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Biomedical subjects

Andrew G Davies

Publications and source records attributed to Andrew G Davies.

6 recordsLinked to original sources
PubMed2006

Do flat detector cardiac X-ray systems convey advantages over image-intensifier-based systems? Study comparing X-ray dose and image quality.

The recent introduction of "flat-panel detector" (FD)-based cardiac catheterisation laboratories should offer improvements in image quality and/or dose efficiency over X-ray systems of conventional design. We compared three X-ray systems, one image-intensifier (II)-based system (system A), and two FD-based designs (systems B and C), assessing their image quality and dose efficiency. Phantom measurements were performed to assess dose rates in fluoroscopy and cine acquisition. Phantom dose rates were broadly similar for all systems, with all systems classified as offering "low" dose rates in fluoroscopy on standard phantoms. Patient X-ray dose rate and subjective image quality was assessed for 90 patients. Dose area product (DAP) rates were similar for all systems, except system C, which had a lower DAP rate in fluoroscopy. In terms of subjective image quality, the order of preference was (best to worst): system C, system A, system B. This study indicates that the use of an FD detector does not infer an automatic improvement in image quality or dose efficiency over II based designs. Specification and configuration of all of the components in the X-ray system contribute to the dose levels used and image quality achieved.

Angioplasty, Balloon, Coronary↗
PubMed2006

X-ray dose reduction in fluoroscopically guided electrophysiology procedures.

This study assessed the efficacy of a new dose reduction regime in fluoroscopically guided electrophysiology (EP) procedures, which included diagnostic electrophysiological investigations, radiofrequency ablation, and biventricular pacing. A modified dose regime for fluoroscopy was implemented in one of our cardiac electrophysiology laboratories. The x-ray system was programmed with a hierarchy of three fluoroscopy doses, and therefore image quality and settings. The default (lowest) dose mode was not expected to be suitable for all patient sizes or for the entirety of all procedures. Staff raised the dose level in a stepped manner as and when required to optimize the imaging requirements of the procedure. Phantom studies indicated that the low dose mode provided adequate image quality for visualizing EP catheters, while significantly lowering patient skin dose. In 52 clinical cases, questionnaires were used to assess the subjective clinical image quality. The mean image quality score for the low dose setting was rated between "adequate" and "good." The fluoroscopy dose level was raised from the lowest level for 6% of the total fluoroscopy time. Procedural Dose Area Product (DAP) meter readings were analyzed for patients prior to (n = 85) and after (n = 150) the implementation of the low dose regime and showed an overall reduction in DAP rate of 74%. The hierarchical dose regime proved to be acceptable in routine clinical practice for EP procedures, leading to significant reductions in patient doses.

Body Burden↗
PubMed2004

Natural variation in the npr-1 gene modifies ethanol responses of wild strains of C. elegans.

Variation in the acute response to ethanol between individuals has a significant impact on determining susceptibility to alcoholism. The degree to which genetics contributes to this variation is of great interest. Here we show that allelic variation that alters the functional level of NPR-1, a neuropeptide Y (NPY) receptor-like protein, can account for natural variation in the acute response to ethanol in wild strains of Caenorhabditis elegans. NPR-1 negatively regulates the development of acute tolerance to ethanol, a neuroadaptive process that compensates for effects of ethanol. Furthermore, dynamic changes in the NPR-1 pathway provide a mechanism for ethanol tolerance in C. elegans. This suggests an explanation for the conserved function of NPY-related pathways in ethanol responses across diverse species. Moreover, these data indicate that genetic variation in the level of NPR-1 function determines much of the phenotypic variation in adaptive behavioral responses to ethanol that are observed in natural populations.

Animals↗
PubMed2003

A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans.

The activities of many neuronal proteins are modulated by ethanol, but the fundamental mechanisms underlying behavioral effects of ethanol remain unclear. To identify mechanisms responsible for intoxication, we screened for Caenorhabditis elegans mutants with altered behavioral responses to ethanol. We found that slo-1 mutants, which were previously recognized as having slightly uncoordinated movement, are highly resistant to ethanol in two behavioral assays. Numerous loss-of-function slo-1 alleles emerged from our screens, indicating that slo-1 has a central role in ethanol responses. slo-1 encodes the BK potassium channel. Electrophysiological analysis shows that ethanol activates the channel in vivo, which would inhibit neuronal activity. Moreover, behaviors of slo-1 gain-of-function mutants resemble those of ethanol-intoxicated animals. These results demonstrate that selective activation of BK channels is responsible for acute intoxicating effects of ethanol in C. elegans. BK channel activation may explain a variety of behavioral responses to ethanol in invertebrate and vertebrate systems.

Amino Acid Sequence↗
PubMed2002

MEC-8 regulates alternative splicing of unc-52 transcripts in C. elegans hypodermal cells.

Previous work has shown that C. elegans MEC-8 is a putative RNA-binding protein that promotes specific alternative splices of unc-52 transcripts. unc-52 encodes homologs of mammalian perlecan that are located extracellularly between muscle and hypodermis and are essential for muscle development in both embryos and larvae. We show that MEC-8 is a nuclear protein found in hypodermis at most stages of development and not in most late embryonic or larval body-wall muscle. We have also found that overexpression of MEC-8 in hypodermis but not muscle can suppress certain unc-52 mutant phenotypes. These are unexpected results because it has been proposed that UNC-52 is produced exclusively by muscle. We have constructed various tissue-specific unc-52 minigenes fused to a gene for green fluorescent protein that have allowed us to monitor tissue-specific mec-8-dependent alternative splicing; we show that mec-8 must be expressed in the same cell type as the unc-52 minigene in order to regulate its expression, supporting the view that MEC-8 acts directly on unc-52 transcripts and that UNC-52 must be synthesized primarily by the hypodermis. Indeed, our analysis of unc-52 genetic mosaics has shown that the focus of unc-52 action is not in body-wall muscle but most likely is in hypodermis.

Alternative Splicing↗