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Biomedical subjects

N Davies

Publications and source records attributed to N Davies.

At least 37 records · Page 2Linked to original sources

Cytokine gene polymorphisms and susceptibility to juvenile idiopathic arthritis. British Paediatric Rheumatology Study Group.

OBJECTIVE: To investigate the involvement of candidate cytokine genes in the pathogenesis of juvenile idiopathic arthritis (JIA). METHODS: Single nucleotide polymorphisms and intragenic microsatellite markers within 8 candidate cytokine genes (interleukin-1alpha [IL-1alpha], IL-2, IL-4, IL-6, IL-10, interferon-alpha1 [IFNA1], interferon-gamma [IFNG], and interferon regulatory factor 1 [IRF-1]) were investigated in 417 Caucasian patients with clinically characterized JIA and a panel of 276 unrelated, healthy Caucasian controls, all from the United Kingdom. RESULTS: A novel 3'-untranslated region (3'UTR) polymorphism in IRF-1 was found to be associated with susceptibility to JIA (corrected P = 0.002). No significant association with IL-1alpha, IL-2, IL-4, IL-6, IL-10, IFNA1, or IFNG was observed. CONCLUSION: An association between JIA and a previously unreported 3'UTR polymorphism of IRF-1 was observed. This association was not found to be specific to any particular JIA subgroup. This suggests that IRF-1 may contribute to a common pathogenesis shared by all JIA patients, regardless of clinical phenotype. This is most likely to be a genetic contribution to the chronic inflammatory process that underlies JIA pathology.

3' Untranslated Regions↗

The single-nucleotide polymorphism lottery: how useful are a few common SNPs in identifying disease-associated alleles?

It has been proposed that using association analysis of single nucleotide polymorphism (SNP) markers in candidate genes may be more successful in identifying disease susceptibility genes for complex diseases. Finding all the SNPs within a candidate gene and genotyping a large case-control cohort is a resource-intensive process. As linkage disequilibrium extends across small regions of the genome, the expectation is that a few common anonymous SNPs will be sufficient to detect functional disease-associated alleles. The aim of this investigation was to compare the ability of a number of family- and population-based association methods to identify known susceptibility loci using the Genetic Analysis Workshop 12 simulated data set. As expected, case-control methods were more likely to detect association with individual SNPs but family-based haplotyping methods appeared better able to localize the position of functional polymorphism.

Adult↗

Copurification of the Lac repressor with polyhistidine-tagged proteins in immobilized metal affinity chromatography.

One of the commonly used resins for immobilized metal affinity purification of polyhistidine-tagged recombinant proteins is TALON resin, a cobalt (II)--carboxymethylaspartate-based matrix linked to Sepharose CL-6B. Here, we show that TALON resin efficiently purifies the native form of Lac repressor, which represents the major contaminant when (His)(6)-tagged proteins are isolated from Escherichia coli host cells carrying the lacI(q) gene. Inspection of the crystal structure of the repressor suggests that three His residues (residues 163, 173, and 202) in each subunit of the tetramer are optimally spaced on an exposed face of the protein to allow interaction with Co(II). In addition to establishing a more efficient procedure for purification of the Lac repressor, these studies indicate that non-lacI(q)-based expression systems yield significantly purer preparations of recombinant polyhistidine-tagged proteins.

Aspartic Acid↗

Breast cancer screening for older women with intellectual disability living in community group homes.

Breast cancer is one of the commonest cancers to affect women. Present health service guidelines call for screening and mammography for all women aged between 50 and 65 years in an effort to increase early detection and improve survival rates. Nulliparity is one of the associated risk factors for breast cancer. Women with intellectual disability (ID) are increasing in longevity and are frequently nulliparous, and therefore, they are at increased risk of developing breast cancer. The aim of the present study was to review the uptake and knowledge of women with ID living in the community of breast screening programmes. A postal survey of women aged > or = 50 years with ID living in community group homes was used to gather data. Only one-third of the women carried out regular breast examination and a similar proportion had received invitations to mammography. General practitioners and practice nurses were currently playing very minor roles in breast screening these women. Primary health care professionals may be missing opportunistic health promotion opportunities and the support services for women with ID living in the community could be provided with better training and resources to improve breast cancer screening in this vulnerable group.

Aged↗

Microsomal metabolism of the terpene 1,8-cineole in the common brushtail possum (Trichosurus vulpecula), koala (Phascolarctos cinereus), rat and human.

1. This study reports on the pathways of metabolism and enzyme kinetics of the Eucalyptus terpene, 1,8-cineole, by liver microsomes from the brushtail possum (Trichosurus vulpecula) and koala (Phascolarctos cinereus) (animals that normally include this terpene in their diet), rat and human. 2. The rank order of the ability to metabolize 1,8-cineole with respect to overall 1,8-cineole intrinsic clearance (CL'int = Vmax/Kmax in microl mg protein(-1) min(-1)) was koala (188) > possum (181)>> rat (28) > human (12). This order supports the hypothesis that adaptation to a Eucalyptus diet involves enhanced metabolism of terpenes. 3. The metabolism of 1,8-cineole was also studied in the liver from brushtail possum pretreated with a mixture of terpenes, which have previously been shown to induce cytochrome P450 enzymes. Rats were pretreated with the same mixture of terpenes or phenobarbitone. 4. Terpene pretreatment more than doubled the CL'int of 1,8-cineole by brushtail possum liver microsomes (from 180 to 394 microl mg protein(-1) min(-1)) and increased rat CL'int by nearly 10-fold (from 28 to 259 microl mg protein(-1) min(-1)), but still less than the induced possum value. However, phenobarbitone had the greatest inducing effect, increasing the rat CL'int to 1,825 microl mg protein(-1) min(-1). 5. A regioselective preference of oxidation was evident between adapted and non-adapted species. In rat and human oxidation was preferred at the aliphatic ring carbons over methyl substituents. In possum, many of the available carbons were utilized, however metabolism at methyl substituents was preferred. In the koala, oxidation occurred primarily at the methyl substituents.

Adult↗

A survey of the influence of patients' choice on the increase in the caesarean section rate.

The caesarean section rate in the Royal Gwent Hospital has, as in the rest of the UK, risen significantly over the last 10 years. A commonly proposed reason for this increase is that women themselves are now more likely to request an elective caesarean section, when there is little or no medical indication. The aim of this survey, carried out prospectively, was to find out whether patients' requests for caesarean section are contributing significantly to the rise in the section rate, by attempting to actually quantify the influence of patients' choice on the decision to perform a caesarean section. The results showed that it is possible to quantify this influence, and that maternal request does play a major role in the decision-making process.

Journal Article↗

Ultrafast magnetic resonance imaging of central nervous system abnormalities in utero in the second and third trimester of pregnancy: comparison with ultrasound.

OBJECTIVE: To assess the ability of ultrafast magnetic resonance imaging to visualise abnormalities in the central nervous system of third trimester fetuses in utero and to compare the results with the current 'reference standard' of ultrasound and postnatal imaging or post-mortem data. DESIGN: A prospective, observational study comparing the diagnostic accuracy of two imaging methods: antenatal ultrasound and antenatal magnetic resonance with each other and postnatal or post mortem data. POPULATION: Twenty-one pregnant women of 19-36 weeks of gestation whose fetus were thought to have a central nervous system abnormality on the basis of antenatal ultrasound. The women had either not been offered or had refused a termination and were willing to have a magnetic resonance scan. METHODS: A 1.5T magnetic resonance scanner used a single shot fast spin echo sequence, in three image planes. The results were compared with the ultrasound results obtained by an experienced investigator independently. A series of 21 patients, with a range of pathologies of central nervous system, were imaged. Postnatal ultrasound and/or magnetic resonance imaging, or post-mortem data were used for additional confirmation of the pathology in all cases. RESULTS: The magnetic resonance report was different to the ultrasound in 10/21 (47.6%), magnetic resonance provided information additional to the ultrasound in 5/21 (23.8%), ultrasound and magnetic resonance results agreed in 6/21 cases (28.6%). CONCLUSION: Magnetic resonance in the third trimester provides a useful adjuvant to ultrasound imaging of the fetus when assessing abnormalities of the central nervous system after 19 weeks of gestation particularly if the abnormality involves the posterior fossa.

Adolescent↗

Analytical model of a three-dimensional integral image recording system that uses circular- and hexagonal-based spherical surface microlenses.

A mathematical model for a three-dimensional omnidirectional integral recording camera system that uses either circular- or hexagonal-based spherical surface microlens arrays is derived. The geometry of the image formation and recording process is fully described. Matlab is then used to establish the number of recorded micro-intensity distributions representing a single object point and their dependence on spatial position. The point-spread function for the entire optical process for both close and remote imaging is obtained, and the influence of depth on the point-spread dimensions for each type of microlens and imaging condition is discussed. Comparisons of the two arrangements are made, based on the illustrative numerical results presented.

Journal Article↗

Cyclic stretch induces the expression of vascular endothelial growth factor in vascular smooth muscle cells.

OBJECTIVE: Accumulating evidence links the release of vascular endothelial growth factor (VEGF) by vascular smooth muscle cells (VSMC) to normal endothelial cell (EC) function, repair and maintenance. Using an in vitro model we investigate the role of cyclic stretch on both the release of VEGF by VSMC and the phosphorylation of a VEGF receptor on EC. METHODS: Bovine VSMC and EC were exposed to 10% cyclic strain for 4 hours. VEGF mRNA steady-state levels of VSMC were analysed by northern blot hybridisation. The presence of secreted VEGF from VSMC was determined by assaying the migration of EC. VEGF receptor phosphorylation on stretched EC was assayed by immunoblotting. RESULTS: The steady-state level of VEGF mRNA in stretched VSMC increased 3.3 (+/- 0.6) fold above that of unstretched VSMC (p < 0.005). Migration of EC was stimulated 8.3 (+/- 1.1) and 14.6 (+/- 1.3) fold by media from unstretched and stretched VSMC respectively, demonstrating a 1.8 fold increase due to stretch alone (p < 0.05). Cyclic stretch resulted in phosphorylation of the VEGF receptor KDR. CONCLUSION: Exposure of VSMC to physiological levels of stretch induces a biologically significant increase in VEGF secretion and may provide an arterial stimulus for maintenance of steady state levels of VEGF essential for EC survival.

Animals↗

Matrix metalloproteinases and tissue valve degeneration.

Bioprosthetic heart valves have been used as replacements for diseased heart valves for over 30 years. More than 50% of bioprosthetic valves fail within 15 years because of structural deterioration. The role of proteolytic degradation, with particular reference to the matrix metalloproteinases (MMPs) in the degeneration of aortic bioprostheses, is appraised in this minireview. It is clear that both the intrinsic and host-derived proteolytic activities present in heart-valve bioprostheses may combine with mechanical stress to bring about valve failure.

Bioprosthesis↗

A therapeutic trial of growth hormone in hypopituitary adults and its influence upon continued prescription by general practitioners.

OBJECTIVES: Adult GH deficiency (GHD) is associated with profound alterations in body composition, lipid profiles and quality of life which frequently improve after GH therapy. However, the beneficial effects of treatment are not derived by all and consequently some scepticism persists with regard to the use of GH therapy in adults. We assessed whether a 3-month therapeutic assessment with GH therapy could be used to determine which GHD adults should be treated over the longer term. We also assessed the continued prescription of GH by general practitioners (GPs) following the initial therapeutic assessment. DESIGN: A three month open therapeutic trial of GH in GHD adults. Patients were treated with GH at an initial dose of 0.01 iU/kg/d, increased after 1 month to 0.015 iU/kg/d for males and 0.02 iU/kg/d for females. After completion of the three months the continued prescription of GH by the GPs was assessed. PATIENTS: All adult GHD patients were considered for GH therapy. Thirty-nine GHD adults wanted GH therapy (group 1) and their baseline characteristics such as age, duration of GHD, and IGF-1 concentration were compared with 24 subjects who declined to receive GH (group 2). MEASUREMENTS: Measurements of body composition using bioelectrical impedance analysis, lipids and quality of life measured using a dedicated questionnaire were made before and after GH therapy. The response of the general practitioners to continued GH therapy after the initial therapeutic assessment was also noted. RESULTS: Compared with subjects who declined GH therapy (group 2), subjects of group 1 were younger (46.4 +/- 14.4 vs. 54.2 +/- 15.7 years, P < 0.05) and had lower peak GH responses to provocative testing (1.4 +/- 2.1 vs. 2.9 +/- 2.7 mU/l, P < 0.001), though there were no differences between IGF-1 concentration (11.7 +/- 6.2 vs. 14. 2 +/- 7.9 nmol/l). Following three months of GH therapy, there were significant improvements in all measured parameters including increased free fat mass (50.2 vs. 52.4 kg, P < 0.005) and total body water (37 vs. 38.7 l, P < 0.005), reduced fat mass (31.6 vs. 29.8 kg, P < 0.005), reduced AGHDA score (7 vs. 4, P < 0.001) and reduced cholesterol (6.3 vs. 5.8 mmol/l, P < 0.001), LDL (4 vs. 3.33 mmol/l, P < 0.001) and cholesterol/HDL ratio (5.57 vs. 4.67, P < 0.001). IGF-1 concentrations were significantly increased following treatment (12 vs. 32.4 nmol/l). Six subjects decided to discontinue GH therapy, 2 before the end of the study due to potential drug-related side-effects and 4 subjects derived no benefit from treatment. Despite the demonstrable benefits of treatment for the remaining 33 GHD adults, 6 GPs refused to continue to prescribe GH therapy for reasons of lack of familiarity with the drug or advice from their health authority. CONCLUSION: Patients who wanted GH therapy were usually younger and more severely GHD than counterparts who elect not to be treated. However, a therapeutic trial of GH therapy is required to distinguish those subjects who derive benefit from treatment. We have shown that three months of low dose GH therapy is a sufficient period to elicit significant beneficial responses in quality of life, body composition parameters and lipids for the majority of patients and appears to be a sufficient period for patients to decide whether they want longer term therapy. The initial therapeutic trial also provides the objective evidence for the general practitioners to decide upon the continued prescription of therapy. Despite the positive evidence provided by this study, a small minority of general practitioners still refuse to prescribe GH therapy.

Adult↗

Patients' and carers' perceptions of factors influencing recovery after cardiac surgery.

Stress and anxiety experienced by patients following myocardial infarction are well documented. Moreover, partners feel distress when they realize that they must assume responsibility for day-to-day care once the period of hospitalization is over. However, despite the trend towards early hospital discharge and the role which carers appear to be expected to undertake during the recovery of patients who have had cardiac surgery, few studies have been undertaken with this group outside the United States of America. This omission was filled by a descriptive survey with 60 patients and carers following cardiac surgery. Data were obtained during early recovery (1 week after hospital discharge) and 6 weeks later. The results indicated that carers assumed a heavy burden once the patient had left hospital and were less satisfied with the timing of discharge than the patients. Information provided by nurses was consistently rated more highly than information provided by doctors or physiotherapists but there was scope for increasing input with both groups. High levels of satisfaction with the information provided by health professionals were associated with lower scores on the Hospital Anxiety and Depression Scale. More qualitative, in-depth studies to explore the precise needs of patients and their carers are needed to ensure that in future both groups are better prepared.

Adolescent↗

Updating cardiopulmonary resuscitation skills: a study to examine the efficacy of self-instruction on nurses' competence.

Nurses' competence in cardiopulmonary resuscitation (CPR) has been shown to be consistently poor over the past decade. Studies have suggested that CPR teaching methods need to be evaluated and refined in order to improve practice. Self-instruction has been suggested as one alternative to formal retraining programmes, but has not been evaluated with respect to nurses in the UK. A quasi-experimental design utilizing random allocation of matched subjects to one experimental and two control groups was adopted with a sample of 20 undergraduate nursing students. The subjects' CPR ability was assessed concurrently using a resuscitation manikin and an observational checklist. Subjects undertaking self-instruction produced significantly (P < 0.05) higher ability scores than those who did not participate in retraining. The time spent in self-instruction was evaluated positively by the students. The results are discussed in the light of previous research and current recommendations for regular CPR updating by all clinical nurses.

Adult↗

Carers' opinions and emotional responses following cardiac surgery: cardiac rehabilitation implications for critical care nurses.

The recent joint position statement made by the RCN Critical Care and Rehabilitation Nursing Forums highlights the need for rehabilitation to commence early. This paper reports the findings of a descriptive survey of 59 carers of cardiac surgery patients and presents implications for cardiac rehabilitation. Data were obtained by postal questionnaire during early recovery (one week following discharge) and six weeks later. The questionnaire explored carers' perceptions about the timing of discharge from hospital; opinions of the information provided by hospital staff; and anxiety and depression measured on the Hospital Anxiety and Depression Scale. The results indicated that carers assumed a heavy burden once the patient had left the specialist cardiac centre. Carers responding at one week were less satisfied with the timing of discharge than those questioned at six weeks. Information provided by nurses was rated more highly than that provided by doctors or physiotherapists. However, there was scope for increasing input. The findings suggest that cardiac rehabilitation needs to be aimed at carers as well as patients. Investment in targeted carer support could facilitate patient recovery and rehabilitation. Strategies aimed at the carer need to begin early and commence during the acute stage of the patients' recovery.

Adolescent↗

Providing palliative care in end-stage heart failure.

Little attention has been given to the palliative care needs of heart failure patients. Patients dying from heart disease experience a wide range of symptoms that are frequently distressing, including breathlessness, nausea and vomiting and anxiety. Nurses can draw on the literature relating to the care of cancer patients when devising strategies to care for patients with heart failure.

Heart Failure↗

Importance of dissection of the hernial sac in laparoscopic surgery for large hiatal hernias.

HYPOTHESIS: Laparoscopic repair of large hiatal hernia is an appropriate management strategy. DESIGN: A prospective patient series. SETTING: A university teaching hospital. PATIENTS: All patients with hiatal hernias 10 cm or greater in diameter repaired laparoscopically between February 1, 1992, and September 30, 1998. INTERVENTIONS: Two operative strategies were used for laparoscopic repair: the first, which was used until early 1996, entailed initial esophageal dissection while leaving the sac in the mediastinum. The second involved preliminary dissection of the hernial sac from the mediastinum before dissecting the esophagus. MAIN OUTCOME MEASURES: Successful completion of the procedure using a laparoscopic technique, postoperative complication rate, reoperation rate, and clinical outcome. RESULTS: Eighty-six patients with a large hiatal hernia underwent attempted repair using laparoscopic methods. The median age was 63 years (range, 30-91 years), and 45 patients (52%) were women. There were 30 sliding, 10 rolling, and 46 mixed hiatal hernias. Operating times ranged from 48 to 240 minutes (median, 90 minutes), and 20 procedures (23%) were converted to an open operation. Conversion was significantly more common in the first half of our experience (16 [40%] of 40 patients vs 4 [9%] of 46 patients) before the operative strategy was changed. Esophageal-lengthening procedures were not carried out for any patient. At follow-up of a median of 2 years, 1 patient has moderate dysphagia, 4 patients have reflux symptoms, and 1 patient has undergone further surgery for a recurrent paraesophageal hernia. An overall satisfactory outcome was achieved in 81 patients (94%). CONCLUSIONS: Large hiatal hernias can be treated effectively laparoscopically. Dissecting the sac fully from the mediastinum before dissecting the esophagus helps to safely mobilize the esophagus, and we think changing to this strategy is the main reason for the improved laparoscopic success rate reported in the latter half of this series.

Adult↗