The NORDKEM project and its aims.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C H de Verdier.
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.
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.
Explore the source record for details and available documents.
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.
The distribution of respiratory gases, hydrogen ions, glucose and lactate were studied in red cells suspended in SAGM solution and stored undisturbed at +4 degrees C in plastic (PVC) bags. After 42 days' storage there were considerable concentration differences between the supernatant and the red cell layer, as well as concentration gradients within the latter. Thus, pO2, sO2, pH and the glucose concentration were higher in the supernatant and pCO2 and the lactate concentration were higher in the red cell layer. These findings show that sampling from the mixed content of blood which has been stored sedimented in plastic containers will not be representative for the erythrocyte environment at the end of shelf life. This is of importance in attempts to understand storage effects on red cells.
Red cells supended in saline-adenine-glucose-mannitol solution were stored for 42 days at +4 degrees C. One portion was packed by centrifugation and stored unmixed; the other portion was mixed once a week. Red cell fluidity and adenine nucleotide concentration were significantly lower in unmixed than in mixed units and also differed within the packed layer, showing a decrease towards the bottom. Hemolysis was 2.5-fold and microvesiculation 5-fold higher in cells stored unmixed. It is suggested that, during liquid storage, an early accumulation of acid metabolites in the bottom part of packed red cells may play an important role both for adenylate loss and microvesiculation, but lack of membrane-stabilizing action of diethylhexylphthalate may in part explain the latter. Both of these two changes are factors associated with impaired red cell viability. Mixing appears essential to optimize storage conditions for red cells.
To describe the mechanisms involved in allopurinol kinetics after intravenous injection in humans, a number of alternative computer-based biodynamic models were designed. Distribution processes were described with two-compartment as well as with three-compartment kinetics for both allopurinol and its metabolite oxipurinol. These two major physiological alternatives were combined with biochemical models assuming either competitive or tight-binding-complex inhibition kinetics. The four resulting basic models were evaluated (and successively improved) using sets of plasma allopurinol and oxipurinol concentration curves, measured after intravenous injection in healthy subjects and in patients with different degrees of liver function. A three-compartment model with tight-binding-complex inhibition was selected and used to analyze the 35 loading tests performed. One of the parameters estimated in this way, the fractional rate constant for transport of allopurinol from the central compartment to the metabolically active (liver) compartment (kA31), turned out to be a powerful discriminative parameter between a group of healthy subjects, a group of patients with slightly to moderately reduced overall liver function, and a group with severely reduced overall liver function [kA31(min-1) = 0.136 +/- 0.042 (mean +/- SD, n = 13), 0.072 +/- 0.024 (n = 13), and 0.025 +/- 0.015 (n = 8), respectively].
Red cells collected in CPD, suspended in SAGM solution and stored for 42 days at +4 degrees C, were tested before and after incubation for 1 h at 37 degrees C with respect to autologous 24-hour posttransfusion red cell survival, morphology, fluidity at low shear rate and adenylate content. Warming and to some extent chromium labelling of the cells resulted in improvement of the morphology and fluidity but in no increase in adenosine triphosphate, total adenylate concentration or posttransfusion survival. The conclusion is drawn that short-term improvement of the morphology before transfusion does not result in increased viability.
Therapeutic venesection for polycythaemia vera (PV) produces iron deficiency. If iron supplementation is avoided, the frequency of venesections can be kept lower than if iron is given. This is the standard treatment for PV in our department, and this model for iron deficiency was used to compare serum ferritin, free erythrocyte protoporphyrin (FEP), serum iron and transferrin as indicators of iron deficiency. Eleven patients with PV were studied on a total of 90 occasions. Five patients were followed from normal iron status to iron deficiency, the other six were iron deficient at the start of the study. Serum ferritin and FEP became abnormal approximately simultaneously during the development of iron deficiency, serum ferritin in all patients, FEP in 8 out of 11 patients. There was a correlation between the two in all specimens (r = 0.75, p less than 0.001), but serum ferritin showed fewer false negative results. Serum transferrin alone was elevated only in 25% of the patients, and serum iron, although mostly subnormal, was rather inconsistent. It is concluded that serum ferritin and FEP can both be used to diagnose iron deficiency during venesection treatment of PV, whereas serum iron and transferrin are of little value.
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.
Red cells collected in CPD and suspended in SAGM medium were stored in plastic (PVC) containers for 42 days at +4 degrees C. Comparison was made between aerobic storage (normal air exposure) and anaerobic storage (exposure to nitrogen gas). The air-exposed units showed a strong increase in pO2 and oxygen saturation as a result of oxygen penetration into the bags from outside. This resulted in a decrease in ATP and adenylate energy charge, a slower metabolization of adenine and hypoxanthine to AMP and IMP, respectively, and a faster decrease in red cell fluidity. To explain the findings it is concluded that aerobic storage causes an increased need of high-energy phosphate groups, possibly used for replacement of the phospholipid membrane bilayer or in repair of phosphate bonds in the cytoskeleton. It is further proposed that a slight formation of hydrogen peroxide from free oxygen radicals moderately increases the oxidation of reduced (GSH) to oxidized (GSSG) glutathione and slightly enhances the need for reduced nicotinamide-adenine dinucleotides mainly provided by increased flux through the pentose phosphate shunt.