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Biomedical subjects

J Duncan Young

Publications and source records attributed to J Duncan Young.

6 recordsLinked to original sources
PubMed2006

The use of pre- pro- and synbiotics in adult intensive care unit patients: systematic review.

BACKGROUND & AIMS: This review investigated whether the administration of enteral pre-, pro- and synbiotics compared with controls in adult intensive care unit (ICU) patients reduced the incidence of nosocomial infections, length of ICU stay, hospital mortality and specifically pneumonia. METHODS: Systematic review of randomised controlled trials comparing enteral feeding and pre-, pro- or synbiotics, versus standard enteral feed alone, in patients admitted to adult ICUs. RESULTS: Eight randomised studies with a total of 999 critically ill adult patients met the inclusion criteria. Pre- pro- or synbiotics were not associated with any significant change in the outcomes studied-length of ICU stay, hospital mortality and the incidence of nosocomial infection and more specifically pneumonia incidence. Few data were available for other outcomes. CONCLUSIONS: The use of pre- pro- or synbiotics in adult critically ill patients confers no statistically significant benefit in the outcome criteria studied. There is currently a lack of evidence to support the use of pre- pro- or synbiotics in patients admitted to adult ICUs, and a large well-designed trial is needed in this area.

Critical Care↗
PubMed2005

Systematic review and meta-analysis of studies of the timing of tracheostomy in adult patients undergoing artificial ventilation.

OBJECTIVE: To compare outcomes in critically ill patients undergoing artificial ventilation who received a tracheostomy early or late in their treatment. DATA SOURCES: The Cochrane Central Register of Clinical Trials, Medline, Embase, CINAHL, the National Research Register, the NHS Trusts Clinical Trials Register, the Medical Research Council UK database, the NHS Research and Development Health Technology Assessment Programme, the British Heart Foundation database, citation review of relevant primary and review articles, and expert informants. STUDY SELECTION: Randomised and quasi-randomised controlled studies that compared early tracheostomy with either late tracheostomy or prolonged endotracheal intubation. From 15,950 articles screened, 12 were identified as "randomised or quasi-randomised" controlled trials, and five were included for data extraction. DATA EXTRACTION: Five studies with 406 participants were analysed. Descriptive and outcome data were extracted. The main outcome measure was mortality in hospital. The incidence of hospital acquired pneumonia, length of stay in a critical care unit, and duration of artificial ventilation were also recorded. Random effects meta-analyses were performed. RESULTS: Early tracheostomy did not significantly alter mortality (relative risk 0.79, 95% confidence interval 0.45 to 1.39). The risk of pneumonia was also unaltered by the timing of tracheostomy (0.90, 0.66 to 1.21). Early tracheostomy significantly reduced duration of artificial ventilation (weighted mean difference -8.5 days, 95% confidence interval -15.3 to -1.7) and length of stay in intensive care (-15.3 days, -24.6 to -6.1). CONCLUSIONS: In critically ill adult patients who require prolonged mechanical ventilation, performing a tracheostomy at an earlier stage than is currently practised may shorten the duration of artificial ventilation and length of stay in intensive care.

Critical Care↗
PubMed2003

Effects of endotoxin exposure on cationic amino acid transporter function in ovine peripheral blood mononuclear cells.

Rodent models of sepsis differ from clinical human disease in that humans make substantially less whole-body nitric oxide and have different cellular responses to endotoxin. Sheep, when exposed to endotoxin, behave in a manner more similar to humans. Many studies of rodent peripheral blood mononuclear cells (PBMCs) exposed to endotoxin demonstrate increased cationic amino acid transporter function (particularly through the y+ transporter) to supply arginine substrate to upregulated nitric oxide synthase. Whether this is true in sheep is not known. We have studied cationic amino acid transport in sheep PBMCs stimulated with endotoxin, using labelled lysine. PBMCs stimulated both in vitro and in vivo show an initial reduction in total and y+ lysine transport (after 1-2 h exposure to endotoxin): a previously undescribed effect of endotoxin. In in vitro activated cells, the reduction in y+ transport was prevented by the lipoxygenase inhibitor, nordihydroguaretic acid (NDGA), and the phospholipase inhibitor 4-bromophenacyl bromide (4-BPAB), but not cyclohexamide or a number of other inhibitors of intracellular second-messenger pathways. In contrast after 14 h incubation, the expected increase in total and y+ lysine transport was seen. The increase in y+ transport could be prevented by cyclohexamide, dexamethasone, ibuprofen, the protein kinase C inhibitor sphingosine, NDGA and 4-BPAB. These results suggest that in response to endotoxin exposure there is an initial decrease in y+ activity mediated by a lipoxygenase product, followed by a substantial increase in y+ activity mediated by the products of either cyclo-oxygenase or lipoxygenase. Cyclo-oxygenase and/or lipoxygenase inhibition might be useful in reducing arginine transport, and hence nitric oxide production, in these cells.

Amino Acid Transport System y+↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗