bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug use in the neonate: interrelationships of pharmacokinetics, toxicity, and biochemical maturity.
Authors: Warner A 
Published: January 2020

Abstract
With advances in technology, increasing numbers of premature and very ill neonates are surviving and being referred for treatment to neonatal intensive-care units. A major feature of the treatment they receive is therapy with drugs. However, because of relatively limited information available in the area of neonatal pharmacokinetics, the few drugs that currently can be monitored directly, and the lack of an effective mechanism for measuring the biochemical and functional maturity of the neonate, especially as it relates to drug clearance, therapy of neonates with drugs is certainly more hazardous and possibly less effective than in adult patients. Toxic reactions of neonates to drug therapy can usually be related to the unique pharmacokinetic processes seen in this group, particularly to the maturity of clearance mechanisms. This is the basis for a link between maturity and drug efficacy or toxicity. In this usage, maturity refers to the functional capacity of organs and biochemical pathways. Of particular concern in this regard is kidney function and the activity of drug-metabolizing enzyme systems. Because direct assessment of these functions in the neonate is difficult, other types of maturity markers that can be easily measured and which relate to drug clearance need to be identified. Such markers could serve as a guide to the physician who is planning drug therapy for a neonatal patient. Several studies looking for a gestational age marker have provided some indication that biochemical maturity markers do exist and simply await discovery, thus affording an integration of pharmacokinetics and pathophysiology to achieve a more rational and effective therapeutic approach.
A sensitive radioimmunoassay for human proinsulin, with sequential use of antisera to C-peptide and insulin.
Authors: Ward W K , Paquette T L , Frank B H , Porte D 
Published: January 2020

Abstract
In this assay for immunoreactive human proinsulin (IRPI), it first is separated from plasma by use of an antiserum to human C-peptide. An immunoprecipitate is then formed by using a precipitating antiserum and polyethylene glycol, after which IRPI is dissociated from the antiserum by incubation in warm HCl, pH 2.0. The resulting mixture is assayed for insulin immunoreactivity by a double-antibody tracer-competition method involving incubation for four days with a high-affinity anti-insulin antiserum. Human proinsulin of recombinant-DNA origin is used as the standard. Added C-peptide at supraphysiological concentrations did not interfere with or react in the assay. Human insulin cross reacted by 1.5%. The detection limit for IRPI (2 SD from zero-dose binding) is 3 pmol/L. Proinsulin conversion intermediates are measured nearly as well as intact proinsulin. IRPI concentrations in 10 nondiabetic human subjects averaged 12.0 (SEM 1.6) pmol/L. The ratio of proinsulin to immunoreactive insulin averaged 14.3 (SEM 2.2)%. After intravenous arginine, the increase in proinsulin was less than that of insulin, and it declined more slowly.
Clinical utility of measuring free thyroxin and free triiodothyronine in serum of critically ill patients by ultrafiltration.
Authors: Lee L A , Mooney R A , Woolf P D 
Published: January 2020

Abstract
Free thyroxin (FT4) measurements by ultrafiltration were compared with results obtained by equilibrium dialysis and commercial RIA methods. In a group of critically ill patients, the mean +/- 2 SD FT4 value by ultrafiltration (26.5 +/- 21.4 ng/L) was higher than in the healthy reference population (19.3 +/- 9.8 ng/L, p less than 0.0001), and correlated well with equilibrium dialysis (23.8 +/- 20 ng/L, r = 0.87). By a two-step RIA method (Clinical Assays), the FT4 value was greater in the critically ill (14.7 +/- 9.6 ng/L) than in the reference population (12.8 +/- 5 ng/L, p less than 0.001) and was also correlated with ultrafiltration results (r = 0.71). FT4 values for the ill patients were lower than for the reference population in two one-step RIA methods (Clinical Assays: 8.6 +/- 7.1 ng/L; Corning Medical: 12.7 +/- 9.4 ng/L), neither of which gave results correlated with ultrafiltration (r = 0.16 and 0.22, respectively). The concentration of free triiodothyronine (FT3), also measured by ultrafiltration, was 4.5 +/- 2.2 ng/L in healthy subjects, 12.5 +/- 14.2 ng/L in hyperthyroidism, 1.7 +/- 2.0 ng/L in hypothyroidism, 2.2 +/- 1.9 ng/L in the critically ill subjects, and 3.8 +/- 0.9 ng/L in pregnancy. Thus, FT4 and FT3 measured by ultrafiltration accurately affects assessment of the thyroid status of the patient except in critical illnesses in which FT3 values are indistinguishable from those in hypothyroidism.
Progesterone in saliva: pitfalls and consequent implications for accuracy of the determination.
Authors: Lequin R M , van den Boogaard A , Vermeulen J , Danhof M 
Published: January 2020

Abstract
The concentration of steroid hormones in saliva is believed to reflect the concentration of free hormone in blood. Because the assay for progesterone in saliva has not been rigorously validated, we investigated some of the analytical variables involved. Saliva samples were divided into two portions. One was centrifuged and the supernate used for extraction; the other was homogenized by sonication and used as such for extraction. Progesterone concentrations in homogenized whole saliva were double or triple those in supernates. By equilibrium dialysis we established that 85% of progesterone was in the free form in supernates but only 60 to 70% in homogenized whole saliva, depending upon the phase of the cycle of the subjects. Salivary flow was stimulated by crystals of citric acid; unstimulated and stimulated saliva samples were obtained from the same person. Progesterone concentrations were significantly (p less than 0.02) higher in stimulated samples than in unstimulated ones, particularly in samples collected during the luteal phase.
Error in laboratory reference limits as shown in a collaborative quality-assurance program.
Authors: Compton P J , Stuart M C , Lazarus L 
Published: January 2020

Abstract
Laboratories participate in collaborative quality-assurance programs to maintain and improve the quality of their diagnostic assays, but little attention has been paid to diagnostic quality in these programs. We used a national quality-assurance program to assess the quality of laboratory reference intervals as exemplified by triiodothyronine, thyroxin, and thyrotropin immunoassays. The limits of the reference intervals used by laboratories bear virtually no relationship to laboratory bias, i.e., whether assays read "high" or "low." Further, correcting assay results from different laboratories for the reference limits used increases rather than decreases interlaboratory scatter. We conclude that the analytical quality of immunoassays now exceeds the quality of the reference limits supplied to clinicians to assist diagnosis, and that nationally or internationally defined reference limits would therefore provide more information at less cost than do individual laboratory reference limits.
Evaluation of a cystic fibrosis screening system incorporating a miniature sweat stimulator and disposable chloride sensor.
Authors: Warwick W J , Huang N N , Waring W W , Cherian A G , Brown I , Stejskal-Lorenz E , Yeung W H , Duhon G , Hill J G , Strominger D 
Published: January 2020

Abstract
A new sweat test (CF Indicator; Medtronic, Inc.) for cystic fibrosis (CF) features a compact, portable configuration of electrodes that dispense pilocarpine for iontophoresis. A disposable chloride sensor patch absorbs a specified volume of sweat, in which the chloride concentration is immediately determined as less than 40, 40-60, or greater than 60 mmol/L. We assessed the performance of the system in a five-center study, in relation to the clinical diagnosis and to the Gibson-Cooke sweat test (GCST) as a control test. With sweat chloride concentrations of less than or equal to 40 mmol/L defined as normal and greater than 40 mmol/L as indicating persons at risk for CF, the new system showed 91% specificity and 100% sensitivity for CF, as compared with 92.8% and 100%, respectively, for the GCST. When we used sweat chloride concentrations of less than or equal to 60 mmol/L as probably normal and greater than 60 mmol/L as probably indicative of CF, the new system showed a 99.1% specificity and 98.6% sensitivity, vs 97.8% specificity and 97.9% sensitivity for the GCST test. In both procedures, occasionally insufficient sweat was collected, and this appeared related to the age of the subject. We conclude that the new sweat test system is potentially useful in physicians' offices, in clinics, and similar settings.
Evaluation of a direct fluorometric method for determination of serum retinol.
Authors: Driskell W J , Hewett J S , Bashor M M 
Published: January 2020

Abstract
We evaluated the usefulness of a fluorometric method for determining serum retinol (Futterman et al., Invest Ophthalmol Vis Sci 1975;14:125-30) in which fluorescence (excitation 335 nm; emission 460 nm) of retinol is directly measured in unextracted, diluted serum. Using serum from 466 individual donors, we compared values so obtained with those by a "high-performance" liquid-chromatographic method. The correlation coefficient (r) was 0.74. When we compared fluorometric retinol values with retinol-binding protein values for the 466 samples, r was 0.71. About 1% of the 466 samples had markedly higher values by fluorometry than by chromatography, the result of positive interferences. For two serum pools, we obtained CVs of 1.58% (n = 57) and 1.79% (n = 57) in long-term precision studies lasting 60 days. Although the fluorometric method of Futterman et al. has not been widely adopted, we find that it is simple to perform and that results compare favorably with the chromatographic method in precision and accuracy. It is unique among commonly used serum retinol methods in that the serum need not be extracted with organic solvents.
Retinol, alpha-tocopherol, lycopene, and alpha- and beta-carotene simultaneously determined in plasma by isocratic liquid chromatography.
Authors: Milne D B , Botnen J 
Published: January 2020

Abstract
Retinol, alpha-tocopherol, lycopene, and alpha- and beta-carotene can be simultaneously determined in human plasma by reversed-phase liquid chromatography. Plasma--0.5 mL plus added internal standard, retinyl acetate--is deproteinized with 0.5 mL of ethanol, then extracted with 1.0 mL of petroleum ether. The organic layer is removed and evaporated, the residue is redissolved in 0.25 mL of ethanol, and 8-microL samples are injected into a 60 X 4.6 mm column of Hypersil ODS 3-microns particles at 35 degrees C. An isocratic methanol mobile phase, flow rate 0.9 mL/min, is used for the 9-min run. Retinol and retinyl acetate are monitored at 305 nm, the tocopherols at 292 nm, and the carotenoids at 460 nm. Between-run CVs were 3.1, 6.9, 6.1, and 6.5% for retinol, alpha-tocopherol, lycopene, and beta-carotene, respectively. Small sample requirement, simplicity of extraction, short run time, and good reproducibility make this procedure ideal for clinical or research use.
Stability of catecholamines in whole blood, plasma, and platelets.
Authors: Weir T B , Smith C C , Round J M , Betteridge D J 
Published: January 2020

Abstract
Checking catecholamine stability in whole blood, plasma, and platelets, we found that specimens stored at room temperature or frozen for periods ranging from 1.5 h to three weeks show no significant difference in measured catecholamine concentration. The implications of these findings are discussed.
Automated kinetic assay of angiotensin-converting enzyme in serum.
Authors: Beneteau B , Baudin B , Morgant G , Giboudeau J , Baumann F C 
Published: January 2020

Abstract
We have developed and validated an automated kinetic method for angiotensin-converting enzyme (EC 3.4.15.1) on the Olli C + D analyzer, modified from that of Ronca-Testoni (Clin Chem 1983;29:1093-6) with N-[3-(2-furyl)-acryloyl]-L-phenylalanylglycylglycine used as substrate. We have determined appropriate reaction conditions for the assay, verified the principal analytical reliability criteria (repeatability, reproducibility, sensitivity), and established normal reference intervals (mean +/- SD) for the enzyme's activity, using serum of normal adults (100 +/- 35 U/L, n = 150), newborns (130 +/- 27 U/L, n = 10), women taking oral contraceptives (103 +/- 30 U/L, n = 10), smokers (109 +/- 38 U/L, n = 27), and patients with sarcoidosis (220 +/- 48 U/L, n = 15).
Evaluation of simultaneous measurement of lutropin and follitropin with the SimulTROPIN radioimmunoassay kit.
Authors: Wians F H , Dev J , Powell M M , Heald J I 
Published: January 2020

Abstract
We evaluated the analytical performance of the "SimulTROPIN" (Becton-Dickinson Inc.) radioimmunoassay for the simultaneous measurement of lutropin (LH) and follitropin (FSH) in human serum. Dose response, linearity, analytical recovery, sensitivity, and reagent stability were all acceptable. Cross reactivity with other structurally related hormones [choriogonadotropin (CG) and thyrotropin (TSH)] was minimal. A normal reference interval was established for nonmidcycle, ovulatory women. We confirm the low degree of CG and TSH cross reactivity with LH and FSH reported by Becton Dickinson and conclude that this assay is an acceptable method for laboratory use in the simultaneous quantification of these analytes.
Simplified liquid-chromatographic assay of amiodarone and desethylamiodarone after solid-phase extraction.
Authors: Pollak P T , Carruthers S G , Freeman D J 
Published: January 2020

Abstract
We describe a rapid, simplified isocratic "high-performance" liquid-chromatographic method for simultaneous measurement of the antiarrhythmic drug amiodarone and its major metabolite, desethylamiodarone, in small volumes of sera (100 microL). Compared with liquid-liquid extraction, the solid-phase method of extraction saves time and glassware and improves reproducibility for small sample volumes. Amiodarone and desethylamiodarone could be measured at concentrations as low as 250 micrograms/L. Standard curves for the drug and metabolite are linear over the range of concentrations found in our patients. Within-run CVs (n = 6) ranged from 2.7% to 4.5% for amiodarone and from 4.0% to 5.7% for desethylamiodarone over the range of 250 to 4000 micrograms/L. Between-run CVs (n = 12) were 8.3% and 5.7% for amiodarone and desethylamiodarone, respectively. Commonly used cardiovascular medications do not interfere with the assay.
Thyroid screening of neonates without use of radioactivity: evaluation of time-resolved fluoroimmunoassay of thyrotropin.
Authors: Torresani T E , Scherz R 
Published: January 2020

Abstract
We evaluated the usefulness, in routine newborn screening for congenital hypothyroidism, of a time-resolved fluoroimmunoassay kit (DELFIA Neonatal TSH) for the determination of thyrotropin (TSH) in dried blood spots. A total of 11 531 dried blood samples from newborns were tested in parallel in each of two Swiss screening laboratories, by RIA and DELFIA. Six cases of confirmed congenital hypothyroidism were detected during the study period. The rate of false-positive results, after single TSH determination in the DELFIA assay, was 0.16%. Correlation of RIA and DELFIA results for TSH was very good in both laboratories (0.959 and 0.97, respectively). The new method fulfills the criteria for precision and sensitivity of a screening assay. Screening results are usually available the day after the sample arrives in the laboratory, thus favoring early diagnosis and allowing treatment to begin by the seventh or eighth postnatal day.
Thrombin specificity with tripeptide chromogenic substrates: comparison of human and bovine thrombins with and without fibrinogen clotting activities.
Authors: Sonder S A , Fenton J W 
Published: January 2020

Abstract
To assess the thrombin specificity of tripeptide chromogenic substrates, we determined the Michaelis--Menten (Km), catalytic (kcat), and specificity (kcat/Km) constants for S-2238 (H-D-Phe-Pip-Arg-p-nitroanilide), Chromozym-TH (Tos-Gly-Pro-Arg-p-nitroanilide), and Spectrozyme-TH (H-D-hexahydrotyrosyl-Ala-Arg-p-nitroanilide) with high-purity thrombin preparations. Human and bovine alpha-thrombins, prepared by essentially the same procedure, were each greater than 95% in the form of the enzyme (alpha-thrombin) and had a specific fibrinogen-clotting activity greater than 2000 kilo-clotting units per gram of protein (kcu/g). In contrast, human gamma- and bovine beta-thrombins, made by controlled passage of alpha-thrombin through trypsin agarose, were greater than 98% of their respective forms and had fibrinogen-clotting activity less than 1 kcu/g. With the tripeptide chromogenic substrates these four thrombin forms at pH 7.8 and 23 degrees C had Km values of 1.6 to 16 mol/L, kcat values of 35 to 130 s-1, and kcat/Km ratios of 4.7 to 52 L X mol-1 X s-1. Although Km for an individual substrate was slightly higher for bovine than for human alpha-thrombins and although Km values for the nonclotting forms (human gamma- and bovine beta-thrombins) were higher than for clotting forms (alpha-thrombins), we found no major differences among the kinetic values for the three substrates.
Determination of indoxyl sulfate in plasma of patients with renal failure by use of ion-pairing liquid chromatography.
Authors: Stanfel L A , Gulyassy P F , Jarrard E A 
Published: January 2020

Abstract
Using our newly developed ion-pairing reversed-phase liquid-chromatographic method for assay of indoxyl sulfate, we measured its concentration in plasma of normal subjects and patients in various degrees of renal failure. Response was linear over the range of 50 to 25 000 pmol of indoxyl sulfate injected into the chromatograph. We demonstrated the specificity of the assay for azotemic plasma by using enzymatic conversion with a sulfatase. For a moderately above-normal indoxyl sulfate concentration in azotemic plasma of 134 mumol/L (29 mg/L), the within-day CV was 1.6%, the day-to-day CV 2.8%. Mean analytical recovery was 101.0% (CV = 2.8%). Over a range of 29 to 192 mg of creatinine per liter of plasma (x), indoxyl sulfate (y) concentration (in mumol/L) was positively correlated (y = 1.30x + 0.43). This method should prove valuable for further study of uremic toxins.
Enzyme-linked immunoabsorbant assay of apolipoprotein AII in plasma, with use of a monoclonal antibody.
Authors: Stein E A , DiPersio L , Pesce A J , Kashyap M , Kao J T , Srivastava L , McNerney C 
Published: January 2020

Abstract
We produced a monoclonal antibody (C2-22) to human apolipoprotein (Apo) AII and describe its use in an enzyme-linked immunoabsorbant assay (ELISA) for Apo AII in human plasma and lipoprotein subfractions. No cross reactivity of the antibody with Apo CI, CII, CIII, E, or ablumin was detected. Apo AI and low- and very-low-density lipoprotein cross reacted by 0.25%, less than 0.2%, and less than 0.3%, respectively. Whole plasma high-density lipoprotein (HDL) and HDL subfractions (HDL2 and HDL3) produced parallel displacement curves. This quantitative ELISA is based on competition between solid-phase-bound Apo AII and free Apo AII. Bound C2-22 is detected by alkaline-phosphatase-labeled second antibody. The standard curve for the assay is linear for plasma diluted 500-fold originally containing 140 to 1140 mg of Apo AII per liter. Delipidation of plasma samples exposed no additional antigenic sites. Within- and between-run CVs were respectively 8.4% and 8.7% at 327 mg/L of Apo AII, and 6.8% and 7.4% at 587 mg/L. Results correlated well with those by a polyvalent-antisera-based RIA procedure: r = 0.916, p less than 0.01, RIA = 0.896 ELISA -19.1 mg/L.
Quantification of cotinine in plasma and saliva by liquid chromatography.
Authors: Machacek D A , Jiang N S 
Published: January 2020

Abstract
Measurement of cotinine, a nicotine metabolite, has been studied as a method for monitoring smoking behavior and determining smoking status. We describe a specific, sensitive method for quantifying it in plasma and saliva by reversed-phase paired-ion liquid chromatography and detection by absorbance at 257 nm. The cotinine is extracted with methylene chloride, and 2-phenylimidazole is the internal standard. Cotinine peak heights are linearly related to the amount on the column from 0 to 500 ng. The mean (+/- SD) concentration of cotinine in plasma of 31 passively exposed nonsmokers was 2.1 +/- 1.6 micrograms/L (range, 0-7.9 micrograms/L). The regression of saliva cotinine concentration (y) on plasma cotinine concentration (x) at 0, 24, and 48 h in 10 smokers who refrained from smoking for 48 h was y (micrograms/L) = 1.155x (micrograms/L) + 0.245 (r = 0.986). The efficiency of cotinine as a biological marker was determined at 0, 24, and 48 h of smoking abstinence. Within-run CVs were 3.5% (n = 5) and day-to-day CVs 4.4% (n = 6) at 150 micrograms/L.
Isolation and quantification of apolipoproteins C-I, C-II, and C-III0-2 in very-low-density lipoproteins by "high-performance" anion-exchange chromatography.
Authors: Weisweiler P , Friedl C , Schwandt P 
Published: January 2020

Abstract
Using "high-performance" anion-exchange chromatography, we isolated and quantified human C apolipoproteins (apo C) from very-low-density lipoproteins (VLDL) in serum. As revealed by isoelectric focusing and double immunodiffusion against monospecific antisera, apo C-I, apo C-II, apo C-III0, apo C-III1, and apo C-III2 were purified to homogeneity. Assay reproducibility (coefficients of variation) ranged between 0.9% and 4.7%. The relative percentages of apo C subspecies in VLDL from normal and hypertriglyceridemic serum samples agreed with data obtained by alternative methods. This precise technique is suitable for detecting and analyzing abnormalities of C apolipoproteins in VLDL.
Stability of total cholesterol, high-density-lipoprotein cholesterol, and triglycerides in frozen sera.
Authors: Stokes Y M , Salmond C E , Carpenter L M , Welby T J 
Published: January 2020

Abstract
When human serum must be stored for extended periods before analysis, conditions must be such that samples give results comparable with those for "fresh" (unstored) samples. In a balanced experiment with statistically pre-determined sample size, we assessed, at three-weekly intervals for 18 weeks, the stability of total cholesterol, high-density-lipoprotein cholesterol, and triglycerides in human serum stored at -15 degrees C. No significant changes were observed.
The porphyrias: recent advances.
Authors: Hindmarsh J T 
Published: January 2020

Abstract
Recent research has elucidated several of the hitherto poorly understood steps in heme synthesis. This review describes this metabolic pathway and pinpoints the enzymatic blockages in the various porphyrias. Recent advances in the understanding of the etiology of porphyria cutanea tarda are discussed, as are the abnormalities of porphyrin metabolism seen in chronic renal failure and in lead poisoning. An outline is given of the clinical and biochemical abnormalities seen in the porphyrias. Included is an algorithm to aid in the differential diagnosis of these diseases, and a brief review of the new analytical techniques available for the identification and quantification of porphyrins and their precursors in body fluids.