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Background: The effect of oral calcium (Ca) supplements in preventing citrate-induced symptoms during plateletpheresis was evaluated in a randomized, blinded, placebo-controlled trial., Study Design and Methods: Twenty-three donors (12 men, 11 women) underwent four plateletpheresis procedures each, ingesting either 1 or 2 g of oral Ca carbonate or an equivalent placebo 30 minutes before donation. Ten of these subjects subsequently ingested 4 g of open-label Ca before a fifth procedure. All procedures were conducted at the same citrate infusion rate (1.5 mg/kg/min) for 90 minutes., Results: Ingestion of 2 g of oral Ca resulted in a significant reduction in the severity of paresthesias and a significant, though modest, increase in serum ionized calcium (iCa), but no significant improvement in total symptom scores, compared to placebo. Minimal effects were seen with the 1-g dose. The two factors most highly correlated with development of severe symptoms were decreased levels of iCa and ionized magnesium (iMg) at 30 minutes into apheresis. Lower preapheresis serum albumin, creatinine, vitamin D, iMg, and total Mg concentrations were also significantly associated with symptoms. Women experienced more frequent and severe symptoms than men, however, gender was not associated with symptoms after adjustment for lower serum albumin, creatinine, and Mg levels. Ingestion of 4 g of Ca offered no improvement in symptoms or iCa levels compared with the 2-g dose., Conclusion: Prophylactic oral Ca was associated with modest improvements in citrate-induced symptoms and laboratory parameters. Baseline albumin and Mg levels were strongly predictive of the development of symptoms. In donors with a prior history of uncomfortable citrate-related effects, a 2-g oral Ca dose before apheresis is recommended.

Background: The metabolic effects of oral calcium (Ca) supplementation during plateletpheresis were evaluated in a randomized, placebo-controlled trial., Study Design and Methods: Twenty-three donors underwent four plateletpheresis procedures each, receiving in random order, elemental Ca (Ca) 1 or 2 g orally, or a corresponding placebo, 30 minutes before donation. Ten of these donors underwent a fifth procedure using a 4-g Ca dose. All procedures were performed at a fixed citrate infusion rate of 1.5 mg per kg per minute., Results: Oral Ca induced dose-sensitive changes in parathyroid hormone (iPTH), total (tCa), and ionized (iCa) calcium levels. Compared to placebo, the greatest improvement in tCa and iCa levels occurred after the 2-g Ca dose (tCa of 73, 89, and 25% above placebo levels at 60 min, using 1, 2, and 4 g of oral Ca, respectively). Twenty-four hours after apheresis, serum tCa and iCa levels were higher, and iPTH levels lower, in donors who received oral Ca rather than placebo. Marked increases in urinary Ca and magnesium (Mg) excretion occurred at the completion of apheresis, were unaffected by Ca dose, and returned to baseline within 24 hours. Plateletpheresis also induced significant changes in serum alkaline phosphatase, 1,25-dihydroxyvitamin D, and osteocalcin levels immediately and at 24 hours after apheresis., Conclusion: Plateletpheresis induces marked acute metabolic effects, with sustained changes evident up to 24 hours after the completion of apheresis. Oral Ca supplementation exerts a significant but clinically modest impact on selected laboratory variables associated with these effects. Further studies are indicated to examine the long-term impact of plateletpheresis, with or without Ca supplementation, on donor Ca balance and bone density.

Background: Leukapheresis procedures are generally performed at citrate anticoagulation rates extrapolated from shorter plateletpheresis procedures. However, neither the metabolic effects nor the management of associated symptoms have been critically evaluated during leukapheresis in healthy donors., Study Design and Methods: Symptom assessments (n = 315) and laboratory analyses (n = 49) were performed during 244 procedures performed with and 71 without prophylactic calcium (Ca) chloride or Ca gluconate given at a dose linked to the citrate infusion rate (1.0-2.2 mg/kg/min)., Results: During leukapheresis of 12 to 25 L processed, ionized Ca and ionized magnesium (Mg) decreased as much as 35 and 56 percent, respectively, each exhibiting a tight negative correlation with marked increases in serum citrate levels. Significant increases in urinary Ca and Mg excretion accompanied the renal excretion of a large citrate load. Serum divalent cation levels remained depressed 24 hours after leukapheresis. Symptoms were more frequent in donors who were women, had low initial total Mg levels, and underwent procedures in which larger volumes were processed at higher citrate infusion rates. Ca infusions reduced clinically significant paresthesias by 96 percent and also attenuated decreases in serum potassium. Ca chloride maintained higher Ca levels than Ca gluconate., Conclusions: Prophylactic Ca infusions safely attenuate the marked metabolic effects of citrate administration and promote faster, more comfortable, leukapheresis procedures.

Interleukin 2 (IL-2) can cause partial or complete tumor regression in approximately 20% of patients with renal cell carcinoma. Among the many physiologic effects of IL-2, decreased serum levels of the divalent cations magnesium (Mg) and calcium have been demonstrated, with corresponding decreases in their urinary excretion. We investigated the effect of IL-2 on lymphocyte Mg levels among patients receiving three different dosing regimens. Twenty-eight patients with metastatic renal cell carcinoma were treated with high-dose intravenous, low-dose intravenous, or subcutaneous IL-2 therapy. Serum ionized Mg, urinary Mg, and peripheral blood mononuclear cell Mg levels were measured in samples from patients during treatment and compared with pretreatment levels. Serum Mg and ionized Mg levels decreased for all patients within 12 hours of treatment (P <.005) and remained low for the duration of therapy. Urinary Mg decreased in parallel with serum levels in all patients (P <.005). The peripheral blood mononuclear cell Mg content per cell increased within 24 hours of treatment (P <.005). The magnitude of these changes was similar during the first week of treatment for patients receiving intravenous or subcutaneous administration of IL-2. During IL-2 therapy, lymphocyte Mg increases coincident with serum Mg depletion. Mg availability may have functional implications for lymphocyte proliferation and integrin function.

Background: Although plateletpheresis procedures are generally well tolerated, the clinical and metabolic consequences associated with rapid infusion of up to 10 g of citrate are underappreciated, and a comprehensive description of these events is not available., Study Design and Methods: Clinical and laboratory changes were studied in seven healthy donors undergoing three 90-minute plateletpheresis procedures each, at continuous, fixed citrate infusion rates of 1.1, 1.4, and 1.6 mg per kg per minute., Results: Serum citrate levels increased markedly with increasing citrate infusion rates and did not achieve a stable plateau. As citrate infusion rates increased, the total volume processed and platelet yields also increased, but donor symptoms became more severe. Ionized calcium (iCa) and ionized magnesium (iMg) concentrations decreased markedly, by 33 and 39 percent below baseline, respectively, at a citrate rate of 1.6 mg per kg per minute. Intact parathyroid hormone levels were higher at 30 minutes than at later time points, despite progressive decreases in iCa and iMg. Urine citrate, calcium, magnesium, sodium, and potassium concentrations and urine pH values increased markedly during all procedures., Conclusion: Marked, progressive increases in serum citrate levels occur during plateletpheresis, accompanied by symptomatic decreases in iCa and iMg, with significantly increased renal excretion of calcium, magnesium, and citrate.

The biochemical composition of "unstimulated" whole saliva was determined in healthy adult subjects. Based on their relative concentration, salivary analytes could be classified into three arbitrary categories: concentration lower than in serum (saliva/serum ratio < 0.5; 12 analytes), similar to serum (ratio = 0.5-1.5; five analytes), and higher than in serum (ratio > 1.5; five analytes). Consistent with local production, an elevated lactate dehydrogenase (LDH) activity in the saliva was associated with a non-serum like LDH isoenzyme pattern: LDH5 >> LDH4 > LDH3 >> LDH2 > LDH1. Compared with serum, the concentrations of hydrogen (as reflected in the pH), potassium and inorganic phosphorus were much higher (saliva/serum ratio > or = 3), whereas that of sodium, total magnesium, chloride, and total carbon dioxide were lower (saliva/serum ratio < or = 0.3). The concentration of ionized calcium was similar in saliva and serum (saliva/serum ratio = 0.8), while ionized magnesium was unmeasurable in saliva. The salivary ionized calcium fraction was higher (0.76) than previously suggested (0.51). The difference between the main salivary cations (potassium, sodium), and anions (phosphate, chloride) was similar to serum (anion gap: 4 vs. 11 meq/l). Highly significant (p < or = 0.012) correlations occurred among salivary pH, dihydrophosphate, total calcium, and potassium. Our data suggest that calcium, potassium, chloride and phosphates are the major salivary complex-forming ions. The major compositional differences between serum and saliva show that saliva is not a passive "ultrafiltrate" of serum and salivary constituents may play a distinct physiological role.

In a two-center (Academic Medical Center, The Netherlands, and National Institutes of Health, USA) study, we compared ionized magnesium (iMg2+) results in serum determined with the AVL 988/4, KONE Microlyte 6 and NOVA CRT, which are the currently available analyzers equipped with a magnesium ion-selective electrode. The comparison was performed with frozen serum samples from normal individuals and patients. Imprecision and reference intervals were established. We found the best agreement between the KONE(x) and AVL(y) magnesium ion-selective electrodes (y= 0.972x-0.013; n=138) with samples from patients. With samples from normals, all three analyzers reported significantly different results (p<0.05). Best precision was found using the NOVA; coefficients of variation established at three levels were all < 4.0%. Coefficients of variation for the AVL and KONE were <5% at normal and high iMg2+, but 10.7 and 9.4%, respectively, at iMg2+ approximately 0.30 mmol/l. The reference intervals (mean+/-standard deviation) based on measurements in fresh serum samples were different for each analyzer: 0.55-0.63 mmol/l for AVL, 0.470.57 mmol/l for KONE and 0.43-0.55 mmol/l for NOVA. Thus, significant differences among the ionized magnesium concentration obtained with the three analyzers, limit comparison of results in clinical practice, and need to be resolved (e.g. by improvement of specificity and standardization of calibrators).

We compared physiologically abnormal low and high ionized magnesium (iMg) results determined with the AVL 988-4 (AVL, Graz, Austria) and Nova CRT (Nova Biomedical, Waltham, Mass) ion-selective electrodes (ISEs) in serum samples from randomly selected patients. A result of < 0.39 mmol/L with either ISE constituted the low magnesium group and of > or = 0.65 mmol/L the high magnesium group. Within each group we found significant differences between the iMg results. Major intermethod differences were found for samples with physiologically normal total magnesium concentration: most of the samples in the low magnesium group (83%) had abnormally low results with the Nova ISE, whereas most of the results with the AVL ISE (83%) were normal. In contrast, all results with the AVL ISE for the high magnesium group were abnormally high, but 67% of the results with the Nova ISE were normal. The agreement for the clinical interpretation of iMg results based on the reference interval for each method was only 32%. The differences in iMg results between the two analyzers must be resolved before using the iMg test as measured with ISE for patient care.

Objective: To investigate the effect of smoking on serum ionized magnesium concentration ([Mg2+]) determined by the NOVA and AVL Mg ion-selective electrodes (Mg ISEs)., Methods: Subjects were apparently healthy smokers (n = 30) and nonsmokers (n = 30). We determined NOVA and AVL [Mg2+] in their serum and in test solutions containing compounds increased by smoking. We also determined subjects' white blood cell and differential counts., Results: For smokers, the mean values for NOVA and AVL [Mg2+] differed significantly (0.41 vs 0.52 mmol/L, respectively). We found a significant intramethod difference in NOVA [Mg2+] (0.11 mmol/L, P < .0001) between smokers and nonsmokers. A dose-dependent decrease in NOVA [Mg2+] was observed with an increase in cigarettes/day. NOVA [Mg2+] inversely correlated with white blood cell counts. There was no interference by the test compounds with either Mg ISE., Conclusion: Smoking may induce a serum factor, possibly related to white blood cells, that negatively interferes with the response of the NOVA Mg ISE.

Thiocyanate found in serum ordinarily is the metabolite of cyanide that is inhaled with tobacco smoke and ingested with cyanogenic foods. We investigated the effect of the thiocyanate ion (SCN-) on the ionized magnesium (iMg) and ionized calcium (iCa) results determined with the AVL and Nova magnesium and calcium ion-selective electrodes (ISEs). We analyzed saline and pooled serum with added SCN-, and serum from apparently healthy nonsmokers (n = 20) and smokers (n = 20). The mean (and range) of the measured serum SCN- concentration was 0.019 (0.008-0.046) mmol/L for nonsmokers and 0.077 (0.020-0.138) mmol/L for smokers. Only the Nova iMg results decreased with increasing SCN- concentration, and the change was dependent on the baseline iMg concentration. In the absence of Mg, SCN- decreased the voltage response of the Nova Mg ISE to calcium ions. At apparently normal serum iMg and iCa concentrations, the interference by SCN- appeared to be equimolar (iMg = -1.04 x SCN- + 0.52). Thus, the serum SCN- commonly found in smokers causes a significant (P < 0.0001) decrease in the Nova iMg results.

We studied the stability and linearity of the AVL and Nova Mg and Ca ion-selective electrodes and the relation between the ionized Ca and ionized Mg results reported by each analyzer. The response of the electrodes to different concentrations of Mg and Ca was determined for saline solutions, aqueous solutions, and serum samples. The electrodes from both manufacturers demonstrated acceptable stability for the time of the study. The response of the electrodes was linear within the range specified by each manufacturer, but relative nonlinearity and the values for the linear limits differed between the AVL and Nova analyzers. The ionized Mg results varied with the concentration of Ca. The relation between ionized Ca and ionized Mg results was nonlinear and differed between the AVL and Nova electrodes. Intermethod comparison between the electrodes showed poor agreement for ionized Mg results, especially at low and high concentrations of total Ca and total Mg.

We compared the precision of the AVL 988-4 and NOVA CRT instruments for determining ionized magnesium (iMg) and assessed the effect of pH and ionized calcium (iCa) concentration on the results Within-run and day-to-day precision for the iMg electrodes were determined using three levels of control material supplied by each manufacturer. The effect of pH on iMg results was assessed by analyzing anaerobic serum samples from patients, reanalyzing those same samples after pH was increased by in vitro loss of CO2 and comparing the results. To assess the effect of iCa concentration on the iMg results, we added CaCl2 to aqueous standards from both manufacturers and to a normal serum pool. The results show comparable coefficients of variation for the two iMg electrodes both within-run (0.68-2.05 for NOVA; 0.77-2.60 for AVL) and day-to-day (2.90-6.48 for NOVA; 1.71-4.93 for AVL). The AVL results were not affected by the increase in serum pH and agreed with the NOVA results that were adjusted to a pH of 7.4 (paired t-test; p > 0.2). There was a significant direct relationship between the iCa and iMg results for both analyzers, but the AVL slopes were smaller (0.026, 0.083) than the NOVA slopes (0.129, 0.165). Thus, these two iMg electrodes have comparable precision but differ in response to an increase in pH and iCa.