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Biomedical subjects

N Fogh-Andersen

Publications and source records attributed to N Fogh-Andersen.

At least 19 recordsLinked to original sources

Diurnal variations of serum erythropoietin at sea level and altitude.

This study tested the hypothesis that the diurnal variations of serum-erythropoietin concentration (serum-EPO) observed in normoxia also exist in hypoxia. The study also attempted to investigate the regulation of EPO production during sustained hypoxia. Nine subjects were investigated at sea level and during 4 days at an altitude of 4350 m. Median sea level serum-EPO concentration was 6 (range 6-13) U.l-1. Serum-EPO concentration increased after 18 and 42 h at altitude, [58 (range 39-240) and 54 (range 36-340) U.l-1, respectively], and then decreased after 64 and 88 h at altitude [34 (range 18-290) and 31 (range 17-104) U.l-1, respectively]. These changes of serum-EPO concentration were correlated to the changes in arterial blood oxygen saturation (r = -0.60, P = 0.0009), pH (r = 0.67, P = 0.003), and in-vivo venous blood oxygen half saturation tension (r = -0.68, P = 0.004) but not to the changes in 2, 3 diphosphoglycerate. After 64 h at altitude, six of the nine subjects had down-regulated their serum-EPO concentrations so that median values were three times above those at sea level. These six subjects had significant diurnal variations of serum-EPO concentration at sea level; the nadir occurred between 0800-1600 hours [6 (range 4-13) U.l-1], and peak concentrations occurred at 0400 hours [9 (range 8-14) U.l-1, P = 0.02]. After 64 h at altitude, the subjects had significant diurnal variations of serum-EPO concentration; the nadir occurred at 1600 hours [20 (range 16-26) U.l-1], and peak concentrations occurred at 0400 hours [31 (range 20-38) U.l-1, P = 0.02]. This study demonstrated diurnal variations of serum-EPO concentration in normoxia and hypoxia, with comparable time courses of median values. The results also suggested that EPO production at altitude is influenced by changes in pH and haemoglobin oxygen affinity.

Adult

Human erythropoietin response to hypocapnic hypoxia, normocapnic hypoxia, and hypocapnic normoxia.

This study investigated the human erythropoietin (EPO) response to short-term hypocapnic hypoxia, its relationship to a normoxic or hypoxic increase of the haemoglobin oxygen affinity, and its suppression by the addition of CO2 to the hypoxic gas. On separate days, eight healthy male subjects were exposed to 2 h each of hypocapnic hypoxia, normocapnic hypoxia, hypocapnic normoxia, and normal breathing of room air (control experiment). During the control experiment, serum-EPO showed significant variations (ANOVA P = 0.047) with a 15% increase in mean values. The serum-EPO measured in the other experiments were corrected for these spontaneous variations in each individual. At 2 h after ending hypocapnic hypoxia (10% O2 in nitrogen), mean serum-EPO increased by 28% [baseline 8.00 (SEM 0.84) U.l-1, post-hypoxia 10.24 (SEM 0.95) U.l-1, P = 0.005]. Normocapnic hypoxia was produced by the addition of CO2 (10% Co2 with 10% O2) to the hypoxic gas mixture. This elicited an increased ventilation, unaltered arterial pH and haemoglobin oxygen affinity, a lower degree of hypoxia than during hypocapnic hypoxia, and no significant changes in serum-EPO (ANOVA P > 0.05). Hypocapnic normoxia, produced by hyperventilation of room air, elicited a normoxic increase in the haemoglobin oxygen affinity without changing serum-EPO. Among the measured blood gas and acid-base parameters, only the partial pressures of oxygen in arterial blood during hypocapnic hypoxia were related to the peak values of serum-EPO (r = -0.81, P = 0.01). The present human EPO responses to hypoxia were lower than those which have previously been reported in rodents and humans. In contrast with the earlier rodent studies, it was found that human EPO production could not be triggered by short-term increases in pH and haemoglobin oxygen affinity per se, and the human EPO response to hypoxia could be suppressed by concomitant normocapnia without acidosis.

Adult

Endogenous versus exogenous lithium clearance for evaluation of dopamine-induced changes in renal tubular function.

1. The present randomized, double-blind cross-over study compared endogenous and exogenous lithium clearance (CLi) for estimation of the effect of dopamine on tubular sodium reabsorption. Twelve normal, salt-repleted male subjects were investigated on three different occasions with either placebo or 450 mg or 600 mg of lithium given in random order at 22.00 hours. After an overnight fast, renal clearance studies were performed during a 1 h baseline period and subsequently during the second hour of an infusion of 3 micrograms min-1 kg-1 of dopamine. 2. Baseline values of endogenous CLi and fractional excretion of lithium (FELi) [27.0 (23.5-30.5) ml/min and 24.2 (20.3-28.2)% (means with 95% confidence interval)] were lower than exogenous values [lithium, 450 mg: 32.7 (29.9-35.4) ml/min (P < 0.05) and 27.4 (25.2-29.6)% (P < 0.05); lithium, 600 mg: 33.4 (29.2-37.6)ml/min (P < 0.05) and 28.6 (26.3-31.0)% (P < 0.01)]. Both test doses of lithium increased the baseline sodium clearance (CNa), but glomerular filtration rate and urine flow rate remained unchanged. 3. Dopamine increased CNa to similar values on the three study days. CLi increased to 40.9 (35.5-46.5) ml/min (endogenous lithium, P < 0.001), 43.2 (40.8-45.6) ml/min (450 mg of lithium, P < 0.01) and 44.9 (41.3-48.4) ml/min (600 mg of lithium, P < 0.001), respectively. FELi increased to 32.2 (27.5-37.0)% (P < 0.01), 35.4 (33.0-37.7)% (P < 0.01) and 35.9 (32.8-38.9)% (P < 0.01), respectively. Values during dopamine infusion did not differ significantly. 4. The lower baseline values of endogenous CLi and FELi compared with exogenous values suggest that CLi in humans depends on the plasma concentrations of lithium. However, the effect of dopamine on CLi and FELi was expressed to the same extent with endogenous and exogenous lithium, indicating that the two methods are interchangeable for estimation of dopamine-induced changes in tubular function.

Adult

Effects of the prostacyclin analogue iloprost on cyclosporin-induced renal hypoperfusion in stable renal transplant recipients.

BACKGROUND: The synthetic prostacyclin analogues have been proposed to protect against cyclosporin A (CsA) nephrotoxicity. The present study investigated the effect of infusion of the prostacyclin analogue iloprost on the acute CsA-induced renal hypoperfusion and hypofiltration in stable renal-transplant recipients. METHODS: The study included 10 stable renal-transplant recipients with good graft function (s-creatinine 90-170 micromol/l). Renal function and the acute renal haemodynamic and tubular response to an oral CsA-dose (Sandimmun Neoral, 3 mg.kg-1) were investigated with an infusion of iloprost (1 ng.kg-1.min-1) or placebo on 2 separate days. After an overnight fast, seven 30-min renal clearance periods were performed, two before infusion, three during infusion, and two recovery periods. An additional control clearance study without CsA intake or iloprost/placebo infusion was done in eight of the patients. RESULTS: CsA ingestion decreased ERPF and GFR significantly with a maximum decline at the end of the clearance study. Iloprost infusion abolished the CsA-induced decrease in ERPF, but had no effect on the CsA-induced decrease in GFR, leading to a significant decline in FF. Renal clearance of lithium (CLi)), used as an index of proximal tulbular outflow, decreased in parallel with GFR after CsA intake, with no additional effects of iloprost. Iloprost infusion decreased blood pressure and increased heart rate. CONCLUSION: Infusion of iloprost causes systemic and renal vasodilation, but has no effect on the CsA-induced decrease in GFR and CLi in stable renal transplant recipients.

Adult

Transperitoneal transport of sodium during hypertonic peritoneal dialysis.

The mechanisms of transperitoneal sodium transport during hypertonic peritoneal dialysis were evaluated by kinetic modelling. A total of six nested mathematical models were designed to elucidate the presence or absence of diffusive, non-lymphatic convective and lymphatic convective solute transport. Experimental results were obtained from 26 non-diabetic patients undergoing peritoneal dialysis. The model validation procedure demonstrated that only diffusive and non-lymphatic convective transport mechanisms were identifiable in the transperitoneal transport of sodium. Non-lymphatic convective sodium transport was the most important quantitative transport mechanism during the first 90 min of the dwell. Significant sodium sieving was demonstrated and explains the observation of hypernatremia in dialysis with hypertonic dialysis fluid.

Adult

The transport of phosphate between the plasma and dialysate compartments in peritoneal dialysis is influenced by an electric potential difference.

Six kinetic models of transperitoneal phosphate transport were formulated and validated on the basis of experimental results obtained from 22 non-diabetic patients undergoing peritoneal dialysis. The models were designed to elucidate the presence or absence of diffusive, non-lymphatic convective, and lymphatic convective phosphate transport. Calculations allowed for a 20% protein binding of phosphate. The validation procedure demonstrated that only diffusive and non-lymphatic convective phosphate transport mechanisms were identifiable. A lymphatic convective phosphate transport mechanism was not identifiable. Furthermore, it was demonstrated that the electrochemical gradient between plasma water and dialysate favours the diffusive phosphate transport, and both electric and chemical potentials must be taken into account in calculations of the transperitoneal phosphate transport.

Adult

Haematological status in elite long-distance runners: influence of body composition.

In 10 female and eight male Danish elite middle- and long-distance runners, haematological status, including blood volume, was examined. Haemoglobin, haematocrit and serum (s)-ferritin concentrations were all within the normal range. In both men and women, blood volume, plasma volume and erythrocyte volume were increased in relation to various reference values. However, the runners had a low body weight due to a reduced fat level, 9.5% (7.3-15.1%) fat for the women, 5.9% (5.0-8.8%) fat (median and ranges) for the men, measured by dual-energy X-ray absorptiometry (DEXA) scanning. When the runners' body weights were 'normalized' to a reference population (25% fat for women, 15% fat for men), only plasma volume remained increased in relation to body weight for the women, whereas all the volumes remained increased for the men. This confirms that endurance training induces a true increased plasma volume. The lower erythrocyte volume in the women compared with the men could be a consequence of the generally poorer iron status in the women, indicating that a combination of haemolysis, menstruation and low caloric (iron) intake makes it difficult for trained women to obtain optimal effects on erythrocyte volume equal to those obtained by trained men. Furthermore, the study emphasizes the importance of taking body composition into consideration when comparing well-trained athletes with a reference population.

Absorptiometry, Photon

The need for protein containing quality control materials for blood pH and electrolyte analyzers.

In clinical chemistry quality control refers to monitoring of precision and accuracy of the performance of analytical methods. Calibration solutions and (matrixed) control solutions are used in transferring accuracy between definitive method, reference method and field methods. For this purpose aqueous (protein-free), protein-containing and serum-based types of quality control materials having different matrices are available. Here are presented differences in behaviour between aqueous (protein-free) and protein-containing materials. Potentiometry with an electrochemical cell is an often used field method to determine pH and activity of electrolytes with an Ion-Selective Electrode (ISE). Basically, measured e.m.f.'s of calibrators and sample are translated into the activity of the ionic species of the sample by means of the Nernst equation. Besides the standard e.m.f. (E(zero)) of the electrochemical system, the measured e.m.f. includes the ISE-membrane e.m.f. (EISE) and depends on electrolyte type and its concentration and Eij depends on the composition and geometry of the salt bridge. Both EISE and Eij depend on the sample matrix. Protein-containing samples cause a negative bias on the e.m.f. at the liquid junction and a positive bias at the ISE. When EISE and Eij are compared to the mV span of the reference interval, the effects are large for Ca2+, Na+ and Cl-. Exactly the same effects exist for H+, K+, Li+ and Mg2+ but the inaccuracy is less critical for these ions. It may be concluded that only protein containing controls can detect an error that occurs only with measurements on plasma specimens. In practice this means that calibration is checked with protein-free solutions, but that measurements in plasma are best checked with protein-containing solutions.

Acid-Base Equilibrium

Changes in plasma ionized calcium and magnesium in blood donors after donation of 450 mL blood. Effects of hemodilution and Donnan equilibrium.

The plasma concentration of ionized calcium and ionized magnesium in 26 blood donors decreased 0.01 mmol/L during blood donation. The changes could be explained by admixture of interstitial fluid. About 162 mL or 36% of the donated blood was replaced by interstitial fluid during blood donation. From the changes in concentration and hematocrit we could estimate the composition of the added fluid. The concentration of protein was much lower than in plasma. The concentration of protein-bound and free cations was also lower, in accord with the Donnan theory. We conclude that blood donors immediately after blood donation are unsuited as a reference population for proteins and ions.

Albumins

Oxygen status of arterial and mixed venous blood.

OBJECTIVES: To describe system requirements for determination of the oxygen status of the blood using the oxygen status algorithm, a computer program. To define the oxygen extractivity, a term we propose, of the arterial blood and the oxygen extraction tension. To describe the different causes of tissue hypoxia, and the clinical interpretation of mixed venous oxygen tension and oxygen consumption rate. DATA SOURCES: Previous physiological and clinical studies related to oxygen status of the blood. DATA SYNTHESIS: The oxygen status algorithm calculates the oxygen extraction tension and generates the oxygen graph as an aid in interpreting oxygen status of the patient. A cybernetic scheme explains the causes of tissue hypoxia and forms the basis for the interpretation of changes in the mixed venous oxygen tension. A diagram with the mixed venous oxygen tension on the abscissa and the oxygen consumption rate on the ordinate illustrates the oxygen flux dependent oxygen consumption rate. A graph shows the relationship between mixed venous oxygen tension and oxygen delivery. CONCLUSIONS: The oxygen status of arterial blood comprises three groups of quantities related to arterial oxygen tension, hemoglobin oxygen capacity, and hemoglobin oxygen affinity. Disturbances in one of these groups may be compensated by opposite changes in one or both of the other. The oxygen extraction tension indicates the degree of compensation, and mixed venous oxygen tension is the key parameter in evaluating the presence of a state of oxygen flux-dependent oxidative metabolism.

Algorithms

The influence of patent blue V on pulse oximetry and haemoximetry.

Patent Blue V (PBV) is a blue dye solution which is used to visualize lymphatic vessels for surgical procedures. There has been some conflicting reports about the influence of this dye solution on pulse oximetry and haemoximetry, why we decided to: 1) produce a spectrum of PBV in plasma, 2) measure absorbances of full blood before and after addition of PBV and 3) to record the effect on the pulse oximeter and haemoximeter of an intradermal injection of PBV to a patient. Computer analysis of the blood gas measurements were carried out by the Oxygen Status Algorithm (OSA). The spectrum of PBV demonstrated a peak absorption at 640 nm and correspondingly the absorbances of the haemoximeter increased most significantly at 622 and 636 nm. These changes invalidated the determination of haemoglobin pigments, and the results should not be used. Computer analysis interpreted the measurements as a shift of the haemoglobin oxygen binding curve.

Absorption

Base excess or buffer base (strong ion difference) as measure of a non-respiratory acid-base disturbance.

Stewart in 1983 (Can J Physiol Pharmacol 1983: 61: 1444) reintroduced plasma buffer base under the name "strong ion difference" (SID). Buffer base was originally introduced by Singer and Hastings in 1948 (Medicine (Baltimore) 1948: 27: 223). Plasma buffer base, which is practically equal to the sum of bicarbonate and albuminate anions, may be increased due to an excess of base or due to an increased albumin concentration. Singer and Hastings did not consider changes in albumin as acid-base disorders and therefore used the base excess, i.e., the actual buffer base minus the buffer base at normal pH and pCO2, as measure of a non-respiratory acid-base disturbance. Stewart and followers, however, consider changes in albumin concentration to be acid-base disturbances: a patient with normal pH, pCO2, and base excess but with increased plasma buffer base due to increased plasma albumin concentration get the diagnoses metabolic (strong ion) alkalosis (because plasma buffer base is increased) combined with metabolic hyperalbuminaemic acidosis. Extrapolating to whole blood, anaemia and polycytaemia should represent types of metabolic alkalosis and acidosis, respectively. This reveals that the Stewart approach is absurd and anachronistic in the sense that an increase or decrease in any anion is interpreted as indicating an excess or deficit of a specific acid. In other words, a return to the archaic definitions of acids and bases as being the same as anions and cations. We conclude that the acid-base status (the hydrogen ion status) of blood and extracellular fluid is described in terms of the arterial pH, the arterial pCO2, and the extracellular base excess. It is measured with a modern pH-blood gas analyser. The electrolyte status of the plasma is a description of the most important electrolytes, usually measured in venous blood with a dedicated electrolyte analyser, i.e., Na+, Cl-, HCO3-, and K+. Albumin anions contribute significantly to the anions, but calculation requires measurement of pH in addition to albumin and is usually irrelevant. The bicarbonate concentration may be used as a screening parameter of a nonrespiratory acid-base disturbance when respiratory disturbances are taken into account. A disturbance in the hydrogen ion status automatically involves a disturbance in the electrolyte status, whereas the opposite need not be the case.

Acid-Base Equilibrium

Lactate, pH, and blood gas analysis in critically ill patients.

To obtain information about the relationship between different types of circulatory insufficiency, a series of oxygen parameters and plasma lactate, we have performed a pilot study comprising five patients with circulatory insufficiency. Plasma lactate was measured on a Stat Profile 7 (NOVA Biomedical, USA) and pH/blood gases on an ABL 520 (Radiometer Medical A/S, Denmark). Plasma lactate seems to be inversely related to base excess (BE), whereas no relationship to venous oxygen tension pO2(v) of the vein draining the inadequately perfused region seemed to exist. In one patient we made simultaneous measurements from v. cava inferior., v. cava superior., a. pulmonalis and a. radialis. Simultaneously sampled plasma lactate from different sites differed up to 0.6 mmol/L with the highest value obtained from v. cava inferior. This pilot study indicates that the increase of plasma lactate may vary with the type of circulatory disturbance and the sampling site.

Acid-Base Imbalance

Parameter estimation in six numerical models of transperitoneal transport of potassium in patients undergoing peritoneal dialysis.

The mechanisms of transperitoneal potassium transport during peritoneal dialysis were evaluated by validation of different mathematical models. The models were designed to elucidate the presence or absence of diffusive, non-lymphatic convective and lymphatic convective solute transport. Experimental results were obtained from 26 non-diabetic patients undergoing peritoneal dialysis. The validation procedure demonstrated that models including both diffusive and non-lymphatic convective solute transport were superior to the other models. Lymphatic convective solute transport was not identifiable. Furthermore, it was demonstrated experimentally that the equilibrium distribution of potassium between plasma water and dialysate did not differ from a Donnan equilibrium, although the precondition of the Donnan equilibrium was not fulfilled, i.e. the volumes on each side of the membrane were not constant and dialysate was not an ultrafiltrate of plasma.

Adult

No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients.

Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healthy volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium clearance, and urinary excretion of beta 2-microglobulin in any of the groups. The infusion of amino acids induced a comparable increase in GFR, lithium clearance, and the urinary excretion rate of beta 2-microglobulin in all three groups with no additional effect of fish oil. Thus, long-term renal transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.

Adult

An evaluation of twelve nested models of transperitoneal transport of urea: the one-compartment assumption is valid.

Models of transperitoneal urea transport are generally based on the one-compartment assumption, i.e. that the plasma water urea concentration in the peritoneal capillary bed is equal to the plasma water urea concentration in the peripheral veins. The aim of this study was to investigate the mechanism(s) of transperitoneal urea transport and to test the one-compartment assumption for urea. A total of 12 nested models were formulated and validated on the basis of experimental results obtained from 23 non-diabetic patients undergoing peritoneal dialysis. The validation procedure demonstrated that transperitoneal transport of urea probably involves diffusion, non-lymphatic convection and lymphatic convection. It was furthermore demonstrated that the inclusion of lymphatic convection changes the mass transfer area coefficient considerably. Finally, no deviation from the one-compartment assumption was demonstrated by our results.

Adult

International Federation of Clinical Chemistry (IFCC), Committee on pH, Blood Gases and Electrolytes: approved IFCC recommendation on definitions of quantities and conventions related to blood gases and pH.

Terminology in blood pH and gas analysis can be confusing, both because more than one name has been used for the same quantity, and because the same name has been used for more than one quantity. In addition, several calculated quantities are commonly used, but in some cases many different algorithms have been published for a single quantity. This document contains definitions of the most useful quantities in blood pH and gas analysis, and presents algorithms for the most useful calculated quantities. Use of these should lessen confusion among users and should also result in data that are more comparable among laboratories.

Algorithms

Composition of interstitial fluid.

In several previous experiments to determine the composition of interstitial fluid, the results varied depending on the collecting technique, and the electrolyte concentrations differed from those of a hypothetical ultrafiltrate of plasma. In our approach, since a change of position from standing to supine is accompanied by hemodilution with interstitial fluid, we used the changes in hematocrit and composition of plasma in 20 subjects before and after lying down to calculate the composition of added interstitial fluid. The estimated protein concentration was 20.6 g/L, and the concentrations of total calcium and magnesium were low, in accord with a lower concentration of protein-bound calcium and magnesium. The activity of free cations was also lower, in agreement with a Donnan equilibrium potential of 1 mV across the endothelium. The concentration of leukocytes and platelets decreased according to the hemodilution, implying no escape or mobilization of these elements.

Adult