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Biomedical subjects

E C Wang

Publications and source records attributed to E C Wang.

At least 19 recordsLinked to original sources
PubMed2001

Use of an interactive tool to assess patients' willingness-to-pay.

Assessment of willingness to pay (WTP) has become an important issue in health care technology assessment and in providing insight into the risks and benefits of treatment options. We have accordingly explored the use of an interactive method for assessment of WTP. To illustrate our methodology, we describe the development and testing of an interactive tool to administer a WTP survey in a dental setting. The tool was developed to measure patient preference and strength of preference for three dental anesthetic options in a research setting. It delivered written and verbal formats simultaneously, including information about the risks and benefits of treatment options, insurance, and user-based WTP scenarios and questions on previous dental experience. Clinical information was presented using a modified decision aid. Subjects could request additional clinical information and review this information throughout the survey. Information and question algorithms were individualized, depending on the subject's reported clinical status and previous responses. Initial pretesting resulted in substantial modifications to the initial tool: shortening the clinical information (by making more of it optional reading) and personalizing the text to more fully engage the user. In terms of results 196 general population subjects were recruited using random-digit dialing in southwestern Ontario, Canada. Comprehension was tested to ensure the instrument clearly conveyed the clinical information; the average score was 97%. Subjects rated the instrument as easy/very easy to use (99%), interesting/very interesting (91%), and neither long nor short (72.4%). Most subjects were comfortable/very comfortable with a computer (84%). Indirect evaluation revealed most subjects completed the survey in the expected time (30 min). Additional information was requested by 50% of subjects, an average of 2.9 times each. Most subjects wanted this type of information available in the provider's office for use in clinical decision making (92%). Despite extensive pretesting, three "bugs" remained undiscovered until live use. We have demonstrated that the detailed information, complex algorithms, and cognitively challenging questions involved in a WTP survey can be successfully administered using a tailor-made, patient-based, interactive computer tool. Key lessons regarding the use of such tools include allowing the user to set the pace of information flow and tailor the content, engaging the user by personalizing the textual information, inclusion of tests of comprehension and offering opportunities for correction, and pretesting by fully mimicking the live environment.

Adult↗
PubMed2001

Methodology standards associated with quality reporting in clinical studies in pediatric surgery journals.

BACKGROUND/PURPOSE: Reports of clinical trials often lack adequate descriptions of design and analysis; recent attention has focused on improving this omission so readers can properly assess the strength of the findings and draw their own conclusions. Similar analysis of study design and methodologic standards associated with quality reporting has not been carried out for pediatric surgery journals. METHODS: All studies (n = 642) published in 1998 in Journal of Pediatric Surgery (JPS) and Pediatric Surgery International (PSI), were reviewed for demographic data and study design. The frequency of reporting of 11 basic elements of design and analysis was evaluated in randomized clinical trials (RCT), nonrandomized clinical trials (NRCT), and retrospective cohorts (RC) from JPS by consensus of 2 assessors. RESULTS: Of the 642 studies, 17% of articles (111 of 642) were classified as clinical studies. Sixty-three were comparative studies and consisted of RC (n = 48), NRCT (n = 12), and RCT (n = 3). Two-thirds of articles published were either case reports or case series (431 of 642), and 16% were basic science articles. Demographic analysis showed a wide range of topics addressed, 4 authors per article, and multiple country of origin of authors. More than 66% of all RCT in JPS reported on eligibility criteria, admission before allocation, random allocation, method of randomization, patients' blindness to treatment, treatment complications, statistical analyses, statistical methods, loss to follow-up, and statistical methods; 2 elements of design and analysis, however, were poorly reported: blind assessment of outcome (33%) and power (17%). CONCLUSIONS: There were few randomized, controlled trials in pediatric surgery journals, and further attention should be given to evaluate the causal factors. Nine elements of quality reporting were well reported; however, 2 others were poorly reported; this may improve if editors of pediatric surgical journals provide authors with guidelines on how to report clinical trial design and analysis.

Authorship↗
PubMed2001

Functional differences between influenza A-specific cytotoxic T lymphocyte clones expressing dominant and subdominant TCR.

We have shown that the dominance of CD8+ T cells expressing TCR Vbeta17 in the adult HLA-A*0201-restricted influenza A/M1(58-66)-specific response is acquired following first antigen exposure. Despite the acquired dominance of Vbeta17+ cells, subdominant M1(58-66)-specific clones expressing non-Vbeta17+ TCR persist in all individuals. To determine whether the affinity of the expressed TCR for the HLA-A*0201/M1(58-66) complex could influence functional properties, M1(58-66)-specific clones expressing subdominant (non-Vbeta17+) TCR were compared to cytotoxic T lymphocyte (CTL) clones expressing dominant (Vbeta17+) TCR. The Vbeta17+ CTL required up to 10,000-fold lower amounts of M1 peptide to mediate lysis compared to CTL clones expressing other Vbeta gene segments. All Vbeta17+ CTL clones tested bound HLA-A*0201/M1(58-66) tetramer, but two of three CTL clones expressing other TCR did not bind tetramer. The inability of non-Vbeta17+ CTL to bind tetramer did not correlate with phenotype, CD8 dependence or with cytokine production profiles. This suggests a limitation for the use of tetramers in examining subdominant T cell responses. Together these findings suggest that Vbeta17+ CTL which dominate the HLA-A*0201-restricted CTL response against influenza A are not functionally distinct from subdominant non-Vbeta17+ CTL. The dominance of Vbeta17+ CTL is likely to result from a competitive advantage due to superior CTL avidity for the HLA-A*0201/M1(58-66) complex.

Adult↗
PubMed2001

DR3 regulates negative selection during thymocyte development.

DR3 (Ws1, Apo3, LARD, TRAMP, TNFSFR12) is a member of the death domain-containing tumor necrosis factor receptor (TNFR) superfamily, members of which mediate a variety of developmental events including the regulation of cell proliferation, differentiation, and apoptosis. We have investigated the in vivo role(s) of DR3 by generating mice congenitally deficient in the expression of the DR3 gene. We show that negative selection and anti-CD3-induced apoptosis are significantly impaired in DR3-null mice. In contrast, both superantigen-induced negative selection and positive selection are normal. The pre-T-cell receptor-mediated checkpoint, which is dependent on TNFR signaling, is also unaffected in DR3-deficient mice. These data reveal a nonredundant in vivo role for this TNF receptor family member in the removal of self-reactive T cells in the thymus.

Animals↗
PubMed2000

Cost-effectiveness analysis of budesonide aqueous nasal spray and fluticasone propionate nasal spray in the treatment of perennial allergic rhinitis.

BACKGROUND: An economic evaluation was performed analyzing direct medical costs in Canada for the treatment of perennial allergic rhinitis (PAR) with budesonide aqueous nasal spray and fluticasone propionate nasal spray. Three hundred fourteen patients with at least a 1-year history of PAR were randomized into a double-blind, parallel-group study of 6 weeks' duration. The treatments were daily doses of budesonide 256 microg, fluticasone propionate 200 microg, or placebo. Both active treatments produced significantly lower mean scores for overall nasal symptoms compared with placebo, and both were well tolerated. Budesonide was significantly more effective than fluticasone in reducing "blocked nose." METHOD: A retrospective cost-effectiveness analysis utilizing the clinical trial data was performed on the total costs of (1) budesonide-based and (2) fluticasone-based treatment strategies, including the relative importance of the drug costs in both strategies. RESULTS: The average treatment cost per patient in Canada over 12 months in the budesonide group was CAD 389.85 which was 23.3% lower than in the fluticasone group, which was CAD 508.06, due to lower drug acquisition costs (for the year 1998). CONCLUSION: Budesonide aqueous nasal spray was shown to be more cost-effective than fluticasone propionate nasal spray in the treatment of perennial allergic rhinitis. This result is valid in the province of Ontario, Canada and in many other settings with the same structure of relative prices. The result is mainly driven by a difference in drug cost.

Androstadienes↗
PubMed1999

A central role for alpha beta T cells in the pathogenesis of murine lupus.

We have previously shown that female transgenic mice expressing IFN-gamma in the epidermis, under the control of the involucrin promoter, develop inflammatory skin disease and a form of murine lupus. To investigate the pathogenesis of this syndrome, we generated female IFN-gamma transgenic mice congenitally deficient in either alpha beta or gamma delta T cells. TCR delta-/- transgenics continued to produce antinuclear autoantibodies and to develop severe kidney lesions. In contrast, TCR beta-/- IFN-gamma transgenic mice failed to produce antinucleosome, anti-dsDNA, or antihistone autoantibodies, and kidney disease was abolished. Both alpha beta- and gamma delta-deficient transgenics continued to develop IFN-gamma-associated skin disease, lymphadenopathy, and splenomegaly. The data show that the autoantibody-mediated pathology of murine lupus in IFN-gamma transgenic mice is completely alpha beta T cell dependent and that gamma delta T cells cannot drive autoantibody production. These results imply that production of antinuclear autoantibodies in IFN-gamma transgenic animals is Ag driven, and we identified clusters of apoptotic cells in the epidermis of the mice as a possible source of self Ags. Our findings emphasize the relevance of this murine lupus model to the human disease.

Animals↗
PubMed1999

The measurement of stress-related immune dysfunction in psychoneuroimmunology.

In recent years there has been a dramatic increase in research dedicated to the psycho-behavioural modulation of immune function, i.e. the field of Psychoneuroimmunology (PNI). This has led, necessarily, to the use of several in vitro and in vivo techniques in attempts to delineate the relationship between these two phenomena. However, since the field's inception, considerable uncertainty has existed over the significance of the immune outcomes detected and this has been compounded by the equivocal nature of some of the published data. A great deal of this uncertainty could, however, be overcome if a clearer understanding was achieved on the advantages and limitations conferred by the manifold immune assays described in the literature. This would, in turn, encourage their more appropriate use within PNI. Hence, in this review we describe the rationale behind, and offer an evaluation of, some of the more frequently used in vitro and in vivo immunological and virological techniques. We hope that a clear understanding of the rationale behind such assays and their inherent advantages and limitations will inform the discussion of the significance of stress-related immune impairment.

Animals↗
PubMed1999

Dysfunctional glucocorticoid receptor with a single point mutation ablates the CCAAT/enhancer binding protein-dependent growth suppression response in a steroid-resistant rat hepatoma cell variant.

We used glucocorticoid-resistant and -sensitive hepatoma cell variants to characterize the mechanism of hepatoma cell resistance to the growth inhibitory effects of glucocorticoids. BDS1 hepatoma cells express transcriptionally active glucocorticoid receptors and undergo a stringent G1 cell cycle arrest in response to glucocorticoids that is dependent on the induced expression of the CCAAT/enhancer binding protein alpha (C/EBPalpha) transcription factor. In contrast, EDR1 hepatoma cells, which express normal levels of glucocorticoid receptors, fail to growth arrest or express C/EBPalpha when treated with glucocorticoids. Ectopic expression of wild-type rat glucocorticoid receptors into EDR1 cells restored the growth suppression response, suggesting a defect in the EDR1 receptor. DNA sequence analysis revealed a single point mutation causing a cysteine-to-tyrosine substitution at amino acid position 457 (C457Y-GR) in the zinc finger region of the glucocorticoid receptor that mediates both receptor-DNA and receptor-protein interactions. Glucocorticoid activation of the alpha1-acid glycoprotein (AGP) promoter, a liver acute-phase response gene, requires receptor-DNA binding as well as an interaction with C/EBPalpha. In contrast to the wild-type glucocorticoid receptor, ectopic expression of C/EBPalpha in EDR1 cells, or coexpression of C/EBPalpha along with the C457Y-GR into receptor-deficient EDR3 cells was required to partially restore glucocorticoid responsiveness of the AGP promoter by the EDR1 glucocorticoid receptor. Constitutive expression of the wild-type glucocorticoid receptor, but not the C457Y-GR mutant, was sufficient to restore the glucocorticoid growth suppression response to receptor-deficient EDR3 cells. Thus, we have identified a glucocorticoid-resistant hepatoma cell variant with a single point mutation in the zinc finger region of the glucocorticoid receptor gene that ablates the glucocorticoid growth suppression response and attenuates transcriptional activation of the AGP promoter.

Animals↗
PubMed1999

Applying epidemiology-based outcomes research to clinical decision-making. A hypothetical model of biotechnology therapy in gram-negative sepsis.

OBJECTIVE: Sepsis occurs in a heterogeneous population. A prospective nationwide surveillance study found that populations stratified by infection type had significant differences in the incidence of sepsis syndrome, rate of complications and mortality. The objective of this study was to explore whether successful identification of population-specific risk factors for disease-associated morbidity and mortality may allow for more accurate assessment of the cost effectiveness of treatment strategies. DESIGN: A decision analytic model was developed using outcomes data on incidence and resolution of major complications in sepsis syndrome. Healthcare resource utilisation data were based on length of hospital stay, intensive care unit stay versus hospital ward stay, and cost of treating sepsis-related complications. SETTING: This modelling study, conducted from the perspective of the healthcare institution, used actual outcomes data on 2 infection-specific patient populations. PATIENTS AND PARTICIPANTS: The 2 populations studied were patients with nosocomial respiratory tract infection or community-acquired urinary tract infection who subsequently developed sepsis syndrome. INTERVENTIONS: Treatment options modelled were standard therapy plus biotechnology therapy versus standard therapy alone in the treatment of gram-negative sepsis complications. MAIN OUTCOME MEASURES AND RESULTS: The incremental cost-effectiveness ratios differed between the 2 study populations, due to differences in the incidence and rate of resolution of major sepsis-associated complications. The use of biotechnology therapy is always more cost effective in the respiratory tract infection population. CONCLUSIONS: Cost-effectiveness results for a therapy may change when the epidemiology of the disease state is known and incorporated into the decision analytic model. An infection-specific approach is important in the treatment of sepsis.

Decision Making↗
PubMed1998

Human cytomegalovirus infection downregulates expression of the cellular aminopeptidases CD10 and CD13.

During the course of a productive infection, human cytomegalovirus (HCMV) has a sophisticated relationship with its host cell. An increasing number of virus-encoded genes are being identified which act specifically to usurp or modulate functions in the host cell associated with transcriptional control, cell signalling, and protein synthesis. While HCMV infection is associated with a general upregulation of cellular gene expression, the expression a small subset of cellular proteins, including the MHC-1 heavy chain and fibronectin, is downregulated. This study now identifies two additional cellular proteins, aminopeptidase N (CD13) and neutral endopeptidase (CD10), that are downregulated during HCMV infection. While aminopeptidase N and neutral endopeptidase exhibit no significant sequence homology, both are expressed on the cell surface and have very similar enzymatic properties. HCMV infection was associated with reduced surface expression and enzyme activity of CD13 and CD10, an apparent decrease in the rate of synthesis of both proteins in metabolic-labelling experiments, and inhibited glycosylation of the nascent CD13 and CD10 polypeptide chains that were synthesized. Levels of CD10 poly A+ RNA were suppressed efficiently at all stages of virus infection; however, the reduction in CD13 poly A+ RNA levels was much less pronounced. This differential effect suggests that HCMV may be downregulating expression of CD10 and CD13 by independent mechanisms. Indeed, treatment of cells with an inhibitor of viral DNA synthesis blocks downregulation of CD13, whilst downregulation of CD10 is unaffected. While it is not yet clear what advantage is bestowed on the virus by downregulating expression of CD13 and CD10, aminopeptidases are known to have a role in peptide processing in both the MHC class I the MHC class II antigen presentation pathways.

CD13 Antigens↗
PubMed1998

Glucocorticoids stimulate p21 gene expression by targeting multiple transcriptional elements within a steroid responsive region of the p21waf1/cip1 promoter in rat hepatoma cells.

Glucocorticoids can induce a G1 arrest in the cell cycle progression of BDS1 rat hepatoma cells. In these cells, dexamethasone, a synthetic glucocorticoid, stimulated a rapid and selective increase in expression of the p21 cyclin-dependent kinase (CDK) inhibitor mRNA and protein and virtually abolished CDK2 phosphorylation of the retinoblastoma protein. Expression of the p27 CDK inhibitor, and other G1-acting cell cycle proteins, remained unaffected. Dexamethasone stimulated p21 promoter activity in a p53-independent manner that required functional glucocorticoid receptors. Transforming growth factor-beta, which also induced a G1 cell cycle arrest of the hepatoma cells, failed to elicit this response. Analysis of 5' deletions of the p21 promoter uncovered a glucocorticoid responsive region between nucleotides -1481 and -1184, which does not contain a canonical glucocorticoid response element but which can confer dexamethasone responsiveness to a heterologous promoter. Fine mapping of this region uncovered three distinct 50-60-base pair transcriptional elements that likely function as targets of glucocorticoid receptor signaling. Finally, ectopic expression of p21 had no effect on hepatoma cell growth in the absence of glucocorticoids but facilitated the ability of dexamethasone to inhibit cell proliferation. Thus, our results have established a direct transcriptional link between glucocorticoid receptor signaling and the regulated promoter activity of a CDK inhibitor gene that is involved in the cell cycle arrest of hepatoma cells.

Animals↗
PubMed1998

Role of the CCAAT/enhancer binding protein-alpha transcription factor in the glucocorticoid stimulation of p21waf1/cip1 gene promoter activity in growth-arrested rat hepatoma cells.

The preceding paper (Cha, H. H., Cram, E. J., Wang, E. C., Huang, A. J., Kasler, H. G., and Firestone, G. L. (1998) J. Biol. Chem. 273, 0000-0000(478563) defined a glucocorticoid responsive region within teh promoter of the p21 CDK inhibitor gene that contains a putative DNA-binding site for the transcription factor CCAAT/ enhancer binding protein-alpha (C/EBP alpha). Wild type rat BDS1 hepatoma cells as well as as4 hepatoma cells, which express antisense sequences to C/EBP alpha and ablate its protein production, were utilized to investigate the role of this transcription factor in the glucocorticoid regulation of p21 gene expression. The stimulation of p21 protein levels and promoter activity, as well as inhibition of CDK2-mediated retinoblastoma protein phosphorylation, by the synthetic glucocorticoid, dexamethasone, required the expression of C/EBP alpha. Overexpression of C/EBP alpha in as4 cells rescued the dexamethasone responsiveness of the p21 promoter. Site-directed mutagenesis of the p21 promoter revealed that dexamethasone stimulation of p21 promoter activity required the C/EBP consensus DNA-binding site. Furthermore, in glucocorticoid receptor-defective EDR1 hepatoma cells, dexamethasone failed to stimulate C/EBP alpha and p21 protein expression and promoter activities. Our results have established a functional link between the glucocorticoid receptor signaling pathway that mediates a G1 cell cycle arrest of rat hepatoma cells and the transcriptional control of p21 by a cascade that requires the steroid induction of C/EBP alpha gene expression.

Animals↗
PubMed1998

A longitudinal study of immunological status in Chinese haemophiliacs: importance of the heat viral inactivation of factor concentrates. II. Improvements of CD4/CD8 ratio after treatments with heat-inactivated factor concentrates.

Screened and heated clotting factor concentrates of intermediate purity have been used in Taiwanese haemophiliacs since the end of 1986. A significant improvement of CD4/CD8 ratio during the years 1987-1989 as compared with those during the years 1984-1986 was observed in haemophilia A patients [mean +/- SD (median), 1.191 +/- 0.495 (1.163) vs. 0.880 +/- 0.325 (0.838), P = 0.0020] who were seronegative for human immunodeficiency virus. Almost all patients received an increased amount of factor VIII concentrates and total plasma products since 1987. Multiple linear regression analysis for the association of CD4/CD8 ratio with changes in dosage of plasma products revealed that there was a significant positive association of CD4/CD8 ratio measured during 1987-1989 with dosage of factor VIII concentrate administered during 1984-1986 (P = 0.0230), which is an indicator for changes in viral load, but not with changes in dosage of plasma products, which are indicators for changes in plasma protein intake. Our data indicate that immunological abnormalities after replacement therapy observed in haemophiliacs are mainly attributed to virus infection through infusion of factor concentrates, not to allogeneic proteins existing in plasma products.

Adolescent↗
PubMed1998

Traumatic posterior fossa extradural haematomas (PFEDH).

OBJECTIVES: While posterior fossa extradural haematomas (PFEDH) may lead to rapid neurological deterioration and death because of brainstem compression, prompt treatment often leads to a good outcome. The non-specific clinical signs and the rarity of this lesion in craniocerebral trauma adds to the difficulty in diagnosis. The aim of this study was to identify features which could lead to an early diagnosis. METHODS: Seventeen patients with posterior fossa extradural haematomas were operated on over 4 1/2 years, accounting for 7.5% of the 226 surgically operated extradural haematomas in the Department of Neurosurgery, Tan Tock Seng Hospital, Singapore. Four patients were excluded from this study due to non-availability of the case records. The remaining 13 patients formed the study group in this retrospective analysis. RESULTS: The majority of cases (77%) presented acutely within 24 hours. The mechanism of injury varied from a fall in 7 cases, a road traffic accident in 4 cases and assault in 2. Nine patients had evidence of external injury to the occiput, 8 patients had skull fractures, and diastasis of the lambdoid suture was seen in 2 cases. Presence of aerocele was noted in the CT scan of 4 cases. All 9 cases admitted with a high GCS score of more than 8 had a very good outcome. CONCLUSION: An early CT scan head is recommended if a combination of the following features is present: occipital soft tissue injury, drowsiness, occipital fracture or diastasis of the lambdoid suture.

Accidental Falls↗
PubMed1997

CD8high+ (CD57+) T cells in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the development and T cell receptor (TCR) usage of CD8+, CD57+ T cells in rheumatoid arthritis (RA) patients. METHODS: Three-color flow cytometry using monoclonal antibodies (MAb) to CD8, CD57 and different TCR V beta gene products. RESULTS: The proportion of CD8+ T cells expressing CD57 (CD57/CD8) was significantly higher in RA patients compared with age-matched controls. Expanded TCR V beta populations were more frequent, and were found in both RA patient-derived CD8high+ (CD57+) and CD8+, CD57- populations. TCR V beta 5+ and TCR V beta 13+ expansions were present at high frequency (5 of 26 and 7 of 26, respectively). TCR V beta expansions in CD8high+ (CD57+) lymphocytes from RA patients were significantly larger than those in age-matched controls (expansion index 2.38 +/- 0.28, n = 41 and 1.63 +/- 0.09, n = 32, respectively), and were stable over time. CONCLUSION: RA leads to an increase in the frequency of expanded CD8+ T cell subsets expressing selected TCR, due to expansion of TCR V beta + populations in CD8high+ (CD57+) T cells. Their restricted TCR usage suggests potential specificity for RA antigens and, therefore, a potential role in the pathogenesis of RA.

Aged↗
PubMed1997

Consequences of live poliovirus vaccine administration in chronic fatigue syndrome.

The effect of live oral polio virus vaccination on chronic fatigue syndrome (CFS) patients was examined in a double-blind study. CFS patients were allocated randomly to placebo (N = 7) or vaccine (N = 7) conditions. All controls subjects received the vaccine (9). Vaccine administration was not associated with clinical exacerbation of CFS. However, objective responses to the vaccine revealed differences between patients and controls: increased poliovirus isolation, earlier peak proliferative responses, lower T-cell subsets on certain days post vaccination and a trend for reduced gamma-interferon in the CFS-vaccine group. Polio vaccination was not found to be clinically contraindicated in CFS patients, however, there was evidence of altered immune reactivity and virus clearance.

Adult↗