PubMed Health⌕ Search

Biomedical subjects

E Wilson

Publications and source records attributed to E Wilson.

At least 37 records · Page 2Linked to original sources
PubMed2002

Direct and indirect cost of general aviation crashes.

BACKGROUND: There have been few well-designed studies which estimate the costs inflicted on society from injuries, fatalities, and property damage caused by aviation crashes. Furthermore, indirect cost estimates from the human capital (HC) approach tend to be substantially smaller than those obtained from the willingness-to-pay (WTP) approach. OBJECTIVES: To estimate the direct and indirect costs of general aviation crashes in New Zealand, and to contrast the HC and WTP approaches used to estimate indirect costs. METHODS: The incidence, morbidity, and mortality from aviation crashes between 1988 and 1997 were estimated from national health and aviation records. Direct costs included medical treatment, damage to aircraft and property, and the cost of crash investigation. For the HC approach, we valued losses to society as the value of lost production from both employed work and household activity. For the WTP approach, we used the Land Transport Safety Authority's estimated values of society's willingness to pay to avoid a fatality or injury. RESULTS: The annual average direct cost of aviation crashes was $9.1 m (range: $8.0 m to $11.4 m). The annual average indirect cost using the HC approach was $13.6 m ($5.6 m to $32.2 m). Using the WTP approach the annual average indirect costs was $49.3 m ($20.6 m to $106.5 m). Indirect costs from premature deaths were the key cost drivers. A sensitivity analysis showed that these values were relatively robust to changes in parameters. CONCLUSION: The annual average cost of general aviation crashes in New Zealand was between $22.6 m and $58.4 m. Indirect costs using the WTP approach were 3.5 times greater than those estimated using the HC approach.

Accidents, Aviation↗
PubMed2001

Merging nitrogen management and renewable energy needs.

The ARBRE (ARable Biomass Renewable Energy) project, the first large-scale wood-fueled electricity generating plant in the U.K., represents a significant development in realising British and European policy objectives on renewable energy. The plant is fueled by a mix of wood from short rotation coppice (SRC) and forest residues. Where feasible, composted/conditioned sewage sludge is applied to coppice sites to increase yields and improve soil structure. In the Yorkshire Water region, typical total N:P:K composition of composted/conditioned sludge is 2.9:3.8:0.3, respectively. Sludge application is calculated on the basis of total nitrogen (N) content to achieve 750 kg N ha(-1), for 3 years" requirement. Willow coppice forms a dense, widely spaced, root network, which, with its long growing season, makes it an effective user of nutrients. This, in combination with willow"s use as a nonfood, nonfodder crop, makes it an attractive route for the recycling of sewage sludge in the absence of sea disposal, banned under the EC Urban Waste Water Treatment Directive (UWWTD). Further work is required on the nutritional requirements of SRC in order to understand better the quantities of sludge that can be applied to SRC without having a detrimental impact on the environment. This paper suggests the source of N rerouting under the UWWTD and suggests the likely expansion of SRC as an alternative recycling pathway.

Biomass↗
PubMed2001

Regulation of the L-type calcium channel by alpha 5beta 1 integrin requires signaling between focal adhesion proteins.

The L-type calcium channel is the major calcium influx pathway in vascular smooth muscle and is regulated by integrin ligands, suggesting an important link between extracellular matrix and vascular tone regulation in tissue injury and remodeling. We examined the role of integrin-linked tyrosine kinases and focal adhesion proteins in regulation of L-type calcium current in single vascular myocytes. Soluble tyrosine kinase inhibitors blocked the increase in current produced by alpha(5) integrin antibody or fibronectin, whereas tyrosine phosphatase inhibition enhanced the effect. Cell dialysis with an antibody to focal adhesion kinase or with FRNK, the C-terminal noncatalytic domain of focal adhesion kinase, produced moderate (24 or 18%, respectively) inhibition of basal current but much greater inhibition (63 or 68%, respectively) of integrin-enhanced current. A c-Src antibody and peptide inhibitors of the Src homology-2 domain or a putative Src tyrosine phosphorylation site on the channel produced similar inhibition. Antibodies to the cytoskeletal proteins paxillin and vinculin, but not alpha-actinin, inhibited integrin-dependent current by 65-80%. Therefore, alpha(5)beta(1) integrin appears to regulate a tyrosine phosphorylation cascade involving Src and various focal adhesion proteins that control the function of the L-type calcium channel. This interaction may represent a novel mechanism for control of calcium influx in vascular smooth muscle and other cell types.

Actinin↗
PubMed2001

Gene therapy for the treatment of hemophilia B using PINC-formulated plasmid delivered to muscle with electroporation.

Gene therapy, as a safe and efficacious treatment or prevention of diseases, is one of the next fundamental medical innovations. Direct injection of plasmid into skeletal muscle is still a relatively inefficient and highly variable method of gene transfer. However, published reports have shown that application of an electric field to the muscle immediately after plasmid injection increases gene expression at least 2 orders of magnitude. Using this methodology, we have achieved potentially therapeutic circulating levels of human factor IX (hF.IX) in mice and dogs. A plasmid encoding hF.IX formulated with a protective, interactive, noncondensing (PINC) polymer was injected into the skeletal muscle followed by administration of multiple electrical pulses (electroporation). In mice long-term expression was achieved and the ability to readminister formulated plasmid was demonstrated. In normal dogs, expression of hF.IX reached 0.5-1.0% of normal levels. The transient response in dogs was due to the development of antibodies against hF.IX. Elevated circulating creatine kinase levels and histological examination indicated transient minor trauma associated with the procedure. These data show that gene delivery using a plasmid formulated with a PINC polymer augmented with electroporation is scalable into large animal models and represents a promising approach for treating patients with hemophilia B.

Animals↗
PubMed2001

Fusogenic activity of vesicular stomatitis virus glycoprotein plasmid in tumors as an enhancer of IL-12 gene therapy.

We have characterized the fusogenic activity of a plasmid expression system encoding vesicular stomatitis virus G protein (VSVG) in vitro and in vivo. Over 70% of murine colon and renal carcinoma cells (MC38 and Renca, respectively) transfected with VSVG plasmid in vitro fused and formed polykaryons upon incubation with pH 5.5 media. Using a plasmid expression system encoding VSVG and bacterial green fluorescent protein (GFP) formulated in a polyvinyl pyrrolidone (PVP) delivery system, diffusion of GFP throughout the VSVG-induced syncytia was shown in vivo in MC38 and Renca tumors. Moreover, tumor-bearing mice showed tumor growth inhibition following in vivo transfection with VSVG plasmid at an optimal dose of 48 microg. We have previously shown that direct injection of interleukin -12 (IL -12) plasmid complexed with PVP into tumors induces a strong immune response. In the current study, we assessed the ability of VSVG to elicit an antitumor response by enhancing cytokine gene delivery within the tumor mass. Tumor-bearing mice treated intratumorally with both VSVG/PVP and IL-12/PVP (48 and 24 microg, respectively) showed increase in tumor rejection when compared to IL- 12 plasmid alone (75% vs. 50%, respectively). These data suggest that VSVG gene therapy can be used in combination with other therapeutic genes to induce an antitumor response in vivo by enhancing the expression of the gene of interest.

Animals↗
PubMed2001

Free flap reconstruction of the head and neck: analysis of 241 cases.

OBJECTIVE: We undertook this study of free flap reconstruction of the head and neck to stratify patients and procedures, to determine how donor site preference changed over time, to assess medical and surgical outcomes, and to identify variables associated with complications. METHODS: We analyzed computerized medical records from 236 patients who underwent a total of 241 reconstructions at a tertiary academic medical center in St. Louis between 1989 and 1998. We created a more detailed retrospective database of 141 of those patients by using 48 perioperative variables and 7 adverse outcome measures. Multivariate statistical models were used to analyze associations between variables and outcomes. RESULTS: The fibula became the preferred donor site for mandibular reconstruction, and the radial forearm became the preferred donor site for pharyngoesophageal reconstruction. For the 241 procedures, the mortality rate was 2.1%, the median length of stay was 11 days, and the flap survival rate was 95%. Administration of more than 7 L of crystalloid during surgery and age over 55 were associated with major medical complications. Blood transfusion, prognostic comorbidity, and number of surgeons correlated with length of stay. Cigarette smoking and receipt of more than 7 L of crystalloid during surgery were associated with overall flap complications, and weight loss of more than 10% before surgery, more than one operating surgeon, and cigarette smoking were associated with major flap complications. CONCLUSIONS: Risk to patients and transferred tissue is low in free flap head and neck reconstruction. Age, smoking history, and weight loss should be considered during patient selection. Fluid balance should be considered during and after surgery. Division of labor for patient care should be carefully delineated among surgeons in a teaching setting.

Adolescent↗
PubMed2001

Regulation of ion channels by protein tyrosine phosphorylation.

Ion channels are regulated by protein phosphorylation and dephosphorylation of serine, threonine, and tyrosine residues. Evidence for the latter process, tyrosine phosphorylation, has increased substantially since this topic was last reviewed. In this review, we present a comprehensive summary and synthesis of the literature regarding the mechanism and function of ion channel regulation by protein tyrosine kinases and phosphatases. Coverage includes the majority of voltage-gated, ligand-gated, and second messenger-gated channels as well as several types of channels that have not yet been cloned, including store-operated Ca2+ channels, nonselective cation channels, and epithelial Na+ and Cl- channels. Additionally, we discuss the critical roles that channel-associated scaffolding proteins may play in localizing protein tyrosine kinases and phosphatases to the vicinity of ion channels.

Animals↗
PubMed2001

Mortality during the winter flu epidemic--two cases of death associated with self-medication.

We report two cases of mortality associated with the recent winter influenza outbreak. Both cases were associated with self-medication. In one case an elderly lady died from haemorrhagic duodenitis induced by over the counter ibuprofen. In the second case the lady died from the consequences of exceeding the recommended doses of paracetamol by combining doses of the generic product with proprietary flu-remedies and Tylex (paracetamol and codeine).

Acetaminophen↗
PubMed2000

Synthetic glycopeptide-based delivery systems for systemic gene targeting to hepatocytes.

PURPOSE: To design, synthesize, and test synthetic glycopeptide-based delivery systems for gene targeting to hepatocytes by systemic administration. METHODS: All peptides were synthesized by the solid phase method developed using Fmoc chemistry on a peptide synthesizer. The binding of galactosylated peptides to HepG2 cells and accessibility of the galactose residues on particle surface was demonstrated by a competition assay using 125I-labeled asialoorosomucoid and RCA lectin agglutination assay, respectively. DNA plasmid encoding chloramphenicol acetyl transferase (CAT) gene was complexed with a tri-galactosylated peptide (GM245.3) or tri-galactosylated lipopeptide (GM246.3) in the presence of an endosomolytic peptide (GM225.1) or endosomolytic lipopeptide (GM227.3) to obtain DNA particles of 100-150 nm in size. The plasmid/peptide complexes were added to HepG2 cell cultures or intravenously administered by tail vein injection into normal mice or rats. Plasmid uptake and expression was quantified by qPCR and ELISA, respectively. RESULTS: Multiple antennary glycopeptides that have the ability to condense and deliver DNA plasmid to hepatocytes were synthesized and complexed with DNA plasmid to obtain colloidally stable DNA/peptide complexes. Addition of DNA/GM245.3/GM225.1 peptide complexes (1:3:1 (-/+/-)) to HepG2 cell cultures yielded CAT expression in transfected cells. The transfection efficiency was significantly reduced in the absence of galactose ligand or removal of endosomolytic peptide. Intravenous administration of DNA/GM245.3 peptide complexes (1:0.5 (-/+)) into the tail vein of normal rats yielded DNA uptake in the liver. Substitution of GM245.3 by galactosylated lipopeptide GM246.3 resulted in more stable DNA particles, and a 10-fold enhancement in liver plasmid uptake. CAT expression was detectable in liver following intravenous administration of DNA/GM246.3 complexes. Addition of endosomolytic lipopeptide GM227.3 into the complexes (DNA/ GM246.3/GM227.3 (1:0.5:1 (-/+/-))) yielded a 5-fold increase in CAT expression. Liver expression was 8-fold and 40-fold higher than lung and spleen, respectively, and localized in the hepatocytes only. The transfection efficiency in liver was enhanced by increasing DNA dose and injection volume. The plasmid uptake and expression in liver using DNA/GM246.3/GM227.3 complexes was 100-200-fold higher than DNA formulated in glucose. Tissue examination and serum biochemistry did not show any adverse effect of the DNA/GM246.3/ GM227.3 (1:0.5:1 (-/+/-)) complexes after intravenous delivery. CONCLUSIONS: Gene targeting to hepatocytes was achieved by systemic administration of a well-tolerated synthetic glycopeptide-based delivery system. The transfection efficiency of this glycopeptide delivery system was dependent on peptide structure, endosomolytic activity, colloidal particle stability, and injection volume.

Amino Acid Sequence↗
PubMed2000

Ultrasound enhancement of cationic lipid-mediated gene transfer to primary tumors following systemic administration.

The impact of a localized application of ultrasound on gene transfer to primary tumors following systemic administration of cationic lipid based transfection complexes was investigated. We have previously shown that systemic administration of DOTMA (N-[(1-(2-3-dioleyloxy) propyl)]-N-N-N-trimethylammonium chloride):cholesterol-based transfection complexes to tumor-bearing mice resulted in expression in the tumor and other tissues, primarily the lungs. Application of ultrasound to the tumor before or after the injection resulted in a significant increase in gene transfer to the tumor with no increase observed in other tissues. The magnitude of increased expression ranged from three- to 270-fold depending upon the DNA dose. The following parameters were optimized for maximal increase: duration of ultrasound application, the time interval between plasmid injection and sonoporation, and plasmid dose. A combination of plasmid quantitation and fluorescence microscopy showed that ultrasound increased tumor uptake of the plasmid and that uptake was limited to the tumor vasculature. Using an IL- 12 expression plasmid, the combination of a single plasmid dose (10 microg) and ultrasound treatment produced significantly higher levels of IL-12 in tumor. This increased expression was sufficient to inhibit tumor growth compared with the control conditions. These data demonstrate the potential application of sonoporation as an effective method for enhancing the expression of systemically administered genes in tumor endothelium for cancer gene therapy.

Animals↗
PubMed2000

The conditioned response erection (CRE)--a new approach to modelling erectile responses in the rat.

Several animal models are currently used in erectile (dys)function research; these models fail to account for the conditions involving the more spontaneous erections in humans. Recently, we observed an increase in the number of 'spontaneously' occurring erections in rats with previous exposure to apomorphine (APO), a centrally acting drug that initiates penile erections and yawns. Based on this observation, we designed a series of experiments to characterize the development of enhanced, non-apomorphine-induced erections or 'spontaneous' erectile responses to vehicle administration in rats with previous exposure to APO. We further examined the effects of castration on these conditioned erections. Naive (ie never received APO) rats were administered vehicle (1 ml/kg saline) to determine the frequency of baseline erections and yawns. An alternating series of APO (80 microg/kg s.c.) and vehicle administrations were performed over several days and subsequent erectile and yawning responses were recorded. Following 3 sets of 3 APO administrations (with vehicle administered between sets), and the 3rd vehicle administration, these rats were then surgically castrated and allowed 30 days to recover. Following this, APO was administered 3 times to determine erectile and yawning responses post-castration, followed by vehicle administration to determine the effects of castration on conditioned APO responses. The major findings were: (1) that although naive rats had a basal spontaneous erectile response (0.75 +/- 0.88; 4 of 8 rats with at least one erection), repetitive administration (up to 22 treatments) of the central initiator apomorphine significantly increased the number of erections (1.8 +/- 0.7; 7 of 8 rats with at least one erection) and yawning (2.5 +/- 2.47) responses to vehicle administration; and (2) both spontaneous yawning and erectile responses were found to be androgen dependent since castration dramatically lowered the number of erections (0.13 +/- 0.35; 1 of 8 rats with at least one erection) and yawns (0). Therefore, this method of producing erections without a pharmacological manipulation provides an additional animal model which can be used in conjunction with the APO-induced erections in characterizing the physiology and pathophysiology of erectile function in conscious rats.

Androgens↗