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Biomedical subjects

R Powell

Publications and source records attributed to R Powell.

At least 19 recordsLinked to original sources

Are the Peer Assessment Rating Index and the Index of Treatment Complexity, Outcome, and Need suitable measures for orthognathic outcomes?

The aim of this study was to determine which of two occlusal indices were the most appropriate for use in the assessment of orthognathic outcome. The indices used were the Peer Assessment Rating (PAR) Index and the Index of Treatment Complexity, Outcome, and Need (ICON). These indices were validated against the subjective assessments of treatment outcome and treatment improvement obtained from a panel of experienced orthodontic consultants. For the subjective assessment, intraexaminer agreement for ranking treatment outcome, from patient study models (30 models), was good. Interexaminer agreement for ranking treatment outcome, in the same way, was good or moderate. Intraexaminer agreement for ranking treatment improvement (30 start and finish pairs of models) was very good or good. Interexaminer agreement for ranking treatment improvement ranged from good to fair. All the patient study models were scored using PAR and ICON. The level of correlation between PAR and ICON scores of treatment outcome and the subjective ranking of treatment outcome was significant (P < 0.001). The level of correlation between PAR and ICON scores of treatment improvement and the subjective ranking of treatment improvement was also significant (P < 0.001). It is concluded that both PAR and ICON are suitable indices for assessing the clinical outcome of combined orthodontic treatment and orthognathic surgery.

Humans↗

From pro defensins to defensins: synthesis and characterization of human neutrophil pro alpha-defensin-1 and its mature domain.

Human neutrophil alpha-defensins (HNPs) are small, cationic, Cys-rich antimicrobial proteins that play important roles in innate immunity against infectious microbes such as bacteria, fungi and enveloped viruses. Synthesized as inactive precursors in vivo (pre-proHNPs), HNPs are activated through proteolytic removal of the inhibitory pro-peptide required for subcellular sorting and correct folding. We seek to understand the molecular basis for the recognition between the 45-residue pro-peptide and the C-terminal functional domain. Here we described, total chemical synthesis of the 75-residue human neutrophil pro alpha-defensin-1 (proHNP1) via native chemical ligation. After oxidative folding, proHNP1 is cleaved by cyanogen bromide at the Met45-Ala46 peptide bond to release the mature form. The native disulfide connectivity in HNP1, i.e. Cys1-Cys6, Cys2-Cys4 and Cys3-Cys5, is verified by mass mapping of peptide fragments generated by proteolytic digestion and Edman degradation. Fluorescence spectroscopy studies and antimicrobial activity assays further support that synthetic proHNP1 and HNP1 are correctly folded. While largely unstructured in aqueous solution, the pro-peptide binds to HNP1 intermolecularly with an apparent Kd value of 6.2 microM at pH 7.4, confirming the mode of intramolecular inactivation of human alpha-defensin precursors.

Amino Acid Sequence↗

Identification of novel expressed sequences, up-regulated in the leucocytes of chronic fatigue syndrome patients.

BACKGROUND: Chronic fatigue syndrome (CFS) is an increasing medical phenomenon of unknown aetiology leading to high levels of chronic morbidity. Of the many hypotheses that purport to explain this disease, immune system activation, as a central feature, has remained prominent but unsubstantiated. Supporting this, a number of important cytokines have previously been shown to be over-expressed in disease subjects. The diagnosis of CFS is highly problematic since no biological markers specific to this disease have been identified. The discovery of genes relating to this condition is an important goal in seeking to correctly categorize and understand this complex syndrome. OBJECTIVE: The aim of this study was to screen for changes in gene expression in the lymphocytes of CFS patients. METHODS: 'Differential Display' is a method for comparing mRNA populations for the induction or suppression of genes. In this technique, mRNA populations from control and test subjects can be 'displayed' by gel electrophoresis and screened for differing banding patterns. These differences are indicative of altered gene expression between samples, and the genes that correspond to these bands can be cloned and identified. Differential display has been used to compare expression levels between four control subjects and seven CFS patients. RESULTS: Twelve short expressed sequence tags have been identified that were over-expressed in lymphocytes from CFS patients. Two of these correspond to cathepsin C and MAIL1 - genes known to be upregulated in activated lymphocytes. The expression level of seven of the differentially displayed sequences have been verified by quantifying relative level of these transcripts using TAQman quantitative PCR. CONCLUSION: Taken as a whole, the identification of novel gene tags up-regulated in CFS patients adds weight to the idea that CFS is a disease characterized by subtle changes in the immune system.

Expressed Sequence Tags↗

Threshold 2: the reliability, validity and sensitivity to change of the Threshold Assessment Grid (TAG).

OBJECTIVE: This study investigated the psychometric properties of the Threshold Assessment Grid (TAG), a new assessment of the severity of mental health problems. METHOD: A total of 605 patients were recruited from 10 mental health adult and elderly services in London, UK. TAG ratings and other standardized definitions of severe mental illness were completed by referrers. TAG, Global Assessment of Functioning (GAF), Camberwell Assessment of Need Short Appraisal Schedule (CANSAS) and Health of the Nation Outcome Scale (HoNOS) ratings were completed by mental health service staff. Construct validation on extreme groups was investigated. RESULTS: Construct and concurrent validity were good. Referrer TAG scores predicted mental health team view of referral suitability, but not whether assessments were offered. Test-retest reliability was good, interrater reliability ranged from good to poor in different domains (but adequate for total TAG score), internal consistency was appropriate. Sensitivity to change requires further investigation. CONCLUSION: The TAG can be recommended for use by all agencies when making referrals to mental health services.

Adult↗

A survey of genes in the Atlantic salmon (Salmo salar) as identified by expressed sequence tags.

We describe the construction and quality analysis of six cDNA libraries from the liver, ovary, testis, brain, spleen and muscle tissues of adult Atlantic salmon. The cDNA libraries were then screened with total cDNA probes to catalogue clones representing the abundant and rare mRNA populations in each tissue. Subsequently, the 5'-terminal DNA sequences of 1152 cDNA clones, composed of 96 clones from each of the abundant and rare mRNA populations in the six tissues, were determined. Bioinformatic analysis revealed that 510 (50%) of the salmon expressed sequence tags (ESTs) of sufficient length showed significant homology to previously identified genes from salmonid and other species, while 517 (50%) of salmon ESTs were unidentified or novel. After accounting for multi-EST redundancy, the 510 identified ESTs provided DNA sequence markers for 178 salmon genes which are listed in terms of tissue of origin and mRNA abundance class.

Animals↗

Threshold 3: the feasibility of the Threshold Assessment Grid (TAG) for routine assessment of the severity of mental health problems.

BACKGROUND: Evidence-based practice requires the development of measures which are suitable for everyday clinical use ('feasible'). There is no consensus as to how to establish feasibility. METHOD: The feasibility of a new assessment - the Threshold Assessment Grid (TAG) - for use when making referrals to mental health services was tested by training mental health teams in using the TAG and other standardised assessments, asking referrers to ten mental health services in London also to complete a TAG, surveying TAG users, and evaluating a feedback meeting at which TAG data were presented. RESULTS: One hundred and one (61%) mental health staff received training, and 445 (74%) referrers of 600 patients completed TAGs. Sixty-five (65%) questionnaires from TAG users were completed, and 24 (80%) people attending feedback meetings evaluated the TAG. These allowed the extent to which the TAG is brief, simple, relevant, acceptable, available and valuable to be investigated. CONCLUSION: The TAG exhibited good feasibility when used by mental health staff, and moderate feasibility when used by referrers. This approach can be used to investigate the feasibility of other standardised assessments.

Adult↗

Head lice infestation: bug busting vs. traditional treatment.

The two main methods of managing head lice infestation in the UK are head lice lotions and bug busting; there is no conclusive evidence as to which of these methods is most effective. The aim of this study was to compare the effectiveness of the bug busting method with lotion. A pilot study in the form of a randomized controlled trial involving two semi-rural general practices was used. Thirty children aged 4-16 years were randomly assigned to two intervention groups. After initial dry combing to detect the presence of head lice, one group was treated with phenothrin lotion. The bug busting group received combing using special combs provided in the bug busting pack and hair conditioner. The main outcome measure was the number of adult live lice and nymphs at day 14. On day 14 in the bug busting group, total eradication of head lice had occurred in eight children; in the lotion group, total eradication had occurred in two children (P=0.052); number needed to treat 2.5 (95% CI: 2.19-2.81). These results suggest that bug busting performed by nurses in a controlled situation is an effective method of managing head lice infestation.

Adolescent↗

Limited efficacy of thalidomide in the treatment of febrile attacks of the hyper-IgD and periodic fever syndrome: a randomized, double-blind, placebo-controlled trial.

Hyper-IgD and periodic fever syndrome (HIDS) is an autosomal recessive disorder featured by recurrent febrile attacks. Previous unpublished experience (J. van der Meer and R. Powell) suggested that thalidomide may prevent febrile attacks. Six HIDS patients (5 male and 1 female) who had at least one febrile attack every 6 weeks, entered a randomized, double-blind, placebo-controlled crossover trial to explore the efficacy of a daily 200-mg thalidomide dose in the treatment of recurrent febrile attacks of HIDS. The patients received either thalidomide, 200-mg daily, or placebo for 16 weeks, followed by a 4-week washout period and another 16-week treatment (crossover) with either thalidomide or placebo. Patients completed a weekly diary card noting attacks and side effects. During the study, C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-1 receptor antagonist, soluble TNF receptor p55 and p75, and lipopolysaccharide-stimulated IL-1 beta and TNF-alpha production were measured at six different points, whereas urine neopterin levels were measured weekly. During the active treatment with thalidomide, there were 10 attacks compared with 13 attacks with placebo. Thalidomide resulted in a nonsignificant decrease of CRP and SAA, but the concentrations of other inflammatory mediators, including urine neopterin, remained unchanged. One patient developed sensory polyneuropathy, but this resolved when thalidomide administration was stopped. The effect of thalidomide in HIDS is limited to a decrease in acute phase protein synthesis without an effect on the attack rate.

Acute-Phase Reaction↗

A truncated plasminogen activator inhibitor-1 protein induces and inhibits angiostatin (kringles 1-3), a plasminogen cleavage product.

Plasminogen activator inhibitor-1 (PAI-1) is a serpin protease inhibitor that binds plasminogen activators (uPA and tPA) at a reactive center loop located at the carboxyl-terminal amino acid residues 320-351. The loop is stretched across the top of the active PAI-1 protein maintaining the molecule in a rigid conformation. In the latent PAI-1 conformation, the reactive center loop is inserted into one of the beta sheets, thus making the reactive center loop unavailable for interaction with the plasminogen activators. We truncated porcine PAI-1 at the amino and carboxyl termini to eliminate the reactive center loop, part of a heparin binding site, and a vitronectin binding site. The region we maintained corresponds to amino acids 80-265 of mature human PAI-1 containing binding sites for vitronectin, heparin (partial), uPA, tPA, fibrin, thrombin, and the helix F region. The interaction of "inactive" PAI-1, rPAI-1(23), with plasminogen and uPA induces the formation of a proteolytic protein with angiostatin properties. Increasing amounts of rPAI-1(23) inhibit the proteolytic angiostatin fragment. Endothelial cells exposed to exogenous rPAI-1(23) exhibit reduced proliferation, reduced tube formation, and 47% apoptotic cells within 48 h. Transfected endothelial cells secreting rPAI-1(23) have a 30% reduction in proliferation, vastly reduced tube formation, and a 50% reduction in cell migration in the presence of VEGF. These two studies show that rPAI-1(23) interactions with uPA and plasminogen can inhibit plasmin by two mechanisms. In one mechanism, rPAI-1(23) cleaves plasmin to form a proteolytic angiostatin-like protein. In a second mechanism, rPAI-1(23) can bind uPA and/or plasminogen to reduce the number of uPA and plasminogen interactions, hence reducing the amount of plasmin that is produced.

Angiostatins↗

Genetic diversity of the fish pathogen Aeromonas salmonicida demonstrated by random amplified polymorphic DNA and pulsed-field gel electrophoresis analyses.

The current taxonomy of Aeromonas salmonicida includes 4 subspecies. A. salmonicida subsp. salmonicida is associated with salmonid furunculosis, and A. salmonicida subsp. achromogenes, A. salmonicida subsp. masoucida, and A. salmonicida subsp. smithia are strains that show variation in some biochemical properties. This classification does not readily encompass isolates from a wide range of fish hosts currently described as atypical A. salmonicida. This study examined 17 typical strains, 39 atypical strains and 3 type A. salmonicida subspecies strains for genetic similarity using the random amplified polymophic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE) techniques. On the basis of RAPD- and PFGE-derived profiles, similarity matrices and dendrograms were constructed. The results showed that species A. salmonicida constituted a genetically heterogeneous group of strains, encompassing within an homogeneous or clonal lineage comprised solely of typical strains and the A. salmonicida subsp. salmonicida type strain.

Aeromonas↗

Threshold Assessment Grid (TAG): the development of a valid and brief scale to assess the severity of mental illness.

BACKGROUND: Lack of consensus about the meaning of severe mental illness makes it difficult to prioritise the severely mentally ill for specialist mental health care. The goal of this study was to develop a valid and brief assessment of severity of mental illness. METHOD: Six search workshops (n = 57) using consensus techniques developed a draft assessment acceptable to users, carers, practitioners and policy makers. A two-round Delphi consultation (n = 58) was held to identify consensus on this instrument. RESULTS: Search workshops agreed seven domains relevant to identifying the severely mentally ill: intentional and unintentional self-harm, risk from and to others, and survival, psychological, and social needs and disabilities. The Delphi consultation indicated at least agreement with all aspects in both rounds. CONCLUSIONS: The Threshold Assessment Grid (TAG) is a brief method of identifying the severely mentally ill, which has adequate face, concurrent, construct and content validity.

Delphi Technique↗

Comparative Analysis of Two Populations of the Brittle Star Amphiura filiformis (Echinodermata: Ophiuroidea) with Different Life History Strategies Using RAPD Markers.

Random amplified polymorphic DNA (RAPD) analysis was applied to individuals of Amphiura filiformis sampled from two geographic locations that have previously been reported to have different life history strategies. Of thirty-one 10-mer RAPD primers screened initially, four were chosen and used in a comparative analysis of A. filiformis individuals collected from Galway Bay (Ireland) and Concarneau Bay (France). The results show much variation within A. filiformis populations. Although there are some rare alleles particular to each population, overall the populations were not genetically differentiated with the methods employed. Analysis of molecular variance (AMOVA) showed that a minimum of 93% of genotypic variance occurred among individuals within populations. The statistical significance of this pattern was supported by permutation tests. F(ST) values were not significantly different from and UPGMA cluster analyses based on three distance metrics did not separate the two populations.

Journal Article↗

Improving foot care for people with diabetes mellitus--a randomized controlled trial of an integrated care approach.

AIMS: To evaluate a model of integrated diabetic footcare, for identification and clinical management of the high risk diabetic foot, centred on the primary care-based diabetic annual review. METHODS: A pragmatic randomized controlled study was undertaken with matched cluster randomization of practices from 10 towns drawn from mid and east Devon responsible for the care of 1,939 people with diabetes (age > or =18 years). Outcome measures were patients' attitudes regarding the value and importance of footcare, patients' footcare knowledge, healthcare professionals' footcare knowledge and pattern of service utilization. RESULTS: Attitudes towards footcare improved in both intervention and control groups (mean percentage change 3.91, 0.68) with a significant difference in change of 3.18 (95% confidence interval (CI) 1.29-5.07) between the groups. Patients' knowledge about diabetic foot problems improved significantly in both groups (mean percentage change 1.09, 1.32) but with no significant difference in change: -0.09 (95% CI -1.81-1.63) between groups. Health professionals' knowledge scores improved in the intervention group (mean percentage change 13.2; P < 0.001). No improvement was seen in the control group (mean percentage change -0.2; P = 0.1) with a significant difference in change of 13.46 (95% CI 8.30-18.62) between groups. Appropriate referrals from intervention practices to the specialized foot clinic rose significantly (P = 0.05) compared with control practices (P = 0.14). CONCLUSIONS: Provision of integrated care arrangements for the diabetic foot has a positive impact on primary care staffs' knowledge and patients' attitudes resulting in an increased number of appropriate referrals to acute specialist services.

Adult↗

Healing at skin graft donor sites dressed with chitosan.

Chitosan is a derivative of chitin, extracted from the exoskeleton of lobsters, crabs and shrimps. As a semi-permeable biological dressing, it maintains a sterile wound exudate beneath a dry scab, preventing dehydration and contamination of the wound to optimise conditions for healing. In this study, evaluation of healing at split skin graft donor sites, dressed half with chitosan and half with a conventional dressing, showed that chitosan facilitated rapid wound re-epithelialisation and the regeneration of nerves within a vascular dermis. In addition, digital colour separation analysis of donor site scars demonstrated an earlier return to normal skin colour at chitosan-treated areas.

Adolescent↗

Specificity and prevalence of natural bovine anti-alpha galactosyl (Galalpha1-6Glc or Galalpha1-6Gal) antibodies.

Immunity against the carbohydrate components of microorganisms mediated by antibodies is an important part of host defenses. Humans and closely related primates, but not other mammals, possess natural anti-Galalpha1-3Gal antibodies which also, although less avidly, react with melibiose (Galalpha1-6Glc). Using an enzyme-linked immunosorbent assay (ELISA) with melibiose-bovine serum albumin as an antigen, we analyzed bovine anti-alpha galactosyl antibodies with respect to specificity and distribution in individual animals. Inhibition assays showed that melibiose was the strongest inhibitor, followed equally by stachyose (Galalpha1-6Galalpha1-6Glcbeta1-2Fru) and raffinose (Galalpha1-6Glcbeta1-2Fru) and then by Galbeta1-6Gal, Gal, and Galalpha1-2Gal. Others, including Galalpha1-3Gal and Galalpha1-4Gal, only exhibited minor inhibition. Thus, these bovine anti-alpha galactosyl antibodies appeared to preferentially react with Galalpha1-6Glc or Galalpha1-6Gal. The distinction of this specificity from that (Galalpha1-3Gal) of human antibodies was further demonstrated by the poor reaction of bovine serum to the Galalpha1-3Gal antigen in comparison to human serum. All 27 healthy bovine serum samples of the three age groups (newborn, calf, and adult) tested contained such antibodies with titers increasing with age. The antibodies purified by affinity chromatography using a melibiose-agarose column were mainly of the immunoglobulin G (IgG) isotype with a concentration of >23 microg/ml in most samples. IgG1 was found to be the primary antimelibiose IgG isotype in all age groups by isotype-specific ELISA, but a significant increase in IgG2, an isotype more related to innate immunity, was observed in calves and adults, compared to newborns. The purified antibodies reacted with the type II bovine strain of Streptococcus agalactiae, a common pathogen of bovine mastitis. Thus, these anti-Galalpha1-6Glc or Galalpha1-6Gal antibodies in cattle might be involved in defense against microbes bearing this or the related epitopes.

Age Factors↗

Suicide in the farming community: methods used and contact with health services.

Farmers have a high rate of suicide (1% of suicides in England and Wales). This study sought to test whether farmers would be less likely to have been in contact with primary or mental health services before death due to their reluctance to seek help. The study also sought to identify other characteristics that differentiated suicide among male farmers from other professional groups. A retrospective case-control design was used comparing male farmers with an age and sex matched control group. Cases were all members of the farming community within the Exeter Health District on whom suicide or open verdict had been recorded between 1979 and 1994. 63 Cases were identified and entered into the study. Controls were non-farmers with the same verdict who were matched for age (5 year age bands) sex and social class. Farmers were significantly more likely to use firearms to kill themselves (42% of farmers v 11% controls). They were less likely to use a car exhaust or to die by poisoning (9% farmers v 50% controls). Farmers were significantly less likely to leave a suicide note (21% farmers v 41% controls). There was no significant difference between farmers and controls for numbers in contact with their general practitioner or mental health services in the 3 months before death. There may be some differences in help seeking behaviour between farmers and the general population as over 30% of farmers presented with exclusively physical symptoms. General practitioners should consider depressive and suicidal intention in farmers presenting with physical problems. When depression is diagnosed consideration should be given to the temporary removal of firearms as the high rate of suicide in the farming community may be strongly influenced by access to means.

Agriculture↗