Search

Reference intervals of total cholesterol concentrations in plasma and of their fractions low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-and non-HDL concentrations are seldom studied with respect to the relevance of age and sex. Therefore, the effect of age and sex on the reference intervals was reinvestigated with 2 indirect procedures.

The glucose concentration in plasma or serum is one of the most often requested analytical values in laboratory medicine. Whereas the analytical part of the glucose determination is well standardised, the standardisation of the pre-examination part (pre-analytical phase) is not sufficiently solved, yet. In view of the present controversial discussion regarding the most efficient prevention of pre-analytical glycolysis, the question arises whether the economical and logistic expenses for inhibiting glycolysis determining random glucose concentration are justified. In hospitals with adequate logistics (e.g. pneumatic tube systems for blood tubes) to guarantee a blood sample transport time of about 1 – 2 h, plasma or serum without prevention of glycolysis can be applied for random glucose concentrations if the reference limits are estimated by the laboratory. If such logistics are not available, especially in primary care services, either plasma or serum samples or whole blood in special tubes with anti-glycolytic additives may be sent to the laboratory.

A new model for the indirect estimation of reference limits (RLs) has been proposed recently and was coined TMC approach (truncated minimum chi-square estimation) which can be performed with R statistic. A spline function is applied to the RLs to get a continuous function if age is graphically presented vs. the RLs avoiding artificial “jumps” between different age groups. Most indirect models assume a power normal distribution and fail if this assumption is not fulfilled as e.g. if a relatively high percentage of measured values is below the detection limit and the data are distributed extremely skewed. This problem is handled by the TMC model. High-sensitive cardiac troponin T (hs cTnT) was chosen as an example. The hs cTnT concentration in serum or plasma is well accepted as a valuable marker in the diagnosis of acute myocardial infarction. Currently, the 99th percentile derived from a “healthy” subpopulation is the decision limit recommended by consensus groups. However, this decision limit is questioned by several authors for many reasons. In the present report, the 97.5th and the 99th percentile limits were reinvestigated by the TMC model with different subpopulations stratified according to age and sex and were finally compared to presently recommended decision limits. In summary, the generally recommended 99th percentile as a fixed decision limit should be reconsidered. It is suggested to apply more specific reference limits stratified for age and sex instead of a fixed decision limit.

Reference intervals (RIs) can be determined by direct and indirect procedures. Both approaches identify a reference population from which the RIs are defined. The crucial difference between direct and indirect methods is that direct methods select particular individuals after individual anamnesis and medical examination have confirmed the absence of pathological conditions. These individuals form a reference subpopulation. Indirect methods select a reference subpopulation in which the individuals are not identified. They isolate a reference population from a mixed population of patients with pathological and non-pathological conditions by statistical reasoning.

Although the concentration of uric acid in serum or plasma is known to depend on sex and age and is subject to diurnal variation, the influence of these covariates on the reference interval (RI) is often neglected. Consequently, the values in the literature vary considerably. Therefore, we reinvestigated the reference limits and their dependence on covariates.

Copyright of Journal of Laboratory Medicine / Laboratoriums Medizin is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The current dogma of establishing intra-laboratory reference limits (RLs) and their periodical reviewing cannot be fulfilled by most laboratories due to the expenses involved. Thus, most laboratories adopt RLs from external sources often neglecting the problems of transferability. Presently accepted validation concepts still require experimental expenses. Several attempts were undertaken to derive RLs from the large data pools stored in modern laboratory information systems. Former indirect procedures were not generally accepted, but were recently further developed and combined with direct exclusion criteria and applied to estimate RLs of the catalytic activity concentrations of enzymes. This approach was now applied to several electrolytes in serum and plasma most commonly applied in clinical chemistry.Methods: A smoothed kernel density function was estimated for the distribution of the mixed data of the sample group (combined data of non-diseased and diseased subjects). It was assumed that the 'central' part of the distribution of all data represents the non-diseased ('healthy') population (non-pathological values) with high probability. The central part was defined by truncation points using an optimisation method, and was used to estimate a Gaussian distribution of the values of non-diseased subjects. This distribution was now considered as the distribution of the non-diseased subgroup. The percentiles of this parametrical distribution were calculated to obtain unimodal reference intervals.Results: The RLs obtained from different laboratories were similar to recently published values established by direct procedures. Stratification for gender was not necessary, but in some cases for age. With rising age, an increase of the upper RL and of the reference range was observed for potassium. Hospitalisation affected the RLs of sodium, potassium, calcium and magnesium, but not of phosphate. In the case of sodium, the data of at least five regional laboratories could be combined to common RLs. The presented indirect procedure was further validated with a large dataset of potassium concentrations from the NHANES III study with five groups of different health status.Conclusions: The proposed strategy of combining exclusion criteria with an indirect method led to RLs from intra-laboratory data pools for electrolytes which were plausible in comparison to published data obtained by the generally accepted direct approach. The combined concept, however, still requires further investigations. Therefore, it is presently only recommended for checking and reviewing already existing RLs. [ABSTRACT FROM AUTHOR]

Information on prevalences of grossly visible diseases and parasites of flounder (Platichthys flesus) from the Baltic Sea is presented for 11 sampling areas on a transect from the Mecklenburg Bight to the Gulf of Finland. Among the 3008 flounder examined, highest overall prevalences were observed for lymphocystis (14.4%) and acute/healing stages of the skin ulcer disease (5.9%). The prevalences of liver neoplasms >2 mm in diameter (0.4%), skeletal deformities (0.6%), and fin rot/erosion (0.5%) were low. The only externally visible parasite recorded was Cryptocotyle concavum (28.2%). The results of a multivariate statistical analysis reveal that the diseases are influenced by a variety of host-specific (length, age, sex) and area-specific (salinity, temperature) factors as well as their interactions. By calculating the expected prevalence for a standardized fish population for each area and disease, the extent of area-specific effects not attributable to host-specific factors was estimated. [ABSTRACT FROM PUBLISHER]

Abstract Background Spontaneous cessation of growth is a frequent finding in uterine fibroids. Increasing evidence suggests an important role of cellular senescence in this growth control. Deciphering the underlying mechanisms of growth control that can be expected not only to shed light on the biology of the tumors but also to identify novel therapeutic targets. Methods We have analyzed uterine leiomyomas and matching normal tissue for the expression of p14Arf and used explants to see if reducing the MDM2 activity using the small-molecule inhibitor nutlin-3 can induce p53 and activate genes involved in senescence and/or apoptosis. For these studies quantitative real-time RT-PCR, Western blots, and immunohistochemistry were used. Statistical analyses were performed using the student's t test. Results An in depth analysis of 52 fibroids along with matching myometrium from 31 patients revealed in almost all cases a higher expression of p14Arf in the tumors than in the matching normal tissue. In tissue explants, treatment with the MDM2 inhibitor nutlin-3 induced apoptosis as well as senescence as revealed by a dose-dependent increase of the expression of BAX as well as of p21, respectively. Simultaneously, the expression of the proliferation marker Ki-67 drastically decreased. Western-blot analysis identified an increase of the p53 level as the most likely reason for the increased activity of its downstream markers BAX and p21. Because as a rule fibroids express much higher levels of p14Arf, a major negative regulator of MDM2, than matching myometrium it was then analyzed if fibroids are more sensitive against nutlin-3 treatment than matching myometrium. We were able to show that in most fibroids analyzed a higher sensibility than that of matching myometrium was noted with a corresponding increase of the p53 immunopositivity of the fibroid samples compared to those from myometrium. Conclusions The results show that uterine fibroids represent a cell population of advanced cellular age compared to matching myometrium. Moreover, the data point to members of the p53-network as to potential novel therapeutic targets for the treatment of uterine fibroids.

Reference intervals are established either by direct or indirect approaches. Whereas the definition of direct is well established, the definition of indirect is still a matter of debate. In this paper, a general definition that covers all indirect models presently in use is proposed. With the upcoming popularity of indirect models, it has become evident that further partitioning strategies are required to minimize the risk of patients' false classifications. With indirect methods, such partitions are much easier to execute than with direct methods. The authors believe that the future of reference interval estimation belongs to indirect models with big data pools either from one laboratory or combined from several regional centres (if necessary). Independent of the approach applied, the quality assurance of the pre-analytical and analytical phase, considering biological variables and other confounding factors, is essential., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

The concept of reference change values (RCVs) for diagnosis and monitoring of diseases has become well established. Several models habe been developed, e. g. one assuming a normal distribution and another one for a log-normal distribution. RCV values calculated for some measurands with both models are compared with each other and led to similar results. A few examples led to RCV values which are not plausible for diagnostic purposes. Although statistical concepts of RCV values are well established, their clinical relevance remains questionable at least for some measurands. Studies with clinicians are required whether RCVs are of practical usefulness., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: There are generally two major reasons for the comparison of reference intervals (RIs): when externally determined RIs (from the literature or provided by a manufacturer) are compared with presently used intra-laboratory RIs and when indirectly estimated RIs are compared with directly established RIs. Discrepancies within these comparisons may occur for two reasons: 1. the pre-analytical and/or analytical conditions do not agree and/or 2. biological variables influencing the establishment of RIs have not been considered adequately. If directly and indirectly estimated reference intervals (RIs) are compared with each other, they very often agree. Sometimes, however, a comparison may differ, with the reason for any discrepancy not being further studied. A major reason for differences in the comparison of RIs is that the requirement for stratification has been neglected., Methods: The present report outlines the consequences to RI comparison if stratification is neglected during RI determination with the main variables affecting RIs being sex and age. Alanine aminotransferase was chosen as an example in which the RIs depend on both these factors., Results: Both direct and indirect approaches lead to erroneous RIs if stratification for variables which are known to affect the estimation of RIs is not performed adequately. However, failing to include a required stratification in procedures for directly determined RIs affects the outcome in a different way to indirectly determined RIs., Conclusions: The resulting difference between direct and indirect RIs is often misinterpreted as an incorrect RI estimation of the indirect method., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)