[Specification, evaluation and assurance are the 3 steps to the quality of the laboratory medicine].
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Biomedical subjects
Publications and source records attributed to C H de Verdier.
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Red cells were stored at 4 degrees C in a storage solution containing alanine or alanine plus phosphoenolpyruvate (PEP). The intention was to investigate whether alanine and PEP might act synergistically to maintain a normal level of both red cell ATP and 2.3 diphosphoglycerate (2.3 DPG) under normal liquid storage conditions. Storage in the presence of alanine kept the red cell concentration of 2.3 DPG higher than the reference solution for an extended period of time, provided the initial pH was about 7.0 (37 degrees C). When the pH of the storage solution containing alanine plus PEP was lowered to facilitate the transport of PEP into the red cells, the concentration of 2.3 DPG was lowered to a rate equal to that in the reference solution. The level of ATP was also about the same as in the reference solution. The majority of the added PEP was continuously converted to 2 phosphoglycerate and 3 phosphoglycerate in the extracellular fluid. A small amount of unconverted PEP penetrated the red cell membrane when the pH went below 6.5; this occurred after 3 weeks of storage. The intracellularly located PEP, however, was not metabolized to 2.3 DPG to any significant extent within the first 6 weeks of storage. These findings indicate that PEP is not suitable as an additive for liquid storage of red cells at 4 degrees C. The combination of alanine and PEP that theoretically could be a suitable additive for liquid storage of red cells was not satisfactory in practice.
The three main aspects of analytical quality are 'goals for analytical quality', 'creation of analytical quality', and 'control of analytical quality'. In the NORDKEM-project 'medical need for quality specifications within laboratory medicine' the aspects of analytical quality are combined. The aims is to make an appraisal of the different approaches to goal setting, and to develop a practical procedure for assessing analytical quality requirements. The goals are used to define which demands should be met by the process of establishing and maintaining the quality, and for design of internal as well as external quality assurance procedures. The project is an umbrella project with three main subprojects and several satellite projects. In this presentation a model for evaluation of influence of analytical bias and imprecision on the outcome from a diagnostic classification based on bimodal distribution is described.
A knowledge-based information system has been constructed to facilitate and standardize the interpretation of data obtained from specialized analyses in clinical chemistry. For illustration the system was applied to metabolic studies of erythrocytes from patients in whom hereditary disorders are suspected to explain the presence of a haemolytic anaemia or a polycythaemia. The study includes assay of the catalytic activity of 10 different enzymes and the concentration of some key metabolites. The knowledge-based system is an excellent tool for documentation, updating and transfer of knowledge of the interpretative process. This will reduce the risk of changes in this process being made without sound motivation and documentation. Furthermore, the statistical and graphic features of the system provide data for long-term quality assessment and insights into reference sample groups which are used to update decision levels.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A knowledge based-information system has been constructed to facilitate and standardize the interpretation of data obtained from specialized analyses in laboratory medicine. For illustration the system was applied to metabolic studies of erythrocytes from patients in whom hereditary disorders are suspected to explain the presence of a hemolytic anemia or polycythemia. The study includes assay of the catalytic activity of ten different enzymes and the concentration of some key metabolites. The knowledge based system is an excellent tool for documentation, updating and transfer of knowledge about the interpretative process. This will reduce the risk that changes in this process are made without sound motivation and documentation. Furthermore, the statistical and graphic features of the system provide data for long-term quality assessment and insights into reference sample groups which are used to update decision limits. A few cases are used to illustrate the advantages of the system.
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Red cells stored in saline-adenine-glucose-mannitol (SAGM) medium were rejuvenated by incubation with phosphoenolpyruvate (PEP) under conditions that can be achieved easily in ordinary blood banking. Regeneration of 2,3 diphosphoglycerate (2,3 DPG) and adenine nucleotides of stored red cells was dependent on the pH of the incubation medium and the incubation time. In red cells stored for 3 and 5 weeks, the optimal pH and incubation time for regeneration of 2,3 DPG and adenine nucleotides were 5.8 and 90 minutes and 6.1 and 60 minutes, respectively. During the incubation of red cells with PEP, methemoglobin was formed; it increased when the medium pH was below 6.0 and the incubation time exceeded 60 minutes. We conclude that incubation at a medium pH of 6.1 for 60 minutes is optimal for the rejuvenation of stored red cells with PEP. Under such incubation conditions, the concentrations of 2,3 DPG and adenine nucleotides in red cells stored for 5 weeks were restored to normal without methemoglobin formation.
Fresh and stored erythrocytes from normal and ITP-pyrophosphohydrolase (ITP-ase, EC 3.6.1.19) deficient individuals were incubated with hypoxanthine, guanine, allopurinol, and inosine. Differences in the purine metabolism between the normal and the ITP-ase deficient erythrocytes were observed only in the IMP-ITP cycle. Hypoxanthine, guanine and allopurinol were converted to nucleotides at the same rate. Hypoxanthine (2.5 mumol/l) inhibited the salvage of allopurinol (40 mumol/l). A slow decrease (0.7%/day) in salvage rate was observed in both types of cells upon storage at +4 degrees C. Erythrocyte ITP-ase activity was measured in a reference sample group of 48 healthy volunteers. Two distinct groups were found with mean activities equal to 48.3 +/- 13.1 nkat/g Hb (means +/- SD, n = 38) and 11.4 +/- 4.3 nkat/g Hb (n = 10). In two previously selected subjects, the ITP-ase activity was 0.2 and 2.4 nkat/g Hb. A hypothetical genetic mechanism is discussed. The maximal energy turnover in the IMP-ITP cycle during hypoxanthine incubation was found to be less than 10% of the basal erythrocyte energy turnover.
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The basal plasma concentration of adenine and its renal excretion was studied in two men. For its analysis partly new chromatographic techniques were developed. The plasma concentration varied around 70 nmol/l; the renal excretion rate was, as reported earlier by other investigators, around 10 nmol/min. Loadings, intravenously during about 3 h and orally, both with about 30 nmol adenine per kg body mass revealed that most of the adenine was metabolized to nucleotide form. In the experiments with intravenous administration of adenine only about 2% of the given dose appeared in the urine as adenine and somewhat less as the easily precipitable metabolite 2,8-dihydroxyadenine. In the peroral loads, with higher plasma adenine concentrations, the ratios of the renally excreted two compounds were one to a few per cent higher.
1. Changes of Gibbs energy, enthalpy and entropy in red cells during steady-state glycolysis were discussed. 2. The heat production of red cells at various metabolic conditions was measured on a flow microcalorimeter with simultaneous analyses of lactate and other metabolites. The results were discussed in relation to enthalpy changes of the different metabolic steps in the glycolytic pathway.
When assessing the performance of an internal quality control system, it is useful to determine the probability for false rejections (pfr) and the probability for error detection (ped). These performance characteristics are estimated here by use of a computer stimulation procedure. The control rules studied include those commonly employed with Shewhart-type control charts, a cumulative sum rule, and rules applicable when a series of control measurements are treated as a single control observation. The error situations studied include an increase in random error, a systematic shift, a systematic drift, and mixtures of these. The probability for error detection is very dependent on the number of control observations and the choice of control rules. No one rule is best for detecting all errors, thus combinations of rules are desirable. Some appropriate combinations are suggested and their performance characteristics are presented.