilitation? Results of a randomized controlled trial : II: cost minimization analysis at 6 months.

BACKGROUND AND PURPOSE: The goal of the present study was to examine the resource and economic implications of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke. METHODS: A cost minimization analysis in conjunction with a randomized controlled trial was carried out at 2 affiliated teaching hospitals in the southern metropolitan region of Adelaide, South Australia, between 1997 and 1998. Eighty-six hospitalized patients with acute stroke who required rehabilitation were randomized to receive both early hospital discharge and home-based rehabilitation, or conventional in-hospital rehabilitation and community care. Direct and indirect costs related to stroke rehabilitation were calculated, including hospital bed days, home-based intervention program, community services, and personal expenses during the 6 months after randomization. RESULTS: The mean cost per patient was lower for patients randomized to the early hospital discharge and home-based rehabilitation ($8040) compared with those who received conventional care ($10 054). This cost saving was not statistically significant (P=0.14). However, sensitivity analyses indicated that the cost of home-based rehabilitation was consistently lower than that of conventional care except when hospital costs were assumed to be 50% less than those used in the main analysis. Multiple regression analysis demonstrated that the cost of the home-based program was significantly related to a patient's level of disability after adjustment for age, comorbidity, and the presence or absence of a caregiver. CONCLUSIONS: The early hospital discharge and home-based rehabilitation scheme was less costly than conventional hospital care for patients with stroke. Limitation of the provision of such services to patients with mild disability is likely to be most cost effective.

Cost Savings↗

Forearm and calf blood flow in response to cortical arousal in normal male and female subjects.

The aim of this study was to investigate cardiovascular changes, particularly in forearm and calf blood flows, in response to acute emotional stress in men and women. The study was approved by the Ethics Committee of the Queen's Medical Centre, Nottingham University. Fifty-six healthy non-smokers (29 men and 27 women) aged 19 to 22 years participated. Blood flow was measured by venous occlusion plethysmography using mercury-in-silastic strain gauges. Acute emotional stress (2 min) was elicited by a visual orientation task. During acute emotional stress, there were increases in heart rate (males = 40 +/- 3%, females = 49 +/- 5%) and mean arterial pressure (males = 24 +/- 2%, females = 22 +/- 2%), and hyperaemia and vasodilatation were observed in the forearm (males = 162 +/- 15%, females = 239 +/- 31%) and calf (males = 78 +/- 16%, females = 131 +/- 24%). Vasoconstriction also occurred in some subjects. Forearm vasodilatation was significantly greater than calf vasodilatation. Gender variation was apparent in the calf, where vasodilatation was significantly greater in females, and vasoconstriction was significantly greater in males. In some subgroups of men and women, mean values indicated that acute emotional stress elicited increases in forearm, but not in calf, blood flows and vascular conductances. This pattern is similar to that reported by Rusch et al. (see text), but the present findings indicate that vasodilatation in the forearm and calf in response to acute emotional stress is more common.

Adult↗

A randomised comparison of the effects of oral versus transdermal 17beta-oestradiol, each combined with sequential oral norethisterone acetate, on serum lipoprotein levels.

OBJECTIVE: To investigate the effects of oral versus transdermal 17beta-oestradiol, given in both cases with sequential addition of oral norethisterone acetate, on serum lipid and lipoprotein levels in postmenopausal women. DESIGN: Open, randomised, parallel groups study. SETTING: University Clinical Research Group. POPULATION: Sixty-four postmenopausal women with climacteric complaints who were otherwise healthy were screened. Of these, 58 fulfilled the entry criteria. METHODS: Fifty-eight postmenopausal women were randomised to receive either oral 17beta-oestradiol/oestriol (Trisequens) or transdermal 17beta-oestradiol (Estrapak) together with cyclical addition of norethisterone acetate for 48 weeks. MAIN OUTCOME MEASURES: Serum levels of total cholesterol, triglycerides, high density lipoproteins (HDL), low density lipoproteins (LDL), very low density lipoproteins (VLDL), apolipoproteins, and lipoprotein(a) at baseline, and after 46 weeks (oestrogen-alone phase), and 48 weeks (oestrogen-progestogen phase) of treatment. RESULTS: Oral oestradiol therapy did not affect serum total cholesterol levels during the oestrogen-alone phase, but during the combined phase there was a 5% fall (P < 0.05) due to a 7% decrease in LDL cholesterol levels (P < 0.01). Oral therapy also increased serum triglyceride levels by 9.4% during the oestrogen-alone phase (P < 0.05). During the combined phase of transdermal therapy, there was a 19% fall in serum triglyceride levels (P < 0.05) and a 6% fall in HDL levels (P < 0.05). Oral oestradiol reduced lipoprotein(a) levels by 31% during the oestrogen-alone phase and by 37% with norethisterone acetate addition (P < 0.05). Transdermal therapy had no significant effect on lipoprotein(a). CONCLUSIONS: Other than a minor fall in HDL3 in women receiving transdermal 17beta-oestradiol, coadministration of oral progestogen in general improved, rather than worsened, this serum lipoprotein profile.

Administration, Cutaneous↗

Epirubicin: a review of its efficacy as adjuvant therapy and in the treatment of metastatic disease in breast cancer.

UNLABELLED: Epirubicin is a semisynthetic derivative of doxorubicin which has been extensively evaluated in patients with breast cancer. It is effective in the management of metastatic disease and as adjuvant therapy in patients with early breast cancer. In the adjuvant setting, epirubicin-based therapy appears to have efficacy at least equivalent to that of the standard therapy cyclophosphamide, methotrexate and fluorouracil (CMF), with the most recent trials, predominantly in premenopausal patients, reporting significant gains in relapse-free survival and overall survival for epirubicin-based vs CMF therapy. In a single trial, the 5-year relapse-free survival of postmenopausal patients receiving long term hormonal therapy (tamoxifen) was significantly increased when epirubicin was added as single-agent chemotherapy and compared with tamoxifen alone. In patients with metastatic disease, epirubicin- and doxorubicin-containing regimens (with cyclophosphamide and fluorouracil; FEC and FAC) are therapeutically equivalent. Increasing the dose of epirubicin appears to improve response rates in patients with either metastatic or early disease but, with the exception of 1 adjuvant study, improved overall survival has not been demonstrated. Quality of life (QOL) has yet to be adequately evaluated with epirubicin. The major adverse effects of epirubicin are acute dose-limiting haematotoxicity and cumulative dose-related cardiotoxicity. Other important adverse effects include mucositis, nausea and vomiting, reversible alopecia and local cutaneous reactions. However, the tolerability of epirubicin is better than that of doxorubicin at equimolar doses. CONCLUSION: Epirubicin has been extensively investigated in patients with breast cancer and has been found to be a highly effective agent, both for the treatment of patients with metastatic disease and as an adjuvant therapy. Recent trials have confirmed that, in selected patients requiring adjuvant therapy, FEC therapy is at least as effective as CMF, a standard treatment. FEC is also therapeutically equivalent to FAC in patients with metastatic breast cancer, and because the therapeutic index appears to be better the opportunity exists to increase dose intensity in an effort to improve efficacy. Such trials, and those of combinations of epirubicin with newer or alternative agents, should result in the introduction of more effective and better tolerated epirubicin-based protocols for adjuvant therapy and the management of patients with advanced breast cancer. In the meantime there is sufficient evidence to justify consideration of epirubicin for inclusion in first-line therapies for patients with early or metastatic breast cancer.

Adjuvants, Pharmaceutic↗

Caspase inhibition prevents staurosporine-induced apoptosis in CHO-K1 cells.

Apoptosis is a distinct form of programmed cell death that plays an important role in many biological processes. Although the phenotypes of apoptotic cells are well documented, little is known of the central mechanism leading to programmed cell death. Over the past few years, a number of ICE/CED-3 family proteases (also termed caspases) have been discovered and implicated as the common effectors of apoptosis. In this report, we demonstrate that induction of apoptosis in CHO-K1 cells by staurosporine, a broad spectrum inhibitor of protein kinases, results in an increase in DEVD-dependent protease activity. These events were followed by nuclear DNA fragmentation and cell death. Inhibition of the DEVD-cleaving activity by a synthetic tetrapeptide inhibitor DEVD-CHO, blocked staurosporine-induced downstream apoptotic phenotypes, such as morphological characteristics and DNA fragmentation. These results suggest that staurosporine-induced apoptosis in CHO-K1 cells is mediated through the CPP32/caspase-3-like cysteine proteases.

Journal Article↗

Regulation of calreticulin gene expression by calcium.

We have isolated and characterized a 12-kb mouse genomic DNA fragment containing the entire calreticulin gene and 2.14 kb of the promoter region. The mouse calreticulin gene consists of nine exons and eight introns, and it spans 4.2 kb of genomic DNA. A 1.8-kb fragment of the calreticulin promoter was subcloned into a reporter gene plasmid containing chloramphenicol acetyltransferase. This construct was then used in transient and stable transfection of NIH/ 3T3 cells. Treatment of transfected cells either with the Ca2+ ionophore A23187, or with the ER Ca2+-ATPase inhibitor thapsigargin, resulted in a five- to sevenfold increase of the expression of chloramphenicol acetyltransferase protein. Transactivation of the calreticulin promoter was also increased by fourfold in NIH/3T3 cells treated with bradykinin, a hormone that induces Ca2+ release from the intracellular Ca2+ stores. Analysis of the promoter deletion constructs revealed that A23187- and thapsigargin-responsive regions are confined to two regions (-115 to -260 and -685 to -1,763) in the calreticulin promoter that contain the CCAAT nucleotide sequences. Northern blot analysis of cells treated with A23187, or with thapsigargin, revealed a fivefold increase in calreticulin mRNA levels. Thapsigargin also induced a fourfold increase in calreticulun protein levels. Importantly, we show by nuclear run-on transcription analysis that calreticulin gene transcription is increased in NIH/3T3 cells treated with A23187 and thapsigargin in vivo. This increase in gene expression required over 4 h of continuous incubation with the drugs and was also sensitive to treatment with cycloheximide, suggesting that it is dependent on protein synthesis. Changes in the concentration of extracellular and cytoplasmic Ca2+ did not affect the increased expression of the calreticulin gene. These studies suggest that stress response to the depletion of intracellular Ca2+ stores induces expression of the calreticulin gene in vitro and in vivo.

3T3 Cells↗

CAG trinucleotide RNA repeats interact with RNA-binding proteins.

Genes associated with several neurological diseases are characterized by the presence of an abnormally long trinucleotide repeat sequence. By way of example, Huntington's disease (HD), is characterized by selective neuronal degeneration associated with the expansion of a polyglutamine-encoding CAG tract. Normally, this CAG tract is comprised of 11-34 repeats, but in HD it is expanded to > 37 repeats in affected individuals. The mechanism by which CAG repeats cause neuronal degeneration is unknown, but it has been speculated that the expansion primarily causes abnormal protein functioning, which in turn causes HD pathology. Other mechanisms, however, have not been ruled out. Interactions between RNA and RNA-binding proteins have previously been shown to play a role in the expression of several eukaryotic genes. Herein, we report the association of cytoplasmic proteins with normal length and extended CAG repeats, using gel shift and UV crosslinking assays. Cytoplasmic protein extracts from several rat brain regions, including the striatum and cortex, sites of neuronal degeneration in HD, contain a 63-kD RNA-binding protein that specifically interacts with these CAG-repeat sequences. These protein-RNA interactions are dependent on the length of the CAG repeat, with longer repeats binding substantially more protein. Two CAG repeat-binding proteins are present in human cortex and striatum; one comigrates with the rat protein at 63 kD, while the other migrates at 49 kD. These data suggest mechanisms by which RNA-binding proteins may be involved in the pathological course of trinucleotide repeat-associated neurological diseases.

Aged↗

Mental rotation of a tactile layout by young visually impaired children.

Mental rotation tasks have been used to probe the mental imagery both of sighted and of visually impaired people. People who have been blind since birth display a response pattern which is qualitatively similar to that of sighted people but tend to respond more slowly or with a higher error rate. It has been suggested that visually impaired people code the stimulus and its (or their own) motion in a different way from sighted people-in particular, congenitally blind people may ignore the external reference framework provided by the stimulus and surrounding objects, and instead use body-centred or movement-based coding systems. What has not been considered before is the relationship between different strategies for tactually exploring the stimulus and the response pattern of congenitally blind participants. Congenitally blind and partially sighted children were tested for their ability to learn and recall a layout of tactile symbols. Children explored layouts of one, three, or five shapes which they then attempted to reproduce. On half the trials there was a short pause between exploring and reproducing the layouts. In an aligned condition children reproduced the array from the same position at which they had explored it; in a rotated condition children were asked to move 90 degrees round the table between exploring and reproducing the layout. Both congenitally blind and partially sighted children were less accurate in the rotated condition than in the aligned condition. Five distinct strategies used by the children in learning the layout were identified. These strategies interacted with both visual status and age. We suggest that the use of strategies, rather than visual status or chronological age, accounts for differences in performances between children.

Blindness↗