PubMed Health⌕ Search

Biomedical subjects

Stephen Williams

Publications and source records attributed to Stephen Williams.

10 recordsLinked to original sources
PubMed2005

Software support in automation of medicinal product evaluations.

Medicinal product evaluation is one of the most important tasks undertaken by government health departments and their regulatory authorities, in every country in the world. The automation and adequate software support are critical tasks that can improve the efficiency and interoperation of regulatory systems across the world. In this paper we propose a software solution that supports the automation of the (i) submission of licensing applications, and (ii) evaluations of submitted licensing applications, according to regulatory authorities' procedures. The novelty of our solution is in allowing licensing applications to be submitted in any country in the world and evaluated according to any evaluation procedure (which can be chosen by either regulatory authorities or pharmaceutical companies). Consequently, submission and evaluation procedures become interoperable and the associated data repositories/databases can be shared between various countries and regulatory authorities.

Automation↗
PubMed2004

Multiplex mRNA assay using electrophoretic tags for high-throughput gene expression analysis.

We describe a novel multiplexing technology using a library of small fluorescent molecules, termed eTag molecules, to code and quantify mRNA targets. eTag molecules, which have the same fluorometric property, but distinct charge-to-mass ratios possess pre-defined electrophoretic characteristics and can be resolved using capillary electrophoresis. Coupled with primary Invader mRNA assay, eTag molecules were applied to simultaneously quantify up to 44 mRNA targets. This multiplexing approach was validated by examining a panel of inflammation responsive genes in human umbilical vein endothelial cells stimulated with inflammatory cytokine interleukin 1beta. The laser-induced fluorescence detection and electrokinetic sample injection process in capillary electrophoresis allows sensitive quantification of thousands of copies of mRNA molecules in a reaction. The assay is precise, as evaluated by measuring qualified Z' factor, a dimensionless and simple characteristic for applications in high-throughput screening using mRNA assays. Our data demonstrate the synergy between the multiplexing capability of eTag molecules by sensitive capillary electrophoresis detection and the isothermal linear amplification characteristics of the Invader assay. eTag multiplex mRNA assay presents a unique platform for sensitive, high sample throughput and multiplex gene expression analysis.

Cells, Cultured↗
PubMed2004

Direct measurement of multiple mRNAs in nerve growth factor-induced PC12 cells using electrophoretic tags to monitor biomarkers of neuronal differentiation in 96-well format.

Pheochromocytoma-12 (PC12) cells recapitulate the program of neuronal differentiation by developing neurites after about 12 days of nerve growth factor (NGF) treatment. This model can be used to evaluate the neuroprotective/neurotrophic effect of compounds. Specific mRNAs such as cfos and c-jun are early biomarkers of the irreversible commitment into the differentiation program as they appear after only 30-40 min of NGF treatment. Monitoring the level of these mRNAs instead of the neurite outgrowth dramatically reduces the time needed to identify the drug potential of compounds. The electrophoretic tags, or eTag reporters (ACLARA Biosciences, Inc., Mountain View, CA), are a new class of fluorescent reporters that have unique migration properties in capillary electrophoresis, which allows for their separation and identification. (The eTag Multiplex Invader Assay and products incorporate Invader technology and Cleavase enzyme licensed for use from Third Wave Technologies, Inc. [Madison, WI] for multiplexed gene expression applications.) Each eTag molecule used begins as a phosphoramidite that is incorporated into a specific oligonucleotide using standard oligonucleotide synthesis procedures. A set of distinct probes labeled with different eTag molecules can then be mixed together to simultaneously quantify the levels of different mRNAs from the same sample. When compared to existing methods for measuring multiplexed gene expression from the same sample, the eTag assay allows a direct quantification of the mRNA from cells without any extraction/purification and still provides multiplexing capability, high sensitivity, miniaturization, and reproducibility compatible with medium-throughput screening methods. The eTag technology was used to simultaneously measure the level of expression of four mRNAs-c-fos, c-jun, c-myc, and gapdh-in NGF-treated PC12 cells in a standard 96-well format. The experimental data shown here demonstrate the use of eTag technology as a new screening tool, which uniquely combines robustness, sensitivity, multiplexing capability, and direct measurement of mRNA without any sample preparation steps, such as RNA extraction/purification or a reverse transcription step.

Animals↗
PubMed2004

Influenza A associated morbidity and mortality in a Paediatric Intensive Care Unit.

This paper reports the clinical features and outcome of all children with a laboratory proven diagnosis of influenza A virus infection admitted to a major Paediatric Intensive Care Unit (PICU) in 2003. Eight of the 22 patients with influenza A virus infection (A/Fujian/411/2002-like type) presented with encephalopathy and three of the 22 patients died. This can be compared with 44 admissions and seven (16%) deaths of patients with influenza virus admitted in the same PICU in the preceding 15 years. In the present cohort, four (18%) of the 22 patients, including one child who died, should have received influenza vaccine according to the current Australian immunisation recommendations. We have no documented evidence that any of the 22 children received influenza vaccination. During the 2003 influenza season there was an increased number of children admitted to our PICU with influenza A infection and an increased number of deaths compared with previous years. Influenza infection causes significant morbidity and mortality in young children, most of whom are not currently recommended for annual influenza vaccination.

Adolescent↗
PubMed2003

Medical errors related to discontinuity of care from an inpatient to an outpatient setting.

OBJECTIVE: To determine the prevalence of medical errors related to the discontinuity of care from an inpatient to an outpatient setting, and to determine if there is an association between these medical errors and adverse outcomes. PATIENTS: Eighty-six patients who had been hospitalized on the medicine service at a large academic medical center and who were subsequently seen by their primary care physicians at the affiliated outpatient practice within 2 months after discharge. DESIGN: Each patient's inpatient and outpatient medical record was reviewed for the presence of 3 types of errors related to the discontinuity of care from the inpatient to the outpatient setting: medication continuity errors, test follow-up errors, and work-up errors. MEASUREMENTS: Rehospitalizations within 3 months after the initial postdischarge outpatient primary care visit. MAIN RESULTS: Forty-nine percent of patients experienced at least 1 medical error. Patients with a work-up error were 6.2 times (95%confidence interval [95% CI], 1.3 to 30.3) more likely to be rehospitalized within 3 months after the first outpatient visit. We did not find a statistically significant association between medication continuity errors (odds ratio [OR], 2.5; 95%CI, 0.7 to 8.8) and test follow-up errors (OR, 2.4; 95%CI, 0.3 to 17.1) with rehospitalizations. CONCLUSION: We conclude that the prevalence of medical errors related to the discontinuity of care from the inpatient to the outpatient setting is high and may be associated with an increased risk of rehospitalization.

Ambulatory Care↗
PubMed2002

Undergraduates' understanding of cardiovascular phenomena.

Undergraduates students in 12 courses at 8 different institutions were surveyed to determine the prevalence of 13 different misconceptions (conceptual difficulties) about cardiovascular function. The prevalence of these misconceptions ranged from 20 to 81% and, for each misconception, was consistent across the different student populations. We also obtained explanations for the students' answers either as free responses or with follow-up multiple-choice questions. These results suggest that students have a number of underlying conceptual difficulties about cardiovascular phenomena. One possible source of some misconceptions is the students' inability to apply simple general models to specific cardiovascular phenomena. Some implications of these results for teachers of physiology are discussed.

Cardiovascular Diseases↗
PubMedDate not supplied

Levosimendan for low cardiac output: a pediatric experience.

This was a retrospective observational study in a pediatric intensive care unit, in which 19 patients received levosimendan. There were no adverse events attributable to levosimendan and no instances where the clinical condition worsened after administration. Arterial lactate levels decreased significantly following levosimendan administration during cardiopulmonary bypass for anticipated low cardiac output. In those with established low cardiac output, trends toward improved hemodynamics were seen, with heart rate reduction, an increase in mean blood pressure, a reduction in arterial lactate, and reduced conventional inotrope use. Levosimendan was safely used in a small number of pediatric patients with established low cardiac output state who demonstrated improved hemodynamics and tissue perfusion, with a tendency to reduced conventional inotrope usage, and this warrants its evaluation as an inotrope in the pediatric population.

Adolescent↗