bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Pregnancy on the Pharmacokinetics of Total and Unbound Dolutegravir and Its Main Metabolite in Women Living With Human Immunodeficiency Virus
Authors: Bollen Pauline , Freriksen Jolien , Konopnicki Deborah , Weizsäcker Katharina , Hidalgo Tenorio Carmen , Moltó José , Taylor Graham , Alba-Alejandre Irene , van Crevel Reinout , Colbers Angela , Burger David ,   Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women Network, Nellen J , Lyons F , Lambert J , Wyen C , Faetkenheuer G , Rockstroh J K , Schwarze-Zander C , Tariq Sadiq S , Gilleece Y , Wood C , Schalkwijk S , Bukkems V 
Published: January 2020

Abstract

Background
Pharmacokinetic and efficacy data on dolutegravir in pregnant women living with human immunodeficiency virus (HIV) are still limited but needed to support its use as one of the preferred antiretroviral agents.

Methods
Within the multicenter Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) study, pregnant women living with HIV and using dolutegravir once daily (50 mg, with food) underwent 24-hour pharmacokinetic profiling in their third trimester and postpartum. Dolutegravir exposure in the third trimester was considered adequate if geometric mean unbound, pharmacologically active, minimal plasma concentrations (Cmin, unbound) and ≥90% of individual Cmin, unbound levels were &gt;0.85 µg/L, the proposed 90% inhibitory concentration for unbound dolutegravir. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) for comparison of total and unbound pharmacokinetic parameters in the third trimester and postpartum were calculated, including the metabolic ratio for dolutegravir-glucuronide. Safety and virological data were collected.

Results
Seventeen women (76% black) were enrolled (25 evaluable pharmacokinetic profiles; 15 in the third trimester, 10 in postpartum). In the third trimester, geometric mean (coefficient of variation, %) Cmin, unbound was 2.87 (87) µg/L and 93% of individual Cmin, unbound levels were &gt;0.85 µg/L. The GMR (90% CI) in the third trimester vs postpartum was 0.86 (.68–1.10) for area under the curve (AUC0-24h), and for Cmax, 0.93 (.77–1.13). GMR (90% CI) for the trough concentrations was 0.71 (.49–1.02), based on total dolutegravir concentrations. Four serious adverse events were reported, unlikely related to dolutegravir. The HIV polymerase chain reaction test was negative in 14/17 infants (result unknown for 3 infants).

Conclusions
Pharmacokinetic changes for dolutegravir in late pregnancy are not clinically relevant and support the use of dolutegravir 50 mg once daily with food in pregnancy.

Clinical Trials Registration
NCT00825929.
Alternative statistical approach to evaluating interlaboratory performance.
Authors: Ehrmeyer S S , Laessig R H 
Published: January 2020

Abstract
We report a new technique for realistic assessment of laboratory performance as measured by proficiency testing. Interlaboratory results accumulated from 129 participants during 18 months provide the baseline data from which we established "state-of-the-art" performance criteria for three ranges of pH, pCO2, and pO2. By concurrent use of two statistical measurement techniques, the cumulative percentile rank and the algebraic and absolute mean error, laboratories can accurately evaluate their performance in terms of acceptable state-of-the-art criteria, total error, or medical usefulness. The approach facilitates assessment of the nature of the errors that have led to inferior performance and identification of probable areas where improvement is possible. If criteria based on regulatory standards or medical usefulness goals are included, the system can provide a basis for licensure or professional quality improvement.
Pitfalls in, and new methods for, the radioimmunoassay for digoxin in urine.
Authors: O'Brien M S , Huston J R , Reid R J , Gibson T P 
Published: January 2020

Abstract
Examining techniques for radioimmunoassay of digoxin in urine, we found that the apparent concentration of digoxin is affected by endogenous substances, independent of the concentration of digoxin itself. We describe a modification of the Becton Dickinson solid-phase RIA that makes it more nearly accurate and more easily performed, and obviates the endogenous interference. Digoxin concentrations from 5.0 to at least 1000 micrograms/L can be measured.
Determination of plasma beta-endorphin and beta-lipotropin by cation-exchange liquid chromatography and radioimmunoassay.
Authors: Laatikainen T , Salminen K , Stenman U H , Leppäluoto J 
Published: January 2020

Abstract
In this method for rapid separation of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) in plasma, most of the plasma proteins in a 0.5- to 2.0-mL sample of plasma are precipitated with acetonitrile at pH 4.7. beta-EP and beta-LPH in the supernate are completely separated by liquid chromatography on a cation-exchange column, with gradient elution with volatile buffers, and are eluted in 1.5- to 2.0-mL volumes. After lyophilization, the redissolved beta-EP and beta-LPH are determined by radioimmunoassay. The respective mean concentrations of immunoreactive beta-EP and beta-LPH in plasma of nonpregnant women were 4.0 (SD 2.0) and 5.1 (SD 3.0) pmol/L; during labor, 33.3 (SD 25) and 69.6 (SD 41) pmol/L; and in venous plasma from umbilical cords after spontaneous labor, 38.6 (SD 18) and 38.7 (SD 19) pmol/L.
Radioimmunoassay for 1,25-dihydroxyvitamin D in serum or plasma.
Authors: De Leenheer A P , Bauwens R M 
Published: January 2020

Abstract
For this sensitive RIA for 1 alpha,25-dihydroxyvitamin D, we used antibodies to 1 alpha,25-dihydroxycholecalciferol-3-hemisuccinate conjugated to bovine serum albumin, raised in rabbits. These antibodies show a high affinity for 1 alpha,25-dihydroxyvitamin D3 but cross react with other vitamin D metabolites as well. Extraction and liquid chromatography are required to isolate the 1 alpha,25-dihydroxyvitamin D from human serum or plasma with benzene (analytical recovery, 96%) and chromatographed by "high-performance" liquid chromatography on a silica column. The sensitivity of the assay is 2 pg/tube. The between-assay CV is 12.6% (means = 61.8 ng/L, n = 27) and the within-assay CV is 7.4% (means = 61.8 ng/L, n = 15). The reference interval, obtained from data on serum of healthy persons, is 51.8 +/- 15.1 ng/L (means +/- SD, n = 91), with no sex-related difference. Patients with chronic renal failure have lower concentrations in serum, and patients suffering from calcium nephrolithiasis have increased concentrations. Our assay offers the advantage of a relatively short prepurification procedure and the production of large amounts of stable gamma-globulins that can be used for several years without loss of binding properties.
A compound from uremic plasma and from normal urine isolated by liquid chromatography and identified by nuclear magnetic resonance.
Authors: Gallice P , Monti J P , Crevat A , Durand C , Murisasco A 
Published: January 2020

Abstract
A compound present in normal urine and in ultrafiltrates of uremic plasma in the fraction of so-called "uremic middle molecules" was isolated by liquid chromatography. Preliminary studies, including amino acid analysis, characterization of uronic acids, and ultraviolet spectroscopy, show that the molecule contains glycine, a uronic acid, and an aromatic ring. Characterization by 1H and 13C nuclear magnetic resonance spectrometry shows conclusively that this compound is a double conjugate of glucuronidate--o-hydroxyhippuric acid, which has been previously described by Zimmerman et al., using quite different techniques of isolation and identification (Clin Nephrol 14: 107, 1980; FEBS Lett 129: 237, 1981).
Kinetic determination of blood coagulation Factor XIII in plasma.
Authors: Muszbek L , Polgár J , Fésüs L 
Published: January 2020

Abstract
We have designed a new kinetic assay for estimating Factor XIII in plasma. Plasma fibrinogen is removed by treatment with bentonite (colloidal aluminum silicate) before measurement. During the lag phase, Factor XIII is transformed by thrombin and Ca2+ into active transglutaminase (EC 2.3.2.13), which attaches the substrate ethylamine to a glutamine residue in acetylated, dephosphorylated beta-casein. During the reaction, ammonia is released, which can be continuously monitored in an NADPH-dependent indicator reaction catalyzed by glutamate dehydrogenase (EC 1.4.1.4). We determined the optimal concentrations of substrate and activator and found that, to eliminate the clottable fibrinogen from the plasma samples, bentonite treatment was more advantageous than the traditional heat treatment. Results by the method correlate well with those by the most widely used amine incorporation and immunoinhibition assays for Factor XIII. We established a reference interval of 12.1-22.7 U/L; at optimal conditions, the variance of the method was less than 3% within this range. The method has several theoretical and practical advantages over traditional determinations of Factor XIII.
Uremic toxins, and their effect on intermediary metabolism.
Authors: Wills M R 
Published: January 2020

Abstract
In the late stages of chronic renal damage the functional mass of the kidney is reduced and there is progression to renal insufficiency, usually called uremia, in which all aspects of renal function are affected. The complexity of the biochemical aspects of the syndrome of uremia is a manifestation of the wide variety and nature of the individual disorders that contribute to the pathogenesis of the final clinical syndrome. One major feature is the retention of metabolic end products and their effects, as toxins, on intermediary metabolism. The retained end products, working singly or in combination, probably affect metabolic pathways by some modification of enzymic reactions. They act at the cell membrane level. Although "middle molecules" have been incriminated as uremic toxins, recent attention has also focused on trace elements--especially aluminum, which has been implicated in the pathogenesis of two major disorders, osteomalacic dialysis osteodystrophy and dialysis encephalopathy.
Indican interference with six commercial procedures for measuring total bilirubin.
Authors: Poon R , Hinberg I H 
Published: January 2020

Abstract
We have studied the effect of indican on six commercial procedures for the measurement of total bilirubin in serum. Total bilirubin measured by the Bilirubin A-Gent (Abbott) 2,4-dichlorophenyl diazonium procedure increased by 50 mg/L for each 1 mmol/L of added indican. Similarly, total bilirubin measured by the Bilirubin C-System (Boehringer Mannheim) 2,5-dichlorophenyl diazonium procedure increased by 33 mg/L per mmol/L of indican. Indican also interfered with the Micro Bilirubin Reagent Set (Harleco) Malloy-Evelyn procedure, but to a much lesser extent. The Jendrassik Bilirubin Reagent System (American Monitor) and a modified Jendrassik-Grof procedure (Hoffmann-LaRoche) adapted to the Cobas Bio analyzer were unaffected by the presence of indican. The amount of interference with the 2,5-dichlorophenyl diazonium procedure increased significantly with color development time and was twice the initial amount after 30 min. Concentrations of indican as high as 0.38 mmol/L have been found in sera of patients with renal failure, which would increase total bilirubin values measured by the first two procedures above by 19 and 12 mg/L, respectively. Users of these procedures should therefore be suspicious of unexpectedly high bilirubin values obtained with sera from patients with chronic renal disease.
Thromboplastic activity of cerebrospinal fluid in neurological disease.
Authors: Tutuarima J A , Hische E A , van Trotsenburg L , van der Helm H J 
Published: January 2020

Abstract
Estimates of thromboplastic activity in 1100 samples of cerebrospinal fluid indicate that an increased activity of this clotting factor is a nonspecific indicator of abnormality in the central nervous system, much like (e.g.) an increased count of mononuclear cells and an increased protein content. However, the proportion of abnormal results obtained by these three tests can differ markedly in different neurological disorders. Increased thromboplastic activity is about 14-fold more common in bacterial meningitis than in viral meningitis; thus the thromboplastin determination can be of value in discriminating between bacterial and viral meningitis.
Peroxidase-coupled method for kinetic colorimetry of total creatine kinase activity in serum.
Authors: Wimmer M C , Artiss J D , Zak B 
Published: January 2020

Abstract
We describe a peroxidase-coupled method involving a colorimetric indicator reaction for determining the total activity of creatine kinase (EC 2.7.3.2) in serum. The kinetically favorable reverse reaction is exploited to generate adenosine 5'-triphosphate, which is used in the glycerol kinase-catalyzed phosphorylation of glycerol. The glycerol 3-phosphate so generated is oxidized in the presence of alpha-glycerophosphate oxidase to produce hydrogen peroxide, which is reduced in the presence of peroxidase with the simultaneous oxidation and coupling of 4-aminoantipyrene and 2-hydroxy-3,5-dichlorobenzenesulfonate to produce an intensely colored red chromogen. Results of the proposed method (y) correlate well with those of the Boehringer-Mannheim "CK-NAC UV" method as applied to the Hitachi 705 chemistry analyzer (y = 1.025 chi - 18.1, r = 0.9985, n = 100, range = 19-4531 U/L). The sensitivity of the method, based on molar absorptivities, is nearly fourfold that of procedures involving the reduction of NADP+.
Comprehensive study of a thyroxin-analog-based assay for free thyroxin ("Amerlex FT4").
Authors: Wilkins T A , Midgley J E , Barron N 
Published: January 2020

Abstract
The basic theory of thyroxin-analog-based radioimmunoassays for free thyroxin has been extended to evaluate definitively the effects arising from residual binding of the tracer analog to serum proteins. Using experimentally determined binding constants and computer simulation techniques, we studied the effects of thyroxin-analog binding to serum proteins on results of Amerlex FT4 radioimmunoassay, using this improved mathematical model. Results from computer-simulation studies were compared both directly with in vitro experimental results and indirectly with clinical studies. Agreement was good among all three approaches. The relatively weak binding of analog to thyroxin-binding globulin and prealbumin does not significantly perturb Amerlex FT4 assay results. Binding of the analog by albumin has a small but quantifiable effect on assay results, amounting to an intrinsic bias of 0.08 pmol of free thyroxin per liter per gram of albumin per liter for euthyroid serum samples. This bias is unlikely to be important for most clinical laboratory samples, but it may be significant when one is interpreting results for those rare patients with genetic albumin abnormalities such as analbuminemia or familial dysalbuminemic hyperthyroxinemia. Massively increased concentrations of nonesterified fatty acids (e.g., after treatment with heparin) will lead to a spurious increase in free thyroxin in this and most other techniques, including equilibrium dialysis.
Monoclonal antibodies can precipitate low-density lipoprotein. I. Characterization and use in determining apolipoprotein B.
Authors: Marcovina S , France D , Phillips R A , Mao S J 
Published: January 2020

Abstract
We produced 20 mouse monoclonal antibodies against human plasma low-density lipoprotein (LDL). Individually they failed to precipitate LDL in agarose gel by the double-immunodiffusion technique; collectively they did, or as few as two combined monoclonal antibodies could do so. To mimic polyclonal antibodies in determination of apolipoprotein B (apo B) by radial immunodiffusion, a combination of four particular monoclonal antibodies (clones A, B, C, and D) was necessary. We characterized these four clones with respect to temperature dependency, affinity, total binding to 125I-labeled LDL, and specificity to the different species of apolipoprotein B. Two monoclonal antibodies (B and C) bound 100% of 125I-labeled LDL; clones A and D bound 80% and 87%, respectively. All four clones bound maximally to LDL at 4 degrees C. The affinity constants for clones A, B, C, and D were 0.6, 2.1, 3.8, and 2.3 X 10(9) L/mol, respectively. By the Western blotting technique, the four monoclonal antibodies all reacted with the species B-100 and B-74 of apolipoprotein B, and to various degrees with B-48 and B-26. Radial immunodiffusion (chi) and direct enzyme-linked immunosorbent assay (y) with a mixture of the four monoclonal antibodies gave almost identical results for 70 patients: y = 0.921 chi-2.58; r = 0.933.
Liquid chromatography of free hydroxyproline in serum.
Authors: Turpeinen U , Pomoell U M 
Published: January 2020

Abstract
We report a "high-performance" liquid-chromatographic method for measuring free hydroxyproline in serum. After separating the free hydroxyproline from the protein- and peptide-bound forms by centrifugal ultrafiltration, we derivatize the free form with 4-dimethylaminoazobenzene-4'-sulfonyl ("dabsyl") chloride and separate and quantify the derivative on a C18 chromatographic column. The mobile phase is sodium acetate buffer and acetonitrile, in a multilinear solvent gradient. The derivative is detected at 436 nm. Mean analytical recovery was 73%. The assay curve is linear from 14 to 213 pmol of hydroxyproline per 5-microL injection. The within- and interassay CVs were 8% at 10.7 mumol/L hydroxyproline and 10% at 13.5 mumol/L hydroxyproline, respectively.
Liquid-chromatographic assay of diazepam and its major metabolites in serum, and application to pharmacokinetic study of high doses of diazepam in schizophrenics.
Authors: Tada K , Moroji T , Sekiguchi R , Motomura H , Noguchi T 
Published: January 2020

Abstract
In this rapid, sensitive method for simultaneously determining diazepam and its biologically active metabolites--nordiazepam, oxazepam, and temazepam--in serum, 250 to 1000 microL of serum is extracted with ether and the extracted compounds are quantified by "high-performance" liquid chromatography on a Shimpack FLC-C8 microparticulate column. Absorbance of the effluent is monitored at 254 nm. The limit of detection in serum is about 10 micrograms/L for each drug. Analytical recovery of each drug added to the serum varied from 91 to 102% for oxazepam and temazepam, from 82 to 99% for nordiazepam and diazepam. Within-day and between-day CVs ranged from 2 to 5% for oxazepam and temazepam, and from 2 to 7% for nordiazepam and diazepam. We also report results on using this assay in a pharmacokinetic study of high doses of diazepam used to treat chronic schizophrenic patients.
Anion-exchange chromatography to determine the concentration of chloride in sweat for diagnosis of cystic fibrosis.
Authors: Miller M E , Cosgriff J M , Schwartz R H 
Published: January 2020

Abstract
For the diagnosis of cystic fibrosis, we use the "Macroduct Sweat Collection System" (Wescor) to sample sweat, and anion-exchange chromatography to determine its chloride content. The chromatographic system consists of a Whatman Partisil SAX 10-microns column, an isocratic phosphate-buffered mobile phase, and ultraviolet detection at 200 nm. The sweat chloride concentrations of 10 individuals with cystic fibrosis ranged from 101 to 131 mmol/L (mean 111, SD 9 mmol/L). For 11 controls the values ranged from 13 to 54 mmol/L (mean 28, SD 11 mmol/L). We conclude that the procedure is reliable for the diagnosis of cystic fibrosis.
University of Virginia case conference. Macroamylase, macro creatine kinase, and other macroenzymes.
Authors: Mifflin T E , Bruns D E , Wrotnoski U , MacMillan R H , Stallings R G , Felder R A , Herold D A 
Published: January 2020

Abstract
The importance of macroenzymes has become increasingly apparent in recent years (1,2). Macroamylase (EC 3.2.1.1) and macro CK (EC 2.7.3.2) are the macroenzymes most commonly noted in the clinical laboratory, and they are frequently responsible for diagnostic confusion. Several methods are available for the confirmation and analysis of macroenzymes, many of which require expensive equipment or complicated techniques. In this report we summarize two cases of macro creatine kinase and two cases of macroamylase that illustrate the clinical importance of recognizing these macroenzymes. We review the features of these macroenzymes, discuss their laboratory evaluation, and describe a simple method that we have used to detect the macroenzymes in these (and other) patients at our institution. Finally, we review the literature on other, less commonly observed macroenzymes in human blood. We stress (a) the impact of methodology on clinical impressions and (b) the importance of discussing laboratory observations with the patient's physician and communicating them to the patient's medical record in writing.
Use of proton nuclear magnetic resonance spectroscopy in detection and study of organic acidurias.
Authors: Iles R A , Hind A J , Chalmers R A 
Published: January 2020

Abstract
We used high-resolution proton nuclear magnetic resonance spectroscopy to detect, identify, and study the major normal and abnormal organic acid metabolites in urine from patients with propionic acidemia, methylmalonic aciduria, branched-chain ketoaciduria, isovaleric acidemia, and glutaric aciduria type I. Characteristic and diagnostic spectra were obtained at 400 MHz for each disorder in all the patients studied and neutral and basic compounds, including amino acids and acylcarnitines, were also detected. The technique is rapid (10 min) and requires small samples (0.5 mL) and no preliminary extraction or derivative preparation. We believe that it is particularly suitable for the rapid and acute diagnosis of inborn errors of metabolism, especially the organic acidurias, and for acute pediatric clinical care, when rapid monitoring of major metabolic alterations is required in a time scale suitable to influence directly and immediately the therapy of the patients concerned.
Measurement of creatine kinase MM sub-type by anion-exchange liquid chromatography.
Authors: Wu A H , Gornet T G 
Published: January 2020

Abstract
Electrophoretic and isoelectric focusing studies have demonstrated the presence of multiple sub-forms of the major creatine kinase isoenzymes, and preliminary work has suggested that measurement of the mm sub-forms provides early diagnostic information concerning acute myocardial infarction. We developed an isocratic method based on liquid chromatography to examine further the clinical potential of measuring these sub-forms. An anion-exchange column is used coupled with the fluorometric detection of NADPH after reaction of the sub-forms with CK reagents, which are added through a post-column pump. We examined various chromatographic variables in producing the best separations. Results for blood collected from normal individuals and patients with acute myocardial infarction and skeletal muscle diseases are compared. We conclude that for routine CK-MM sub-form analysis, this chromatographic procedure is better suited than isoelectric focusing because of the faster turn-around and lower costs.
Direct-calibration method for determination of aluminum in serum is comparable with the protein-precipitation technique.
Authors: Bradley C , Leung F Y , Slavin W , Henderson A R 
Published: January 2020

Abstract
We compared results by two methods for serum Al determination: matrix modification with direct calibration in a stabilized-temperature platform furnace (Clin Chem 28, 2139, 1982) and a technique involving extraction with nitric acid before atomic absorption spectrometry (Clin Chem 30, 1216, 1984). The two methods gave similar results with use of either a deuterium or a Zeeman system of background correction, but gave different slopes for standard additions (mA X s per microgram/L), depending on the Al content of the serum, an effect not seen with aqueous solutions. These differences do not affect the accuracy of the Al determination up to 150 micrograms/L.