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Biomedical subjects

S Davies

Publications and source records attributed to S Davies.

At least 109 records · Page 6Linked to original sources
PubMed2000

The health status of diabetic patients receiving orthotic therapy.

Diabetes has a major impact on the quality of life and those with related foot ulcers are among those most affected. The main aim of the study, which was carried out over an 18-month time period, was to compare the self-reported health status of a group of diabetic patients receiving orthotic therapy with that of other groups who did not receive the therapy. A sample of 280 was recruited from patients with type I and type II diabetes. The study group comprised four groups of patients: those receiving orthotic therapy (insoles) for pedal complications as a result of their diabetes; those with diabetes mellitus, without complications of the disease affecting their foot; those with unilateral lower limb amputation and those with active ulceration who had not been prescribed footwear. The specialised orthotic intervention resulted in statistically significant improvements in health status (p < 0.05), (measured using the SF-36) both physically and mentally, for patients with at-risk feet and should become an integral part of the treatment regime for diabetics with at-risk feet.

Chi-Square Distribution↗
PubMed2000

A refined physical and transcriptional map of the SPG9 locus on 10q23.3-q24.2.

Hereditary spastic paraplegia (HSP) is a genetically heterogeneous disorder characterised by progressive spasticity of the lower limbs. Beside 'pure' forms of HSP, 'complicated' forms are reported, where spasticity occurs associated with additional symptoms. We recently described an Italian family with a complicated dominant form of HSP (SPG9) and we mapped the gene responsible to 10q23.3-q24.2, in a 12cM interval between markers D10S564 and D10S603. The phenotypic manifestations in our family are reminiscent of those already described in a smaller British pedigree. We typed individuals from this British family using markers located in the SPG9 critical interval and haplotype reconstruction showed the disorder co-segregating with SPG9. To characterise the SPG9 region better, we constructed a contig of 22 YACs, assigned it to 18 polymorphic markers and positioned 54 ESTs. Furthermore, we searched for ESTs containing a trinucleotide repeat sequence, since anticipation of symptoms was reported in both families. Finally, analysis of a muscle biopsy specimen from one patient was normal, suggesting that, contrary to SPG7, mitochondrial disturbance could not be a primary feature of SPG9.

Biopsy↗
PubMed2000

The biological sciences in mental health nursing: stakeholders' perspectives.

To date, relatively little attention has been paid to optimizing the development of education programmes to support safe and effective health care professionals. In particular, the wider stakeholders, particularly health service users, are rarely consulted on the knowledge base expected of practitioners. We report here on an evaluation, involving students, lecturers, nurses and service users, aimed at reviewing the bioscience component of the preregistration mental health nursing course. Students and lecturers agreed that the current common foundation course in bioscience was biased towards the adult branch students, and failed to meet the needs of mental health nurses. The mental health lecturers' solution to the 'bioscience problem' was to curtail the input. In contrast, service users described serious shortfalls in professionals' abilities to inform them of common side-effects of medication; these problems were attributable to inadequate educational preparation. The knowledge deficits identified could be rectified by making pharmacology an important part of the mental health education programme. However, for the curriculum to accommodate applied pharmacology, its supporting bioscience, and essential preparation in psychosocial interventions, some restructuring of the biological science programme for mental health nurses will be necessary. Our findings suggest that such restructuring should be informed by service users' views of their needs.

Attitude of Health Personnel↗
PubMed2000

Promoting autonomy and independence for older people within nursing practice: an observational study.

Although autonomy and independence are widely held to be important goals of care for older people, these terms lack precise definition and operationalization in the literature. This paper reports on observational data gathered as part of an evaluation of educational programmes in the nursing care of older people. Strategies which appear both to promote and inhibit autonomy and independence of older patients in a range of care settings are described. Recommendations are made for further research to explore the extent to which autonomy and independence are appropriate goals of care for older people with cognitive impairment.

Activities of Daily Living↗
PubMed2000

Regulation of endometrial cancer cell growth by luteinizing hormone (LH) and follicle stimulating hormone (FSH).

Gonadotrophin releasing hormone analogues (GnRHa) have been used to treat recurrent endometrial cancer. However, the mode of action is uncertain. Our previous studies showed no direct effect of GnRHa on endometrial cancer cell growth in vitro. We have now examined the effect of luteinizing hormone (LH) and follicle stimulating hormone (FSH) on endometrial cancer cell growth. The aim was to determine whether suppression of pituitary LH and FSH by GnRHa could explain the tumour regression seen in up to 44% of patients treated with this drug. We show that recombinant human LH and FSH (rhLH and rhFSH) produce a concentration dependent stimulation of the endometrial cancer cell line HEC-1A, in serum-free medium (maximum increase of 62 and 50% respectively relative to untreated controls). This increase is equivalent to that obtained by addition of 10% newborn calf serum. Growth of the Ishikawa cell line in culture increases in the presence of rhLH (maximum increase of 67%) but not with rhFSH. Using RT-PCR, we show that the Ishikawa cell line intermittently expresses receptor mRNA of LH but not of FSH; there is no expression of either mRNA by HEC-1A. Classically, both LH and FSH act via cAMP linked membrane receptors. However, neither rhLH nor rhFSH elicit cAMP production in either of our endometrial cancer cell lines. Thus, although a growth response to LH and FSH can be shown, and some cells express the LH receptor, stimulation appears to be via a pathway separate from that of the classical gonadotrophin receptor.

Cell Division↗
PubMed2000

Bioscience in the pre-registration curriculum: finding the right teaching strategy.

With the transition of pre-registration nursing programmes into higher education, a disproportionate number of problems have arisen in relation to the bioscience component of the curriculum. Therefore, a survey was undertaken to obtain the views of students (n = 294) and staff (n = 57) to identify effective teaching strategies to facilitate students' learning and understanding of this difficult area of the curriculum. In contrast to the staff, the majority of students found all three teaching strategies (lectures, tutorials and laboratory sessions) of approximately equal value to their learning and practice. Our findings suggest that students' problems with the biosciences could be ameliorated by adjustments in curriculum apportionment. Our data would support the continuation of lead lectures and laboratory work in bioscience. However, a tutorial system, specifically designed to overcome the particular difficulties experienced by nursing students in this area, is needed. This should augment, not replace, lectures and teaching laboratories. There was little indication that such a redistribution of resources would be favoured by the majority of the staff.

Attitude of Health Personnel↗
PubMed2000

Reality orientation for dementia: a systematic review of the evidence of effectiveness from randomized controlled trials.

The effectiveness of classroom reality orientation (RO) in dementia was evaluated by conducting a systematic literature review. This yielded 43 studies, of which 6 were randomized controlled trials meeting the inclusion criteria (containing 125 subjects.) Results were subjected to meta-analysis. Effects on cognition and behavior were significant in favor of treatment (cognition standardized mean difference [SMD] = -0.59; 95% confidence interval [CI] -0.95(-)-0.22; behavior SMD = -0.64, 95% CI = -1.20(-)-0.08). The evidence indicates that RO has benefits on both cognition and behavior for dementia sufferers. However, a continued program may be needed to sustain potential benefits. Future research should evaluate RO in well-designed multicenter trials.

Aged↗
PubMed2000

Enterocolitis in children with developmental disorders.

OBJECTIVE: Intestinal pathology, i.e., ileocolonic lymphoid nodular hyperplasia (LNH) and mucosal inflammation, has been described in children with developmental disorders. This study describes some of the endoscopic and pathological characteristics in a group of children with developmental disorders (affected children) that are associated with behavioral regression and bowel symptoms, and compares them with pediatric controls. METHODS: Ileocolonoscopy and biopsy were performed on 60 affected children (median age 6 yr, range 3-16; 53 male). Developmental diagnoses were autism (50 patients), Asperger's syndrome (five), disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD) (one), schizophrenia (one), and dyslexia (one). Severity of ileal LNH was graded (0-3) in both affected children and 37 developmentally normal controls (median age 11 yr, range 2-13 yr) who were investigated for possible inflammatory bowel disease (IBD). Tissue sections were reviewed by three pathologists and scored on a standard proforma. Data were compared with ileocolonic biopsies from 22 histologically normal children (controls) and 20 children with ulcerative colitis (UC), scored in an identical manner. Gut pathogens were sought routinely. RESULTS: Ileal LNH was present in 54 of 58 (93%) affected children and in five of 35 (14.3%) controls (p < 0.001). Colonic LNH was present in 18 of 60 (30%) affected children and in two of 37 (5.4%) controls (p < 0.01). Histologically, reactive follicular hyperplasia was present in 46 of 52 (88.5%) ileal biopsies from affected children and in four of 14 (29%) with UC, but not in non-IBD controls (p < 0.01). Active ileitis was present in four of 51 (8%) affected children but not in controls. Chronic colitis was identified in 53 of 60 (88%) affected children compared with one of 22 (4.5%) controls and in 20 of 20 (100%) with UC. Scores of frequency and severity of inflammation were significantly greater in both affected children and those with UC, compared with controls (p < 0.001). CONCLUSIONS: A new variant of inflammatory bowel disease is present in this group of children with developmental disorders.

Adolescent↗
PubMed2000

Increases in intrahepatic CD68 positive cells, MAC387 positive cells, and proinflammatory cytokines (particularly interleukin 18) in chronic hepatitis C infection.

BACKGROUND: Upregulation of Th1 associated intrahepatic cytokines in chronic hepatitis C virus (HCV) infection should lead to a significant non-specific cellular immune response, a prerequisite for viral clearance. However, to date, the role of this non-specific response in HCV has been understudied. AIMS: To analyse the intrahepatic macrophage activity in chronic HCV infection by immunostaining and by quantitation of cytokine mRNA. METHODS: HCV positive liver tissues (chronic hepatitis, n=10; cirrhosis, n=5) were immunostained for CD68, MAC387, and semiquantitated by polymerase chain reaction for intrahepatic cytokine mRNAs (interferon gamma (IFNgamma), interleukin 1beta (IL-1beta), IL-6, IL-18, tumour necrosis factor alpha (TNFalpha), and macrophage inflammatory protein 1beta (MIP1beta)). HCV negative normal liver tissues (for cytokines, n=6; for immunostaining, n=5) were included as controls. RESULTS: MAC387(+) cells were focally increased in areas of erosion at the limiting plate while lobular staining was minimal. CD68(+) staining was diffuse in both portal (increased in HCV) and lobular areas. The portal tract (mean) density of CD68(+) and MAC387(+) cells was significantly increased in patients with HCV compared with normal tissue. IFNgamma and IL-18 mRNA levels were highly correlated and significantly upregulated in chronic hepatitis and cirrhotic tissue versus controls. TNFalpha mRNA was upregulated in chronic hepatitis without cirrhosis, while IL-6 mRNA was significantly downregulated. IL-1beta, IL-6, and MIP1beta mRNA levels were significantly correlated with portal tract MAC387(+) cell density. CONCLUSIONS: The significant upregulation of IFNgamma and IL-18 mRNA and significant correlations between IFNgamma and other proinflammatory cytokines, suggest a Th1/cell mediated intrahepatic immune response in chronic HCV infection. However, further clarification of the cellular sources of these cytokines is required.

Adult↗
PubMed2000

Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin.

PURPOSE: A fluorescent component of lipofuscin, A2-E (N-retinylidene-N-retinylethanol-amine) has been shown to impair lysosomal function and to increase the intralysosomal pH of human retinal pigment epithelial (RPE) cells. In addition to its lysosomotropic properties A2-E is known to be photoreactive. The purpose of this study was to determine the phototoxic potential of A2-E on RPE cells. METHODS: A2-E (synthesized by coupling all-trans-retinaldehyde to ethanolamine) was complexed to low-density lipoprotein (LDL) to allow for specific loading of the lysosomal compartment. Human RPE cell cultures were loaded with the A2-E-LDL complex four times within 2 weeks. A2-E accumulation was confirmed by fluorescence microscopy and flow cytometry analysis. Acridine orange staining allowed assessment of lysosomal integrity and intralysosomal pH. The phototoxic properties of A2-E were determined by exposing A2-E-free and A2-E-fed RPE cell cultures to short wavelength visible light (400-500 nm) and assessing cell viability and lysosomal integrity. RESULTS: Fluorescence microscopy and flow cytometry analysis demonstrated that the intralysosomal accumulation of A2-E in cultured RPE cells increased with the number of feedings. Acridine orange staining confirmed that the A2-E was located in the lysosomal compartment and induced an elevation of intralysosomal pH. Exposure of A2-E-fed cells to light resulted in a significant loss of cell viability by 72 hours, which was not observed in either RPE cells maintained in the dark or A2-E-free cultures exposed to light. Toxicity was associated with a loss of lysosomal integrity. CONCLUSIONS: A2-E is detrimental to RPE cell function by a variety of mechanisms: inhibition of lysosomal degradative capacity, loss of membrane integrity, and phototoxicity. Such mechanisms could contribute to retinal aging as well as retinal diseases associated with excessive lipofuscin accumulation-for example, age-related macular degeneration and Stargardt's disease.

Acridine Orange↗
PubMed2000

Methicillin-resistant Staphyloccocus aureus: evaluation of five selective media.

This study evaluates the performance in isolating methicillin-resistant Staphylococcus aureus (MRSA) of three media: the reduced salt formulation of mannitol salt agar plus oxacillin (MMSAO); CHROMagar Staph aureus plus ciprofloxacin (CHRAC); and Halifax MRSA medium (HMO), against the previously recommended mannitol salt agar (7% salt) plus oxacillin (OMSAO) and Baird-Parker medium plus ciprofloxacin (BPC). MRSA screening swabs were plated out onto the five selective media and the plates examined at 24 and 48 h. Suspected colonies were confirmed as MRSA by detection of heat-labile DNase, coagulase and/or protein A, and by confirming resistance to methicillin. Of 719 specimens examined, 191 grew MRSA on at least one medium. The relative sensitivities of the five media at 48 h were as follows: BPC, 94%; CHRAC, 70%; OMSAO, 61%; HMO, 56%; and MMSAO, 46%. In addition, BPC gave the least number of unnecessary investigations for non-MRSA isolates. The current advantage of BPC when performing direct culture for MRSA was confirmed. The other ciprofloxacin-containing medium also produced reasonable results. Of the two mannitol salt agar media, the formulation with 7% salt gave better results. HMO proved unreliable at isolating MRSA.

Anti-Infective Agents↗
PubMed1999

A novel cell permeant and far red-fluorescing DNA probe, DRAQ5, for blood cell discrimination by flow cytometry.

The deep red fluorescing agent (DRAQ5) is a synthetic anthraquinone with a high affinity for DNA and a high capacity to rapidly enter living cells or stain fixed cells. DRAQ5 is optimally excited by red-light emitting sources and yields a deep red emission spectrum which extends into the low infra-red. DRAQ5 shows excitation at sub-optimal wavelengths including the 488 nm line and the multi-line UV wavelengths emitted by argon-ion lasers. Single beam (488 nm) flow cytometry has been used to demonstrate the utility of DRAQ5-nuclear DNA fluorescence as a discriminating parameter for human leucocytes and lymphoma cells, in combination with fluorochrome-labelled antibodies for the detection of surface antigens and subpopulation recognition. DRAQ5 fluorescence was found to reflect cellular DNA content as evidenced by cell cycle distribution profiles for asynchronous and cell cycle-perturbed populations. Importantly, DRAQ5 can be used in combination with FITC and RPE-labelled antibodies, without the need for fluorescence compensation.

Anthraquinones↗
PubMed1999

The photoreactivity of the retinal age pigment lipofuscin.

The presence of the age pigment lipofuscin is associated with numerous age-related diseases. In the retina lipofuscin is located within the pigment epithelium where it is exposed to high oxygen and visible light, a prime environment for the generation of reactive oxygen species. Although we, and others, have demonstrated that retinal lipofuscin is a photoinducible generator of reactive oxygen species it is unclear how this may translate into cell damage. The position of lipofuscin within the lysosome infers that irradiated lipofuscin is liable to cause oxidative damage to either the lysosomal membrane or the lysosomal enzymes. We have found that illumination of lipofuscin with visible light is capable of extragranular lipid peroxidation, enzyme inactivation, and protein oxidation. These effects, which were pH-dependent, were significantly reduced by the addition of the antioxidants, superoxide dismutase and 1,4-diazabicyclo(2,2,2)-octane, confirming a role for both the superoxide anion and singlet oxygen. We postulate that lipofuscin may compromise retinal cell function by causing loss of lysosomal integrity and that this may be a major contributory factor to the pathology associated with retinal light damage and diseases such as age-related macular degeneration.

Aged↗
PubMed1999

Suicide within 12 months of contact with mental health services: national clinical survey.

OBJECTIVE: To describe the clinical circumstances in which psychiatric patients commit suicide. DESIGN: National clinical survey. SETTING: England and Wales. SUBJECTS: A two year sample of people who had committed suicide, in particular those who had been in contact with mental health services in the 12 months before death. MAIN OUTCOME MEASURES: Proportion of suicides in people who had had recent contact with mental health services; proportion of suicides in inpatients; proportion of people committing suicide and timing of suicide within three months of hospital discharge; proportion receiving high priority under the care programme approach; proportion who were recently non-compliant and not attending. RESULTS: 10 040 suicides were notified to the study between April 1996 and March 1998, of whom 2370 (24%; 95% confidence interval 23% to 24%) had had contact with mental health services in the year before death. Data were obtained on 2177, a response rate of 92%. In general these subjects had broad social and clinical needs. Alcohol and drug misuse were common. 358 (16%; 15% to 18%) were psychiatric inpatients at the time of death, 21% (17% to 25%) of whom were under special observation. Difficulties in observing patients because of ward design and nursing shortages were both reported in around a quarter of inpatient suicides. 519 (24%; 22% to 26%) suicides occurred within three months of hospital discharge, the highest number occurring in the first week after discharge. 914 (43%; 40% to 44%) were in the highest priority category for community care. 488 (26% excluding people whose compliance was unknown; 24% to 28%) were non-compliant with drug treatment while 486 (28%; 26% to 30%) community patients had lost contact with services. Most people who committed suicide were thought to have been at no or low immediate risk at the final service contact. Mental health teams believed suicide could have been prevented in 423 (22%; 20% to 24%) cases. CONCLUSIONS: Several suicide prevention measures in mental health services are implied by these findings, including measures to improve compliance and prevent loss of contact with services. Inpatient facilities should remove structural difficulties in observing patients and fixtures that can be used in hanging. Prevention of suicide after discharge may require earlier follow up in the community. Better suicide prevention in psychiatric patients is likely to need measures to improve the safety of mental health services as a whole, rather than specific measures for people known to be at high risk.

Adolescent↗
PubMed1999

Mental disorder and clinical care in people convicted of homicide: national clinical survey.

OBJECTIVES: To estimate the rate of mental disorder in those convicted of homicide and to examine the social and clinical characteristics of those with a history of contact with psychiatric services. DESIGN: National clinical survey. SETTING: England and Wales. SUBJECTS: Eighteen month sample of people convicted of homicide. MAIN OUTCOME MEASURES: Offence related and clinical information collected from psychiatric court reports on people convicted of homicide. Detailed clinical data collected on those with a history of contact with psychiatric services. RESULTS: 718 homicides were reported to the inquiry between April 1996 and November 1997. Of the 500 cases for whom psychiatric reports were retrieved, 220 (44%; 95% confidence interval 40% to 48%) had a lifetime history of mental disorder, while 71 (14%; 11% to 17%) had symptoms of mental illness at the time of the homicide. Of the total sample, 102 (14%; 12% to 17%) were confirmed to have been in contact with mental health services at some time, 58 (8%; 6% to 10%) in the year before the homicide. The commonest diagnosis was personality disorder (20 cases, 22%; 13% to 30%). Alcohol and drug misuse were also common. Only 15 subjects (18%; 10% to 26%) were receiving intensive community care, and 60 (63%; 53% to 73%) were out of contact at the time of the homicide. CONCLUSIONS: There are substantial rates of mental disorder in people convicted of homicide. Most do not have severe mental illness or a history of contact with mental health services. Inquiry findings suggest that preventing loss of contact with services and improving the clinical management of patients with both mental illness and substance misuse may reduce risk, but clinical trials are needed to examine the effectiveness of such interventions.

Adult↗
PubMed1999

Endothelial function in Marfan syndrome: selective impairment of flow-mediated vasodilation.

BACKGROUND: The cardiovascular complications of Marfan syndrome arise due to alterations in the structural and functional properties of fibrillin, a constituent of vascular connective tissues. Fibrillin-containing microfibrils are closely associated with arterial endothelial cells, indicating a possible functional role for fibrillin in the endothelium. Plasma concentrations of endothelial cell products are elevated in Marfan subjects, which indirectly indicates endothelial dysfunction. This study directly assessed flow- and agonist-mediated endothelium-dependent brachial artery reactivity in Marfan subjects. METHODS AND RESULTS: In 20 Marfan and 20 control subjects, brachial artery diameter, blood flow, and blood pressure were measured by ultrasonic wall tracking, Doppler ultrasound, and photoplethysmography, respectively. Measurements were taken during hand hyperemia (a stimulus for endothelium-derived nitric oxide [NO] release in the upstream brachial artery) and after sublingual administration of the endothelium-independent vasodilator nitroglycerin. In 9 Marfan and 6 control subjects, the above parameters were also assessed during intra-arterial infusions of acetylcholine and bradykinin (agonists that stimulate NO production) and NG-monomethyl-L-arginine (L-NMMA, an inhibitor of NO production). Flow-mediated responses differed markedly between Marfan and control subjects (-1.6+/-3.5% versus 6. 50+/-4.1%, respectively; P<0.0001), whereas nitroglycerin produced similar vasodilation (14.2+/-5.7% versus 15.2+/-7.8%; P=NS). Agonist-induced vasodilation to incremental intra-arterial infusions of acetylcholine and bradykinin were not significantly different between Marfan and control subjects, and intra-arterial L-NMMA produced similar reductions in brachial artery diameter in both groups. CONCLUSIONS: These data demonstrate impaired flow-mediated but preserved agonist-mediated endothelium-dependent vasodilation in Marfan subjects and suggest preservation of basal NO release. Selective loss of flow-mediated dilation suggests a role for fibrillin in endothelial cell mechanotransduction.

Acetylcholine↗
PubMed1999

Genetic alterations in 'normal' luminal and myoepithelial cells of the breast.

Chromosomal loci exhibiting loss of heterozygosity (LOH) at high frequency in invasive breast cancer have been investigated in 'normal' breast tissue from patients with carcinoma and from reduction mammoplasty specimens. Duct-lobular units dissected from paraffin-embedded tissues and 485 'normal' luminal and myoepithelial cell clones were studied. Overall, LOH was found in normal cells in 5/10 breast cancer cases and 1/3 reduction mammoplasty specimens. LOH was identified in normal cells adjacent to and distant from the tumour. In one case, all luminal and myoepithelial samples exhibited loss of the same allele on chromosome 13q. One case in which the patient had a germline truncating mutation in the BRCA1 gene exhibited LOH on 17q in 3/33 normal clones. One of these clones showed loss of wild-type allele indicating gene inactivation. This sample also had LOH at markers on chromosomes 11p and 13q. One of 93 clones from three reduction mammoplasties showed allele loss at a locus on chromosome 13q. The identification of LOH in breast lobules suggests that they may be clonal. The demonstration of genetic alteration in luminal and myoepithelial cells provides evidence for the presence of a common stem cell for the two epithelial cell types. LOH has been demonstrated in normal tissues near and away from the carcinoma, suggesting that genetic alterations are likely to be more heterogeneous and widespread than is currently envisaged, and probably occur very early in breast development. Homozygous deletion of BRCA1 per se does not appear to provide clonal advantage.

Adult↗