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Biomedical subjects

M J Clancy

Publications and source records attributed to M J Clancy.

At least 19 recordsLinked to original sources

Should UK emergency physicians undertake diagnostic ultrasound examinations?

From the published evidence there is no doubt that emergency physicians in America can undertake focused ultrasound examinations and that, by extrapolation, this would also be the case for UK emergency physicians. If this skill is to become part of the diagnostic armamentarium of the emergency physician, however, it needs to be demonstrated to be cost effective compared with the alternatives already available to the hospital. Trials to test for this benefit should adopt a hospital and not an emergency department perspective if the results are to influence health policy and specialty training.

Clinical Competence↗

Point of care testing in the accident and emergency department: a cost analysis and exploration of financial incentives to use the technology within the hospital.

OBJECTIVES: To compare the costs of current arrangements for testing emergency blood samples from patients attending an accident and emergency (A&E) department in a large teaching hospital in England with point of care testing (POCT). METHODS: Estimates were made of the fixed and variable costs of two options: a supplemental option, in which POCT was introduced to A&E only; and a replacement option, in which POCT was introduced to A&E and the intensive therapy unit (ITU), thereby entirely replacing an existing process. RESULTS: For the supplemental option, current arrangements cost 68,466 Pounds in total per year; average costs per test were 5.53 Pounds (venous in the central laboratory) and 3.60 Pounds (arterial on the ITU). Introducing POCT would increase total hospital costs by 35,929 Pounds, and average costs per test would be 5.32 Pounds (venous) and 4.28 Pounds (arterial). For the replacement option, current arrangements cost 132,630 Pounds in total, and average cost per test (for all tests) was 4.06 Pounds. Introducing POCT would make hospital savings ranging from 8332 Pounds to 20,000 Pounds, and average cost per test would be 3.78 Pounds. CONCLUSIONS: Introducing POCT results in lower average costs per test. The supplemental option will result in significantly increased costs to the hospital. The replacement option can lead to significant savings. The internal cross-charging arrangements between departments that exist in this hospital may mean that supplemental implementation of POCT could be potentially 'profitable' for the A&E department, but would result in higher expenditure for the hospital as a whole.

Blood Chemical Analysis↗

Meiosis: step-by-step through sporulation.

A transcription factor, Ndt80p, has been identified that has a critical role in the pathway that controls meiosis--sporulation--in budding yeast. Ndt80p coordinately controls genes that mediate spore formation and progression through the two meiotic divisions; it may also be a target of a checkpoint control.

Animals↗

The S. cerevisiae nitrogen starvation-induced Yvh1p and Ptp2p phosphatases play a role in control of sporulation.

Starvation for nitrogen in the absence of a fermentable carbon source causes diploid Saccharomyces cerevisiae cells to leave vegetative growth, enter meiosis, and sporulare; the former nutritional condition also induces expression of the YVH1 gene that encodes a protein phosphatase. This correlation prompted us to determine whether the Yvh1p phosphatase was a participant in the network that controls the onset of meiosis and sporulation. We found that expression of the IME2 gene, encoding a protein kinase homologue required for meiosis- and sporulation-specific gene expression, is decreased in a yvh1 disrupted strain. We also observed a decrease, albeit a smaller one, in the expression of IME1 which encodes an activator protein required for IME2 expression. Under identical experimental conditions, expression of the MCKI and IME4 genes (which promote sporulation but do not require Ime1p for expression) was not affected. These results demonstrate the specificity of the yvh1 disruption phenotype. They suggest that decreased steady-state levels of IME1 and IME2 mRNA were not merely the result of non-specific adverse affects on nucleic acid metabolism caused by the yvh1 disruption. Sporulation of a homozygous yvh1 disruption mutant was delayed and less efficient overall compared to an isogenic wild-type strain, a result which correlates with decreased IME1 and IME2 gene expression. We also observed that expression of the PTP2 tyrosine phosphatase gene (a negative regulator of the osmosensing MAP kinase cascade), but not the PTP1 gene (also encoding a tyrosine phosphatase) was induced by nitrogen-starvation. Although disruption of PTP2 alone did not demonstrably affect sporulation or IME2 gene expression, sporulation was decreased more in a yvh1, ptp2 double mutant than in a yvh1 single mutant; it was nearly abolished in the double mutant. These data suggest that the YVH1 and PTP2 encoded phosphatases likely participate in the control network regulating meiosis and sporulation. Expression of YVH1 and PTP2 was not affected by nitrogen source quality (asparagine compared to proline) suggesting that nitrogen starvation-induced YVH1 and PTP2 expression and sensitivity to nitrogen catabolite repression are on two different branches of the nitrogen regulatory network.

Cell Cycle Proteins↗

Volumetric flow estimation in vivo and in vitro using pulsed-Doppler ultrasound.

The measurement of volumetric blood flow in small vessels in vitro and in vivo poses a significant technological challenge. In this study, two pulsatile flow models were developed, one with a 3.2-mm lumen diameter and one with a 12.7-mm lumen diameter, to assess the accuracy of volumetric flow estimation of two pulsed-Doppler devices, a Crystal Biotech VF1 20-MHz system with either a cuff-mounted or a needle-mounted probe and an Advanced Technology Laboratories Ultramark 9 High Definition Imaging system with a 5-MHz linear array transducer. The VF1 volumetric flow error was measured in the 3.2-mm phantom over a variety of pulsatile and continuous waveforms. The accuracy of the VF1 was also tested in porcine femoral and renal arteries. VF1 volumetric flow error ranged from 4.8% to 54.3% in the in vivo studies. The ATL demonstrated similar volumetric flow errors in the porcine femoral artery (approximately 3.2 mm diameter), but these errors were reduced to < or = 17.4% in the 12.7-mm-diameter in vitro flow model.

Animals↗

Changes in stroke distance in response to haemorrhage in a swine model.

OBJECTIVE: To determine, using an animal model of blood loss, (1) if stroke distance, derived non-invasively from the time integral of the maximum velocity of red cells in the aorta, changed to a greater extent than heart rate and mean arterial pressure (MAP), which are recognised to be unreliable indicators of blood loss; (2) if changes in stroke distance reflected changes in stroke volume derived from thermodilution cardiac output measurements. METHODS: Eight anaesthetised swine had baseline measurements of heart rate, MAP, stroke volume, and stroke distance and were then exsanguinated at a rate of 1 ml/kg/min. Percentage changes from baseline of heart rate, MAP, stroke volume, and stroke distance were compared after 10, 20, and 30 ml/kg blood loss. The animal's blood was then reinfused at the rate of 2 ml/kg/min for 15 min, followed by normal saline 1 ml/kg/min. Percentage changes from baseline measurement of stroke volume and stroke distance over the whole experiment were evaluated by regression analysis. RESULTS: Heart rate, MAP, and stroke distance changed +7.9%, -22.5%, and -18.1% respectively (from baseline values) after 10 ml/kg blood loss; +23.2%, -44.0%, and -47.4% after 20 ml/kg blood loss; and +55.7%, -62.0%, and -69.8% after 30 ml/kg blood loss. Regression analysis of percentage changes in stroke volume and stroke distance from their baseline values at experimental time zero is stroke volume = 1.014 x stroke distance -2.156, r = 0.92, n = 54, P < 0.0001. CONCLUSIONS: (1) At maximal blood loss, stroke distance changes to a greater extent than heart rate and MAP. (2) Changes in stroke distance reflected changes in stroke volume but with less variability at lower values. Stroke distance may be a more useful measure of blood loss than heart rate and MAP.

Animals↗

The SPR3 gene encodes a sporulation-specific homologue of the yeast CDC3/10/11/12 family of bud neck microfilaments and is regulated by ABFI.

The SPR3 gene is selectively activated only during the sporulation phase of the Saccharomyces cerevisiae (Sc) life cycle. The predicted amino acid (aa) sequence has homology to microfilament proteins that are involved in cytokinesis and other proteins of unknown function. These include the products of Sc cell division cycle (CDC) genes involved in bud formation (Cdc3p, Cdc10p, Cdc11p and Cdc12p), Candida albicans proteins that accumulate in the hyphal phase (CaCdc3p and CaCdc10p), mouse brain-specific (H5p) and lymphocyte (Diff6p) proteins, Drosophila melanogaster (Dm) protein Pnutp (which is localized to the cleavage furrow of dividing cells), a Diff6p homologue (DmDiff6p), and the Sc septin protein (Sep1hp), a homologue of the 10-nm filament proteins of Sc. One strongly conserved region contains a potential ATP-GTP-binding domain. Primer extension analysis revealed six major transcription start points (tsp) beginning at -142 relative to the ATG start codon. The sequence immediately upstream from the tsp contains consensus binding sites for the HAP2/3/4 and ABFI transcription factors, a T-rich sequence and two putative novel elements for mid to late sporulation, termed SPR3 and PAL. Electrophoretic mobility shift assay (EMSA) and footprint analyses demonstrated that the ABFI protein binds to a region containing the putative ABFI site in vitro, and site-directed mutagenesis showed that the ABFI motif is essential for expression of SPR3 at the appropriate stage in sporulating cells.

Actin Cytoskeleton↗