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W Chan

Publications and source records attributed to W Chan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Community health promotion and the randomized controlled trial: approaches to finding common ground.

The randomized controlled trial is the model against which research designs are judged. Concurrent with rising standards of evidence, however, is a trend toward greater inclusiveness in community-based research, exemplified by the Centers for Disease Control and Prevention-funded Prevention Research Centers, a nationwide network of academic-community partnerships engaged in community-based health promotion and disease prevention research. The Yale-Griffin Prevention Research Center developed a replicable process for devising randomized trials in the context of community collaboration. Several examples of trials developed this way and their interim results are provided.

Cardiovascular Diseases↗
PubMed2001

Mixed-effects models for the evaluation of long-term trends in exposure levels with an example from the nickel industry.

Longitudinal studies play an important role in evaluating the temporal behavior of occupational exposures. The purpose of this paper is to examine certain features of longitudinal data and to present a general conceptual framework by which these features may be taken into account so that statistically valid inferences can be made. Statistical methods that rely on the application of mixed-effects models are proposed for evaluating long-term trends in exposures to workplace contaminants. The mixed-effects model presented herein has fixed effects for trend components and random effects for workers, job groups, buildings and plants. These models differ from conventional techniques in that they accommodate hierarchically structured data and account for the correlation that may arise due to the clustering of measurements based on when and where the data were collected. While primary interest is focused on determining the magnitude of trends in exposure levels over time, the model also provides information about the magnitude of the sources of variation associated with different groupings of workers. Application of the mixed-effects model is illustrated with a large database of shift-long personal exposure measurements collected on workers exposed to nickel aerosols in the nickel-producing industry.

Cluster Analysis↗
PubMed2001

Prognosis of body fluid level by fuzzy logic technique.

Surgical fluid replacement is a critical issue in medicine as the fluid volume excess or deficit can both complicate the patient's condition. Currently, the administration of fluid volume is carried out primarily based on the experience and expertise of the anaesthetist as there is no analytical method available to estimate the patient's fluid level. The development of a decision support system (DSS) to assist the anaesthetist in estimating the required fluid infusion rate for a particular patient has been the focus of this research paper. The DSS is developed based on Fuzzy Logic Control (FLC) technique which is ideal for developing input/output models in an unstructured and/or complex environment. The fuzzy rules used in the DSS are derived automatically from the clinical data produced in surgical operations. The DSS employs a Multi Rule Base (MRB) learning scheme to adapt its model according to the significant variation in the physiological parameters of a patient. The performance of the developed algorithms is validated through experimental work using clinical data. The results obtained so far are encouraging.

Diagnosis, Computer-Assisted↗
PubMed2001

Heterogeneity in sources of exposure variability among groups of workers exposed to inorganic mercury.

Many exposure assessment strategies rely on the occupational group as the unit of analysis in which workers are classified on the basis of job title, location, or on other characteristics related to the workplace or the job. Although statistical methods that combine exposure data collected on workers from different occupational groups are more efficient, the underlying assumption that the degree of variation over time and among workers is the same for all groups has yet to be fully investigated. Given the utility of different modeling approaches when assessing exposures, we investigated assumptions of homogeneity of variance within and between workers using both random- and mixed-effects models. In our study of four groups of workers exposed to inorganic mercury (Hg) at a chloralkali plant, there was no evidence of significant heterogeneity in the levels of variation over time or between workers for air Hg levels. For the biological monitoring data, however, our findings indicate that groups did not share common levels of variability and that it was not appropriate to pool the data and obtain single estimates of the within- and between-worker variance components. Classification of job group as a random or fixed effect had no effect on the results and yielded the same conclusions when the models were compared. To illustrate effects related to the proper specification of a model, the likelihood of exceeding certain levels (which is a function of the parameters of the underlying distribution of the natural log-transformed exposures) was evaluated using the results obtained from the different models. Although the probability that workers' mean exposures exceeded occupational exposure limits for air, urine and blood Hg was generally low (<10%) for all groups except maintenance workers, the estimated values sometimes varied depending upon the particular model that was applied. Given the growing use of random- and mixed-effects models that combine data across occupational groups, additional studies are warranted to evaluate whether it is reasonable to assume common variances and covariances among measurements collected on workers from different groups.

Analysis of Variance↗
PubMed2000

Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit apoptosis and maintain cell functionality.

Caspases have been strongly implicated to play an essential role in apoptosis. A critical question regarding the role(s) of these proteases is whether selective inhibition of an effector caspase(s) will prevent cell death. We have identified potent and selective non-peptide inhibitors of the effector caspases 3 and 7. The inhibition of apoptosis and maintenance of cell functionality with a caspase 3/7-selective inhibitor is demonstrated for the first time, and suggests that targeting these two caspases alone is sufficient for blocking apoptosis. Furthermore, an x-ray co-crystal structure of the complex between recombinant human caspase 3 and an isatin sulfonamide inhibitor has been solved to 2.8-A resolution. In contrast to previously reported peptide-based caspase inhibitors, the isatin sulfonamides derive their selectivity for caspases 3 and 7 by interacting primarily with the S(2) subsite, and do not bind in the caspase primary aspartic acid binding pocket (S(1)). These inhibitors blocked apoptosis in murine bone marrow neutrophils and human chondrocytes. Furthermore, in camptothecin-induced chondrocyte apoptosis, cell functionality as measured by type II collagen promoter activity is maintained, an activity considered essential for cartilage homeostasis. These data suggest that inhibiting chondrocyte cell death with a caspase 3/7-selective inhibitor may provide a novel therapeutic approach for the prevention and treatment of osteoarthritis, or other disease states characterized by excessive apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Phospholipase A(2) activity, heat shock protein, and superoxide dismutase in rat remnant kidney.

Male Sprague-Dawley rats (150-200 g) were randomly assigned to sham operation (n=6) or 5/6 nephrectomy (n=12) procedures. Two weeks after the completion of the 5/6 nephrectomy, these animals were again randomly assigned to two groups: non-treatment or treatment with vitamin E supplementation at 200 IU/kg chow. Two weeks later, all animals were sacrificed and the kidneys harvested. The secretory phospholipase A(2) (PLA(2)) activity was elevated (150%) in the untreated remnant kidney but returned to sham values in the vitamin E-treated kidneys. The cytoprotective heat shock protein (HSP70) and the intracellular antioxidant superoxide dismutase (MnSOD, Cu/ZnSOD) were similar in sham, remnant, and vitamin E-treated remnant kidneys. We conclude that the sudden reduction of renal mass secondary to the 5/6 nephrectomy procedure stimulates PLA(2) activity but not HSP70, MnSOD, or Cu/ZnSOD. This increased activity of PLA(2) in the remnant kidney returned to sham values after vitamin E treatment. The intrinsic cellular antioxidant enzymes, MnSOD, Cu/ZnSOD, as well as the cytoprotective heat shock protein HSP70, showed no significant changes in either vitamin E-treated or untreated kidneys compared with sham. These data are suggestive that the elevation of PLA(2) is a specific and localized response to the sudden reduction of renal mass.

Animals↗
PubMed2000

Nitric oxide mediated endothelium-dependent relaxation induced by glibenclamide in rat isolated aorta.

OBJECTIVES: Glibenclamide was found to act as both a selective ATP-sensitive K(+) channel blocker and a vasorelaxant. The exact mechanisms underlying the relaxant effect of glibenclamide are unknown. The present study was designed to examine the role of endothelium/nitric oxide in glibenclamide-induced relaxation in rat isolated aortic rings. METHODS: A combination of experimental approaches including isometric force measurement, cell culture, Ca(2+) fluorescence measurement and radioimmunoassay were used to examine the vascular effect of glibenclamide. RESULTS: Glibenclamide induced a concentration-dependent relaxation more effectively in rings with endothelium (IC(50) of 32+/-4 microM) than those without endothelium (IC(50) of 365+/-29 microM). Incubation with N(G)-nitro-L-arginine methyl ester (L-NAME) or methylene blue significantly reduced and L-arginine (3 mM) potentiated the glibenclamide-induced relaxation. L-Arginine (3 mM) partially antagonized the effect of L-NAME. Glibenclamide (100 microM) increased the cyclic GMP content of endothelium-intact tissues. Pretreatment with N(G)-nitro-L-arginine (100 microM) or removal of endothelium significantly suppressed the effect of glibenclamide on cyclic GMP production. Glibenclamide elevated the intracellular Ca(2+) levels in cultured rat aortic endothelial cells. Glibenclamide also inhibited the endothelium-independent contractile response to 60 mM K(+) (IC(50) of 137+/-21 microM) and caused a rightward shift in the concentration-contraction curve for CaCl(2). Besides, glibenclamide inhibited phorbol-12,13-diacetate (1 microM)-induced contraction in Ca(2+)-free Krebs solution. CONCLUSION: These results indicate that glibenclamide-induced endothelium-dependent relaxation involves nitric oxide release and this effect may be related to its stimulatory effect on endothelial Ca(2+) levels. However, the glibenclamide-induced endothelium-independent relaxation may be associated with its inhibitory effect on Ca(2+) influx through Ca(2+) channels and on the protein kinase C-mediated contractile mechanism.

Animals↗
PubMed2000

The global diabetes model: user friendly version 3.0.

The attributes of Release 3.0 of the user friendly version (UFV) of the global diabetes model (GDM) are described and documented in detail. The GDM is a continuous, stochastic microsimulation model of type 2 diabetes. Suitable for predicting the medical futures of both individuals with diabetes and representative diabetic populations, the GDM predicts medical events (complications of diabetes), survival, utilities, and medical care costs. Incidence rate functions for microvascular and macrovascular complications are based on a combination of published studies and analyses of data describing diabetic members of Kaiser Permanente Northwest Region, a non-profit group-model health maintenance organization. Active risk factors include average blood glucose (HbAlc), systolic blood pressure (SBP), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides, smoking status, and use of prophylactic aspirin. Events predicted include diabetic eye disease, diabetic nephropathy, peripheral neuropathy amputation, myocardial infarction, stroke, peripheral artery disease, congestive heart failure, coronary artery surgery, coronary angioplasty, and death.

Age Factors↗
PubMed2000

The Mt. Hood challenge: cross-testing two diabetes simulation models.

Starting from identical patients with type 2 diabetes, we compared the 20-year predictions of two computer simulation models, a 1998 version of the IMIB model and version 2.17 of the Global Diabetes Model (GDM). Primary measures of outcome were 20-year cumulative rates of: survival, first (incident) acute myocardial infarction (AMI), first stroke, proliferative diabetic retinopathy (PDR), macro-albuminuria (gross proteinuria, or GPR), and amputation. Standardized test patients were newly diagnosed males aged 45 or 75, with high and low levels of glycated hemoglobin (HbA(1c)), systolic blood pressure (SBP), and serum lipids. Both models generated realistic results and appropriate responses to changes in risk factors. Compared with the GDM, the IMIB model predicted much higher rates of mortality and AMI, and fewer strokes. These differences can be explained by differences in model architecture (Markov vs. microsimulation), different evidence bases for cardiovascular prediction (Framingham Heart Study cohort vs. Kaiser Permanente patients), and isolated versus interdependent prediction of cardiovascular events. Compared with IMIB, GDM predicted much higher lifetime costs, because of lower mortality and the use of a different costing method. It is feasible to cross-validate and explicate dissimilar diabetes simulation models using standardized patients. The wide differences in the model results that we observed demonstrate the need for cross-validation. We propose to hold a second 'Mt Hood Challenge' in 2001 and invite all diabetes modelers to attend.

Albuminuria↗
PubMed2000

Activation of emergency medical services for acute stroke in a nonurban population: the T.L.L. Temple Foundation Stroke Project.

BACKGROUND AND PURPOSE: Activating emergency medical services (EMS) is the most important factor in reducing delay times to hospital arrival for stroke patients. Determining who calls 911 for stroke would allow more efficient targeting of public health initiatives. METHODS: The T.L.L. Temple Foundation Stroke Project is an acute stroke surveillance and intervention project in nonurban East Texas. Prospective case ascertainment allowed chart abstraction and structured interviews for all hospitalized stroke patients to determine if EMS was activated, and if so, by whom. RESULTS: Of 429 validated strokes, 38.0% activated EMS by calling 911. Logistic regression analysis comparing those who called 911 with those who did not activate EMS found that individuals who were employed were 81% less likely to have EMS activated (OR 0.19, 95% CI 0.04 to 0.63). Of the 163 cases in which 911 was called, the person activating EMS was: self (patient), 4.3%; family member of significant other, 60. 1%; paid caregiver, 18.4%; and coworker or other, 12.9%. Significant associations between the variables age group (P=0.02), insurance status (P=0.007), and living alone (P=0.05) with who called 911 was found on chi(2) analysis. CONCLUSIONS: Educational efforts directed at patients themselves at risk for stroke may be of low yield. To increase the use of time dependent acute stroke therapy, interventions may wish to concentrate on family, caregivers, and coworkers of high-risk patients. Large employers may be good targets to increase utilization of EMS services for acute stroke.

Acute Disease↗
PubMed2000

Robust transformation with applications to structural equation modelling.

Data sets in social and behavioural sciences are seldom normal. Influential cases or outliers can lead to inappropriate solutions and problematic conclusions in structural equation modelling. By giving a proper weight to each case, the influence of outliers on a robust procedure can be minimized. We propose using a robust procedure as a transformation technique, generating a new data matrix that can be analysed by a variety of multivariate methods. Mardia's multivariate skewness and kurtosis statistics are used to measure the effect of the transformation in achieving approximate normality. Since the transformation makes the data approximately normal, applying a classical normal theory based procedure to the transformed data gives more efficient parameter estimates. Three procedures for parameter evaluation and model testing are discussed. Six examples illustrate the various aspects with the robust transformation.

Humans↗
PubMed1999

A prospective study of elective stenting in unprotected left main coronary disease.

The standard treatment of left main coronary artery (LMCA) disease has been bypass surgery (CABG). Recent reports suggested that stenting of LMCA disease might be feasible. From January 1995 to April 1998, we carried out a prospective study of elective stenting of unprotected LMCA disease to evaluate its immediate and long-term results. Of 61 consecutive patients with unprotected LMCA disease, 6 were excluded. Acute procedural success was 100% for the remaining 55 patients, without any complications such as stent thrombosis, myocardial infarction, CABG, or death. During a mean follow-up of 16.1+/-9.6 months, 11 patients (20%) had symptomatic recurrence, between 2 to 6 months after their procedure. Seven patients underwent CABG, two had repeat intervention, one continued with medical therapy, and one died before planned angiography. There was no late sudden death. Forty-four patients (80%) remained asymptomatic. We conclude that elective stenting may be a safe alternative to CABG in unprotected LMCA disease.

Aged↗
PubMed1999

In situ expression of angiopoietins in astrocytomas identifies angiopoietin-2 as an early marker of tumor angiogenesis.

Angiopoietin-1 (Ang-1) and its naturally occurring antagonist angiopoietin-2 (Ang-2) are novel ligands that regulate tyrosine phosphorylation of the Tie2/Tek receptor on endothelial cells. Proper regulation of Tie2/Tek is absolutely required for normal vascular development, seemingly by regulating vascular remodeling and endothelial cell interactions with supporting pericytes/smooth muscle cells. We investigated the expression of Ang-1 and Ang-2 in human astrocytomas by in situ hybridization and compared them to the distribution of pericytes/smooth muscle cells by immunohistochemistry for alpha-smooth muscle actin (SMA). Ang-1 mRNA was localized in tumor cells and Ang-2 mRNA was detected in endothelial cells of hyperplastic and nonhyperplastic tumor vessels. Ang-2 was also expressed in partially sclerotic vessels and in vascular channels surrounded by tumor cells in brain adjacent to the tumor. Neither Ang-1 nor Ang-2 was detected in normal brain. Dynamic changes in SMA expression during glioma tumorigenesis appear to progress from fragmentation in early vascular hyperplasia to subsequent reassociation and enhanced expression in later stages of vascular proliferation in hyperplastic complexes in high-grade gliomas. All these vessels displaying dynamic changes in SMA immunoreactivity also expressed Ang-2 mRNA. Moreover, SMA immunoreactive intratumoral vascular channels lacking morphological evidence of hyperplasia also showed upregulation of Ang-2. These results suggest that angiopoietins are involved in the early stage of vascular activation and in advanced angiogenesis, and they identify Ang-2 as an early marker of glioma-induced neovascularization. The association between Ang-2 expression and alterations in SMA immunoreactivity suggests a role for Ang-2 in tumor-associated activation of pericytes/smooth muscle cells.

Angiopoietin-1↗
PubMed1999

Influence of alpha-tocopherol over the time course of experimental IgA nephropathy.

The present study investigated the pathogenesis and the time course of kidney injury in experimental IgA nephropathy. In order to determine an appropriate period in the course of experimental IgA nephropathy to study renal injury and repair, we examined proteinuria and IgA deposition in the renal mesangium after 4, 8, and 16 weeks of mucosal challenge by bovine gamma globulins (BGG) provided in the drinking water. The hallmark of IgA deposition in the mesangium was present after 4 weeks and 8 weeks of BGG inoculation, but by 16 weeks, the mesangial IgA deposition had resolved. In addition, we confirmed our previous report on the beneficial effects of alpha-tocopherol in reducing proteinuria in IgA nephropathy at 8 weeks, and extended this observation to investigate the effects of dietary supplementation of alpha-tocopherol at both 4 weeks and 16 weeks. Proteinuria resolved spontaneously at 16 weeks. There is oxidative stress, as suggested by the elevation in plasma and renal malondialdehyde content, and increased fibrogenic cytokine message, as suggested by elevated transforming growth factor beta1 mRNA. These increases were clearly blunted by alpha-tocopherol at both 4 weeks and 8 weeks. Treatment with alpha-tocopherol was associated with a significant reduction in the severity of proteinuria. Thus, our data suggest that the period between 4 and 8 weeks of BGG vaccination could be relevant in designing an appropriate model to study the molecular biology of the pathogenesis of renal injury and the effects of treatment. The 16-week model may be useful in exploring gene expression involved with spontaneous resolution.

Animals↗
PubMed1999

Vitamin E suppresses oxidative stress and glomerulosclerosis in rat remnant kidney.

Previous studies have shown that reduction of renal mass in the rat remnant kidney model induces overproduction of transforming growth factor beta1 (TGFbeta1). We investigated whether an antioxidant, vitamin E, administered before the renal mass reduction, could prevent oxidative stress, reduce the overproduction of TGFbeta1, and mitigate against the subsequent glomerulosclerosis. Our results revealed that the oxidative stress, as measured by the change in plasma malondialdehyde, is significantly reduced by prior vitamin E dietary supplementation. Finally, our data show that dietary vitamin E supplementation ameliorates the rise in TGFbeta1 secondary to renal mass reduction and inhibits the glomerular sclerosis of the remnant kidney over the time course of this experiment.

Animals↗
PubMed1999

Retinal breaks.

Explore the source record for details and available documents.

Humans↗
PubMed1999

Psychosocial predictors of delay of first sexual intercourse by adolescents.

This investigation predicted adolescents' delay of intercourse onset from attitudes, social norms, and self-efficacy about refraining from sexual intercourse. Age, gender, ethnicity, and parental education were also examined as predictors and moderators of the relationships among the 3 psychosocial determinants and onset. The participants (N = 827), part of a cohort initially surveyed in the 9th grade, reported at baseline that they had never engaged in intercourse. The multivariable proportional hazards regression model suggested that adolescents with more positive attitudinal and normative beliefs, as well as those with a parent who graduated from college, were less likely to engage in intercourse in the follow-up period (up to approximately 2 years). Interventions that include an objective to delay onset may benefit from addressing psychosocial determinants, especially attitudes and norms about sexual intercourse.

Adolescent↗