Biomedical subjects

D J Evans

Publications and source records attributed to D J Evans.

At least 19 recordsLinked to original sources

PubMed2004

Anticonvulsants for neonates with seizures.

BACKGROUND: Neonatal seizures are a common problem and most neonates with seizures are treated with anticonvulsants. There is wide variation in clinical practice in both diagnosis and treatment of such seizures and this reflects the lack of clear evidence of the relative benefit and harm of the anticonvulsants used. The routine use of anticonvulsants to treat seizures in neonates needs to be evaluated. OBJECTIVES: To assess and compare (with respect to benefits and harm) different anticonvulsants administered to neonates for the treatment of established seizures. SEARCH STRATEGY: Relevant randomised controlled trials were identified using a combination of electronic database searches (MEDLINE 1966 - March 2004, EMBASE 1980 - March 2004), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004) and hand searches. Identification of ongoing or unpublished trials was attempted by contacting prominent authors in the field and searching electronic registers of ongoing trials. SELECTION CRITERIA: All randomised or quasi-randomised controlled clinical trials with reported data comparing the following outcomes: mortality, neurodevelopmental disability, need for additional anticonvulsants, need for maintenance anticonvulsants at discharge and adverse events (hypotension requiring volume or inotropic support, arrhythmia, respiratory depression, hepatotoxicity) in neonates treated for seizures with systemic anticonvulsants compared to placebo, no drug or alternative anticonvulsants. DATA COLLECTION AND ANALYSIS: Methodological quality and validity were assessed without consideration of the results. The first reviewer screened the title and abstracts of studies identified by the above search strategy. Full text versions of studies of potential relevance were re-screened by both reviewers. Studies meeting the pre-specified inclusion criteria were included. Relevant data were extracted and analysed separately and any disagreements were resolved by discussion. MAIN RESULTS: Only two randomised controlled trials published in full could be identified. Painter 1999 showed that both of the two most commonly used anticonvulsants (phenobarbital and phenytoin) were similarly effective (RR 1.03 95% CI 0.96 to 1.62), controlling seizures in less than fifty percent of infants. Painter 1999 did not report mortality or neurodevelopmental outcome. Boylan 2004 randomised infants who failed to respond to phenobarbital to receive either lidocaine or midazolam as second-line agents. There was a trend for lidocaine to be more effective in reducing seizure burden (RR 0.40 95% CI 0.14 to 1.17) but both groups had similarly poor long term outcomes assessed at one year. REVIEWERS' CONCLUSIONS: At present there is little evidence from randomised controlled trials to support the use of any of the anticonvulsants currently used in the neonatal period. In the literature, there remains a body of opinion that seizures should be treated because of the concern that seizures in themselves may be harmful, although this is only supported by relatively low grade evidence (Levene 2002; Massingale 1993). Development of safe and effective treatment strategies relies on future studies of high quality (randomised controlled trials with methodology that assures validity) and of sufficient size to have the power to detect clinically important reductions in mortality and severe neurodevelopmental disability in addition to any short term reduction in seizure burden.

Anticonvulsants↗

PubMed2004

Physico-chemical controls on phosphorus cycling in two lowland streams. Part 1 -- the water column.

This paper investigates phosphorus (P) transport and transformation dynamics in two contrasting sub-catchments of the River Kennet, England. Samples were collected daily under baseflow and hourly under stormflow conditions using autosamplers for 2 years and analysed for a range of determinands (full P fractionation, suspended sediment (SS), cations, pH, alkalinity, temperature and oxygen). Concentrations of SRP, SUP, PP and SS were higher in the flashy River Enborne (means of 0.186, 0.071, 0.101 and 34 mg l(-1), respectively) than the groundwater-fed River Lambourn (0.079, 0.057, 0.028 and 9 mg l(-1), respectively). A seasonal trend in the daily P dataset was evident, with lower concentrations during intermediate flows and the spring (caused by a dilution effect and macrophyte uptake) than during baseflow conditions. However, in the hourly P dataset, highest concentrations were observed during storm events in the autumn and winter (reflecting higher scour with increased capacity to entrain particles). Storm events were more significant in contributing to the total P load in the River Enborne than the River Lambourn, especially during August to October, when dry antecedent conditions were observed in the catchment. Re-suspension of P-rich sediment that accumulated within the channel during summer low flows might account for these observations. It is suggested that a P-calcite co-precipitation mechanism was operating during summer in the River Lambourn, while adsorption by metal oxyhydroxide groups was an important mechanism controlling P fractionation in the River Enborne. The influence of flow conditions and channel storage/release mechanisms on P dynamics in these two lowland rivers is assessed.

Journal Article↗

PubMed2004

Physico-chemical controls on phosphorus cycling in two lowland streams. Part 2--the sediment phase.

This article investigates the temporal and spatial controls on sediment-phosphorus (P) dynamics in two contrasting sub-catchments of the River Kennet, England. Suspended sediment (collected under representative flow conditions) and size-fractionated bedload (collected weekly for one year) from the Rivers Lambourn and Enborne was analysed for a range of physico-chemical determinands. Total P concentrations were highest in the most mobile fractions of sediment: suspended sediment, fine silt and clay and organic matter (mean concentrations of 1758, 1548 and 1440 microg P g(-1) dry sediment, respectively). Correlation analysis showed significant relationships between total P and total iron (n= 110), total manganese (n= 110), organic matter (n= 110) and specific surface area (n= 28) in the Lambourn (r2 0.71, 0.68, 0.62 and 0.52, respectively) and between total P and total iron (n= 110), total manganese (n= 110) and organic matter (n= 110) in the Enborne (r2 0.74, 0.85 and 0.68, respectively). These data highlight the importance of metal oxyhydroxide adsorption of P on fine particulates and organic matter. However, high total P concentrations in the granule gravel and coarse sand size fraction during the summer period (mean concentration 228 microg P g(-1) dry sediment) also highlight the role of calcite co-precipitation on P dynamics in the Lambourn. P to cation ratios in Lambourn sediment indicated that fine silt and clay and granule gravel and coarse sand size fractions were potential sources of P release to the water column during specific periods of the summer and autumn. In the Enborne, however, only the granule gravel and coarse sand size fraction had high ratios and a slow, constant release of P was observed. In addition, scanning electron microscopy work confirmed the association of P with calcite in the Lambourn and P with iron on clay particles in the Enborne. The study highlighted the importance of the chemical and physical properties of the sediment in influencing the mechanisms controlling P storage and release within river channels.

Journal Article↗

PubMed2004

Complement regulation at the molecular level: the structure of decay-accelerating factor.

The human complement regulator CD55 is a key molecule protecting self-cells from complement-mediated lysis. X-ray diffraction and analytical ultracentrifugation data reveal a rod-like arrangement of four short consensus repeat (SCR) domains in both the crystal and solution. The stalk linking the four SCR domains to the glycosylphosphatidylinositol anchor is extended by the addition of 11 highly charged O-glycans and positions the domains an estimated 177 A above the membrane. Mutation mapping and hydrophobic potential analysis suggest that the interaction with the convertase, and thus complement regulation, depends on the burial of a hydrophobic patch centered on the linker between SCR domains 2 and 3.

CD55 Antigens↗

PubMed2004

Naloxone for preventing morbidity and mortality in newborn infants of greater than 34 weeks' gestation with suspected perinatal asphyxia.

BACKGROUND: Studies in animal models have suggested that naloxone, a specific opiate antagonist, may improve outcomes for newborn infants with perinatal asphyxia. OBJECTIVES: In newborn infants of greater than 34 weeks' gestation with suspected perinatal asphyxia: to assess the effects of naloxone versus placebo or no drug, and of single versus multiple doses of naloxone, on mortality, long term neurological problems, severity of hypoxic-ischaemic encephalopathy, and frequency of neonatal seizures. SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2003), MEDLINE (1966 - August 2003), EMBASE (1980 - August 2003), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing naloxone versus placebo, or no drug, or another dose of naloxone, in newborn infants of greater than 34 weeks' gestation with suspected perinatal asphyxia. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two authors. The pre-specified outcomes for this review were: death before hospital discharge, severe neurodevelopmental disability, severity of hypoxic-ischaemic encephalopathy, and seizures in the neonatal period. MAIN RESULTS: We identified only one eligible randomised controlled trial. This study compared the use of naloxone with placebo in newborn infants with an Apgar score of six or less at one minute after birth. There were not any data on the pre-specified outcomes for this review. REVIEWER'S CONCLUSIONS: There are insufficient data available to evaluate the safety and effectiveness of the routine use of naloxone for newborn infants of greater than 34 weeks' gestation with suspected perinatal asphyxia. A further randomised controlled trial is needed to determine if naloxone benefits newborn infants with suspected perinatal asphyxia. Such a trial should assess clinically important outcomes such as mortality, and adverse short and long term neurological outcomes.

Asphyxia Neonatorum↗

PubMed2004

Detailed mapping of RNA secondary structures in core and NS5B-encoding region sequences of hepatitis C virus by RNase cleavage and novel bioinformatic prediction methods.

There is accumulating evidence from bioinformatic studies that hepatitis C virus (HCV) possesses extensive RNA secondary structure in the core and NS5B-encoding regions of the genome. Recent functional studies have defined one such stem-loop structure in the NS5B region as an essential cis-acting replication element (CRE). A program was developed (STRUCTUR_DIST) that analyses multiple rna-folding patterns predicted by mfold to determine the evolutionary conservation of predicted stem-loop structures and, by a new method, to analyse frequencies of covariant sites in predicted RNA folding between HCV genotypes. These novel bioinformatic methods have been combined with enzymic mapping of RNA transcripts from the core and NS5B regions to precisely delineate the RNA structures that are present in these genomic regions. Together, these methods predict the existence of multiple, often juxtaposed stem-loops that are found in all HCV genotypes throughout both regions, as well as several strikingly conserved single-stranded regions, one of which coincides with a region of the genome to which ribosomal access is required for translation initiation. Despite the existence of marked sequence conservation between genotypes in the HCV CRE and single-stranded regions, there was no evidence for comparable suppression of variability at either synonymous or non-synonymous sites in the other predicted stem-loop structures. The configuration and genetic variability of many of these other NS5B and core structures is perhaps more consistent with their involvement in genome-scale ordered RNA structure, a structural configuration of the genomes of many positive-stranded RNA viruses that is associated with host persistence.

Computational Biology↗

PubMed2003

Refinement of the nickel site structure in Desulfovibrio gigas hydrogenase using range-extended EXAFS spectroscopy.

We have reexamined the Ni EXAFS of oxidized, inactive (as-isolated) and H(2) reduced Desulfovibrio gigas hydrogenase. Better spatial resolution was achieved by analyzing the data over a 50% wider k-range than was previously available. A lower k(min) was obtained using the FEFF code for phase shifts and amplitudes. A higher k(max) was obtained by removing an interfering Cu signal from the raw spectra using multiple energy fluorescence detection. The larger k-range allowed us to better resolve the Ni-S bond lengths and to define more accurately the Ni-O and Ni-Fe bond lengths. We find that as-isolated, hydrogenase has two Ni-S bonds at approximately 2.2 A, but also 1-2 Ni-S bonds in the 2.35+/-0.05 A range. A Ni-O interaction is evident at 1.91 A. The as-isolated Ni-Fe distance cannot be unambiguously determined. Upon H(2) reduction, two short Ni-S bonds persist at approximately 2.2 A, but the remaining Ni-S bonds lengthen to 2.47+/-0.05 A. Good simulations are obtained with a Ni-Fe distance at 2.52 A, in agreement with crystal structures of the reduced enzyme. Although not evident in the crystal structures, an improvement in the fit is obtained by inclusion of one Ni-O interaction at 2.03 A. Implications of these distances for the spin-state of H(2) reduced H(2)ase are discussed.

Absorption↗

PubMed2003

Prolonged antibiotics for purulent bronchiectasis.

BACKGROUND: The vicious cycle hypothesis for bronchiectasis predicts that bacterial colonisation of the respiratory tract perpetuates inflammatory change. This damages the mucociliary escalator preventing bacterial clearance and allowing the persistence of pro-inflammatory mediators. Conventional treatment with physiotherapy and intermittent antibiotics are felt to improve the condition of bronchiectasis patients although there are no conclusive data showing that these interventions influence the natural history of the condition. Various strategies have been tried to interrupt this cycle of infection and inflammation and one of these is to prolong antibiotic treatment in the hope of allowing the airway mucosa to heal. OBJECTIVES: This systematic review brings together the evidence and where possible presents a meta-analysis of the data available to answer the question 'Does treatment with prolonged courses of antibiotics influence the outcome in purulent bronchiectasis?' SEARCH STRATEGY: The Cochrane Airways Group trials register and reference lists of identified articles were searched. SELECTION CRITERIA: Randomised trials looking at the use of prolonged antibiotic therapy in the treatment of bronchiectasis. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extraction was carried out by the reviewers independently. Study authors were contacted for missing information. MAIN RESULTS: 447 abstracts were found and reviewed for suitability. Six trials were included and 302 patients were randomised amongst these trials. 40% of the patients were contributed by one trial. Antibiotics were given for between 4 weeks and one year. There were 40 withdrawals due to treatment failure and intolerable side effects. Only limited meta-analysis was possible due to the diversity of the trials. Response rates showed significant effects in favour of prolonged antibiotic treatment (Peto OR (95% CI), 3.37 (1.60 to 7.09)). Conversely for exacerbation rates there was no significant difference between prolonged antibiotics and placebo (Peto OR (95% CI), 0.96 (0.27 to 3.46)). For withdrawals there was no significant difference between treatment and placebo management (Peto OR (95% CI), 1.06 (0.42 to 2.65)). Data for lung function showed no significant benefit in favour of antibiotic treatment (% predicted FEV1, WMD (95% CI) -1.05 (-6.93 to 4.83)). REVIEWER'S CONCLUSIONS: The evidence available shows a small benefit for the use of prolonged antibiotics in the treatment of bronchiectasis. This review is limited by the diversity of the trials. Further randomised controlled trials with adequate power and standardised end points are required.

Adult↗

PubMed2003

Long-term antibiotics in the management of non-CF bronchiectasis--do they improve outcome?

In addition to bacteria and inflammatory cells, the sputum of patients with bronchiectasis contains mediators that damage the airway epithelium and promote inflammatory change. The deleterious effects of these mediators, such as neutrophil elastase, reduce host defences and consequently perpetuate the propensity to recurrent infection. This 'vicious cycle' of infection and inflammation in bronchiectasis suggests that long-term antibiotic therapy might be beneficial in these patients by reducing microbial load and, in doing so, inhibit inflammation in the lung allowing tissue repair to occur. Short courses of antibiotics achieve clinical improvements and also have been shown to reduce the levels of harmful mediators in the sputum. This article will cite the studies reported for long-term antibiotic treatment in bronchiectasis and overall there seems to be benefits for patients with chronic sputum purulence. The evidence that supports the postulated pathological mechanisms will also be discussed. Important issues in clinical practice such as the usefulness of antibiotic sensitivities, the evolution of resistance patterns, and drug delivery will also be discussed.

Anti-Bacterial Agents↗

PubMed2003

General dental practitioners' perception of their role within child protection: a qualitative study.

AIM: This was to assess general dental practitioners' knowledge, attitudes and practice regarding their role within child protection in relation to child abuse. METHODS: Structured interviews with seven key informants from general dental practice (2), local dental committees (1), social services (2), paediatric dentistry (1) and community child health (1), together with five focus groups comprising 23 general dental practitioners (GDPs) on Health Authority Lists in Tyne and Wear and Northumberland (UK). RESULTS: GDPs reported feelings of isolation with little communication with other health professionals or local authority services. The majority had scarcely considered child protection issues in their clinical practice although those qualified for less than 15 years were more aware. GDPs acknowledged a lack of awareness of signs and symptoms of physical abuse and even less confidence in dealing with emotional or sexual abuse. Dentists expressed concern, even fear, about the outcomes of reporting suspicions, and had little knowledge of the local Child Protection mechanisms. CONCLUSION: GDPs in Tyne and Wear and Northumberland feel unprepared to undertake a role in the child protection process with confidence. National and local initiatives may be required to address existing barriers.

Attitude of Health Personnel↗

PubMed2002

Analysis of CHK2 in vulval neoplasia.

Structure and expression of the Rad53 homologue CHK2 were studied in vulval neoplasia. We identified the previously described silent polymorphism at codon 84 (A>G at nucleotide 252) in the germ-line of six out of 72, and somatic mutations in two out of 40 cases of vulval squamous cell carcinomas and none of 32 cases of vulval intraepithelial neoplasia. One mutation introduced a premature stop codon in the kinase domain of CHK2, whereas the second resulted in an amino acid substitution in the kinase domain. The two squamous cell carcinomas with mutations in CHK2 also expressed mutant p53. A CpG island was identified close to the putative CHK2 transcriptional start site, but methylation-specific PCR did not detect methylation in any of 40 vulval squamous cell carcinomas, irrespective of human papillomavirus or p53 status. Consistent with this observation, no cancer exhibited loss of CHK2 expression at mRNA or protein level. Taken together, these observations reveal that genetic but not epigenetic changes in CHK2 occur in a small proportion of vulval squamous cell carcinomas.

Adult↗

PubMed2002

E7 proteins from oncogenic human papillomavirus types transactivate p73: role in cervical intraepithelial neoplasia.

In common with other E2F1 responsive genes such as p14(ARF) and B-myb, the promoter of p73 is shown to be positively regulated in cell lines and primary human keratinocytes by E7 proteins from oncogenic human papillomavirus (HPV) types 16, 18, 31 and 33, but not HPV 6. Mutational analysis revealed that transactivation of the p73 promoter by HPV 16E7 requires association with pRb. Expression of p73 in normal cervical epithelium is confined to the basal and supra-basal layers. In contrast, expression in neoplastic lesions is detected throughout the epithelium and increases with grade of neoplasia, being maximal in squamous cell cancers (SCC). Deregulation of expression of the N-terminal splice variant p73Delta2 was observed in a significant proportion of cancers, but not in normal epithelium. The frequent over-expression of p73Delta2, which has recognized transdominant properties, in malignant and pre-malignant lesions suggests a role in the oncogenic process in cervical epithelium.

Carcinoma, Squamous Cell↗

PubMed2002

The dental caries experience of 12-year-old children in England and Wales. Surveys coordinated by the British Association for the Study of Community Dentistry in 2000/2001.

DESIGN: This paper reports the results of standardised clinical caries examinations of 106,694 twelve-year-old children from England, Wales, the Isle of Man and Jersey. These 2000/01 coordinated surveys are the latest in a series which seek to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating health authorities and boards, and caries was diagnosed at the caries into dentine (D3) threshold using a visual method without radiography or fibre-optic transillumination. RESULTS: Once again a wide variation in caries prevalence across the United Kingdom was demonstrated, with mean values for D3MFT for the English 'regions' (of the National Health Service) and Wales ranging from 0.63 in the West Midlands to 1.31 in Wales. The mean value for DMFT across England Wales was 0.89 (D3T=0.39, MT=0.07, FT=0.43). Overall, 38% of children had evidence of caries experience at the dentinal level of detection (D3MFT>0), although the means ranged between 30% (West Midlands) and 51% (Wales). The mean D3MFT for those with disease at this threshold was 2.35. Trends over time demonstrate an improvement of 11% in overall D3MFT since 1996/97, compared to the 15% seen over the previous four year period. FT and care index fell. The number of fillings provided in 2000/01 and thus the care index, remained low. On average across England and Wales, only 48% of the dentinal caries experience identified by survey examinations of permanent teeth was seen as fillings (range in individual districts: 30% to 78%). The use of the SiC index highlights dental health inequalities. CONCLUSION: Taken together, these findings demonstrate the continuing need for more effective preventive strategies and treatment services for this important age group.

Child↗

PubMed2001

Out-of-hours emergency dental services--development of one possible local solution.

This paper describes the development of a local solution to the problem of the provision of out-of-hours dental care in Newcastle and North Tyneside in the north east of England. Focus groups were used to review the current provision of, and problems with, dental out-of-hours emergency provision. A consensus conference involving both general dental and medical practitioners, was subsequently used to develop possible alternative methods for the provision of out-of-hours emergency dental services. A centralised service delivered from a secure location in conjunction with general medical practitioners was developed which was dependent on a nurse-led triage. The linkage with NHS Direct may be an opportunity, in some locations, to integrate dental services more fully with other out-of-hours primary care services. The method described allowed a solution to be generated by practitioners themselves, thus giving ownership and acceptance to the chosen option.

Consensus Statements as Topic↗

PubMed2001

1H-Pyrrole-2-carbothioamide.

The reaction of ethoxycarbonylpyrrole-2-thiocarboxamide with sodium hydroxide affords the known title compound, C(5)H(6)N(2)S, whose structure shows a three-dimensional hydrogen-bonded lattice.

Crystallography, X-Ray↗

PubMed2001

Multiple nonequilibrium steady states for one-dimensional heat flow.

A nonequilibrium molecular dynamics model of heat flow in one-dimensional lattices is shown to have multiple steady states for any fixed heat field strength f(e) ranging from zero to a certain positive value. We demonstrate that, depending on the initial conditions, there are at least two possibilities for the system's evolution: (i) formation of a stable traveling wave (soliton), and (ii) chaotic motion throughout the entire simulation. The percentage of the soliton-generating trajectories is zero for small field strength f(e), but increases sharply to unity over a critical region of the parameter f(e).

Journal Article↗

PubMed2001

Computation of the viscosity of a liquid from time averages of stress fluctuations.

The shear viscosity can be calculated from the standard deviation of an equilibrium ensemble of time averages of the shear stress computed along finite duration phase space trajectory segments. The mean square of the segment averages of the shear stress is proportional to the shear viscosity and inversely proportional to the duration of the trajectory segments and the number of particles. We test the fluctuation relation for the shear viscosity and show that it provides a simple but viable means of computing the zero strain rate shear viscosity. We decompose the shear viscosity computed using this fluctuation method, into its "kinetic" and "configurational" components. We also calculate the relevant relaxation times. We compare the computed results with standard nonequilibrium molecular dynamics simulations. Finally we compute the bulk viscosity using an analogous fluctuation method.

Journal Article↗

PubMed2001

Fluctuation theorem for Hamiltonian systems: Le Chatelier's principle.

For thermostated dissipative systems, the fluctuation theorem gives an analytical expression for the ratio of probabilities that the time-averaged entropy production in a finite system observed for a finite time takes on a specified value compared to the negative of that value. In the past, it has been generally thought that the presence of some thermostating mechanism was an essential component of any system that satisfies a fluctuation theorem. In the present paper, we point out that a fluctuation theorem can be derived for purely Hamiltonian systems, with or without applied dissipative fields.

Journal Article↗