Immunochemical methods for measurement of transferrin in serum: effects of analytical errors and inappropriate reference intervals on diagnostic utility.

1985 ◽  
Vol 31 (10) ◽  
pp. 1601-1605 ◽  
Author(s):  
Z L Bandi ◽  
I Schoen ◽  
D E Bee
Keyword(s):  
Serum Proteins ◽  
Reference Interval ◽  
Reference Intervals ◽  
Confidence Limits ◽  
Serum Samples ◽  
Normal Reference ◽  
Two Samples ◽  
Reference Preparation ◽  
Immunochemical Methods ◽  
Analytical Errors

Abstract We estimated analytical errors of the Calbiochem, Kallestad, Hyland, Meloy, Helena, and Beckman immunochemical methods for serum transferrin. Intermethod biases were determined by analysis of the "Reference Preparation for Serum Proteins" of the College of American Pathologists and by analysis of 106 patients' serum samples. We judged the acceptability of errors by comparing confidence limits for total errors with 1/4 of the normal reference intervals. The transferrin status of each patient's sample was interpreted by comparing the result of each method with the normal reference interval claimed by the corresponding manufacturer. We found that the combined effects of medically unacceptable analytical errors and inappropriate normal intervals caused results of the tested methods not to be interchangeable. The Calbiochem method identified 61 serum samples (57%) as having abnormally high transferrin concentrations. In contrast, for the same specimen, with the Meloy method we found abnormally high transferrin concentrations for only two samples (1.8%).

Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mary Kathryn Bohn ◽  
Siobhan Wilson ◽  
Alexandra Hall ◽  
Khosrow Adeli
Keyword(s):  
Clinical Decision Making ◽  
De Novo ◽  
Reference Interval ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Healthy Children ◽  
Confidence Limits ◽  
Test Results ◽  
Serum Samples ◽  
Abbott Architect

Abstract Objectives The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. Methods Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. Results Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. Conclusions Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.

Pediatric reference interval verification for common biochemical assays on the Abbott Alinity system

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mary Kathryn Bohn ◽  
Siobhan Wilson ◽  
Alexandra Hall ◽  
Youssef Massamiri ◽  
Ed Randell ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Package Insert ◽  
Reference Interval ◽  
Reference Intervals ◽  
Confidence Limits ◽  
Serum Samples ◽  
Laboratory Service ◽  
Biochemical Assays ◽  
Pediatric Healthcare ◽  
Abbott Architect

Abstract Objectives The quality of clinical laboratory service depends on quality laboratory operations and accurate test result interpretation based on reference intervals (RIs). As new analytical systems continue to be developed and improved, previously established RIs must be verified. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has established comprehensive RIs for many biomarkers on several analytical systems. Here, published CALIPER RIs for 28 chemistry assays on the Abbott ARCHITECT were assessed for verification on the newer Alinity system. Methods An analytical validation was first completed to assess assay performance. CALIPER serum samples (100) were analyzed for 28 chemistry assays on the Alinity system. The percentage of results falling within published pediatric ARCHITECT reference and confidence limits was determined for each analyte. Based on Clinical and Laboratory Standards Institute (CLSI) guidelines, if ≥90% of test results fell within confidence limits of ARCHITECT assay RIs, they were considered verified. Results Of the 28 assays assessed, 26 met the criteria for verification. Reference values for calcium and magnesium did not meet the criteria for verification with 87% and 35% falling within previously established ARCHITECT confidence limits, respectively. However, both assays could be verified using pediatric RIs provided in the Abbott Alinity package insert. Conclusions In this study, CALIPER ARCHITECT RIs were verified on the Alinity system for several chemistry assays. These data demonstrate excellent concordance for most assays between the Abbott ARCHITECT and Alinity systems and will assist in the implementation of the Alinity system in pediatric healthcare institutions.

Pediatric reference intervals for 1,25-dihydroxyvitamin D using the DiaSorin LIAISON XL assay in the healthy CALIPER cohort

2018 ◽  
Vol 56 (6) ◽  
pp. 964-972 ◽  
Author(s):  
Victoria Higgins ◽  
Dorothy Truong ◽  
Nicole M.A. White-Al Habeeb ◽  
Angela W.S. Fung ◽  
Barry Hoffman ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Critical Role ◽  
Reference Interval ◽  
Reference Intervals ◽  
Biologically Active ◽  
Specific Reference ◽  
Healthy Children ◽  
Serum Samples ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

Abstract Background: 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active vitamin D metabolite, plays a critical role in calcium and phosphate homeostasis. 1,25(OH)2D is measured to assess calcium and phosphate metabolism, particularly during periods of profound growth and development. Despite its importance, no reliable pediatric reference interval exists, with those available developed using adult populations or out-dated methodologies. Using the fully automated chemiluminescence immunoassay by DiaSorin, we established 1,25(OH)2D pediatric reference intervals using healthy children and adolescents from the CALIPER cohort. Methods: Serum samples from healthy subjects (0 to <19 years) were analyzed for 1,25(OH)2D using the DiaSorin LIAISON XL assay and age-specific reference intervals were established. The Mann-Whitney U-test was used to determine seasonal differences. Pooled neonatal and infantile samples were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine if elevated concentrations during the first year of life may be attributed to cross-reacting moieties. Results: Three reference interval age partitions were required with highest levels in subjects 0 to <1 year (77–471 pmol/L), which declined and narrowed after 1 year (113–363 pmol/L) and plateaued at 3 years (108–246 pmol/L). 1,25(OH)2D concentration was not significantly affected by seasonal variation or sex. Elevated 1,25(OH)2D concentrations in neonatal and infantile samples may be the result of an interfering substance. The absence of 3-epi-1,25-dihydroxyvitamin D in the pooled samples makes it unlikely to be the interfering moiety. Conclusions: Pediatric reference intervals for 1,25(OH)2D were established to improve test result interpretation in children and adolescents. 1,25(OH)2D is elevated in a proportion of neonates and infants, which may be the result of a cross-reacting moiety.

Intra-individual variation in the concentrations of IgA, IgG, IgM, and complement component C3 in serum of a normal adult population.

1977 ◽  
Vol 23 (3) ◽  
pp. 511-514 ◽  
Author(s):  
W C Butts ◽  
G E James ◽  
M Keuhneman
Keyword(s):  
Individual Variation ◽  
Serum Proteins ◽  
Adult Population ◽  
Reference Interval ◽  
Relative Magnitude ◽  
Reference Intervals ◽  
Complement Component ◽  
Interindividual Variation ◽  
Diffusion Technique ◽  
Complement Component C3

Abstract A recent study [Clin. Chem. 22, 1635 (1976)] reported intra-individual variation in 10 serum proteins to be much smaller than interindividual variation. We report results of a similar study involving about 700 apparently healthy adults in whom we estimated the relative magnitude of the intra- and interindividual variation in serum IgA, IgG, IgM and complement component C3. Specimens were collected from each subject weekly for as long as 10 weeks (average, four weeks). The four serum proteins were quantitated by radial immunodiffusion by the maximal-diffusion technique. Traditional 95% reference intervals were computed relative to WHO reference preparations for the immunoglobulins. For C3, the reference interval was computed relative to a commercial reference preparation. We, too, found the ratios of intra-individual to interindividual variation for adults to be so small that the traditional reference intervals do not have the assumed diagnostic sensitivities. Furthermore, these ratios did not change after dividing the study population into subgroups according to sex and age; evidently such subgrouping do not improve the diagnostic sensitivity. The relatively small intra-individual variations were also observed at the extremes of protein concentration ranges.

Reference intervals and biological variation for kallikrein 6: influence of age and renal failure

2012 ◽  
Vol 50 (5) ◽  
Author(s):  
Eduardo Martínez-Morillo ◽  
Anastasia Diamandis ◽  
Eleftherios P. Diamandis
Keyword(s):  
Renal Failure ◽  
Significant Positive Correlation ◽  
Reference Interval ◽  
Serum Marker ◽  
Reference Intervals ◽  
Biological Variation ◽  
Serum Samples ◽  
Positive Correlation ◽  
Reference Change Value ◽  
Kallikrein 6

AbstractKallikrein 6 (KLK6) is a serine protease involved in numerous cellular processes, up-regulated in many cancers and associated with some neurodegenerative disorders. The aim of this study was to establish a reference interval and estimate the biological variation of KLK6 in serum samples of adults. Furthermore, levels of this protein in patients with renal failure were also studied.Serum samples from healthy volunteers (n=136) were collected. Between 15 and 18 additional samples from four of these subjects were obtained over a period of 2 months. Samples from individuals (n=1043) who visited the University Health Network for a routine check-up were collected to study the association between KLK6 with age and gender. Samples from patients with renal failure (n=106) were also obtained and KLK6 and creatinine concentrations were analyzed by ELISA and an automated enzymatic method, respectively.The reference interval was established to be 1.04–3.93 ng/mL. The index of individuality was 0.43 and the reference change value was 35%. Only two serum samples would be required to estimate the homeostatic setting point of an individual. There is a weak but highly significant positive correlation between KLK6 and age (p<0.0001). Furthermore, there is a significant positive correlation between serum concentrations of KLK6 and creatinine (p<0.0001), in patients with renal failure.The established reference interval for KLK6 and the estimation of its biological variation will further aid in the clinical use of this protein as a serum marker of malignancy and other diseases.

scholarly journals Establishment of Normal Reference Intervals for CD3+, CD4+, CD8+, and CD4+to CD8+Ratio of T Lymphocytes in HIV Negative Adults from University of Gondar Hospital, North West Ethiopia

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Addisu Gize ◽  
Biniam Mathewos ◽  
Beyene Moges ◽  
Meseret Workineh ◽  
Lealem Gedefaw
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Reference Interval ◽  
Reference Intervals ◽  
University Hospital ◽  
T Lymphocyte Subsets ◽  
Cross Sectional ◽  
North West ◽  
Normal Reference

Background.Reference values for the CD3+, CD4+, CD8+, and CD4+to CD8+ratio T lymphocyte subsets are adopted from textbooks. But for appropriate diagnosis, treatment, and follow-up of patients, correct interpretations of the laboratory results from normal reference interval are mandatory. This study was, therefore, planned to establish normal reference interval for T lymphocytes subset count and CD4+to CD8+ratio.Methods.A cross-sectional study was conducted on apparently healthy adult individuals who visited voluntary counseling and HIV testing clinic Gondar University Hospital from April to May, 2013. Whole blood was analyzed using fluorescence-activated cell sorting (BD FACS, San Jose, CA) machine to enumerate the T-cell subpopulations.Results.Out of the total 320 study participants, 161 (50.3%) were men and 159 (49.7%) were women. The normal reference intervals were (655–2,823 cells/μL), (321–1,389 cells/μL), and (220–1,664 cells/μL) for CD3+, CD4+, and CD8+T lymphocyte subsets, respectively, and CD4+to CD8+ratio was 0.5–2.5.Conclusion.The overall CD3+T lymphocytes reference interval in the current study was wide; low CD4+T lymphocytes, CD4 to CD8 ratio, and high CD8+T lymphocytes values were observed.

Normal reference interval for thyrotropin response to thyroliberin: dependence on age, sex, free thyroxin index, and basal concentrations of thyrotropin.

1984 ◽  
Vol 30 (2) ◽  
pp. 196-199 ◽  
Author(s):  
E M Erfurth ◽  
N E Nordén ◽  
P Hedner ◽  
A Nilsson ◽  
L Ek
Keyword(s):  
Linear Regression Analysis ◽  
Reference Interval ◽  
Multiple Linear Regression Analysis ◽  
Reference Intervals ◽  
Multivariate Statistical Methods ◽  
Individual Values ◽  
Multivariate Statistical ◽  
Normal Reference ◽  
Age Related ◽  
Basal Concentration

Abstract We measured the thyrotropin response (delta TSH) to 200 micrograms of thyroliberin in 131 subjects without thyroid dysfunction or other disease and with basal values for thyroid function that were within the normal reference intervals for our laboratory. By univariate and multivariate statistical methods we found delta TSH to be significantly influenced by the basal concentration of thyrotropin (TSH0) and the free thyroxin index (FT4I). When the effects of variations in TSH0 and FT4I were eliminated, delta TSH in men under 40 years of age did not differ from that in women. A decrease in delta TSH with increasing age was found in men but not in women. Thus a reference interval for delta TSH should consider TSH0, FT4I, and, in men, age. On the basis of multiple linear regression analysis, we constructed a formula for delta TSH reference intervals that takes into account individual values for TSH0 and FT4I. The formula should be applicable for women, regardless of age, up to 77 years and for men under 40 years. For older men a correction for the age-related decrease in delta TSH must be applied.

scholarly journals Sources of Variation of Commonly Measured Serum Analytes in 6 Asian Cities and Consideration of Common Reference Intervals

2008 ◽  
Vol 54 (2) ◽  
pp. 356-365 ◽  
Author(s):  
Kiyoshi Ichihara ◽  
Yoshihisa Itoh ◽  
Christopher W K Lam ◽  
Priscilla M K Poon ◽  
Jeong-Ho Kim ◽  
...  
Keyword(s):  
Serum Proteins ◽  
Selection Process ◽  
Reference Interval ◽  
Reference Intervals ◽  
Retinol Binding Protein ◽  
Complement Components ◽  
Common Reference ◽  
Lifestyle Questionnaire ◽  
Sources Of Variation ◽  
Genetic And Environmental Factors

Abstract Background: In a previous study to determine the feasibility of common reference intervals in Asia, we found significant differences among populations from 6 cities. In this study, we attempted to define the sources of these differences. Methods: We enrolled 580 healthy volunteers (279 men, 301 women, 20–62 years old), after a selection process that was based on the Clinical and Laboratory Standards Institute guidelines, and used a lifestyle questionnaire. All sera were obtained at a basal state and frozen at −80 °C until the collective assay was done. We measured 21 basic chemical analytes and 10 serum proteins. Results: We used 3-level nested ANOVA to separate the variation (SD) into between-city (SD-city), between-sex (SD-sex), between-age (SD-age), and between-individual (SD-indiv) components. SD-indiv corresponds to one-quarter of the “pure” reference interval obtained after removing variations due to city, sex, and age. The SD-sex to SD-indiv ratio was &gt;0.8 for creatinine, urate, retinol-binding protein, and transthyretin. We observed high SD-city to SD-indiv ratios, ranging from 0.4 to 0.7, for 11 analytes including lactate dehydrogenase (LDH), electrolytes, IgG, and complement components and SD-age to SD-indiv ratios &gt;0.4 for LDH, alkaline phosphatase, and total cholesterol. Multiple regression analysis demonstrated several other relevant sources of variation, including body mass index, alcohol consumption, and cigarette smoking, although their contributions were generally smaller than those for sex, region, or age. Conclusion: We observed unacceptably large regional differences in measured values of some analytes even after adjustment for age, sex, and lifestyle variables. Genetic and environmental factors may account for the residual differences.

scholarly journals Reference Intervals for Hematology and Clinical Chemistry for the African Elephant (Loxodonta africana)

2021 ◽  
Vol 8 ◽  
Author(s):  
Christine Steyrer ◽  
Michele Miller ◽  
Jennie Hewlett ◽  
Peter Buss ◽  
Emma H. Hooijberg
Keyword(s):  
National Parks ◽  
Clinical Chemistry ◽  
Clinical Pathology ◽  
Loxodonta Africana ◽  
Reference Interval ◽  
Reference Intervals ◽  
Small Sample ◽  
African Elephant ◽  
Serum Samples ◽  
American Society

The African elephant (Loxodonta africana) is listed as vulnerable, with wild populations threatened by habitat loss and poaching. Clinical pathology is used to detect and monitor disease and injury, however existing reference interval (RI) studies for this species have been performed with outdated analytical methods, small sample sizes or using only managed animals. The aim of this study was to generate hematology and clinical chemistry RIs, using samples from the free-ranging elephant population in the Kruger National Park, South Africa. Hematology RIs were derived from EDTA whole blood samples automatically analyzed (n = 23); manual PCV measured from 48 samples; and differential cell count results (n = 51) were included. Clinical chemistry RIs were generated from the results of automated analyzers on stored serum samples (n = 50). Reference intervals were generated according to American Society for Veterinary Clinical Pathology guidelines with a strict exclusion of outliers. Hematology RIs were: PCV 34–49%, RBC 2.80–3.96 × 1012/L, HGB 116–163 g/L, MCV 112–134 fL, MCH 35.5–45.2 pg, MCHC 314–364 g/L, PLT 182–386 × 109/L, WBC 7.5–15.2 × 109/L, segmented heterophils 1.5–4.0 × 109/L, band heterophils 0.0–0.2 × 109/L, total monocytes 3.6–7.6 × 109/L (means for “regular” were 35.2%, bilobed 8.6%, round 3.9% of total leukocytes), lymphocytes 1.1–5.5 × 109/L, eosinophils 0.0–0.9 × 109/L, basophils 0.0–0.1 × 109/L. Clinical chemistry RIs were: albumin 41–55 g/L, ALP 30–122 U/L, AST 9–34 U/L, calcium 2.56–3.02 mmol/L, CK 85–322 U/L, GGT 7–16 U/L, globulin 30–59 g/L, magnesium 1.15–1.70 mmol/L, phosphorus 1.28–2.31 mmol/L, total protein 77–109 g/L, urea 1.2–4.6 mmol/L. Reference intervals were narrower than those reported in other studies. These RI will be helpful in the future management of injured or diseased elephants in national parks and zoological settings.

Determination of prostate-specific antigen in serum by immunoradiometric assay

1990 ◽  
Vol 36 (1) ◽  
pp. 53-58 ◽  
Author(s):  
G Lindstedt ◽  
A Jacobsson ◽  
P A Lundberg ◽  
H Hedelin ◽  
S Pettersson ◽  
...  
Keyword(s):  
Detection Limit ◽  
Los Angeles ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Reference Interval ◽  
Clinical Analysis ◽  
Detectable Effect ◽  
Serum Samples ◽  
Strict Adherence ◽  
Normal Reference

Abstract A better understanding is needed of the role of pre-analytical factors if prostate-specific antigen (PSA) is to be reliably used as a tumor marker. Reports on the analytical performance of TANDEM-R PSA (Hybritech, Inc., San Diego, CA) differ considerably with respect to detection limit and imprecision, differences that might be due (e.g.) to the use of different control matrices, to between-batch variations in reagent composition, or to nonrobustness of the assay. During nine months we determined PSA in 986 serum samples from 728 male urology patients and 54 samples from women (25 assay runs). As controls we used two serum pools with low PSA concentration and two widely used commercial controls. The within-assay CV for patients' samples was similar to that found with the commercial controls: 2.6% to 3.4% in the upper part of the normal reference interval. Precision was worse at lower concentrations (CVs 5-10% at about 0.5 micrograms/L). Imprecision tended to be higher at the end of runs. Assay drift for 100-tube runs was -4%. PSA was stable at -20 degrees C during six months. Neither the polyester polymer in SST tubes nor a hemolysate had any detectable effect on PSA values. Clinical analysis of the first 322 patients and all patients with PSA less than or equal to 0.20 micrograms/L highlighted the requirements for strict adherence to sampling instructions and to stringent quality control also at low analyte concentrations (analyte-free sera and sera with PSA concentrations 0.2-0.5 micrograms/L). Values with TANDEM-R PSA and IRMA-Count PSA (Diagnostic Products Corp., Los Angeles, CA) correlated well with no difference in detection limit or with samples from women. Within-assay precision was better with IRMA-Count PSA in the upper part of the normal reference interval and above. The designs of the two assays were compared in a format that is generally applicable for immunoassay kits (NORDKEM kit group, unpublished), and subjective impressions were recorded.

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