Interpreting laboratory results.

Fraser, Callum G.; Fogarty, Yvonne

doi:10.1136/bmj.298.6689.1659

Cited by 78 publications

(37 citation statements)

References 6 publications

(1 reference statement)

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“…Our results show that ALT reagent should be used with caution when liver injury is severe. Optimization of the dilution of serum or plasma samples is critical to accurately estimate liver injury in order to avoid either under or overestimation of liver damage [20]. This becomes particularly relevant when the study involves the assessment of therapeutic intervention in modulating liver injury.…”

Section: Resultsmentioning

confidence: 99%

Liver Injury Assessment by Vetscan VS2 Analyzer and Most Frequently Used ALT/GTP Reagent

Vatsalya

Avila

Frimodig

et al. 2016

GHOA

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Background and aim Liver injury is estimated by serum alanine aminotransferases (ALT) levels in experimental animal models. Laboratories use various techniques to measure ALT levels including assay reagents and chemistry analyzers. VetScan VS2 (VS2) is widely used in veterinary clinics and research laboratories for highly reproducible, convenient and effective testing. Alternatively, ALT liquid reagent is used by laboratories to estimate liver injury in animal studies. The aim of this study was to perform comparative analyses of data obtained from these two assays in two different animal models. Methods In this study, we used two different mouse models and compared the ALT levels measured using VetScan VS2 chemistry analyzer and ALT liquid reagent. Immunohistochemical analysis of hepatic tissue was also performed to document liver pathology. The first model is a high fat diet feeding model that results in a mild hepatic steatosis (fat accumulation in the liver) without elevation of ALT levels. For a severe liver injury model, we employed a hepatotoxin-induced liver injury model (carbon tetrachloride, CCl4), which leads to the development of hepatic fibrosis and very high ALT levels. Results VetScan VS2 and ALT reagent gave different values of ALT for all animal groups. However, linear regression analysis showed a significantly high association between ALT levels obtained by VS2 and ALT liquid reagent in a high-fat feeding model with no liver injury. For the CCl4 induced liver injury model, serum dilution (5 and 10 times) was performed to obtain accurate results with ALT reagent. ALT levels acquired from both techniques showed a close association. Interestingly, this correlation was closer when serum was diluted 5 fold. Conclusion This study demonstrates that both methods give similar results when evaluating liver injury in animal studies. However, the serum dilution factor is critical for severe liver injury assessment when using ALT reagent and requires some optimization. In this regard, VetScan VS2 is easier to use and gives comparable results.

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Section: Resultsmentioning

confidence: 99%

Liver Injury Assessment by Vetscan VS2 Analyzer and Most Frequently Used ALT/GTP Reagent

Vatsalya

Avila

Frimodig

et al. 2016

GHOA

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“…For no quantity is the index> 1.4 and for many it is <0.6. Numerical knowledge of the magnitude of within-subject biological variation allows an objective analysis of the significance of differences in serial results from the individual being monitored (Fraser & Fogarty 1989). Changes are not due only to the patient getting better or getting worse but also to preanalytical (CVp), analytical and withinsubject variation.…”

Section: Individuality and Monitoringmentioning

confidence: 99%

Age-Related Changes in Laboratory Test Results

Fraser

1993

Drugs & Aging

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Many quantities assayed in clinical laboratories demonstrate age-related changes. Particularly important periods are early life, adolescence, old age, and after the menopause in females. The changes that occur until adulthood are well documented. Fewer data are available on elderly people even though they consume a large component of healthcare resources. In diagnosis, and prior to initiation of drug therapy, when no previous results are available, reference values must be available to aid interpretation. Reference intervals generated from elderly people are sometimes wider than in younger adults. It is suggested that conventional adult reference values should be used in general for the very elderly since, at least in part, the wider intervals are probably due to inclusion of individuals who are unhealthy in the reference sample group. Most quantities have marked individuality, and serial values for an individual span only a part of the reference interval. Individuals can have values which are very unusual for them but still lie within the reference limits; this implies that clinical laboratory tests will be less than ideal in the detection of latent or early disease. The average within-subject variation in healthy elderly people and younger adults is similar. Therefore, the large database on biological variation can be used, with analytical imprecision, to calculate critical differences for serial results in an elderly individual which must be exceeded before significance can be claimed. These critical differences are of value in monitoring the effects of drug therapy.

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“…Early information about response could contribute to the treatment being continued despite serious complications and, for patients on treatment, an ineffective therapy could be stopped and an alternative treatment instituted. Any effective monitoring procedure of ovarian cancer patients using serum markers should take into consideration that increments and decrements of marker concentrations are due not only to a patient´s conditions but also to normal intra-individual biological variation and analytical imprecision (13)(14)(15). Small changes are probably within the range of laboratory imprecision and physiological variation and should not be considered as evidence of disease response or progression.…”

Section: Introductionmentioning

confidence: 99%

Interpretation of Sequential Measurements of Cancer Antigen 125 (CA 125), Carcinoembryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) Based on Analytical Imprecision and Biological Variation in the Monitoring of Ovarian Cancer

Tuxen

Sölétormos²,

Petersen³

et al. 2001

Clinical Chemistry and Laboratory Medicine

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The main objective with cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) monitoring of ovarian cancer patients is to detect an early change of disease activity with high reliability. We hypothesized that a monitoring scheme for ovarian cancer patients with serological tumor markers should take into account the stochastic variation, i.e. the probability that observed increases and decreases may solely be due to analytical imprecision and normal intra-individual biological variation. The aim of this study was to provide a detailed characteristic of the within-subject mean steady state concentrations and the associated variability in healthy individuals with an age distribution representative for ovarian cancer patients. Thirty-one healthy women with a median age of 55 years comprised the study population. Sixteen blood samples were collected from each subject in four series, with four samples per series, over a period of approximately 1 year. We found that, i) natural logarithmic-transformed concentrations were more homogeneously distributed between individuals than the original concentrations, ii) the within-subject mean steady state levels, the standard deviations, and the coefficients of variation differed among subjects, and iii) the steady state variability differed among the markers. In conclusion, our data indicate that the assessment of sequential CA 125, CEA, and TPA concentrations is more complex than hitherto recognized. We suggest that it is necessary to adjust the assessment criteria to the type of marker, and that assessment may be facilitated if based on natural logarithmic transformed concentrations.

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Interpreting laboratory results.

Cited by 78 publications

References 6 publications

Liver Injury Assessment by Vetscan VS2 Analyzer and Most Frequently Used ALT/GTP Reagent

Liver Injury Assessment by Vetscan VS2 Analyzer and Most Frequently Used ALT/GTP Reagent

Age-Related Changes in Laboratory Test Results

Interpretation of Sequential Measurements of Cancer Antigen 125 (CA 125), Carcinoembryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) Based on Analytical Imprecision and Biological Variation in the Monitoring of Ovarian Cancer

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