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Biomedical subjects

L Wallace

Publications and source records attributed to L Wallace.

At least 19 recordsLinked to original sources
PubMed2006

Leptin enhances NR2B-mediated N-methyl-D-aspartate responses via a mitogen-activated protein kinase-dependent process in cerebellar granule cells.

It is well documented that the hormone leptin regulates energy balance via its actions in the hypothalamus. However, evidence is accumulating that leptin plays a key role in numerous CNS functions. Indeed, leptin receptors are expressed in many extrahypothalamic brain regions, with high levels found in the hippocampus and cerebellum. In the hippocampus leptin has been shown to facilitate N-methyl-D-aspartate receptor function and modulate synaptic plasticity. A role for leptin in cerebellar function is also indicated as leptin-deficient rodents display reduced mobility that is unrelated to obesity. Here we show that leptin receptor immunolabeling can be detected in cultured cerebellar granule cells, being expressed at the somatic plasma membrane and also concentrated at synapses. Furthermore, leptin facilitated NR2B N-methyl-D-aspartate receptor-mediated Ca2+ influx in cerebellar granule cells via a mitogen-activated protein kinase-dependent pathway. These findings provide the first direct evidence for a cellular action of leptin in cerebellar neurons. In addition, given that N-methyl-D-aspartate receptor activity in the cerebellum is crucial for normal locomotor function, these data also have important implications for the potential role of leptin in the control of movement.

Animals↗
PubMed2004

Syphilis surveillance and epidemiology in the United Kingdom.

The aim of this article is to describe trends in infectious syphilis in the UK, and specifically the epidemiology of the London syphilis outbreak, the largest in the UK to date. Analysis of routine surveillance data from genitourinary medicine (GUM) clinics was performed as well as data collection through enhanced surveillance systems. There have been substantial increases in diagnoses of infectious syphilis between 1998 and 2003, with a 25-fold increase seen in men who have sex with men (MSM) (from 43 to 1028 diagnoses); 6-fold (138 to 860) in heterosexual men and 3-fold (112 to 338) in women. The national rise in syphilis was driven by a series of local outbreaks, the first of which occurred in 1997. To date, 1910 cases have been reported in the London outbreak, first detected in April 2001. High rates of HIV co-infection were seen among MSM, with MSM likely to be of white ethnicity and born in the UK. In contrast, heterosexuals were more likely to be of black ethnicity and born outside the UK. Most syphilis infections were acquired in London. MSM bear the brunt of the national resurgence in infectious syphilis. Substantial rises in male heterosexual cases has resulted in a divergence between male heterosexual and female cases, which now requires further investigation.

Adolescent↗
PubMed2003

Tackling children's road safety through edutainment: an evaluation of effectiveness.

The burgeoning market in electronic media has encouraged a trend toward 'edutainment', where entertaining, media-based materials are used to facilitate educational outcomes. In this study, we evaluated the effectiveness of a video that has recently been released by a popular children's entertainment group to help tackle Britain's poor record on children's road safety. We wished to determine whether the video had an impact on either children's knowledge or parents' awareness of pedestrian skills, when used in a standard home-based fashion. A total of 120 families participated, all of whom had children 5 years of age. Half the families received videos at the beginning of the study, while the other half served as a control group against which to measure change in the treatment group. Data were gathered at baseline and again 1 month later, using a series of tailored questionnaire items. A robust pattern of null findings indicated that the video, when used in this casual fashion, had no educational impact on either parents or children. Crucially, however, parents strongly believed that it had. The discussion explores the implications of such a mismatch and highlights similarities with outcomes of other health education interventions.

Accidents, Traffic↗
PubMed2001

Ductular morphogenesis and functional polarization of normal human biliary epithelial cells in three-dimensional culture.

BACKGROUND/AIMS: The understanding of the physiology and function of human biliary epithelial cells (hBEC) has been improved by studies in monolayer culture systems. The aim was to develop a polarized model to elucidate the mechanisms of ductular morphogenesis and functional differentiation of hBEC. METHODS: The morphological, phenotypic and functional properties of hBEC cultured as three-dimensional aggregates in collagen gel were assessed in medium supplemented with (or without) human hepatocyte growth factor (hHGF) and foetal bovine serum. RESULTS: In the absence of added mitogens and serum, cells maintained as morphologically polarized aggregates, organized around a central lumen, were positive for phenotypic markers of biliary epithelium and negative for markers of other cell types. Functional markers, gamma-glutamyl-transferase, anion exchanger-2, responses to gamma interferon and forskolin induced secretion, were preserved. hHGF increased both the size and number of aggregates and induced hBEC to invade the gel and lumena forming anastomosing networks of cells. CONCLUSIONS: Collagen gel culture in the absence of added growth factors and serum provides a model for analysis of the polarized functions of hBEC. The formation of poorly organized cords of cells in response to hHGF suggests that collagen gel culture may provide a model for the investigation of atypical ductular morphogenesis of the human biliary tract.

Adult↗
PubMed2001

Notch receptor expression in adult human liver: a possible role in bile duct formation and hepatic neovascularization.

Notch signaling is an evolutionarily conserved mechanism, used to regulate cell fate decisions. Four Notch receptors have been identified in man (Notch-1 to -4). In this study, semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were used to examine the expression pattern of Notch receptor genes in whole adult human liver and isolated liver cell preparations. All 4 receptors were expressed in the adult liver, with no significant differences in the levels of Notch-1, -2, and -4 messenger RNA (mRNA) between normal and diseased liver. However, Notch-3 expression appeared to be increased in diseased tissue. The distribution of Notch-1 and -4 in normal tissue was similar, with Notch-1 also detectable at low levels in the sinusoidal endothelium. Notch-2 expression was more widely distributed, and detectable in hepatocytes, medium-sized bile ducts, and the sinusoidal endothelium. Notch-3 expression was seen on hepatocytes, with weaker expression detectable in portal veins, hepatic arteries, and the sinusoids. In normal liver tissue Notch-1, -2, and -3 were found to be coexpressed on bile duct epithelium; however, with the exception of Notch-3 in primary sclerosing cholangitis (PSC) livers, expression was absent on proliferating ductules in all disease states examined. Interestingly, the expression of Notch-2 and -3 was associated with numerous small vessels within the portal tract septa of diseased tissue. The absence of Notch receptor expression on proliferating bile ductules and its presence on neovessels suggests that Notch signaling may be important for normal bile duct formation and the aberrant neovascularization seen in diseased liver tissue.

Adult↗
PubMed2001

The external review of quality improvement in health care organizations: a qualitative study.

OBJECTIVE: To explore the use of external approaches to quality improvement in health care organizations, through a descriptive evaluation of the process and impact of external reviews of clinical governance arrangements at health care provider organizations in the National Health Service (NHS) in England. DESIGN: A qualitative study, involving the use of face-to-face and telephone interviews with senior managers and clinicians in health care provider organizations and with members of a regional clinical governance review team. SETTING: The West Midlands region of England, in which there are 47 NHS trusts (health care provider organizations). STUDY PARTICIPANTS: A total of 151 senior clinicians and managers at NHS trusts in the West Midlands and 12 members of a specially constituted regional clinical governance review team. INTERVENTION: Clinical governance review visits which were undertaken by the regional clinical governance review team to all NHS trusts between April 1999 and February 2000. Interviews with senior managers and clinicians took place before and after the review visits had taken place; interviews with members of the clinical governance review team took place when they had undertaken most of their visits. RESULTS: The prospect of external review produced mixed reactions in health care provider organizations, and preparing for such a review was a substantial and time-consuming task. The review itself was often productive, although differences in attitudes and expectations between health care provider organizations and review team members created tensions, especially when the results of the review were reported back. External reviews rarely generated wholly new knowledge, were more confirmatory than revelatory, and did not usually lead to major changes in policy, strategy or practice. CONCLUSIONS: External review systems are widely used in health care to promote quality improvement in health care provider organizations, but their effectiveness is little researched and the optimal design of systems of external review is not well understood. More attention to the design and impact of external review would help to maximize its benefits and minimize costs and adverse effects.

Accreditation↗
PubMed2001

Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy.

Efavirenz (also known as DMP 266 or SUSTIVA) is a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity and of HIV-1 replication in vitro and in vivo. Most patients on efavirenz-containing regimens have sustained antiviral responses; however, rebounds in plasma viral load have been observed in some patients in association with the emergence of mutant strains of HIV-1. Virus isolates from the peripheral blood mononuclear cells (PBMCs) of patients with such treatment failures, as well as recombinant viruses incorporating viral sequences derived from patient plasma, show reduced in vitro susceptibility to efavirenz in association with mutations in the RT gene encoding K103N, Y188L, or G190S/E substitutions. Patterns of RT gene mutations and in vitro susceptibility were similar in plasma virus and in viruses isolated from PBMCs. Variant strains of HIV-1 constructed by site-directed mutagenesis confirmed the role of K103N, G190S, and Y188L substitutions in reduced susceptibility to efavirenz. Further, certain secondary mutations (V106I, V108I, Y181C, Y188H, P225H, and F227L) conferred little resistance to efavirenz as single mutations but enhanced the level of resistance of viruses carrying these mutations in combination with K103N or Y188L. Viruses with K103N or Y188L mutations, regardless of the initial selecting nonnucleoside RT inhibitor (NNRTI), exhibited cross-resistance to all of the presently available NNRTIs (efavirenz, nevirapine, and delavirdine). Some virus isolates from nevirapine or delavirdine treatment failures that lacked K103N or Y188L mutations remained susceptible to efavirenz in vitro, although the clinical significance of this finding is presently unclear.

Alkynes↗
PubMed2001

Children and road safety: increasing knowledge does not improve behaviour.

BACKGROUND: Programmes designed to teach children about road safety have often failed to assess their effectiveness in terms of either an increase in children's knowledge or an improvement in children's behaviour. AIM: The two studies reported here sought to address both issues, by focusing on the abilities of Primary 1 children (5 years old). SAMPLE: A total of 120 Primary 1 children within the age range 4-5 years old participated in this study, drawn from three different primary schools within an educational district of Scotland. METHODS: In the first study the effects of three different road safety interventions were tested, all of which employed commercially marketed products: 1) a three-dimensional model of the traffic environment; 2) a road safety board game; and 3) illustrated posters and flip-chart materials. In the second study the transfer of knowledge to children's behaviour in a real-life traffic environment was tested, using a subsample of 47 children who had taken part in the first study. RESULTS: Results from the first study showed, surprisingly, that all three interventions were effective in increasing children's knowledge about safe and dangerous locations at which to cross the street, and that this knowledge was retained for a period of six months. Study 2, however, showed that increased knowledge did not result in improved traffic behaviour. Children who had received training performed no better than children in a control group. CONCLUSION: These findings highlight the need to distinguish between children's road safety knowledge and their behaviour, particularly for teachers and parents, who may mistakenly believe that children who know more will be safer on the road.

Accident Prevention↗
PubMed2000

Probing the electronic structures of coordination compounds by transient spectral hole-burning. Applications to specifically deuterated [Ru(bpy)3]2+ complexes.

Transient spectral hole-burning (THB), a powerful technique for probing the electronic structures of coordination compounds, is applied to the lowest excited 3MLCT states of specifically deuterated [Ru(bpy)3]2+ complexes doped into crystals of racemic [Zn(bpy)3](ClO4)2. Results are consistent with and complementary to conclusions reached from excitation-line-narrowing experiments. Two sets of 3MLCT transitions are observed in conventional spectroscopy of [Ru(bpy-d(n))(3-x)(bpy-d(m))x]2+ (x = 1, 2; n = 0, 2; m = 2, 8; n not = m) complexes doped into [Zn(bpy)3](ClO4)2. The two sets coincide with the 3MLCT transitions observed for the homoleptic [Ru(bpy-d(m))3]2+ and [Ru(bpy-d(n))3]2+ complexes and can thus be assigned to localized 3MLCT transitions to the bpy-d(m) and bpy-d(n) ligands. The THB experiments presented in this paper exclude a two-site hypothesis. When spectral holes are burnt at 1.8 K into 3MLCT transitions associated with the bpy and bpy-d2 ligands in [Ru(bpy)(bpy-d8)2]2+, [Ru(bpy)2(bpy-d8)]2+, and [Ru(bpy-d2)2(bpy-d8)]2+, side holes appear in the 3MLCT transitions associated with the bpy-d8 ligands approximately 40 and approximately 30 cm(-1) higher in energy. Since energy transfer to sites 40 or 30 cm(-1) higher in energy cannot occur at 1.8 K, the experiments unequivocally establish that the two sets of 3MLCT transitions observed for [Ru(bpy-d(n))(3-x)(bpy-d(m))x]2+ (x = 1, 2) complexes in [Zn(bpy)3](ClO4)2 occur on one molecular cation.

Journal Article↗
PubMed2000

Clinical governance. Scope to improve.

A survey of all 47 trusts in the West Midlands found that clinical governance had not been advanced beyond the production of strategies, establishing committees and appointing leads. There is little evidence of the cultural change clinical governance requires. Clinical governance has yet to make a real difference at the clinical workface.

Data Collection↗
PubMed2000

Cloning and chromosomal localization of the human BARX2 homeobox protein gene.

The human BARX2 gene encodes a homeodomain-containing protein of 254 amino acids, which binds optimally to the DNA consensus sequence YYTAATGRTTTTY. BARX2 is highly expressed in adult salivary gland and is expressed at lower levels in other tissues, including mammary gland, kidney, and placenta. The BARX2 gene consists of four exons, and is located on human chromosome 11q25. This chromosomal location is within the minimal deletion region for Jacobsen syndrome, a syndrome including craniosynostosis and other developmental abnormalities. This chromosomal location, along with the reported expression of murine barx2 in craniofacial development, suggests that BARX2 may be causally involved in the craniofacial abnormalities in Jacobsen syndrome.

Amino Acid Sequence↗
PubMed2000

Mergers. Question of attitude.

Research with staff in two organisations involved in a merger revealed some convergence of cultures one year after the merger. But staff from the smaller organisation perceived some losses. Staff from both organisations felt poorly rewarded for their work. Staff from the smaller organisation perceived relationships in the organisation more positively than those in the larger one, before and after the merger. Staff saw their employers as very concerned with safety before and after the merger.

Attitude of Health Personnel↗
PubMed2000

Real-time monitoring of particles, PAH, and CO in an occupied townhouse.

Beginning in October 1996, indoor and sometimes outdoor air at an occupied house in a suburban area of Virginia has been monitored continuously for particles, PAH, and CO. Two Climet monitors have been used to count particles in six size ranges between 0.3 and > 10 microns, with 1-minute averages being collected every 5 minutes. Two Ecochem PAH monitors have been used to sample for particle-bound PAHs once every minute. Also, two Langan CO monitor-data loggers have measured CO once each minute while logging the PAH data. Two Aethalometers measure black carbon. A single Scanning Mobility Particle Sizer (SMPS) measures ultrafine particles. The pairs of monitors are set up either to provide an indoor/outdoor or an upstairs office/downstairs kitchen comparison. Air exchange is occasionally measured using a Bruel & Kjaer 1302 SF6 monitor, as a parameter necessary for estimating deposition rates for particles and PAH. Results from the first 16 months of monitoring (approximately 10 M observations) include: neighborhood woodburning and morning rush hour traffic are the most important sources of PAH and black carbon outdoors; candles, matches, incense, and frying, sauteeing, broiling, deep-frying, and stir-frying are additional important indoor sources of PM. One citronella candle was an extremely powerful PAH source. Neither woodburning nor vehicles appears to be an important source of particles indoors, but frying, grilling, and sauteeing are extremely strong indoor sources, together with combustion events such as use of matches and candles. Physical movement was an important source of coarse but not fine particles. Use of the gas stove for extended periods of time led to increased CO concentrations--vehicles and woodburning were relatively minor sources in comparison. The gas oven, gas burners, and electric toaster oven were important sources of ultrafine particles (< 0.1 micron). A source-proximity effect was noted with the kitchen monitor reading two to five times higher than the upstairs monitor for particles from kitchen events, while the upstairs monitor often read higher than the kitchen monitor for events caused by physical activity alone.

Activities of Daily Living↗
PubMed2000

Predicting particulate (PM10) personal exposure distributions using a random component superposition statistical model.

This paper presents a new statistical model designed to extend our understanding from prior personal exposure field measurements of urban populations to other cities where ambient monitoring data, but no personal exposure measurements, exist. The model partitions personal exposure into two distinct components: ambient concentration and nonambient concentration. It is assumed the ambient and nonambient concentration components are uncorrelated and add together; therefore, the model is called a random component superposition (RCS) model. The 24-hr ambient outdoor concentration is multiplied by a dimensionless "attenuation factor" between 0 and 1 to account for deposition of particles as the ambient air infiltrates indoors. The RCS model is applied to field PM10 measurement data from three large-scale personal exposure field studies: THEES (Total Human Environmental Exposure Study) in Phillipsburg, NJ; PTEAM (Particle Total Exposure Assessment Methodology) in Riverside, CA; and the Ethyl Corporation study in Toronto, Canada. Because indoor sources and activities (smoking, cooking, cleaning, the personal cloud, etc.) may be similar in similar populations, it was hypothesized that the statistical distribution of nonambient personal exposure is invariant across cities. Using a fixed 24-hr attenuation factor as a first approximation derived from regression analysis for the respondents, the distributions of nonambient PM10 personal exposures were obtained for each city. Although the mean ambient PM10 concentrations in the three cities varied from 27.9 micrograms/m3 in Toronto to 60.9 micrograms/m3 in Phillipsburg to 94.1 micrograms/m3 in Riverside, the mean nonambient components of personal exposures were found to be closer: 52.6 micrograms/m3 in Toronto; 52.4 micrograms/m3 in Phillipsburg; and 59.2 micrograms/m3 in Riverside. The three frequency distributions of the nonambient components of exposure also were similar in shape, giving support to the hypothesis that nonambient concentrations are similar across different cities and populations. These results indicate that, if the ambient concentrations were completely controlled and set to zero in all three cities, the median of the remaining personal exposures to PM10 would range from 32.0 micrograms/m3 (Toronto) to 34.4 micrograms/m3 (Phillipsburg) to 48.8 micrograms/m3 (Riverside). The highest-exposed 30% of the population in the three cities would still be exposed to 24-hr average PM10 concentrations of 47-74 micrograms/m3; the highest 20% would be exposed to concentrations of 56-92 micrograms/m3; the highest 10% to concentrations of 88-131 micrograms/m3; and the highest 5% to 133-175 micrograms/m3, due only to indoor sources and activities. The distribution for the difference between personal exposures and indoor concentrations, or the "personal cloud," also was similar in the three cities, with a mean of 30-35 micrograms/m3, suggesting that the personal cloud accounts for more than half of the nonambient component of PM10 personal exposure in the three cities. Using only the ambient measurements in Toronto, the nonambient data from THEES in Phillipsburg was used to predict the entire personal exposure distribution in Toronto. The PM10 exposure distribution predicted by the model showed reasonable agreement with the PM10 personal exposure distribution measured in Toronto. These initial results suggest that the RCS model may be a powerful tool for predicting personal exposure distributions and statistics in other cities where only ambient particle data are available.

Air Pollution↗
PubMed1999

Clinical governance. The late show.

A survey of 30 trusts in the West Midlands, conducted last summer, found only four ready to implement a plan for evidence-based medicine and clinical governance. Most chief executives had no plans to implement clinical quality systems. Shortage of clinicians' time and poor IT systems were seen as the main barriers to implementation.

Attitude of Health Personnel↗