Kinetic analysis of the rapid intraoperative parathyroid hormone assay in patients during operation for hyperparathyroidism.

BACKGROUND: Rapid intraoperative parathyroid hormone (RI-PTH) assay is used to guide adequacy of resection during operation for hyperparathyroidism. We compared the RI-PTH assay (15 minutes) with a standard PTH assay, determined whether the PTH half-life varied between patients, and constructed a kinetic analysis of the RI-PTH data. METHODS: Forty-five patients with hyperparathyroidism had blood sampled at baseline and at times after parathyroid resection. Intact PTH was determined using RI-PTH and a standard assay. Values were fitted to an exponential decay curve using the baseline and the follow-up time points. PTH half-life and the new postexcision baseline value were calculated from the decay curve. RESULTS: The RI-PTH assay and the standard PTH assay correlated well. Average PTH half-life was 1.68 +/- 0.94 minutes (0.42 to 3.81 minutes). A kinetic analysis yielded a formula for the generation of a PTH decay curve. Using a 50% reduction in RI-PTH at 5 minutes as the criterion for adequate resection, 2 patients were incorrectly classified as not being cured. These patients were correctly classified using the kinetic analysis. CONCLUSIONS: PTH half-life can vary substantially. A kinetic analysis may be more accurate in assessing adequacy of resection. This method allows the surgeon to interpret RI-PTH data independent of the timing of samples.

Blood magnesium parameters do not differ with age.

The relationship between age and blood magnesium (Mg) parameters has not been defined. Mg measurements in plasma, red blood cells (RBCs), and mononuclear blood cells (MBCs) were made in 104 normal volunteers (43 males and 61 females, ages 11-75 years). MBCs were separated from blood using a discontinuous Ficoll-Hypaque gradient. The mean values (+/- SEM) were as follows: plasma Mg 1.63 +/- 0.01 mEq/L, RBC Mg 4.55 +/- 0.06 mEq/L, MBC Mg content 72.8 +/- 1.0 fg/cell, and MBC Mg concentration 19.6 +/- 0.3 mEq/L. We compared these parameters with age (intervals of 10 years) using analysis of variance (ANOVA) and found no significant differences (p greater than 0.05). Thus, plasma, RBC, and MBC Mg parameters do not vary significantly between the ages of 11 and 75 years.

Intravenous fluorescein interference with clinical laboratory tests.

The results of laboratory tests performed after fluorescein angiography may be erroneous because of interference by intravenous fluorescein. We investigated this potential interference in four adults at intervals of five minutes, three hours, six hours, and 12 hours after fluorescein injection. We used a panel of serum and urine chemistry tests on seven commonly used instruments. A significant change in the reported concentration of a serum or urine analyte was defined as a result beyond +/- 3 coefficients of variation of the preinjection baseline value for the test on a specific instrument. The determinations of creatinine, total protein, cortisol, digoxin, quinidine, and thyroxine in serum were affected by intravenous fluorescein. The urine tests were unaltered. The physician must be aware of the problem of interpreting clinical chemistry results after fluorescein angiography.

Etretinate. Persistent serum levels after long-term therapy.

In 47 patients who received long-term etretinate therapy, we measured serum etretinate concentrations from one to 244 weeks after the discontinuation of therapy. The earliest posttreatment, nondetectable serum concentration of etretinate was observed at five weeks after treatment. Detectable serum concentrations (0.05 to 1.2 micrograms/dL) were observed more than two years (108, 111, 131, 136, and 150 weeks) following the discontinuation of therapy. Sequential serum concentrations obtained on eight individual patients were used to determine half-lives for this late-phase elimination. The median half-life for the 12 curves obtained was 12.5 weeks (range, 5.3 to 24.8 weeks). Since etretinate is stored in fat, we compared each patient's deviation from ideal body weight as a measure of excess body fat with various pharmacokinetic factors of etretinate elimination. Overweight patients tended to have slower elimination, maintain higher serum concentrations, and clear etretinate later.

Comparison of magnesium in human lymphocytes and mononuclear blood cells.

The population of mononuclear blood cells (MBCs) separated by a discontinuous gradient from healthy normal volunteers consists of lymphocytes (L), monocytes (M) and relatively few granulocytes (G). We attempted to remove the phagocytic cells (M and G) by pretreatment of the blood with carbonyl iron particles (CIP). In 50 volunteers (21 males and 29 females, ages 17-75, mean 33.3 years), we determined the content and concentration of Mg in MBCs before and after pretreatment with CIP. The results (mean +/- SEM) show a significant decrease in the MBC Mg content (from 3.12 +/- 0.08 to 2.39 +/- 0.05 fmol/cell; p less than 0.0001), concentration (from 10.4 +/- 0.2 to 9.6 +/- 0.3 mmol/l; p less than 0.004) and M percentage (from 14.5 +/- 1.0 to 1.0 +/- 0.2%; p less than 0.0001) after CIP pretreatment. The L percentage significantly increased from 81.6 +/- 1.0 to 96.1 +/- 0.2% (p less than 0.0001) after CIP pretreatment. These date suggest that M have both a larger content and concentration of Mg than L.

The method of determination must be considered in interpreting blood cholesterol levels.

Based on the results of recent clinical trials, physicians have been encouraged to screen and treat patients for hypercholesterolemia. Since the data from the Lipid Research Clinics (LRC) have been used to define the patient population that should be treated, a comparison of LRC cholesterol results with those obtained with two commonly used clinical laboratory instruments was performed. Both the Technicon SMAC and the Du Pont aca had positive bias compared with the LRC method. Therefore, many patients with cholesterol concentrations greater than 265 mg/dL (6.85 mmol/L) as determined by these routinely used methods have markedly lower levels determined by LRC methods. These findings not only indicate that rigorous interlaboratory standardization is required to conform to LRC reference values, but they also suggest that the clinician should be aware of these methodological considerations when the decision to treat hypercholesterolemia is made.

Hemoglobin interference from in vivo hemolysis.

Laboratory values for specimens from a case of intravascular hemolysis showed that hemoglobin was significantly increased and thus could interfere with the determination of other analytes. We studied this problem by adding increasing amounts of purified hemoglobin (to a maximum concentration of 19.3 mg/L) to aliquots of pooled serum samples. The hemoglobin significantly interfered with the determination of only five analytes: albumin, aspartate aminotransferase, direct bilirubin, and total protein on the SMAC, and creatinine on the Astra. We propose that for cases of proven intravascular hemolysis, values for only the analytes not affected by hemoglobin should be reported. We find lactate dehydrogenase activity useful in assessing the components of in vivo hemolysis; the differences between serum and plasma values for potassium, lactate dehydrogenase, and hemoglobin are related to in vitro hemolysis. Criteria for specimen collection and assessment of type of hemolysis are proposed.

Etretinate: effect of milk intake on absorption.

Since etretinate, an aromatic retinoid useful in the treatment of psoriasis and other skin disorders is lipid-soluble, it may be poorly absorbed in the absence of a fat load. We therefore studied serum concentrations of etretinate and its major metabolite (Ro 10-1670) after the controlled administration of etretinate. After an overnight fast, 6 Darier's disease and 4 psoriatic patients received a 1 mg/kg morning dose of etretinate with water or 1 pint of whole milk (fat load). There was a 260% increase (p less than 0.0005) in the mean of each patient's increase in the baseline-corrected peak serum concentration of etretinate after administration with milk (115 +/- 15 micrograms/dl) compared to after administration with water (32 +/- 4 micrograms/dl). Over a 24-h period there was an overall 296 +/- 26% (p less than 0.0005) increase in serum etretinate after administration with milk compared to water in 5 patients with Darier's disease. In contrast to the serum etretinate, there was a 17% mean decrease (p less than 0.025) in the corrected peak serum concentration of Ro 10-1670 in all 10 patients after administration of etretinate with milk compared to water. The net result of these alterations is that the mean corrected serum concentration of etretinate is higher than Ro 10-1670 at all time points measured after milk administration. In contrast, after administration of etretinate with water the major retinoid in the serum is Ro 10-1670. Establishing the clinical significance of these alterations may require controlled clinical trials.

Evaluation of four gentamicin and tobramycin assay procedures for clinical laboratories.

Accuracy, precision, and clinical laboratory utility of the TDX (Abbott Laboratories), Auto-ICS (Beckman Instruments, Inc.), COBAS-Bio (Roche Analytical Instruments, Inc.) with reagent kits (Syva), and EMIT (Syva) for gentamicin and tobramycin serum assay were assessed. TDX, COBAS-Bio, and EMIT analytical systems showed a proportional bias of less than 10% for recovery studies and a coefficient of variation less than 5% for within-run precision. The results of the recovery studies with the Auto-ICS showed a proportional bias of 25% with gentamicin and 16% with tobramycin. The within-run precision expressed as the coefficient of variation for the Auto-ICS was 6.7% for gentamicin and 8.6% for tobramycin. In comparisons involving gentamicin- and tobramycin-containing patient samples, the results with the TDX analytical system showed the best agreement with the COBAS-Bio. For the determination of these two antibiotics, the TDX analytical system provided the best overall accuracy and precision.

Liquid-chromatographic assay for retinol (vitamin A) and retinol analogs in therapeutic trials.

A "high-performance" liquid-chromatographic separation of retinoids (retinol, isotretinoin, all-trans retinoic acid, retinal, etretinate, and retinyl acetate) in serum is described. The separation was used in developing a quantitative assay for retinol (vitamin A) and two therapeutic analogs, isotretinoin (13-cis-retinoic acid) and etretinate (Ro 10-9359). The procedure requires 1 mL of serum. Overall analytical recovery for retinol, isotretinoin, and etretinate from serum was 100% (SD 7%). The between-day coefficient of variation for specimens with concentrations ranging from 0.70 to 0.95 mg/L was less than 4%. Normal reference intervals for serum retinol in men and women are 0.61 to 1.33 and 0.44 to 1.19 mg/L, respectively.