bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter evaluation of a homogeneous assay for HDL-cholesterol without sample pretreatment
Authors: Nauck Matthias , März Winfried , Jarausch Jochen , Cobbaert Christa , Sägers Anja , Bernard Dirk , Delanghe Joris , Honauer Gunter , Lehmann Paul , Oestrich Evelyn , von Eckardstein Arnold , Walch Stephan , Wieland Heinrich , Assmann Gerd 
Published: January 2020

Abstract
We evaluated a new homogeneous assay for the measurement of HDL-cholesterol (HDL-C) in six European laboratories. The assay includes two reagents and is applicable to most autoanalyzers, which allows full automation. The total CVs of the new method ranged between 1.3% and 6.7%. Thereby determined HDL-C values were in good agreement with those obtained by precipitation with phosphotungstic acid/MgCl2 or by a combination of ultracentrifugation and precipitation (0.956&lt; r &lt;0.994). The assay was linear up to at least 1500 mg/L HDL-C. Hemoglobin did not interfere, whereas icteric samples with bilirubin &gt;100 mg/L showed discrepancies between the homogeneous and the precipitation assay. Lipemia up to total triglyceride concentrations of 8000 mg/L did not interfere with the homogeneous HDL-C assay. The homogeneous HDL-C assay was easy to handle and produced similar results in all laboratories participating in this study. This method will significantly facilitate the screening of individuals at increased risk for cardiovascular disease.
Blood substitutes: evolution and future applications
Authors: Scott Mitchell G , Kucik Dennis F , Goodnough Lawrence T , Monk Terri G 
Published: January 2020

AbstractThe development of oxygen-carrying blood substitutes has progressed significantly in the last decade with phase I and phase II clinical trials of both hemoglobin-based and perfluorocarbon-based oxygen carriers nearing completion. As these products approach clinical use it is important for the laboratory medicine community to be aware of their effects on routine laboratory testing and the settings in which they might be used. Here we review the forces driving the development of oxygen-carrying blood substitutes, the clinical settings in which they might be used, the major categories of oxygen carriers in clinical trials, and the challenges faced by these products as they approach clinical use.
Effect of hemoglobin- and Perflubron-based oxygen carriers on common clinical laboratory tests
Authors: Ma Zhongmin , Monk Terri G , Goodnough Lawrence T , McClellan Adrain , Gawryl Maria , Clark Terri , Moreira Paulo , Keipert Peter E , Scott Mitchell G 
Published: January 2020

Abstract
Polymerized hemoglobin solutions (Hb-based oxygen carriers; HBOCs) and a second-generation perfluorocarbon (PFC) emulsion (Perflubron) are in clinical trials as temporary oxygen carriers (“blood substitutes”). Plasma and serum samples from patients receiving HBOCs look markedly red, whereas those from patients receiving PFC appear to be lipemic. Because hemolysis and lipemia are well-known interferents in many assays, we examined the effects of these substances on clinical chemistry, immunoassay, therapeutic drug, and coagulation tests. HBOC concentrations up to 50 g/L caused essentially no interference for Na, K, Cl, urea, total CO2, P, uric acid, Mg, creatinine, and glucose values determined by the Hitachi 747 or Vitros 750 analyzers (or both) or for immunoassays of lidocaine, N-acetylprocainamide, procainamide, digoxin, phenytoin, quinidine, or theophylline performed on the Abbott AxSym or TDx. Gentamycin and vancomycin assays on the AxSym exhibited a significant positive and negative interference, respectively. Immunoassays for TSH on the Abbott IMx and for troponin I on the Dade Stratus were unaffected by HBOC at this concentration. Tests for total protein, albumin, LDH, AST, ALT, GGT, amylase, lipase, and cholesterol were significantly affected to various extents at different HBOC concentrations on the Hitachi 747 and Vitros 750. The CK-MB assay on the Stratus exhibited a negative interference at 5 g/L HBOC. HBOC interference in coagulation tests was method-dependent—fibrometer-based methods on the BBL Fibro System were free from interference, but optical-based methods on the MLA 1000C exhibited interferences at 20 g/L HBOC. A 1:20 dilution of the PFC-based oxygen carrier (600 g/L) caused no interference on any of these chemistry or immunoassay tests except for amylase and ammonia on the Vitros 750 and plasma iron on the Hitachi 747.
Interferences of o-raffinose cross-linked hemoglobin in three methods for serum creatinine
Authors: Ali Arlene C Y , Mihas Chrystina C , Campbell Janet A 
Published: January 2020

Abstract
The interferences of o-raffinose cross-linked hemoglobin (HemolinkTM) were examined and compared in two serum creatinine methods on the Hitachi 717 [Boehringer Mannheim (BMC) and Synermed] and in an enzymatic creatinine method on the Vitros 750 (Johnson & Johnson). Interference was considered significant when the change in creatinine concentration from the control exceeded the 95% confidence limits of each method. Significant interference was observed for the BMC/Hitachi 717 method with Hemolink ≥5 g/L. No interference was observed for the Synermed/Hitachi 717 assay with Hemolink up to 30 g/L in normal samples and up to 50 g/L in samples with increased creatinine. No interference was observed for the Vitros 750 assay with Hemolink up to 50 g/L at both normal and increased concentrations of creatinine. Although the BMC/Hitachi 717 method was considered unacceptable, the Synermed/Hitachi 717 and the Vitros 750 methods allow accurate quantification of serum creatinine in the presence of Hemolink.
Statistically accurate estimation of hormone concentrations and associated uncertainties: methodology, validation, and applications
Authors: Straume Martin , Johnson Michael L , Veldhuis Johannes D 
Published: January 2020

Abstract
We describe a data reduction procedure to assign statistically accurate estimates of unknown hormone concentrations, with associated uncertainties, based on experimental uncertainties in sample replicates and the fitted calibration curve. Three mathematical calibration curve functions are considered. The one providing optimal statistical characterization of reference calibrators is chosen for unknown evaluation. Experimental error is addressed by assigning and propagating uncertainty estimates for each measured response (including zero-dose responses) by an empirically determined discrete uncertainty profile and by propagating calibration curve uncertainty. Discrete uncertainty profiles account for both response precision (replicability) and accuracy (deviation from predicted calibration curves) without relying on assumed theoretical response variance–assay response relations. The validity of assigning variable response weighting by this procedure was assessed by Monte Carlo simulations based on chemiluminescence growth hormone calibration curves. Much-improved accuracy and estimated precision are achieved for unknown hormone concentrations, particularly extremely low concentrations, by using this variable response weighting procedure.
Plasma apolipoproteins A-I and B in survivors of myocardial infarction and in a control group
Authors: Graziani Maria Stella , Zanolla Luisa , Righetti Gabriella , Marchetti Cristina , Mocarelli Paolo , Marcovina Santica M 
Published: January 2020

Abstract
The values of apolipoproteins (apo) A-I and B were determined in a population sample of hospital outpatients with a standardized method to verify if the cutpoints calculated in a cross-sectional study in the US are usable with other populations. We also tested the apolipoproteins’ ability to discriminate between healthy people and survivors of myocardial infarction. In the studied population the apo A-I value corresponding to the HDL-cholesterol decisional centile is 1.12 g/L for males and 1.17 g/L for females; the apo B value corresponding to the LDL-cholesterol decisional centile is 1.23 g/L for males and 1.14 g/L for females. These values are quite close to the cutpoints proposed for the American population (1.20 g/L for both apolipoproteins). In comparison with the LDL- and HDL-cholesterol decisional concentrations, the cutpoints for apolipoproteins allow a correct classification of a greater percentage of postmyocardial infarction patients (16% higher for apo B and 5% for apo A-I). Standardized assays coupled with a reference database allow a better clinical use of apolipoprotein measurements.
Exon 5 of the p53 gene is a target for deletions in ovarian cancer
Authors: Angelopoulou Katerina , Levesque Michael A , Katsaros Dionyssios , Shipman Rob , Diamandis Eleftherios P 
Published: January 2020

Abstract
Missense point mutations, leading to inactivation of the p53 tumor suppressor gene product, are currently the most frequent alterations in human cancer. Little, however, is known about small intragenic deletions or insertions occurring in this locus of chromosome 17. We have analyzed 56 primary ovarian tumors for the presence of such abnormalities. The analysis was based on multiplex PCR amplification of exons 1 through 11 of the p53 gene and fragment analysis of the generated PCR products. Mutations were detected in 14% (8 of 56) of the tumors. Deletions were much more prevalent than insertions (seven vs one). Six of the deletions and the insertion affected exon 5, and the other deletion was in exon 7. Two deletions and the insertion did not disrupt the reading frame; the protein product was expressed in the tumor at high concentrations in all three cases. The other five deletions generated a frameshift, which is predicted to result in the production of a truncated protein product. In the case of the deletions, a 2–5-bp repeat was present close to the detected deletion, whereas the insertion duplicated the sequence immediately upstream of the insertion site. Overall our findings indicate that small intragenic p53 deletions/insertions are not rare events in ovarian cancer, and that p53 exon 5 is the target in the vast majority (88%) of the cases.
Rapid, automated assay for progesterone on the Abbott AxSYM™ analyzer
Authors: Wilson David H , Groskopf William , Hsu Stephen , Caplan Diane , Langner Tom , Baumann Michael , DeManno Deborah , Williams Gregg , Payette Don , Dagel Cheryl , Lynch Don , Manderino George 
Published: January 2020

Abstract
We describe an automated assay for progesterone (P4) in human serum and plasma with the Abbott AxSYMTM random-access immunoassay analyzer. In this one-step competitive assay, P4 immobilized onto latex microparticles competes with sample P4 for binding to a conjugate of alkaline phosphatase (AP) and anti-P4 antibody. Total CVs ranged from 3.4% to 8.2% in multiple precision studies conducted according to the 20-day NCCLS EP5-T protocol. The detection limit (zero calibrator + 2 SD) was 0.10 μg/L across 36 experiments. Values for diluted samples were 83–116% of expected. Recovery of P4 added to serum specimens was 92–115%. Cross-reactivities with 43 natural and synthetic steroids were 0–6.3%. No significant interference was detected from bilirubin, protein, erythrocytes, hemoglobin, triglycerides, or cholesterol. In a multisite correlation study, AxSYM P4 results compared well with results from a commercial RIA method (n = 1156; r = 0.976; slope = 1.03; y-intercept = 0.04). Assay throughput is &gt;80 tests per hour in batch mode, 60 tests per hour with mixed load list configurations.
Cyclosporin whole blood immunoassays (AxSYM, CEDIA, and Emit): a critical overview of performance characteristics and comparison with HPLC
Authors: Schütz Ekkehard , Svinarov Dobrin , Shipkova Maria , Niedmann Paul-Dieter , Armstrong Victor W , Wieland Eberhard , Oellerich Michael 
Published: January 2020

Abstract
Assays with different specificity are used for cyclosporin monitoring in clinical transplantation. A recent survey of 35 centers showed that 86% used immunoassays for cyclosporin A (CsA). In consensus documents the following performance criteria were recommended: (a) imprecision ≤10% at 50 μg/L and ≤5% at 300 μg/L; and (b) comparison with the reference method (HPLC) should yield a slope of 0.9–1.1, an intercept of −15 to 15 μg/L, and Sy‖x ≤15 μg/L. The newly developed CsA assays for the AxSYM (Abbott) and the CEDIATM (Boehringer Mannheim) as well as the EmitTM assay (Behring Diagnostica) were evaluated. Results from samples of heart, kidney, and liver recipients (100 specimens each) were compared with a validated HPLC-ultraviolet detection method. Between-series imprecision (CV) with commercial controls was 5.8% and 1.7% for AxSYM (70 and 300 μg/L), 11% and 5.5% for CEDIA (90 and 200 μg/L), and 8.1% and 4.5% for Emit (63 and 172 μg/L). In the presence of 300 μg/L parent CsA, cross-reactivities were (for AxSYM, CEDIA, and Emit, respectively) 7%, 4%, and none for AM1 (1 mg/L) and 12.6%, 25%, and 6% for AM9 (0.5 mg/L). Comparison with HPLC showed in heart and kidney recipients an average overestimation with the Emit and the CEDIA of ∼22%, with overestimation in the AxSYM of 32%. In liver recipients, the most challenging patient group, the CEDIA and the AxSYM showed a mean overestimation of 43% and 47%, respectively, and the Emit differed by 31% compared with HPLC. None of the immunoassays fully satisfied the performance criteria recommended in the consensus documents. In terms of specificity, Emit ranks before CEDIA, which ranks before AxSYM. Regarding imprecision, the ranking is AxSYM &lt; Emit &lt; CEDIA. These limitations must be considered when using these assays for therapeutic drug monitoring of CsA in clinical transplantation.
Electrospray ionization mass analysis of normal and genetic variants of human serum albumin
Authors: Brennan Stephen O 
Published: January 2020

AbstractBoth normal albumin (Al A) and genetically modified forms were isolated from six heterozygous subjects. Albumins from each individual were analyzed by electrospray ionization mass spectrometry (ESI MS), and the mass was compared with that predicted from the protein sequence. In all cases, the Al A was heterogeneous, with components of mass (± SE) 66 463 ± 4, 66 586 ± 3, and 66 718 ± 5 Da. Each genetic variant showed similar heterogeneity. The mass increase in Al Casebrook (2214 Da) was very close to that predicted (2205 Da) from protein and carbohydrate sequence analysis, whereas the increase in Al Redhill (2378 Da) was close to that expected (2392 Da) for an Arg-albumin with a disialylated N-linked biantennary oligosaccharide and an Ala→Thr mutation. The circulating proalbumins, Christchurch and Blenheim, had mass increases of 748 and 756 Da, respectively, over Al A; in excellent agreement with theoretical values of 744 and 756. Clear shifts in mass were also detected for the point substitutions 177Cys→Phe (44 Da), 1Asp→Val (20 Da), and Arg-albumin (160 Da).
Time-dependent changes of serum carboxy-terminal peptide of type I procollagen and carboxy-terminal telopeptide of type I collagen concentrations in patients with acute myocardial infarction after successful reperfusion: correlation with left ventricular volume indices
Authors: Murakami Takashi , Kusachi Shozo , Murakami Masahiro , Sano Issei , Uesugi Tadahisa , Murakami Masaaki , Hirami Ryouichi , Kajiyama Akio , Kondo Jun , Tsuji Takao 
Published: January 2020

Abstract
To test the hypothesis that in patients with acute myocardial infarction (AMI), changes in the concentrations of the serum carboxy-terminal peptide of type I procollagen (PICP) and the carboxy-terminal telopeptide of type I collagen (ICTP) reflect extracellular matrix reformation and degradation, respectively, in the infarct healing processes, we measured these serum concentrations by RIA and compared their values with left ventricular (LV) indices obtained by left ventriculography. We studied 13 consecutive patients with their first AMI who underwent successful reperfusion. Blood samples were taken the day of admission and on days 2, 3, 4, 5, 7, and 14. LV volume indices were determined at 1 month after AMI, when LV remodeling was almost completed. The serum concentrations of both PICP and ICTP changed in a time-dependent manner. The average serum PICP concentration was lower than 1 SD below the mean control values on days 2 and 3 and increased thereafter, returning to the lower end of the control range at day 14. The area under the curve (AUC) for PICP was significantly correlated with the LV end systolic (ES) and end diastolic (ED) volume indices and LV ejection fraction for the first 14 days after AMI. The serum PICP on days 5–14 was inversely correlated or tended to be correlated with the LVES and LVED volume indices. The average serum ICTP concentrations on admission were within the control range, began to increase on day 2, and reached maximal concentrations on day 5, remaining at a plateau concentration until day 14. Although the AUC of ICTP for 14 days, the ICTP concentrations on days 1 and 14, and the minimal and maximal concentrations were significantly correlated with creatine kinase (CK) release and the period from AMI onset to the peak CK time, the concentrations were not significantly correlated with any LV indices except for the concentration on day 4, which was weakly correlated with the LVES volume index. The serum concentrations of PICP showed a significant time-dependent change that correlated with LV indices, indicating that PICP may provide additional information for evaluating the healing process because it affects LV remodeling after AMI. Although the serum concentration of ICTP changed in association with CK release, the ICTP concentration was found to be a poor indicator for LV indices.
Smoking, obesity, and hypertension alter the dose–response curve and test sensitivity of carbohydrate-deficient transferrin as a marker of alcohol intake
Authors: Whitfield John B , Fletcher Linda M , Murphy Theresa L , Powell Lawrie W , Halliday June , Heath Andrew C , Martin Nicholas G 
Published: January 2020

Abstract
Serum carbohydrate-deficient transferrin (CDT) is a specific and comparatively sensitive marker of excessive alcohol use; however, reports of its sensitivity vary according to the population or patient groups studied and their average alcohol intake. We have characterized the dose–response curve between alcohol intake and CDT concentrations in a study of 1400 men and women from a community-based twin registry. Our results show that mean CDT increases with increasing reported alcohol consumption even within the range of alcohol use considered to be nonhazardous. We found significant effects of sex, age, smoking, previous alcohol dependence, body mass index, and diastolic hypertension on the alcohol-CDT dose–response curve. These variables either affect test sensitivity or require adjustment of reference intervals. The results also provide insight into the physiological and biochemical factors that affect CDT concentration.
Urinary and plasma urodilatin measured by a direct RIA using a highly specific antiserum
Authors: Meyer Markus , Armbruster Franz P , Maier Ina , Schwing Jens , Haller Christlieb , Missbichler Albert , Adermann Knut , Forssmann Wolf-Georg , Woloszczuk Wolfgang 
Published: January 2020

AbstractUrodilatin (95–126) (URO) appears to play a major physiologic role in fluid homeostasis and produces major changes when administered intravenously. Here we describe a monospecific, high-affinity antiserum against URO with no cross-reactivity (&lt;0.01%) against the structural highly homologous atrial natriuretic peptide 99-126 (ANP-99-126), ANP analogs, and related peptides such as brain natriuretic peptide. A competitive RIA was developed, based on this antiserum. Urine samples with or without ethanol extraction and plasma samples without pretreatment were analyzed by the RIA, which had a detection limit of 10.5 ng/L, a linear measuring range between 10.5 and 1000 ng/L, and recoveries of 93–102% in urine and 90–104% in plasma. The intraassay CVs were 8.2% and 8.1% for urine samples with 269 and 669 ng/L URO; the interassay CV was 9.7% at 839 ng/L. Using this assay, we present URO data for urine from healthy volunteers receiving low and routine sodium diets and from clinical urine specimens; we also present pharmacokinetic data for URO in plasma from patients suffering from bronchial asthma and treated by URO infusion.
A family with high serum leucine aminopeptidase activity derived from a novel variant CD13
Authors: Kawai Makoto , Hara Yukichi , Kubota Tetsuo , Shiba Kiyoko , Hosaki Seijin 
Published: January 2020

AbstractWe investigated a family in which some individuals showed extremely high serum leucine aminopeptidase (LAP) (EC 3.4.11.2) activity, mainly derived from a variant CD13. The isoelectric points of the variant and normal CD13 were 3.3 and 4.1, respectively, and both points converged at 4.4 after treatment with neuraminidase, indicating that more sialic acids are bound to the variant CD13 than normal. The molecular masses of both CD13s were 144 kDa by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. After treatment with neuraminidase, N-glycosidase, and O-glycosidase, apparent molecular masses of the variant and normal CD13 were 106 kDa and 100 kDa, respectively, suggesting that the variant CD13 contains a longer peptide than normal. This is the first case of familial high serum LAP activity in which the origin could be demonstrated by anti-CD13 monoclonal antibodies to be a variant CD13 inherited in an autosomal dominant mode. The isoelectric point of the LAP activity after neuraminidase treatment was different from that previously reported.
Simultaneous determination of methylenetetrahydrofolate reductase C677T and factor V G1691A genotypes by mutagenically separated PCR and multiple-injection capillary electrophoresis
Authors: Ulvik Arve , Ren Jicun , Refsum Helga , Ueland Per Magne 
Published: January 2020

Abstract
The C677T mutation of the methylenetetrahydrofolate reductase gene and the G1691A (Leiden) mutation of the factor V gene are established risk factors for thromboembolic disease. We here present an assay for the simultaneous genotyping of these common genetic variants. The assay involves a strategy based on multiplex mutagenically separated PCR performed in a single tube containing six primers. Separation of the resulting four PCR products (197, 207, 233, and 246 bp) was performed by capillary electrophoresis coupled with laser-induced fluorescence detection. The time for the automated electrophoresis was reduced to 2.5 min per sample by performing the capillary electrophoresis analysis in a multiple-injection mode.
Therapeutic drug monitoring in special populations
Authors: Walson Philip D 
Published: January 2020

Abstract
Therapeutic drug monitoring (TDM) is commonly used to maintain “therapeutic” drug concentrations. Even in compliant patients, with “average” drug kinetics, TDM is useful to identify the causes of unwanted or unexpected responses, prevent unnecessary diagnostic testing, improve clinical outcomes, and even save lives. TDM has greatest promise in certain special populations who are: (a) prone to under- or overrespond to usual dosing regimens, (b) least able to tolerate, recognize, or communicate drug effects, or who are (c) intentionally or accidentally misdosed. TDM is especially useful in patients at the extremes of age, in adolescents, and in patients who are either taking multiple drugs or expressing unusual pharmacokinetics as a result of physiological, environmental, or genetic causes. Less-well-appreciated uses of TDM include prevention of dangerousunderdosing of patients, investigation of adverse drug reactions, and identification of serious medication errors, even for a number of drugs that are not traditionally monitored. TDM can be useful for some drugs in any patient and for most drugs in some special populations.