bluuebunny/crossref_metadata_2025_split huggingface dataset:
Desirable standards for laboratory tests if they are to fulfill medical needs
Authors: Fraser C G , Petersen P H 
Published: January 2020

Abstract
Many strategies to define desirable standards for laboratory tests to fulfill medical needs have been proposed over the last three decades. Traditional approaches are based on reference (normal) values, opinions of clinicians, the state of the art, views of experts, data on biological variation, and assessment of the effect of error on clinical use. All these approaches have advantages and disadvantages, but the consensus of experts reached over a decade ago that imprecision desirably be less than one-half of the within-subject biological variation still seems to provide the best set of generally applicable performance standards. Desirable bias is less than one-quarter of the group (within-subject plus between-subject) biological variation. Recent proposals are either restatements of traditional recommendations, further empirical suggestions, or models based on assessment of clinical needs, and have not been widely accepted. Both old and new studies on clinical opinions, sought by using structured questionnaires containing clinical vignettes designed to seek views on the magnitude of significant change, are flawed in design, execution, and data analysis. Until clinicians are more aware of test-result variability and clinical chemists gain quantitative knowledge on the interpretation of test results, it will be difficult to set desirable standards that fulfill actual medical needs, except in a few well-defined screening situations.
Variability of lipid measurements: relevance for the clinician
Authors: Schectman G , Sasse E 
Published: January 2020

Abstract
Decreasing the large test variability associated with measurements of blood cholesterol, triglyceride, and high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol is likely to improve the classification of coronary heart disease (CHD) risk and allow improved monitoring of lipid-lowering treatments. However, improving test precision will benefit the clinician only if (a) the analytical test variability is high relative to the biological test variability and (b) detecting subtle responses to diet or drug therapy is clinically important. Improving HDL- and LDL-cholesterol test precision can be expected to increase the clinical usefulness of these measurements because values for HDL- and LDL-cholesterol correlate closely with CHD risk; are associated with small, yet clinically important, changes in response to diet and (or) drug therapy; and have substantial analytical test variability relative to biological variability. On the other hand, measurements of both blood cholesterol and triglyceride have high biological relative to analytical variability, and do not correlate as closely with CHD risk. Therefore, further improvements in precision for these measurements are less likely to be useful to the clinician.
Medically relevant laboratory-performance goals: a listing of the complexities and a call for action
Authors: Witte D L 
Published: January 2020

Abstract
This 1992 Clinical Chemistry Forum asks if accuracy and precision goals for the laboratory can be specified by reference to medical requirements, which are a function of the total laboratory testing process as well as the needs of patients, clinicians, and societal institutions. Furthermore, medical decisions and decisions about medical requirements must be made in situations of uncertainty and thus are subject to predictable cognitive errors. The interaction of all these factors must be considered by patients, laboratorians, and clinicians to identify practical and effective performance goals. Pathologists and clinical chemists are uniquely trained to identify thoughtful clinicians who are knowledgeable in quantitative judgment to participate in this goal-setting endeavor. It is time for these parties to accumulate the available data and engage in the synthesis of effective performance goals.
Comparison of quality-control rules used in clinical chemistry laboratories
Authors: Bishop J , Nix A B 
Published: January 2020

Abstract
Numerous papers have been written to show which combinations of Shewhart-type quality-control charts are optimal for detecting systematic shifts in the mean response of a process, increases in the random error of a process, and linear drift effects in the mean response across the assay batch. One paper by Westgard et al. (Clin Chem 1977;23:1857-67) especially seems to have attracted the attention of users. Here we derive detailed results that enable the characteristics of the various Shewhart-type control schemes, including the multirule scheme (Clin Chem 1981;27:493-501), to be calculated and show that a fundamental formula proposed by Westgard et al. in the earlier paper is in error, although their derived results are not seriously wrong. We also show that, from a practical point of view, a suitably chosen Cusum scheme is near optimal for all the types and combinations of errors discussed, thereby removing the selection problem for the user.
Estimation of plasma and urinary hemoglobin by a rate spectrophotometric method
Authors: Chalmers A H , Snell L E 
Published: January 2020

Abstract
A method is described for estimating plasma and urinary hemoglobin concentrations as low as 3 mg/L. The assay measures at 528 nm the rate of peroxidation of chlorpromazine by hemoglobin and is not affected by ascorbate and bilirubin concentrations up to 500 mumol/L. Results by this method (mean +/- SD: 54.4 +/- 41.6 mg/L; n = 19) correlated well with those by a scanning spectrophotometric method (52.5 +/- 41.6 mg/L; r = 0.96) and a Coulter Instrument method (r = 0.99; Coulter method: 125 +/- 15 g/L; rate method: 122 +/- 15 g/L; n = 10, r = 0.99). The correlation for assays of 20 plasma samples by our method and a tetramethylbenzidine method was also good (r = 0.95) though the latter gave lower results (31.1 +/- 31.6 mg/L) than the chlorpromazine method (50.9 +/- 41.1 mg/L). The chlorpromazine rate method gave an intra- and interday CV of 7.9% and 9.7%, respectively, at a hemoglobin concentration of 31 mg/L.
Rapid multicomponent analysis of hemoglobin derivatives for controlled antidotal use of methemoglobin-forming agents in cyanide poisoning
Authors: Zijlstra W G , Buursma A 
Published: January 2020

Abstract
When cyanide poisoning is treated with a methemoglobin-forming agent, oxidative metabolism is protected at the expense of the oxygen capacity of the blood. The affinity of methemoglobin for CN- is high enough to compete with cytochrome oxidase, which protects the latter from becoming blocked, but all hemoglobin used for this purpose is lost for the transport of oxygen. Therefore, the fractions of the various hemoglobin derivatives present in the blood should be carefully monitored during this kind of treatment. After we had developed a multiwavelength spectrophotometric method for this purpose, we studied the feasibility of using a modified commercial six-wavelength hemoglobin photometer (Radiometer OSM3) for easy and rapid analysis of methemoglobin and methemoglobin cyanide in small samples of blood. All conditions appeared to be fulfilled for the construction of a practical multiwavelength photometer for reliably monitoring methemoglobin therapy in patients with cyanide poisoning, even in the presence of carboxyhemoglobin, as often occurs in fire victims.
Measurement of carboxyhemoglobin and total hemoglobin by five specialized spectrophotometers (CO-oximeters) in comparison with reference methods
Authors: Mahoney J J , Vreman H J , Stevenson D K , Van Kessel A L 
Published: January 2020

Abstract
We measured total hemoglobin (CtHb) and carboxyhemoglobin (COHb) in 100 patients' blood samples by using five specialized spectrophotometers (CO-oximeters)--IL 482 CO-Oximeter, Corning 2500 CO-oximeter, Radiometer OSM 3 Hemoximeter, Corning 270 CO-oximeter, and the AVL 912 CO-Oxylite--and compared the results with those obtained with the manual cyanmethemoglobin method and a gas-chromatographic (GC) method, respectively. For the CtHb measurements, the differences between the cyanmethemoglobin method and the CO-oximeters were not clinically important for any model. For the blood COHb measurements, the direction of the bias relative to GC was dependent on COHb concentration. In general, the CO-oximeters underestimated COHb concentration for COHb &gt; 2.5% of total hemoglobin but overestimated COHb concentration for COHb &lt; or = 2.5%. We conclude that all five CO-oximeters compared favorably with the reference methods for CtHb and for high concentrations of COHb. However, the inaccuracy of CO-oximeters for low-concentration (&lt; or = 2.5%) COHb measurements may make these instruments unsuitable for some applications.
Within- and between-subject biological variations of follitropin, lutropin, testosterone, and sex-hormone-binding globulin in men
Authors: Valero-Politi J , Fuentes-Arderiu X 
Published: January 2020

Abstract
The within-subject and between-subject biological variation of the serum concentrations of follitropin, lutropin, sex-hormone-binding globulin, and testosterone; the ratio between the serum concentrations of testosterone and sex-hormone-binding globulin; and the concentration of testosterone in saliva have been studied in a group of 20 men during 12 months. The between-subject coefficients of variation (CVs) were 36.0% for follitropin, 37.0% for lutropin, 42.7% for sex-hormone-binding globulin, 21.3% for testosterone in serum, 28.8% for testosterone in saliva, and 51.6% for the ratio between serum concentrations of testosterone and sex-hormone-binding globulin. The medians of the within-subject CVs for the respective analyses and ratio were 17.3%, 24.0%, 12.1%, 10.9%, 17.3%, and 9.4%. These data were used to calculate the desirable imprecision, the critical difference for significant change detection, and the index of individuality.
Factitious hyperthyroxinemia due to a monoclonal IgA in a case of multiple myeloma
Authors: Cissewski K , Faix J D , Reinwein D , Moses A C 
Published: January 2020

Abstract
A clinically euthyroid 53-year-old woman with an IgA-lambda-secreting multiple myeloma presented with increased serum concentrations of thyroid hormones. Laboratory studies revealed increased total thyroxine (T4) and triiodothyronine (T3) concentrations, a high-normal free T4 concentration, and a normal basal thyrotropin (TSH) concentration with a normal response to thyroliberin (TRH). Her serum concentration of IgA was 11,040 mg/L (normal range 900-4500 mg/L) and immunoelectrophoresis revealed it to be monoclonal. This monoclonal IgA bound both T4 and T3, as determined by serum immunoelectrophoresis and direct binding studies. Immunoelectrophoresis in the presence of [125I]T4 or [125I]T3 localized the radiolabeled iodothyronines to a band corresponding exactly to the precipitin arc of the monoclonal IgA. We performed direct binding studies with IgA purified by affinity chromatography with the lectin jacalin. Purified IgA (50 micrograms) bound both [125I]T4 (12.3%) and [125I]T3 (2.7%) specifically and in a dose-dependent manner. Scatchard analysis of competitive-binding data utilizing [125I]T4 and unlabeled T4 revealed a Kd of 2.2 x 10(-7) mol/L. The binding capacity for T4 was approximately 7 mumol/L. Thus, in this case of IgA-secreting myeloma, the monoclonal IgA acts as an additional thyroid hormone-binding protein in serum that interferes in the T4 and T3 RIAs. This is the first report of a monoclonal IgA producing an apparent euthyroid hyperthyroxinemia.
Total homocysteine in plasma or serum: methods and clinical applications
Authors: Ueland P M , Refsum H , Stabler S P , Malinow M R , Andersson A , Allen R H 
Published: January 2020

Abstract
Total homocysteine is defined as the sum of all homocysteine species in plasma/serum, including free and protein-bound forms. In the present review, we compare and evaluate several techniques for the determination of total homocysteine. Because these assays include the conversion of all forms into a single species by reduction, the redistribution between free and protein-bound homocysteine through disulfide interchange does not affect the results, and total homocysteine can be measured in stored samples. Total homocysteine in whole blood increases at room temperature because of a continuous production and release of homocysteine from blood cells, but artificial increase is low if the blood sample is centrifuged within 1 h of collection or placed on ice. Different methods correlate well, and values between 5 and 15 mumol/L in fasting subjects are considered normal. Total homocysteine in serum/plasma is increased markedly in patients with cobalamin or folate deficiency, and decreases only when they are treated with the deficient vitamin. Total homocysteine is therefore of value for the diagnosis and follow-up of these deficiency states and may compensate for weaknesses of the traditional laboratory tests. In addition, total homocysteine is an independent risk factor for premature cardiovascular diseases. These disorders justify introduction of the total homocysteine assay in the routine clinical chemistry laboratory.
Characterization and mathematical correction of hemolysis interference in selected Hitachi 717 assays
Authors: Jay D W , Provasek D 
Published: January 2020

Abstract
The effect of hemolysis on several assays performed with the Hitachi 717 was quantified by relating the amount of error to the concentration of hemoglobin. Hemolysis interference was judged clinically significant when analyte concentration varied by &gt; 10% from the initial value. Hemolysis interference was significant for alkaline phosphatase, aspartate aminotransferase, alpha-amylase, bilirubin, creatine kinase, gamma-glutamyltransferase, lactate dehydrogenase, lactate dehydrogenase-1, potassium, and theophylline assays. Error (expressed in absolute terms) was linearly dependent on hemoglobin concentration and independent of the initial analyte concentration in each case, except for bilirubin and theophylline, where multiple regression analysis was required to quantify the effect. Relative error was dependent on the initial analyte concentration in all cases. Correction formulas were calculated from linear regression of absolute error vs hemoglobin concentration. Clinical application of correction formulas and mechanisms of hemolysis interference for each assay are discussed.
Unusual thermolability properties of leukocyte beta-hexosaminidase: implications in screening for carriers of Tay-Sachs disease
Authors: Prence E M , Natowicz M R , Zalewski I 
Published: January 2020

Abstract
Tay-Sachs disease (TSD), an autosomal recessive neurodegenerative condition, is the result of a deficiency of beta-hexosaminidase A (hex A). Heterozygotic individuals are screened by analysis for hex A and hex B activities; the percent of hex A is the critical determinant of carrier vs noncarrier status. Most laboratories use a heat-inactivation assay that exploits the differential thermolability of the isoenzymes. However, we have found a reciprocal relation between the apparent leukocyte hex A activity and the amount of the sample used in the assay; i.e., a significant increase in the percent of hex A activity with decreasing amounts of sample. Three sets of data indicate that this phenomenon was caused by an effect on the hex B isoenzyme and not on hex A. This variation in hex A activity with sample amount was not observed when a hex A-specific substrate was used. This phenomenon was also not seen in assays of leukocytes from carriers for Sandhoff disease, a condition associated with a reduction in the amount of hex B. Finally, when leukocytes from a TSD homozygote, containing almost no hex A, were analyzed, marked increases in the percent of hex A were observed with decreasing sample concentrations. These data indicate that misdiagnoses could result from variations in sample concentrations used for TSD carrier testing and support the view that the leukocyte concentrations used for these assays should be standardized.
Urinary metanephrine and normetanephrine determined without extraction by using liquid chromatography and coulometric array detection
Authors: Gamache P H , Kingery M L , Acworth I N 
Published: January 2020

Abstract
We describe a procedure for the direct measurement of metanephrine (MN) and normetanephrine (NMN) in hydrolyzed urine, using HPLC with coulometric array detection. Acid-hydrolyzed samples were diluted and filtered before separation by isocratic reversed-phase ion-pair chromatography. Eight serial coulometric sensors, set at incrementally increasing anodic potentials, were used to screen lower-oxidizing interferences and provide stepwise oxidation of the metanephrines. Voltammetric behavior across three adjacent sensors was used to assess resolution and aid in peak identification. Values obtained in commercial controls were consistently within the specified target range. Variability, expressed as CV, was 5.45-9.22% between runs and 1.60-4.52% within-run for both compounds. The limit of detection was 2.6 micrograms/L for MN and 2.8 micrograms/L for NMN, with a linear response to 15.0 mg/L for both analytes. Results from patients' samples correlated well with those by a method involving dual ion-exchange extraction (r = 0.963, n = 82 for MN; r = 0.9768, n = 83 for NMN). This procedure provided high selectivity and objective peak purity information while greatly simplifying sample preparation.
Interference in immunoassay measurements of total and free phenytoin in uremic patients: a reappraisal
Authors: Roberts W L , Rainey P M 
Published: January 2020

Abstract
Accumulation of phenytoin metabolites in uremia has been shown to interfere with some immunoassay methods for phenytoin measurement. We evaluated the effects of uremia (serum creatinine &gt; 13 mg/L) on free and total phenytoin concentrations measured by the Abbott TDx fluorescence polarization immunoassay, and the DuPont aca and Syva EMIT homogeneous enzyme-multiplied immunoassay methods, using HPLC as the comparison method. In uremic patients, the TDx assay showed both fixed and proportional bias in comparison with the HPLC for both total phenytoin concentration (TDx = 1.24 x HPLC + 1.9 mg/L) and free phenytoin concentration (TDx = 1.52 x HPLC + 0.24 mg/L). The total bias was as great as 100% for both total and free phenytoin. Cross-reactive substances other than 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH) and HPPH-glucuronide appeared to be responsible. In contrast, there was minimal interference with aca and EMIT assays.
Reference standards for quantification of skeletal alkaline phosphatase activity in serum by heat inactivation and lectin precipitation
Authors: Farley J R , Hall S L , Herring S , Libanati C , Wergedal J E 
Published: January 2020

Abstract
Putative standards of skeletal alkaline phosphatase (ALP) (from bone, bone cells, osteosarcoma cells, and Pagetic serum) and hepatic ALP (from cholestatic serum and bile) were used to compare three methods for quantifying skeletal ALP activity in serum: heat inactivation, precipitation with wheat germ agglutinin (WGA), and precipitation with concanavalin A (Con A). All the skeletal ALP standards were similarly sensitive to heat inactivation, as were the hepatic ALP standards. Heat inactivation separated skeletal from hepatic ALP by a 50% difference in remaining ALP activities (e.g., 23% and 74% remaining skeletal and hepatic ALP activities after 30 min at 52 degrees C). Differential precipitations with WGA and with Con A were less efficient at separating skeletal from hepatic ALP (maximum differences of &lt; 30% remaining ALP activity). Although both types of hepatic ALP standard (cholestatic serum and bile) were precipitated with similar efficiencies by WGA and Con A, the skeletal ALP standards were not (e.g., at 2.7 g/L, WGA precipitated 78-86% of the ALP activity in Pagetic serum, but only 49% of the ALP activity in extracts of human bone). These data suggest that heat inactivation is preferable to precipitation with WGA or Con A for quantifying skeletal ALP activity in serum: it better separates skeletal from hepatic ALP activity and is not sensitive to glycosyl heterogeneity.
Severe isopropanolemia without acetonemia or clinical manifestations of isopropanol intoxication
Authors: Chan K M , Wong E T , Matthews W S 
Published: January 2020

Abstract
This is the first reported case of severe isopropanolemia in a patient who did not experience associated clinical manifestations and acetonemia. The patient was found lying face down in a hotel lobby but at admission was alert and oriented to place and person. Toxicological analysis of the patient's serum revealed the presence of isopropanol at a concentration of 72 mmol/L. An increased serum osmolal gap (81 mOsm/kg) was also observed. The serum concentration of isopropanol decreased to 9.5 mmol/L 15.5 h after admission with an estimated half-life of elimination of 5-7 h. No serum acetone was detected throughout the patient's hospitalization. The identity of isopropanol was confirmed by gas chromatography/mass spectrometry. The patient remained awake and alert while in the hospital and was discharged 5 days after admission. These unusual findings raise some fundamental questions about the role of isopropanol conversion to acetone in the manifestation of symptoms usually associated with isopropanol intoxication.
Mass spectrometry of proteins and peptides: sensitive and accurate mass measurement and sequence analysis
Authors: Arnott D , Shabanowitz J , Hunt D F 
Published: January 2020

Abstract
The study of proteins and peptides by mass spectrometry has been advanced by the development of matrix-assisted laser desorption/ionization and electrospray ionization. Proteins with masses &gt; 100 kDa may be measured accurately at picomole sensitivities. Sequence analysis of peptides in mixtures at subpicomole quantities is possible by tandem mass spectrometry. Practical applications of the new technology to biological research are illustrated.