Wide variation in serum anion gap measurements by chemistry analyzers.

The traditional anion gap [AG = Na-Cl-(total CO2)] mean value of 12 mEq/L was established during the 1970s with analyzer methods that are no longer used widely. No studies have systematically compared mean AG values from analyzers in current use. We used data from healthy subjects obtained from 27 clinical laboratories, 5 manufacturers, and 8 publications to compute mean AG values from 1970s analyzers and 8 current analyzers. We also compared mean AG values by evaluating Na, Cl, and total CO2 data from the College of American Pathologists Chemistry Surveys (1990-1996). Data from healthy subjects showed that overall mean AG values of the 9 analyzers ranged from 5.9 to 12.4 mEq/L. The pooled (i.e., average) AG SD was 2.3 mEq/L. We then used the data of the Surveys and the mean value from 1 analyzer to compute predicted mean values for the other 7 current analyzers. Almost all mean AG values predicted from the Surveys agreed (within 1.5 mEq/L) with mean values from healthy subjects. These results show that mean values of analyzers vary widely, indicating that analytic bias strongly influences the AG. The results should be a useful guide for the AG measurements that can be expected from different analyzers.

Lactate dehydrogenase isoenzyme 1. A rapid assay for ischemic myocardial disease.

A rapid immunochemical method (Isomune-LD) for the determination of lactate dehydrogenase isoenzyme 1 (LD1) activity in serum was investigated, and the sensitivity and specificity of the assay were determined for the diagnosis of a myocardial infarction (MI). Multiple serum samples were obtained (on admission and at 12, 24, and 48 hours) from 85 patients (30 with proven MI and 55 without MI). The sensitivity of LD1 on admission and at 12, 24, and 48 hours was 43%, 84%, 96%, and 100%, respectively, and the specificity at these same time intervals was 95%, 100%, 97%, and 97%, respectively. Thus, the determination of LD1 by this rapid immunochemical method appears to allow a rapid laboratory evaluation of MI with a high degree of sensitivity and specificity.

Sodium measurements in multiple myeloma: two techniques compared.

Sodium was determined by flame photometry and by direct potentiometry in 56 serum or plasma samples from 24 patients with multiple myeloma or macroglobulinemia. We observed differences between the two techniques as large as 17 mmol/L (12%). The flame-photometric values decreased relative to the direct-potentiometric values as protein increased or water content decreased. Moreover, the two sodium measurements could not be interconverted simply on the basis of correcting for protein or water content. There was significantly lower residual variance (p less than 0.005) when the direct-potentiometric sodium values were compared with the osmolality (corrected for the influence of glucose and urea nitrogen) than when the flame-photometric values for sodium were so compared. We conclude that direct potentiometric measurements of sodium in patients with multiple myeloma gives clinically relevant results but flame photometry does not. Clearly, the method by which sodium is measured in patients with multiple myeloma must be considered if results are to be interpreted correctly.

Influence of fatty acids on the binding of calcium to human albumin. Correlation of binding and conformation studies and evidence for distinct differences between unsaturated fatty acids and saturated fatty acids.

The influence of various fatty acids of 14-18 carbon chain lengths on the binding of calcium to human serum albumin was studied. The cis-unsaturated fatty acids (myristoleic, palmitoleic, oleic, and linoleic) caused a much larger increase in the affinity and maximum binding of calcium for albumin than did saturated fatty acids (myristic, palmitic, and stearic). For the unsaturated fatty acids, the influence on calcium-albumin binding increased as the degree of unsaturation increased or the chain length decreased. With oleic or linoleic acid, increases in calcium binding were observed at approximately 2-3 mol of fatty acid/mol of albumin, while for myristic, palmitic, or elaidic acid, concentrations of 5-7 fatty acids/mol of albumin were required. The maximum fluorescence emission of albumin was found to change in parallel with the calcium binding for oleic, palmitic, and elaidic acids. We conclude that 1) cis-unsaturated and saturated or trans-unsaturated fatty acids have very different effects on the binding of calcium to human albumin, 2) the alteration in calcium binding is likely due to a conformational change in the albumin molecule, and 3) changes in calcium binding to albumin are observed at levels of cis-unsaturated fatty acids which are obtainable in vivo.

Interferences of mannitol with phosphate determination.

Methods commonly used for serum phosphate analysis depend upon the combination of inorganic phosphorus with molybdate and subsequent quantitation of the resultant phosphomolybdate by spectrophotometry. This is a case report of mannitol interference with phosphate quantitation by a method not employing dialysis (DuPont ACA) but not with another method which includes a dialysis step (Technicon SMAC). This interference, occurring at an extremely high level of serum mannitol (3.5 g/dl) in a patient with acute renal failure, appears to be due to direct inhibition of the formation of the phosphomolybdate complex by mannitol.

Charcoal hemoperfusion for treatment of carbamazepine poisoning.

We report a case of carbamazepine (Tegretol) poisoning that was treated with charcoal hemoperfusion. When admitted, the patient was comatose and required ventilatory support. Hemoperfusion with coated activated charcoal successfully decreased her serum carbamazepine concentration from 60 mg/L to 36 mg/L within 2 h, with subsequent clinical improvement. Approximately 39 h would have been required to obtain this decrease via the patient's inherent elimination rate. Activated charcoal hemoperfusion may be useful as an adjunctive therapy for patients in advanced comatose states with associated respiratory depression and potentially fatal outcome.

Comparison of the carbohydrate and amino acid composition of normal and S-variant alpha-1-antitrypsin.

alpha-1-Antitrypsin has been isolated and purified from the serum of an individual with the Pi S phenotype whose serum contains only 50--60% as much alpha-1-antitrypsin as normal M-type serum. The preparation was homogeneous by the criteria of sodium dodecyl sulfate polyacrylamide gel electrophoresis and sedimentation equilibrium ultracentrigufation. When analyzed in the ultracentrifuge, the S-type alpha-1-antitrypsin exhibited a molecular weight of 47,500 which was essentially the same as that of the M-type (47,300) and the Z-type (47,500) alpha-1-antitrypsin. The S-type alpha-1-antitrypsin contains 15.2% carbohydrate consisting of 16.4 residues/mol of N-acetylglucosamine, 7.8 residues/mol of mannose. 6.7 residues/mol of galactose and 7.1 residues/mol of sialic acid which is essentially the same as the carbohydrate composition of the M-type alpha-1-antitrypsin. In addition, M- and S-type alpha-1-antitrypsin have very similar amino acid compositions.

Protein synthesis and degradation in a leucine auxotroph of Escherichia coli.

The synthesis and degradation of the soluble and sodium dodecyl sulfate-(SDS)-solubilized protein fractions of Escherichia coli were studied in both growing and nongrowing cultures. When separated according to molecular weight on SDS-polyacrylamide gels, the proteins of both fractions of growing cells undergo no measureable differential synthesis or degradation during logarithmic growth. However, when a leucine auxotroph is suspended in medium containing 5.3 muM leucine (a level that will not sustain growth), the SDS-solubilized protein of such a nongrowing culture shows a rapid synthesis of two protein components (32,000 and 12,000 daltons) found only in the out membrane.

Correlation of degradative rates of proteins with a parameter calculated from amino acid composition and subunit size.

A parameter is developed which relates the amino acid composition and subunit size of a protein to the degradative rate in vivo. This parameter was calculated for 11 rat liver proteins and a plot versus the half-lives of these proteins is linear and has a coefficient of correlation of -0.96. Evidence is presented which suggests that the density of excess acidic amino acids on the surface of the protein is the most important factor in determining differential turnover.