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Biomedical subjects

Stephen Wilson

Publications and source records attributed to Stephen Wilson.

At least 19 recordsLinked to original sources

Effect of cardiac motion on body surface electrocardiographic potentials: an MRI-based simulation study.

This paper describes an electrical model of cardiac ventricles incorporating real geometry and motion. The heart anatomy and its motion through the cardiac cycle are obtained from segmentations of multiple-slice MRI time sequences; the special conduction system is constructed using an automated mapping procedure from an existing static heart model. The heart model is mounted in an anatomically realistic voxel model of the human body. The cardiac electrical source and surface potentials are determined numerically using both a finite-difference scheme and a boundary-element method with the incorporation of the motion of the heart. The electrocardiograms (ECG) and body surface potential maps are calculated and compared to the static simulation in the resting heart. The simulations demonstrate that introducing motion into the cardiac model modifies the ECG signals, with the most obvious change occurring during the T-wave at peak contraction of the ventricles. Body surface potential maps differ in some local positions during the T-wave, which may be of importance to a number of cardiac models, including those incorporating inverse methods.

Algorithms↗

An MRI investigation into the function of the transversus abdominis muscle during "drawing-in" of the abdominal wall.

STUDY DESIGN: An operator blinded dual modality trial of measurement of the abdominal muscles during "drawing-in" of the abdominal wall. OBJECTIVES: 1) To investigate, using magnetic resonance imaging (MRI), the function of the transversus abdominis muscle bilaterally during a drawing-in of the abdominal wall. 2) To validate the use of real-time ultrasound imaging as a measure of the deep abdominal muscle during a drawing-in of the abdominal wall. SUMMARY OF BACKGROUND DATA: Previous research has implicated the deep abdominal muscle, transversus abdominis, in the support and protection of the spine and provided evidence that training this muscle is important in the rehabilitation of low back pain. One of the most important actions of the transversus abdominis is to "draw-in" the abdominal wall, and this action has been shown to stiffen the sacroiliac joints. It is hypothesized that in response to a draw in, the transversus abdominis muscle forms a deep musculofascial "corset" and that MRI could be used to view this corset and verify its mechanism of action on the lumbopelvic region. METHODS: Thirteen healthy asymptomatic male elite cricket players aged 21.3 +/- 2.1 years were imaged using MRI and ultrasound imaging as they drew in their abdominal walls. Measurements of the thickness of the transversus abdominis and internal oblique muscles and the slide of the anterior abdominal fascia were measured using both MRI and ultrasound. Measurement of the whole abdominal cross-sectional area (CSA) was conducted using MRI. RESULTS: Results of the MRI demonstrated that, as a result of draw-in, there was a significant increase in thickness of the transversus abdominis (P < 0.001) and the internal oblique muscles (P < 0.001). There was a significant decrease in the CSA of the trunk (P < 0.001). The mean slide (+/-SD) of the anterior abdominal fascia was 1.54 +/- 0.38 cm for the left side and 1.48 +/- 0.35 cm for the right side. Ultrasound measurements of muscle thickness of both transversus abdominis and the internal oblique, as well as fascial slide, correlated with measures obtained using MRI (interclass correlations from 0.78 to 0.95). CONCLUSIONS: The MRI results demonstrated that during a drawing-in action, the transversus abdominis contracts bilaterally to form a musculofascial band that appears to tighten (like a corset) and most likely improves the stabilization of the lumbopelvic region. Real-time ultrasound imaging can also be used to measure changes in the transversus abdominis during the draw-in maneuver.

Abdominal Muscles↗

Generation of genetically modified embryonic stem cells for the development of knockout mouse animal model systems.

The aim of our lab is to understand the contributions made by cell adhesion molecules in the processes of disease. Much of our recent work has focused on the role played by beta3-integrin in mediating pathological angiogenesis. It is fair to state that without the ability to manipulate the mouse genome, and specifically to create knockout mice, the advances we have made in this field would not be nearly as significant as they are. The ability to generate knockout mice depends on the two technological breakthroughs of the ability to isolate and culture mouse embryonic stem (ES) cells and the methods employed for achieving targeted gene replacement in these cells by homologous recombination. Here, we present the methods we have found to be successful, and that we routinely employ to grow and manipulate ES cells, as well as those to screen and identify homologous recombinants.

Animals↗

Balancing efficacy and safety in the use of oral sedation in dental outpatients.

BACKGROUND: Concerns about the safety of pediatric oral sedation and the incremental use of triazolam in adults prompted a workshop cosponsored by several professional organizations. OVERVIEW: There is a strong need and demand for adult and pediatric sedation services. Using oral medication to achieve anxiolysis in adults appears to have a wide margin of safety. Mortality and serious morbidity, however, have been reported with oral conscious sedation, especially in young children. Most serious adverse events are related to potentially avoidable respiratory complications. CONCLUSIONS: Clinical trials are needed to evaluate oral sedative drugs and combinations, as well as to develop discharge criteria with objective quantifiable measures of home readiness. Courses devoted to airway management should be developed for dentists who provide conscious sedation services. State regulation of enteral administration of sedatives to achieve conscious sedation is needed to ensure safety. PRACTICE IMPLICATIONS: Safety in outpatient sedation is of paramount concern, with enteral administration of benzodiazepines appearing safe but poorly documented in the office setting. Conscious sedation by the enteral route, including incremental triazolam, necessitates careful patient evaluation, monitoring, documentation, facilities, equipment and personnel as described in American Dental Association and American Academy of Pediatric Dentistry guidelines.

Adult↗

Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: an update.

The safe sedation of children for procedures requires a systematic approach that includes the following: no administration of sedating medication without the safety net of medical supervision; careful presedation evaluation for underlying medical or surgical conditions that would place the child at increased risk from sedating medications; appropriate fasting for elective procedures and a balance between depth of sedation and risk for those who are unable to fast because of the urgent nature of the procedure; a focused airway examination for large tonsils or anatomic airway abnormalities that might increase the potential for airway obstruction; a clear understanding of the pharmacokinetic and pharmacodynamic effects of the medications used for sedation, as well as an appreciation for drug interactions; appropriate training and skills in airway management to allow rescue of the patient; age- and size-appropriate equipment for airway management and venous access; appropriate medications and reversal agents; sufficient numbers of people to carry out the procedure and monitor the patient; appropriate physiologic monitoring during and after the procedure; a properly equipped and staffed recovery area; recovery to presedation level of consciousness before discharge from medical supervision; and appropriate discharge instructions. This report was developed through a collaborative effort of the American Academy of Pediatrics and the American Academy of Pediatric Dentistry to offer pediatric providers updated information and guidance in delivering safe sedation to children.

Child↗

Development of the palatine tonsil in conventional and germ-free piglets.

Palatine tonsils, like the Peyer's patches, are considered to be major inductive sites for the mucosa-associated lymphoid tissue (MALT), providing sampling and effector functions for the upper respiratory tract. Consistent with this, they have the architecture required of a classic inductive site (B-cell follicles, immunoglobulin class switching and the presence of naïve and memory T-cells). Here we show that much of this architecture develops after birth in the neonatal piglet, the numbers of T-cells, B-cells and accessory cells increasing with age. Conventional piglets also had higher levels of activated and memory T-cell subsets than germ-free piglets, consistent with development occurring as a result of microbial stimulus. The results suggest that the microbial environment influences the development of the tonsil immunological architecture. Given the role of the tonsil in induction of mucosal responses, this raises questions as to the effectiveness of the tonsil in dealing with colonising organisms in the neonate.

Age Factors↗

A roadmap for the immunomics of category A-C pathogens.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), recently awarded 14 contracts to fund the Large-Scale Antibody and T Cell Epitope Discovery Program. This initiative is designed to identify immune epitopes from selected infectious agents utilizing complementary methods for epitope discovery. NIAID will make information on each newly identified epitope freely available to scientists worldwide through the Immune Epitope Database and Analysis Resource (IEDB), currently under development. On October 12-14, 2004, representatives of NIAID met in San Diego, California, with a group of investigators from various research institutions to discuss progress and plans for the large-scale epitope discovery projects and for the establishment of the IEDB. It is anticipated that these initiatives will establish detailed maps of immune reactions toward several important complex pathogens, which in turn will foster development of new diagnostic, immune-based therapeutic, and vaccine programs. Herein is an account of the meeting and its results.

Animals↗

Continued in situ DNA fragmentation of microglia/macrophages in white matter weeks and months after traumatic brain injury.

Paraffin-embedded material from the pons of head-injured patients whose disability could be attributed to diffuse traumatic axonal injury, and controls, was identified from the department's archive. The cases were divided into three groups based on survival, viz Group 1 (n = 5) who survived for between 4 and 8 weeks, Group 2 (n = 5) for between 3 and 9 months, and Group 3 (n = 5) who survived for more that 12 months. Sections were stained by the TUNEL (TdT-mediated UTP nick end labelling) technique, and by H&E, LFB/CV and immunohistochemically for astrocytes (GFAP) and microglia/macrophages (CD68). Microscopic abnormalities were mapped onto line diagrams of two levels of the pons and quantitation of the response determined by an eye-piece graticule placed over the medial lemmisci, cortico-spinal and transverse fiber tracts. Data were pooled by region of interest. In the H&E and LFB/CV stained sections, there was variable pallor of staining in ascending and descending fiber tracts due to loss of myelin: within these same tracts there was an astrocytosis and increased numbers of microglia/macrophages compared with controls. In the white matter tracts of the controls, there was on average 1-2 TUNEL+ cells per unit area. In contrast, there were on average 2-16 TUNEL+ cells in the cortico-spinal tracts and in the medial lemnisci of all groups of head-injured patients. CD68+ cells co-located with the TUNEL+, and their number mirrored the TUNEL + staining with on average 16-30 cells per unit area in Group 1, 14-27 cells per unit area in Group 2, and 12-14 cells per unit area in Group 3. There was a statistical association between the TUNEL+ and CD68+ cells. Few changes were seen in the transverse fiber tracts of the pons. These findings indicate that most of the in situ DNA fragmentation occurred in microglia/macrophages in ascending and descending fiber tracts of the brain stem in which by conventional light microscopy there is Wallerian degeneration. However, in addition, a few TUNEL+ oligodendrocyte-like cells were also seen.

Adolescent↗

Left hemisphere motor facilitation in response to manual action sounds.

Previous studies indicate that the motor areas of both hemispheres are active when observing actions. Here we explored how the motor areas of each hemisphere respond to the sounds associated with actions. We used transcranial magnetic stimulation (TMS) to measure motor corticospinal excitability of hand muscles while listening to sounds. Sounds associated with bimanual actions produced greater motor corticospinal excitability than sounds associated with leg movements or control sounds. This facilitation was exclusively lateralized to the left hemisphere, the dominant hemisphere for language. These results are consistent with the hypothesis that action coding may be a precursor of language.

Adolescent↗

Lexically specific constructions in the acquisition of inflection in English.

Children learning English often omit grammatical words and morphemes, but there is still much debate over exactly why and in what contexts they do so. This study investigates the acquisition of three elements which instantiate the grammatical category of 'inflection'--copula be, auxiliary be and 3sg present agreement-in longitudinal transcripts from five children, whose ages range from 1;6 to 3;5 in the corpora examined. The aim is to determine whether inflection emerges as a unitary category, as predicted by some recent generative accounts, or whether it develops in a more piecemeal fashion, consistent with constructivist accounts. It is found that for each child the relative pace of development of the three morphemes studied varies significantly, suggesting that these morphemes do not depend on a unitary underlying category. Furthermore, early on, be is often used primarily with particular closed-class subjects, suggesting that forms such as he's and that's are learned as lexically specific constructions. These findings are argued to support the idea that children learn 'inflection' (and by hypothesis, other functional categories) not by filling in pre-specified slots in an innate structure, but by learning some specific constructions involving particular lexical items, before going on to gradually abstract more general construction types.

Child↗

Randomised controlled trial of home based care of patients with chronic obstructive pulmonary disease.

OBJECTIVES: To evaluate usefulness of limited community based care for patients with chronic obstructive pulmonary disease after discharge from hospital. DESIGN: Randomised controlled trial. SETTING: Liverpool Health Service and Macarthur Health Service in outer metropolitan Sydney between September 1999 and July 2000. PARTICIPANTS: 177 patients randomised into an intervention group (84 patients) and a control group (93 patients) which received current usual care. INTERVENTIONS: Home visits by community nurse at one and four weeks after discharge and preventive general practitioner care. MAIN OUTCOME MEASURES: Frequency of patients' presentation and admission to hospital; changes in patients' disease-specific quality of life, measured with St George's respiratory questionnaire, over three months after discharge; patients' knowledge of illness, self management, and satisfaction with care at discharge and three months later; frequency of general practitioner and nurse visits and their satisfaction with care. RESULTS: Intervention and control groups showed no differences in presentation or admission to hospital or in overall functional status. However, the intervention group improved their activity scores and the control group worsened their symptom scores. While intervention group patients received more visits from community nurses and were more satisfied with their care, involvement of general practitioners was much less (with only 31% (22) remembering receiving a care plan). Patients in the intervention group had higher knowledge scores and were more satisfied. There were no differences in general practitioner visits or management. CONCLUSIONS: This brief intervention after acute care improved patients' knowledge and some aspects of quality of life. However, it failed to prevent presentation and readmission to hospital.

Adult↗

Establishment of the telencephalon during gastrulation by local antagonism of Wnt signaling.

Cells at the anterior boundary of the neural plate (ANB) can induce telencephalic gene expression when transplanted to more posterior regions. Here, we identify a secreted Frizzled-related Wnt antagonist, Tlc, that is expressed in ANB cells and can cell nonautonomously promote telencephalic gene expression in a concentration-dependent manner. Moreover, abrogation of Tlc function compromises telencephalic development. We also identify Wnt8b as a locally acting modulator of regional fate in the anterior neural plate and a likely target for antagonism by Tlc. Finally, we show that tlc expression is regulated by signals that establish early antero-posterior and dorso-ventral ectodermal pattern. From these studies, we propose that local antagonism of Wnt activity within the anterior ectoderm is required to establish the telencephalon.

Animals↗

Bispectral EEG index monitoring of high-dose nitrous oxide and low-dose sevoflurane sedation.

This single-blind controlled clinical study characterized the effects of 30-70% nitrous oxide (N2O) and 0.2-0.8% sevoflurane conscious sedation on quantitative electroencephalographic (EEG) readings of 22 healthy dental students as measured by the bispectral index (BIS). The study verified the 2 previously published BIS/N2O investigations showing no correlation between N2O dosage up to 70% and BIS. Observer's Assessment of Alertness and Sedation scores (OAA/S), however, correlated well with increasing doses of N2O from approximately 35 to 70%. A near linear dose-response relationship was established between OAA/S and end tidal (ET) sevoflurane concentrations of 0.4-0.7%. Only at the highest level of end tidal sevoflurane recorded, 0.7%, was statistically significant BIS depression seen. Subjects evaluated the acceptability of the sedative effect of the 2 gases, showing a slight preference for N2O. Comparable partial anterograde amnesia and sedation (OAA/S) were produced by both agents in administered concentrations of 40-70% N2O and 0.6-0.8% sevoflurane. Female subjects exhibited better memory and significantly less amnesia than males. No statistically significant changes occurred in any of the monitored vital signs. EMG readings demonstrated a statistically significant difference from control values only at the highest, 0.7%, ET concentration of sevoflurane. BIS does not appear useful for evaluating the level of nitrous oxide sedation in the dental setting but may have some value in assessing depth of sedation at deeper levels of sevoflurane sedation.

Adult↗

Pharmacokinetics of lidocaine delivered from a transmucosal patch in children.

The DentiPatch lidocaine transoral delivery system (Noven Pharmaceuticals) is indicated for mild topical anesthesia of mucosal membranes in the mouth. The DentiPatch is a mucoadhesive patch containing 46.1 mg of lidocaine (20% concentration). Current studies in adults report that DentiPatch application produces very low plasma concentrations of lidocaine. However, it is not known what plasma levels are obtained when the same dosage is used in children. The purpose of this study was to determine whether the plasma lidocaine concentrations generated by the DentiPatch are within a safe range for children. The sample in this study was 11 children aged 2-7 years requiring general anesthesia for comprehensive dental care. A lidocaine DentiPatch was placed on the buccal mucosa above the maxillary incisors for 5 minutes. Blood samples were drawn before placing the DentiPatch and at various time intervals after removing it. Blood samples were analyzed by fluorescence polarization immunoassay to determine the plasma concentrations of lidocaine and its major metabolite, monoethylglycinexylidide. The lidocaine and monoethylglycinexylidide absorbed from the DentiPatch did not reach toxic plasma levels in children. However, plasma concentrations were much higher than in adults and were high enough to require inclusion in the calculation of total lidocaine administered to a pediatric patient.

Administration, Buccal↗