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Biomedical subjects

K Fox

Publications and source records attributed to K Fox.

At least 19 recordsLinked to original sources
PubMed2006

Prion infectivity in variant Creutzfeldt-Jakob disease rectum.

BACKGROUND: Disease-related prion protein (PrP(Sc)) is readily detectable in lymphoreticular tissues in variant Creutzfeldt-Jakob disease (vCJD), but not in other forms of human prion disease. This distinctive pathogenesis, with the unknown population prevalence of asymptomatic vCJD infection, has led to significant concerns that secondary transmission of vCJD prions will occur through a wide range of surgical procedures. To date PrP(Sc):prion infectivity ratios have not been determined in vCJD, and it is unknown whether vCJD prions are similar to experimental rodent prions, where PrP(Sc) concentration typically reflects infectious prion titre. AIM: To investigate prion infectivity in vCJD tissue containing barely detectable levels of PrP(Sc). METHODS: Transgenic mice expressing only human PrP (Tg(HuPrP129M(+/+)Prnp(o/o))-35 and Tg(HuPrP129M(+/+)Prnp(o/o))-45 mice) were inoculated with brain or rectal tissue from a previously characterised patient with vCJD. These tissues contain the maximum and minimum levels of detectable PrP(Sc) that have been observed in vCJD. RESULTS: Efficient transmission of prion infection was observed in transgenic mice inoculated with vCJD rectal tissue containing PrP(Sc) at a concentration of 10(4.7)-fold lower than that in vCJD brain. CONCLUSIONS: These data confirm the potential risks for secondary transmission of vCJD prions via gastrointestinal procedures and support the use of PrP(Sc) as a quantitative marker of prion infectivity in vCJD tissues.

Animals↗
PubMed2006

Pleiotropic role of VEGF-A in regulating fetal pulmonary mesenchymal cell turnover.

Tight regulation of VEGF-A production and signaling is important for the maintenance of lung development and homeostasis. VEGF null mice have provided little insight into the role of VEGF during the later stages of lung morphogenesis. Therefore, we examined the in vitro effects of autocrine and paracrine VEGF-A production and the inhibition of VEGF-A signaling on a Flk-1-negative subset of fetal pulmonary mesenchymal cells (pMC). We hypothesized that VEGF-A receptor signaling regulates turnover of fetal lung mesenchyme in a cell cycle-dependent manner. VEGF receptor blockade with SU-5416 caused cell spreading and decreased proliferation and bcl-2 localization. Nuclear expression of the cell cycle inhibitory protein, p21, was increased with SU-5416 treatment, and p27 was absent. Autocrine VEGF production by pMC resulted in proliferation and p21/p27-dependent contact inhibition. In contrast, exogenous VEGF-A increased cell progression through the cell cycle. Selective activation of Flt by placental growth factor demonstrated the importance of this receptor/kinase in the VEGF-A responsiveness of pMC. The expression and localization of the survival factor bcl-2 was dependent on VEGF. These results provide evidence that VEGF-A plays a critical role in the regulation of fetal pulmonary mesenchymal proliferation, survival, and the subsequent development of normal lung architecture through bcl-2 and p21/p27-dependent cell cycle control.

Animals↗
PubMed2006

Undergraduate training as preparation for vocational training in England: a survey of vocational dental practitioners' and their trainers' views.

AIMS: To compare the views of new vocational dental practitioners (VDPs) and their trainers regarding how undergraduate dental education has prepared them for their vocational training (VT) in England. This study also aims to identify areas of relative weakness in dental undergraduate education that could influence the future training needs of vocational trainees. METHOD: Structured postal questionnaires were completed by VDPs and trainers from five Deaneries in England. The usable response rate was 71% (n = 186 VDPs and 186 trainers). RESULTS: The vast majority of VDPs and trainers perceived the undergraduate training in history taking, diagnosis and treatment planning for general practice to have been covered 'well' or even 'very well'. Undergraduate training in routine restorative dentistry, oral pathology and paediatric dentistry was also perceived to have been covered well. However, a large proportion of VDPs and trainers reported that they felt that undergraduate training in orthodontics, molar endodontics, surgical endodontics and surgical extraction of teeth had not adequately prepared them for VT. CONCLUSIONS: Newly qualified dentists appear to lack certain competencies recommended by the General Dental Council in The First Five Years. This has implications for dental undergraduate education, but also highlights current training needs during VT.

Attitude of Health Personnel↗
PubMed2006

Economic evaluation of the impact of nicorandil in angina (IONA) trial.

OBJECTIVE: To estimate the net cost of adding nicorandil to usual treatment for patients with angina and to compare this with indicators of health benefit. DESIGN: Cost effectiveness analysis. SETTING: Based on results of the IONA (impact of nicorandil on angina) trial. PATIENTS: Patients with angina fulfilling the entry criteria for the IONA trial. INTERVENTIONS: In one arm of the trial nicorandil was added to existing antianginal treatment and compared with existing treatment alone. MAIN OUTCOME MEASURES: Costs were for use of hospital resources (for cardiovascular, cerebrovascular, and gastrointestinal reasons), nicorandil, and care after hospital discharge. Benefits were assessed in three ways: (1) IONA trial primary outcome (coronary heart disease (CHD) death, non-fatal myocardial infarction, or hospital admission for cardiac chest pain); (2) acute coronary syndrome (CHD death, non-fatal myocardial infarction, or unstable angina); and (3) event-free survivors at the end of the trial. RESULTS: The net cost for each additional IONA trial end point averted was -5 pounds sterling (-7 euros). The net cost for each case of acute coronary syndrome averted was -8 pounds sterling (-12 euros). The net cost for each event-free survivor was -5 pounds sterling (-7 euros). These figures are based on gastrointestinal events that were judged definitely or probably related to nicorandil. When all gastrointestinal events were included these three ratios rose to 567 pounds sterling (835 euros), 886 pounds sterling (1305 euros), and 516 pounds sterling (760 euros), respectively. CONCLUSIONS: A substantial amount of the additional cost of nicorandil is offset by reduced use of hospital services. The limited comparisons possible with other CHD interventions suggest that nicorandil compares favourably.

Angina Pectoris↗
PubMed2005

Estimating population served by sewage treatment works from readily available GIS data.

Environmental risk assessment of household chemicals at the catchment scale requires an estimate of the load at individual Sewage Treatment Works (STWs). This can be achieved based upon population served and market consumption data. Although the population served is difficult to obtain, this paper shows that reasonable estimates can be made using readily available spatially referenced data. A new method is developed using STW data from the Exe and the Aire and Calder catchments and validated using 193 STWs within the Environment Agency's Anglian region. The estimated populations served were compared with available estimates of Population Equivalents (PEs). The population estimates were broadly similar to PEs for small works but agreement was lower for larger plants. The discrepancy for larger works is consistent with trade influent inclusion in the PE. The method is suitable for application to both rural areas and large urbanised areas, although the interpretation of corroborating data becomes increasingly difficult in very large urban areas serving more than one STW.

Geographic Information Systems↗
PubMed2005

Evaluation of anemia, neutropenia and skin toxicities in standard or dose-dense doxorubicin/cyclophosphamide (AC)-paclitaxel or docetaxel adjuvant chemotherapy in breast cancer.

BACKGROUND: Results of CALGB 9741 demonstrated that administering standard doxorubicin/cyclophosphamide (AC)-paclitaxel therapy for adjuvant therapy of breast cancer in a dose-dense fashion with colony-stimulating factors increases efficacy, decreases severe neutropenia, but may increase the need for blood transfusions. A chart review was performed to evaluate the rates of anemia, neutropenia and skin toxicities with dose-dense and traditional AC-taxane chemotherapy. PATIENTS AND METHODS: A total of 112 patients received one of four treatments: non-dose-dense AC-paclitaxel (NDD Pac), dose-dense AC-paclitaxel (DD Pac), non dose-dense AC-docetaxel (NDD Doc), or dose-dense AC-docetaxel (DD Doc). RESULTS: Transfusion rates were not increased in the dose-dense population; however, rates of grade 2-4 anemia (23% versus 0%, P=0.029), as well as erythropoietin use (58% versus 0%, P <0.0001), were significantly increased in the DD Pac group compared with the NDD Pac group. Grade 3 skin toxicities were significantly increased in the DD Doc group compared with the NDD Doc group (70% versus 11%, P <0.0001). CONCLUSIONS: These results demonstrate that dose-dense AC-taxane therapy may increase rates of anemia and the need for erythropoietin, and decrease rates of neutropenia. The utility of DD Doc appears limited by skin toxicities and its use outside of a clinical study should not be recommended.

Adult↗
PubMed2004

Flux and instrumentation upgrade for the epithermal neutron beam facility at Washington State University.

An epithermal neutron beam facility for preclinical neutron capture therapy research has been constructed at the Washington State University TRIGA research reactor installation. Subsequent to a recent upgrade, this new facility offers a high-purity epithermal beam with intensity on the order of 1.2x10(9)n/cm(2)s. Key features include a fluoride-based design for the neutron filtering and moderating components as well as a novel collimator design that allows ease of assembly and disassembly of the beamline components.

Animals↗
PubMed2004

A clinical report of 85 fractured metallic post-retained crowns.

AIM: To determine any patient, technique or material factors that were significantly associated with post fracture in metallic post systems. SUMMARY: Eighty-five fractured metal posts were retrieved over a 5-year period from a total of 84 patients who attended a dental hospital for treatment. A record was kept of the patient's dentition to identify the tooth with the fractured post, the number of teeth present, the excursive guidance scheme and the likely post design and material. Radiographs of 67 of these teeth were available. The presence or absence of a periapical lesion was noted as was the quality of the root filling. Maxillary lateral incisors, followed by maxillary centrals were associated with most of the fractured posts. The median survival to fracture was 36 months. The number of teeth in the dentition had a mode of 28. The most commonly fractured post design was a serrated and parallel design with an average diameter of 1.2 mm at the site of fracture. Apical lesions were found in 67% of the teeth with radiographs. Only 12% of teeth with a 'good' apical filling as opposed to 55% with a 'poor' apical filling had apical lesions. KEY LEARNING POINTS: . Maxillary lateral incisors, followed by maxillary central incisors are at greatest risk of having a fractured metallic post. . Having a large number of teeth in the dentition or an adequate length of post was not protective against metallic post fracture. . Teeth with fractured post-retained crowns had a high incidence of apical lesions.

Crowns↗
PubMed2003

Alcohol and drug use among vocational dental practitioners.

OBJECTIVE: This study was designed to investigate the prevalence of alcohol and drug use in vocational dental practitioners (VDPs). DESIGN: Anonymous self-report questionnaire. SUBJECTS AND METHODS: All UK vocational dental practitioners (n = 719) who started practice in the summer of 1999 were questioned on their use of alcohol, tobacco, cannabis and other illicit drugs whilst a VDP and before graduation. RESULTS: Eighty-nine per cent of males and 88% of females reported alcohol use. Of these, 35% of males and 36% of females drank above sensible levels (up to 21 units per week for males, 14 units for females), with 48% of males and 52% of females "binge drinking". Thirty-three per cent of respondents reported cannabis use whilst a VDP. Regular drug use (use at least once a month) other than cannabis whilst a VDP was found to be highest among males, with regular ecstasy use reported by 4% and regular cocaine use reported by 2%. Regular tobacco use (ten or more cigarettes per day) was reported by 9% of VDPs. Regular tobacco users were found to be six times more likely to use cannabis on a regular basis, three times more likely to use ecstasy on a regular basis and four times more likely to use cocaine on a regular basis than those VDPs who reported non regular tobacco use. CONCLUSION: VDPs are drinking above sensible limits, binge drinking, using tobacco and indulging in illicit drug use to a degree that will cause health problems. However, use of all substances had reduced since qualification.

Alcohol Drinking↗
PubMed2003

Certification of the European reference soil set (IRMM-443--EUROSOILS). Part I. Adsorption coefficients for atrazine, 2,4-D and lindane.

The European Commission has characterised and certified a set of six European soils (the EUROSOILS) under the number IRMM-443. After a successful validation and trial period with a preliminary batch it was decided to produce a new batch of certified reference materials. Part I of this paper describes the certification of adsorption coefficients for atrazine, 2,4-D and lindane in these soils. The adsorption coefficients were determined according to OECD Test Guideline 106. Additionally, the underlying principles for the value assignment process according to the GUM and their practical application to the numerical data obtained during the certification exercise according to ISO Guide 34 and 35 are discussed.

Journal Article↗
PubMed2003

Certification of the European Reference Soil Set (IRMM-443--EUROSOILS). Part II. Soil-pH in suspensions of water and CaCl2.

IRMM-443 re-groups a set of six European Reference Soils (EUROSOILS), which had been certified for their adsorption coefficients for atrazine, 2,4-D and lindane (Certification of the European Reference Soil Set (IRMM-443-EUROSOILS)-Part I. Adsorption coefficients for atrazine, 2,4-D and lindane. Sci Total Environ, in press). The certification of these parameters was complemented by an additional certification of pH in suspension as well by the determination of indicative values for total nitrogen, organic and total carbon content. While Part I explained the principles of the value assignment process and discussed their application to the adsorption coefficients, Part II presents the certified values for pH as well as the indicative values for N(tot), C(tot) and C(org). In addition, the assessment of uncertainty components for stability and homogeneity, which have been included in the final uncertainty budget, is discussed.

Journal Article↗
PubMed2003

The value of routine non-invasive tests to predict clinical outcome in stable angina.

BACKGROUND: Chronic stable angina is a common condition, but considerable differences exist in the likelihood of acute coronary events such as CHD death, non-fatal myocardial infarction (MI) and unstable angina between individual patients. Effective risk prediction is necessary for optimum management. The aim of this study was to identify clinical features and non-invasive test parameters associated with high risk of these coronary events in stable angina and compose a clinically useful model to predict adverse outcomes in this population. METHODS: Six hundred and eighty-two patients with stable angina and a positive exercise test (1mm ST depression) from the Total Ischaemic Burden European Trial (TIBET) study, were studied. Resting ECG, exercise tolerance testing and echocardiography were performed at baseline, off anti-anginal therapy. The patients were then randomised to treatment with atenolol, nifedipine or a combination of both. Clinical follow up continued for an average of 2 years (range 1-3 years). RESULTS AND CONCLUSIONS: Prior MI or prior CABG were the clinical parameters associated with adverse outcome in patients with stable angina and a positive exercise test. On the ECG, left ventricular hypertrophy was predictive, and on echocardiogram, increased left ventricular dimensions were predictive of adverse events. When combined with time to ischaemia on exercise testing in a simple clinically applicable table these factors could be used to predict of 2 year probability of events for an individual patient.

Adult↗
PubMed2003

Changes in water quality parameters due to in-sewer processes.

Combined sewer systems contain a large number of organic and inorganic pollutants from both domestic and industrial sources. These pollutants are often retained within the combined sewer system for significant lengths of time before entering sewage treatment works, or being spilt to a watercourse via a combined sewer overflow (CSO) during storm conditions. Currently little knowledge exists concerning the effects of in sewer processes on pollutants. Understanding of in-sewer processes is important for the effective and efficient design of treatment works and CSO chambers and for impact assessments on receiving waters. A series of studies covering storm and dry weather flow conditions were undertaken with the aim of investigating the nature of in-sewer processes. These studies consisted of marking a body of water with a fluorescent tracer. The tracer was then monitored at a series of downstream sites, and discrete samples collected from the body of water as it progressed through the sewer. The samples were analysed for water quality parameters and these results investigated in tandem with the detailed hydraulic information gained through the tracer studies. The results highlight the hydraulic differences between storm and dry weather conditions such as increased travel times and mixing under storm conditions. The Advection Dispersion Equation (ADE) and Aggregated Dead Zone (ADZ) model parameters have been quantified for the tracer data. The ADE mixing coefficient is shown to increase by an order of magnitude for storm conditions. The ADZ dispersive fraction parameter is shown to be approximately constant with flow. Chemical reactions and decay within the sewer system were found to be consistent with oxygen limitation.

Environmental Monitoring↗
PubMed2002

Natriuretic peptides in the diagnosis of heart disease--first amongst equals?

The natriuretic peptides and their role in neurohumoral regulation of the cardiovascular system have become the focus of considerable interest from the scientific and clinical community in recent years. BNP in particular has been shown to be an important diagnostic and prognostic marker of use in a wide range of applications. As measurement techniques develop and are refined, routine evaluation of serum levels of these markers is expected to become more widespread. We have reviewed the biochemistry of the natriuretic peptide family, their role in cardiovascular pathophysiology and the evidence supporting their use in the clinical setting.

Atrial Natriuretic Factor↗
PubMed2002

Anatomical pathways and molecular mechanisms for plasticity in the barrel cortex.

The barrel cortex has yielded a wealth of information about cortical plasticity in recent years. Barrel cortex is one of the few cortical areas studied so far where plasticity can be examined from birth through to adulthood. This review looks at plasticity mechanisms in three periods of life: early post-natal development, adolescence and adulthood. Separate consideration is given to depression and potentiation mechanisms. Plasticity can be induced in barrel cortex by whisker deprivation. Single whisker experience leads to expansion of the area of cortex responding to the spared whisker. In early post-natal life, plasticity occurs in thalamocortical pathways, while later in adolescence, intracortical pathways become more important. Ablation of the spared whisker's barrel prevents expression of plasticity in the cortex. A row of lesions between the spared and an adjacent barrel prevents expression of plasticity in the adjacent barrel. This evidence, together with latency of response data and an analysis of pathways capable of inducing long-term potentiation (LTP) within barrel cortex, leads to the view that horizontal and/or diagonal pathways between barrels are responsible for plasticity expression. The mouse has become the most commonly mutated mammalian species and has a well-developed barrel cortex. Therefore, mutations can be used to study the role of particular molecules in experience-dependent plasticity of barrel cortex. Through this work, it has become clear that the major post-synaptic density protein, alpha-CaMKII, and its T286 autophosphorylation site are essential for experience-dependent plasticity. This points to a major role for excitatory transmission in cortical plasticity and raises the possibility that LTP like mechanisms are involved. Furthermore, transgenic mice carrying a reporter gene for CRE have provided evidence that CRE-mediated gene expression is also involved in barrel cortex plasticity. This view is supported by studies on alpha/delta CREB knockouts, and provides a starting point for studying the role of gene expression in experience-dependent cortical plasticity.

Age Factors↗