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Biomedical subjects

D Murray

Publications and source records attributed to D Murray.

At least 19 recordsLinked to original sources
PubMed2006

Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes.

BACKGROUND: Zinc carnosine (ZnC) is a health food product claimed to possess health-promoting and gastrointestinal supportive activity. Scientific evidence underlying these claims is, however, limited. AIM: To examine the effect of ZnC on various models of gut injury and repair, and in a clinical trial. METHODS: In vitro studies used pro-migratory (wounded monolayer) and proliferation ([(3)H]-thymidine incorporation) assays of human colonic (HT29), rat intestinal epithelial (RIE) and canine kidney (MDCK) epithelial cells. In vivo studies used a rat model of gastric damage (indomethacin/restraint) and a mouse model of small-intestinal (indomethacin) damage. Healthy volunteers (n = 10) undertook a randomised crossover trial comparing changes in gut permeability (lactulose:rhamnose ratios) before and after 5 days of indomethacin treatment (50 mg three times a day) with ZnC (37.5 mg twice daily) or placebo coadministration. RESULTS: ZnC stimulated migration and proliferation of cells in a dose-dependent manner (maximum effects in both assays at 100 micromol/l using HT29 cells), causing an approximate threefold increase in migration and proliferation (both p<0.01). Oral ZnC decreased gastric (75% reduction at 5 mg/ml) and small-intestinal injury (50% reduction in villus shortening at 40 mg/ml; both p<0.01). In volunteers, indomethacin caused a threefold increase in gut permeability in the control arm; lactulose:rhamnose ratios were (mean (standard error of mean)) 0.35 (0.035) before indomethacin treatment and 0.88 (0.11) after 5 days of indomethacin treatment (p<0.01), whereas no significant increase in permeability was seen when ZnC was coadministered. CONCLUSION: ZnC, at concentrations likely to be found in the gut lumen, stabilises gut mucosa. Further studies are warranted.

Animals↗
PubMed2006

Net1 and Myeov: computationally identified mediators of gastric cancer.

Gastric adenocarcinoma (GA) is a significant cause of mortality worldwide. The molecular mechanisms of GA remain poorly characterised. Our aim was to characterise the functional activity of the computationally identified genes, NET 1 and MYEOV in GA. Digital Differential Display was used to identify genes altered expression in GA-derived EST libraries. mRNA levels of a subset of genes were quantitated by qPCR in a panel of cell lines and tumour tissue. The effect of pro- and anti-inflammatory stimuli on gene expression was investigated. Cell proliferation and invasion were measured using in an in-vitro GA model following inhibition of expression using siRNA. In all, 23 genes not previously reported in association with GA were identified. Two genes, Net1 and Myeov, were selected for further analysis and increased expression was detected in GA tissue compared to paired normal tissue using quantitative PCR. siRNA-mediated downregulation of Net1 and Myeov resulted in decreased proliferation and invasion of gastric cancer cells in vitro. These functional studies highlight a putative role for NET1 and Myeov in the development and progression of gastric cancer. These genes may provide important targets for intervention in GA, evidenced by their role in promoting invasion and proliferation, key phenotypic hallmarks of cancer cells.

Adenocarcinoma↗
PubMed2006

Tissue engineering of blood vessels.

BACKGROUND: Tissue engineering techniques have been employed successfully in the management of wounds, burns and cartilage repair. Current prosthetic alternatives to autologous vascular bypass grafts remain poor in terms of patency and infection risk. Growing biological blood vessels has been proposed as an alternative. METHODS: This review is based on a literature search using Medline, PubMed, ISIS and CAS of original articles and reviews, and unpublished material and abstracts. RESULTS AND CONCLUSIONS: Complete incorporation into host tissues and the maintenance of a viable and self-renewing endothelial layer are the fundamental goals to be achieved when developing a tissue-engineered blood vessel. Sourcing of cells and modulating their interaction with extracellular matrix and supporting scaffold have been the focus of intense research. Although the use of tissue-engineered blood vessels in humans is so far limited, advances in our knowledge of stem cell precursors and the development of new biomaterials should enable this technology to reach routine clinical practice within a decade.

Biotechnology↗
PubMed2006

Synchronized, interactive teleconferencing with digital cardiac images.

St James's Hospital is a tertiary referral center for percutaneous intervention and cardiothoracic surgery for a number of referring hospitals. This article reports on the development and implementation of a synchronized, interactive teleconferencing system for cardiac images that links St. James's Hospital with a remote site (Sligo General Hospital) and overcomes the problems of transmission of large image files. Teleconferencing was achieved by setting up lossless auto transmission of patient files overnight and conferencing the next morning with linked control signals and databases. As a suitable product was not available, a commercially new software was developed. The system links the imaging databases, monitors and synchronizes progress through imaging sequences, and links a range of image processing and control functions. All parties to the conference are ensured that they are looking at the same images as they are played or at specific aspects of an image that the other party is highlighting. The system allows patient management decisions to be made at a weekly joint teleconference with cardiothoracic surgeons and interventional cardiologists from both sites. Rapid decision making was facilitated with 70% of decisions obtained within 24 h, and 88% within 1 week of their procedure. In urgent cases, data can be transmitted within 20 min of the diagnostic procedure. The system allows increased access to angiography for patients living in rural areas, and provides a more focused referral for revascularization. Participation of the referring cardiologist has improved the quality of decision making.

Academic Medical Centers↗
PubMed2006

Computed tomographic colonography (CTC) performance: one-year clinical follow-up.

AIM: Computed tomographic colonography (CTC) represents a valuable advance in imaging technology for patients with colonic symptoms who are unfit for or fail to complete investigation with conventional techniques of colonoscopy or barium enema. The aim of this study was to examine whether CTC was sufficient to exclude colorectal cancer in such a population. As our patients were unfit for or unable to complete conventional investigations, we used 1 year clinical follow-up to exclude colonic malignancy. MATERIALS AND METHODS: CTC examination was performed using multi-slice CT in patients fitting pre-determined criteria. All patients who had completed 12 months of follow-up after CTC were included. Data were extracted from patient records and lack of presentation within the 12 months following a negative CTC was assumed to equate to lack of colorectal cancer at initial investigation. RESULTS: One hundred and twelve patients underwent CTC with a median age of 78 years (range 39-95) and median follow-up of 18 months (range 12-26). CTC detected 7 colorectal cancers, with 3 false positives and 1 false negative, giving a sensitivity of 87.5% and specificity of 97.1% for the detection of colorectal cancer. CONCLUSIONS: CTC is a good imaging tool for the exclusion of colorectal cancer in a population unfit for or unable to complete colonoscopy or barium enema, with reasonable sensitivity and specificity for detection of colorectal cancer. However, the optimum investigative strategy for fitter symptomatic individuals is still debated and should be clarified by the results of ongoing randomised controlled trials.

Adult↗
PubMed2006

Chromogenic in situ hybridization analysis of melastatin mRNA expression in melanomas from American Joint Committee on Cancer stage I and II patients with recurrent melanoma.

OBJECTIVE: To determine whether loss of melastatin (MLSN) is a universal phenomenon in American Joint Committee on Cancer (AJCC) stage I and II melanoma patients who experienced recurrence. MATERIAL AND METHODS: Paraffin blocks of primary melanomas (PMs) were retrieved from 30 patients who had a negative sentinel lymph node biopsy and developed recurrent melanoma (AJCC stage I and II). Chromogenic in situ hybridization (CISH) methods were utilized to evaluate the expression of MLSN mRNA. These results were correlated with clinicopathologic data. RESULTS: Variable, heterogeneous expression of MLSN mRNA was identified in normal, in situ and invasive melanocytes within and between cases. For the invasive PM component, 24 (80%) had focal, regional or complete loss of MLSN mRNA. The remaining 20% had either regional or total partial downregulation of MLSN mRNA. Intact MLSN mRNA expression was present regionally in 14/30 (47%), with mean relative tumor area of 38%, range 5-85%. Increasing loss of MLSN mRNA significantly correlated with increasing tumor depth and microsatellites (r = 0.1/0.4, p = 0.04). However, thin, AJCC T stage 1a PM had higher relative mean loss than intermediate AJCC T stage 2a/2b/3a thickness PM (65% vs. 34%/48%/25%). Increasing loss of MLSN mRNA significantly impacted on disease free survival (DFS) by multivariate analysis (58 vs. 0% 2 years DFS, < or = 75 vs. > 75% mRNA loss, p = 0.02). Decreased overall survival significantly correlated with increasing age and vascular invasion on multivariate analysis. CONCLUSION: Extensive loss of MLSN in PM correlated with aggressive metastatic melanoma. Ancillary testing for MLSN mRNA expression by CISH could offer a means to more accurately identify AJCC stage I and II patients at risk for metastatic disease, who could benefit from adjuvant therapy.

Adult↗
PubMed2005

Colonic epithelial apoptosis during conventional and endoluminal aortic surgery.

BACKGROUND: This study characterized the initial modes of colonic mucosal injury during aneurysm surgery and correlated these with proinflammatory cytokine release into the colonic and systemic circulations. METHODS: Twenty-four patients undergoing conventional open aortic aneurysm repair and ten who had endovascular aneurysm repair (EVAR) were recruited. Mucosal biopsies were taken from the sigmoid colon immediately before and after surgery, for histological examination. Inferior mesenteric vein (IMV) and peripheral blood from patients who had conventional surgery was assayed for interleukin (IL) 1 beta, IL-6 and tumour necrosis factor (TNF) alpha. Only peripheral blood from patients who had EVAR was assayed. RESULTS: Conventional aneurysm repair resulted in a threefold increase in columnar epithelial apoptosis. There was a 26-fold increase in IL-6 in IMV blood within 5 min of reperfusion, with an equivalent rise in peripheral blood after 30 min. A 20-fold rise in peripheral blood TNF-alpha was observed after surgery. Splanchnic IL-6 correlated positively with cross-clamp time and increased apoptosis. No histological changes were seen after EVAR. There were no intraoperative cytokine changes during EVAR, although a postoperative increase in IL-6 and TNF-alpha was observed. CONCLUSION: The lack of columnar epithelial apoptosis following EVAR reflects the relatively minor ischaemic injury incurred during this procedure.

Aged↗
PubMed2005

The influence of asymptomatic significant carotid disease on mortality and morbidity in patients undergoing coronary artery bypass surgery.

OBJECTIVES: Controversy exists regarding the optimal management of patients with coexisting coronary and extracranial carotid artery disease. This study investigates the incidence of death, cerebrovascular events and myocardial infarction (MI) in patients with asymptomatic significant carotid artery disease undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Prospective cohort. METHODS: Fifty patients with asymptomatic carotid stenoses > or =70% associated with cervical bruits undergoing CABG without prophylactic carotid endarterectomy (CEA) were followed up over a median period of 68 months following surgery cerebrovascular events, MI and mortality were recorded. All patients received optimal secondary prevention for cardiovascular disease unless contraindicated. RESULTS: No cerebrovascular events occurred within 30 days of surgery. One patient suffered an ipsilateral transient ischaemic attack (TIA) 14 months after CABG. Two patients died within 30 days; one from an MI, the other from pancreatitis. Three deaths occurred after 30 days; one from MI, one from primary lung cancer and one following rupture of an abdominal aortic aneurysm. No non-fatal MIs occurred. CONCLUSIONS: In this patient group the overall risk of death, cerebrovascular events and MI was 4% during the first 30 days postoperatively and 8% thereafter. This compares favourably with published series for staged or combined CEA-CABG procedures. For asymptomatic significant carotid disease, prophylactic CEA prior to CABG does not appear to confer any advantage over CABG alone.

Aged↗
PubMed2005

Is there a place for shelf acetabuloplasty in the management of adult acetabular dysplasia? A survivorship study.

We followed up 76 consecutive hips with symptomatic acetabular dysplasia treated by acetabular shelf augmentation for a mean period of 11 years. Survival analysis using conversion to hip replacement as an end-point was 86% at five years and 46% at ten years. Forty-four hips with slight or no narrowing of the joint space pre-operatively had a survival of 97% at five and 75% at ten years. This was significantly higher (p = 0.0007) than that of the 32 hips with moderate or severe narrowing of the joint-space, which was 76% at five and 22% at ten years. There was no significant relationship between survival and age (p = 0.37) or the pre- and post-operative centre-edge (p = 0.39) and acetabular angles (p = 0.85). Shelf acetabuloplasty is a reliable, safe procedure offering medium-term symptomatic relief for adults with acetabular dysplasia. The best results were achieved in patients with mild and moderate dysplasia of the hip with little arthritis.

Acetabulum↗
PubMed2004

Altered circadian relationship between serum nitric oxide, carbon dioxide, and uric acid in multiple sclerosis.

The free radical nitric oxide (NO*) is involved in a variety of diverse biological processes from acting as a vasodilator in the cardiovascular system to being the rate-limiting component in the production of peroxynitrite (ONOO-), a contributor to neurodegenerative disorders such as multiple sclerosis (MS). Uric acid (UA), the end product of purine metabolism in humans and a selective inhibitor of toxic reactions attributed to radicals formed by the interaction of ONOO- and CO2, is generally low in MS patients. We investigated the relationship between serum ONOO-, CO2, and UA in MS patients and normal controls by comparing the circadian characteristics of the NO* metabolites nitrite/ nitrate (NO), CO2, and UA. In this preliminary study, we found the functional relationship ascribed to the circadian timing of the peak and trough levels of NO, CO2, and UA in healthy subjects to be clearly altered in MS patients. These findings suggest that alterations in the temporal relationship between the 24h pattern in serum ONOO- formation and UA may either contribute to or reflect the disease processes in MS.

Adult↗
PubMed2004

The value of an elastic tissue stain in detecting venous invasion in colorectal cancer.

BACKGROUND: Venous invasion by tumour is an independent prognostic indicator of both prognosis and risk of development of distant metastases in colorectal carcinoma. The use of special stains to aid its detection in pathology specimens is not currently universally recommended. AIMS: To determine whether an elastica stain significantly increases the incidence of detection of vascular invasion compared with routinely stained sections. METHODS: Serial sections from the 75 cases of colorectal carcinoma were stained by haematoxylin and eosin (H&E) only and elastica counterstained with H&E. The incidence of both intramural and extramural venous invasion was recorded and compared with that seen when the tumours were originally reported. RESULTS: Extramural venous invasion had been noted in 14 of the pathology reports and was seen in 18 cases when only the H&E sections were viewed in the study. It was present in 32 cases when elastica stained sections were analysed. Intramural venous invasion was seen in eight cases on H&E sections and 30 cases on elastica stained sections. CONCLUSION: The use of elastica stained serial sections to detect venous invasion in tumours should be recommended in guidelines for the reporting of colorectal carcinomas.

Blood Vessels↗
PubMed2003

The effect of sleep disruption on performance of anaesthetists--a pilot study.

Fatigue has been implicated in the occurrence of critical incidents. Using a driving simulator to assess vigilance, we investigated the effect of sleep disruption on the ability of anaesthetists to maintain vigilance after a night on-call. Following an undisturbed night of sleep, subjects demonstrated a significant improvement in their vigilance scores. Subjects failed to demonstrate this following a disturbed night. The timing of disturbance had a bearing on performance. Subjects' performance was worse if their sleep had been disturbed in the first third of the night. The effect of sleep disruption on vigilance has implications for patient safety during anaesthesia.

Anesthesia↗