bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Standards for Laboratory Automation
Authors: Hawker Charles D , Schlank Marc R 
Published: January 2020

Abstract
In clinical laboratories, the installation of total laboratory automation systems and/or modular systems has grown dramatically in the 1990s, particularly in the US, Japan, and Europe. As the number of installations and level of interest grew, several individuals and corporations active in the automation field recognized that the development of prospective standards might enable customers of such systems or equipment to purchase analyzers, automation systems or devices, and software from different vendors and retain interconnectivity of such equipment. These individuals also believed that the total market for automation systems and equipment would be significantly greater with standards than without standards, especially if customers were not forced to purchase everything from one vendor, and that there might be competitive pricing and new technology fostered via the standards. This early interest in standards development led to the initiation of a program by NCCLS in 1996 to develop prospective standards for laboratory automation. Part of the NCCLS effort has involved interaction and cooperation with other standards organizations in the US and other countries. This report describes the current status of the development of prospective standards for laboratory automation by NCCLS and the relationship of those standards to those of other standards organizations.
Leptin in Cerebrospinal Fluid from Children: Correlation with Plasma Leptin, Sexual Dimorphism, and Lack of Protein Binding
Authors: Landt Michael , Parvin Curtis A , Wong Michael 
Published: January 2020

AbstractBackground: Previous studies in adults have established that leptin is present at very low concentrations in cerebrospinal fluid (CSF), but few data exist concerning CSF leptin in children. Current evidence suggests that CSF leptin concentrations interact with hypothalamic centers controlling food intake. Serum leptin concentrations manifest a sexual dimorphism that arises during puberty.Methods: Leptin concentrations were determined in CSF from 42 pre- and postpubertal children who had been objectively classified into non-neurological disease or aseptic meningitis groups. Multivariate analysis of the dependence of CSF leptin on gender, pubertal state, body mass index (BMI), presence of aseptic meningitis, and CSF protein concentration was performed.Results: CSF leptin concentrations correlated with log-transformed plasma leptin concentrations in concomitantly collected samples (r = 0.582; P = 0.029). BMI and gender were significant determinants of CSF leptin in postpubertal children, but only BMI was significant in prepubertal children. Analysis with HPLC to separate protein-bound and free forms of leptin found only free leptin in CSF.Conclusions: CSF leptin concentrations in children reflect plasma leptin concentrations, including the advent of sexual dimorphism at puberty. Only free leptin is detectable in CSF, suggesting that it is the biologically active form.
Accurate and Rapid “Multiplex Heteroduplexing” Method for Genotyping Key Enzymes Involved in Folate/Homocysteine Metabolism
Authors: Barbaux Sandrine , Kluijtmans Leo A J , Whitehead Alexander S 
Published: January 2020

Abstract
Background: Hyperhomocysteinemia, which is often associated with low folate status, is an independent risk factor for cardiovascular diseases and several other pathologies. The four most common functional polymorphisms in genes involved in folate/homocysteine metabolism are methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MS) A2756G, and cystathionine β-synthase (CBS) 844ins68. The pathogenic impact of these variants is under active investigation in many laboratories. However, conventional genotyping methods, mostly using PCR followed by restriction enzyme digestion, often are compromised by partial fragment digestion. There is, therefore, a need to develop more reliable approaches to genotyping the above polymorphisms that may be applied in large-scale studies.
Methods: Sequence-specific heteroduplex generators for each of the MTHFR and MS single nucleotide polymorphisms were generated by site-directed mutagenesis. These were subcloned into a single construct, pHcyHG-1, which could be multiplexed with a simple PCR amplification across the CBS 844ins68 polymorphic site to generate composite genotype-specific banding patterns from individual genomic DNA samples that could be electrophoretically resolved.
Results: The “multiplex heteroduplexing” method yielded unambiguous MTHFR, MS, and CBS genotypes in a single-tube reaction that could be analyzed in a single gel run.
Conclusions: This method permits unambiguous genotyping of the four most common functional variants of enzymes involved in folate/homocysteine metabolism. It is rapid, reproducible, and inexpensive, and requires no special preparative or analytic facilities; consequently, it will facilitate large-scale studies of the genetic basis of hyperhomocysteinemia and the many pathologies that have been associated with this phenotype.
Total and Pancreatic Amylase Measured with 2-Chloro-4-nitrophenyl-4-O-β-d-galactopyranosylmaltoside
Authors: Morishita Yoshitaka , Iinuma Yoshitsugu , Nakashima Nobuo , Majima Keiichi , Mizuguchi Katsuhiko , Kawamura Yoshihisa 
Published: January 2020

AbstractBackground: Many different methods have been used to assay amylase activity, using nitrophenylated oligosaccharides as substrate; however, the hydrolysis steps in these methods are complex.Methods: We developed a new continuously monitoring assay for amylase activity in biological fluids, using 2-chloro-4-nitrophenyl-4-O-β-d-galactopyranosylmaltoside (GalG2CNP) as the substrate; this assay was used with anti-human salivary amylase monoclonal antibodies for specific determination of the pancreatic isoenzyme. Amylase converted GalG2CNP into β-d-galactopyranosylmaltose and 2-chloro-4-nitrophenol, which was measured at 405 nm.Results: GalG2CNP was cleaved between 2-chloro-4-nitrophenol and β-d-galactopyranosylmaltose and did not undergo transfer reactions. The within-assay CVs (n = 20) for total amylase (T-AMY) and pancreatic amylase (P-AMY) were 0.6–1.6% and 0.5–2.5%, respectively; and day-to-day CVs (n = 10) for T-AMY and P-AMY were 0.8–3.7% and 0.6–4.1%, respectively. T-AMY and P-AMY activities in serum or urine obtained by the proposed method correlated well with those determined by the 2-chloro-4-nitrophenyl 4-O-β-d-galactopyranosyl-β-maltotetraoside method or the modified IFCC method.Conclusions: This novel assay for T-AMY and P-AMY measures both activities stoichiometrically, directly, and easily, and may be suitable for routine procedures.
Immunoradiometric Assay of Circulating C-Reactive Protein: Age-related Values in the Adult General Population
Authors: Hutchinson Winston L , Koenig Wolfgang , Fröhlich Margit , Sund Malte , Lowe Gordon D O , Pepys Mark B 
Published: January 2020

Abstract
Background: Increased values of C-reactive protein (CRP), the classical acute phase protein, within the range below 5 mg/L, previously considered to be within the reference interval, are strongly associated with increased risk of atherothrombotic events, and are clinically significant in osteoarthritis and neonatal infection.
Methods: A robust new polyclonal-monoclonal solid- phase IRMA for CRP was developed, with a range of 0.05–10.0 mg/L.
Results: Plasma CRP values in general adult populations from Augsburg, Germany (2291 males and 2203 females; ages, 25–74 years) and Glasgow, Scotland (604 males and 650 females; ages, 25–64 years) were very similar. The median CRP approximately doubled with age, from ∼1 mg/L in the youngest decade to ∼2 mg/L in the oldest, and tended to be higher in females.
Conclusion: This extensive data set, the largest such study of CRP, provides valuable reference information for future clinical and epidemiological investigations.
Laboratory Costs in the Context of Disease
Authors: Young Donald S , Sachais Bruce S , Jefferies Leigh C 
Published: January 2020

Abstract
Background: To determine the contribution of laboratory costs to the overall costs of managing hospital patients with different diseases, we studied the costs of laboratory testing overall and in relation to the other costs incurred during hospitalization.
Methods: We used a database developed by the University HealthSystems Consortium containing &gt;1 million patients in 60 University Hospitals with diseases included in 486 diagnosis-related groups (DRGs). Laboratory costs included in the database comprised those associated with testing in the clinical laboratory together with those incurred in point-of-care testing and anatomic pathology but not those involving blood products and their transfusion.
Results: The mean laboratory costs to manage surgical patients were greater than those to manage medical patients in 19 of the 25 major diagnostic categories. The median laboratory costs for patients with liver transplants exceeded $8000, and the laboratory costs to support other organ transplants were among the highest. The highest proportion of total costs attributable to the laboratory was 18.3% for acute leukemia and kidney and urinary tract signs and symptoms, both in children. Laboratory costs were &lt;1.0% of the total costs for only 15 DRGs. The highest median daily laboratory cost, $416, was attributable to liver transplant patients. Several conditions had median laboratory costs less than $30 per day, in spite of lengths of stay that exceeded 10 days in some cases.
Conclusions: Although laboratory costs generally average 6% of the total costs for surgical conditions and 9% of the total costs for medical conditions, there is considerable variability. In general, laboratory costs were relatively poorly correlated with total costs. However, observation of high daily laboratory costs for many DRGs suggests that reducing length of stay would reduce both laboratory and total costs.
Evidence-based Laboratory Medicine: Supporting Decision-Making
Authors: Price Christopher P 
Published: January 2020

Abstract
There is an implicit acceptance that an evidence-based culture underpins the practice of laboratory medicine, in part because it is perceived as the scientific foundation of medicine. However, several reviews of specific test procedures or technologies have shown that the evidence base is limited and in many cases flawed. One of the key deficiencies in the scientific literature on diagnostic tests often is the absence of an explicit statement of the clinical need, i.e., the clinical or operational question that the use of the test is seeking to answer. Several reviews of the literature on specific procedures have also demonstrated that the experimental methodology used is flawed with, in some cases, significant bias being introduced. Despite these limitations it is recognized that a more evidence-based approach will help in the education and training of health professionals, in the creation of a research agenda, in the production of guidelines, in the support of clinical decision-making, and in resource allocation. Furthermore, as knowledge and technologies continue to be developed, an evidence-based strategy will be critical to harnessing these developments.
Riboflavin as a Determinant of Plasma Total Homocysteine: Effect Modification by the Methylenetetrahydrofolate Reductase C677T Polymorphism
Authors: Hustad Steinar , Ueland Per Magne , Vollset Stein Emil , Zhang Ying , Bjørke-Monsen Anne Lise , Schneede Jørn 
Published: January 2020

AbstractBackground: Plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease. tHcy concentrations are partly determined by folate, cobalamin, and vitamin B6 status, and methylenetetrahydrofolate reductase (MTHFR) and other flavoenzymes are important for the biotransformation of these vitamins. This motivates the investigation of the possible relationship between riboflavin status and tHcy.Methods: The study had a cross-sectional design and included 423 healthy blood donors, ages 19–69 years. We determined plasma tHcy, serum folate, serum cobalamin, serum creatinine, and MTHFR C677T genotype. In addition, we measured riboflavin and its two coenzyme forms, flavin mononucleotide and flavin adenine dinucleotide, in EDTA plasma by capillary electrophoresis and laser-induced fluorescence detection.Results: Riboflavin determined tHcy independently in a multiple linear regression model with adjustment for sex, age, folate, cobalamin, creatinine, and MTHFR genotype (P = 0.008). tHcy was 1.4 μmol/L higher in the lowest compared with the highest riboflavin quartile. The riboflavin-tHcy relationship was modified by genotype (P = 0.004) and was essentially confined to subjects with the C677T transition of the MTHFR gene.Conclusions: Plasma riboflavin is an independent determinant of plasma tHcy. Studies on deficient populations are needed to evaluate the utility of riboflavin supplementation in hyperhomocysteinemia.
Prognostic Significance of Low Serum Cholesterol after Cardiothoracic Surgery
Authors: Stachon Axel , Böning Andreas , Weisser Heike , Laczkovics Axel , Skipka Guido , Krieg Michael 
Published: January 2020

AbstractBackground: The precise prognostic significance of critically low cholesterol concentrations in patients undergoing cardiothoracic surgery is unknown.Methods: In a retrospective case-control study, we analyzed the database of 2074 patients, of whom 87 died postoperatively in hospital. All patients underwent cardiothoracic surgery using a heart-lung machine. Age, sex, body mass index, preoperative ejection fraction, smoking, diabetes mellitus, type of operation, emergency surgery, renal deficiency, pulmonary hypertension, and endocarditis were considered together with serum concentrations of cholesterol, C-reactive protein, alanine aminotransferase, and triglycerides. The statistics included sensitivity, specificity, predictive value, odds ratio, and the ROC curve.Results: Cholesterol decreased sharply immediately after surgery in both the deceased and the survivors. In the deceased, the mean cholesterol concentration (± SE) remained rather low between days 4 and 7 after surgery [2.46 ± 0.16 mmol/L (95 ± 6 mg/dL)]. In the survivors at that time, the mean cholesterol concentration was significantly (P &lt;0.001) higher [4.37 ± 0.03 mmol/L (169 ± 1 mg/dL)]. The positive predictive value of a critically low cholesterol concentration [&lt;3.10 mmol/L (&lt;120 mg/dL)] was 25.4%, increasing to 66.6% at a cutoff value of 1.55 mmol/L (60 mg/dL). The odds ratio under those circumstances was 15.5, and the area under curve (C-statistic) was 0.90.Conclusions: The cholesterol concentration between days 4 and 7 after cardiothoracic surgery possesses a high prognostic significance in terms of in-hospital mortality.
Glyceraldehyde Preserves Glucose Concentrations in Whole Blood Specimens
Authors: Landt Michael 
Published: January 2020

Abstract
Background: Glucose concentrations decrease in blood specimens during transport/processing, primarily because of continuing metabolism (glycolysis) by erythrocytes. Several means to reduce the loss of glucose in blood specimens have been developed, but all have major drawbacks. Glyceraldehyde, which has antiglycolytic activity, was assessed for potential in preserving glucose in blood specimens.
Methods: Heparinized blood from volunteers was treated with glyceraldehyde and other agents. After incubation for various times, plasma concentrations of glucose and other common analytes were determined with prevalent commercial analyzers.
Results: The racemic mixture of glyceraldehyde (d,l-GA) preserved glucose concentrations for up to 8 h at room temperature. Half-maximal effect was attained with 0.9 mmol/L d,l-GA. Trials of the d and l stereoisomers individually indicated that the l isomer (l-GA) was responsible for all or most of the antiglycolytic activity of the racemic mixture. Other related compounds were ineffective. Measurements of most common clinical laboratory analytes were unaffected by the presence of d,l-GA or l-GA.
Conclusions: Glyceraldehyde (d,l-GA or l-GA) effectively preserves glucose concentrations in whole blood specimens for up to 8 h. Specimens collected with d,l-GA or l-GA are suitable for analysis of many analytes commonly comeasured with glucose.
Evaluation of Novel Assays in Clinical Chemistry: Quantification of Plasma Total Homocysteine
Authors: Nexo Ebba , Engbaek Frode , Ueland Per Magne , Westby Christina , O’Gorman Paudy , Johnston Carole , Kase Bengt Frode , Guttormsen Anne B , Alfheim Ingrid , McPartlin Joseph , Smith David , Møller Jan , Rasmussen Karsten , Clarke Robert , Scott John M , Refsum Helga 
Published: January 2020

Abstract
Background: There is a need for systematic evaluation of methods before their release to the market. We addressed this problem in novel homocysteine assays as part of an European Demonstration Project involving six centers in four countries.
Methods: Two immunological methods for measurement of plasma total homocysteine (P-tHcy), the fluorescence polarization immunoassay (FPIA) and the enzyme immunoassay (EIA), were compared with two comparison methods, HPLC and gas chromatography–mass spectrometry (GC-MS). All laboratories performed the following procedures: (a) familiarization; (b) determination of linearity and precision by analyzing five plasma samples with interrelated concentrations for 20 days; (c) correlation using patients’ samples; and (d) assessment of long-term performance.
Results: Both immunological methods were linear for P-tHcy between 5 and 45 μmol/L. The intralaboratory imprecision (CV) was &lt;5% for FPIA and &lt;9% for EIA used with a sample processor. The bias was −2% to 3% for FPIA and 2–4% for EIA used with a sample processor.
Conclusions: The immunological methods provide results with little bias compared with HPLC and GC-MS. The imprecision of the assays must be considered in the context of their intended use(s).
Nonalcoholic Red Wine Extract and Quercetin Inhibit LDL Oxidation without Affecting Plasma Antioxidant Vitamin and Carotenoid Concentrations
Authors: Chopra Mridula , Fitzsimons Patricia E E , Strain John J , Thurnham David I , Howard Alan N 
Published: January 2020

AbstractBackground: Antioxidant enrichment of LDL can increase its resistance to oxidation and hence reduce its atherogenicity. The objective of the present study was to investigate whether in vivo supplementation with nonalcoholic red wine extract and quercetin can increase the oxidative resistance of LDL, and also whether the supplementation has any effect on other antioxidative micronutrients present in the blood.Methods: Twenty-one male subjects were supplemented with a placebo drink for 2 weeks and randomized into two groups. One group (n = 11) received the red wine extract (1 g/day, equivalent to 375 mL of red wine) and the other group (n = 10) quercetin (30 mg/day) for 2 weeks, followed by a 5-week washout period.Results: In the red wine extract-supplemented group, ex vivo copper-initiated oxidation of LDL (lag phase, mean ± SD) was 40 ± 11 min at the baseline, and increased significantly to 47 ± 6 min [P &lt;0.05 compared with placebo (38 ± 4 min) and the washout values (40 ± 5 min)]. In the quercetin-supplemented group, the lag phase was 44 ± 11 and 40 ± 5 min for the baseline and placebo, respectively, and increased significantly to 51 ± 7 min [P &lt;0.05 compared with placebo and washout (41 ± 9 min)] after supplementation. Plasma lipids (triglycerides, total cholesterol, LDL- and HDL-cholesterol) did not change during the study period. Supplementation with red wine extract or quercetin had no effect on plasma vitamin C and E, retinol, and carotenoid concentrations.Conclusions: Alcohol-free red wine extract and one of its components, quercetin, can inhibit LDL oxidation after in vivo supplementation; such “inhibition” is unrelated to changes in antioxidant vitamin and carotenoid concentrations.
Bone Marrow and Peripheral Blood Hematopoietic Stem Cell Transplantation: Focus on Autografting
Authors: Baynes Roy D , Hamm Caroline , Dansey Roger , Klein Jared , Cassells Lucinda , Karanes Chatchada , Abella Esteban , Peters William P 
Published: January 2020

Abstract
This review focuses on certain of the principles involved in high-dose chemotherapy and radiation therapy along with autologous hematopoietic stem cell transplantation for the treatment of certain malignancies. In addition, the evidence, wherever possible based on randomized data, for the application of this approach in certain malignancies is reviewed. The malignancies highlighted include acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin disease, and breast cancer.
Coagulation and Bleeding Disorders: Review and Update
Authors: Triplett Douglas A 
Published: January 2020

AbstractHemostasis is initiated by injury to the vascular wall, leading to the deposition of platelets adhering to components of the subendothelium. Platelet adhesion requires the presence of von Willebrand factor and platelet receptors (IIb/IIIa and Ib/IX). Additional platelets are recruited to the site of injury by release of platelet granular contents, including ADP. The “platelet plug” is stabilized by interaction with fibrinogen. In this review, I consider laboratory tests used to evaluate coagulation, including prothrombin time, activated partial thromboplastin time, thrombin time, and platelet count. I discuss hereditary disorders of platelets and/or coagulation proteins that lead to clinical bleeding as well as acquired disorders, including disseminated intravascular coagulation and acquired circulating anticoagulants.
Transfusion Medicine: An Overview and Update
Authors: Ness Paul M 
Published: January 2020

Abstract
The discovery of AIDS in the 1980s and its rapid evolution as a major concern for physicians and their patients have led to many questions about the safety of the blood supply. The attention placed on AIDS has led to new discoveries and technologies to reduce the risk of other transfusion complications such as hepatitis, bacterial contamination, and transfusion-associated graft-vs-host disease. Concerns about blood safety have focused much attention on alternative blood transfusion strategies such as autologous blood, viral inactivation, and artificial blood substitutes. This review describes the transfusion medicine delivery system in the United States, with special emphasis on evolving developments and their implications for the discipline of chemical pathology.