bluuebunny/crossref_metadata_2025_split huggingface dataset:
The freckle plot (daily turnaround time chart): a technique for timely and effective quality improvement of test turnaround times
Authors: Pellar T G , Ward P J , Tuckerman J F , Henderson A R 
Published: January 2020

Abstract
Test turnaround times are often monitored on a monthly basis. However, such an interval usually means that not all causes for delay in test reporting can be unequivocally identified for institution of remedial action. We have devised a daily chart--the freckle plot--that graphically displays the test turnaround times by laboratory receipt time. Different symbols are used to designate specimens reported within the test's turnaround time limit, those within 10 min beyond that limit, and those well outside the limit. These categories are adjustable to suit different limits of stringency. Freckle plots are produced on a daily basis and can be used to track down causes for test delays. Using the 1-h turnaround time "stat" potassium test as a model, we found 16 causes for test delay, of which 9 were potentially remediable. By applying these remedies, we were able to increase test compliance, in the day shift, from 91.5% (95% confidence interval 88.8%-93.7%) to 97.6% (95% confidence interval 96.4-98.55%), which is significant at P &lt; 10(-7). This daily plot is a useful quality assurance tool, supplementing the more conventional tests used to ensure laboratory quality improvement.
Stability of intact chorionic gonadotropin (hCG) in serum, liquid whole blood, and dried whole-blood filter-paper spots: impact on screening for Down syndrome by measurement of free beta-hCG subunit
Authors: Spencer K , Macri J N , Carpenter P , Anderson R , Krantz D A 
Published: January 2020

Abstract
The use of multiple maternal serum biochemical markers in screening for Down syndrome is gaining worldwide acceptance. We sought to study the impact of the potential instability of intact human chorionic gonadotropin (hCG) on free beta-hCG subunit, a marker that has recently been used successfully in such screening. We found that, in practice, any changes in free beta-hCG due to the instability of intact hCG do not inhibit the effectiveness of free beta-hCG as a marker for Down syndrome. This was proven by controlled laboratory experiments at various stress temperatures, freeze-thaw studies, and analysis of a large set of screening data with particular reference to time in transit for individual samples. Data from controlled dissociation studies demonstrate that any apparent increase in free beta-hCG due to the instability of intact hCG cannot be attributed simply to the dissociation of intact hCG. Finally, for large-scale mass population screening in areas of the world where transport delays, safety concerns, and high temperatures preclude the shipment of liquid whole blood, dried whole-blood spots in filter paper provide a suitable delivery system with many advantages.
Comparison of hypertonic and isotonic reference electrode junctions for measuring ionized calcium in whole blood: a clinical study
Authors: Masters P W , Payne R B 
Published: January 2020

Abstract
We measured ionized calcium concentrations in whole blood from 91 patients who had no clinical or biochemical evidence of disturbed calcium homeostasis and who had a wide range of serum albumin concentrations. We used both a standard Ciba-Corning 634 analyzer, which has a membrane-restricted saturated KCl reference electrode bridge, and a modified instrument with a 150 mmol/L NaCl bridge. After adjusting the externally standardized values from each instrument for their least-squares regressions on pH, there was a significant correlation between ionized calcium and albumin only with the standard analyzer. In contrast, only values from the modified instrument correlated with serum chloride; this was not explained by ionic strength or organic anion interferences. We conclude that there is unlikely to be any major advantage in using a membrane-restricted isotonic NaCl reference electrode for in vitro clinical measurements, although it may be of value for in vivo monitoring. The importance of measuring serum albumin when using most commercial ionized calcium analyzers is emphasized.
Simultaneous determination of free testosterone and testosterone bound to non-sex-hormone-binding globulin by equilibrium dialysis
Authors: Barini A , Liberale I , Menini E 
Published: January 2020

Abstract
We describe a procedure based on equilibrium dialysis that allows the simultaneous determination of free testosterone and testosterone bound to non-sex-hormone-binding globulin (non-SHBG) in plasma. After saturating SHBG with 5 alpha-dihydrotestosterone (DHT) according to a technique recently described, the percentage of free testosterone in the treated and the untreated samples is measured by equilibrium dialysis with use of a semiautomated instrument that allows rigorous standardization of the experimental conditions. The present method is simpler and faster than the previously described technique in which, after the saturation of SHBG with DHT, the unbound fractions were measured by centrifugal ultrafiltration dialysis. The method is also reproducible and suited for the analysis of a large number of samples. The technique has been applied to the determination of the fractional distribution of testosterone in plasma pools from normally menstruating, pregnant, and postmenopausal women and from normal men.
Whole-blood cyclosporin G in renal transplant recipients determined by two immunoassays and liquid chromatography
Authors: McBride J H , Kim S S , Danovitch G M , Rodgerson D O , Reyes A F , Ota M K 
Published: January 2020

Abstract
Cyclosporin G (CsG) is less nephrotoxic than cyclosporin A (CsA) and is undergoing clinical trials for use as an immunosuppressive agent after renal transplantation. Three assays for whole-blood CsA-HPLC, RIA (INCSTAR, Cyclo-Trac SP), and FPIA (Abbott TDx)--were adapted for use with CsG and were assessed for analytical suitability and to determine which assay was capable of deriving CsG values rapidly after transplantation. The assays were acceptable in terms of sensitivity, linearity, analytical recovery, and precision. When considering blood samples (n = 107) from renal transplant recipients receiving a low dose of CsG (5 mg/kg per day) and a high dose (10 mg/kg per day), we obtained the following correlation data: RIA = 0.974HPLC + 27.89 (r = 0.9798, Sy/x = 39.24); FPIA = 0.964HPLC + 33.59 (r = 0.9819, Sy/x = 36.66); and FPIA = 0.977RIA + 9.50 (r = 0.9894, Sy/x = 28.12). The FPIA of CsG is recommended as the most rapid method, although it is the most expensive. HPLC, RIA, and FPIA were capable of accurately deriving projected CsG concentrations at various stages of the clinical trial when the low- and high-dose regimes were tapered over a period of 16 weeks.
Electrochemical homogeneous enzyme immunoassay of theophylline in hemolyzed, icteric, and lipemic samples
Authors: Yao H , Jenkins S H , Pesce A J , Halsall H B , Heineman W R 
Published: January 2020

Abstract
We demonstrate here an electrochemical homogeneous enzyme immunoassay for theophylline, which can be performed in hemolyzed, lipemic, and icteric samples. The assay used an unmodified Syva EMIT theophylline kit. One of the enzymatic reaction products, NADH, reacted with 2,6-dichloroindophenol (DCIP) to reduce DCIP to DCIPH2, which was detected electrochemically with flow-injection analysis. The inter- and intraassay coefficients of variation of this manual technique were &lt; 9% at theophylline concentrations of 14 to 34 mg/L. The CVs were 9-15% at low concentrations (6.3 mg/L), which is below the therapeutic range. Analytical recoveries were 91-97% for normal serum and 92-111% for hemolyzed, icteric, or lipemic sera. The measured concentrations (y) were compared with those obtained by the fluorescence polarization immunoassay (x); a scatter plot of the results showed a linear relationship of y = 1.00 x - 0.57 mg/L (r = 0.966, Sy/x = 1.51). This alternative way to measure the serum concentration of theophylline overcomes the shortcomings of spectrophotometric methods, by which it is difficult to measure theophylline in severely hemolyzed, icteric, or lipemic sera.
Time-resolved immunofluorometry and other frequently used immunoassay types for follicle-stimulating hormone compared by using identical monoclonal antibodies
Authors: Madersbacher S , Shu-Chen T , Schwarz S , Dirnhofer S , Wick G , Berger P 
Published: January 2020

Abstract
The influence of assay design and quantification system on assay performance was investigated by developing, optimizing, and comparing a time-resolved immunofluorometric assay (IFMA), an immunoenzymometric assay (IEMA), an immunoradiometric assay (IRMA), and a competitive radioimmunoassay (RIA), all performed with the same monoclonal antibodies (MCA) directed against human follicle-stimulating hormone (hFSH). The lowest detection limit (2 ng/L for hFSH-I-3, corresponding to 2.5 mIU of 1st International Reference Preparation of hFSH 78/549 per liter), the widest measuring range (2-160,000 ng/L), and the greatest signal-to-noise ratio (13,000:1 at 160,000 ng/L) were obtained in the IFMA. For analysis of serum samples from 101 male (ages 2-91 years) and 99 female (ages 2-90 years) individuals at a single dilution, 100% of samples were within the measuring range of the IFMA, whereas only 87%, 55%, 32%, and 8% of the sera were for the IRMA, the IEMA evaluated with double-wavelength measurement, the conventional IEMA, and the competitive MCA-based RIA, respectively. These studies demonstrate clear advantages of the IFMA in sensitivity and assay range, which allows reliable and cost- and time-effective determination of hFSH in individuals from infancy to senescence.
Stable liposomes for assays of human sera
Authors: Ishimori Y , Rokugawa K 
Published: January 2020

Abstract
We report a novel homogeneous immunoassay system involving protein-bearing liposome-encapsulated carboxyfluorescein as a release marker. We applied this system to determine protein antigens, e.g., ferritin, in human serum samples by a sandwich-type assay. Liposomal lysis was observed in many samples, even though no second antibody was added to the reaction mixture. We demonstrated that the functional groups used to immobilize an antibody on liposomes are related to this phenomenon. Stable liposomes in human sera were prepared by incorporating bromoacetyl groups instead of the dithiopyridyl groups used previously. A good correlation (y = 0.98x - 8.81, r = 0.98, Sx/y = 66.9, range approximately 10-2000 micrograms/L) with results by RIA was obtained in the ferritin measurement of 53 patients' sera by using these liposomes.
Tolerance limits for short-term analytical bias and analytical imprecision derived from clinical assay specificity
Authors: Klee G G 
Published: January 2020

Abstract
I propose a method for defining tolerance limits for assay bias and assay imprecision, based on the effects of these tolerance limits on the clinical specificity of the assay. An analytical "error budget" is defined as the squared sums of the imprecision and bias errors. The maximum limit for this error budget is set at a value corresponding to a 50% increase in the false-positive rate for classifying healthy subjects. For gaussian distributions with +/- 2 SD used as decision limits, this error budget equates to 0.45 SD of combined within-person and between-person biological variation (SDBiol). To provide reasonable power for bias detection in an assay, I recommend that the SD of the assay be kept at less than half the bias limit. Then, for the gaussian distribution, the maximum bias limit should be &lt; 0.36 SDBiol and the SD of the assay should be &lt; 0.18 SDBiol. Procedures are provided for using the same principles to define tolerance limits for decision limits other than +/- 2 SD and for nongaussian distributions.
New Insight into the Comparative Power Quality-Control Rules That Use Control Observations within a Single Analytical Run
Authors: Parvin Curtis A 
Published: January 2020

Abstract
Vol. 39:
p. 441 In the article by C.A. Parvin Entitled "New Insight into the comparative power of quality-control rules that use control observations within a single analytical run," 1993;39;440-7, the means in the first line on page 441 should have been µ1 + σb1E1 and µ2 + σb2E1. In the third paragraph on page 441, in the Sentence "Finally, I assume that total analytical imprecision increases from its stable value, σtj, to REw = 1.5σtj, because of an increase in the between-run component of imprecision from its stable value, σwj, to an out-of-control value, σwj," the word "between" should have been "within."
pp. 565-572. In the review by M.H. zweig and G. Campbell entitled "Receiver operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine," 1993;39:561-77, the label for the x-axis at the bottom of each of Figures 4 through 12 should read "False-positive fraction (1 - specificity)." Correspondingly, the label at the top of each Figure should read "True-negative fraction (specificity)." Note that the (corect) dual labeling of the x-axis solves the problem of whether to plot specificity or 1 - specificity on the x-axis.
pp. 767-769. In the article by K. Emancipator and M.H. Kroll entitled "A quantitative measure of nonlinearity," 1993;39:766-772, three equations were printed incorrectly. They should have read as follows:
Equation 6a (p. 767)
Equation 8b (p. 768)
and on p. 769, the last unnumbered equation
Serum cholesterol determined by liquid chromatography with 6-chlorostigmasterol as internal standard
Authors: Chen W X , Li P Y , Wang S , Dong J , Li J Z 
Published: January 2020

Abstract
We describe an accurate and precise method for determining serum cholesterol by high-performance liquid chromatography (HPLC). After addition of 6-chlorostigmasterol as internal standard, serum is treated with alcoholic potassium hydroxide. Subsequently the cholesterol and internal standard are extracted from the mixture into n-hexane and then derivatized to phenylurethanes for measurement by HPLC with ultraviolet detection. The effective chromatographic separation and the use of an appropriate internal standard make this procedure free from interferences by other serum sterols and precise. The mean cholesterol concentration in Standard Reference Material (SRM) 909 (human serum) assayed by this procedure (4.346 mmol.g-1 x L-1) agreed well with the value assigned by the National Institute of Standards and Technology (4.359 mmol.g-1 x L-1). Within-run and total CVs were 0.56% and 0.78%, respectively. Therefore the performance of this procedure is sufficiently good to allow its use as a candidate reference method for serum cholesterol determination.
Calcium determination in serum with stable alkaline Arsenazo III and triglyceride clearing
Authors: Morgan B R , Artiss J D , Zak B 
Published: January 2020

Abstract
We describe an analytical procedure for determining serum calcium, using the ligand Arsenazo III in an aqueous alkaline medium. The choice of pH for the proposed technique differs from current procedures, which are for the most part carried out in a slightly acidic medium. An acidic medium avoids interference from magnesium, but is spectrophotometrically suboptimal for this pH-dependent reaction: the molar absorptivity of the Arsenazo III complex with calcium at acid pH is 13,787 L mol-1 cm-1, about one-half of that at a more optimal alkaline pH (26,574 L mol-1 cm-1). We have included a clearing technique in the reagent to avoid spectral aberrations from hypertriglyceridemic samples. alpha-Cyclodextrin absorbs the nonesterified fatty acids liberated from triglycerides by a microbial lipase. This modification may also be helpful for binding nonesterified fatty acids, which are known to interfere with calcium procedures by forming calcium soaps and thus preventing the reaction with intended ligands. The use of 8-hydroxyquinoline sulfonate as the magnesium-masking agent facilitates the use of alkaline pH. The less-water-soluble alternative, 8-hydroxyquinoline, commonly used as a precipitating agent for several methods, is difficult to solubilize in the alkaline reagent and tends to precipitate when complexed to magnesium. Finally, the use of alkaline pH results in a prolonged (&gt; or = 6 weeks) shelf life for the reagent.
Time-resolved immunofluorometric assay of human growth hormone
Authors: Albertsson-Wikland K , Jansson C , Rosberg S , Novamo A 
Published: January 2020

Abstract
We describe a time-resolved immunofluorometric assay (trIFMA) for human growth hormone (hGH), in which monoclonal antibody (mAb)-coated microtiter strip wells and a europium (Eu) chelate-labeled mAb are used. We compare the new trIFMA, in which two mAbs are used, with an immunoradiometric assay (IRMA) in which polyclonal antibodies are used. Serum samples (n = 185) from 36 children with various diagnoses were analyzed. In addition, 24-h profile samples (72 per child) from 39 children were analyzed. The trIFMA was more sensitive (detection limit, 0.03 mIU/L) than existing IRMAs. Both the intra- and interassay CVs were &lt; or = 10.6% for hGH concentrations between 1 and 100 mIU/L. The trIFMA is technically simple and rapid, requires no centrifugation or separation reagent, and has a counting time of only 1 s per sample. In addition, the Eu label is nontoxic, presents no waste-disposal problems, and has a long shelf-life. Finally, the assay requires only small volumes of serum (25 muL), which is of considerable importance in pediatric use. The mAbs used for the trIFMA selectively bind the 22-kDa form of hGH, with the result that the assay detects about 80% of the amount detected by the polyclonal IRMA.
Space-resolved fluoroimmunoassay for quantifying alpha-fetoprotein in serum
Authors: Wang W K , Ho L T , Chiang Y 
Published: January 2020

Abstract
A nickel-coated surface was used to adsorb a monolayer of anti-human alpha-fetoprotein antibody. After incubation with a patient's serum, the sample was stained with fluorescein isothiocyanate (FITC)-conjugated anti-human alpha-fetoprotein antibody. These slides were then read with a space-resolved fluorometer to determine the amount of FITC adsorbed onto the metal surface. We used an argon laser as the light source in the fluorometer. The parallel laser beam was tilted at about 45 degrees to the sample surface. The fluorescence from FITC was read with a perpendicular photon counter to reduce noise. The CV for these tests was approximately 10%. Comparison of these results (y) with those of a conventional radioimmunoassay (x) produced the regression equation y = 0.99x + 0.5, over the range 10-140 micrograms/L (n = 51).
Early diagnosis of acute myocardial infarction with use of a rapid immunochemical assay of creatine kinase MB isoenzyme
Authors: Collins D R , Wright D J , Rinsler M G , Thomas P , Bhattacharya S , Raftery E B 
Published: January 2020

Abstract
In 195 patients presenting with chest pain and referred acutely for cardiological assessment, blood was taken immediately for assay of creatine kinase (CK; EC 2.7.3.2) MB isoenzyme by an immunochemical method and results [mass units of enzyme per liter of plasma (microgram/L)] were obtained within 30 min of sampling. Diagnosis of acute myocardial infarction in the patients was made independently, based on electrocardiograms and conventional cardiac enzyme profiles. The administration of any thrombolytic therapy in response to the CK-MB concentration result was also noted, allowing assessment of the assay's potential influence on patient management in addition to the diagnostic efficiency evaluation. The study demonstrated that, when blood samples were collected on admission to hospital and the decision level suggested by the manufacturers was utilized, the assay had an immediate sensitivity of 52% and a specificity of 97%. Of the 81 patients who were shown by conventional means to have had acute myocardial infarction, 8 (10%) had equivocal electrocardiograms but positive CK-MB concentration results. In four of these patients (5%), thrombolytic therapy was given on the basis of the clinical features and a positive CK-MB concentration result alone.
Albuminuria in people at least 40 years old: effect of alcohol consumption, regular exercise, and cigarette smoking
Authors: Metcalf P A , Baker J R , Scragg R K , Dryson E , Scott A J , Wild C J 
Published: January 2020

Abstract
We investigated the relation between albuminuria and life-style factors in 5670 people, ages 40 years and over, who participated in a health screening survey of a local workforce. The degree of albuminuria showed piecewise log-linear relationships with alcohol consumption and cigarette smoking, with changes in slope (and 95% confidence interval) corresponding with 5 (2, 8) g of alcohol/day and 10 (6, 14) cigarettes/day. After adjusting for age, gender, ethnicity, and other life-style variables, relative risks (95% confidence interval) of slight albuminuria for people consuming &gt; 32 g of alcohol/day compared with nondrinkers, and for cigarette smokers compared with nonsmokers, were 1.74 (1.02, 2.98) and 1.37 (1.01, 1.88), respectively. However, there was no significant effect of exercise. We conclude that slight albuminuria is significantly associated with cigarette smoking and heavy alcohol consumption, consistent with its role as an index of risk of cardiovascular disease.
Potential use of ketoconazole in a dynamic endocrine test to differentiate between biological outliers and testosterone use by athletes
Authors: Kicman A T , Oftebro H , Walker C , Norman N , Cowan D A 
Published: January 2020

Abstract
Determination of the ratio of testosterone to epitestosterone (T/E) in urine is used to detect testosterone administration in athletes, with a ratio &gt; 6 considered as evidence of an offense. We show that administration of ketoconazole, which inhibits testosterone biosynthesis, may be useful for differentiating between an athlete who is using testosterone and one who naturally gives a ratio &gt; 6. In a control subject pretreated with testosterone, ketoconazole caused the ratio to increase; conversely, it caused a decrease in the ratio in an athlete under investigation. Repeated administration of ketoconazole to two normal men caused a decrease in the ratio due to a large decrease in the urinary excretion rate of testosterone relative to epitestosterone. Stimulation with human chorionic gonadotropin exacerbated the differences in excretion rates. A single administration of ketoconazole to six normal men caused the T/E ratios to decrease significantly within 8 h, a suitable time scale for use in a dynamic test.
Intra- and interlaboratory quality control for assay of amino acids in biological fluids: 14 years of the French experience
Authors: Parvy P , Bardet J , Rabier D , Gasquet M , Kamoun P 
Published: January 2020

Abstract
The functioning of an external quality-control scheme for amino acids set up in 1978 is described. Two measurements were made each month by participating laboratories on a control plasma sample provided by the quality-control center; freeze-dried samples were used from 1978 to 1989 and liquid samples since 1990. In addition, two "blind" samples were sent to the laboratories each year. Every 3 months, the overall results and those of the individual laboratories were analyzed statistically. The validity of the liquid sample control is demonstrated. The progressive improvement of results is commendable. In 1990, the coefficients of variation for all participants ranged from 8.4% for alanine to 23.5% for methionine. The standards used for calibration could contribute to the broad range of results, especially those for histidine and ornithine. The use of blind samples made it possible to detect problems of calibration, of linearity of measurement, of contamination, and of identification of unusual amino acids.