bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dabigatran overload in acute kidney injury: haemodialysis or idarucizumab? A case report and proposal for a decisional algorithm
Authors: Galassi Andrea , Podda Gianmarco , Monciino Paola , Stucchi Andrea , Del Nero Alberto , Cozzolino Mario 
Published: January 2020

Abstract
Dabigatran overload has been reported in acute kidney injury (AKI), leading to occasional major bleeding. Haemodialysis (HD) was the method used for reversing dabigatran anticoagulant effects before the approval of idarucizumab, which is now indicated for dabigatran reversal in major bleeding or surgical emergencies. There have been reports of rebound of dabigatran levels following idarucizumab administration in AKI, requiring HD to achieve effective dabigatran clearance. However, a decisional algorithm to individualize treatments for dabigatran overload seems lacking. We present a case of dabigatran accumulation in obstructive AKI with minor bleeding that was successfully treated with HD and tranexamic acid without using idarucizumab, and propose a decision-making algorithm including different pathways in the management of suspected dabigatran overload in AKI.
Effect of assay methodology on pharmacokinetic differences between cyclosporine Neoral® and Sandimmune® formulations
Authors: Aspeslet Launa J , LeGatt Donald F , Murphy Gerard , Yatscoff Randall W 
Published: January 2020

Abstract
The new oral formulation of cyclosporine (CsA), Neoral® (CsA-N), results in increased area under the curve (AUC) and decreased intra- and interindividual variation in blood concentrations and other pharmacokinetic (PK) parameters when compared with the current Sandimmune® (CsA-S) formulation. The present study examines the effect of assay methodology on variability in blood concentrations and PK parameters for renal transplant patients receiving CsA-N and CsA-S and whether this variation is reduced with CsA-N. The results show that interindividual variations in PK parameters for patients receiving CsA-N were less than those for patients receiving CsA-S. Both blood concentrations and dose of CsA better correlated with abbreviated (4-h) AUC after administration of CsA-N. For both CsA-S and CsA-N, blood concentrations at 4 h postdose exhibited the best correlation with AUC. All samples were analyzed by three common procedures: HPLC, RIA, and fluorescence polarization immunoassay (FPIA). There were no significant differences observed in blood concentrations or PK parameters obtained from FPIA and RIA. HPLC results, however, were lower because of specificity of this method for the parent drug. The assay methodology did not have an effect on interindividual variability, indicating that the cross-reactivity of metabolites in commonly used immunoassays for CsA does not contribute to the PK variability observed in renal transplant patients.
Development and validation of a particle-enhanced turbidimetric inhibition assay for urine albumin on the Dade aca® analyzer
Authors: Thakkar Hansa , Newman David J , Holownia Peter , Davey Carol L , Wang Chi-Chin , Lloyd Joseph , Craig Alan R , Price Christopher P 
Published: January 2020

AbstractThe measurement of urine albumin now has a well-established role in the monitoring of patients with diabetes mellitus. We have developed a particle-enhanced immunoturbidimetric inhibition assay for urine albumin on the Dade aca® analyzer. The inhibition approach removes any of the potential antigen excess difficulties that could be expected from the wide clinical range of urine albumin, but retains the sensitivity advantages of latex-enhanced immunoturbidimetry. Human serum albumin (HSA) is covalently attached to 40-nm poly(chloromethyl)styrene-modified latex particles. This reagent, along with monoclonal antibody to HSA, is aliquoted into the aca reagent pack along with polyethylene glycol 8000 in a tablet form (giving a final reaction concentration of 15 g/L). A 150 mmol/L phosphate buffer, pH 7.8, is used to fill the reagent pack in the instrument and the agglutination reaction is monitored at 340 nm. The sample volume is 100 μL and the calibration curve covers the range 2–250 mg/L. Evaluation of commercial scale reagents against the Beckman Array nephelometric immunoassay system gave a Deming regression correlation of aca = 0.87 × Beckman + 8.5,r = 0.995, n = 145. Mean analytical recovery was 104 ± 4.5%, n = 20, and there was no evidence of a lack of parallelism. Interassay precision was 8.8% at 10.0 mg/L and &lt;2.5% at &gt;65 mg/L. Calibrator stability was in excess of 60 days. A small reference range study (24-h urine collections, n = 27) gave a mean of 5.6 mg/L with a range of 0.5–16.2 mg/L. Analytical sensitivity (2.5 SD from zero) was 0.40 mg/L.
Reference values for plasma concentrations of vitamin E and A and carotenoids in a Swiss population from infancy to adulthood, adjusted for seasonal influences
Authors: Winklhofer-Roob Brigitte M , Hof Martin A van’t , Shmerling David H 
Published: January 2020

AbstractIn a cross-sectional survey, plasma concentrations of α- and γ-tocopherol, α- and β-carotene (cis and trans isomers), lycopene, and retinol were determined by reversed-phase HPLC, and ratios of plasma α-tocopherol to cholesterol were calculated in 208 Swiss individuals ages 0.4–38.7 years. The influence of age, sex, and season of sampling was studied. Age was a significant predictor of all plasma concentrations except α-carotene. No sex-related differences were observed. Season of sampling affected α-tocopherol and retinol (higher in winter) and γ-tocopherol and cholesterol concentrations (higher in winter and spring than in the other seasons). After correction for seasonal influences, age differences were 0.24 μmol/L per year for α-tocopherol, 0.04 μmol/L per year for retinol, and 0.04 μmol/L per year for cholesterol concentrations; ratios of plasma α-tocopherol to cholesterol were not affected by age. We constructed age-specific reference intervals from the regression line and a multiple of the standard deviation. Separate regression equations are presented for seasons with low and high values.
Standards of laboratory practice: evaluation of fetal lung maturity
Authors: Ashwood Edward R 
Published: January 2020

AbstractIn this standard of laboratory practice I recommend guidelines for fetal lung maturity (FLM) testing. If possible, obtain a 10-mL uncontaminated sample by amniocentesis. Keep the amniotic fluid at 4 °C and mix well before testing. If centrifugation is required, strictly adhere to the protocol. Most laboratories should offer a rapid test, such as fluorescence polarization, phosphatidylglycerol, or foam stability index, daily on both a routine and emergency basis. Requests for lecithin/sphingomyelin ratio may be referred to a reference laboratory. Communicate immediately the results of any FLM test to the ordering location. The report should contain the result, sample contamination, and reference information. Separate reference intervals for diabetic patients are not recommended.
Evaluation of the newborn’s blood gas status
Authors: Brouillette Robert T , Waxman David H 
Published: January 2020

AbstractBlood gas measurements and complementary, noninvasive monitoring techniques provide the clinician with information essential to patient assessment, therapeutic decision making, and prognostication. Blood gas measurements are as important for ill newborns as for other critically ill patients, but rapidly changing physiology, difficult access to arterial and mixed venous sampling sites, and small blood volumes present unique challenges. This paper discusses considerations for interpretation of blood gases in the newborn period. Blood gas measurements and noninvasive estimations provide important information about oxygenation. The general goals of oxygen therapy in the neonate are to maintain adequate arterial PaO2 and SaO2, and to minimize cardiac work and the work of breathing. Pulse oximetry and transcutaneous oxygen monitoring are extraordinarily useful techniques of estimating and noninvasively monitoring the neonate’s oxygenation, but each method has limitations. Arterial blood gas determinations of pCO2 provide the most accurate determinations of the adequacy of alveolar ventilation, but capillary, transcutaneous, and end-tidal techniques are also useful. An approach to and examples of acid-base disorders are presented. Three hemoglobin variants relevant to the newborn are considered: fetal hemoglobin, carboxyhemoglobin, and methemoglobin. Blood gases obtained in the immediate perinatal period can help assess perinatal asphyxia, but particular attention must be paid to the sampling site, the time of life, and the possible and proven diagnoses.
Therapeutic drug monitoring principles in the neonate
Authors: Koren Gideon 
Published: January 2020

AbstractTherapeutic drug monitoring in the newborn infant is necessary because dose requirements differ greatly from those for older children. These differences stem from major changes in kinetic disposition at the absorption, distribution, and elimination phases. The small blood volume of neonates makes them sensitive to iatrogenic blood loss. Similarly, the small size of these patients means that medication errors frequently lead to morbidity and even mortality. The clinical laboratory must set up strict, high-standard, carefully updated guidelines to ensure the safety of infants who need drug therapy at this very vulnerable phase of their lives.
Development of ELISA to estimate thymosin α1, the N terminus of prothymosin α, in human tumors
Authors: Loidi Lourdes , Vidal Anxo , Zalvide Juan B , Puente José L , Reyes Francisco , Domínguez Fernando 
Published: January 2020

AbstractWe reported that tumor content of prothymosin α (ProT α) is a proliferation index of human breast tumors that might be used to identify patients at high risk for distant metastasis (Dominguez et al., Eur J Cancer 1993;29A:893–7). In that study ProT α concentrations were measured by a RIA; here we present an alternative nonisotopic assay that could be used in a standard clinical laboratory. Main features of the ELISA are: (a) A recombinant fusion protein glutathione S-transferase (GST)–human ProT α was used to coat the microtiter plates; (b) we used a polyclonal antiserum raised in rabbits that detects thymosin α1, the NH2-terminal fragment of ProT α; (c) it is as sensitive as the RIA; (d) it is faster than the RIA. ProT α concentrations in various human tumors (skin, esophagus, colorectal, and breast) as assessed by ELISA were comparable with, although twofold greater than, the values previously estimated by RIA.
Direct detection of multiple point mutations in mitochondrial DNA
Authors: Wong Lee-Jun C , Senadheera Dinithi 
Published: January 2020

Abstract
Mitochondrial defects can be caused by mutations in nuclear or mitochondrial DNA. Large deletion/duplication and point mutations are the two major types of mitochondrial DNA (mtDNA) mutations. Comprehensive molecular diagnosis requires the analysis of multiple point mutations. We developed an effective multiplex PCR/allele-specific oligonucleotide (ASO) method to simultaneously screen multiple point mutations in mtDNA. The system involved three pairs of primers to amplify mutation “hot spots” at tRNAleu(UUR), tRNAlys/ATPase, and ND4 regions, followed by detection of point mutations with ASO probes. Over 2000 specimens were analyzed and the results were compared with those from previous studies with the PCR/restriction fragment length polymorphism method. Our data demonstrate that the multiplex PCR/ASO method is much more sensitive in the detection of low mutant heteroplasmy. It is simple and cost effective, especially if a large number of samples are to be screened for multiple point mutations.
Determination of total cholesterol in serum by liquid chromatography–isotope dilution mass spectrometry
Authors: Kock Ruediger , Delvoux Bert , Greiling Helmut 
Published: January 2020

AbstractWe have developed a liquid chromatography–isotope dilution mass spectrometry procedure to quantify total cholesterol in serum. A particle-beam interface was used for coupling the liquid chromatograph and the mass spectrometer. After electron impact ionization the ions m/z = 386 and m/z = 389 were used for selective ion monitoring of cholesterol and the internal standard [25,26,27-13C]cholesterol. The sample preparation steps required for serum materials are alkaline hydrolysis and an extraction of the cholesterol into the cyclohexane phase. Imprecision for the determination of cholesterol in control materials is typically &lt;1.0%. The deviation from the certified reference values was &lt;0.75% for all control materials tested. A method comparison of the results obtained by this method with those obtained by gas chromatography–isotope dilution mass spectrometry for n = 28 pooled human sera derived from samples analyzed in our routine laboratory did not show differences &gt;2.5%.
Quality assessment of blood glucose testing in general practitioners’ offices improves quality
Authors: Stahl Marta , Brandslund Ivan , Iversen Steffen , Filtenborg Jens Anton 
Published: January 2020

Abstract
Measurement of blood glucose is a frequent test in Danish physicians’ offices. We describe here a new design of external quality assessment wherein fresh, unstabilized whole-blood samples were analyzed by the physicians’ office methods and by a hospital laboratory comparison method (glucose dehydrogenase assay, calibrated against NIST 909a). This approach was used in the offices of 171 general practitioners in our county during a 5-year period. The first survey, in 1992, revealed unsatisfactory performance in terms of our criterion that no difference between the physician’s office and the hospital laboratory’s single result should exceed ±20% of the laboratory result. After initiation of a program of consultation and assistance, the proficiency testing rounds of 1994 and 1996 showed considerable improvement. Thus, whereas in 1992 12% of the values were outside the acceptance limits, in 1994 and 1996 the respective values were 4% and 3%. We believe the effect was mainly related to improvements in choice of technology, procedures, and handling of specimens. We conclude that the use of bedside instruments should be restricted to diagnosis of only severe hypo- or hyperglycemia and to monitoring glucose &gt;5 mmol/L in already diagnosed diabetics. Our program differs from previous approaches to quality assessment and could also be useful for large hospitals’ in-house proficiency testing.
Improved detection of minor ischemic myocardial injury with measurement of serum cardiac troponin I
Authors: Apple Fred S , Falahati Alireza , Paulsen Pamela R , Miller Elizabeth A , Sharkey Scott W 
Published: January 2020

Abstract
This study compared the diagnostic accuracy of the measurement of serum cardiac troponin I (cTnI) with creatine kinase (CK) MB mass in patients with minor myocardial injury whose measured total CK activity did not exceed twice the upper reference limit (300 U/L for men; 200 U/L for women). Forty-eight consecutive patients presenting with chest pain and with in-hospital documentation of myocardial injury were enrolled. Electrocardiogram, echocardiogram, and serial serum CK-MB mass, cTnI, and total CK were measured over 36 h after admission. Peak total CK activity was within normal limits in 28 patients (58%). The mean (±SD) peak CK-MB mass and cTnI concentrations were: 16.4 (11.8) μg/L and 132 (13.0) μg/L; respectively. The peak biochemical marker index (defined as CK-MB or cTnI divided by its respective upper reference limit) was significantly (P &lt;0.05) higher for cTnI than for CK-MB from 7 to 36 h. The clinical sensitivity for detection of myocardial injury for cTnI was 100% [95% confidence interval (CI): 87.2% to 100%], compared with 81.8% (CI: 67.3% to 91.8%) for CK-MB. Thus, cTnI was more sensitive than CK-MB mass for detection of myocardial injury in patients with small increases of total CK.
Direct comparison of performance characteristics of two immunoassays for bone isoform of alkaline phosphatase in serum
Authors: Price Christopher P , Milligan Thomas P , Darte Claude 
Published: January 2020

Abstract
A clinical need exists for a sensitive and specific assay for the quantitation of the bone isoform of alkaline phosphatase in serum. The majority of methods do not meet this requirement; however, the recent development of immunoassays for this isoform may provide a solution. In a detailed evaluation of two immunoassays, we found a degree of imprecision that enables the discrimination of changes within the reference range. The cross-reactivity of the liver isoform was found to be between 7.1% and 12.7% when two different methods of assessment were used. The comparison of results with an electrophoretic procedure showed that the immunocapture method recovered less of the bone isoform in samples from children than in samples from patients with Paget disease; no such difference was found with the immunometric method. This suggests that the immunocapture antibody may discriminate between different bone isoforms in children whereas the immunometric assay does not.
Clinical evaluation of Toxi · Prep™: a semiautomated solid-phase extraction system for screening of drugs in urine
Authors: Steinberg David M , Sokoll Lori J , Bowles Kathy C , Nichols James H , Roberts Roger , Schultheis Stephen K , O’Donnell C Michael 
Published: January 2020

AbstractA prototype Toxi · Prep (TP) system that utilizes solid-phase extraction (SPE) has been developed as a method for broad-spectrum drug screening and identification of tetrahydrocannabinol (THC) metabolites in urine. TP can simultaneously extract up to seven specimens while automating the process of sample extraction, washing, and elution onto a chromatogram. TP was compared with the Toxi · Lab A (TL-A) system for extraction of basic drugs only. In a blind study, 33 distinct drugs and metabolites were detected in 55 urines over 13 runs. Of the drug occurrences, 68.8% (141 of 205) were detected on both TP and TL-A. Of the 13 runs, quinidine and quinine, nortriptyline metabolites, and diphenhydramine were noted more frequently on TP than TL-A, whereas nicotine and metabolites, morphine, and methadone metabolites were more frequently noted on TL-A. Twenty specimens were analyzed for THC metabolites. Of the cases positive for THC metabolites, 100% (16 of 16) were positive by both methods. Time and motion studies for all runs proved an overall labor reduction for extraction and spotting by ∼40%.
GC-MS determination of organic acids with solvent extraction after cation-exchange chromatography
Authors: Suh Ja Won , Lee Seon Hwa , Chung Bong Chul 
Published: January 2020

Abstract
We combined column and partition chromatography to isolate, purify, and quantify biological organic acids in urine and cerebrospinal fluid (CSF). Urine and CSF samples were introduced onto a preconditioned cation-exchange column (Dowex 50W × 8 resin) to remove the biological interferences. The effluent with water was extracted with ethyl acetate two times (pH 1 and 3) and the organic acids were quantitatively converted into their trimethylsilyl derivatives for detection by gas chromatography–mass spectrometry. The good quality-control data were obtained through precision and accuracy tests. Inter- and intraassay CVs were 0.01–10.2% and 0.02–12.2%, respectively. Analytical recoveries compared favorably with results from the commonly used solvent extraction method. This method was used for the measurement of the 14 organic acids in the urine and CSF of healthy volunteers. The values obtained were in the range of the published data.
Secretory carbonic anhydrase isoenzyme (CA VI) in human serum
Authors: Kivelä Jyrki , Parkkila Seppo , Waheed Abdul , Parkkila Anna-Kaisa , Sly William S , Rajaniemi Hannu 
Published: January 2020

AbstractCarbonic anhydrase VI (CA VI) is a secretory isoenzyme that, by analogy to α-amylase, is produced in the salivary glands and delivered into saliva. To determine whether CA VI is transferred into the circulation and is detectable in human serum, we collected blood samples from four healthy subjects at 3-h intervals throughout a 24-h period and measured concentrations of CA VI by a specific time-resolved immunofluorometric assay. All serum samples contained CA VI, the concentrations being ∼22 times lower in serum than in the corresponding saliva samples. The presence of CA VI in serum was confirmed by Western blotting, which under reducing conditions identified a 42-kDa polypeptide band corresponding to the monomeric CA VI. The described time-resolved immunofluorometric assay for CA VI might be useful to identify or exclude diseases of the salivary glands in the differential diagnosis of patients whose serum amylase concentrations are increased.
Polyclonal pancreatic elastase assay is superior to monoclonal assay for diagnosis of acute pancreatitis
Authors: Keim Volker , Teich Niels , Reich Andrea , Fiedler Fritz , Mössner Joachim 
Published: January 2020

AbstractWe compared the clinical values for diagnosis of acute pancreatitis of two commercial assays for pancreatic elastase: an ELISA procedure with monoclonal antibodies and a RIA technique with polyclonal antibodies. In 14 patients with acute pancreatitis, serum concentrations of elastase determined by ELISA (ELISA-elastase) decreased much faster (half-life 0.4 days) than those of elastase determined by RIA (RIA-elastase) (2.2 days), amylase (0.8 days), or lipase (0.9 days). Serum samples from 253 additional patients with abdominal pain (32 of these with acute pancreatitis) were analyzed. In sera collected up to 48 h after the onset of disease, the ROC curves showed a slightly higher diagnostic value of RIA-elastase. In samples taken later, at a sensitivity of 90% the specificity of RIA-elastase was 95% (ELISA-elastase 40%). We conclude that serum ELISA-elastase is of much lower clinical value than RIA-elastase for diagnosis of acute pancreatitis.
C677T mutation of methylenetetrahydrofolate reductase gene determined in blood or plasma by multiple-injection capillary electrophoresis and laser-induced fluorescence detection
Authors: Ulvik Arve , Refsum Helga , Kluijtmans Leo A J , Ueland Per Magne 
Published: January 2020

Abstract
We constructed an assay to detect the common C677T mutation in the methylenetetrahydrofolate reductase gene. The mutation creates a Hinfl recognition site detected by restriction cleavage of a 198-bp fragment amplified in the polymerase chain reaction (PCR). Digested samples were subjected to capillary electrophoresis with laser-induced fluorescence detection (CE-LIF), with hydroxypropylmethylcellulose as the sieving matrix and SYBR Green I as the fluorescent dye. After amplification but before digestion, we added to the PCR mixture a fragment with the HinfI recognition site and a 15-bp truncation at the 3′ end. Using this procedure, we could (a) verify completeness of digestion and monitor injection, (b) assign genotypes on the basis of pattern recognition, and (c) develop a multiple-injection mode with simultaneous separation of as many as eight samples. A seminested PCR protocol in combination with CE-LIF allowed genotyping of plasma/serum samples 20 years old.