North Wales radioactivity study.
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Geologic Sediments↗
Biomedical subjects
Paul McDonald
Publications and source records attributed to Paul McDonald.
The pharmacokinetics of an albumin-binding Fab (AB.Fab) can be modulated as a function of affinity for albumin.
An AB.Fab (albumin-binding Fab) consists of a Fab and a phage-derived albumin-binding peptide. This molecule is capable of binding both antigen and albumin simultaneously. Using a Fab derived from Herceptin we generated a panel of AB.Fab variants with wide-ranging affinities for albumin. An assay that measured AB.Fab binding to albumin in solution was developed to most accurately reflect the binding affinity for albumin in vivo. Affinity varied depending upon the species of albumin tested. For rat and rabbit albumin, affinities ranged from 0.04 to 2.5 microM. Reduced affinity for albumin correlated with a reduced half-life and higher clearance rates in both species; the beta half-life ranged 6-fold while clearance ranged over 50-fold in rats and 20-fold in rabbits. To estimate the pharmacokinetic properties of an AB.Fab in humans, AB.Fab variants with similar affinities for rat and rabbit albumin were selected. Using their pharmacokinetic parameters and the principles of allometric scaling for albumin, we estimate an approximate beta half-life for an AB.Fab with 0.5 microM affinity for albumin of up to 4 days in humans with a clearance of 76 ml/h. These variants demonstrate the ability to modulate the clearance of a Fab fragment in vivo and help to establish guidelines for pharmacokinetic engineering of molecules through albumin binding.
Albumins↗
Accumulation of technetium-99 in the Irish Sea?
An assessment has been carried out to determine the impact of continued (99)Tc discharges into the Irish Sea from the nuclear fuels reprocessing plant at Sellafield. Samples of surface and bottom seawater and sediment have been collected from the Irish Sea and analysed for (99)Tc. The information has been used, together with supporting data, to determine the effect of summer stratification upon the seawater concentrations and to evaluate whether sediments provide a sink for (99)Tc. Hydrographic data provide clear evidence of thermal stratification of waters above the muddy sediment in the western Irish Sea. Surface water contained higher (99)Tc concentrations than bottom water, and concentrations were inversely related to water salinity. This inverse relationship was not observed in the eastern Irish Sea close to Sellafield. (99)Tc activities in surficial sediments were greatest (>20 Bq/kg) at sites closest to the Cumbrian coastline. Activity, from equivalent sampling sites, remained similar between surveys carried out in 1995 and 1998. The muted response of the seabed sediments, to fluctuations in the Sellafield discharges, compared with the water column is to be expected given that they reflect the integrated radionuclide discharge history.
Environmental Monitoring↗
Histamine-induced Ca(2+) signaling in human valvular myofibroblasts.
In this study, we examined histamine-induced calcium signaling in cultured human valvular myofibroblasts (hVMFs), which are the most prominent interstitial cells in cardiac valves mediating valvular contraction, extracellular matrix secretion, and wound repair. Despite the functional importance of VMFs in cardiac valves, the cellular-signaling pathways, especially those mediated by Ca(2+), are still poorly understood. Using fluorescence imaging microscopy, we measured intracellular Ca(2+) ([Ca(2+)](i)) levels in fura-2-loaded hVMFs. Activation of H(1) receptors released Ca(2+) from one compartment of the endoplasmic reticulum (ER) of hVMFs, but did not induce Ca(2+) entry. This histamine-induced Ca(2+) release was oscillatory and dependent on Ca(2+) re-uptake into the ER by sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA). Application of the reversible SERCA blocker, cyclopiazonic acid (CPA), after depletion of the histamine-sensitive Ca(2+) store revealed the presence of a second, smaller histamine-insensitive Ca(2+) store in the ER. The Ca(2+) content ratio of the histamine-sensitive and histamine-insensitive Ca(2+) stores in the ER was found to be approximately 1.15:1. Another effect of CPA in hVMFs was the activation of store-operated Ca(2+) channels, as demonstrated by maintained [Ca(2+)](i) elevation as well as accelerated Mn(2+) entry. In conclusion, this study establishes for the first time an agonist-induced Ca(2+)-signaling pathway in hVMFs.
Calcium Signaling↗
Seeking advice from NHS direct on common childhood complaints: does it matter who answers the phone?
BACKGROUND: National Health Services (NHS) Direct is a national nurse-led, call-centre based, telephone triage, health information and advice service in the United Kingdom (UK). Forty percent of calls to NHS Direct are about children. There is a need to identify whether there is a difference in the time taken for nurses to triage calls about children. AIM: The aim of the study was to determine if the call length and outcomes of Registered Sick Children's Nurses and Registered Nurses were different when triaging children who presented with 'rash' or 'fever' by telephone. SAMPLE: This study was carried out at NHS Direct, West Midlands, and involved analysis of 1281 calls taken by 22 nurses. METHODS: This study examined the frequency of referral by the two nurse groups to five triage outcome groups. Information about the calls was extracted from routinely collected data generated by the computerized clinical decision support software. The data were used for secondary analysis. DATA ANALYSIS: The data were analysed using Statistics Package for Social Sciences version 10 and nonparametric Mann-Whitney U -tests were performed to compare call lengths of the two groups. The chi-square test was used to analyse differences in frequency of triage to outcome groups. RESULTS: The mean call length of the Registered Sick Children's Nurses was statistically significantly shorter than that of the Registered Nurses (P < 0.001). With the exception of referral for a routine appointment with a general medical practitioner, both Registered Sick Children's Nurses and Registered Nurses referred to other triage outcomes groups with equal frequency. LIMITATIONS: Inaccuracy of call length measurement of less than 1 minute and more than 20 minutes was because of the limitations of the data extraction software. This system-led definition and measured length of a call limits both the analysis and conclusions that could be drawn about the content of NHS Direct nurse consultation. CONCLUSIONS: Registered Sick Children's Nurses take less time than Registered Nurses to triage calls about children presenting with 'rash' or 'fever'. Further investigation is required into the content and consultation process of the nurses, and also the safety and appropriateness of referral.
Adolescent↗
Better practices for youth tobacco cessation: evidence of review panel.
OBJECTIVES: To offer programmers, policy makers, and researchers a scientific basis for developing and selecting smoking cessation treatments for adolescents. METHODS: An evidence review panel systematically rated published and unpublished reports of cessation treatments for youth to make recommendations on theoretical foundations, delivery settings, types of intervention, and provider type. RESULTS: Twenty studies had sufficient validity to inform the recommendations. The 9 studies that reported treatments that increased cessation were based on social cognitive theory. CONCLUSIONS: Cognitive-behavioral interventions are a promising approach for helping young smokers quit smoking. Evidence is insufficient to draw other conclusions at this time.
Adolescent↗
Improving the future of youth smoking cessation.
OBJECTIVES: To provide recommendations that will build a better foundation for research on youth smoking cessation. METHODS: The Youth Tobacco Collaborative Cessation panel evaluated youth tobacco cessation literature and convened meetings to reach consensus. RESULTS: Methodological issues include design, recruitment and retention, follow-up, measurement, and youth vernacular. Research gaps include youth characteristics, theoretical approaches, delivery settings, and type of provider. Thirteen key research components for reporting are addressed. CONCLUSIONS: Given the dearth of studies on youth smoking cessation, scientifically rigorous studies need to be conducted with attention to methodological issues, research gaps, and reporting of key research components.
Adolescent↗
Methodological issues in measuring treatment outcome in adolescent smoking cessation studies.
As the prevalence of adolescent smoking and, notably, regular smoking has increased over the last decade, researchers and practitioners have called for a consideration of treatment programs to promote cessation among adolescents who smoke. The adolescent smoking cessation treatment field is still in its infancy, though. The literature addressing adolescent cessation is rather limited to date, often plagued by methodological problems and characterized by little success. Many basic methodological questions remain for researchers to address before we will be able to answer questions such as which treatment approaches work best for which adolescent smokers. The purpose of this paper is to review briefly what is known about adolescent smoking cessation, to identify some important methodological issues to consider in treatment outcome studies, and to make recommendations to researchers to help provide a common ground for future comparisons of results across studies. We will address the natural history of adolescent smoking cessation, treatment outcomes, validity of self-reports and biochemical validation, and research recommendations.
Adolescent↗