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Biomedical subjects

C Hughes

Publications and source records attributed to C Hughes.

At least 37 records · Page 2Linked to original sources

Evaluation of the IRIS 939 UDx flow microscope as a screening system for urinary tract infection.

AIMS: To evaluate the IRIS flow microscope for the examination of urine specimens and to compare its performance with that of manual methods; in addition, to assess its usefulness as a screening system for the detection of significant bacteriuria in a routine clinical laboratory. METHODS: The IRIS system was compared with manual quantitative microscopy for the detection of formed elements and with a variety of culture methods to detect urinary tract infection. RESULTS: The IRIS had a higher sensitivity for the detection of clinically significant formed elements than did manual methods, and using a combination of bacterial and white cell counts produced a sensitivity and specificity of 94.9% and 54.4%, respectively, for predicting positive significant growth, with a 98.5% predictive value for a negative result. Approximately 50% of specimens could be reported as negative on the day of receipt using the screening algorithm. CONCLUSIONS: The sensitivity and specificity of the IRIS is equivalent to that of other automated screening systems and would remove the need for manual microscopy for most specimens. The system was easy to operate and is a useful addition to the methods currently available for the examination of urine specimens.

Bacteriuria↗

Malaria prophylaxis for long-term travellers.

These guidelines are designed to assist healthcare workers who are advising long-term travellers on malaria prophylaxis, defined for the purpose of this document as those travelling for longer than 6 months. The document focuses on long-term use of antimalarials for adults, but also identifies specific issues for women and children. However, data on the long-term use of antimalarials is limited for all travellers and few data are available on the incidence of malaria in travellers overseas or, indeed, deaths overseas from malaria. Whilst all available evidence is taken into account, the advice provided also reflects experienced professional opinion. This document has been written on behalf of the Health Protection Agency's Advisory Committee on Malaria Prevention for UK Travellers, and is designed to act as a supplement to the 'Guidelines for malaria prevention in travellers from the United Kingdom for 2003'. The latter document contains a more complete description of antimalarials and additional preventive measures, together with recommendations for malaria chemoprophylaxis for individuals countries. Decisions on the terms under which different drugs are licensed for use are the responsibility of the Committee on Safety of Medicines. This paper should also, therefore, be used in conjunction with Summary of Product Characteristics (data sheets).

Adult↗

Electrophysiological behavior of the TolC channel-tunnel in planar lipid bilayers.

Escherichia coli TolC assembles into the unique channel-tunnel structure spanning the outer membrane and periplasmic space. The structure is constricted only at the periplasmic entrance of the tunnel and this must be opened to allow export of substrates bound by cognate inner membrane complexes. We have investigated the electrophysiological behavior of TolC reconstituted into planar lipid bilayers, in particular the influence of the membrane potential, the electrolyte concentration and pH. TolC inserted in one orientation into the membrane. The resultant pores were stable and showed no voltage-dependent opening or closing. Nevertheless, TolC could adopt up to three conductance substates. The pores were cation-selective with a permeability ratio of potassium to chloride ions of 16.5. The single-channel conductance was higher when the protein was inserted from the side with negative potential. It showed a nonlinear dependence on the concentration of the electrolyte in the bulk solution and decreased as the pH was lowered. The calculated pK of the apparent closing was 4.5. The electrophysiological characterization is discussed in relation to the TolC structure, in particular the periplasmic entrance.

Bacterial Outer Membrane Proteins↗

Extracranial fasciitis in childhood: a sheep in wolf's clothing.

Soft tissue tumours in children are rare, and the differentiation between pseudosarcomatous tumours and sarcomas is difficult. Rapidly-enlarging masses within the head and neck region in infants require rapid diagnosis and prompt definitive treatment to lessen psychological burden on the parents and the surgical team. We present a case of a 17-month-old girl who had a large, rapidly-enlarging soft tissue mass within the maxilla which was excised. The diagnosis of childhood extracranial fasciitis was confirmed histopathologically. We emphasise the importance of conservative excision once the diagnosis has been confirmed.

Diagnosis, Differential↗

Metallothionein in bovine spongiform encephalopathy.

An increase in metallothionein I and II (MT I/II) mRNA concentrations has been reported in the central nervous system of scrapie-infected rodents. In this study we compared cattle with bovine spongiform encephalopathy (BSE), cattle affected by neurological disease other than BSE, and clinically healthy cattle in respect of MT I/II immunoreactivity in brainstem medullary tissue. Marked astrocytic MT I/II immunolabelling was seen in all BSE-affected animals, in contrast to clinically healthy cases, in which no such labelling was detected. In BSE, MT I/II immunoreactive astrocytes were confined specifically to areas of vacuolation or abnormal prion protein (PrP(BSE)) deposition, or both. MT I/II immunolabelling was also seen in a small number of animals with a neurological disease other than BSE. These findings complement previous studies by demonstrating increased levels of MT I/II in transmissible spongiform encephalopathy (TSE)-infected brain tissue, indicating that MT I/II may play some as yet unidentified role in the response to TSE infection.

Animals↗

A test battery of child development for examining functional vision (ABCDEFV).

A battery of 22 tests is described, intended to give an integrated assessment of children's functional visual capacities between birth and four years of age. As well as sensory visual measures such as acuity, visual fields and stereopsis, the battery is intended to tap a range of perceptual, motor, spatial and cognitive aspects of visual function. Tests have been drawn from practice in ophthalmology and orthoptics, vision research, paediatric neurology, and developmental psychology to give an overall view of children's visual competences for guidance in diagnosis, further investigation, management and rehabilitation of children with developmental disorders. 'Core vision tests' require no motoric capacities beyond saccadic eye movements or linguistic skills and so assess basic visual capacities in children of any age. 'Additional tests' have age-specific requirements and are designed to pinpoint specific deficits in the perceptual, visuo-motor and spatio-cognitive domains. Normative data are reported on nine age groups between 0-6 weeks and 31-36 months, each including 32-43 typically developing children. Pass/fail criteria for each test are defined. These data allow the selection of a subset of tests for each age group which are passed by at least 85% of normally developing children, and so are appropriate for defining normal development. The normalized battery has been applied to a range of at-risk and clinical groups. Aspects of children's visual performance are discussed in relation to neurobiological models of visual development.

Child Development↗

Caring for the chronically ill: a clinic for final-year medical students.

In 2000 the Diabetes Centre and the Medical Oncology Department of St Vincent's Hospital, Sydney established a joint clinic for the teaching of final-year medical students. The clinic was established amid concerns that hospitals are increasingly focused on acute care and have few resources available for teaching about chronic conditions. The clinic aimed to improve both patient care and learning opportunities by engaging students in useful activities with chronically ill patients. The students met with their patients regularly to monitor progress, adjust medication (under supervision) and arrange support services. The students and staff from both units met once a week in a coordination meeting where cases were reviewed and learning issues discussed. Students had informal interactions with medical and allied health staff at other times. Overall the clinic provided a rich learning environment for students with a focus on the development of the integrated skills required in the care of chronically ill people, rather than on the specific medical disciplines involved.

Adult↗

Substrate-triggered recruitment of the TolC channel-tunnel during type I export of hemolysin by Escherichia coli.

A defining event in type I export of hemolysin by Escherichia coli is the substrate-triggered recruitment of the TolC channel-tunnel by an inner membrane complex. This complex comprises a traffic ATPase (HlyB) and the 478 residue adaptor protein (HlyD), which contacts TolC during recruitment. HlyD has a large periplasmic domain (amino acid residues 81-478) linked by a single transmembrane helix to a small N-terminal cytosolic domain (1-59). Export was disabled by deletion of the ca 60 amino acid residue cytosolic domain of HlyD, even though the truncated HlyD (HlyDDelta45) was, like the wild-type, able to trimerise in the cytosolic membrane, and interact with the traffic ATPase. The mutant HlyB/HlyDDelta45 inner membrane complex engaged the hemolysin substrate, but this substrate-engaged complex failed to trigger recruitment of TolC. Further analyses showed that HlyDDelta45 was specifically unable to bind the substrate. The result suggests that substrate engagement by the traffic ATPase alone is insufficient to trigger TolC recruitment, and that substrate binding to the HlyD cytosolic domain is essential. Analysis of three further N-terminal deletion variants, HlyDDelta26, HlyDDelta26-45 and HlyDDelta34-38, indicated that an extreme N-terminal amphipathic helix and a cytosolic cluster of charged residues are central to the cytosolic domain function. The cytosolic amphipathic helix was not essential for substrate engagement or TolC recruitment, but export was impaired without it. In contrast, when the charged amino acid residues were deleted, the substrate was still engaged by HlyD but engagement was unproductive, i.e. TolC recruitment was not triggered. Our results are compatible with the HlyD cytosolic domain mediating transduction of the substrate binding signal directly, presumably to the HlyD periplasmic domain, to trigger recruitment of TolC and assemble the type I export complex.

ATP-Binding Cassette Transporters↗

A guinea pig model of low-dose Mycobacterium bovis aerogenic infection.

In order to develop a model of Mycobacterium bovis infection with pathogenetical relevance, a modified version of the Henderson apparatus was used to deliver infectious aerosols directly to the snouts of guinea pigs. Aerosols generated from 10(6), 10(7), 10(8)CFU/ml M. bovis suspensions established disease in every animal, with estimated retained doses of 10, 100, 1000 CFU, respectively. For comparison, other guinea pigs were inoculated with 100 CFU M. bovis intramuscularly (i.m.). Pathology and bacterial colonisation of lungs and spleen varied according to the dose and route of inoculation. Animals inoculated i.m. gave a significant cutaneous tuberculin hypersensitivity reaction earlier after testing than those infected aerogenically. A serological response to M. bovis antigens was detected in all infected animals. Intensity of antigen recognition was dose-dependent and although the range of antigens recognised varied between animals, a 25 kDa antigen present in the cell fraction was serodominant. Thus, a reproducible guinea pig model has been defined that may be suitable for virulence, vaccination, and immunological studies.

Administration, Intranasal↗

Flagellin polymerisation control by a cytosolic export chaperone.

Assembly of the long helical filament of the bacterial flagellum requires polymerisation of ca 20,000 flagellin (FliC) monomeric subunits into the growing structure extending from the cell surface. Here, we show that export of Salmonella flagellin is facilitated specifically by a cytosolic protein, FliS, and that FliS binds to the FliC C-terminal helical domain, which contributes to stabilisation of flagellin subunit interactions during polymerisation. Stable complexes of FliS with flagellin were assembled efficiently in vitro, apparently by FliS homodimers binding to FliC monomers. The data suggest that FliS acts as a substrate-specific chaperone, preventing premature interaction of newly synthesised flagellin subunits in the cytosol. Compatible with this view, FliS was able to prevent in vitro polymerisation of FliC into filaments.

Bacterial Proteins↗

Statistical assessment of violations of water quality standards under Section 303(d) of the clean water act.

Section 303(d) of the Clean Water Act requires states to assess the condition of their waters and to implement plans to improve the quality of waters identified as impaired. U.S. Environmental Protection Agency guidelines require a stream segment to be listed as impaired when greater than 10% of the measurements of water quality conditions exceed numeric criteria. This can be termed a "raw score" assessment approach. Water quality measurements are samples taken from a population of water quality conditions. Concentrations of pollutants vary naturally, measurement errors may be made, and occasional violations of a standard may be tolerable. Therefore, it is reasonable to view the assessment process as a statistical decision problem. Assessment of water quality conditions must be cognizant of the possibility of type I (a false declaration of standards violation) and type II (a false declaration of no violation) errors. The raw score approach is shown to have a high type I error rate. Alternatives to the raw score approach are the Binomial test and the Bayesian Binomial approach. These methods use the same information to make decisions but allow for control of the error rates. The two statistical methods differ based on consideration of prior information about violation. Falsely concluding that a water segment is impaired results in unnecessary planning and pollution control implementation costs. On the other hand, falsely concluding that a segment is not impaired may pose a risk to human health or to the services of the aquatic environment. An approach that recognizes type I and type II error in the water quality assessment process is suggested.

Bayes Theorem↗

Transition to adulthood: supporting young adults to access social, employment, and civic pursuits.

"Transition support" is a concept new to the field of secondary transition. This paper describes the development of a model of transition support as derived from the empirical literature (Hughes and Carter. [2000] The Transition Handbook. Baltimore, MD: Paul H. Brookes). The components of the Transition Support Model are both empirically based and field-tested among practitioners. The over 500 transition support strategies that compose the model have been used by practitioners in the field to improve educational and postschool outcomes for high school students. These strategies are grouped according to two main goals (i.e., "developing support in the environment" and "increasing students' competence") and corresponding components. Literature supporting the Transition Support Model is described as well as the use of the model in the transition planning process. Suggestions are made for application of transition support in high schools and the need for future research. MRDD Research Reviews 7:84-90, 2001. (c) 2001 Wiley-Liss, Inc.

Adolescent↗

Streptavidin paramagnetic particles provide a choice of three affinity-based capture and magnetic concentration strategies for retroviral vectors.

Three strategies have been designed to concentrate infectious retroviral vectors from the supernatants of human- (HT1080) and murine- (NIH 3T3) based packaging cells. Streptavidin-conjugated paramagnetic particles in conjunction with (i) antibodies directed against murine fibronectin, (ii) biotinylated lectins, or (iii) biotin-modified packaging cell-surface proteins allow affinity-mediated magnetic concentration of retroviral vectors. Retroviral titers (assayed by colony formation of human myeloid K562 cells) are increased by 1-4 x 10(3)-fold after volume reductions of only 125-fold. Using these procedures, preparations of 5 x 10(8) cfu/ml are routinely made from relatively low-titer (2-5 x 10(5) cfu/ml) starting material. High-titer (paramagnetic) retroviral vector preparations can be used for magnetic field-dependent retroviral infection in vitro. Magnetic field-dependent localization such as this may enable the in vivo administration of formulations that concentrate retroviral infection to the required target tissues and organs.

3T3 Cells↗

Smoking is associated with increased hepatic lipase activity, insulin resistance, dyslipidaemia and early atherosclerosis in Type 2 diabetes.

We have studied the relationships between hepatic lipase activity, smoking, dyslipidaemia insulin resistance, and early atherosclerosis in 67 Type 2 diabetic subjects, 47 non-smokers and 20 smokers. Insulin resistance was measured using an insulin modified frequently sampled intravenous glucose tolerance test. Early atherosclerosis was assessed using high-resolution ultrasound to measure carotid intima media thickness (IMT) and an arterial ultrasonic score (AUS). Smokers had higher serum cholesterol and triglyceride, lower HDL and HDL2 cholesterol as well as increased hepatic lipase activity. They were also more insulin resistant than non-smokers. Smokers also had higher patient AUS scores. On multiple regression analysis, hepatic lipase activity emerged as the most significant variable affecting patient AUS. We suggest that smoking accentuates the dyslipidaemia of Type 2 diabetic subjects and this is associated with increased hepatic lipase activity. This may be one mechanism whereby smoking further increases the risk of cardiovascular disease in Type 2 diabetes.

Adult↗

Gait characteristics of patients with knee osteoarthritis.

The knee kinematics and kinetics of 139 patients (47 males and 92 females) with Grade II knee osteoarthritis (OA) were measured during level walking, stair ascent and stair descent. There was no significant difference in knee motion between the patients and normal subjects. The patients with knee OA had a significantly reduced internal knee extensor moment compared to normal subjects. This difference reflects the patient's compensation to reduce the knee joint loading. Further, subjects with OA and a higher body mass index have a lower knee extensor moment. The female subjects had significantly greater knee flexion and a greater knee extensor moment. This gender difference may partially explain the increased prevalence of OA in females. Most tests of OA treatments are assessed by criteria that do not reflect functional activities. This study demonstrates that objective gait analysis can be used to document gait adaptations used by patients with knee OA.

Adaptation, Physiological↗

Parental communication of BRCA1/2 genetic test results to children.

The aim of this study was to evaluate the likelihood, correlates, and psychological impact of parental communication to children of parents' BRCA1/2 genetic test results for breast cancer risk. Subjects were 133 adult members of high risk families. Sociodemographic, clinical, and psychological distress variables were assessed during a baseline telephone interview conducted prior to patient education and test result notification. Parental communication of test results to children and parental psychological distress and coping efforts were assessed 1 month post-genetic counseling and receipt of test results. Mothers (versus fathers), and persons with higher levels of baseline general distress, were significantly more likely to communicate their test results to children. Post-counseling coping efforts, both active and avoidant, were positively associated with post-counseling distress levels. However, communication of test results to children did not relate to changes in distress. In conclusion, parents with higher levels of pre-counseling general psychological distress may be more likely to communicate their genetic test results to children; however, this act does not minimize their distress and could possibly generate distress in their youngsters. Research is needed to evaluate the process and content of post-test disclosure episodes and the impact on participant, child, and family functioning.

Adaptation, Psychological↗

Protein export and drug efflux through bacterial channel-tunnels.

The bacterial protein TolC assembles into an alpha-helical trans-periplasmic tunnel, which is embedded in the outer membrane by a contiguous beta-barrel channel. TolC and its homologues thus provide large exit ducts for a wide range of substrates, including protein toxins and antibacterial drugs, that are engaged by specific recognition proteins in the cytosolic membrane.

Bacterial Outer Membrane Proteins↗