bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lowering the federally mandated cannabinoid immunoassay cutoff increases true-positive results
Authors: Huestis M A , Mitchell J M , Cone E J 
Published: January 2020

Abstract
Proposed changes to the Health and Human Services Guidelines for forensic urine drug testing will lower the required cannabinoid immunoassay cutoff concentration from 100 to 50 micrograms/L. We investigated the effect of this change on the sensitivity, specificity, and efficiency of eight cannabinoid immunoassays: Syva Emit d.a.u. 100; Syva Emit II 100; Syva Emit d.a.u. 50; Syva Emit II 50; Roche Abuscreen Online; Roche Abuscreen radioimmunoassay; Diagnostic Reagents; and Abbott ADx. All specimens also were assayed by gas chromatography/mass spectrometry. Lowering the cutoff concentration from 100 to 50 micrograms/L increased efficiencies and sensitivities for all immunoassays, with minor decreases in specificity (1.0-2.6%). There was a 23.2-53.6% increase in the number of true-positive specimens identified. Thus, lowering the cannabinoid immunoassay cutoff concentration from 100 to 50 micrograms/L resulted in detection of a substantial number of additional true-positive specimens, with an accompanying small increase in unconfirmed positive results.
Immunoradiometric assay of human intact proinsulin applied to patients with type 2 diabetes, impaired glucose tolerance, and hyperandrogenism
Authors: Chevenne D , Ruiz J , Lohmann L , Laudat A , Leblanc H , Gray I P , Passa P , Porquet D 
Published: January 2020

Abstract
We describe an immunoradiometric assay for human intact proinsulin in serum. In this method, one monoclonal antibody, coated onto polyacrylamide beads, cross-reacts with proinsulins and insulin. A sandwich is formed with intact proinsulin, split (65-66) proinsulin, and des (64-65) proinsulin binding with an 125I-labeled monoclonal antibody specific for an epitope at the intact B-C junction of proinsulin. Because split (65-66) and des (64-65) proinsulin concentrations are very low in serum, this assay essentially measures intact proinsulin. When we used 1-mL serum samples, the mean detection limit was 0.4 pmol/L. Mean proinsulin concentrations (pmol/L) were 3.4 (range 1-9.1) in healthy fasting subjects, 28.5 (9.7-101) in patients with type 2 diabetes (treated with metformin and sulfonylureas), 5.0 (1.6-9.3) in women with hyperandrogenism and normal insulinemia, 10.3 (2.6-36) in women with hyperandrogenism and hyperinsulinemia, and 8.5 (4.8-21.3) in patients with impaired glucose tolerance.
Development of indices for determining extracellular fluid sodium and water status in acute diabetic ketoacidosis: possible tools for clinical audit
Authors: Davidson D F , Williamson J , Boag D E , Millar T 
Published: January 2020

Abstract
The limitation of plasma sodium concentration as an indicator of extracellular hydration status in cases of acute diabetes is well recognized and could lead to individually inappropriate fluid therapy. However, in view of the small analytical and biological variations exhibited by plasma concentrations of protein, water, and sodium in health, we have developed simple laboratory indices that may better describe the extracellular environment. Preliminary data presented here for 20 patients with acute diabetic ketoacidosis admitted as emergencies to Crosshouse Hospital suggest that the type of approach we describe has the potential to supply meaningful therapeutic data to the managing physician and, therefore, merits further study in a clinical setting.
Iron-deficiency anemia is associated with high concentrations of transferrin receptor in serum
Authors: Punnonen K , Irjala K , Rajamäki A 
Published: January 2020

Abstract
We evaluated the use of transferrin receptor (TfR) in serum as an index of iron deficiency in 19 patients diagnosed as having iron-deficiency anemia, in 17 patients with anemia of chronic disease, and in a control group of 19 nonanemic patients who underwent elective ocular or nasopharyngeal surgery. The assessment of iron status of the anemic patients was based on the presence of stainable iron on bone marrow examination. In the patients with iron-deficiency anemia, the serum TfR concentration was 5.3 +/- 1.8 mg/L (mean +/- SD), significantly higher than in the control group (1.7 +/- 0.5 mg/L) or in the patients with anemia of chronic disease (1.6 +/- 0.4 mg/L). This study suggests that serum TfR measurement is a reliable index of iron depletion and potentially of importance in the diagnosis of iron-deficiency anemia.
Lithium determinations evaluated in eight analyzers
Authors: Sampson M , Ruddel M , Elin R J 
Published: January 2020

Abstract
We compared five ion-selective electrodes (ISEs; AVL 985S, Baxter Lytening 2Z, Beckman EL-ISE, Ciba-Corning 654 Na/K/Li, and Nova CRT 11) and a colorimetric method (Ektachem) for determination of lithium with flame atomic absorption and atomic emission spectroscopy. We evaluated precision, recovery, interference by drugs (procainamide, N-acetylprocainamide, quinidine, lidocaine, carbamazepine, and valproic acid) and inorganic analytes (Na, K, Ca, Mg, and Br), and performance with sera from patients receiving lithium. Imprecision was &lt; 5% (CV) for all analyzers except Ektachem and Beckman. Analytical recovery was 100% +/- 5% for all analyzers except Ektachem and Baxter. Some drug interference was seen with all analyzers except AVL and Corning. Calcium caused interference with AVL, Corning, and Ektachem analyzers, and sodium and potassium interfered with the Ektachem analyzer. The results with the Baxter, Beckman, and Corning analyzers were closest to those by flame atomic emission (mean differences, 0.01 to 0.02 mmol/L); the AVL and Nova analyzers gave lower results (mean differences, -0.11 to -0.13 mmol/L) and the Ektachem gave higher results (mean difference, 0.08 mmol/L).
SR1 assays of alpha-fetoprotein, carcinoembryonic antigen, and prostate-specific antigen compared with corresponding established commercial assays
Authors: Jolley N L , Bacarese-Hamilton T 
Published: January 2020

Abstract
We compared results obtained with the newly developed alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and prostate-specific antigen (PSA) assays for the fully-automated Serono SR1 analyzer with those obtained with the major, established methods for these analytes: Serono Serozyme and Bridge, Abbott IMx, Kodak Amerlite, Boehringer Mannheim ES600, Pharmacia Delfia, Hybritech Tandem-E and Tandem-R, Ciba Corning ACS180, and DPC IRMA-Count. The correlations were good for all methods studied (r &gt; or = 0.94). For AFP, numerical agreement was good, with linear regression slopes of 0.88 to 1.15; for CEA, correlation slopes of 1.03 to 1.16 were observed. The SR1 PSA assay agreed well with five of the seven methods studied (slopes of 0.98 to 1.22), but the Ciba Corning ACS180 PSA assay gave results higher than all other methods studied (slope 0.54 vs SR1 at low doses) and the Abbott IMx PSA assay gave results lower than all other methods studied (slope 1.47 vs SR1).
Cardiac troponin-T immunoassay for diagnosis of acute myocardial infarction
Authors: Wu A H , Valdes R , Apple F S , Gornet T , Stone M A , Mayfield-Stokes S , Ingersoll-Stroubos A M , Wiler B 
Published: January 2020

Abstract
We evaluated the analytical and clinical performance of an immunoassay for cardiac troponin T (cTnT). Within-run and total imprecision ranged from 1.6 to 11.3%. The sensitivity and linear range was 0.015 and 13 micrograms/L, respectively. Frozen samples were stable for at least 8 weeks. No interferences were seen with lipids or bilirubin (total and conjugated). Hemoglobin caused a negative bias at concentrations &gt; 4 g/L. Heparinized plasma showed a 6% negative bias compared with serum. The clinical utility of cTnT was compared with that of creatine kinase (CK)-MB (mass assay). The sensitivity of cTnT measurements from 63 patients with acute myocardial infarction (AMI) (cTnT cutoff 0.1 microgram/L) was 60% at 0-3 h, 59% at 3-6 h, 94% at 6-9 h, 90% at 9-12 h, 99% at 12-24 h, 92% at 24-48 h, 83% at 48-72 h, and 100% at 72-96 h. Corresponding results for CK-MB (cutoff 5.0 micrograms/L and 2.5% relative index) were 45%, 64%, 82%, 97%, 87%, 81%, 54%, and 59%. The specificity of the markers from 49 non-AMI patients was 46% and 79% for cTnT and CK-MB, respectively. We show that CK-MB is more specific for diagnosis of AMI, and propose that cTnT is more sensitive to myocardial injury.
HPLC analysis of oligosaccharides in urine from oligosaccharidosis patients
Authors: Peelen G O , de Jong J G , Wevers R A 
Published: January 2020

Abstract
Analysis of urinary oligosaccharides by thin-layer chromatography (TLC) is used as screening procedure for 10 different lysosomal diseases. We tested the usefulness of HPLC in screening, using a CarboPac PA1 column (Dionex), pulsed amperometric detection (PAD), and post-column derivatization (PCD). Patterns from six types of oligosaccharidoses were compared with normal urinary patterns and with the TLC patterns. PAD appeared to be nonspecific and therefore is applicable only to desalted urine samples. PCD was more specific and applicable to nondesalted urine samples, albeit with a lower resolving power. Peaks in urines from oligosaccharidoses patients were identified on the basis of retention times of commercially available oligosaccharides or TLC bands after isolation and HPLC of the corresponding oligosaccharides. Abnormal oligosaccharide peaks were seen in urines from patients with alpha-mannosidosis, GM1-gangliosidosis (juvenile), GM2-gangliosidosis (Sandhoff disease), Pompe disease, and beta-mannosidosis. HPLC detected no abnormal oligosaccharides in urine from patients with fucosidosis. Although TLC is a simple and reliable screening procedure for detecting classical lysosomal diseases with oligosaccharide excretion, HPLC, by its higher resolution and possibility of quantification, can more generally be used for recognition of abnormal oligosaccharides or detection of increased excretion or content for known oligosaccharides in urine, other body fluids, and cells.
New international reference preparation for proteins in human serum (RPPHS)
Authors: Whicher J T , Ritchie R F , Johnson A M , Baudner S , Bienvenu J , Blirup-Jensen S , Carlstrom A , Dati F , Ward A M , Svendsen P J 
Published: January 2020

Abstract
Quality-control surveys in recent years, in various parts of the world, have shown poor between-laboratory agreement for measurements of plasma proteins. Despite the existence of international reference materials distributed by the World Health Organization, standards produced by diagnostics manufacturers and professional organizations differ significantly in their ascribed values. The reasons for this are complex but include poor availability of the primary materials, confusion about their use, and the fact that their turbidity on reconstitution precludes their use in modern optical immunoassays. This unfortunate situation led to an important initiative to produce sufficient quantities of a widely available, optically clear secondary reference material for plasma proteins that could be used worldwide by manufacturers, professional organizations, and laboratories. Here we present an overview on how the laboratory community, including manufacturers, clinical laboratories, professional societies, and regulators, has reached what we consider is a successful conclusion to a difficult problem.
European specifications for imprecision and inaccuracy compared with operating specifications that assure the quality required by US CLIA proficiency-testing criteria
Authors: Westgard J O , Seehafer J J , Barry P L 
Published: January 2020

Abstract
Proposed and interim European quality specifications for imprecision and inaccuracy have been compared with the US CLIA total error criteria for proficiency testing (PT). To assess the relative demands of separate imprecision and inaccuracy specifications vs total error criteria, we derived the imprecision and inaccuracy that would be allowable if a testing process were to provide 90% assurance of achieving the analytical quality required by CLIA PT criteria. Charts of operating specifications (OPSpecs charts) were prepared for commonly used single-rule and multi-rule quality control procedures with 2 and 4 control measurements per run. Of the 23 tests studied, the proposed European specifications for imprecision and inaccuracy were more demanding than the CLIA requirements for 12 tests (albumin, alkaline phosphatase, amylase, calcium, chloride, creatinine, lactate dehydrogenase, lithium, magnesium, total protein, sodium, and thyroxine). The CLIA total error criteria were more demanding than the proposed European specifications for nine tests (alanine aminotransferase, aspartate aminotransferase, total bilirubin, cholesterol, creatine kinase, iron, triglycerides, uric acid, and urea nitrogen). Two tests (glucose, potassium) showed different requirements at different decision levels. Manufacturers and laboratory analysts need to compare these different quality specifications on a test-by-test basis to guide the development, selection, evaluation, and control of laboratory measurement procedures.
Stable expression of enzymatically active human pancreatic lipase in V79 cells: purification and characterization of the recombinant enzyme
Authors: Canalias F , Visvikis A , Thioudellet C , Siest G 
Published: January 2020

Abstract
The serum activity of human pancreatic lipase (HPL; EC 3.1.1.3), the main lipolytic enzyme secreted by the pancreas, is a valuable marker of pancreatic disorders. However, determining lipase activity in human serum is difficult because the substrates used vary in their lipase specificity. A lipase reference material is therefore needed. We describe the production of recombinant HPL (rHPL) in V79 Chinese hamster lung cells. A cDNA encoding the sequence of HPL was subcloned into the pcDNAI eukaryotic expression vector, which was then used to transfect V79 cells. The 50-kDa purified recombinant enzyme is fully active, is glycosylated, and has a pI of 7.0. The catalytic properties of rHPL, determined by using triolein as the substrate, were similar to those of the native enzyme. The V79rHPL cell line we developed might be useful for the production of rHPL suitable for the preparation of a reference material.
Alkaline phosphatase isoforms in serum after liver allograft surgery
Authors: Randolph-Habecker J , Lott J A , Tesi R J 
Published: January 2020

Abstract
Orthotopic liver transplantation (OLT) is now the only available treatment for end-stage liver disease; the major postoperative complications of OLT are rejection and infection. Fractionation of alkaline phosphatase (ALP) isoforms in serum by isoelectric focusing can be used to identify patients with complications. Reference ranges for liver-function tests (LFT) and liver ALP isoforms were established for post-OLT patients with stable postoperative courses and compared with those of patients with complications. We found canalicular, hepatocyte, and high-molecular-mass ALP to be statistically higher in nearly all patients with complications as compared with patients who had a stable postoperative course; these tests may identify patients requiring a liver biopsy. When used in conjunction with LFT and other clinical findings, ALP isoforms could aid in the monitoring of complications and treatment and in the adjustment of immunosuppressive therapy in stable OLT cases.
Relevance of macro creatine kinase type 1 and type 2 isoenzymes to laboratory and clinical data
Authors: Lee K N , Csako G , Bernhardt P , Elin R J 
Published: January 2020

Abstract
From 8322 patients for whom creatine kinase (CK; EC 2.7.3.2) isoenzyme analysis was ordered, we identified 136 patients with macro CK isoenzyme in their serum. There were 36 cases with type 1 (prevalence: 0.43%) and 100 cases with type 2 isoenzyme (prevalence: 1.20%). About three-fourths of the patients were ambulatory at the time of testing, and approximately 90% of the first 68 patients identified survived at least 1 year after macro CK was found in their serum. Age and gender did not differ significantly between the two groups. The serum total CK was significantly higher (P &lt; 0.0005), and an increased CK-MB proportion (&gt; 0.05 of total CK) was also significantly more common (P &lt; 0.0005) in patients with macro CK type 1 than in those with type 2. On average, macro CK type 2 accounted for approximately 25% and macro CK type 1 for approximately 10% of the serum total CK activity. Patients with macro CK type 1 most often had myositis, whereas those with macro CK type 2 most commonly had a malignancy. We conclude that the presence of macro CK isoenzymes has a low prognostic value for impending death, but may support the diagnosis of an autoimmune process (type 1) or malignant cell proliferation (type 2).
Rapid automated enzyme immunoassay of serum amyloid A
Authors: Wilkins J , Gallimore J R , Tennent G A , Hawkins P N , Limburg P C , van Rijswijk M H , Moore E G , Pepys M B 
Published: January 2020

Abstract
Serum amyloid A (SAA), a sensitive acute-phase protein, is the precursor of AA fibrils in reactive amyloidosis. However, SAA is poorly immunogenic, and development and standardization of immunoassays of this protein have been difficult. We established an automated polyclonal/monoclonal microparticle capture enzyme immunoassay, standardized with the World Health Organization prospective reference standard for SAA. A stabilized concentrate of SAA was used for controls and calibrators. The assay range was 1-750 mg/L with CVs &lt; 7% throughout. Plasma and serum gave identical results and no interferences were observed. Linear regression against radial immunodiffusion assay gave a slope of 1.04 (95% confidence interval 0.99-1.10), intercept of -9 mg/L (95% confidence interval -14-3), and residual SD (SEE) of 20 for samples containing &lt; or = 200 mg/L (n = 173). In 105 apparently healthy adults the mean (SD) SAA concentration was 3.7 (3.6) mg/L, the median was 3.0 mg/L, and the range, 0.7-26.4 mg/L. In clinical acute-phase sera, values up to 2200 mg/L were seen. This method will facilitate measurement and investigation of SAA in clinical practice generally and in AA amyloidosis.
Automated HPLC assay of fluoxetine and norfluoxetine in serum
Authors: Nichols J H , Charlson J R , Lawson G M 
Published: January 2020

Abstract
This automated assay determines the concentration of the antidepressant fluoxetine (Prozac) and its active metabolite norfluoxetine in serum by reversed-phase HPLC with spectrophotometric detection. Extraction, injection, and quantification are performed by the Gilson Aspec automated sample handler. The patient's specimen, with added protriptyline as internal standard, is extracted with solid-phase and liquid-liquid methods. Separation is conducted isocratically on a 5-microns (particle size) Supelcosil LC-8-DB reversed-phase column with a triethylamine acetate:acetonitrile mobile phase. The detection limit is 10 micrograms/L and absorbance varies linearly with concentration between 20 and 1,000 micrograms/L for both compounds. Mean recovery was 62% for fluoxetine and 70% for norfluoxetine over linear limits. Within-run and day-to-day imprecision (CV), evaluated at three concentrations (50, 200, and 500 micrograms/L), ranged from 2% to 7%. An extensive interference study of 108 drugs was conducted. Results (n = 58) by the automated method (y) correlated well with those by a manual HPLC method (x): y = 0.96x + 10.20 (r = 0.951, Sylx = 42.9) for fluoxetine, and y = 0.95x - 1.37 (r = 0.917, Sylx = 47.2) for norfluoxetine.
Changes in biliary (high-molecular-mass) and liver isoforms of alkaline phosphatase after baboon-to-human liver transplantation
Authors: Mercer D , Tang M , Marino I R , Demetris A , Fung J , Starzl T , Warty V 
Published: January 2020

Abstract
We report a case of hyperphosphatasemia in a 35-year-old patient with hepatitis B who underwent an orthotopic xenogeneic liver transplant. Marked increases in total alkaline phosphatase (ALP; EC 3.1.3.1) activity began 5 days posttransplantation (six times human normal) and increased to approximately 17 times normal at day 11. Increased ALP persisted for &gt; 40 days and steadily increased to 75 times normal in the patient's last 30 days. Gel electrophoresis detected both liver (LALP) and biliary (high-molecular-mass, BALP) isoforms. LALP measured with ion-exchange columns revealed an activity time course pattern similar to that of total ALP. Results for BALP activity also obtained with ion-exchange columns exhibited broad variability, ranging from 2 to 428 times normal.
Aspartate aminotransferase macroenzyme complex in serum identified and characterized
Authors: Stasia M J , Surla A , Renversez J C , Pene F , Morel-Femelez A , Morel F 
Published: January 2020

Abstract
Macromolecular aspartate aminotransferase was found in the serum of an apparently healthy patient. This complex was composed of aspartate aminotransferase (AST; EC 2.6.1.1) and immunoglobulin. Electrophoresis of the patient's serum showed an abnormal band migrating between mitochondrial (m) and cytosolic (s) AST. The macromolecular complex was purified by gel filtration on Sephacryl S300. The molecular mass of the complex was estimated to be 250 kDa, suggesting that the complex probably consists of one immunoglobulin molecule associated with one AST molecule. By immunoelectrophoresis, the immunoglobulin was found to be an IgG with kappa-lambda type light chain. When we used polyclonal antibodies against human mAST or sAST, the sAST antibodies strongly inhibited the AST activity of the macrocomplex, whereas the mAST antibodies had no effect. Thus the AST molecule of the macrocomplex is an sAST type.
Critical evaluation of current concepts in exposure assessment
Authors: Heinzow B G , McLean A 
Published: January 2020

Abstract
The exploitation of natural resources and the improper use and disposal of thousands of chemicals have resulted in environmental pollution and a potential threat to human health on a global scale. Increasing public concern about environmental exposure to and consequent ill health from contaminants demands informed answers based on valid risk assessment. By assessing internal exposure to pollutants, human biomonitoring focuses on early markers of potential risks to prevent serious adverse effects. Exposure assessment may provide a rational basis for risk assessment, with knowledge of the adequacy of limit values; it may also uncover long-term changes in body burdens and thus help identify the sources and transfer pathways of environmental pollutants. The techniques of biological exposure assessment should be incorporated into epidemiological studies if suitable specimens are available, such as exhaled air, blood, urine, breast milk, or adipose or keratinous tissue. Special precautions must be taken in sampling, storage, and analysis if the findings are to be interpreted correctly and reliable conclusions drawn.
Validity of lead exposure markers in diagnosis and surveillance
Authors: Graziano J H 
Published: January 2020

Abstract
Extensive research has been devoted to the development of biomarkers of environmental and occupational exposure to lead (Pb). This body of work can serve as a paradigm for biomarker development for other chemical exposures. Early efforts focused on indirect measurements of exposure by analyzing precursors and enzymes of a biosynthetic pathway (heme) in blood and urine. However, the direct measurement of Pb in blood has become increasingly simple and reliable and is now widely accepted for pediatric surveillance programs, in part because of known associations of Pb with adverse health outcomes. Other markers of exposure include measurements of Pb in important compartments: bone Pb, tooth Pb, and chelatable Pb. In addition, the technique of stable isotope dilution is available, since Pb exists in numerous nonradioactive isotopic forms. The strengths and weaknesses of all Pb biomarkers for confirming a diagnosis or for epidemiologic research vary widely depending upon the hypothesis under investigation.