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Quality assessment programs use internal and external quality control monitoring to assess test performance and emphasize adequate user training through periodic assessment of their competency. For point-of-care testing (POCT) of glucose within an institution, a 2-step quality assessment procedure is suggested. The first step of point-of-care (POC) glucose analyzer quality control involves the use of appropriate control materials to assess analyzer functionality, and the next step involves POC sample result confirmation by the central laboratory, to ensure consistent resulting for patients. Point-of-care glucose measurements and routine control material analysis are to be performed by the POCT personnel. The second step of quality assessment for glucose POCT involves qualified personnel from the central laboratory and requires periodic confirmatory testing of patient samples using appropriately qualified and traceable procedures of known analytical performance (eg, the routine chemistry analyzer glucose assay).

The most recent HemoCue glucose meter measures B-Glucose and converts the result to a plasma-equivalent glucose concentration (P-Glucose) by multiplying with 1.11. The authors studied the accuracy and precision of such a conversion with 120 samples from Herlev Hospital. The imprecision (CV) of the HemoCue glucose meter was 1.5%. HemoCue's conversion of B-Glucose to P-Glucose yielded a less than 10% difference from their routine method for P-Glucose (Eppendorf EBIO+) in more than 90% of samples. The mean bias was not statistically significantly different from zero. This performance satisfies the requirements for self-monitoring, point-of-care testing, and diagnostic determination of P-Glucose. The bias between HemoCue P-Glucose and Eppendorf P-Glucose in individual samples was related to hematocrit. The magnitude of the bias could only be partly explained by the difference in water concentration between blood and plasma. The glucose concentration in blood, but not in plasma, decreases with increasing hematocrit, because glucose in blood distributes like water, and the water concentration is lower in erythrocytes than in plasma. An additional hematocrit effect of the same magnitude and direction, perhaps caused by a slightly incorrect algorithm for background absorbance, was observed for HemoCue's B-Glucose. The two effects together could explain the observed bias in P-Glucose that was related to hematocrit.

Effects of hypobaric hypoxemia on endocrine and renal parameters of body fluid homeostasis were investigated in eight normal men during a sojourn of 8 days at an altitude of 4,559 m. Endocrine and renal responses to an osmotic stimulus (5% hypertonic saline, 3.6 ml/kg over 1 h) were investigated at sea level and on day 6at altitude. Several days of hypobaric hypoxemia reduced body weight (−2.1 ± 0.4 kg), increased plasma osmolality (+5.3 ± 1.4 mosmol/kgH2O), elevated blood pressure (+12 ± 1 mmHg), reduced creatinine clearance (122 ± 6 to 96 ± 10 ml/min), inhibited the renin system (19.5 ± 2.0 to 10.9 ± 0.9 mU/l) and plasma vasopressin (1.14 ± 0.16 to 0.38 ± 0.06 pg/ml), and doubled circulating levels of norepinephrine (103 ± 16 to 191 ± 35 pg/ml) and endothelin-1 (3.0 ± 0.2 to 6.3 ± 0.6 pg/ml), whereas urodilatin excretion rate decreased from day 2(all changes P< 0.05 compared with sea level). Plasma arginine vasopressin response and the antidiuretic response to hypertonic saline loading were unchanged, but the natriuretic response was attenuated. In conclusion, chronic hypobaric hypoxemia 1) elevates the set point of plasma osmolality-to-plasma vasopressin relationship, possibly because of concurrent hypertension, thereby causing hypovolemia and hyperosmolality, and 2) blunts the natriuretic response to hypertonic volume expansion, possibly because of elevated circulating levels of norepinephrine and endothelin, reduced urodilatin synthesis, or attenuated inhibition of the renin system.

AbstractA reference measurement procedure for substance concentration determination of total CO2in blood, plasma (the anticoagulant is usually heparin) or serum is described. The document covers the principle of the method, the materials and equipment needed and essential aspects of the procedure. The substance concentration of total CO2in blood, plasma or serum is accurately determined and therefore this procedure is recommended for assigning reference values to reference materials and for blood gas quality assurance in laboratories and by manufacturers of blood gas equipment.

AbstractA reference method is described for the determination of the substance concentration of ionized calcium in plasma by which ionized calcium (free or unbound) may be reliably determined on the basis of calibration with aqueous solutions with known concentration of ionized calcium. The composition of the calibration solutions is chosen such that the activity coefficient of the calcium ion is assumed to be identical both in the calibration solutions and in “normal” plasma, i.e.by convention, the ionic strength (Im) is 0.160 mol/kg. The convention is adopted of reporting ionized calcium measurements as concentration expressed as mmol/l.The proposed reference method for ionized calcium measurement in plasma is based on the use of a cell consisting of an external reference electrode with a saturated potassium chloride liquid/liquid junction in combination with a calcium ion-selective membrane electrode of defined construction and performance.Procedures for using the reference cell and a protocol for sample measurement are described. The preparation of the calibration solutions to be used are described in detail in Appendix A, secondary calibration solutions and check standards in Appendix B, and reference cell vessel design in Appendix C.

AbstractIon-selective electrodes (ISEs) respond to ion-activity and therefore do not sense substance concentration directly. However, it is recognized that sodium and potassium in plasma will continue to be expressed for clinical purposes in terms of substance concentration (mmol/l). A convention is proposed whereby for routine clinical purposes results of ISE measurements of sodium and potassium in undiluted plasma should be reported in terms of substance concentration (mmol/l). In specimens with normal concentrations of plasma water, total CO2, lipids, protein and pH, the values will concur with the total substance concentration as determined for example by flame atomic emission spectrometry (FAES) or ISE measurements on diluted samples. In specimens with abnormal concentrations of plasma water, the results will differ. However, under these circumstances, measurements of sodium and potassium by ISE in the undiluted sample will more appropriately reflect the activity of sodium and potassium and are therefore clinically more relevant than the determination in diluted samples. Detailed recommendations are made about practical procedures to achieve this. The recommended name for this quantity is the substance concentration of ionized sodiumor ionized potassiumin plasma, as opposed to total sodium or total potassium determined by, e.g.FAES, or ISE measurements on diluted samples.

The present study investigated whether the nitric oxide (NO) system is involved in cyclosporin A (CsA)-induced changes in cardiovascular and renal function in man.

Nabumetone, a newer non-steroidal anti-inflammatory drug (NSAID) which preferentially blocks cyclo-oxygenase-2 activity, may be less nephrotoxic than indomethacin. This study tested whether nabumetone has effects different from those of indomethacin on exercise-induced changes in renal function and the renin–aldosterone system. In a randomized fashion, ten subjects were studied after indomethacin (100 mg), nabumetone (1 g) or no medication (control) administered orally at 22.00 hours on the day before each study day, and again at 8.00 hours upon arrival at the laboratory. Renal function was studied at baseline, during graded 20-min exercise sessions at 25%, 50% and 75% of the maximal oxygen uptake rate, and subsequently during two 1-h recovery periods. Heart rate, arterial blood pressure, cardiac output and plasma catecholamines at rest and during exercise were not altered by indomethacin or nabumetone. Indomethacin decreased urinary rates of excretion of 6-oxo-prostaglandin F1α (6-oxo-PGF1α) and thromboxane B2 in all study periods. Nabumetone decreased 6-oxo-PGF1α excretion during and after exercise. Excretion rates for PGE2 did not change. Neither indomethacin nor nabumetone changed baseline values or exercise-induced decreases in renal plasma flow or glomerular filtration rate. Indomethacin, but not nabumetone, decreased sodium excretion, urine flow rate and free water clearance. The renal response to exercise, however, remained unchanged. In contrast with nabumatone, indomethacin decreased the plasma renin concentration. Thus, during exercise, nabumetone may decrease the excretion of 6-oxo-PGF1α by inhibition of cyclo-oxygenase-1 or by inhibition of specific exercise-induced activation of cyclo-oxygenase-2, or both. None of the drugs changed the renal response to exercise. Inhibition by indomethacin of angiotensin II and thromboxane A2 synthesis may, during exercise, counterbalance renal vasoconstriction caused by blockade of vasodilatory prostaglandins.

“Ionized calcium”, in clinical chemistry, designates the free calcium ions which are present in the biological fluids as hydrated ions: Ca2+, 12 H2O. The calcium ion selective electrode measures differences in activity, however, values are reported not as the activity, but as the activity divided by the activity coefficient (γ) of Ca2+ in “normal plasma”. The latter is assumed to be equal to the activity coefficient (γ) in a calibration solution of CaCl2+ NaCl with an ionic strength of 0,16 mol kg-1.We have estimated the activity coefficient in this calibration solution to be γCa2+ = 0,3040 (molal basis) or γCa2+ = 0,3048 (substance concentration basis). The derivation of γCa2+ is based on a convention for derivation of the activity coefficient of the chloride ion. We have used the Debye-Huckel equation extended by the Stokes-Robinson hydration theory plus the Bates-Staples-Robinson convention that the hydration number for Cl- is zero.International consensus is needed concerning the convention to be used for deriving the activity coefficient of Ca2+ in the calibration solutions and concerning the most appropriate value for γCa2+ in normal plasma.

The effects of short and long duration exercise on serum erythropoietin concentrations [EPO]s were studied in seven male cross-country skiers of national team standard and eight male marathon runners, respectively. The short duration exercise was performed as 60 min of cycling at an intensity of 80%–95% of maximal heart rate. Arterial blood oxygen saturations monitored by pulse-oximetry remained unchanged throughout exercise. The partial pressure of O2 at which haemoglobin was half-saturated with O2 calculated from forearm venous blood gas tension and blood O2 saturation, and the erythrocyte 2,3-diphosphoglycerate did not change significantly during the exercise. Blood lactate concentrations were increased at the end of exercise [from 1.3 (SEM 0.1) to 3.6 (SEM 0.3) mmol · 1-1]. The [EPO]s determined (by enzyme-linked immunosorbent assay) pre-exercise, 5 min, 6 h, 19 h, and 30 h after the exercise were unchanged [from 16.1 (SEM 2.6) to 19.1 (SEM 3.2), 17.9 (SEM 3.0), 17.0 (SEM 2.5), and 18.6 (SEM 2.9) U·l-1, respectively]. The [EPO]s were not correlated to the earlier parameters. The long duration exercise consisted of habitual training, a 3 week break from training followed by 2 and 4 weeks of re-training. The [EPO]s, body fat (BF), and serum free-testosterone concentrations determined at the end of each period remained unchanged. The maximal oxygen uptakes were decreased after the break from training and increased during retraining (P=0.04). Body mass (mb) increased after the break in training (P=0.02). The [EPO]s were correlated to BF,r=0.42,P=0.02;mb,r=0.45,P=0.01; and free-testosterone concentrations,r=0.44,P=0.01. Thus, short and long-duration exercise had no direct influence on [EPO]s; but relationships among [EPO]s, free-testosterone concentrations and body composition were noted.

1.Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic renal cell carcinoma. 2.Patients were studied before and after 72 h of continuous intravenous infusion of recombinant interleukin-2 (18×106 i.u.·24 h-1·m-2) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium (CLi) was used as an index of proximal tubular outflow. 3.Treatment caused a transient decrease in mean arterial blood pressure and systemic vascular resistance, but cardiac output remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance decreased from 1.10 (0.63/1.19) ml/min to 0.17 (0.18/0.32) ml/min (P = 0.003). Glomerular filtration rate remained unchanged, whereas the median CLi decreased from 26 (17/32) ml/min to 17 (10/21) ml/min (P = 0.008). Calculated absolute proximal reabsorption rate of water increased from 63 (40/69) ml/min to 71 (47/82) ml/min (P = 0.04). The urinary excretion rate of thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto-prostaglandin-F1α increased by 98% (P = 0.022) and 175% (P = 0.022) respectively. 4.The study suggests a specific recombinant interleukin-2-induced renal vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment.

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 μg 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 (203–28.2)% (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.

1. Previous histological studies have demonstrated partial reinnervation of the human transplanted kidney. However, it remains unknown whether this reinnervation is of any functional significance. 2. The effects of noradrenaline infusion (2 μgh−1kg−1) and lower body negative pressure (−27 mmHg) on renal haemodynamics, sodium excretion and tubular function were investigated in 25 renal transplant recipients and 10 normal subjects. Sixteen of the transplant recipients had all been transplanted for more than 27 months, and nine had all been transplanted for less than 2 months. 3. After an overnight fast, the subjects were water-loaded, and clearance studies were performed with a 1 h baseline period, a 1 h period with noradrenaline infusion, another 1 h baseline period, and a final 1 h period with lower body negative pressure. 4. During noradrenaline infusion the relative decrease in effective renal plasma flow, glomerular filtration rate and clearance of lithium and sodium was significantly more pronounced in the long-term transplanted patients than in the control subjects. 5. Lower body negative pressure only depressed the glomerular filtration rate significantly in the control subjects. Further, the relative decrease in effective renal plasma flow and clearance of lithium and sodium was significantly greater in the control subjects than in the two groups of transplanted patients. 6. The present study thus demonstrated that in short- and long-term transplanted kidneys in man, supersensitivity to circulating noradrenaline and an inadequate response to lower body negative pressure was present. This strongly suggests that the human transplanted kidney remains functionally denervated.

302 samples from 22 normal pregnancies were frozen and kept for the analysis of free calcium ion concentration [Ca2+ 7.4 at 37°c and pH 7.40, after equilibration with CO2. Individual regressions were performed, and the concentration was found to increase slightly but significantly (5%, p<0.005) with the progress of the pregnancy. This increase excludes hypocalcemia as the cause of parathyroid overactivity during pregnancy, and a higher set point of the parathyrin (PTH) secretion is suggested.

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·1^-1, post-hypoxia 10.24 (SEM 0.95) U·1^-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.

To investigate the effect of cyclosporine A (CsA; Sandimmun Neoral) on systemic and renal hemodynamics, tubular function, and sodium excretion in healthy volunteers. Furthermore, we studied whether CsA enhances the systemic and renal hemodynamic sensitivity to norepinephrine.

The model of the hemoglobin-oxygen equilibrium represented by the TANH-equation is incorporated in the Oxygen Status Algorithm, a computer program for calculating and displaying the oxygen status and the acid-base status of the blood. In the presence of carbon monoxide it is necessary to take the Haldane equation into account. We here describe the necessary equations and methods for iterative solutions. The validity of the Haldane equation has previously been demonstrated by Zwart et al.(J Appl Physiol 1984; 57: 14-20). We have performed a few experiments to confirm this. Like Zwart et al.we find a small deviation from the theory, but in the opposite direction, i.e. the measured p50values are slightly higher than predicted.We conclude that the Haldane equation adequately accounts for the carbon monoxide effect up to 30 % carboxy-hemoglobin, but further studies are needed to confirm or exclude any minor deviation from the Haldane relationship which may be significant at higher carboxy-hemoglobin fractions.

Fogh-Andersen N, Siggaard-Andersen O. Standardizing and Reporting Results from Mg2+ISEs, with Some Notes on Sample Handling. Scand J Clin Lab Invest 1994; 54, Suppl 217: 89-96.Mg by ion-selective electrode (ISE) is a direct measure of the reactivity of magnesium ions in plasma, which may be clinically and physiologically more relevant than the concentration of total magnesium. The Mg2+-ISE will build up an electric potential which exactly matches the chemical potential of Mg2+in the sample. Chemical potential (= chemical work per unit of Mg2+) has no absolute value and is difficult to visualize. The results must be standardized, either to the magnesium concentration in a protein-free calibrator or to the concentration of total magnesium in plasma. The constant factor relationship will assure identical clinical discrimination, no matter how the Mg2+-ISE results are reported. The general opinion of a conference held in Orlando, Florida in March of 1993 was to define free Mg2+in plasma as the concentration of magnesium in a saline standard with the same magnesium activity as the sample, and report it in SI units (mmol/L). The small differences in liquid junction potential and water concentration will provide a value for free Mg2+in plasma of approximately 103% of the true concentration, or 96% of the true molality. Differences between plasma and interstitial fluid and Donnan equilibria across the vascular endothelium will affect the result, so sampling should take place with the patient at rest to assure a stable plasma volume. Since heparin binds magnesium, it is preferable to use serum or plasma with a minimum of heparin which has been titrated with magnesium. Binding of Mg2+depends on pH, and pH of circulating plasma is not constant. Furthermore, pH may change during and after sampling. The Mg2+-ISE system should therefore include pH and allow correction of free Mg2+to pH 7.4.

The renal plasma clearance of the 51Chromium labeled complex with ethyl-enediaminetetraacetic acid ([51Cr]EDTA) underestimates that of inulin by 5-15%. Interaction of the anionic CrEDTA with polyanions in the glomerular filter and tubular reabsorption may add to the difference. A re-examination of the protein binding of CrEDTA showed that the protein binding is not negligible, because following ultra filtration in vitro, the morality of CrEDTA was 5 % lower in the ultra filtrates than in the retentates. With a correction for the distribution of small ions this indicates at least 10% bincling to human albumin. pKA ⇔ 7.36 was found for the equilibrium CrEDTA(H2O)- ⇔ CrEDTA(OH)2- +H +. One CrEDTA molecule carries one or two negative charges at near physiological pH. Renal plasma clearance of [51Cr]EDTA may be corrected to glomerular filtration rate (GFR) by multiplication with 1.10.

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.

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 CO 2 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% O 2 in nitrogen), mean serum-EPO increased by 28% [baseline 8.00 (SEM 0.84) U·1 -1, post-hypoxia 10.24 (SEM 0.95) U·1 -1, P=0.005]. Normocapnic hypoxia was produced by the addition of CO 2 (10% Co 2 with 10% O 2) 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.

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 hematwrit 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.

The present study evaluated whether chronically administered low-dose (<5 mg/kg) ciclosporin A (CsA) affects renal haemodynamics and tubular function in renal transplant recipients (RTx) when studied at nadir CsA blood levels. The renal clearance of lithium was used as an index of proximal tubular outflow of sodium and water. Effective renal plasma flow, glomerular filtration rate, and renal clearance of lithium were studied in 67 stable non-diabetic RTx and 44 healthy controls. Forty-eight of the RTx were treated with CsA, prednisone, and azathioprine. Nineteen were treated exclusively with prednisone and azathioprine. In RTx with a good graft function (serum-creatinine <125 µmol/l), no specific CsA-induced renal haemodynamic and tubular dysfunctions were evident. In CsA-treated RTx with a slightly reduced renal function (serum creatinine 125–180 µmol/l) a decrease in fractional proximal tubular reabsorption was found. The renal clearances of urate and magnesium were comparable between RTx treated with or without CsA, and a significant correlation between glomerular filtration rate and renal clearance of urate was found. CsA-treated RTx had a significantly higher blood pressure, independent of glomerular filtration rate and segmental tubular function. In conclusion, at nadir CsA blood levels, no specific CsA-induced tubular dysfunction evaluated by the renal lithium clearance method could be demonstrated in RTx receiving chronically low-dose CsA. The hyperuricaemia commonly seen in RTx seems to be mainly caused by the reduced glomerular filtration rate.

Continuous measurement of sO2and hematocrit during extracorporeal circulation has become feasible using reflection spectrophotometry. We have compared simultaneous measurements with in-line reflection spectrophotometry (OxySat-2® American Bent-ley), and in-vitro transmission spectrophotometry (OSM3 Hemoximeter® Radiometer) on discrete samples.In 8 patients undergoing open heart surgery during hypothermic extracorporeal circulation with hemodilution arterial and venous sO2and hematocrit were measured continuous in-line in the extracorporeal circuit. Simultaneous and anaerobically collected blood samples were analyzed within one minute in the OSM3. The relationship between hemoglobin concentration (cHb) measured in the OSM3 and hematocrit (Hct) measured by the OxySat-2 was estimated from a mean cell hemoglobin concentration of 20 mmol·l-1, i.e. Hct () 100 cHb20.There was a systematic difference between the OxySat-2 and the reference method for sO 2

“Ionized calcium”, in clinical chemistry, designates the free calcium ions which are present in the biological fluids as hydrated ions: Ca2, 12 H2O. The calcium ion selective electrode measures differences in activity, however, values are reported not as the activity, but as the activity divided by the activity coefficient (γ) of Ca2in “normal plasma”. The latter is assumed to be equal to the activity coefficient (γ) in a calibration solution of CaCl2 NaCl with an ionic strength of 0,16 mol kg−1.We have estimated the activity coefficient in this calibration solution to be γCa2 0,3040 (molal basis) or γCa2 0,3048 (substance concentration basis). The derivation of γCa2is based on a convention for derivation of the activity coefficient of the chloride ion. We have used the Debye-Hückel equation extended by the Stokes-Robinson hydration theory plus the Bates-Staples-Robinson convention that the hydration number for Cl−is zero.International consensus is needed concerning the convention to be used for deriving the activity coefficient of Ca2in the calibration solutions and concerning the most appropriate value for γCa2in normal plasma.

Summary: To investigate the effect of low doses of intranasal salmon calcitonin on plasma cyclic AMP (cAMP) and serum ionized calcium, 40 healthy postmenopausal women were randomized to receive a single dose of either placebo or 50, 100, or 200 IU of salmon calcitonin as a nasal spray. Blood samples were collected throughout an 8-hour period. None of the doses could provoke detectable hypocalcemia, whereas 100 and 200 IU of salmon calcitonin were associated with an increase in plasma cAMP after 15 minutes. Measurable plasma levels of salmon calcitonin were demonstrated in all active treatment groups, and the calculated areas under the curves showed a dose-dependent increase.

Objective - To determine: 1) if 18 mg iron daily is sufficient to cover the iron need during normal pregnancy, and 2) if women, who will not need iron supplementation during pregnancy, can be identified by early screening.Design - In a prospective study the women were randomized to receive either 18 or 100 mg iron daily from the 16th week until delivery. Investigations were performed in the 16th, 30th, and 38th week.Subjects - Healthy nulliparae (n = 43) experiencing a normal singleton pregnancy. Only women with a normal hemoglobin concentration and intact iron stores (S-Ferritin 15 ug/ I) in the 16th week were included.Variables - These measurements were done consecutively: 1) the total hemoglobin mass (with carbon monoxide), 2) S-Ferritin, 3) S-Transferrin, 4) S-Iron, 5) red cell indices (hemoglobin concentration, hematocrit, MCV, MCHC).Results - Changes in red cell indices and S-Transferrin were equal in the two groups. There was no significant difference in S-Ferritin in the 16th week. In the 30th week 3 women (14%) in the 100 mg group and 11 (52%) in the 18 mg group had empty iron stores (p<0.05). The numbers were 1 (5%) and 15 (72%) in the 38th week (p< 0.0001). The increment in total hemoglobin mass was equal in the two groups from the 16th to the 30th week (13% in the 100 mg group and 12% in the 18 mg group). From the 30th to the 38th week the increment in total hemoglobin mass was largest in the 100 mg group (8.1% versus 2.7%, p<0.05). Conclusion - Despite a normal hemoglobin concentration and intact iron stores in the 16th week, an iron supplementation of 18 mg daily is not sufficient to cover the iron need in many pregnant women in the 3rd trimester.

Background. The reports on plasma concentrations and physiological function of atrial natriuretic peptide (ANP) during pregnancy are conflicting. In a recent prospective study, including 40 healthy primigravidae, we found a highly significant decrease in the plasma concentration of ANP (p-ANP) during the third trimester and the results indicated that ANP takes part in regulation of blood volume and renal function during pregnancy as in the nonpregnant state. In order to test these results, a study was performed in primigravidae with twin pregnancy to test if the accentuated physiological changes here were followed by a corresponding greater decrease in p-ANP.Methods. Ten healthy primigravidae with twin pregnancy were examined four times during pregnancy plus 12 weeks after delivery. Each time the following were measured: p-ANP, aldosterone, renin, blood volume (carbon monoxide), cardiac output (Doppler), blood pressure and sodium excretion. Interdependence of the changes in ANP and in the other parameters was tested using Spearman's rank correlation test on the delta (ΔΔ)-values (the differences in measurements between investigations). The results were compared to the results obtained during singleton pregnancy using the Mann-Whitney rank sum test.Results. All pregnant values of p-ANP during twin pregnancy were lower than 12 weeks after delivery, p< 0.01. In the 20th, 28th, and 32nd week p-ANP was lower in twin pregnancy than in singleton pregnancy, p< 0.05. There was a negative correlation between changes in p-ANP and changes in: a) blood volume, R=-0.8, p< 0.0001, b) aldosterone, R=-0.66, p< 0.0001, c) renin, R=-0.52, p< 0.01, d) cardiac output, R=-0.68, p< 0.0001. There was a positive correlation between changes in p-ANP and changes in: a) fractional excretion of sodium, R = 0.73, p< 0.0001, and b) total peripheral resistance, R = 0.61, p< 0.0001.Conclusion. The results suggest that the competitive relationship between ANP and the renin-aldosterone system in regulating sodium balance and fluid volume is preserved during pregnancy. The vasodilatation during pregnancy is not mediated by ANP.

Thomsen HS, Vestergaard A, Nielsen SL, Fogh-Andersen N, Golman K, Dorph S. Renal clearance of an ionic high-osmolar and a nonionic low-osmolar contrast medium. Invest Radiol 1991;26564-568.

Continuous measurement of sO2 and hematocrit during extracorporeal circulation has become feasible using reflection spectrophotometry. We have compared simultaneous measurements with in-line reflection spectrophotometry (OxySat-2® American Bent-ley), and in-vitro transmission spectrophotometry (OSM3 Hemoximeter® Radiometer) on discrete samples.In 8 patients undergoing open heart surgery during hypothermic extracorporeal circulation with hemodilution arterial and venous sO2 and hematocrit were measured continuous in-line in the extracorporeal circuit. Simultaneous and anaerobically collected blood samples were analyzed within one minute in the OSM3. The relationship between hemoglobin concentration (cHb) measured in the OSM3 and hematocrit (Hct) measured by the OxySat-2 was estimated from a mean cell hemoglobin concentration of 20 mmol·l-1, i.e. Hct (%) = 100 cHb/20.There was a systematic difference between the OxySat-2 and the reference method for sO 2

18 chronic dialysis patients with renal anemia were examined before and after three months of regular treatment with recombinant human erythropoietin (EPO). All patients responded with an increase in hemoglobin concentration (cHb). The target cHb of 7.0 mmol/L was subsequently maintained by one subcutaneous injection a week, obviating the need of blood transfusions. The amount of circulating hemoglobin and the volume of erythrocytes increased, but the plasma volume simultaneously decreased, maintaining a constant blood volume. Although some of the individual blood volumes varied, the relation between circulating hemoglobin and the hemoglobin concentration still existed. We conclude that the hemoglobin concentration gives an accurate measure of the degree of anemia, and measurement of circulating hemoglobin is unnecessary during routine treatment of dialysis patients with EPO.

Fogh-Andersen N, Siggaard-Andersen O. Standardizing and Reporting Results from Mg2+ ISEs, with Some Notes on Sample Handling. Scand J Clin Lab Invest 1994; 54, Suppl 217: 89-96.Mg by ion-selective electrode (ISE) is a direct measure of the reactivity of magnesium ions in plasma, which may be clinically and physiologically more relevant than the concentration of total magnesium. The Mg2+-ISE will build up an electric potential which exactly matches the chemical potential of Mg2+ in the sample. Chemical potential (= chemical work per unit of Mg2+) has no absolute value and is difficult to visualize. The results must be standardized, either to the magnesium concentration in a protein-free calibrator or to the concentration of total magnesium in plasma. The constant factor relationship will assure identical clinical discrimination, no matter how the Mg2+-ISE results are reported. The general opinion of a conference held in Orlando, Florida in March of 1993 was to define free Mg2+ in plasma as the concentration of magnesium in a saline standard with the same magnesium activity as the sample, and report it in SI units (mmol/L). The small differences in liquid junction potential and water concentration will provide a value for free Mg2+ in plasma of approximately 103% of the true concentration, or 96% of the true molality. Differences between plasma and interstitial fluid and Donnan equilibria across the vascular endothelium will affect the result, so sampling should take place with the patient at rest to assure a stable plasma volume. Since heparin binds magnesium, it is preferable to use serum or plasma with a minimum of heparin which has been titrated with magnesium. Binding of Mg2+ depends on pH, and pH of circulating plasma is not constant. Furthermore, pH may change during and after sampling. The Mg2+-ISE system should therefore include pH and allow correction of free Mg2+ to pH 7.4.

The model of the hemoglobin-oxygen equilibrium represented by the TANH-equation is incorporated in the Oxygen Status Algorithm, a computer program for calculating and displaying the oxygen status and the acid-base status of the blood. In the presence of carbon monoxide it is necessary to take the Haldane equation into account. We here describe the necessary equations and methods for iterative solutions. The validity of the Haldane equation has previously been demonstrated by Zwart et al. (J Appl Physiol 1984; 57: 14-20). We have performed a few experiments to confirm this. Like Zwart et al. we find a small deviation from the theory, but in the opposite direction, i.e. the measured p50 values are slightly higher than predicted.We conclude that the Haldane equation adequately accounts for the carbon monoxide effect up to 30 % carboxy-hemoglobin, but further studies are needed to confirm or exclude any minor deviation from the Haldane relationship which may be significant at higher carboxy-hemoglobin fractions.

Exposure to acute hypoxia is associated with changes in body fluid homeostasis and plasma volume (PV). This study compared a dye dilution technique using Evans' blue (PV Evans') with a carbon monoxide (CO) rebreathing method (PV CO) for measurements of PV in ten normal subjects at sea level and again 24 h after rapid passive ascent to high altitude (4,350 m). Hypobaric hypoxia decreased arterial oxygen saturation to 79 (74–83)% (mean with 95% confidence intervals). The PV Evans' remained unchanged from 3.49 (3.30–3.68) l at sea level to 3.46 (3.24–3.68) l at high altitude. In contrast PV CO decreased from 3.39 (3.17–3.61) l at sea level to 3.04 (2.75–3.33) l at high altitude ( P < 0.05). Compared with sea level, this resulted in an increase of the mean bias between the two methods [from 0.11 (-0.05–0.27) l at sea level to 0.43 (0.26–0.60) l at high altitude] so that the ratio between PV Evans' and PV COincreased from 1.04 (0.99–1.09) at sea level to 1.15 (1.06–1.24) at high altitude ( P < 0.05). In conclusion, the two methods were not interchangeable as measures of hypoxia-induced changes in PV. The mechanism responsible for the bias remains unknown, but it is suggested that the results may reflect a redistribution of albumin caused by the combined effects in hypoxia of both an increased capillary permeability to albumin and a decrease in PV. As a result, the small perivascular compartment of albumin beyond the endothelium may increase without changes in the overall albumin distribution volume.

1. The effect of a single dose of lithium on renal function before and during intravenous infusion of dopamine (3 μg min−1 kg−1) was investigated in 12 healthy males. In a double-blind and randomized design, 450 mg or 600 mg of lithium carbonate or placebo was administered orally at 22.00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1 h baseline period and three 1 h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 ± 0.35 ml/min, but with lithium it increased to 1.25 ± 0.44 (P < 0.001) and 1.17 ± 0.46 ml/min (P < 0.01) after 450 and 600 mg, respectively. Urine flow rates were unchanged compared with placebo. Lithium did not significantly affect glomerular filtration rate, but both doses slightly increased effective renal plasma flow by 7% (P < 0.05) and 10% (P < 0.01), respectively. 3. The maximal natriuretic and diuretic effects of dopamine were not reduced by lithium, but the percentage increases in sodium clearance were significantly diminished after 450 mg (P < 0.01) and 600 mg (P < 0.001) of lithium. Lithium had no effect on dopamine-induced changes in effective renal plasma flow, glomerular filtration rate or osmolal clearance. Neither lithium nor dopamine influenced plasma concentrations of renin, aldosterone or atrial natriuretic peptide. 4. In conclusion, single test doses of lithium, as normally used in lithium clearance studies, increase baseline values of sodium clearance and effective renal plasma flow. Although these effects of lithium do not reduce the maximal renal responses to low-dose dopamine, they result in an underestimation of the percentage increase in sodium excretion.

In solutions containing 160 mmol/1 Na+and K+, respectively, measurements with an ion-selective electrode system (KNA1, Radiometer), showed apparent falls in the respective Na+and K+concentrations when CI- was replaced by HCO-3. After correction for the change in liquid junction potential, the fall was 9.2 mmol/1 for Na+and 7.3 mmol/1 for K+. On the basis of these findings we conclude that sodium bicarbonate and potassium bicarbonate are not fully dissociated in solution, and that NaHCO3d` and KHCO3d` do exist as chemical components with association constants of 0.72 and 0.55, respectively. Using these association constants, normal plasma will contain 1.2 mmol/1 NaHCO3d` and 0.03 mmol/1 KHCO3d`. Thus NaHCO3d` accounts for virtually the same amount of CO2as the physically dissolved fraction. A review of all the currently known CO2species in plasma suggests that there may be a residue of about 2 mmol/1 of unknown CO2species in normal plasma.

The observation that the ionised calcium concentration is higher if measured in the original serum sample than in an ultrafiltrate is examined by means of a theoretical model. It is concluded that this difference is a predictable consequence of the Donnan equilibrium and is not a result of protein interference with the calcium-specific electrode.

A real point-of-care analysis system for counting platelets and white blood cells (with three-part differential counts: lymphocytes, monocytes, and granulocytes) and measurement of hemoglobin in whole blood is described. The system comprises a disposable cartridge and a stationary instrument with a cradle for insertion of the cartridge. The procedure for analysis is very simple. The user is required only to apply a drop of blood to the capillary inlet of the cartridge and place it into the instrument cradle. The remainder of the test is carried out automatically, and the result is obtained within 3 minutes.

As it has been suggested that parathyroid hormone (PTH) is implicated in the pathophysiology of essential hypertension, the effects of PTH(1-34) were assessed during infusion over 120 min in ten men with essential hypertension and in ten healthy men. Ionized calcium was kept constant by a clamping technique. Mean arterial blood pressure fell slightly in the patients (116 mm Hg, median, before, and 108 mm Hg during the infusion, P < .01), but remained unchanged in the controls (median 87 mm Hg). The pulse rate rose to a similar extent in the two groups, but cardiac output, measured by the CO2 rebreathing technique, was unchanged. The glomerular filtration rate (GFR) was slightly lower in the hypertensives than in the controls at baseline (92 v 109 mL/min, P < .02), but it increased similarly during PTH infusion in both groups (+13% v +9%, medians), as did the effective renal plasma flow (+50% v +38%). The urinary rate of sodium excretion, which was similar at baseline, increased more in the patients than in the controls (+191% v +46%, P < .05); this was mainly attributable to a reduction in the tubular reabsorption of sodium. Calculations based on lithium clearance indicated that mainly the proximal tubular reabsorption of sodium decreased during PTH infusion. Baseline plasma PTH(1-84) was higher in the patients than in the controls (20.5 ng/L v 16.5 ng/L, P < .05). The baseline plasma values of renin, aldosterone, atrial natriuretic peptide, endothelin, and noradrenaline were similar in the two groups. During infusion of PTH, renin increased less in the patients than in the controls (P < .02), and aldosterone increased only in the controls (P < .01). The other hormonal values remained unchanged. In conclusion, the patients with essential hypertension had increased baseline PTH values, but nevertheless PTH had more marked vasodilative and natriuretic effects than in the controls. PTH thus seems to counteract rather than aggravate elevation of blood pressure in these patients. Am J Hypertens 1997;10:1326–1334 © 1997 American Journal of Hypertension, Ltd.