bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ciba Corning ACS:180 benchtop immunoassay analyzer
Authors: Boland J , Carey G , Krodel E , Kwiatkowski M 
Published: January 2020

Abstract
We describe a new clinical laboratory instrument, the ACS:180, used to automate heterogeneous immunoassay testing. The ACS:180 automates immunoassays in which paramagnetic particles are the solid phase and changes in chemiluminescence are measured. The system can accommodate both competitive and sandwich-type assay configurations. The microprocessor-based instrument fully automates each step of the assay, including sample and reagent addition, separation and wash of paramagnetic particles, and generation and acquisition of the chemiluminescent signal. The instrument has the flexibility to operate in random-access or batch mode. The time from application of sample to first result is less than 15 min; throughput is as much as 180 tests per hour.
Precision requirements for cost-effective operation of analytical processes
Authors: Westgard J O , Burnett R W 
Published: January 2020

Abstract
Current performance criteria for analytical methods are often based on recommendations developed many years ago. A common criterion for imprecision requires that two times the standard deviation (s) of the method be less than the allowable total error (TEa). Unfortunately, when this criterion is minimally satisfied, commonly used control procedures cannot achieve reliable detection of medically important errors. Studies of the power functions for statistical quality-control (QC) procedures show that the magnitude of medically important errors must be at least 3s to fall near the plateau of the power curves and be readily detected by current QC procedures. For methods that just meet the precision criterion 2s less than TEa, however, medically important errors will fall on the rising portion of the power curves and typically be detected less than half of the time. From a "reverse engineering" perspective, the 2s less than TEa criterion is inadequate because it does not allow for the known performance limitations (lack of sensitivity) of commonly used control procedures. A strong case can be made for using a criterion of at least '4s less than TEa, which calls for a twofold improvement in imprecision over, the current minimum requirements. This recommendation is consistent with current industrial guidelines for process capability and would lead to more reliable detection of medically important errors.
The ontogeny of human hepatic microsomal glucose-6-phosphatase proteins
Authors: Burchell A , Gibb L , Waddell I D , Giles M , Hume R 
Published: January 2020

Abstract
We have studied 250 human liver biopsy samples to determine the ontogeny of the microsomal glucose-6-phosphatase (EC 3.1.3.9) system. Human hepatic glucose-6-phosphatase enzyme activity develops at 11 weeks' gestation and slowly increases to approximately 10% of adult activity at term. In the first week after birth, activity rises to adult values. Increases in enzyme activity coincide with increasing concentrations of the glucose-6-phosphatase enzyme protein. The phosphate/pyrophosphate transport protein (T2) of the human hepatic glucose-6-phosphatase complex develops at a different rate from that of the enzyme. Our study shows that the development of rat and human glucose-6-phosphatase activities are completely different. We conclude that deficiencies of the proteins in the microsomal glucose-6-phosphatase complex can be diagnosed with much more certainty perinatally than prenatally.
Use of serum cholesterol/triglyceride ratio to discern for which individuals the Friedewald formula can be used confidently
Authors: González Estrada M , Rodríguez Ferrer C R , Astarloa I R , Lahera E M 
Published: January 2020

Abstract
The values of low-density lipoprotein cholesterol obtained according to the Friedewald formula (Clin Chem 1972; 18:499-502), or by the De Long transformation (J Am Med Assoc 1986;256:2372-7), were compared with the values obtained when the individual cholesterol/triglyceride ratio of very-low-density lipoprotein was used for estimating the contribution of this lipoprotein to the total cholesterol. We found that these formulas gave the greatest errors for individuals with a low serum cholesterol/triglyceride ratio. We propose criteria for deciding when the numerically calculated value of low-density cholesterol is appropriate, and when it is not.
Three highly sensitive "bedside" serum and urine tests for pregnancy compared
Authors: Christensen H , Thyssen H H , Schebye O , Berget A 
Published: January 2020

Abstract
We examined three enzyme-linked immunosorbent assay (ELISA) kits for human choriogonadotropin (hCG) (pregnancy tests) for use with urine and serum samples: the Tandem Icon II hCG Urine and Tandem Icon II hCG Serum, the NovoClone Target hCG Test, and the Abbott TestPacks hCG-urine and hCG-serum. Paired comparison of the results from each kit indicated that the NovoClone Target assay showed significantly lower diagnostic sensitivity (P less than 0.05) than did the Tandem Icon II or Abbott TestPack, both for urine and for serum samples. None of the products demonstrated any significant difference (P greater than 0.05) in diagnostic specificity, but the NovoClone Target kit showed several serious false-negative results with both urine and serum. Paired testing of urine kits vs serum kits also showed no significant differences (P greater than 0.05) in diagnostic sensitivity or specificity. We found the Abbott kits to be the most convenient to use and to read.
Detection of simultaneous self-administration of testosterone and epitestosterone in healthy men
Authors: Dehennin L 
Published: January 2020

Abstract
Combined self-administration of testosterone (T) and epitestosterone (ET) by athletes counteracts the efficiency of the corresponding urinary glucuronides (G) ratio, (T/ET)G, as an indicator of T abuse. I therefore propose 5-androstene-3 beta, 17 alpha-diol (5A3 beta 17 alpha), the immediate metabolic precursor of ET, as a new reference compound for the expression of relative excretions of T and ET. Thus (T/5A3 beta 17 alpha)G and (ET/5A3 beta 17 alpha)G become potential criteria to indicate joint administration of T and ET, since their respective threshold values (2.5 and 1.5) are exceeded even when (T/ET)G remains below the critical value of 6.
Simplified isoelectric focusing/immunoblotting determination of apoprotein E phenotype
Authors: Kataoka S , Paidi M , Howard B V 
Published: January 2020

Abstract
We developed a rapid, accurate method for phenotyping apoprotein E that can be used for large-scale population studies. In this method, adapted from the method of Kamboh et al. (J Lipid Res 1988;29:1535-43), 10-microL plasma samples are incubated with dithiothreitol and Tween-20 for 15 min and then applied to 5% polyacrylamide gels containing ampholyte (pH 4.5-8) and urea (3 mol/L). After 2 h of isoelectric focusing, the apoprotein E bands are made visible by immunoblotting. Utilizing whole plasma, this method does not require time-consuming ultracentrifugation, delipidation of samples, or dialysis. Small amounts of plasma are required, electrofocusing time is short, and as many as 160 samples can be processed per day. Identification of phenotype is easily accomplished by noting the location and number of protein bands instead of their intensity. Because identification of phenotype is not affected by sialylation, neuraminidase treatment is not necessary. Agreement in identification of 301 individuals from blinded duplicates was 96%, and there was 98% concordance of results for 431 samples that had undergone genetic typing. This method is thus well suited for large-scale population studies.
Total interleukin-6 in plasma measured by immunoassay
Authors: Brailly H , Montero-Julian F A , Zuber C E , Flavetta S , Grassi J , Houssiau F , vanSnick J 
Published: January 2020

Abstract
Determinations of total cytokine concentration in biological fluids by immunoassays face two major problems: the biochemical heterogeneity of the analyte and the interference of cytokine-binding proteins. We developed an ultrasensitive enzyme immunoassay for interleukin-6 (IL-6), using monoclonal antibodies and acetylcholinesterase as the tracer enzyme. The antibodies recognized recombinant and glycosylated forms of IL-6 equally. The antibodies measured dimeric recombinant IL-6, yet we could not detect IL-6 oligomers in plasma samples. We investigated the potential interference of soluble IL-6 receptor (sIL-6R), which is present at high concentrations in plasma samples (1 to 2 nmol/L). Heat treatment of the sample obviated the sIL-6R interference. Using calibrators in a plasma matrix, we demonstrated by fractionation, dilution, and recovery experiments that the immunoassay accurately measured total IL-6 in both normal and pathological serum and plasma samples.
StatPal II pH and Blood Gas Analysis System evaluated
Authors: Wong R J , Mahoney J J , Harvey J A , Van Kessel A L 
Published: January 2020

Abstract
We evaluated a new portable instrument, the PPG StatPal II pH and Blood Gas Analysis System, designed for "point-of-care" measurements of blood gases and pH. Inaccuracy (% of target value) and imprecision (CV%) were assessed by blood tonometry and comparison with a Corning 178. Within-day results for PCO2 inaccuracy and imprecision ranged from 98.2% to 102.9% and 3.3% to 3.9%, respectively; for PO2, these were 95.5% to 102.3% and 2.3% to 3.0%, respectively. Between-day results for PCO2 inaccuracy and imprecision ranged from 99.2% to 99.3% and from 2.9% to 3.2%, respectively; for PO2, the ranges were 96.2% to 98.2% and 2.6% to 3.0%, respectively. Two PCO2 outliers (in 645 samples = 0.3%) were observed. In general, tonometry recovery, measurement stability, and pH bias results for the StatPal II and Corning 178 were comparable. We conclude that the StatPal II performs within acceptable ranges of inaccuracy and imprecision.
Association of low serum concentration of bilirubin with increased risk of coronary artery disease
Authors: Schwertner H A , Jackson W G , Tolan G 
Published: January 2020

Abstract
We examined serum bilirubin and various liver-function enzymes as possible risk factors for angiographically documented coronary artery disease (CAD). The studies involved a "training" set of 619 men for whom complete data on all risk factors considered were available, and a "test" set of 258 men for whom some risk factor data were not available. In both study groups, the liver enzymes were not related to CAD; however, In[total bilirubin] was inversely and statistically significantly related to the presence of CAD, both univariately and multivariately after adjustment for the established risk factors of age, total cholesterol, high-density lipoprotein cholesterol, smoking history, and systolic blood pressure. A 50% decrease in total bilirubin was associated with a 47% increase in the odds of being in a more severe CAD category. Our data suggest that serum bilirubin is an inverse and independent risk factor for CAD, with an association equivalent in degree to that of systolic blood pressure.
Quantitative determination of CD4/CD8 molecules by a cell marker ELISA
Authors: Franke L , Nugel E , Döcke W D , Porstmann T 
Published: January 2020

Abstract
Determination of percentages of CD4+ and CD8+ T cells from patients with human immunodeficiency virus infection is usually done by flow cytometric analysis. We compared a cell marker ELISA with flow cytometry for quantitation of CD4 and CD8 molecules on T lymphocytes, and correlated the values both with the number of CD4+ and CD8+ T lymphocytes and with clinical data. Results by cell marker ELISA (y) correlated well with those by flow cytometric analysis (x); r = 0.69, P &lt; 0.001 (y = 0.01x + 3.9) for CD4; r = 0.81, P &lt; 0.001 (y = 0.03x + 5.4) for CD8; n = 343. The ELISA detected changes in numbers of CD8 molecules on the cells earlier than flow cytometry recognized changes in CD8+ T-cell counts. The advantages of the ELISA are the small sample volume required (0.5 mL of blood), its internal standardization by a CD4+/CD8+ cell line, and its simple and fast performance. The cell marker ELISA appears to be an efficient alternative to flow cytometry.
Manipulation and flow of biological fluids in straight channels micromachined in silicon
Authors: Wilding P , Pfahler J , Bau H H , Zemel J N , Kricka L J 
Published: January 2020

Abstract
Analysis of minute sample volumes is a major analytical challenge that requires an understanding of fluid flow in microstructures. Accordingly, flow dynamics of biological fluids and cell suspensions in straight glass-capped silicon microchannels (40 to 150 microns wide, 20 and 40 microns deep) were studied. We demonstrated that these microstructures are appropriate components for microfluidic analytical devices. Different fluids were easily manipulated in the microchannels, and measurements of flow rate as a function of pressure for whole human blood, serum, plasma, and cell suspensions revealed non-Newtonian behavior. By means of micromachined filters (5 microns) located in channels, blood cells and microparticles were effectively separated from nanoliter-sized samples, clearly indicating the future role of microstructures for a variety of analytical purposes.
Simultaneous determination of endogenous retinoic acid isomers and retinol in human plasma by isocratic normal-phase HPLC with ultraviolet detection
Authors: Meyer E , Lambert W E , De Leenheer A P 
Published: January 2020

Abstract
We describe a rapid and simple procedure for the simultaneous quantitation of endogenous 13-cis-retinoic acid, all-trans-retinoic acid, and retinol by isocratic normal-phase HPLC with ultraviolet detection, in 0.5 mL of human plasma. A silica adsorption column was eluted with n-hexane:2-propanol:acetic acid (200:0.7:0.135 by vol) at 0.9 mL/min, and the effluent monitored at 350 nm. The arotinoid ethylsulfonic acid Ro 15-1570 was used as the internal standard. High sensitivity, allowing quantitation of physiological concentrations, was achieved, particularly for the retinoic acid isomers. The detection limits were 0.5 microgram/L in plasma for both 13-cis- and trans-retinoic acid, and 10 micrograms/L for retinol. The CVs for between-day determinations of the lowest quality-control concentration (n = 12) were 4.8% for 13-cis-retinoic acid, 3.4% for trans-retinoic acid, and 3.0% for retinol. The mean (+/- SD) concentrations of 13-cis-retinoic acid (1.79 +/- 0.56 microgram/L), trans-retinoic acid (1.35 +/- 0.42 microgram/L), and retinol (533 +/- 58 micrograms/L) measured in plasma from 22 healthy volunteers agreed well with those previously reported.
Measurement of blood volume with an enriched stable isotope of chromium (53Cr) and isotope dilution by combined gas chromatography-mass spectrometry
Authors: Veillon C , Patterson K Y , Nagey D A , Tehan A M 
Published: January 2020

Abstract
We used an established isotope dilution gas chromatography-mass spectrometry method to measure blood volumes with an enriched stable isotope of chromium. The results were compared with those of the conventional method, which involves radioactive 51Cr. The two methods were compared simultaneously in two male subjects of different sizes, and essentially identical volumes were obtained. The isotope dilution method is insensitive to contamination with natural (unenriched) chromium and can be used to measure all of the stable isotopes of chromium. The method has potential applications in simultaneous erythrocyte survival studies. The absence of radioactivity makes possible an accurate means of studying blood volume changes in children and during pregnancy.
Serotonin, catecholamines, histamine, and their metabolites in urine, platelets, and tumor tissue of patients with carcinoid tumors
Authors: Kema I P , de Vries E G , Slooff M J , Biesma B , Muskiet F A 
Published: January 2020

Abstract
We monitored long-term (median 11 months) concentrations of platelet serotonin and urinary serotonin, 5-hydroxyindoleacetic acid, and seven catecholamine metabolites in 44 patients with carcinoid tumors. Tumor serotonin and catecholamine contents (11 patients) and urinary histamine and N-methylhistamine (15 patients) were determined. Consistently increased concentrations of indoles, notably platelet serotonin, were observed in 96%, 43%, and 0% of patients with mid-, fore-, and hindgut carcinoids, respectively. Urinary dopamine metabolites, notably 3-methoxytyramine, were consistently increased in 38%, 20%, and 7% of patients with mid-, hind-, and foregut carcinoids, respectively. For urinary norepinephrine/epinephrine metabolites, notably normetanephrine and metanephrine, these data were 33%, 20%, and 14%, respectively. Midgut carcinoid tumors had the highest serotonin contents, whereas concentrations of catecholamines were independent of primary localization. There was no consistent relation between biogenic amine contents in tumors and urinary excretion of the amine metabolites. Occurrence of carcinoid syndrome was related to increased serotonin production rate. Increased histamine production is not an important feature in patients with lung carcinoids or liver-metastasized ileum carcinoids.
Free light chains of immunoglobulins: clinical laboratory analysis
Authors: Levinson S S , Keren D F 
Published: January 2020

Abstract
The increased sensitivity of immunofixation electrophoresis (IFE) over prior electrophoretic methods has led to renewed interest in the study of free light chains. Here, we discuss problems associated with the identification of monoclonal free light chains (Bence Jones proteins) in urine. Besides reviewing the nature of the sample specimens and the assays themselves, we discuss the physiology, biochemistry, genetics, and immunological properties of these molecules. Direct measurement of kappa/lambda ratios may ultimately be useful, but all commercial methods available now lack sufficient sensitivity. IFE is the preferred method because of its sensitivity and ease of interpretation. There are, however, difficulties associated with the interpretation of urinary IFE patterns, because the technique does not include an intrinsic mechanism for antibody-antigen titration and because of its great sensitivity in the absence of quantification. Problems of interpretation are discussed.
Tiglylglycine excreted in urine in disorders of isoleucine metabolism and the respiratory chain measured by stable isotope dilution GC-MS
Authors: Bennett M J , Powell S , Swartling D J , Gibson K M 
Published: January 2020

Abstract
Tiglyglycine (TG), an intermediate product of the catabolism of isoleucine, is increased in the urine of patients with beta-ketothiolase deficiency or with disorders of propionate metabolism. It is also implicated as a useful diagnostic marker in disorders of the respiratory chain. We present a method for the synthesis of TG and tiglyl[13C, 15N]glycine and the development of a stable isotope dilution mass spectrometric assay for TG. We compare data from controls with that from subjects with beta-ketothiolase deficiency and propionyl-CoA carboxylase deficiency, and with six patients with enzyme-confirmed disorders of the respiratory chain. TG was increased in the urine from all of the patient groups. The increased TG excretion did not persist in one patient with a respiratory chain defect, which suggests that, in some patients, multiple sample analysis may be necessary to identify a respiratory chain defect. This is the first urinary compound to be implicated as a potential marker of disorders of the respiratory chain.
Immunoassay with recombinant Trypanosoma cruzi antigens potentially useful for screening donated blood and diagnosing Chagas disease
Authors: Pastini A C , Iglesias S R , Carricarte V C , Guerin M E , Sánchez D O , Frasch A C 
Published: January 2020

Abstract
A new enzyme immunoassay (EIA), the Dia Kit Bio-Chagas assay (Gador S.A.), is potentially useful for detecting antibodies to Trypanosoma cruzi in the diagnosis of infected individuals and the screening of blood in blood banks. The EIA is carried out on test strips of plastic backing covered with a nitrocellulose membrane to which a mixture of recombinant T. cruzi antigens 1, 2, shed acute-phase antigen, 13, and 30 has been applied as a horizontal line. A horizontal line of human IgG is included to monitor the test procedure. The test strips exhibited homogeneity in the adsorption of the mixture of recombinant antigens (CV = 6.0%) and the human IgG (CV = 8.6%). The EIA results obtained with sera positive by xenodiagnosis showed 100% agreement between both types of tests; tested against sera with positive and negative matched results of indirect hemagglutination, immunofluorescence, and ELISA, the EIA results agreed for 99.1% (347 of 350) and 99.6% (299 of 300) of the samples, respectively.
Digoxin immunoassay with cross-reactivity of digoxin metabolites proportional to their biological activity
Authors: Miller J J , Straub R W , Valdes R 
Published: January 2020

Abstract
Our objective was to identify commercially available digoxin immunoassays whose cross-reactivity with digoxin metabolites paralleled the pharmacological activity of the metabolites. We measured the immunoreactivity of digoxigenin bis- and monodigitoxosides, digoxigenin, and dihydrodigoxin in four immunoassays and compared the immunoactivities with pharmacological activities from studies involving whole-animal and receptor (Na,K-ATPase)-based assays. Correlation coefficients for comparisons of immunoassay reactivity and human heart receptor reactivities were: ACS, 0.96; TDx, 0.60; Stratus, 0.57; and Magic, 0.42. Comparison with other biological assays showed a similar trend. The major difference in metabolite cross-reactivities among the immunoassays was that of digoxigenin (ACS, 0.7%; TDx, 103%; Stratus, 108%; Magic, 153%), which has approximately 10% bioactivity relative to digoxin. Measured recovery of mixtures of digoxin and metabolites confirmed these findings. We conclude that the monoclonal antibody in the ACS digoxin assay closely mimics Na,K-ATPase in detecting digoxin and its metabolites. This finding provides a basis for developing therapeutic drug monitoring immunoassays capable of approximating the true pharmacological activity of a mixture of drug metabolites.
Serum cystatin C, determined by a rapid, automated particle-enhanced turbidimetric method, is a better marker than serum creatinine for glomerular filtration rate
Authors: Kyhse-Andersen J , Schmidt C , Nordin G , Andersson B , Nilsson-Ehle P , Lindström V , Grubb A 
Published: January 2020

Abstract
We describe a fully automated particle-enhanced turbidimetric assay for cystatin C in undiluted serum and EDTA-plasma. The throughput is 90 samples per hour and urgent samples can be analyzed in 7 min. The assay range (0.4-14.1 mg/L) covers the concentration range in health and disease. The within- and between-run imprecision is 0.9% and 2.2%, respectively. Analytical recovery of additions of recombinant cystatin C averaged 98%. Rheumatoid factors (&lt; or = 323,000 IU/L), bilirubin (&lt; or = 150 mumol/L), hemoglobin (&lt; or = 1.2 g/L), and triglycerides (&lt; or = 8.5 mmol/L) do not interfere in the assay. In view of the superior (by ROC analysis) diagnostic accuracy of serum concentrations of cystatin C for reduced glomerular filtration rate (GFR) in comparison with creatinine, cystatin C seems an attractive alternative to creatinine for estimation of GFR.