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Edward Wang

Publications and source records attributed to Edward Wang.

34 records · Page 2Linked to original sources
PubMed2005

Analytic bias of thyroid function tests: analysis of a College of American Pathologists fresh frozen serum pool by 3900 clinical laboratories.

CONTEXT: In proficiency testing surveys, there are differences in the values reported by users of various analytic methods. Two contributors to this variation are calibrator bias and matrix effects of proficiency testing materials. OBJECTIVES: (1) To quantify the biases of the analytic methods used to measure thyroid-stimulating hormone, thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine levels; (2) to determine if these biases are within allowable limits; and (3) to ascertain if proficiency testing materials correctly identify these biases. DESIGN: A fresh frozen serum specimen was mailed as part of the 2003 College of American Pathologists Ligand and Chemistry surveys. The means and SDs for each analytic method were determined for this sample as well as for a proficiency testing sample from both surveys. In the fresh frozen serum sample, target values for thyroxine and triiodothyronine were determined by isotope dilution/liquid chromatography/tandem mass spectrometry. All other target values in the study were the median of the means obtained for the various analytic methods. MAIN OUTCOME MEASURES: Calibration biases were calculated by comparing the mean of each analytic method with the appropriate target values. These biases were evaluated against limits based on intra- and interindividual biological variation. Matrix effects of proficiency testing materials were assessed by comparing the rank of highest to lowest analytic method means (Spearman rank test) for each analyte. PARTICIPANTS: Approximately 3900 clinical laboratories were enrolled in the College of American Pathologists Chemistry and Ligand surveys. RESULTS: The number of methods in the Ligand Survey that failed to meet the goals for bias was 7 of 17 for thyroid-stimulating hormone and 11 of 13 for free thyroxine. The failure rates were 12 of 16 methods for thyroxine, 8 of 11 for triiodothyronine, and 9 of 11 for free triiodothyronine. The means of the analytic method for the proficiency testing material correlated significantly (P < .05) only with the fresh frozen serum means for thyroxine and thyroid-stimulating hormone in the Chemistry Survey and free triiodothyronine in the Ligand Survey. CONCLUSIONS: A majority of the methods used in thyroid function testing have biases that limit their clinical utility. Traditional proficiency testing materials do not adequately reflect these biases.

Calibration↗
PubMed2005

Total long-term within-laboratory precision of cortisol, ferritin, thyroxine, free thyroxine, and thyroid-stimulating hormone assays based on a College of American Pathologists fresh frozen serum study: do available methods meet medical needs for precision?

CONTEXT: It is important that the total long-term precision of laboratory methods meet the medical needs of the patients being served. OBJECTIVES: To determine the long-term within- and between-laboratory variation of cortisol, ferritin, thyroxine, free thyroxine, and thyroid-stimulating hormone measurements using commonly available methods and to determine if these variations are within accepted medical needs. DESIGN: Two vials of pooled frozen serum were mailed 6 months apart to laboratories participating in 2 separate College of American Pathologists surveys. The data from those laboratories that analyzed an analyte in both surveys were used to determine for each method the total variance and the within- and between-laboratory components. SETTING: The study included the A mailing of the 2003 College of American Pathologists Ligand Survey and the C mailing of the Chemistry Survey. MAIN OUTCOME MEASURES: For each analyte, total variance was partitioned into within- and between-laboratory components for each analytic method. The within-laboratory variations were then compared with imprecision criteria based on biological variation. PARTICIPANTS: The laboratories that reported results on the same analyte using the same method in both surveys. RESULTS: For each analyte, the median of the long-term within-laboratory variances of each peer group was 78% to 95% of its total-survey variance, and the median long-term within-laboratory coefficients of variation varied from 5.1% to 7.6%. The number of methods that met within-laboratory imprecision goals based on biological criteria were 5 of 5 for cortisol; 5 of 7 for ferritin; 0 of 7 for thyroxine and free thyroxine; and 8 of 8 for thyroid-stimulating hormone. CONCLUSIONS: For all analytes tested, the total within-laboratory component of variance was the major source of variability in this study. In addition, there are several methods, especially for thyroxine and free thyroxine, that may not meet analytic goals in terms of their imprecision.

Clinical Laboratory Techniques↗
PubMed2005

Comparison of fresh frozen serum to traditional proficiency testing material in a College of American Pathologists survey for ferritin, folate, and vitamin B12.

CONTEXT: Comparison of different analytical methods in proficiency surveys may be affected by the artificial nature of the survey material. OBJECTIVE: To compare intermethod differences in proficiency survey results between 2 types of survey material, conventional proficiency testing material (PTM) and fresh frozen human serum (FFS), for 3 markers of anemia: ferritin, folate, and vitamin B12. DESIGN: Data were gathered from a 2003 survey event in the College of American Pathologists Ligand ("K") Series, in which the specimens to be tested by each participating laboratory included 1 vial of FFS and 2 vials of PTM with different analyte concentrations. The more than 1600 laboratories subscribing to the survey were not advised as to the nature of the specimens. MAIN OUTCOME MEASURES: The bias of each method relative to the median of method means for each analyte and each type of survey material, and the interlaboratory coefficient of variation for each method. RESULTS: For each of the 3 analytes, moderate to large method biases were observed. For ferritin, method biases correlated strongly between comparable PTM and FFS specimens (Spearman r = 0.863, P < .001), whereas virtually no correlation was found for folate (r = -0.224, P = .48), and a marginally significant correlation existed for B12 (r = 0.55, P = .049). CONCLUSIONS: With ferritin, proficiency survey performance of PTM is similar to that of FFS, implying that method biases relate mainly to calibration. With folate and to a lesser extent with B12, PTM and FFS exhibit different method biases, implying that the biases reflect analyte heterogeneity and/or matrix effects.

Clinical Laboratory Techniques↗
PubMed2005

Comparison of fresh frozen serum to proficiency testing material in College of American Pathologists surveys: alpha-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin, and prostate-specific antigen.

CONTEXT: Most proficiency testing materials (PTM) contain an artificial matrix that may cause immunoassays to perform differently with this material than with clinical samples. We hypothesized that matrix effects would be reduced by using fresh frozen serum (FFS). OBJECTIVE: To compare the performance of an FFS pool to standard PTM for measurement of alpha-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin (hCG), and prostate-specific antigen (PSA). DESIGN: One FFS specimen and 4 different admixtures of PTM were distributed in the 2003 College of American Pathologists K/KN-A (for alpha-fetoprotein, carcinoembryonic antigen, hCG, and total and free PSA) and C-C (hCG only) Surveys. PARTICIPANTS: The number of laboratories that participated in the surveys varied from a low of 288 (free PSA, K/KN-A Survey) to a high of 2659 (hCG, C-C Survey). MAIN OUTCOME MEASURES: Method imprecision and method bias were compared between the FFS specimen and the standard PTM specimen with the closest value. Method imprecision was determined by calculating the coefficients of variation for each method and for all methods combined. Bias was defined as the proportional difference between peer-group mean and the median of all method means. RESULTS: The FFS specimen gave significantly higher imprecision than PTM for the analytes alpha-fetoprotein, carcinoembryonic antigen, total PSA, and free PSA. For hCG, no substantial imprecision differences were observed in both surveys. Bias was significantly greater for the alpha-fetoprotein, carcinoembryonic antigen, and total PSA assays and significantly lower for the hCG and free PSA assays when comparing the FFS with the PTM. CONCLUSIONS: Fresh frozen serum did not provide consistently lower imprecision or bias than standard PTM in a survey of commonly ordered tumor markers.

Carcinoembryonic Antigen↗
PubMed2005

Menopausal status, moderate-intensity walking, and symptoms in midlife women.

The purpose of this randomized clinical trial study was to determine the effectiveness of a 24-week, home-based, moderate-intensity, walking intervention in improving symptoms (vasomotor, uro-genital/sexual, sleep, psychological, cognitive, physical) experienced by midlife women. One hundred and seventy-three Caucasian and African American women aged 45 to 65 who were not on hormone therapy, had no major signs or symptoms of cardiovascular disease, and were sedentary in their leisure activity were randomly assigned to the moderate-intensity walking group or the nonexercise control group. The exercise prescription was walking at a frequency of 4 times a week for a duration of 20 to 30 minutes. The symptom impact inventory included the frequency, intensity, and bothersomeness of 33 symptoms collected at baseline and 24 weeks. Adherence was measured with a heart rate monitor and exercise log. Average adherence to frequency of walking was 71.6% of the expected walks. After 24 weeks, there were no differences between the walking and control group on change in symptoms. However, multiple regression revealed that frequency of adherence to walking along with change in physical symptoms and menopausal status were significant predictors of change in sleep symptoms. While walking did not improve most symptoms experienced by midlife women, frequency of walking may improve sleep.

Aged↗
PubMed2004

Development and validation of AIMFREE: Accessibility Instruments Measuring Fitness and Recreation Environments.

PURPOSE: The purpose of this study was to develop and validate a series of 16 survey instruments measuring fitness and recreation accessibility, collectively referred to as AIMFREE (Accessibility Instruments Measuring Fitness and Recreation Environments). General domains of assessment included the built environment, equipment, programmes, policies, and training and behaviour. METHODS: Fitness and recreation professionals (n=35) assessed fitness centres/swimming pools (n=35) in nine regions across the US. Rasch analysis was used to assess the psychometric properties of the instrument. RESULTS: The AIMFREE evidenced adequate to good fit to the Rasch model and adequate to good internal consistency (r=0.70 - 0.90). Test-retest reliability ranged from 0.70 (entrance areas) to 0.97 (swimming pools). Analysis of differential item functioning indicated that item calibrations generally did not differ significantly between urban and suburban environments. CONCLUSION: The AIMFREE instruments demonstrated adequate to good fit to the Rasch model with several of the subscales demonstrating well to excellent separation of facility accessibility.

Architectural Accessibility↗
PubMed2004

Distribution of the tight junction proteins ZO-1, occludin, and claudin-4, -8, and -12 in bladder epithelium.

In mammals, the bladder stores urine without permitting the passage of urine contents into the bloodstream, a function, in part, of the uroepithelial-associated tight junction complex. The protein constituents that make up this high-resistance barrier in the bladder are currently unknown, although the claudins, a multigene family, are thought to govern paracellular transport in other epithelia. Reverse transcriptase-polymerase chain reaction analysis was used to define that mRNA for claudin-2, -4, -8, -12, and -13 was expressed in mouse bladder tissue. The localization of these claudins, as well as the tight junction-associated proteins zonula occludens-1 (ZO-1) and occludin, within the bladder epithelium was determined by immunofluorescence microscopy. As expected, occludin and ZO-1 were localized to the tight junctions of rat, mouse, and rabbit umbrella cells. Intriguingly, ZO-1 in mouse epithelium, ZO-1 in the dome region of rabbit bladders and occludin in rat and mouse bladders were also expressed in the underlying intermediate and basal cell layers. Claudin-4, -8, and -12 were found in the umbrella cell tight junction; however, additional staining of claudin-4 was observed along the sites of cell-cell contact in the underlying cell layers of rat, mouse, and rabbit tissue. No claudin-2 staining was associated with tight junctions in the uroepithelium. Our results indicate that claudin-4, -8, and -12 are expressed in umbrella cells, where they may impart the high-resistance phenotype associated with this cell type, and that in some instances tight junction proteins are also associated at the sites of cell contact of the underlying cell layers, perhaps playing some role in cell-cell adhesion.

Animals↗
PubMed2004

Physical activity participation among persons with disabilities: barriers and facilitators.

BACKGROUND: The purpose of this study was to identify various barriers and facilitators associated with participation in fitness and recreation programs/facilities among persons with disabilities. METHODS: Focus groups were conducted in ten regions across the United States in 2001 to 2002 with four types of participants: (1) consumers with disabilities, (2) architects, (3) fitness and recreation professionals, and (4) city planners and park district managers. Sessions were tape-recorded and content analyzed; focus group facilitators took notes of identified barriers and facilitators to access. RESULTS: Content analysis of tape recordings revealed 178 barriers and 130 facilitators. The following themes were identified: (1) barriers and facilitators related to the built and natural environment; (2) economic issues; (3) emotional and psychological barriers; (4) equipment barriers; (5) barriers related to the use and interpretation of guidelines, codes, regulations, and laws; (6) information-related barriers; (7) professional knowledge, education, and training issues; (8) perceptions and attitudes of persons who are not disabled, including professionals; (9) policies and procedures both at the facility and community level; and (10) availability of resources. CONCLUSIONS: The degree of participation in physical activity among people with disabilities is affected by a multifactorial set of barriers and facilitators that are unique to this population. Future research should utilize this information to develop intervention strategies that have a greater likelihood of success.

Adult↗
PubMed2004

Improvements in physical fitness in adults with Down syndrome.

The effectiveness of an exercise training program for 52 adults with Down syndrome (M age = 39.4 years) was evaluated. The training program consisted of cardiovascular (30 minutes) and strength exercise (15 minutes) for 12 weeks, 3 days a week for 45-minutes per session. Compared to control subjects, the training group improved significantly in cardiovascular fitness and muscular strength and endurance and had a slight but significant reduction in body weight. Greater effort must be made to promote increases in physical activity participation among persons with Down syndrome and developmental disabilities in order to reduce the potential health risks associated with low fitness and sedentary behavior.

Adult↗
PubMed2003

Analysis of hydrostatic pressure-induced changes in umbrella cell surface area.

All cells experience and respond to external mechanical stimuli including shear stress, compression, and hydrostatic pressure. Cellular responses can include changes in exocytic and endocytic traffic. An excellent system to study how extracellular forces govern membrane trafficking events is the bladder umbrella cell, which lines the inner surface of the mammalian urinary bladder. It is hypothesized that umbrella cells modulate their apical plasma membrane surface area in response to hydrostatic pressure. Understanding the mechanics of this process is hampered by the lack of a suitable model system. We describe a pressure chamber that allows one to increase hydrostatic pressure in a physiological manner while using capacitance to monitor real-time changes in the apical surface area of the umbrella cell. It is demonstrated that application of hydrostatic pressure results in an increase in umbrella cell apical surface area and a change in the morphology of umbrella cells from roughly cuboidal to squamous. This process is dependent on increases in cytoplasmic Ca(2+). This system will be useful in further dissecting the mechanotransduction pathways involved in cell shape change and regulation of exocytic and endocytic traffic in umbrella cells.

Animals↗
PubMed2003

A longitudinal replicate study of immunosuppressive drugs: a College of American Pathologists study.

OBJECTIVE: To identify the sources of analytical variation for cyclosporine and tacrolimus in a 3-year longitudinal study. DESIGN: Two pools of whole blood were spiked with cyclosporine and tacrolimus, respectively. One aliquot of cyclosporine and 2 of the tacrolimus pool were distributed in the first and last mailing for years 1999 to 2001. For both drugs, the total variance for each method was partitioned into within- and between-laboratory components. SETTING: The A and C mailings of the 1999, 2000, and 2001 AACC/CAP [American Association for Clinical Chemistry/College of American Pathologists] Immunosuppressive Drugs (CS) Monitoring Survey. MAIN OUTCOME MEASURES: For each drug, total variance was partitioned into specimen, mailing, year, and interlaboratory effects for each analytical method. PARTICIPANTS: The 292 laboratories for cyclosporine and 177 laboratories for tacrolimus enrolled in the survey from 1999 to 2001. RESULTS: For both cyclosporine and tacrolimus, the major source of imprecision came from within-laboratory factors, which accounted for nearly 85% (range, 77% to 90%) of the total variance. For cyclosporine, the major component of within-laboratory variance was between-mailing, within-year effect, whereas for tacrolimus it was the between-year, within-laboratory variation. CONCLUSION: The major source of long-term survey imprecision for cyclosporine and tacrolimus is within-laboratory factors. The finding that 85% of the total variance was due to within-laboratory variation is similar to other therapeutic drugs.

Analysis of Variance↗
PubMed2003

Productivity of Veterans Health Administration laboratories: a College of American Pathologists Laboratory Management Index Program (LMIP) study.

CONTEXT: The Veterans Health Administration (VA) operates the largest integrated laboratory network in the United States. OBJECTIVE: To assess whether the unique characteristics of VA laboratories impact efficiency of operations, we compared the productivity of VA and non-VA facilities. DESIGN: Financial and activity data were prospectively collected from 124 VA and 131 non-VA laboratories enrolled in the College of American Pathologists Laboratory Management Index Program (LMIP) during 2002. In addition, secular trends in 5 productivity ratios were calculated for VA and non-VA laboratories enrolled in LMIP from 1997 through 2002. RESULTS: Veterans Health Administration and non-VA facilities did not differ significantly in size. Inpatients accounted for a lower percentage of testing at VA facilities than non-VA facilities (21.7% vs 37.3%; P <.001). Technical staff at the median VA facility were paid more than at non-VA facilities (28.11/h dollars vs 22.60/h dollars, salaries plus benefits; P <.001), VA laboratories employed a smaller percentage of nontechnical staff (30.0% vs 41.9%; P <.001), and workers at VA laboratories worked less time per hour paid (85.5% vs 88.5%; P <.001). However, labor productivity was significantly higher at VA than at non-VA facilities (30 448 test results/total full-time equivalent (FTE)/y vs 19 260 results/total FTE; P <.001), resulting in lower labor expense per on-site test at VA sites than at non-VA sites (1.79 dollars/result vs 2.08 dollars/result; P <.001). Veterans Health Administration laboratories paid less per test for consumables (P =.003), depreciation, and maintenance than their non-VA counterparts (all P <.001), resulting in lower overall cost per on-site test result (2.64 dollars vs 3.40 dollars; P <.001). Cost per referred (sent-out) test did not differ significantly between the 2 groups. Analysis of 6-year trends showed significant increases in both VA (P <.001) and non-VA (P =.02) labor productivity (on-site tests/total FTE). Expenses at VA laboratories for labor per test, consumables per test, overall expense per test, and overall laboratory expense per discharge decreased significantly during the 6-year period (P <.001), while in non-VA facilities the corresponding ratios showed no significant change. CONCLUSIONS: Overall productivity of VA laboratories is superior to that of non-VA facilities enrolled in LMIP. The principal advantages enjoyed by the VA are higher-than-average labor productivity (tests/FTE) and lower-than-average consumable expenses.

Efficiency, Organizational↗
PubMed2003

Lack of specificity of cyclosporine immunoassays. Results of a College of American Pathologists Study.

OBJECTIVE: To evaluate the cross-reactivity of the 6 most abundant cyclosporine A (CsA) metabolites in commonly used assays for CsA. DESIGN: Whole blood samples containing either only 62 ng/mL CsA (A) or 62 ng/mL CsA and between 49 and 86 ng/mL of 1 of the 6 most abundant CsA metabolites (B) were lyophilized. One sample of A and 1 of B were mailed to each of the laboratories participating in the College of American Pathologists Proficiency Testing Program quarterly during a 3-year period (1999-2001). Method means and coefficients of variation were calculated for each mailing. RESULTS: The study showed significant cross-reactivity of metabolites in all the immunoassay systems studied. Overall degree of interference decreased from Abbott TDx polyclonal > Abbott TDx monoclonal > DiaSorin > Syva EMIT. High-performance liquid chromatography methods gave results close to those found using mass spectrometric techniques. CONCLUSIONS: Significant metabolite interference was found to occur with the immunoassay systems studied.

Chromatography, High Pressure Liquid↗
PubMed2002

Beta-adrenoceptor agonists stimulate endothelial nitric oxide synthase in rat urinary bladder urothelial cells.

We have investigated the intracellular signaling mechanisms underlying the release of nitric oxide (NO) evoked by beta-adrenoceptor (AR) agonists in urinary bladder strips and cultured bladder urothelial cells from adult rats. Reverse transcription-PCR revealed that inducible NO synthase and endothelial NOS but not neuronal NOS genes were expressed in urothelial cells. NO release from both urothelial cells and bladder strips was decreased (37-42%) in the absence of extracellular Ca2+ (100 microm EGTA) and was ablated after incubation with BAPTA-AM (5 microm) or caffeine (10 mm), indicating that the NO production is mediated in part by intracellular calcium stores. NO release was reduced (18-24%) by nifedipine (10 microm) and potentiated (29-32%) by incubation with the Ca2+ channel opener BAYK8644 (1-10 microm). In addition, beta-AR-evoked NO release (isoproterenol; dobutamine; terbutaline; 10(-9) to 10(-5) m) was blocked by the NOS inhibitors N(G)-nitro-L-arginine methyl ester (30 microm) or N(G)-monomethyl-L-arginine (50 microm), by beta-adrenoceptor antagonists (propranol, beta1/beta2; atenolol, beta1; ICI 118551; beta2; 100 microm), or by the calmodulin antagonist trifluoperazine (50 microm). Incubating cells with the nonhydrolyzable GTP analog GTPgammaS (1 microm) or the membrane-permeant cAMP analog dibutyryl-cAMP (10-100 microm) directly evoked NO release. Forskolin (10 microm) or the phosphodiesterase IBMX (50 microm) enhanced (39-42%) agonist-evoked NO release. These results indicate that beta-adrenoceptor stimulation activates the adenylate cyclase pathway in bladder epithelial cells and initiates an increase in intracellular Ca2+ that triggers NO production and release. These findings are considered in light of recent reports that urothelial cells may exhibit a number of "neuron-like" properties, including the expression of receptors/ion channels similar to those found in sensory neurons.

Adrenergic beta-Agonists↗
PubMed2002

Stretch-regulated exocytosis/endocytosis in bladder umbrella cells.

The epithelium of the urinary bladder must maintain a highly impermeable barrier despite large variations in urine volume during bladder filling and voiding. To study how the epithelium accommodates these volume changes, we mounted bladder tissue in modified Ussing chambers and subjected the tissue to mechanical stretch. Stretching the tissue for 5 h resulted in a 50% increase in lumenal surface area (from approximately 2900 to 4300 microm(2)), exocytosis of a population of discoidal vesicles located in the apical cytoplasm of the superficial umbrella cells, and release of secretory proteins. Surprisingly, stretch also induced endocytosis of apical membrane and 100% of biotin-labeled membrane was internalized within 5 min after stretch. The endocytosed membrane was delivered to lysosomes and degraded by a leupeptin-sensitive pathway. Last, we show that the exocytic events were mediated, in part, by a cyclic adenosine monophosphate, protein kinase A-dependent process. Our results indicate that stretch modulates mucosal surface area by coordinating both exocytosis and endocytosis at the apical membrane of umbrella cells and provide insight into the mechanism of how mechanical forces regulate membrane traffic in non-excitable cells.

Animals↗