bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methods for Measurement of LDL-Cholesterol: A Critical Assessment of Direct Measurement by Homogeneous Assays versus Calculation
Authors: Nauck Matthias , Warnick G Russell , Rifai Nader 
Published: January 2020

AbstractBackground: Because LDL-cholesterol (LDL-C) is a modifiable risk for coronary heart disease, its routine measurement is recommended in the evaluation and management of hypercholesterolemia. We critically examine here the new homogeneous assays for direct determination of LDL-C.Approach: This review relies on published studies and data of the authors using research and routine methods for LDL-C determination. We review experience with methods from their earlier use in lipid research laboratories through the transition to routine clinical testing and the recent development of homogeneous assays. We focus on comparative evaluations and characterizations and the performance of the assays.Content: Homogeneous assays seem to be able to meet current National Cholesterol Education Program (NCEP) requirements for LDL-C testing for precision (CV &lt;4%) and accuracy (bias &lt;4%), when samples collected from nonfasting individuals are used. In addition, all five currently available assays have been certified by the Cholesterol Reference Methods Laboratory Network. The homogeneous methods also appear to better classify individuals into NCEP cutpoints than the Friedewald calculation. However, the limited evaluations to date raise questions about their reliability and specificity, especially in samples with atypical lipoproteins.Conclusions: Available evidence supports recommending the homogeneous assays for LDL-C to supplement the Friedewald calculation in those cases where the calculation is known to be unreliable, e.g., triglycerides &gt;4000 mg/L. Before the homogeneous assays can be confidently recommended to replace the calculation in routine practice, more evaluation is needed.
Inaccuracy of Lipid Measurements with the Portable Cholestech L·D·X Analyzer in Patients with Hypercholesterolemia
Authors: Stein James H , Carlsson Cynthia M , Papcke-Benson Kristi , Einerson Jean A , McBride Patrick E , Wiebe Donald A 
Published: January 2020

Abstract
Background: Although total cholesterol concentrations measured by portable lipid analyzers have acceptable bias and precision in young and middle-aged adults, clinically relevant differences in HDL-cholesterol (HDL-C) and triglyceride values have been described. Furthermore, the accuracy of portable lipid analyzers in older hyperlipidemic individuals, who have a high incidence of coronary heart disease, has not been validated. This study determined the biases and variability in portable lipid measurements in older patients with hypercholesterolemia and related them to National Cholesterol Education Program Adult Treatment Panel III guidelines.
Methods: Participants were ≥70 years of age with fasting serum LDL-cholesterol (LDL-C) concentrations &gt;1.40 g/L. Fasting fingerstick samples were analyzed on a Cholestech L·D·X desktop analyzer. Antecubital venous samples were analyzed in a proficiency-certified clinical laboratory.
Results: Portable measurements systematically overestimated triglycerides (0.296 g/L; P &lt;0.001) and HDL-C (0.015 g/L; P = 0.026). LDL-C concentrations were underestimated (0.043 g/L; P = 0.046). Total and non-HDL cholesterol calculations based on the portable lipid device provided unbiased estimates, but wide variability was present. Significant variability in lipid determinations limited their clinical usefulness in individual patients, especially because 2 SD of the mean bias between the laboratory and the portable determinations of LDL-C and non-HDL cholesterol exceeded the 0.30 g/L cutoff that defines treatment targets in the current lipid guidelines.
Conclusions: Lipid values obtained from portable lipid analyzers may be useful for screening, but they should not be used to make clinical decisions regarding the diagnosis and management of dyslipidemia in individual patients.
Diagnostic Biochip Array for Fast and Sensitive Detection of K-ras Mutations in Stool
Authors: Prix Lothar , Uciechowski Peter , Böckmann Beatrix , Giesing Michael , Schuetz Andreas J 
Published: January 2020

Abstract
Background: Tumor cells that shed into stool are attractive targets for molecular screening and early detection of colon or pancreatic malignancies. We developed a diagnostic test to screen for 10 of the most common mutations of codons 12 and 13 of the K-ras gene by hybridization to a new biochip array.
Methods: DNA was isolated from 26 stool samples by column-based extraction from 9 cell lines. Peptide nucleic acid (PNA)-mediated PCR clamping was used for mutant-specific amplification. We used a biochip, consisting of a small plastic support with covalently immobilized 13mer oligonucleotides. The read out of the biochip was done by confocal time-resolved laser scanning. Hybridization, scanning, and data evaluation could be performed in &lt;2 h.
Results: Approximately 80 ng of DNA was obtained from 200-mg stool samples. No inhibition of the PCR by remaining impurities from stool was observed. Mutation detection was possible in 1000-fold excess of wild-type sequence. Discrimination ratios between the mutations were &gt;19 as demonstrated by hybridization with tumor cell line DNA. Stool samples (n = 26) were analyzed in parallel with PNA-PCR, restriction assay for K-ras codon 12 mutations, sequencing, and hybridization to the biochip. Nine mutations were found by hybridization, all confirmed by sequencing. PNA-PCR alone leads to an overestimation of mutations because suppression of the wild type is not effective enough with high concentrations of wild-type DNA. The restriction assay found only four mutations.
Conclusions: The K-ras biochip is well suited for fast mutation detection from stool in colorectal cancer screening.
Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus
Authors: Sacks David B , Bruns David E , Goldstein David E , Maclaren Noel K , McDonald Jay M , Parrott Marian 
Published: January 2020

AbstractBackground: Multiple laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially.Approach: An expert committee drafted evidence-based recommendations for the use of laboratory analysis in patients with diabetes. An external panel of experts reviewed a draft of the guidelines, which were modified in response to the reviewers’ suggestions. A revised draft was posted on the Internet and was presented at the AACC Annual Meeting in July, 2000. The recommendations were modified again in response to oral and written comments. The guidelines were reviewed by the Professional Practice Committee of the American Diabetes Association.Content: Measurement of plasma glucose remains the sole diagnostic criterion for diabetes. Monitoring of glycemic control is performed by the patients, who measure their own plasma or blood glucose with meters, and by laboratory analysis of glycated hemoglobin. The potential roles of noninvasive glucose monitoring, genetic testing, autoantibodies, microalbumin, proinsulin, C-peptide, and other analytes are addressed.Summary: The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are of minimal clinical value at the present time, and measurement of them is not recommended.
Determination of Anti-Acetylcholine Receptor Antibodies in Myasthenic Patients by Use of Time-resolved Fluorescence
Authors: Říčný Jan , Šimková Libuše , Vincent Angela 
Published: January 2020

AbstractBackground: Autoantibodies against nicotinic acetylcholine receptor (nAChR) in myasthenia gravis (MG) patients are usually detected by radioimmunoprecipitation assays using extracted acetylcholine receptors labeled irreversibly with 125I-α-bungarotoxin (α-BuTx). To provide a nonradioactive immunoassay, we established an assay using nAChRs labeled with Eu3+-α-cobratoxin (α-CTx).Methods: We derivatized α-CTx with a diethylenetriaminepentaacetate moiety and formed a complex with Eu3+. The complex was purified by HPLC, and the fractions were tested for binding to Torpedo and human nAChRs. The most active fractions were used to label nAChRs for the immunoprecipitation assay, and the bound Eu3+ was quantified by time-resolved fluorescence.Results: Eu3+-labeled α-CTx competed with 125I-α-BuTx for binding to Torpedo nAChRs and saturated the binding sites of human nAChRs, with a Kd of 7.2 × 10−9 mol/L. Results of the immunoassay performed with Eu3+-labeled α-CTx were similar to those obtained with 125I-α-BuTx, with a slightly higher limit of detection [0.3 nmol/L (n = 6) vs ∼0.1 nmol/L for isotopic assay]. None of 34 negative sera tested (16 healthy controls, 10 patients with nonmyasthenia-related disease, 8 patients seronegative for MG) gave a value &gt;0.3 nmol/L. Of the 35 positive myasthenic sera (with antibody values, previously determined by isotopic assay, of 0.4–1290 nmol/L) compared in the two assays, 32 tested positive with the Eu3+ assay. Linear regression analysis yielded the equation: y = 1.035x − 0.013 nmol/L; Sy|x = 0.172 nmol/L; r2 = 0.977.Conclusions: The new time-resolved fluorescence method for quantification of antibodies to nAChRs in MG patients provides a performance similar to that of the widely used isotopic assay and could be used in laboratories with restricted use of isotopes.
Age-related Reference Values for Serum Selenium Concentrations in Infants and Children
Authors: Muntau Ania C , Streiter Monika , Kappler Matthias , Röschinger Wulf , Schmid Irene , Rehnert Albert , Schramel Peter , Roscher Adelbert A 
Published: January 2020

AbstractBackground: Children are at particular risk for selenium deficiency, which has potentially serious medical implications. Reliable age-specific reference values for serum selenium concentrations in children are sparse, but are essential for the identification of selenium deficiency and decisions regarding selenium supplementation.Methods: Using electrothermal atomic absorption spectrometry, we analyzed serum selenium concentrations from 1010 apparently healthy children (age range, 1 day to 18 years) and from 60 patients on a protein-restricted diet because of inborn errors of metabolism. Reference intervals were defined according to recommended guidelines.Results: Medians for serum selenium concentrations showed a statistically significant age dependency: a decrease from the age &lt;1 month (0.64 μmol/L) to 4 months (0.44 μmol/L); an increase to 0.62 μmol/L in the 4–12 months age group; constant values in children between 1 and 5 years of age (0.90 μmol/L); and an additional slight increase to reach a plateau between 5 and 18 years (0.99 μmol/L). Of 43 children older than 1 year and on a protein-restricted diet, 87% showed serum selenium concentrations below the 2.5 percentile.Conclusions: Because of nutritional changes, serum selenium concentrations are significantly higher in older children than in infants under 1 year of age. The application of age-adjusted reference values may provide more specific criteria for selenium supplementation. Long-term protein restriction in children is reflected by a failure to achieve higher serum selenium concentrations with increasing age.
Highly Sensitive Cholesterol Assay with Enzymatic Cycling Applied to Measurement of Remnant Lipoprotein-Cholesterol in Serum
Authors: Kishi Koji , Ochiai Koji , Ohta Yohsuke , Uemura Yahiro , Kanatani Kazushi , Nakajima Katsuyuki , Nakamura Masakazu 
Published: January 2020

AbstractBackground: Remnant lipoprotein-cholesterol (RLP-C) concentrations in sera of healthy individuals are very low (0.080–0.437 mmol/L), making conventional cholesterol methods poorly suited to this purpose. We have developed a highly sensitive cholesterol assay (CD method) and applied it to the RLP-C assay.Methods: The CD shuttled cholesterol reversibly between reduced and oxidized forms in the presence of thio-NAD and NADH. The production rate of thio-NADH correlated with the cholesterol concentration and was measured by the absorbance at 404/500 nm. This CD method was combined with an immunoaffinity separation procedure with specific monoclonal antibodies to apolipoprotein (apo) A1 and apo B-100 and used for RLP-C assay. Results were compared with a RLP-C method that uses cholesterol oxidase, peroxidase, and chromogenic substrate.Results: The CD method could detect 0.10 × 10−3 mmol/L cholesterol and was at least 5 times more sensitive than the conventional enzymatic method. Within- and between-day imprecision (as CVs) of the RLP-C assay with the CD method was &lt;4%. Regression analysis of RLP-C assays with the new (y) and conventional (x) cholesterol methods yielded: y = 1.02x − 0.008 mmol/L (Sy|x = 0.0065 mmol/L; r = 0.997; n = 297).Conclusions: Serum RLP-C can be measured by the CD method. The CD method may be useful for other assays that require sensitive cholesterol measurements in biological materials.
Effect of Atorvastatin and Fish Oil on Plasma High-Sensitivity C-Reactive Protein Concentrations in Individuals with Visceral Obesity
Authors: Chan Dick C , Watts Gerald F , Barrett P Hugh R , Beilin Lawrence J , Mori Trevor A 
Published: January 2020

AbstractBackground: Chronic low-grade inflammation may contribute to the increased risk of atherosclerosis in visceral obesity. Statin and fish oil have been reported to have antiinflammatory effects. We studied whether dyslipidemic, obese individuals have increased plasma high-sensitivity C-reactive protein (hs-CRP) concentrations and whether treatment with atorvastatin and fish oil lowered plasma hs-CRP concentrations.Methods: We compared plasma hs-CRP, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) concentrations in 48 obese individuals with the concentrations in 10 lean normolipidemic men. The obese individuals were then randomized to treatment with atorvastatin (40 mg/day), fish oil (4 g/day), atorvastatin plus fish oil, or matching placebo for 6 weeks.Results: Compared with controls, obese individuals had increased hs-CRP [geometric mean, 2.19 mg/L (95% confidence interval, 2.15–3.15 mg/L) vs 0.49 mg/L (0.30– 0.93 mg/L); P &lt;0.001] and IL-6 [351 pg/L (318–449 pg/L) vs 251 pg/L (211–305 pg/L); P &lt;0.01]. Atorvastatin treatment had a significant main effect of decreasing plasma hs-CRP (−0.87 mg/L; 95% confidence interval, −0.10 to −1.60 mg/L; P &lt;0.01) and IL-6 (−70 pg/L; 10 to −140 pg/L; P &lt;0.01), but this was not seen with fish oil. The reductions in hs-CRP with atorvastatin were not significantly correlated to changes in plasma lipids, IL-6, insulin resistance, or cholesterogenesis. Plasma TNF-α concentrations in obese individuals, however, were neither statistically different from concentrations in the lean controls nor altered with atorvastatin or fish oil treatment.Conclusions: This study shows that visceral obesity is associated with increased plasma hs-CRP and IL-6 and, hence, a low-grade chronic inflammatory state and that treatment with atorvastatin or atorvastatin with fish oil, but not fish oil alone, reverses this abnormality.
Quantification and Utility of Monosialylated α-Fetoprotein in the Diagnosis of Hepatocellular Carcinoma with Nondiagnostic Serum Total α-Fetoprotein
Authors: Poon Terence CW , Mok Tony SK , Chan Anthony TC , Chan Charles ML , Leong Veronica , Tsui Steven HT , Leung Thomas WT , Wong Herman TM , Ho Stephen KW , Johnson Philip J 
Published: January 2020

AbstractBackground: At concentrations &lt;500 μg/L, serum α-fetoprotein (AFP) has low specificity in the diagnosis of hepatocellular carcinoma (HCC), but monosialylated AFP (msAFP) is more specific for HCC. We describe two strategies for quantitative analysis of msAFP and explore their diagnostic accuracy in cases of HCC with nondiagnostic serum total AFP concentrations.Methods: We first used isoelectric focusing, Western blot, and densitometry (IEF-Western blot assay). We then developed a second assay, a novel glycosylation immunosorbent assay (GISA), based on the specificity of sialyltransferase and immunosorbent technology. Both assays were used to measure msAFP and msAFP percentage relative to total AFP in sera with nondiagnostic AFP concentrations from 36 patients with newly diagnosed HCC and from 18 patients with liver cirrhosis.Results: The msAFP percentages and concentrations were significantly higher in the HCC patient group regardless of the quantification methods. The msAFP concentrations and msAFP percentages obtained by the two assays were highly correlated (r = 0.70 and 0.49, respectively). For discrimination of HCC with nondiagnostic serum total AFP from liver cirrhosis, the areas under the ROC curves were 0.81 (95% confidence interval, 0.70–0.92) for msAFP by IEF-Western blot assay, 0.73 (0.58–0.87) for msAFP by GISA, 0.89 (0.80–0.97) for msAFP percentage by IEF-Western blot assay, and 0.74 (0.59–0.89) for msAFP percentage by GISA.Conclusions: Both the serum concentration and percentage of msAFP are potential diagnostic markers for HCC with nondiagnostic AFP. GISA can quantify a specific glycoform of a serologic marker.
Relationship between Genetic Polymorphisms of Alcohol-metabolizing Enzymes and Changes in Risk Factors for Coronary Heart Disease Associated with Alcohol Consumption
Authors: Hashimoto Yoshiaki , Nakayama Toshifumi , Futamura Azusa , Omura Miho , Nakarai Hideo , Nakahara Kazuhiko 
Published: January 2020

AbstractBackground: There are large individual variations in the responses of risk factors for coronary heart disease to alcohol consumption. To clarify the factors responsible for these individual variations, we studied the relationship between blood pressure, serum lipids, and uric acid and the genetic polymorphisms of alcohol dehydrogenase (ADH) 2 and aldehyde dehydrogenase (ALDH) 2 in alcohol drinkers.Methods: We examined 133 male workers who drank &gt;300 g of alcohol per week. Information regarding lifestyle habits was obtained by questionnaire. The ADH2 genotype was determined by PCR and subsequent digestion with MaeIII. The ALDH2 genotype was determined based on amplified product length polymorphisms.Results: When the workers were divided into three groups: the ADH21/21, ADH21/22, and ADH22/22 groups, the mean triglycerides and γ-glutamyl transpeptidase concentrations were significantly higher in the ADH22/22 group than in the ADH21/21 group. In addition, multiple logistic regression analysis showed that the frequencies of individuals whose systolic blood pressure, triglycerides, and uric acid values were in the highest one third were significantly higher in the ADH22/22 group than in the ADH21/21 group. In contrast, no difference was observed between the ALDH21/21 and (ALDH21/22 + ALDH22/22) groups with regard to the mean value of any variable and to the frequency of individuals with any variable value in the highest one third.Conclusion: Individuals with the ADH21/21 genotype might suffer fewer negative effects of drinking.
Plasma Nucleic Acids in the Diagnosis and Management of Malignant Disease
Authors: Johnson Philip J , Lo YM Dennis 
Published: January 2020

AbstractBackground: There is a need for development of molecular markers of cancer that can be used clinically for the detection, prognostication, and monitoring of cancer. Recently, there has been much interest in the potential use of nucleic acid markers in plasma and serum for this purpose.Approach: We reviewed published literature up to 2002 on the topic, with a particular emphasis on reports published between 1996 and 2002.Content: The nucleic acid markers described in plasma and serum include oncogene mutations/amplifications, microsatellite alterations, and gene rearrangements. Such markers have been described in many cancer types, including lung, colon, and breast. Epigenetic alterations, such as aberrant promoter methylation, have been identified in plasma and serum. Viral nucleic acid markers, such as Epstein–Barr virus DNA in plasma and serum, are reviewed in detail with regard to their application to virus-associated cancers such as nasopharyngeal carcinoma and various lymphomas. More recently, mitochondrial DNA and tumor-related mRNAs have been identified in plasma and serum from patients with several types of tumors.Conclusions: Circulating nucleic acids are an emerging class of molecular tumor markers. Their wide applicability and clinical relationship with the malignant state will likely grant them increasing clinical importance in the near future.
Measurement of Prostate-specific Antigen by Use of a Novel Blood Collection and Analytical System
Authors: Grzeda Barbara R , Le Bui Tuan , Warner Cheryl N , Pirucki Tracy L , Dewey Lisa M , Babich Milan , Maggiore Jack A 
Published: January 2020

AbstractBackground: Prostate-specific antigen (PSA) is widely used in the detection and monitoring of prostate cancer. We developed a system for the self-collection and transport of capillary whole blood for PSA analysis, with the goal of reducing phlebotomy visits and, thus, increasing the access and utilization of PSA in prostate cancer screening and monitoring.Methods: The blood collection device [BIOSAFE Blood Transport System (BTSTM)] collects 70 μL of blood through a heparin-coated material into 200 μL of stabilizing solution. The diluted whole blood is used for measurement of PSA by a modified version of the Hybritech® Tandem-MP PSA Assay. Results were compared for matched samples of professionally and self-collected BTS blood and for matched BTS samples sera from blood collected by venipuncture. Imprecision for the whole-blood PSA measurement was estimated from analysis of whole-blood controls in duplicate, twice per day, over 20 days.Results: BTS samples (n = 140) collected by a qualified healthcare professional compared with serum samples yielded the regression equation: y =1.02x + 0.04 (Sy|x = 0.35; r = 0.99). Comparison of the results for samples (n = 128) collected by the patient without professional assistance with serum samples yielded: y = 1.08x + 0.02 (Sy|x = 0.31; r = 0.99). The between-run CVs at 0.069, 0.53, 2.9, and 10.7 μg/L were 21%, 6.0%, 3.5%, and 3.8%, respectively. PSA was stable in BTS samples stored for 21 days at 18–24 °C and for 7 days at 37 °C.Conclusion: The BIOSAFE BTS system allows accurate and convenient measurement of circulating PSA by a precise method for diluted whole blood.