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Biomedical subjects

William L Roberts

Publications and source records attributed to William L Roberts.

At least 19 recordsLinked to original sources
PubMed2007

Asymmetric dimethylarginine, cortisol/cortisone ratio, and C-peptide: markers for diabetes and cardiovascular risk?

BACKGROUND: Diabetes and prediabetic conditions are growing cardiovascular risk factors. Better understanding and earlier recognition and treatment of dysglycemia-related risk are health priorities. We assessed the predictive value of 3 proposed new markers for diabetes and cardiovascular risk. We tested whether the plasma levels of (1) asymmetric dimethylarginine (ADMA), (2) cortisol/cortisone (Cl/Cn) ratio, and (3) C-peptide predicted glycemic status, coronary artery disease, and death or myocardial infarction (MI) in a nested case-control cohort (N = 850) with normal fasting glucose (< 110 mg/dL), impaired fasting glucose (110-125), or diabetic (> or = 126) status. METHODS: High-sensitivity C-reactive protein (hsCRP) served as a control risk marker. Follow-up averaged 2.6 +/- 1.4 years. High-pressure liquid chromatography with pre-column derivitization and fluorescence was used to assay ADMA, liquid chromatography/tandem mass spectrometry for Cl and Cn, and chemiluminescent immunoassay for C-peptide. RESULTS: Asymmetric dimethylarginine levels were positively associated with glycemic category (P < .001). Quartiles 2 to 4 ADMA also conferred increased risk of death/MI independent of hsCRP and other risk factors (adjusted hazard ratio, 2.1; P = .002). Cortisol/Cortisone ratios (P = .013) and C-peptide (P = .047) were associated with glycemic categories but less strongly than ADMA. Quartiles 2 to 4 Cl/Cn were protective against incident death/MI (adjusted hazard ratio, 0.48; P < .001), whereas C-peptide did not predict outcomes. CONCLUSIONS: Among a high coronary risk case-control cohort, ADMA (strongly), Cl/Cn (moderately), and C-peptide (weakly) predicted glycemic categories. Asymmetric dimethylarginine and Cl/Cn also predicted clinical outcome independent of and more strongly than hsCRP. Asymmetric dimethylarginine and Cl/Cn represent promising new candidate markers of dysglycemia and associated cardiovascular risk.

Arginine↗
PubMed2006

Performance characteristics of seven automated thyroxine and T-uptake methods.

BACKGROUND: Estimates of the free thyroxine concentration can be made using measurements of thyroxine (T4) and the thyroid hormone binding ratio (THBR, usually reported as T-uptake) according to the formula free thyroxine index (FTI)=T4xTHBR. We evaluated the performance characteristics of 7 pairs of automated T4 and T-uptake methods. METHODS: We evaluated the Architect i2000, AxSYM, ADVIA Centaur, UniCel DxI 800, Immulite 2000, Modular E170 and Vitros ECi methods for T4 and T-uptake. Imprecision was assessed by duplicate determinations on 3 levels of quality control material per run, 2 runs per day, on 5 separate days. Method comparison studies were performed with 205 patient samples and 68 samples from subjects in the second or third trimester of pregnancy. Results for both imprecision and method comparison were converted to the THBR as outlined by each method's manufacturer. RESULTS: Overall CVs for T4 and THBR methods were 3.2-8.9% and 1.2-6.7%, respectively. T4 methods generally agreed well. The THBR methods did not agree nearly as well. Comparison of FTI results with free T4 by equilibrium dialysis showed good correlation but different slopes. CONCLUSIONS: All methods show adequate precision but the THBR and FTI results are not well standardized.

Thyroxine↗
PubMed2006

Performance characteristics of 5 automated thyroglobulin autoantibody and thyroid peroxidase autoantibody assays.

BACKGROUND: Measurement of thyroid peroxidase autoantibodies (TPOAb) is useful in diagnosing patients with autoimmune thyroid disease. Measurement of thyroglobulin autoantibodies (TgAb) is used to detect potential interferences with thyroglobulin immunoassays and in limited situations for the diagnosis of autoimmune thyroid disease. METHODS: The limit of detection, imprecision, reference interval, method comparison and diagnostic concordance for the ADVIA Centaur, ARCHITECT i2000, AxSYM, Immulite 2000, Modular E170 (TPOAb only), and UniCel DxI 800 (TgAb only) methods were evaluated. The Advantage was used as the comparison method. RESULTS: Total imprecision ranged from 2.6% to 14.9% for TgAb and 2.1% to 15.8% for TPOAb. Passing-Bablok slopes ranged from 0.51 to 10.4 (TgAb) and 1.05 to 7.12 (TPOAb) with correlation coefficients of 0.48 to 0.82 (TgAb) and 0.66 to 0.78 (TPOAb). Assay cutoffs were adjusted using a common set of reference interval samples. Concordance with the Advantage assay using the new cutoffs was found to be improved and ranged from 68.5% to 84.7% (TgAb) and 77.5% to 84.7% (TPOAb). CONCLUSIONS: Although all assays generally performed well, assay concordance for a negative or positive result ranged from 54.2 to 84.7%. Quantitative agreement between methods was generally poor and methods could not be used interchangeably. Additional standardization efforts are required to improve inter-method agreement.

Autoantibodies↗
PubMed2006

Development and performance evaluation of a tandem mass spectrometry assay for 4 adrenal steroids.

BACKGROUND: Congenital adrenal hyperplasia is a group of autosomal recessive disorders caused by a deficiency of 1 of 4 enzymes required for the synthesis of glucocorticoids, mineralocorticoids, and sex hormones. Analysis of 11-deoxycortisol (11DC), 17-hydroxyprogesterone (17OHP), 17-hydroxypregnenolone (17OHPr), and pregnenolone (Pr) in blood allows detection of these enzyme defects. METHODS: The steroids were extracted from 200 microL of serum or plasma by solid-phase extraction, derivatized to form oximes, and extracted again with methyl t-butyl ether. Instrumental analysis was performed on an API 4000 tandem mass spectrometer with electrospray ionization in positive mode and multiple reaction-monitoring acquisition. RESULTS: The limits of detection were 0.025 microg/L for 11DC, 17OHP, and Pr and 0.10 microg/L for 17OHPr. The method was linear to 100 microg/L for 11DC, 17OHP, and Pr, respectively, and to 40 microg/L for 17OHPr. Within- and between-run (total) imprecision (CVs) were <7.1% and 11%, respectively. Reference intervals for children in Tanner stages 1 through 5 and adult males and females for 17OHP, 11DC, Pr, and 17OHPr were established. Prepared samples were stable for >72 h. CONCLUSIONS: The detection limit and selectivity of this method and its small sample volume requirement allow analysis of endogenous concentrations of adrenal steroids in serum or plasma from children and adults. The method thus has an important potential role in the evaluation of the status of 4 of the enzymes involved in adrenal steroid biosynthesis.

17-alpha-Hydroxypregnenolone↗
PubMed2006

Pediatric reference intervals for uncommon bleeding and thrombotic disorders.

This study provides pediatric reference intervals and median values for factors II, V, VII, X, fibrinogen, alpha-2-antiplasmin (AP), antithrombin (AT), plasminogen, protein C (PC), and protein S (PS) for children 7 to 17 years of age. All analytes exhibited at least some age dependence in late childhood and adolescence either when compared against adult values or when medians for children were regressed against age.

Adolescent↗
PubMed2006

Lipoprotein-associated phospholipase A2: review and recommendation of a clinical cut point for adults.

Recently, several epidemiologic studies have demonstrated an association between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration and risk of subsequent cardiovascular events. Several major commercial and reference laboratories across the United States are now offering Lp-PLA2 testing for clinical use to evaluate cardiovascular risk and as a guide to intensity of therapy in individuals at intermediate risk for developing coronary heart disease. Each laboratory has established its own cut points, or "decision values," for Lp-PLA2, which vary from the 50th to the 95th percentile values of individual populations tested at each site. Uniform reporting of cut points has not been achieved. The purpose of this manuscript is to recommend appropriate decision values for Lp-PLA2, endorsed by a consensus panel of laboratorians and clinicians from the major laboratories where the test is performed. These coauthors possess considerable experience with assessment of cardiovascular risk marker decision values in general and are familiar with the validation of the Lp-PLA2 immunoassay and the Lp-PLA2 clinical studies conducted thus far. An ideal risk marker, studied in an ideal population, might yield a consistent cut point associated with a sudden increase in cardiovascular risk. While acknowledging that additional studies will be required to test and refine the recommended decision value, this article reviews the most current information with which to provide guidance to practicing clinicians regarding Lp-PLA2 levels. Since several studies have demonstrated increased risk associated with the second and third tertiles vs. the first tertile for Lp-PLA2, the 50th percentile cut point (235 ng/mL) is recommended as a conservative cut point associated with increased risk for cardiovascular disease. This cut point is not proposed as a treatment target, but rather as a level above which clinicians should consider a patient to be at higher risk for cardiovascular events, independent of established risk factors, high- and low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2006

Performance characteristics of seven automated CA 15-3 assays.

Measurements of serum cancer antigen (CA) 15-3 are used to monitor tumor recurrence and treatment of advanced disease. We evaluated the performance characteristics, including limit of detection, linearity, method comparison, and reference intervals, of 7 automated methods for CA 15-3, including the Access 2 (Beckman Coulter, Brea, CA), ADVIA Centaur (Bayer Diagnostics, Tarrytown, NY), ARCHITECT i2000 and AxSYM (Abbott Diagnostics, Abbott Park, IL), Elecsys 2010 (Roche Diagnostics, Indianapolis, IN), IMMULITE 2000 (Diagnostic Products, Los Angeles, CA), and VITROS ECi (Ortho Clinical Diagnostics, Raritan, NJ) assays. The limit of detection for each assay was less than 1.0 kU/L. The maximum deviation for the target values for linearity samples was less than 10% for all methods. Method comparison studies revealed large differences for some individual samples. Overall slopes ranged from 0.50 to 1.48, and correlation coefficients were 0.90 to 0.96 when the ADVIA Centaur was the comparison method. The 97.5 percentile upper reference limit ranged from 23.3 to 51.7 kU/L. Additional standardization efforts are needed, and the availability of reference material is required. Substantial intermethod differences exist for some patient samples, indicating that redetermining the baseline is required when changing methods.

Biomarkers, Tumor↗
PubMed2006

The analytic sensitivity and mutant detection capability of six hepatitis B surface antigen assays.

Hepatitis B virus surface antigen (HBsAg) mutants occur in clinical specimens. We studied the analytic sensitivity and ability to detect recombinant and native mutants of 6 HBsAg assays. The ARCHITECT, AUSZYME MONOCLONAL and AxSYM assays (Abbott Diagnostics, Abbott Park, IL), the ADVIA Centaur assay (Bayer Diagnostics, Tarrytown, NY), and the Test System 3 and VITROS ECi assays (Ortho Clinical Diagnostics, Raritan, NJ) showed comparable sensitivity with wild-type HBsAg. The ARCHITECT, AUSZYME, and AxSYM assays detected all mutants that were tested. The Test System 3 and VITROS ECi assays failed to detect mutants with amino acid substitutions at positions 143, 144, and 145, which are located in the immunodominant "a" determinant. The ADVIA Centaur failed to detect substitutions at position 145 and showed negative or very low positive results for substitutions at position 143. The inability to detect HBsAg mutants may lead to misdiagnosis of hepatitis B virus infection. Further studies on the prevalence of HBsAg mutants and the ability of commercial assays to detect them are needed.

DNA, Viral↗
PubMed2006

Performance characteristics of six IMMULITE 2000 TORCH assays.

TORCH is an acronym for Toxoplasma gondii (Toxo), other microorganisms (eg, syphilis), rubella virus (RV), cytomegalovirus (CMV), and herpes simplex virus (HSV) that are associated with congenital abnormalities from maternal infection. We evaluated linearity, imprecision, and comparison with commercially available methods of the IMMULITE 2000 (Diagnostic Products, Los Angeles, CA) Toxo IgG, Toxo IgM, RV IgG, RV IgM, CMV IgG, and HSV IgG assays. Linearity and imprecision results were acceptable. The IMMULITE 2000 assays show good concordance with other commercially available methods except for Toxo IgM and RV IgM. Toxo IgM showed better concordance with a consensus of 3 of 4 (Access, Beckman Coulter, Fullerton, CA; IMMULITE 2000; Platelia, Bio-Rad Laboratories Diagnostics Group, Redmond, WA; and Vidas, bioMerieux, Hazelwood, MO) assays than with Access alone. The RV IgM assay showed better concordance with the Zeus method than with the Diamedix method (Diamedix, Miami, FL). The IMMULITE 2000 TORCH assays studied show acceptable performance and are suitable for routine clinical use. Some commercial assays for Toxo IgM and RV IgM show rather poor concordance.

Animals↗
PubMed2006

Performance characteristics of seven automated CA 125 assays.

Cancer antigen 125 (CA 125) is a high-molecular-mass glycoprotein that is used as a tumor marker to monitor disease progression and response to therapy and in early detection of recurrence after treatment for ovarian cancer. The Access 2 (Beckman Coulter, Brea, CA), ADVIA Centaur (Bayer Diagnostics, Tarrytown, NY), ARCHITECT i2000 (Abbott Diagnostics, Abbott Park, IL), AxSYM (Abbott Diagnostics), Elecsys 2010 (Roche Diagnostics, Indianapolis, IN), IMMULITE 2000 (Diagnostic Products, Los Angeles, CA), and VITROS ECi (Ortho Clinical Diagnostics, Raritan, NJ) assays for CA 125 were evaluated for detection limit, dilution linearity, imprecision, correlation, and reference intervals. The maximum average deviation from target recoveries for dilution linearity studies ranged from 3.7% for the ADVIA Centaur to 18.2% for the IMMULITE 2000. Imprecision studies yielded total coefficients of variation of 2.0% to 8.3% at CA 125 concentrations of 35 and 114 U/mL (35 and 114 kU/L). Method comparison studies revealed good agreement with the VITROS ECi comparison method, with slopes ranging between 0.88 to 1.19 and correlation coefficients of more than 0.95. All methods show acceptable performance characteristics and generally compare well. However, for some samples, substantial differences exist between methods, necessitating parallel testing when introducing a new method.

Adolescent↗
PubMed2006

Risk factor analysis of plasma cytokines in patients with coronary artery disease by a multiplexed fluorescent immunoassay.

Coronary artery disease (CAD) is the leading cause of death in the United States. Increasing evidence suggests involvement of inflammation in the atherosclerotic process. We examined cytokines and other inflammatory markers in 865 patients with chest pain in whom coronary angiography revealed no evidence of CAD or CAD with or without concomitant myocardial infarction (MI). We developed a multiplexed immunoassay to simultaneously assess the plasma concentrations of 8 cytokines (interferon gamma, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor alpha), IL-2r, and soluble CD40 ligand in the patient groups. Concentrations of C-reactive protein (CRP) and IL-18 also were determined. Significant differences (P < .05) between no CAD and combined CAD groups were found for IL-2, IL-4, IL-6, IL-12, and IL-18. When the no CAD group was compared with the group with CAD with subsequent MI, significant differences were found for proinflammatory markers IL-6 (P pound .001), IL-8 (P = .017), and CRP (P pound .001). Cytokine profiles may have a role in differentiating patients with CAD with MI from those with chest pain due to other disorders and in deciphering the role of inflammation in the pathogenesis of CAD.

Angina Pectoris↗
PubMed2006

Teaching pediatric laboratory medicine to pathology residents.

CONTEXT: Laboratory data are essential to the medical care of fetuses, infants, children, and adolescents. However, the performance and interpretation of laboratory tests on specimens from these patients, which may constitute a significant component of the workload in general hospitals and integrated health care systems as well as specialized perinatal or pediatric centers, present unique challenges to the clinical pathologist and the laboratory. Therefore, pathology residents should receive training in pediatric laboratory medicine. OBJECTIVE: Children's Health Improvement through Laboratory Diagnostics, a group of pathologists and laboratory scientists with interest and expertise in pediatric laboratory medicine, convened a task force to develop a list of curriculum topics, key resources, and training experiences in pediatric laboratory medicine for trainees in anatomic and clinical pathology or straight clinical pathology residency programs and in pediatric pathology fellowship programs. DATA SOURCES: Based on the experiences of 11 training programs, we have compiled a comprehensive list of pediatric topics in the areas of clinical chemistry, endocrinology, hematology, urinalysis, coagulation medicine, transfusion medicine, immunology, microbiology and virology, biochemical genetics, cytogenetics and molecular diagnostics, point of care testing, and laboratory management. This report also includes recommendations for training experiences and a list of key texts and other resources in pediatric laboratory medicine. CONCLUSIONS: Clinical pathologists should be trained to meet the laboratory medicine needs of pediatric patients and to assist the clinicians caring for these patients with the selection and interpretation of laboratory studies. This review helps program directors tailor their curricula to more effectively provide this training.

Child↗
PubMed2005

Performance characteristics of a novel tandem mass spectrometry assay for serum testosterone.

BACKGROUND: Commercial immunoassays for testosterone (Te) may give inaccurate results for samples from women and children, leading to misdiagnosis and inappropriate treatment. We developed a sensitive and specific tandem mass spectrometric assay for measurement of Te at the concentrations encountered in women and children. METHODS: Te was extracted with methyl tert-butyl ether from 100 microL of serum or plasma, derivatized to form an oxime, and reextracted by solid-phase extraction. Instrumental analysis was performed on an API 4000 HPLC tandem mass spectrometer in the multiple-reaction monitoring (MRM) mode. The MRM transitions (m/z) were 304-->124 and 304-->112 for Te and 307-->124 and 307-->112 for d3-Te. RESULTS: Within- and between-run CVs were <12% and 7.9%, respectively. The limit of quantification was 0.0346 nmol/L (1 ng/dL). Reference intervals for sex hormone-binding globulin and total, free, and bioavailable Te were established for children of Tanner stages 1 through 5 and adult males and females. CONCLUSIONS: The sensitivity and specificity of the method are adequate for analysis of Te in samples from women and children. The method requires small sample volumes, has adequate precision, and is not subject to interferences.

Adolescent↗
PubMed2005

Comparison of differing C-reactive protein assay methods and their impact on cardiovascular risk assessment.

A medium-sensitivity assay for C-reactive protein (CRP) was compared with a high-sensitivity, enhanced immunoturbidimetric assay in 803 angiographically studied patients. Different absolute CRP values were found by the assays, but there was a high correlation by quartile rank and similar predictive values for death and myocardial infarction. This suggests that the conclusions of previous studies performed using the medium-sensitivity assay are still valid but that cross-study comparisons should use percentile rank.

Blood Chemical Analysis↗
PubMed2005

Performance characteristics of the IMMULITE 2000 insulin-like growth factor binding protein-3 assay.

BACKGROUND: Insulin-like growth factor binding protein-3 (IGFBP-3) is the chief binding protein for insulin-like growth factors 1 and 2 (IGF-1 and IGF-2). Serum concentrations of IGFBP-3 are regulated by growth hormone (GH) and IGF-1 levels. Serum IGFBP-3 measurements are useful for diagnostic evaluations of short stature in children and acromegaly. METHODS: A IGFBP-3 assay for the IMMULITE 2000 analyzer was evaluated for limit of detection, linearity, intra- and interassay imprecision, comparison to another commercially available assay, interference studies, and an adult reference interval. RESULTS: The limit of detection was 0.006 mg/l. The assay was linear from 0.01 to 15.1 mg/l. The total interassay imprecision was <6% for IGFBP-3 concentrations of 1.1 and 4.4 mg/l. Comparison with a Nichols RIA method showed comparable results. Deming regression analysis gave a slope of 1.02+/-0.02, an intercept of 0.24+/-0.07, and a Sy/x of 0.33 (r=0.98) over the range tested (0.4 to 10.3 mg/l). Interference was <10% for all levels of bilirubin, triglyceride, and hemoglobin tested. The nonparametric reference interval for adults 26 to 61 years was 2.9 to 6.5 ng/ml. CONCLUSIONS: The IMMULITE 2000 IGFBP-3 assay shows acceptable performance and is suitable for routine clinical use.

Adult↗
PubMed2005

Comparative study of two automated high-sensitivity C-reactive protein methods in a large population.

OBJECTIVES: Increased serum C-reactive protein (CRP) is associated with future risk of coronary heart disease in apparently healthy individuals. Numerous high-sensitivity CRP (hs-CRP) methods are available but their comparability in large populations has not been assessed. This study aimed to evaluate the performance of two CRP methods in a large Asian population. DESIGN AND METHODS: We compared the Tina-quant CRP immunoturbidimetric assay (Roche COBAS INTEGRA) to the N high-sensitivity latex-enhanced immunonephelometric (BN 100 nephelometer, Dade Behring) assay using 4118 serum samples from the International Collaborative Study on Atherosclerosis and Stroke in Asia (Inter ASIA). RESULTS: The median hs-CRP value for the N high-sensitivity CRP method (1.23 mg/L) was significantly lower than that for the Tina-quant method (1.50 mg/L), P < 0.001. The two methods were highly associated (r = 0.9916). Deming regression analysis gave a slope of 0.958 [95% confidence interval (CI): 0.954-0.962] with an intercept of 0.280 [95% confidence interval (CI): 0.268-0.292]. The mean of the method differences was 0.19 mg/L and the limits of agreement (LOA), which encompass 95% of results, were -0.36-0.74 mg/L. We found the percentages of low, average, and high-risk results were 42.9, 33.8, and 23.3 for the N high-sensitivity CRP and 33.2, 41.1, and 25.7 for the Tina-quant method. The percentage of samples concordant by both methods was 87.4%. The Tina-quant CRP classified more subjects into the high-risk group. CONCLUSIONS: The two hs-CRP methods were highly associated and are suitable for screening large populations.

C-Reactive Protein↗