Carl-Henric de Verdier

4.1. Pancreatic iso-amylase in serum as a diagnostic test in different clinical situations. A simulation study

The potential use of a pancreatic iso-amylase test has been studied by computer simulation. This simulation was performed to assess the quality requirements on the test in different clinical situations. It was shown that, in most situations studied, an optimal discriminating level and an optimal analytical quality (imprecision and bias) could be established. In one situation studied in more detail, it was found that the influence of pre-analytical variation, duplicate determinations, reclassification of borderline cases and size of reference sample groups were of minor importance. The weighting ratio of false negatives: false positives was found to be critical for the results. It is concluded that a simulation study of this type can be recommended prior to entering the phases of analytical refinement and clinical testing on patients.

Estimation of parameters in a multi-affinity-state model for haemoglobin from oxygen binding data in whole blood and in concentrated haemoglobin solutions☆

Oxygen binding data on whole blood and concentrated haemoglobin solutions at different pH, pCO2 and 2,3-bis-phosphoglycerate concentrations were analysed with the use of a two-quaternary-state model regarding P2-Gri† purely as a quaternary effector (Herzfeld & Stanley, 1972). The model was applied as a multi-affinity-state model and was extended on a molecular mechanistic level in terms of the so-called Perutz mechanisms. n nBinding of oxygen to a subunit contained in the oxy quaternary state was found to be insensitive to changes in pH and pCO2 (Koxy = 0.71 ± 0.05 mm Hg−1). At 37 °C, pH 7.2 and pCO2 = 22 mm Hg, Kdeoxy was estimated to be lower than Koxy by a factor of 130, the allosteric constant was (1.5 ± 0.4)104 and the binding constant of P2-Gri for the deoxy quaternary conformation was estimated to be 25 times higher than that for the oxy quaternary conformation (130 ± 50 1 mol−1). n nWith regard to the influence of protons, carbon dioxide and P2-Gri, the results are consistent with the concepts that (1) P2-Gri acts primarily as a quaternary effector, that (2) protons act as constraint effectors and second-order effectors, and that (3) carbon dioxide acts as a first and second-order quaternary effector. The calculations further indicate that (1) quaternary transition most likely takes place after oxygenation of the second subunit, that (2) the probabilities of intermediary states of oxygenation are surprisingly low, and that (3) the difference in total conformational energy between the two quaternary ligand-free states is almost exclusively confined to molecular constraints, and very little to the difference in quaternary conformational energy.

2. Principles for Assessing Analytical Quality Specifications (“AQSpecs”) and their Use in Design of Control Systems

Interpretation of clinical laboratory data aiming at improved patient care may be considered as a signal-to-noise problem, where the signal contains the information about the individual’s state of health and the noise is due to a mixture of disturbing factors. These factors cover a wide range, from selection of measurands, over sampling and analytical performance, to interpretation of the obtained data (28, 44).

11. Explanation of some other Concepts and Terms Used in this Report

This terminology was in principle introduced already in (1) and is preferred here in order to clearly distinguish between the overall procedure and its component parts. Analytical control procedures can be defined by specification of control rule(s), control limits, control material, and the number of control observations.

Medical Need for Quality Specifications - a Nordkem Project for Selecting the Appropriate Quality in Clinical Laboratories

The Nordic Clinical Chemistry Project (Nordkem) has during its existence run several projects dealing with analytical quality requirements and the specifications of such requirements. The latest project - “Medical Need for Quality Specifications in Laboratory Medicine” - started three years ago and is now to be reported. The project consists of three main subprojects and a large number of associated projects.The main subprojects deal with:* External quality assurance for proteins (Per Hyltoft Petersen et al.)* Transferability of clinical laboratory data (Torgny Groth & C-H de Verdier)* Terminology (Rene Dybkaer)“Clinical goals” are assessed using different kinds of procedures. Comparison with the characteristics of “the analytical procedures” and “the quality assurance programs” gives the Management of the clinical laboratory a background for determining the “analytical quality specifications” of the laboratory.Procedures for setting up clinical goals and analytical quality specifications are given and th...

4. Guidelines for Assessing Analytical Quality Requirements

In ref. (30) (Chapter 2) the main principles of analytical goal-setting and formulation of analytical quality specifications (AQSpecs) were outlined. From this document it is possible to learn how to assess quality specifications according to the state of the art approach and the biological approach, as well as the clinical usefulness approach. Assessment of specifications based on clinical strategies/situations, however, need more preparation, starting with a detailed analysis of the problem. There are no simple formulas, but there are several applicable models for the purpose, which will be described in this chapter.

ITP-Pyrophosphohydrolase and Purine Metabolism in Human Erythrocytes

In a study on liquid erythrocyte preservation (de Verdier et al, 1987), we measured purine nucleotides in erythrocytes from 103 blood donors. We found ITP concentration above detection limit (0.05 mmol/1 in this study) in fresh erythrocytes from one donor and in erythrocytes stored for 42 days in CPD-SAGMAN solution (Hogman et al, 1983) in another donor. The present study was designed in order to explore whether these erythrocytes showed any other sign of aberrant purine metabolism before or after storage. In view of an ongoing study on the use of the commonly prescribed purine analogue allopurinol in liver function evaluation (van Waeg et al, 1988a), the metabolism of allopurinol in normal and ITP-pyrophosphohydrolase (ITPase) deficient erythrocytes was also studied.