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Purpose: The physical compatibility of magnesium sulfate and sodium bicarbonate in a pharmacy-compounded hemofiltration solution was assessed., Methods: Two bicarbonate-buffered hemofiltration solutions (low- and high-magnesium formulations) were compounded in triplicate. The concentrations of magnesium (15 meq/L) and sodium bicarbonate (50 meq/L) in the high-magnesium formulation were chosen to be somewhat below the concentrations reported as being incompatible in a popular reference. The six hemofiltration bags were stored at 22-25 degrees C without protection from light for 48 hours. Physical compatibility was assessed by visual inspection and microscopy. The pH of the solutions was assayed 3-4 and 52-53 hours after compounding. Electrolyte and glucose concentrations of the solutions were assayed at 3-4 and 50-51 hours after preparation., Results: No particulate matter was observed by visual or microscopic inspection in the compounded hemofiltration solutions at 48 hours. The mean +/- S.D. pH values of the low-magnesium solutions were 8.01 +/- 0.02 and 8.04 +/- 0.02 at 3-4 and 52-53 hours after compounding, respectively. The mean +/- S.D. pH values of the high-magnesium solutions were 7.96 +/- 0.02 and 7.98 +/- 0.01 at 3-4 and 52-53 hours after compounding, respectively. The electrolyte and glucose concentrations in the low- and high-magnesium solutions were similar 3-4 and 50-51 hours after preparation., Conclusion: Magnesium sulfate 1.5 meq/L and sodium bicarbonate 50 meq/L were physically compatible in a pharmacy-compounded hemofiltration solution for 48 hours when stored at 22-25 degrees C without protection from light.

Background: Acute increases in serum inorganic phosphorus (Pi) up to 4.75 mmol/l in the absence of hypocalcemia and tissue deposition of calcium phosphate were noted in 3 patients receiving liposomal amphotericin B (L-AMB). We investigated L-AMB as a possible cause of pseudohyperphosphatemia., Methods: Serum samples from the index patient were analyzed for Pi content by our laboratory's primary analyzer (Synchron LX20) and by an alternate analyzer (Vitros). Clear and lipemic serum pools, and normal saline, were spiked with L-AMB and analyzed by the LX20 Pi method. Ultrafiltration studies were performed on patient and spiked sera., Results: Increased Pi values were obtained only from the LX20 analyzer. There was a direct linear relationship between the concentration of L-AMB in the spiked samples and the LX20 Pi results, indicating a 0.9 mmol/l Pi increase for every 100 mg/l increase in L-AMB. Ultrafiltration normalized the Pi results., Conclusion: Serum Pi results may be falsely increased in patients receiving L-AMB when measured by the LX20 analyzer. This novel cause of pseudohyperphosphatemia is due to interference of L-AMB with the method and is corrected by ultrafiltration of the specimen. Since the LX20 analyzer is widely used by the clinical laboratories clinicians and laboratory personnel should recognize this interference in order to avoid unnecessary diagnostic procedures and interventions.

Background: Marked decreases in ionized magnesium (iMg) levels occur during large-volume leukapheresis (LVL); however, the effect of intravenous (IV) magnesium supplementation in this setting has not been carefully studied., Study Design and Methods: Thirty healthy allogeneic peripheral blood progenitor cell donors receiving citrate anticoagulant with IV calcium prophylaxis were randomized to receive either IV magnesium (0.2 mg Mg per mL acid citrate dextrose-A) or placebo during LVL, with a double-blind design., Results: Thirty subjects underwent 75 LVL pro- cedures, 37 with magnesium and 38 with placebo. Group characteristics were similar for sex, weight, citrate infusion rate (1.36 mg/kg/min vs. 1.37 mg/kg/min), and volume processed (16 L vs. 17 L). Serum iMg levels remained within the reference range with magnesium supplementation, but decreased 39+/-11 percent below baseline (p<10(-10)) after placebo, with greater decreases after consecutive procedures. Subjects receiving magnesium had more vigorous parathyroid hormone responses and higher glucose levels and also tended to have higher serum potassium and ionized calcium levels. Mild paresthesias, coldness, and nausea occurred in 28, 20, and 7 percent of donors, respectively, with no significant differences between groups. Severe symptoms (chest tightness) occurred in only one subject receiving placebo., Conclusion: IV magnesium supplementation exerts a significant impact on serum magnesium levels, but does not reduce the frequency or severity of the relatively mild citrate-related effects observed in LVL performed with continuous IV calcium prophylaxis.

Background: Increased total triiodothyronine (TT(3)) assay results in apparently euthyroid patients triggered an investigation of the effect of blood collection tubes on serum TT(3) and other laboratory assays., Methods: We examined potential assay interference for three types of tubes: plastic Greiner Bio-One Vacuette; glass Becton Dickinson (BD) Vacutainer; and plastic BD Vacutainer SST tubes. Serum samples from apparently healthy volunteers (age range, 30-60 years; 15 males and 34 females) were collected in different tube types and analyzed in 17 immunoassays (n = 49), 30 clinical chemistry tests (n = 20), and 33 immunology assays (n = 15). Tube effects were also examined by adding pooled serum to different tube types., Results: TT(3) values, when measured by the IMMULITE 2000 but not the AxSYM analyzer, were significantly higher (P <0.0001) for SST (2.81 nmol/L) than either glass (2.15 nmol/L) or Vacuette (2.24 nmol/L) tubes. The effect was large enough to substantially shift the distribution of patient values, increasing the percentage of values above the reference interval from 11.3% to 35.8%. The degree of interference from SST tubes on TT(3) differed among various tube lots and could be attributed to a tube additive shared by other plastic tubes. Results from several other tests statistically differed among tube types, but differences were not considered to be clinically significant., Conclusions: Assay interferences from blood collection tubes represent challenges to clinical laboratories because they are not detected by the usual quality-control or proficiency testing programs. Laboratories can, however, address this problem by monitoring distribution of patients' results.

Background: Anticoagulant-associated toxicity may exert significant effects on the safety and efficacy of large-volume leukapheresis (LVL) in children, however, few studies specifically address management of this issue., Study Design and Methods: Seventy-four consecutive LVL procedures (mean, 4 blood volumes processed) in children weighing less than or equal to 30 kg (minimum, 10.9 kg) were analyzed. The first 21 procedures were evaluated retrospectively; 11 used heparin alone (Group I) and 10 used heparin plus reduced-dose ACD-A (whole blood to anticoagulant ratio > or =20:1) (Group II). The next 53 procedures were evaluated prospectively and used full-dose ACD-A (whole blood to anticoagulant ratio < or =13:1), intravenous divalent cation prophylaxis and no heparin; 11 used calcium alone (Group III) followed by 42 with calcium plus magnesium (Group IV)., Results: Seventy-four LVL (56 PBPC and 18 MNC) collections were performed in 38 subjects. One donor in Group I experienced a significant groin hematoma at the site of line placement. One donor each in Groups III and IV had mild paresthesias. Despite a mean citrate infusion rate of 2.6 mg per kg per minute, mean postapheresis serum potassium and ionized magnesium and calcium concentrations in Group IV declined by only 9, 8, and 4 percent, respectively, and stable levels of these variables were maintained 24 hours later. Postapheresis PLT counts declined significantly from baseline preapheresis levels in all groups (mean, 52% decrease)., Conclusions: Use of full-dose citrate anticoagulant with prophylactic intravenous divalent cation infusion offers an effective and safe approach to management of anticoagulant-related toxicity in children undergoing LVL.

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.

Suramin has been shown to have an effect on bone resorption in in vitro models. It is not clear if a similar effect is seen in patients treated with suramin. The clinical effect of suramin treatment on total serum calcium was examined in two groups of patients with hormone-refractory prostate cancer. In all, 28 patients in group 1 were examined within 2 weeks before and 2 weeks after suramin treatment and 72 patients in group 2 were examined within 2 weeks before, during, and after treatment with suramin. In addition, calcium controls spiked with suramin were run in three different commercially available assays for evaluation of the effect of suramin dose on calcium determination. Group 1 patients showed a decrease in serum calcium after treatment with suramin. The mean uncorrected serum calcium level was 2.29 +/- 0.025 mmol/l before treatment and 2.09 +/- 0.025 mmol/l after treatment (P < 0.0001, paired Wilcoxon test). The mean serum calcium value corrected for albumin was 2.33 +/- 0.02 mmol/l before treatment and 2.24 +/- 0.02 mmol/l after treatment (P = 0.0022, paired Wilcoxon test). Group 2 patients also displayed a decrease in serum calcium after treatment with suramin. The mean baseline value was 2.23 mmol/l (median 2.26 mmol/l, range 1.20-2.54 mmol/l). The mean level of serum calcium corrected for albumin as determined at the end of treatment was 2.14 mmol/l (median 2.16 mmol/l, range 0.98 2.46 mmol/l). In all, 48 patients for whom pre- and post-treatment values were available for analysis displayed a median calcium decrease of 0.09 mmol/l (P = 0.0005, Wilcoxon signed-rank test for the null hypothesis of no change). For 68 patients in group 2, data on serial serum calcium measurements during treatment were available for analysis. A projected median decrease in serum calcium of 0.06 mmol/l (range 0.43 to 0.72 mmol/l) over an 8-week interval of suramin therapy was found. Overall, 47 of the 68 slopes were negative (P = 0.0022, Wilcoxon signed-rank test). Nine patients were treated with suramin for less than 6 weeks. These patients' calcium levels were significantly higher than those of 50 patients treated for longer periods (median value 2.24 versus 2.16 mmol/l, P = 0.035, Wilcoxon rank-sum test). No correlation was found between suramin dose and calcium level using the Kodak Ektachem, Hitachi 914, or Synchron Clinical System CX3 method. In conclusion, suramin treatment was consistently associated with decreases in serum calcium in two groups of patients with hormone-refractory cancer. Suramin placed in calcium controls did not affect calcium determination using three commercially available methods.

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.

Changes in serum total and ionized magnesium (Mg and Mg2+) and calcium (Ca and Ca2+) were monitored in three patients who transiently developed severe (total Mg < 0.50 mmol/l) to profound hypomagnesemia (total Mg < 0.35 mmol/l) due to cisplatin or interleukin-2 therapies. Mg2+ and Ca2+ were measured with the Nova ion-selective electrodes at 37 degrees C and all results were normalized to pH 7.40. Independent of the etiology, the Mg2+ fraction (Mg2+/total Mg) increased as the concentration of the serum total Mg decreased in all three patients. When the total Mg was around or below 0.35 mmol/l the Mg2+ approached or exceeded total Mg, suggesting an error in the measurement of Mg2+. The findings were extended by including a group of 31 additional patients whose serum total Mg, Mg2+, total Ca, and Ca2+ concentrations varied from abnormally low to above normal. The serum total and ionized concentrations strongly correlated for both Mg (r2 = 0.88) and Ca (r2 = 0.92). The Mg2+ fraction rapidly increased with a fall in the total Mg concentration (r2 = 0.76) and total Mg/total Ca ratio (r2 = 0.71). In fact, with decreasing total Mg concentrations or total Mg/total Ca ratios, the Mg2+ fraction progressively increased to 93-128% of the total, confirming an error in the Mg2+ determinations. The Ca2+ fraction showed a slight and insignificant decrease with falling total Ca concentrations and total Mg/total Ca ratios. The Mg2+ concentration was directly related (r2 = 0.62), whereas the Ca2+ concentration showed a complex relationship to the total Mg/total Ca ratio. Whether this latter relationship represents a technical artifact or a true biological phenomenon requires further study. The apparent overestimation of Mg2+ at very low total Mg concentrations, and in the presence of a very low total Mg/total Ca ratio, could be due to improper chemometric correction of the Ca effect on the Mg electrode, non-linearity, and inadequate calibration. Whatever the mechanism, the failure of this method to correctly measure very low serum Mg2+ concentrations in the sera of patients with severe hypomagnesemia, or likely in any patient with an unusually low total Mg/total Ca ratio, erodes its diagnostic usefulness.

Chronic alcoholism is associated with a marked deficit in total magnesium (tMg). However, little is known about the status of the physiologically active form, ionized magnesium (iMg). We assessed serum iMg (measured with two ion-selective electrodes, AVL 988-4 and NOVA CRT) and tMg concentrations in chronic alcoholics at admission (n = 31) and after abstinence (n = 13) and compared these results with those for a control group (n = 40). At admission, the tMg and NOVA iMg concentrations in alcoholics (0.78 +/- 0.020 and 0.38 +/- 0.016 mmol/L, respectively) were significantly less (P <0.001) than in the controls (0.85 +/- 0.008 and 0.50 +/- 0.006 mmol/L). The AVL iMg results, however, did not differ significantly between the two groups: 0.53 +/- 0.013 vs 0.56 +/- 0.006 mmol/L, respectively (P >0.05). The mean iMg between the two analyzers differed significantly in both groups (P <0.001). After 3 weeks of abstinence, the alcoholics showed a significant increase in tMg (P <0.001) and in both NOVA and AVL iMg values (P <0.01 for each). tMg concentrations were positively correlated with the AVL iMg values in both alcoholics and controls but correlated positively with the NOVA iMg results only in the controls. Thus, the altered status of iMg is instrument-dependent, and the usefulness of the measurement in alcoholics is yet to be determined.

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.

We compared two ion-selective analyzers (AVL 988-4 and NOVA CRT) for determining ionized calcium (iCa2+), ionized magnesium (iMg2+), sodium (Na+), and pH in serum specimens from healthy and diseased individuals. For assays of three levels of protein-based control materials, total imprecision (CV) was < 3% for all analytes except iMg2+ (< or = 6.5% on NOVA, and < or = 4.9% on AVL). We found a significant difference between the analyzers (P < 0.001) for the mean iMg2+ concentration in patients but no significant correlation (r = 0.253) between the analyzers for iMg2+ in specimens from healthy volunteers, even though the mean iMg2+ concentration did not differ significantly between these groups. The reference interval (central 95 percentiles) for iMg2+ with AVL (0.44-0.60 mmol/L) was contained within that of NOVA (0.39-0.64 mmol/L). The AVL gave higher values for iCa2+ (P < 0.001) and lower values for pH (P < 0.001) in specimens from normal volunteers and patients. The mean value for Na+ in patients' samples was significantly higher by the NOVA (P < 0.01) than by the AVL analyzer. Thus, we found significant differences between these two analyzers for all four analytes.

Despite the relatively ready availability of thyroid cyst fluid specimens, little has been published on their biochemical composition. We measured the concentrations of 18 analytes in thyroid cyst fluid specimens from benign (n = 17) and malignant (n = 3) lesions and in homogenates of normal thyroid tissue (n = 5). The concentrations of an additional five analytes were measured in selected cyst fluid specimens only. Compared with normal human serum specimens, we found that in thyroid cyst fluid specimens the activities of acid phosphatase, aspartate aminotransferase, amylase, and lactate dehydrogenase, and the concentrations of iron and total bilirubin were highly increased. The concentration of glucose was low. The gross appearance of the fluids and the presence of certain analytes were consistent with a hemorrhagic origin of most of the benign and malignant cyst fluid specimens. Other biochemical markers, however, indicated colloidlike features and/or an admixture of thyroid tissue components to the cyst fluid. Although we have limited data for cyst fluid specimens from malignant thyroid lesions, we found no evidence that the results of any of the common biochemical tests would distinguish benign from malignant lesions.

We compared the Du Pont aca (phosphotungstate-enzymic cholesterol) and the Dow (dextran sulfate/Mg2+-enzymic cholesterol) methods for the determination of high-density lipoprotein cholesterol (HDLC) and total cholesterol in serum from 113 patients. The aca results for both total cholesterol and HDLC were significantly greater (p less than 0.0001) than the Dow results, the aca method overestimating the HDLC concentration (mean recovery 107.2% in serum samples with values assigned by the Centers for Disease Control). The precision of the aca method for HDLC was essentially the same as that of the Dow method. Bilirubin (up to 0.17 g/L), hemoglobin (up to 4 g/L), and slight lipemia (triglycerides up to 5.4 g/L) did not interfere with the aca method.

Bilirubin interferes with the Du Pont magnesium method in the aca at 510 nm. We determined that bilirubin concentrations in serum samples up to 380 mg/L did not affect the absorbance measured in the aca III at 540 nm, and therefore we modified the Du Pont setting of spectrophotometer for the magnesium method to 540 and 600 nm. Accuracy and precision of the modified method were comparable with the unmodified method and with atomic absorption spectrophotometry. For comparison, we analyzed serum samples with normal (n = 37) and increased (n = 22) bilirubin concentration with the modified method in the aca III (y) and in the atomic absorption spectrophotometer (x). The results (range 0.56-1.25 mmol/L) were in good agreement (x = y = 0.84 mmol/L, D(x - y) = -0.001, SD = 0.004, t = 0.238, P greater than 0.50) and bilirubin did not interfere with the modified method.

Calorimetric analysis depends on the direct proportionality between the heat changes that occur during chemical reactions and the amount of reacting substances. Potential uses of calorimetry in the clinical laboratory are discussed, with examples. The calorimetric technique does not require optically clear specimens, and if the specificity of the measured reaction is assured, calorimetry can be used for quantitative determinations of components that are present in a complex matrix system such as body fluids. Specific enzymic reactions have been used to measure substrates and enzyme activities in biological specimens calorimetrically, with precision, sensitivity, and accuracy comparable to routine photometric techniques. The application of calorimetry in the clinical laboratory is limited now by its slowness, but development of automated instruments may enable the technique to become competitive with conventional analytical techniques in the clinical laboratory.

We measured the concentrations of 29 commonly measured analytes in fresh sera and in sera that had been stored as whole blood at seven different temperatures for 24 h. We determined the effect of storage temperature and prolonged contact with cell clot on the measured concentration of each analyte, with fresh serum as the control. Significant differences were observed for concentrations of creatinine, glucose, inorganic phosphorus, potassium, and both aminotransferases. The extent of these differences was temperature dependent. Values for the remaining 23 analytes examined were essentially unaffected by the storage.

Uric acid in serum was determined calorimetrically with a batch type microcalorimeter, by measuring the heat evolved during a coupled uricase/catalase enzymic reaction in tris(hydroxymethyl)aminomethane HCl buffer (pH 9.0 at 30 degrees C). Heat evolution and concentration are linearly related through the physiological range of serum uric acid concentrations and the method is free of interferences of the sort encountered with spectrophotometric methods. Precision and accuracy are good (CV, 2%) and the results correlate well with those obtained by a mechanized colorimetric uricase/peroxidase system.

Concentrations of free and esterified cholesterol in serum can be determined simultaneously by measuring, with a batch-type microcalorimeter, the heat released during the coupled cholesterol esterase/cholesterol oxidase/catalase enzymic reaction. To differentiate the two forms of cholesterol, we used kinetic calorimetry: the rate of heat output due to enzymic hydrolysis of esterified cholesterol (the rate-determining reaction) was subtracted from the measured heat, the difference being the heat released during the enzymic oxidation of free cholesterol (the fast reaction). Results obtained by the kinetic calorimetric method agreed with those obtained by separate sequential end-point calorimetric determinations of free and total cholesterol. We also compared the kinetic calorimetric method with the cholesterol method of Abell and Kendall and a continuous-flow modification of the Liebermann-Burchard method (Technicon SMAC). De-biased linear-regression analysis of the data indicates acceptable agreement between the calorimetric and the Abell-Kendall methods (y = 0.98x + 11.5). The correlation between results by calorimetric and SMAC methods shows a significant proportional error (y = 1.17x - 159.4). Bilirubin (up to 200 mg/L) does not interfere with the calorimetry.