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Biomedical subjects

M Warner

Publications and source records attributed to M Warner.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy of practised screening methods for detection of cephalosporin-resistant Enterobacteriaceae.

OBJECTIVES: Enterobacteriaceae with extended-spectrum beta-lactamases (ESBLs) are now widespread and simple phenotypic tests are required to detect them in diagnostic laboratories. We investigated the performance of screening methods at 16 hospitals in South-East England. METHODS: Sixteen laboratories in South-East England submitted 1195 consecutive Enterobacteriaceae isolates found to be resistant, by their routine methods, to any or all of cefpodoxime, ceftazidime and cefotaxime. These isolates were re-tested centrally with various cephalosporin/clavulanate combinations and with multiplex PCR for bla(CTX-M) and bla(AmpC) alleles. RESULTS: Screening methods among the laboratories were the following: cefpodoxime discs alone (1 site); cefpodoxime, cefotaxime and ceftazidime discs (9 sites) or agar dilution (1 site); Phoenix (2 sites), Vitek 1 (1 site) and Vitek 2 (2 sites). A total of 8% of isolates submitted based on disc tests proved fully cephalosporin-susceptible, compared with 3% sent based on tests with automated systems and none of those sent based on agar dilution tests. Among isolates submitted solely on cefpodoxime resistance 256/372 (69%) proved cephalosporin-susceptible or had only borderline resistance with no clear mechanism demonstrable; this proportion decreased to 28/160 (18%) for those submitted on the basis of resistance to ceftazidime, 18/122 (15%) for those resistant to cefotaxime and 26/496 (5%) for those resistant to both cefotaxime and ceftazidime. The inference of ESBL production by Vitek 2 had the best agreement with reference laboratory results. CONCLUSIONS: Many isolates found resistant only to cefpodoxime at the source sites proved not to have ESBLs or AmpC; screening with cefotaxime and ceftazidime allowed better specificity for identification of mechanism-based resistance, as did the automated systems. Cefpodoxime disc tests nevertheless remain a useful primary screen for laboratories prepared only to test one agent.

Cephalosporins↗
PubMed2006

Mechanical strains and electric fields applied to topologically imprinted elastomers.

We analyze and predict the behavior of a chirally imprinted elastomer under a mechanical strain and an electric field, applied along the helical axis. As the strain and/or field increases, the system is deformed from a conical or transverse imprinted state towards an ultimately nematic one. At a critical strain and/or field there is a first-order transition to a low imprinting efficiency state. This transition is accompanied by a discontinuous global rotation of the director toward the axis of the imprinted helix, measured by the cone angle, theta . We show that the threshold electric field required for switching this transition can be conveniently low, provided an appropriate prestrain is imposed. We suggest that these properties may give rise to a "chiral pump."

Journal Article↗
PubMed2006

Nonlinear photoresponse of disordered elastomers.

We model the polarization-dependent photocontractions of polydomain nematic elastomers. Contraction initially arises by light-induced director rotation. At higher light intensity, strain recovers because the local order parameter diminishes. Thus we predict photostrains to be nonmonotonic with light intensity and predict the induction of a negative global order parameter for the system of polydomains. Nonmonotonic strains would give curvature reversal in thick samples. Our model also predicts an elongational strain response to nonpolarized light.

Computer Simulation↗
PubMed2006

Comparison of four methods for detection of teicoplanin resistance in methicillin-resistant Staphylococcus aureus.

OBJECTIVES: To determine which method of determining the MIC of teicoplanin produces a result closely related to outcome in the critically ill patient. METHODS: Four methods of teicoplanin susceptibility testing-disc diffusion, Etest, VITEK (Legacy and VITEK 2) and agar incorporation-were compared for 47 methicillin-resistant Staphylococcus aureus (MRSA) isolates from invasive intensive care unit (ICU) infections and 83 isolates from ICU patients colonized with the organism. Clinical outcome was recorded prospectively for all the patients. Another 13 reference laboratory strains of MRSA with reduced susceptibility to teicoplanin were tested. RESULTS: Both VITEK systems failed to demonstrate resistance in the three isolates identified as resistant by Etest or agar incorporation, and disc testing detected only one resistant isolate. A higher MIC, as found by Etest or agar incorporation, was associated with lower survival (n = 130, 95% CI -0.082 to -0.006, P = 0.023, Etest; n = 130, 95% CI -0.156 to -0.020, P = 0.011, agar). The findings for the 13 reference strains were similar, with a > or = 4-fold reduction in MIC between agar incorporation or Etest and VITEK2 for six isolates. CONCLUSIONS: Neither disc diffusion nor the VITEK systems are reliable for detection of teicoplanin resistance in MRSA. Etest and agar incorporation remain the methods of choice.

Anti-Bacterial Agents↗
PubMed2006

Spontaneous shears in smectic elastomers.

We model the spontaneous elastic shear deformations of smectic elastomers as they make the thermal transition between the A and C phases. Tilt of the director is accompanied by shear. Unlike nematic elastomers where spontaneous elongation is associated with changes in the magnitude of order, spontaneous distortion in smectics is instead shear and is associated with rotation of the director of the underlying nematic order. The effect of the multistage cross-linking associated with creating monodomain elastomers is taken into account. The angle of molecular tilt and the angle associated with spontaneous shear deformation are not simply related.

Journal Article↗
PubMed2006

New developments in oestrogen signalling in colonic epithelium.

Epidemiological studies show that oestrogen reduces the risk of colorectal cancer in postmenopausal women and ERbeta (oestrogen receptor beta)-selective ligands have been reported to be very effective treatment in animal models of inflammatory bowel disease. Several studies have shown that ERbeta is the predominant ER in the colonic epithelium, but it is not clear whether the benefit of ERbeta agonists in inflammatory bowel disease are due to their action on the colon epithelium itself, or on the immune system. In order to address this issue, we have compared colons of ERbeta(-/-) and wild-type mice with regard to morphology, histology, proliferation and differentiation. We found that the number of proliferating cells was higher in ERbeta(-/-) mice, and the migration of labelled cells from base to lumen of the crypts was faster. Additionally, immunohistochemical staining revealed fewer apoptotic cells (cleaved caspase 3-positive), a significant decrease in expression of the epithelial differentiation marker, cytokeratin CK20, the adherens junction protein, alpha-catenin, and the hemidesmosomal protein, plectin, in ERbeta(-/-) mice. These findings suggest a role for ERbeta in growth, organization and maintenance of the normal colonic crypt-villus architecture. The next step is to elucidate the molecular mechanisms that underlie the signalling of ERbeta in normal cell growth and assess whether or not ERbeta agonists will be useful drugs in the prevention or treatment of colorectal cancer. Dietary phyto-oestrogens are believed to play a role in protection against colorectal cancer. Lignans, such as enterolactone, an ER agonist, prevent cancer development in animal models. Since ERbeta is the only ER in the colon, there is enough reason to speculate that phyto-oestrogens are acting through ERbeta.

Animals↗
PubMed2006

Haemophilia and ageing.

Men with haemophilia have not only the challenges of living with HIV and/or HCV infection and premature arthritis as complications of their disorder, but they also confront the other ails of ageing. These include genitourinary problems such as prostatic hypertrophy, prostatic cancer and renal stone disease, and arterial disease for which haemophilia is not protective. Progressive arthritis and declining fitness may lead to loss of independence which causes great concern. Associated with the physical aspects of ageing, many patients also suffer from psychological symptoms which may be precipitated by changes in work such as early retirement and altered family dynamics. Many older men with haemophilia may never have consulted primary care physicians because of the rarity and complexity of their disorder. Haemophilia centre staff often assume responsibility for the identification and management of all health problems of their patients. Even when other clinicians are involved, patients require their centre's involvement in the investigation and support of many procedures such as coronary artery surgery and urological surgery. This paper addresses falls in the older man with haemophilia, their causes and consequences and cardiovascular problems in particular. Very little literature has been published about these common problems. We need to be aware of the ageing issues in haemophilia and develop 'wellness' programs which are directed to the early identification of disease as well as preventative strategies to reduce the physical and psychological impacts of ageing.

Accidental Falls↗
PubMed2006

Antimicrobial susceptibility and molecular analysis of Enterococcus faecalis originating from endodontic infections in Finland and Lithuania.

BACKGROUND/AIMS: Enterococcus faecalis strains with multiple antibiotic resistances can cause infections that are difficult to treat. The microbial flora in treatment-resistant apical periodontitis is dominated by E. faecalis, and is a potential source of infections at other sites. MATERIAL AND METHODS: Sensitivities to a range of antibiotics were determined for 59 endodontic E. faecalis isolates from Finland and Lithuania. The DNA sequence of the gene responsible for the species' intrinsic quinupristin-dalfopristin resistance, lsa, was determined from two isolates with diminished resistance. Four pairs of isolates from the same root canal were typed by pulsed-field gel electrophoresis. RESULTS: A high prevalence of resistance to rifampicin was found, whereas all isolates were susceptible or showed intermediate susceptibility to penicillin and ampicillin and four isolates were unusually susceptible to cefotaxime. No vancomycin or high-level gentamicin resistance was detected. Nine of 59 isolates were susceptible to quinupristin-dalfopristin. A fully quinupristin-dalfopristin-susceptible isolate also susceptible to clindamycin produced a truncated Lsa polypeptide, and an isolate with borderline quinupristin-dalfopristin-susceptibility had mutations proximal to the predicted ribosomal binding site. Pulsed-field gel electrophoresis showed that the same root canal could harbor two different strains of E. faecalis during the course of the same infection. CONCLUSION: Despite the differing antibiotic usage in Finland and Lithuania, E. faecalis from endodontic infections in these countries showed similar susceptibility patterns with levels of resistance considered typical for the species, and decreased resistance to clindamycin and quinupristin-dalfopristin as well as lesions in the lsa gene which were similar to those described in other clinical isolates.

ATP-Binding Cassette Transporters↗
PubMed2006

The ICD-10 injury mortality diagnosis matrix.

OBJECTIVE: To standardize the presentation of the more than 1200 ICD-10 "S" and "T" codes from Chapter XIX by cross classifying the body region of injury by the nature of injury using the ICD-10 injury mortality diagnosis matrix. This paper explains the rationale for decisions made when developing the matrix and presents mortality data using the matrix. DESIGN: ICD-10 codes are organized by diagnosis groups and body regions of injury for the purpose of standardizing presentation. The categories can be collapsed to facilitate analysis at varying levels of detail. Findings from the United States 2002 injury mortality data are used as an example. MAIN OUTCOME MEASURES: All injury diagnoses mentioned in deaths with an underlying cause of injury. RESULTS: There were a total of 247,195 injury diagnoses mentioned in the 161,269 deaths with an underlying cause of injury in 2002 in the United States. The matrix can be used to show that 30% of all injury diagnoses mentioned were to the head and neck region; 28% were system wide injuries, 17% were to the torso. Open wounds accounted for 17% of all injury diagnoses mentioned, and close to half of all open wounds were traumatic brain injuries. Twenty eight percent of injury diagnoses mentioned were unspecified as to their nature and 9.5% had no body region specified. CONCLUSIONS: Multiple cause of death data are a rich but underused source of injury data often due to the complexity of the data and of the ICD classification system. Analytic techniques will need to be refined to accommodate deaths with multiple contributing injury diagnoses. The injury mortality diagnosis matrix will facilitate analysis as it is a useful tool for summarizing diagnosis data associated with injury deaths.

Cause of Death↗
PubMed2005

Chiral-mechanical transitions in topologically imprinted elastomers.

We extend a previous model for chirally imprinted monodomain nematic elastomers to allow a director rotation (by an angle pi/2-theta) towards the pitch axes of the imprinted helices. We find that provided the rubber matrix is allowed to spontaneously deform, the director array will make use of this additional degree of freedom, relaxing into a conical state in both the low and high imprinting efficiency regimes. Consequently, the transition between the regimes of differing imprinting efficiency is coupled to angle theta. This interdependence is nontrivial and involves discontinuous director rotation at the transitions.

Journal Article↗
PubMed2005

Effect of medium type, age and aeration on the MICs of tigecycline and classical tetracyclines.

BACKGROUND: Tigecycline is a minocycline derivative, belonging to a chemical class prone to oxidation and to medium-related effects on susceptibility. We therefore studied the effect of medium type and age on the tigecycline MICs found in broth and on agar by the Clinical Laboratory Standards Institute and British Society for Applied Chemotherapy methods. METHODS: MICs of tigecycline, minocycline and tetracycline were determined for 96 non-fastidious bacteria and 20 streptococci using Mueller-Hinton broth (MHB), Mueller-Hinton agar (MHA), Iso-Sensitest broth (ISB) and Iso-Sensitest agar (ISA) as: (i) freshly-prepared media; (ii) fresh media but with the antibiotic added 1 day before inoculation and (iii) media stored for 7 days before antibiotic addition and use. RESULTS: MICs of tigecycline in fresh MHB were up to two doubling dilutions higher than on or in MHA, ISA or ISB. Media with tigecycline or classical tetracyclines added a day before use gave raised MICs, though rarely by more than one dilution. MICs of tigecycline (less so classical tetracyclines) were increased in 7-day-old MHB or ISB, even though the antibiotic was freshly added. This latter effect was greatest for the most susceptible strains and was absent or much reduced for organisms with MICs > or = 8 mg/L; it did not occur in the corresponding agar dilution tests. Addition of blood to MHB largely abrogated the effect, as did steaming the broth before adding the antibiotic. CONCLUSIONS: The raised MICs of tigecycline in aged broth probably reflect inactivation by dissolved oxygen. This accords with the lack of any MIC increase in newly-steamed (i.e. degassed) MHB or on aged agar (which is melted at 100 degrees C before use). Blood, which also abrogated the effect, may increase reducing capacity, protecting the tigecycline. At a practical level, broth MIC determinations for tigecycline should always employ fresh media.

Anti-Bacterial Agents↗
PubMed2005

Getting the measure of spasticity in multiple sclerosis: the Multiple Sclerosis Spasticity Scale (MSSS-88).

Spasticity is most commonly defined as an inappropriate, velocity dependent, increase in muscle tonic stretch reflexes, due to the amplified reactivity of motor segments to sensory input. It forms one component of the upper motor neuron syndrome and often leads to muscle stiffness and disability. Spasticity can, therefore, be measured through electrophysiological, biomechanical and clinical evaluation, the last most commonly using the Ashworth scale. None of these techniques incorporate the patient experience of spasticity, nor how it affects people's daily lives. Consequently, we set out to construct a rating scale to quantify the perspectives of the impact of spasticity on people with multiple sclerosis. Qualitative methods (in-depth patient interviews and focus groups, expert opinion and literature review) were used to develop a conceptual framework of spasticity impact, and to generate a pool of items with the potential to convert this framework into a rating scale with multiple dimensions. This item pool was administered, in the form of a questionnaire, to a sample of people with multiple sclerosis and spasticity. Guided by Rasch analysis, we constructed and validated a rating scale for each component of the conceptual framework. Decisions regarding item selection were based on the integration and assimilation of seven specific analyses including clinical meaning, ordering of thresholds, fit statistics and differential item functioning. The qualitative phase (17 patient interviews, 3 focus groups) generated 144 potential scale items and a conceptual model with eight components addressing symptoms (muscle stiffness, pain and discomfort and muscle spasms,), physical impact (activities of daily living, walking and body movements) and psychosocial impact (emotional health, social functioning). The first postal survey was sent to 272 people with multiple sclerosis and had a response rate of 88%. Findings supported the development of scales for each component but demonstrated that five item response options were too many. The 144-item questionnaire, reformatted with four-item response options, was administered with four validating instruments to an independent sample of 259 people with multiple sclerosis (response rate 78%). From the responses, an 88-item instrument with eight subscales was developed that satisfied criteria for reliable and valid measurement. Correlations with other measures were consistent with predictions. The 88-item Multiple Sclerosis Spasticity Scale (MSSS-88) is a reliable and valid, patient-based, interval-level measure of the impact of spasticity in multiple sclerosis. It has the potential to advance outcomes measurement in clinical trials and clinical practice, and provides a new perspective in the clinical evaluation of spasticity.

Activities of Daily Living↗
PubMed2005

Soft elasticity in smectic elastomers.

We investigate the soft elastic modes of smectic elastomers, that is shape change without energy cost. We use a microscopic model for their nonlinear elasticity, similar to those used for nematic elastomers. We consider two different phases of smectic elastomer; the biaxial smectic A for a simple illustration, and smectic C phases which are of great practical significance. We show that only one nontrivial trajectory of the director gives soft deformations. We give a geometrical interpretation of this soft elastic mode and give an explicit example.

Journal Article↗
PubMed2005

Elasticity of smectic-A elastomers.

We present a fully nonlinear model of the elasticity smectic-A elastomers, and compare our results with a wide range of experimental observations: extreme Poisson ratios, the in-plane modulus, the modulus before and after threshold to layer rotation in response to stretches along the layer normal, the threshold strain, the characteristic, and singular rotation of layers after the threshold. We calculate the x-ray scattering from rotating layers and compare with available data. The model is derived in two ways: from geometrical constraints imposed by layers on a nematic elastomer, and from application of statistical mechanics to a microscopic model of the effect of crosslink points confined in a corrugated potential.

Journal Article↗
PubMed2005

Hairpin rubber elasticity.

We model the elastic properties of main chain liquid crystalline elastomers, formed by cross linking chains in a strongly nematic state, when they have hairpin defects. We study the response of the elastomer to imposed uniaxial extension along the nematic direction, and employ a microscopic model of how the deformation is distributed non-affinely amongst the hairpin and straight chain populations. The rubber shows a plateau in the stress as a function of the elongation imposed along the director. It is a consequence of the depletion of the actively stretching population of hairpin chains and should not be confused with soft elasticity effects associated with director rotation.

Computer Simulation↗