All analyzers with ion-selective electrodes for ionized magnesium (iMg) should yield comparable and unbiased results. The prerequisite to achieve this goal is to reach consensus on sampling, measurement and reporting. The recommended guidelines for sampling, measurement and reporting iMg in plasma ("plasma" refers to circulating plasma and the forms in which it is sampled: the plasma phase of anticoagulated whole blood, plasma separated from blood cells, or serum) or blood, referring to the substance concentration of iMg in the calibrants, will provide results for iMg that are approximately 3% greater than its true concentration, and 4% less than its true molality. Binding of magnesium to proteins and ligands in plasma and blood is pH-dependent. Therefore, pH should be simultaneously measured to allow adjustment of iMg concentration to pH 7.4. The substance concentration of iMg may be physiologically and consequently clinically more relevant than the substance concentration of total magnesium.

Abstract We compared the manually performed LUMItest® procalcitonin (PCT) assay with the newly developed fully mechanized Kryptor® PCT assay and determined the essential assay characteristics of this assay. The new Kryptor® PCT assay was evaluated according to modified NCCLS EP-10/EP-6 protocols in five different laboratories. Samples from 696 patients were assayed using the original LUMItest® PCT assay and the new Kryptor® PCT assay. Possible interference by hemoglobin, triglycerides and bilirubin was evaluated by spiking patient plasma with the appropriate substances. The functional assay sensitivity (FAS) was determined by analyzing samples with low PCT concentrations. The FAS of the new Kryptor® PCT assay was 0.04 ng/ml and the imprecision within- and between-series below 5% and below 10%, respectively. Within the smallest range of determination, from 0.3 ng/ml to 50 ng/ml, common to the LUMItest® PCT assay (x) and the Kryptor® PCT assay (y) the values correlated well: y=0.64+0.94x, s.xy=2.78 ng/ml. The performance characteristics of the Kryptor® PCT assay are fully compatible with the intended clinical use. The assay allows determination of PCT in a turnaround time (TAT) of about 20 minutes and thus is adequate for STAT analyses.

In principle, flame photometry measures substance concentration, and ion-selective electrodes (ISEs) measure ion activity. However, the situation regarding the comparison of results from the two techniques when applied to blood plasma is complex. The problem can be approached experimentally from the point of view of calibration of ion-selective electrodes with concentration calibrators, and similar procedures are adopted for commercial ISE-based clinical analysers. Nevertheless, there is interest in the evaluation of single ion activities in blood plasma and solutions simulating its ionic composition. Solutions are proposed for calibrating ion-selective electrodes for the determination of sodium, potassium and calcium. It is recommended that the values for single ion activities derived from the Pitzer treatment of mixed electrolyte solutions be adopted, because, although this has some empirical features, it has a sounder theoretical basis than the previously used Stokes-Robinson-Bates hydration approach.

In principle, flame photometry measures substance concentration, and ion-selective electrodes (ISEs) measure ion activity. However, the situation regarding the comparison of results from the two techniques when applied to blood plasma is complex. The problem can be approached experimentally from the point of view of calibration of ion-selective electrodes with concentration calibrators, and similar procedures are adopted for commercial ISE-based clinical analysers. Nevertheless, there is interest in the evaluation of single ion activities in blood plasma and solutions simulating its ionic composition. Solutions are proposed for calibrating ion-selective electrodes for the determination of sodium, potassium and calcium. It is recommended that the values for single ion activities derived from the Pitzer treatment of mixed electrolyte solutions be adopted, because, although this has some empirical features, it has a sounder theoretical basis than the previously used Stokes-Robinson-Bates hydration approach.

The relationship between the concentration of ionized magnesium and total magnesium was investigated. Ionized magnesium was determined by an ion-selective electrode (Microlyte 6, KONE) and the result was adjusted to pH 7.4. Total magnesium concentration was measured by flame atomic absorption spectrometry. Total and ionized magnesium were only closely related in marked hypermagnesaemia (> 1.2 mmol/L), but correlation was poor in samples with slightly elevated total concentration or in hypomagnesaemia (< 0.65 mmol/L). The relationship was dependent on protein concentration. The agreement between total and ionized magnesium was acceptable in normoproteinaemia, but in hypoproteinaemia (< 40 g/L) total magnesium concentration was classified in 35% of the samples as below or within the reference interval, whereas the pertinent ionized magnesium concentration was normal or elevated, instead. Studies on paraproteinaemic sera clearly demonstrated that albumin concentration is most important for the size of the protein bound fraction.

The International,Federation of Clinical Chemistry (IFCC) and the National Committee for Clinical Laboratory Standards (NCCLS) are about to recommend to adjust sodium and potassium measurements by ion-selective electrodes in undiluted samples to the amount of substance concentration in the sample as determined, e.g., by flame atomic emission spectrometry. The adjustment is only valid in case of normal standardized sera (or plasma), implying ''normal'' water concentration (normal concentration of proteins, lipids or other macromolecules), ''normal'' binding of the pertinent electrolytes and ''normal'' coefficient of activity. If these criteria are not met, results obtained by ''adjusted'' ISE's will differ from total molar concentration. That is: in individual samples of patients results from ISE's and total molar concentration will differ unpredictably. It forced IFCC to propose new quantities for the measurements by adjusted ISE's: ionized sodium and ionized potassium. The reference interval for ionized sodium and ionized potassium is identical to the pertinent reference interval for molar concentration of total sodium and total potassium, but it is in contrast independent from water concentration and valid, e.g., in hypoproteinaemia as well. as in hyperlipaemia or hyperproteinaemia. Accuracy control of ionized sodium and ionized potassium based on reference method values is hampered by abnormal water concentration and inadequate properties of the matrix of many control sera. Alternative approaches how to report measurements by ISE's in undiluted samples, such as activity or free molal concentration are discussed with their pros and cons regarding accuracy control by reference method values. The need for appropriate control materials with a matrix similar to native human sera is stressed.

Ionised and total magnesium concentrations were determined in the serum of different groups of patients suffering from renal or hepatic diseases. Ionised magnesium was measured by Microlyte 6 (KONE, Espoo, Finland) and total magnesium by atomic absorption spectrometry. In renal insufficiency ionised and total magnesium concentrations were almost equally increased. In proteinuria with a normal glomerular filtration rate, "pseudohypomàgnesaemia" was observed, i.e. decreased total magnesium concentration in parallel with a decreased albumin concentration with no significant change in the concentration of ionised magnesium. Hypermagnesaemia occurred in liver diseases combined with renal insufficiency, whereas "pseudohypomagnesaemia" was most often found in the absence of renal failure. Also treatment with an aldosterone antagonist was associated with a normal ionised magnesium concentration, but the total magnesium concentration was decreased; when additional magnesium was administered, the total magnesium concentration approached a normal value, while ionised magnesium slightly exceeded reference values. Only during cyclosporin treatment did both ionised and total magnesium concentrations become lowered. However, the decrease of total magnesium exceeded that of ionised magnesium due to concomitant hypoalbuminaemia with reduction of the protein-bound fraction. It is concluded that especially low total magnesium concentrations should be investigated by measurement of ionised magnesium to exclude "pseudohypomagnesaemia".

In this study we investigated three groups of patients, the first undergoing liver transplantation (n = 9), the second resection of the liver (n = 7) and the third cardiac surgery (n = 10) with regard to changes of ionized and total magnesium concentration during operation. Liver transplantation: Ionized magnesium concentration decreased from 0.58 mmol/L to 0.34 mmol/L far below the reference interval (0.49-0.72 mmol/L), whereas total magnesium concentration changed only from 0.78 mmol/L to 0.67 mmol/L (reference interval: 0.65-1.05 mmol/L). Citrate concentration increased from 220 mumol/L to 1925 mumol/L (anhepatic stage) because of massive transfusion of blood products. It was inversely correlated to ionized magnesium concentration. Resection of the liver: There was a decline of ionized magnesium from 0.56 mmol/L to 0.43 mmol/L, which slightly exceeded the decline of total magnesium from 0.74 mmol/L to 0.64 mmol/L. Citrate concentration increased moderately even in cases, when no citrate was administered reflecting reduced hepatic function during operation. Cardiac surgery: Only in patients, to whom citrate but not magnesium was infused, ionized magnesium concentration fell slightly below the reference interval (0.45 mmol/L). In the other patients, to whom magnesium was administered, ionized magnesium concentration was within the reference interval or exceeded it. It is concluded that in patients with impaired hepatic function and/or high citrate load the monitoring of ionized magnesium concentration is mandatory.

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.

Although the pathophysiology of postmenopausal osteoporosis has been investigated extensively, it is still not established in what respect PTH is related to the events. Recently, consistent data on the pulsatile secretion of PTH in man have been published. In this study intact PTH was measured in six early postmenopausal women before and after 6 months of hormone replacement therapy (HRT; 0.6 mg conjugated estrogens and 5 mg medrogestone). In addition to parameters of calcium metabolism and bone mass and to control HRT, intact PTH was measured in blood drawn over 6 h every 2 min. With HRT there was a 30% reduction in PTH secretion. Both the amount secreted per pulse (baseline, 26.8 +/- 6.9 ng/L; HRT, 21.4 +/- 7.6 ng/L; P < 0.05) as well as the basal secretion (baseline, 232.6 +/- 117.6 ng/L.h; HRT, 145.5 +/- 80.0 ng/L.h; P < 0.01) were reduced, whereas the pulse count per h remained constant (baseline, 5.1 +/- 2.2; HRT, 5.1 +/- 1.3). Power spectrum analysis showed a shift in spectral maxima consistent with these findings. Ionized and total calcium were slightly, but nonsignificantly, reduced with treatment. In summary we conclude that in early postmenopausal women, HRT reduces the secretion of PTH by reducing both the basal secretion and the amount secreted per pulse. It is conceivable that some of the known effects of HRT on bone metabolism might be mediated by the modulation of PTH secretion.

Pulsatile secretion of PTH in human subjects has been described recently. However, the pattern of PTH secretion in primary hyperparathyroidism (pHPT) remains to be characterized. In this study intact PTH was measured in 9 female patients with pHPT. As a control group we present data from 10 postmenopausal women. In addition to parameters of calcium metabolism and bone mass, PTH was measured in samples drawn over 4 or 6 h every 2 min by central venous blood sampling. The mean intact PTH concentration was 39.0 +/- 20.3 ng/L in healthy women and 193.2 +/- 127.9 ng/L in female patients with pHPT (P < 0.01). Pulse rhythm analysis showed significant differences between both groups for total PTH secretion per h (patients, 1196.4 +/- 485.3 ng/L; control group, 271.7 +/- 132.2 ng/L), basal PTH secretion per h (patients, 852.4 +/- 459.1 ng/L; control group, 185.6 +/- 126.1 ng/L), and average PTH secretion per pulse (patients, 112.6 +/- 54.8 ng/L; control group, 23.2 +/- 7.1 ng/L). Both patients and control subjects had, on an average, five pulses per h, and the pulsatile secretion accounted for about 50% of the total secretion. Differences in power spectrum analysis were consistent with these findings. The cross-correlation of PTH and calcium indicates an impaired feedback regulation in pHPT. PTH secretion in female patients with pHPT results from both an increased basal secretion and an increased amplitude of PTH pulses. Other features of secretion are the same as those in normal women. Feedback regulation of PTH and calcium is impaired in pHPT.

In clinical chemistry two different quantities are determined for electrolytes: 1) Electrolyte concentration (total) in serum (S) e.g. S-sodium (mmol/1), S-calcium (mmol/l) 2) Electrolyte concentration (ionized) in serum water [S(W)] e.g. S(W)-sodium, ionized (mmol/kg), S(W)-calcium, ionized (mmol/kg) ad 1) For the determination of the electrolyte concentration in serum, various methods are used: Sodium, potassium: Flame atomic emission spectrometry, ion-selective electrodes after dilution of the sample, enzymatic methods Chloride: Coulometry, absorption spectrometry after chemical reaction, enzymatic method Calcium, magnesium: Flame atomic absorption spectrometry, flame atomic emission spectrometry (calcium), absorption spectrometry after chemical reaction, enzymatic method (magnesium) A safe and unambiguous medical interpretation of sodium and chloride ion concentration in serum is not possible without knowledge of the water concentration or of the lipid and protein concentration of the individual sample. The same holds true - even though for some other reasons - for calcium concentration in whole serum. The reference intervals of the pertinent ions are valid only for samples, which are "normal" with respect to the size of the electrolyte-free compartment and - depending on the method - the amount of complex-binding ions. ad.2) For the determination of the concentration of the "ionized" or "free" fraction of sodium, potassium, calcium, and magnesium in serum water (or the extracellular water phase of whole blood) the following method is only applicable: Ion selective electrode without dilution of the sample. A safe medical interpretation of the ionized electrolyte concentration in serum water is possible without knowledge of the water concentration of the individual sample, because these quantities are independent from the size of the electrolyte-free compartment. The reference interval is valid also in case of e.g. hyperlipidaemia or hypoproteinaemia. It is independent from the amount of other complex-binding ions.

The determination of sodium and potassium in serum will be performed in the near future mainly by ion-selective electrodes. When the samples are highly diluted before measurement, a demonstrably accurate value of the electrolyte concentration in serum can be obtained. Accuracy control by using the pertinent reference methods of the National Institute of Standards and Technology (NIST) is well established for this purpose. In undiluted samples a potential is measured by ion-selective electrodes, which is dependent on the relative molal activity of the electrolyte, from which free molal concentration can be estimated. Usually, the total molal concentration of e.g. sodium is about 1.5% higher than that of free sodium, as it includes portions bound to e.g. carbonate and proteins. Accuracy control is hampered, because reference methods for either relative molal activity or free molal concentration are not yet available. Reference method values for total molal concentration will differ systematically from an accurate value for free molal concentration. When ion-selective electrodes are calibrated by using "normal" sera, accuracy control can be based on the reference method of the NIST; but this is valid only for a very narrow, at best "normal", concentration range of proteins and lipids, assuming, of course, that binding is normal. The greater the variation of the concentration of macromolecules from normal (lower or higher), the greater the difference between the values obtained by the two methods. Calibration of ion-selective electrodes by using sera (this is the least desirable approach for calibration) requires the introduction of a new unit of measurement, which is not compatible with the rational system of quantities and units.(ABSTRACT TRUNCATED AT 250 WORDS)

Inconclusive reports on pulsatile secretion of PTH in man have been published. In this study PTH was measured by intact and PTH-(44-68) assays. Central venous blood sampling was performed every 2 min in 10 healthy men between 6-9 h and in 3 male patients with osteoporosis for over 6 h. Pulsatile PTH secretion was identified for healthy men and controls. Narrow pulses and bursts of narrow pulses (broad pulse) could be distinguished. Six narrow pulses per h with 26 +/- 16 ng/L amplitude and 1 burst of narrow pulses/h were detected for the intact hormone. One narrow pulse/h with 25 +/- 12 ng/L amplitude and 1 burst of narrow pulses (broad pulse) every 2 h were found (Pulsar) for PTH-(44-68). Intact and PTH-(44-68) exhibit in part a concordant pattern. Results from 3 patients with osteoporosis show a decreased amplitude and frequency of pulsatile PTH secretion. The same decreased pattern was demonstrated in a postmenopausal osteoporotic woman. A constant decline in ionized calcium elicits major secretory episodes of PTH, and ionized calcium increases after major secretory episodes of PTH. We conclude that pulsatile secretion of PTH in healthy young men is the physiological mode of secretion. Low pulsatile secretion of PTH might be related to low turnover osteoporosis.

The concentrations of sodium, potassium, and chloride in various control sera were determined by reference methods. The reference method values were compared with the corresponding method-dependent assigned values. Sodium: Measurements by flame photometry and ion selective electrodes differed on the whole by less than 1% from the reference method value; determinations by photometry differed, however, by -4.7%. Potassium: The mean bias was -1.2% with flame photometry and -0.4% with ion selective electrodes, whereas nephelometric procedures differed by -1.9 or -4.8%. Chloride: Satisfactory agreement was obtained with values given for ion selective electrodes (-0.3%), for some coulometric procedures (-0.7 and 0.4%), and photometric determinations using mercury rhodanide (-0.5 and +0.7%). Values for mercurimetric titration and for photometric determinations using mercury 2,4,6-tri-(2-pyridyl)-s-triazine differed by + 2.5 and + 1.8%. Proposals concerning the allowable deviation from reference method values are discussed.