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Biomedical subjects

D Chambers

Publications and source records attributed to D Chambers.

At least 19 recordsLinked to original sources
PubMed2006

Radiation transfer effects on the spectra of laser-generated plasmas.

Experimental x-ray spectra of the H-like 2p --> 1s (Lyman-alpha) doublet have been obtained using time-integrated high-resolution spectroscopy of a constrained-flow, laser-generated aluminum plasma. These spectra show monotonic alteration of the relative intensities of the doublet components with distance from the target surface. Excellent agreement between experiment and theory is found only if the modeling includes both ion collisional rates between the fine-structure components of the level and, more importantly, the radiative pumping of one Lyman-alpha component by the other component along the direction of the major velocity gradient (i.e., perpendicular to the direction of spectra observation). Understanding radiation transfer in plasmas with high velocity gradients is important in modeling many astrophysical objects, and this experiment acts as a benchmark for such complex calculations.

Journal Article↗
PubMed2005

Factors associated with infection by Pseudomonas aeruginosa in adult cystic fibrosis.

Cross-infection with Pseudomonas aeruginosa is an emerging issue in the care of patients with cystic fibrosis (CF). This study sought to determine the extent of, and patient factors associated with, cross-infection in a tertiary referral adult CF centre. P. aeruginosa isolates were genotyped into two groups between November 2001 and February 2003, using pulsed-field gel electrophoresis after DNA digestion by the SpeI endonuclease, and identified as clustered if there was >80% homology in the macrorestriction profiles. Patient factors and measures of disease severity were identified a priori. In total, 157 out of 227 patients had a P. aeruginosa isolate genotyped. Of these, 94 patients (60%) were infected with clustered genotypes and 47 (30%) were infected with the newly described "Midlands 1" (Md1) genotype. A further 18 patients were infected with the previously identified "Liverpool" genotype and two with the "Manchester" genotype. Logistic regression analysis revealed that the predominant predictor of infection with Md1 was age at the time of referral to the centre, suggesting that infection may have occurred prior to referral in some patients. Md1 demonstrated a relatively benign anti-biogram and did not appear to be associated with more severe disease. In conclusion, the present study provides further evidence of the emerging importance of Pseudomonas aeruginosa cross-infection in cystic fibrosis.

Adult↗
PubMed2005

Oesophageal foreign bodies at the University Hospital of the West Indies.

A retrospective study was conducted of 97 patients with oesophageal foreign bodies (EFB). The patients were admitted to assess characteristics of EFB, modes of presentation and radiological and endoscopic findings. The patients were from the University Hospital of the West Indies and most (42%) were over the fourth decade of life. The commonest EFB were bones. A negative radiological finding was not a reliable means to select patients for endoscopy. Oesophagoscopy is a reliable method in the treatment of EFB impaction. There were no major complications or deaths.

Bone and Bones↗
PubMed2001

Feasibility of postexposure prophylaxis (PEP) against human immunodeficiency virus infection after sexual or injection drug use exposure: the San Francisco PEP Study.

The feasibility of providing postexposure prophylaxis (PEP) after sexual or injection drug use exposures to human immunodeficiency virus (HIV) was evaluated. PEP was provided within 72 h to individuals with exposures from partners known to have or to be at risk for HIV infection. PEP consisted of 4 weeks of antiretroviral medications and individually tailored risk-reduction and medication-adherence counseling. Among 401 participants seeking PEP, sexual exposures were most common (94%; n=375). Among sexual exposures, receptive (40%) and insertive (27%) anal intercourse were the most common sexual acts. The median time from exposure to treatment was 33 h. Ninety-seven percent of participants were treated exclusively with dual reverse-transcriptase inhibitors, and 78% completed the 4-week treatment. Six months after the exposure, no participant developed HIV antibodies, although a second PEP course for a subsequent exposure was provided to 12%. PEP, after nonoccupational HIV exposure, is feasible for persons at risk for HIV infection.

Adolescent↗
PubMed2001

Understanding the role of opinion leaders in improving clinical effectiveness.

We present findings from evaluations of two government-funded initiatives exploring the transfer of research evidence into clinical practice--the PACE Programme (Promoting Action on Clinical Effectiveness), and the Welsh Clinical Effectiveness Initiative National Demonstration Projects. We situate the findings within the context of available research evidence from healthcare and other settings on the role of opinion leaders or product champions in innovation and change--evidence which leaves a number of problems and unanswered questions. A major concern is the difficulty of achieving a single replicable description of what opinion leaders are and what they do--subjective understandings of their role differ from one setting to another, and we identify a range of very different types of opinion leadership. What makes someone a credible and influential authority is derived not just from their own personality and skills and the dynamic of their relationship with other individuals, but also from other context-specific factors. We examine the question of expert versus peer opinion leaders, and the potential for these different categories to be more or less influential at different stages in the innovation process. An often neglected area is the impact of opinion leaders who are ambivalent or hostile to an innovation. Finally, we note that the interaction between individual opinion leaders and the collective process of negotiating a change and reorienting professional norms remains poorly understood. This raises a number of methodological concerns which need to be considered in further research in this area.

Evidence-Based Medicine↗
PubMed2001

Implementation of evidence-based medicine: evaluation of the Promoting Action on Clinical Effectiveness programme.

OBJECTIVES: To evaluate the Promoting Action on Clinical Effectiveness (PACE) programme, which sought to implement clinically effective practice in 16 local sites. METHODS: 182 semi-structured interviews, usually by telephone, with project team members, clinicians, and senior managers and representatives from the Department of Health and the King's Fund. RESULTS: The most influential factors were strong evidence, supportive opinion leaders and integration within a committed organization; without these factors, projects had little chance of success. Other factors (context analysis, professional involvement and good project management) emerged as important, supporting processes; their presence might be an additional help, but on their own they would not be enough to initiate change. A serious problem with any of them could have a strong adverse impact. CONCLUSIONS: Although there is no simple formula for the factors that ensure successful implementation of research-based improvements to clinical practice, certain principles do seem to help. Time and resource need to be devoted to a period of local negotiation and adaptation of good research evidence based on a careful understanding of the local context, in which opinion leader influence is an important component of a well managed and preferably well integrated process of change.

Diffusion of Innovation↗
PubMed2001

Designing a consumer friendly practice.

BACKGROUND: With the threat of corporate practice looming, smaller private general practices need to define their role in order to attract patients (consumers) and doctors, to build and maintain a successful practice. OBJECTIVE: To outline various means of instituting a consumer friendly practice. DISCUSSION: Consider what consumers want. Bearing in mind these aims, build the physical aspects of your practice to respond to the needs of consumers, and develop practice activity, philosophy and culture which satisfy the desires of consumers and those of the doctors and staff who work in your practice. Creating a consumer friendly practice attracts patients, Practice Incentive Payments, and prepares for accreditation. By developing such a culture, general practitioners can build, support and maintain the practice style they prefer, even in the face of competition.

Family Practice↗
PubMed2000

Expression of sprouty2 during early development of the chick embryo is coincident with known sites of FGF signalling.

The Drosophila sprouty protein is a recently-identified intracellular modulator of FGF and EGF receptor tyrosine kinase activity which antagonises ras/MAP kinase signalling. In a differential display analysis to identify genes involved in patterning the mid/hindbrain region of the chick neural tube, we have identified a sprouty orthologue, sprouty2. Here we report expression of sprouty2 transcripts in the developing chick embryo. We find a close correlation with known sites of FGF activity but little correlation with expression patterns of members of the EGF family. Initially, transcripts are associated with the primitive streak. During the period of neural tube patterning expression is detected in the anterior neuropore, in the isthmic region and in neural plate and posterior spinal cord. Transcripts are also detected in the otic placode, tail bud, mesoderm of the branchial arches, somitic myotome, retina, limb buds and gut mesenchyme; all known sites of FGF action.

Animals↗
PubMed2000

Differential display of genes expressed at the midbrain - hindbrain junction identifies sprouty2: an FGF8-inducible member of a family of intracellular FGF antagonists.

Specification and polarization of the midbrain and anterior hindbrain involve planar signals originating from the isthmus. Current evidence suggests that FGF8, expressed at the isthmus, provides this patterning influence. In this study, we have sought to identify novel genes which are involved in the process by which regional identity is imparted to midbrain and anterior hindbrain (rhombomere 1). An enhanced differential display reverse transcription method was used to clone cDNAs derived from transcripts expressed specifically in either rhombomere 1 or midbrain during the period of isthmic patterning activity. This gene expression screen identified 28 differentially expressed cDNAs. A clone upregulated in cDNA derived from rhombomere 1 tissue showed a 91% identity at the nucleotide level to the putative human receptor tyrosine kinase antagonist: sprouty2. In situ hybridization on whole chick embryos showed chick sprouty2 to be expressed initially within the isthmus and rhombomere 1, spatially and temporally coincident with Fgf8 expression. However, at later stages this domain was more extensive than that of Fgf8. Introduction of ligand-coated beads into either midbrain or hindbrain region revealed that sprouty2 could be rapidly induced by FGF8. These data suggest that sprouty2 participates in a negative feedback regulatory loop to modulate the patterning activity of FGF8 at the isthmus.

Amino Acid Sequence↗
PubMed2000

Microperfusion techniques for long-term hypothermic preservation.

BACKGROUND: The aim of this study was to compare several methods of hypothermic heart preservation. METHODS: We preserved isolated pig hearts for 24 hours in cold cardioplegia (4 degrees C), using either continuous microperfusion (Group I) or simple storage (Group II), and with a new preservative solution (NPS, groups IA and IIA) vs St. Thomas' solution (groups IB and IIB). The main characteristics of the NPS include (1) prevention of cell swelling with polyethelene glycol (PEG), (2) low calcium and magnesium, and (3) presence of metabolic substrates, such as glucose, insulin, pyruvate, aspartate, alanyl-glutamine, and membrane stabilization compounds such as ethanol and chlorpromazine. RESULTS: The 4 above groups were compared with hearts harvested and immediately reperfused (control group). During preservation, only Group IB showed significant edema (40% +/- 8.4% water gain). Adenylate charge was 25% to 50% higher in microperfused Groups IA and IB (0.678 +/- 0.049 and 0.795 +/- 0.071, respectively) as compared with simple-storage groups IIA and IIB (0.605 +/- 0.048 and 0.524 +/- 0.160, respectively). Ultrastructural analysis showed that tissue injury occurred mainly in Group IIB (altered mitochondria, chromatin clumping). Functional data showed better recovery of NPS groups as compared with St. Thomas groups: coronary flow was identical in Group IB and control (57.8 +/- 22 and 56.6 +/- 14 ml/min/100 g, respectively), and in IA > IB (p < 0.001) and IIA > IIB (p < 0.01); the rate pressure products were higher in NPS groups compared with St. Thomas groups (IA > IB, p < 0.01); IIA > IIB, p < 0.05). CONCLUSIONS: The microperfusion method associated with the NPS provides excellent protection in long-term hypothermic heart preservation.

Animals↗
PubMed2000

Mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice.

Analysis of classical mouse mutations has been useful in the identification and study of many genes. We previously mapped Sox18, encoding an SRY-related transcription factor, to distal mouse chromosome 2. This region contains a known mouse mutation, ragged (Ra), that affects the coat and vasculature. Here we have directly evaluated Sox18 as a candidate for Ra. We found that Sox18 is expressed in the developing vascular endothelium and hair follicles in mouse embryos. Furthermore, we found no recombination between Sox18 and Ra in an interspecific backcross segregating for the Ra phenotype. We found point mutations in Sox18 in two different Ra alleles that result in missense translation and premature truncation of the encoded protein. Fusion proteins containing these mutations lack the ability to activate transcription relative to wild-type controls in an in vitro assay. Our observations implicate mutations in Sox18 as the underlying cause of the Ra phenotype, and identify Sox18 as a critical gene for cardiovascular and hair follicle formation.

Alleles↗
PubMed2000

ERM-Merlin and EBP50 protein families in plasma membrane organization and function.

The ezrin-radixin-moesin (ERM) family of proteins have emerged as key regulatory molecules in linking F-actin to specific membrane proteins, especially in cell surface structures. Merlin, the product of the NF2 tumor suppressor gene, has sequence similarity to ERM proteins and binds to some of the same membrane proteins, but lacks a C-terminal F-actin binding site. In this review we discuss how ERM proteins and merlin are negatively regulated by an intramolecular association between their N- and C-terminal domains. Activation of at least ERM proteins can be accomplished by C-terminal phosphorylation in the presence of PIP2. We also discuss membrane proteins to which ERM and merlin bind, including those making an indirect linkage through the PDZ-containing adaptor molecules EBP50 and E3KARP. Finally, the function of these proteins in cortical structure, endocytic traffic, signal transduction, and growth control is discussed.

Animals↗
PubMed2000

Transfer of telemedical support to Cornwall from a national telemedicine network during a solar eclipse.

During late 1998 and early 1999, planning officers in Cornwall predicted a huge increase in summer visitors to the county to observe the August solar eclipse. There was the possibility that a mass gathering in Cornwall could overload existing arrangements for handling accident and emergency patients. We therefore set up a telemedicine system to support the county's minor injury units (MIUs) from hospitals throughout the UK. Six main hospital accident and emergency departments outside Cornwall with existing links to their own MIUs were twinned with 10 of the 11 MIUs in Cornwall before the expected date of the gathering. The network was live for nine days, starting four days before the eclipse, and 2045 patients were seen in the 10 MIUs. There were 93 telemedicine calls from the 10 MIUs, involving 91 patients. Overall, 4.6% of the patients required a telemedicine consultation. Fifty-seven calls were made during working hours. Thirty-four patients were referred for further management, of whom 18 were referred on the same day. The transfer of telemedical support to a national network was successful.

Emergency Medical Services↗
PubMed2000

Regulation and function of FGF8 in patterning of midbrain and anterior hindbrain.

In this article, an adjunct to a platform presentation at the Winternational 2000 Symposium, we summarize the recent findings of this group concerning the regulation and functions of FGF8 expressed at the isthmus of the developing brain. We show that several different FGF8 isoforms, ectopically expressed in midbrain or posterior forebrain, are able to mimic the proliferative and patterning functions previously attributed to the isthmus in tissue grafting studies. Moreover, we also show that FGF8 protein is sufficient to induce an ectopic isthmic organiser (Fgf-8+, Gbx2+) in anterior midbrain. We also provide evidence that isthmic FGF8 patterns anterior hindbrain, repressing Hox-a2 expression and setting aside a territory of the brain that includes the cerebellar anlage. We show that these effects of FGF8 are likely to be mediated via FGFR1 and be modulated by the putative FGF antagonist, Sprouty2, identified using a differential display screen. Finally, we provide evidence that the onset of Fgf8 expression is regulated by En1 and that its expression at the isthmus is subsequently maintained by a specific and direct interaction between rhombomere 1 and midbrain.

Animals↗