bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laboratory tests of iron status: correlation or common sense?
Authors: Hastka J , Lasserre J J , Schwarzbeck A , Reiter A , Hehlmann R 
Published: January 2020

Abstract
We demonstrate that simple correlation between the various tests of iron status is not sufficient for examining their value in diagnosing iron deficiency (ID). Three degrees of ID are recognized: Iron depletion (ID grade I) is defined by decreased total body iron and normal iron support to erythropoiesis, as diagnosed by decreased storage iron, decreased ferritin, normal sideroblast count, normal zinc protoporphyrin (ZPP), and transferrin saturation &gt;15%. When the iron supply to erythropoiesis becomes insufficient, as diagnosed by transferrin saturation &lt; or = 15%, increased ZPP, and decreased sideroblast count, iron-deficient erythropoiesis (ID grade II) occurs. When finally hemoglobin is below its normal range, iron-deficiency anemia (ID grade III) results. The various tests for ID cannot be compared without taking into account the severity of the deficiency. Depending on the grade of ID examined, the correlation of markers seen in our patients' data varied considerably. We conclude that a "best" marker of ID does not exist. However, the different tests efficiently complement each other by detecting different stages and individually show the clinical extent of ID. Ferritin reflects the iron stores. ZPP indicates whether the ID in a given patient is clinically relevant or not. Finally, the extent of a clinically relevant ID can be assessed by the measured ZPP, hemoglobin concentration, and red cell indices.
HPLC method for measurement of purine nucleotide degradation products in cerebrospinal fluid
Authors: Kuracka L , Kalnovicová T , Líska B , Turcáni P 
Published: January 2020

Abstract
We describe a convenient method for the separation and quantification of xanthine, hypoxanthine, and uric acid in 20 microL of cerebrospinal fluid (CSF) with use of HPLC and ultraviolet detection. The analysis is performed on a Sepharon SGX C18 column and the elution system consists of potassium phosphate buffer, pH 5.1, with 20 mL/L methanol. The lower limit of detection was 4 pmol for hypoxanthine and xanthine and 6 pmol for uric acid. Analytical recoveries of purine metabolites ranged from 98.6% to 102.9%. The intra- and interassay CVs were &lt;3%. The applicability of the method is illustrated with the determination of micromolar concentrations of xanthine, hypoxanthine, and uric acid in CSF samples obtained from 113 patients with various neurological disorders.
HPLC micromethod for amrinone and metabolites in patients receiving concurrent cephalosporin therapy
Authors: Pappas J B , Allen E M , Ross M , Banner W 
Published: January 2020

Abstract
Amrinone (AMR), a bipyridine derivative, is receiving increasing use in postoperative cardiac patients as an inotrope and vasodilator. The hemodynamic response to amrinone in adults is linearly related to AMR concentrations, warranting therapeutic drug monitoring. We report a rapid microsample HPLC method for monitoring AMR and its principal metabolites, N-acetyl (N-ac) and N-glycolyl (N-gly) AMR. Serum was precipitated with acetonitrile, and the supernatant fluid was then injected into a C18 narrow-bore column. The mobile phase consisted of a 0.1 mol/L sodium phosphate buffer (pH 6) with a gradient of acetonitrile going from 50 to 100 mL/L of eluent. Detection with a diode-array detector (DAD) concurrently monitored the absorbances at 320 and 345 nm. Monitoring 320 nm allows optimal quantification of AMR, N-gly, and N-ac. Patients often receive concurrent cephalosporin therapy, which is detectable at 320 nm but not 345 nm. Because cephalosporins coelute with AMR or metabolites, monitoring at 345 nm allows separation of these antibiotics from AMR and metabolites while retaining a detection limit of 0.5 mg/L.
ELISA for thyroglobulin in serum: recovery studies to evaluate autoantibody interference and reliability of thyroglobulin values
Authors: Erali M , Bigelow R B , Meikle A W 
Published: January 2020

Abstract
An ELISA for measuring thyroglobulin (Tg) in serum was developed with polyclonal antibodies to Tg on the solid phase and two monoclonal antibodies to Tg as the second antibodies. The assay has a detection limit of 1 microgram/L, a within-run imprecision (CV) of &lt;7%, and a between-run CV of &lt; 10%. Parallelism of the assay was shown in dilution studies, in which the percent observed/expected values for n = 5 autoantibody-containing samples gave a mean of 99% (SD 13.1 %); for n = 5 samples with undetectable autoantibody concentrations, the mean was 103% (SD 11.8%). The correlation of the ELISA with an RIA for Tg in 46 normal samples was ELISA = 1.11(RIA) + 0.52, S y/x = 2.23, SD intercept = 0.54, SD slope = 0.03, range = 0 to 53 micrograms/L, r = 0.980. Comparison of the ELISA with a reference laboratory RIA for 29 clinical samples gave a correlation of: ELISA = 1.53(RIA) - 0.48, S y/x = 9.00, SD intercept = 2.19, SD slope = 0.10, range = 0 to 98 micrograms/L, r = 0.950. To provide additional information concerning the reliability of the Tg measurement in samples containing autoantibodies to Tg, we developed a procedure for determining the percent recovery. A percent recovery greater than or equal to 80% indicates minimal interference by autoantibodies in this assay. The assay is straightforward to perform, results can be posted within 8 h, and the routinely good recovery of Tg in the presence of Tg autoantibodies indicates minimal autoantibody interference in this assay.
How to evaluate and implement new technologies in an era of managed care and cost containment
Authors: Koch D D 
Published: January 2020

Abstract
New technologies often enable clinical laboratorians to overcome the challenges we face. These technologies sometimes become available with amazing punctuality, addressing recent problems and keeping the physician-customer satisfied for another day. Traditionally, developments such as a new cancer marker have been implemented into routine use with little circumspection because the benefits diagnostically and financially were perceived to far outweigh the risk that the new test or technology was not as effective as described. The notion of subsequently removing older tests inferior to the new one has hardly been considered. The challenges confronting clinical laboratorians today, however, are affecting that typical pattern dramatically. Four of the most pervasive challenges are comprehensively examined in the 1995 Clinical Chemistry Forum. One of these key areas--the proper implementation of modern technology in the form of new tests or new approaches to producing clinical laboratory results--is the main topic of this review.
Keeping up with new technology: new approaches to diagnosis of Chlamydia infection
Authors: LeBar W D 
Published: January 2020

Abstract
Chlamydia trachomatis infections are among the most common sexually transmitted infections in the US today. One of the keys to the prevention of C. trachomatis infection rests on the ability to make this diagnosis on the basis of accurate laboratory testing. For many years the standard for diagnosis of C. trachomatis infections has been isolation in tissue culture. Numerous nonculture methods, including enzyme immunoassay, have been used as an alternative to cell culture. The performance characteristics of these tests have all been compared with a standard, cell culture, which at best will detect 90% of positive specimens. Nucleic acid amplification techniques, including PCR and ligase chain reaction, have been recently introduced. The advantage of these tests is their ability to detect 10-20% more positive specimens when compared with culture or confirmed nonculture methods performed with a single specimen. The sensitivity of amplified tests also allows us to test specimens from multiple sites (endocervix, urethra, urine), which expands our standard from an infected sample to detection of an infected patient. Tests based on amplified nucleic acid technology have greatly improved our ability to diagnose urogenital C. trachomatis infection. The use of an expanded standard will help us accurately define the true performance and clinical utility of nonculture Chlamydia diagnostic tests.
Use of medians and "average of normals" of patients' data for assessment of long-term analytical stability
Authors: Lott J A , Smith D A , Mitchell L C , Moeschberger M L 
Published: January 2020

Abstract
Using results from patients, we studied several methods for long-term (years) monitoring of the analytical stability of various chemistry tests. For each test, we obtained on a bimonthly basis histograms of &gt; or = 200 to approximately 2000 data points and determined the median, mean, and mean of those data points in the reference range ("average of normal" or AON). Examining approximately 4 years' data, we found that the medians and AON are extremely stable for most tests, and that all observed shifts in the medians or in the AON could be explained by expected or unexpected changes in the laboratory. The means and peak values of the Erlang (gamma) distribution were less useful, owing to shifts caused by extreme outliers, especially for enzymes in serum. We assumed that the underlying patient population and testing patterns were stable. We recommend the use of medians or the AON of patients' data under defined conditions for monitoring the long-term analytical stability of certain tests involving serum or whole blood.
Clinical comparison of three labeled-antibody immunoassays of free triiodothyronine
Authors: Piketty M L , d'Herbomez M , Le Guillouzic D , Lebtahi R , Cosson E , Dumont A , Dilouya A , Helal B O 
Published: January 2020

Abstract
Three labeled-antibody immunoassays of free triiodothyronine (FT3) were studied in hyperthyroid patients, patients with nonthyroidal illness, and patients being treated with amiodarone; we also studied sera presenting known interferences (n for all groups = 465). The results were compared with those of a one-step labeled-analog assay. The precision of the two automated assays were similar to that of the manual assays. The three labeled-antibody FT3 assays demonstrated a satisfactory diagnostic performance for confirming hyperthyroidism and robustness to interference; nevertheless, two assays displayed unusual behavior in some patients with nonthyroidal illness, with chronic renal failure, or after amiodarone therapy.
Radioimmunoassay of leptin in human plasma
Authors: Ma Z , Gingerich R L , Santiago J V , Klein S , Smith C H , Landt M 
Published: January 2020

Abstract
Recent studies suggest that leptin, the ob gene product absent in ob/ob mice, is a negative regulator of adiposity. We developed an RIA to measure human leptin in plasma or serum. The minimum detectable concentration by the assay is 0.5 microg/L leptin and the limit of linearity is 100 microg/L. Recovery of leptin added to serum was 99-104% over by the linear range of the assay. The RIA agreed reasonably well with rough quantification by Western blot (RIA = 0.90 blot + 3.7 microg/L, Sy/x = 10.9 microg/L). CVs within- and between-run ranged from 3.4% to 8.3% and from 3.6% to 6.2%, respectively. Variation in plasma leptin concentrations in specimens collected on consecutive mornings was large (CVs of 10.9% and 22.5%). After an overnight fast, leptin concentrations were similar to those 1-2 h after 1-2 meals. Plasma leptin concentrations in specimens from 83 lean and obese adults correlated directly with body mass index (BMI; kg/m2): r = 0.72, P &lt;0.001. Correlations were significantly improved by separating results by gender (men r = 0.84, women r = 0.87; p &lt;0.001). The increase in leptin concentrations with increasing BMI was greater in women than in men (slope 2.53 vs 0.97 microg/L per unit BMI, respectively). Leptin concentrations determined in lean subjects (BMI between 18 and 25) were higher in women (7.36 +/- 3.73 microg/L) than in men (3.84 +/- 1.79 microg/L) (P &lt;0.001). Plasma leptin varied little with age and no significant difference was observed between whites and blacks. We conclude that: (a) plasma leptin concentrations are accurately and precisely measured by this new RIA; (b) leptin concentrations vary little due to short-term fasting, age, or race; but (c) plasma leptin concentrations are gender specific.
Immunofluorometric assay for sensitive and specific measurement of human prostatic glandular kallikrein (hK2) in serum
Authors: Piironen T , Lövgren J , Karp M , Eerola R , Lundwall A , Dowell B , Lövgren T , Lilja H , Pettersson K 
Published: January 2020

Abstract
Prostate-specific antigen (PSA) and human prostatic glandular kallikrein (hK2) have 79% identity with the primary structure. When we used recombinant hK2 protein, only 7 of 23 monoclonal anti-PSA IgGs (monoclonal antibodies, MAbs) cross-reacted with hK2, which enabled us to design a novel immunofluorometric MAb-MAb assay for the specific detection of hK2. In the first incubation, an excess of MAb 2H11, which does not cross-react with hK2, is added to prevent both free and complexed PSA from reacting in subsequent immunoreactions. In the second incubation, biotinylated MAb H50, which cross-reacts with hK2 by an epitope overlapping with MAb 2H11, served to bind only hK2 to the microtitration wells coated with streptavidin. In the third step, Eu-labeled MAb H117, which cross-reacts with hK2, detected the immobilized hK2. The hK2 assay was calibrated with recombinant hK2. The detection limit of the assay was 0.1 microgram/L, and the cross-reactivity with recombinant PSA was &lt; or = 0.7%. The concentration of hK2 was measured in serum samples from 334 males with total PSA concentrations ranging from 1 to 3400 microgram/L. Most of the samples (57%) had hK2 concentrations below the detection limit. The proportions of hK2 relative to total PSA were 0-2% in 79%, 2-5% in 14%, 5-10% in 4%, and &gt;10% in 3% of the samples. Gel filtration of 10 serum samples with increased hK2 concentrations showed a single peak of hK2 immunoreactivity with an apparent molecular size of approximately 30 kDa, corresponding to that of recombinant hK2 and free PSA.
Prostaglandin D2 synthase: a component of human amniotic fluid and its association with fetal abnormalities
Authors: Melegos D N , Yu H , Diamandis E P 
Published: January 2020

Abstract
Prostaglandin D2 (PGD2) synthase is responsible for PGD2 production in the brain. Western blot analysis of human amniotic fluid and probing with a polyclonal antibody against prostate-specific antigen (PSA) revealed a strong immunoreactive band with a molecular mass of 25 kDa. The immunoreactive species, which does not react with monoclonal anti-PSA antibodies, was purified to homogeneity from 1 L of amniotic fluid through successive cycles of gel filtration and ion-exchange chromatography. Amino acid sequence analysis (15 cycles) revealed that the protein was highly homologous or identical to PGD2 synthase. On semiquantitative analysis, PGD2 synthase concentration appears to increase dramatically during gestational weeks 12-25 and then declines slowly until term. PGD2 synthase concentration in amniotic fluid was altered in many abnormal pregnancies, most notably its decrease in trisomic fetuses and fetuses with renal abnormalities.
Preparation of samples with equally spaced concentrations through mixing
Authors: Vaks J E 
Published: January 2020

Abstract
Linearity, interference evaluations of the performance of clinical chemistry systems, mathematical model selection for nonlinear calibration, and other assessments often involve several human sample pools with equally spaced analyte concentrations. Sequential mixing of equal volumes, first of the low and high pools to produce the middle pool, then of the low and middle pools to produce the mid-low pool, and of the high and middle pools to produce the mid-high pool, is recommended in the NCCLS EP7-P guideline for interference studies. Proportional mixing of the low and high pools to produce all of the required pool concentrations is recommended in the NCCLS EP6-P guideline for linearity studies. Mathematical analysis and computer simulation show that the sequential mixing is much more accurate and precise than the proportional mixing. Therefore, we recommend sequential mixing for clinical chemistry application.
Evidence for presence of a reduced form of digoxin-like immunoreactive factor (dihydro-DLIF) in mammalian tissues
Authors: Qazzaz H M , Jortani S A , Poole J M , Valdes R 
Published: January 2020

Abstract
Digoxin-like immunoreactive factor (DLIF) from adrenal glands is an endogenous ligand structurally related to the plant-derived cardiac glycoside digoxin. Cardiac glycosides regulate the activity of the sodium pump and thus play key roles in disease processes involving regulation of ion transport. We now report the discovery of an endogenous dihydro-DLIF analogous to dihydrodigoxin. We used HPLC, ultraviolet spectrophotometry, and cross-reactivity with two antibodies, one specific for digoxin and one for dihydrodigoxin, to support the hypothesis that dihydro-DLIF contains a chemically reduced lactone ring. The spectral absorbance maximum for dihydro-DLIF is at 196 nm, identical to dihydrodigoxin. DLIF and dihydro-DLIF are 975- and 2588-fold less immunoreactive than digoxin and dihydrodigoxin for their respective antibodies. The molar ratio of dihydro-DLIF to DLIF is approximately 5.3 in bovine adrenocortical tissue and approximately 0.38 in human serum. Dihydrodigoxin (reduced lactone ring) added to microsomes isolated from bovine adrenal cortex produced a 4.5-fold increase in digoxin-like immunoreactivity (oxidized lactone ring) after 3 h of incubation. The biotransformation is likely mediated by a cytochrome P-450 NADPH-dependent process. Our findings demonstrate the presence of a dihydro-DLIF in mammals and suggest a metabolic route for synthesis of endogenous DLIF in mammalian tissue.
Direct determination of plasma endothelin-I by chemiluminescence enzyme immunoassay
Authors: Iwata R , Hayashi T , Nakao Y , Yamaki M , Yoshimasa T , Ito H , Saito Y , Mukoyam M , Nakao K 
Published: January 2020

Abstract
A highly sensitive sandwich-type chemiluminescence enzyme immunoassay for plasma endothelin-I (ET-1), involving no extraction steps, has been developed. Two populations of polyclonal antibodies were used in the present study: One is specific to the C-terminus of the endothelin family of peptides; the other, a Fab' fragment against the N-terminal core region of ET-1, is coupled with horseradish peroxidase (HRP). Labeled HRP activity was measured by using an enhanced chemiluminescence reaction of luminol/hydrogen peroxide. The assay was sensitive enough to detect 0.5 ng/L (0.05 pg/well) of plasma ET-1 and had no significant cross-reactivities with other related peptides, including endothelin-3 and the endothelin precursor peptide, big ET-1. Reliability of the assay was confirmed by comparison with an extraction-based procedure and a commercial kit.
Monoclonal antibody assay for free urinary pyridinium cross-links
Authors: Gomez B , Ardakani S , Evans B J , Merrell L D , Jenkins D K , Kung V T 
Published: January 2020

Abstract
The pyridinium cross-links of collagen, pyridinoline (Pyd) and deoxypyridinoline (Dpd), provide structural integrity and rigidity to collagen fibrils in bone. During bone degradation (resorption), the cross-links are released into the circulation and eventually excreted in urine. Pyridinium cross-link measurements in urine have been shown to be sensitive and specific indicators of resorption by both established HPLC and newer enzyme immunoassay (EIA) techniques. We have developed a monoclonal antibody that preferentially binds to the non-peptide-bound free forms of Pyd & Dpd. We have incorporated the antibody conjugated to alkaline phosphatase in a competitive EIA by using Pyd-coated microtiter strip wells. After a 3-h incubation of sample and antibody-enzyme conjugate, color is developed for 1 h with p-nitrophenyl phosphate as the substrate. The intraassay (n = 52) CVs were 3.0-7.6%, and interassay (n = 8) CVs were 6.1-7.4%. Comparisons of the assay (y) with HPLC (x) and a polyclonal antibody-based EIA (x') gave regression equations of y = 0.46x + 4, r = 0.96, and y = 0.56x' + 8, r = 0.96. The EIA detected increased Pyd & Dpd concentrations in urine from postmenopausal women and patients with osteoporosis, hyperthyroidism, hyperparathyroidism, and Paget disease of bone. EIA concentrations also reflected the reduction in Pyd&Dpd excretion resulting from estrogen replacement in surgically menopausal women. Measurement of pyridinium cross-links with this simple EIA appears to provide an accurate index of the rate of resorption and may be useful for metabolic bone disease assessment and monitoring the effects of antiresorptive therapy.
Hair iron content: possible marker to complement monitoring therapy of iron deficiency in patients with chronic inflammatory bowel diseases?
Authors: Bissé E , Renner F , Sussmann S , Schölmerich J , Wieland H 
Published: January 2020

Abstract
Measurements of the concentration of iron in hair from 10 patients with chronic inflammatory bowel diseases and from 10 healthy controls showed that the iron concentrations were significantly (P &lt; 0.05) lower in patients before iron intake than in controls. Three weeks after beginning iron treatment, the hair iron concentrations were found to be significantly correlated (r = 0.68; P &lt; 0.05) to reticulocyte counts. Changes in the hair iron concentrations were accompanied by similar changes in the concentrations of the markers most commonly used to diagnose and monitor iron deficiency. The results suggest that quantification of hair iron may be useful to complement evaluations of the body iron status.
Titrating cardiovascular drugs
Authors: Marcus F I 
Published: January 2020

Abstract
Titrating cardiovascular drugs is important to ensure efficacy and to minimize the risk of toxicity. A serum assay is extremely useful to guide digoxin therapy. Assessment of the effect of warfarin on blood clotting should be used to adjust dose. Serum cholesterol and lipid measurements guide therapy with antilipemic agents. The antihypertensive drugs, beta blockers, calcium channel blockers, and vasodilators can be assessed by their clinical effects. There is no strict relation between serum concentration of antiarrhythmic drugs and their effects, nor is it clear that the long-term efficacy of these drugs can be assessed by surrogate end points.
Role of the clinical toxicologist in court
Authors: Chamberlain R T 
Published: January 2020

Abstract
The clinical toxicologist may play a role in court when issues arise concerning therapeutic drug monitoring, drug abuse, environmental chemicals, or toxic torts, where the traditional forensic toxicologist may not have expertise. Beyond being credible in court, the toxicologist's testimony must be based on good scientific evidence. The ruler for measuring good scientific evidence had previously been the Frye Test, or the general acceptance test. In 1993, however, the US Supreme Court established four balancing tests that should be used for the admissibility of scientific evidence. Although the ruling is binding only in federal courts, state courts are expected to follow. When testifying, the clinical toxicologist should be aware of other court rules and expectations. As with all testimony, objections from opposing counsel can be raised to disallow the presentation of evidence by a toxicologist. The toxicologist is usually used to establish causation of injury, whether from negligence, prenatal injury, or environmental chemicals. Several examples are presented.