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Biomedical subjects

Andrew Thomson

Publications and source records attributed to Andrew Thomson.

15 recordsLinked to original sources
PubMed2006

SIGMA: a system for integrative genomic microarray analysis of cancer genomes.

BACKGROUND: The prevalence of high resolution profiling of genomes has created a need for the integrative analysis of information generated from multiple methodologies and platforms. Although the majority of data in the public domain are gene expression profiles, and expression analysis software are available, the increase of array CGH studies has enabled integration of high throughput genomic and gene expression datasets. However, tools for direct mining and analysis of array CGH data are limited. Hence, there is a great need for analytical and display software tailored to cross platform integrative analysis of cancer genomes. RESULTS: We have created a user-friendly java application to facilitate sophisticated visualization and analysis such as cross-tumor and cross-platform comparisons. To demonstrate the utility of this software, we assembled array CGH data representing Affymetrix SNP chip, Stanford cDNA arrays and whole genome tiling path array platforms for cross comparison. This cancer genome database contains 267 profiles from commonly used cancer cell lines representing 14 different tissue types. CONCLUSION: In this study we have developed an application for the visualization and analysis of data from high resolution array CGH platforms that can be adapted for analysis of multiple types of high throughput genomic datasets. Furthermore, we invite researchers using array CGH technology to deposit both their raw and processed data, as this will be a continually expanding database of cancer genomes. This publicly available resource, the System for Integrative Genomic Microarray Analysis (SIGMA) of cancer genomes, can be accessed at http://sigma.bccrc.ca.

Adenocarcinoma↗
PubMed2006

Cardiopulmonary complications of ERCP in older patients.

BACKGROUND: Biochemical markers of ERCP-related myocardial injury have not previously been investigated. OBJECTIVE: To evaluate ERCP-related cardiac troponin I (cTnI) release, myocardial ischemia, hemodynamic changes, and arterial hypoxemia in a series of consecutive patients according to age and to determine their relationship to preexisting cardiovascular risk factors (RF) and the development of post-ERCP pancreatitis. DESIGN: Prospective cohort study. SETTING: Tertiary teaching hospital, Canberra, Australia. PATIENTS: Data were collected on 130 consecutive ERCPs performed on 100 unselected patients (aged 18-93 years) by one endoscopist. Patients were divided into two groups: 65 years of age and older (group 1, n = 53; 27 women) and less than 65 years of age (group 2, n = 47; 33 women). INTERVENTIONS: ERCP. MAIN OUTCOME MEASUREMENTS: Cardiovascular RFs were identified, and electrocardiogram (ECG), cTnI, creatine kinase (CK), amylase, and lipase were measured before and 24 hours after ERCP. Oxygen saturation (SpO(2)), heart rate (HR), blood pressure (BP), and ECG were monitored continuously during each procedure. RESULTS: New ECG changes (ischemia, arrhythmias) occurred in 24% of procedures in group 1 and in 9.3% in group 2 (p = 0.168), and episodic arterial hypoxemia (SpO(2) < 90%) in 16.2% (group 1) and 21.4% (group 2) (p = 0.596). A post-ERCP rise in cTnI levels was documented in 6 patients in the older group. Two of these patients died: one from acute myocardial infarction and one from undiagnosed ascending aortic aneurysm. A cTnI rise was not related to any comorbid conditions, total number of RFs, hemodynamic or ECG changes, or arterial desaturation. In patients with a new cTnI rise, the duration of ERCP was significantly longer (59.5 vs. 26.4 minutes, p = 0.026), being 30 minutes or longer in 5 of 6 patients. Post-ERCP pancreatitis was associated with desaturation (relative risk [RR] = 5.9; 95% confidence interval [CI] [1.2, 32.0], p = 0.027) and myocardial ischemia/injury (RR = 4.4; 95% CI [1.4, 7.8]; p = 0.009). CONCLUSIONS: Although the majority of older patients tolerated ERCP well, in 8% of procedures, most of which were prolonged (>30 minutes), myocardial injury, as defined by the release of cTnI, occurred. Desaturation and myocardial ischemia/injury were associated with post-ERCP pancreatitis.

Aged↗
PubMed2006

Enteral versus parenteral nutritional support in acute pancreatitis: a clinical review.

A critical analysis of the trials comparing enteral with parenteral nutritional support in acute pancreatitis is presented with particular scrutiny of the clinical endpoints in each trial. The heterogeneity of the trials and the discrepancies in caloric intake between enterally and parenterally fed patients are discussed. The hazards of each route of nutritional support are highlighted and the concept of 'nutritional bioavailability' in the context of acute pancreatitis is introduced. It is concluded that although there is evidence to support enteral feeding as the preferred option, both routes have a role.

Acute Disease↗
PubMed2005

A comparison of Bayesian spatial models for disease mapping.

With the advent of routine health data indexed at a fine geographical resolution, small area disease mapping studies have become an established technique in geographical epidemiology. The specific issues posed by the sparseness of the data and possibility for local spatial dependence belong to a generic class of statistical problems involving an underlying (latent) spatial process of interest corrupted by observational noise. These are naturally formulated within the framework of hierarchical models, and over the past decade, a variety of spatial models have been proposed for the latent level(s) of the hierarchy. In this article, we provide a comprehensive review of the main classes of such models that have been used for disease mapping within a Bayesian estimation paradigm, and report a performance comparison between representative models in these classes, using a set of simulated data to help illustrate their respective properties. We also consider recent extensions to model the joint spatial distribution of multiple disease or health indicators. The aim is to help the reader choose an appropriate structural prior for the second level of the hierarchical model and to discuss issues of sensitivity to this choice.

Bayes Theorem↗
PubMed2004

Expression and localization of cell adhesion molecules in human fetal membranes during parturition.

There is increasing evidence to support the view that human parturition represents an inflammatory process. We have previously demonstrated that parturition is associated with leukocyte invasion and pro-inflammatory cytokine production in the cervix and myometrium. Furthermore, we have shown that several cell adhesion molecules are upregulated in these tissues during labor. In fetal membranes, previous studies have shown intercellular adhesion molecule-1 (ICAM-1) upregulation in association with labor. The role of other adhesion molecules has not been explored. The aims of this study were, therefore, to determine the expression of ICAM-1, platelet endothelial cell adhesion molecule (PECAM), vascular cell adhesion molecule (VCAM) and E-selectin in pre- and post-laboring amnion and choriodecidua and to identify cell types responsible for their expression. Biopsies of fetal membranes were obtained from pregnant women delivered by caesarean section before the onset of labor (n = 8) and following spontaneous vaginal delivery (n = 8). Cell adhesion molecules were identified using immunohistochemistry and messenger RNA expression quantified using Northern analysis. We found that following labor, ICAM-1 mRNA expression was significantly upregulated in amnion and choriodecidua (P < 0.05). PECAM mRNA expression was also increased in choriodecidua (P < 0.05). The main cell types responsible for adhesion molecule expression were leukocytes, amniotic epithelial cells and endothelial cells. The upregulation of ICAM-1 and PECAM mRNA expression in fetal membranes following labor provides further evidence that fetal membranes play an important role in the inflammatory process of parturition.

Amniotic Fluid↗
PubMed2004

The impact of guidelines on mild hypertension in pregnancy: time series analysis.

OBJECTIVE: To determine the impact of a national strategy to promote implementation of a guideline on the management of mild, non-proteinuric hypertension in pregnancy. DESIGN: Simple, interrupted time series analysis. SETTING: Four maternity units in Scotland. POPULATION: Women delivering a live or stillborn baby. METHODS: Dissemination of the guideline under the auspices of a national clinical effectiveness programme, supported by a national launch meeting and feedback from a survey of obstetricians highlighting aspects of care that could be improved. MAIN OUTCOME MEASURES: Appropriateness of initial investigation and subsequent clinical management, and costs of guideline development and implementation activities. DATA COLLECTION: Twenty-four months pre-intervention and 12 months post-intervention data were abstracted from a random sample of case notes. RESULTS: Initial investigation was consistent with recommendations for 59.9% out of 1263 women and subsequent clinical management for 67.6% out of 1081 in whom a diagnosis could be made from available data. There were no significant changes in the appropriateness of initial investigation (10.6%; 95% confidence interval [CI] -0.1% to 19.3%; decreasing by 1.2% per month post-implementation, 95% CI -2.5% to 0.1%) or clinical management (-0.3%; 95% CI -8.7% to 11.2%). Guideline development and implementation cost an estimated pound 2784 per maternity unit in Scotland. CONCLUSIONS: Clinical care of mild hypertension in pregnancy remains highly inconsistent. The lack of the intervention effect may be related to the complexity of the guideline recommendations and the nature of the implementation strategy.

Adult↗
PubMed2004

Interpreting posterior relative risk estimates in disease-mapping studies.

There is currently much interest in conducting spatial analyses of health outcomes at the small-area scale. This requires sophisticated statistical techniques, usually involving Bayesian models, to smooth the underlying risk estimates because the data are typically sparse. However, questions have been raised about the performance of these models for recovering the "true" risk surface, about the influence of the prior structure specified, and about the amount of smoothing of the risks that is actually performed. We describe a comprehensive simulation study designed to address these questions. Our results show that Bayesian disease-mapping models are essentially conservative, with high specificity even in situations with very sparse data but low sensitivity if the raised-risk areas have only a moderate (less than 2-fold) excess or are not based on substantial expected counts (> 50 per area). Semiparametric spatial mixture models typically produce less smoothing than their conditional autoregressive counterpart when there is sufficient information in the data (moderate-size expected count and/or high true excess risk). Sensitivity may be improved by exploiting the whole posterior distribution to try to detect true raised-risk areas rather than just reporting and mapping the mean posterior relative risk. For the widely used conditional autoregressive model, we show that a decision rule based on computing the probability that the relative risk is above 1 with a cutoff between 70 and 80% gives a specific rule with reasonable sensitivity for a range of scenarios having moderate expected counts (approximately 20) and excess risks (approximately 1.5- to 2-fold). Larger (3-fold) excess risks are detected almost certainly using this rule, even when based on small expected counts, although the mean of the posterior distribution is typically smoothed to about half the true value.

Bayes Theorem↗
PubMed2002

Cholesterol esters regulate apoB48 secretion in CaCo2 cells.

In this study, we investigated the effect of atorvastatin, an HMG-CoA reductase inhibitor and CL277082, an ACAT inhibitor, on apolipoprotein B48 synthesis, degradation and secretion in transformed human intestinal enterocytes (CaCo2 cells). Cells were incubated with atorvastatin or CL277082 in the absence or presence of sterol containing media and pulsed with [S35]-methionine and chased with unlabelled methionine. Concomitantly, the effect of atorvastatin and CL277082 on the relative amount of apoB48 protein in cells and media was also quantified by western blotting using an apoB antibody and enhanced chemiluminescence. Suppression of cholesterol synthesis with atorvastatin did not attenuate the production or secretion of apoB48 from CaCo2 cells under basal conditions. On the other hand, suppression of cholesterol biosynthesis with atorvastatin under stimulatory conditions accelerated the degradation of apoB48 in cells without affecting its synthesis or secretion. There was no effect of exogenous sterols on apoB48 secretion. Taken together, neither endogenous nor exogenous cholesterol appears to acutely modulate apoB48 secretion from intestinal cells. In contrast, inhibition of cholesterol esterification with ACAT inhibitor significantly attenuated apoB48 secretion under basal and stimulatory conditions by a mechanism which enhanced apoB48 degradation. Collectively, our results suggest that in CaCo2 cells, newly synthesized cholesterol ester may be an immediate regulator apoB48 secretion.

Apolipoprotein B-48↗