Serum sulfate concentration and the anion gap in hemodialysis patients.

First-of-the-month predialysis serum sulfate (SO4) and other blood chemistry values were measured prospectively for 5 to 7 months in 14 patients undergoing single pass chronic tri-weekly maintenance hemodialysis with bicarbonate dialysate. Blood was also obtained predialysis and again immediately postdialysis from seven patients (five of whom also participated in the chronic study). As expected, the patients manifested a high anion gap (AG) metabolic acidosis. Serum SO4 was only moderately stable from month to month (the average coefficient of variation was 0.30; correlation between the serum SO4 value of month one and months two and five were r = 0.59, p = 0.026; and r = 0.38, p = 0.182, respectively). The ratio of mean serum SO4 to mean AG (5.0 +/- 0.4 [SE] mEq/L divided by 19.1 +/- 0.5 mEq/L) was 0.26. Although there was a statistically significant correlation between the serum SO4 and the blood urea nitrogen (BUN), there was no such correlation between SO4 and AG. A single hemodialysis reduced serum SO4 by 54% (from 3.5 +/- 0.5 mEq/L to 1.6 +/- 0.1 mEq/L), but there was no correlation between the change in SO4 and the change in AG. The authors concluded that SO4 contributes importantly to the elevated AG in patients receiving chronic hemodialysis. Single pass bicarbonate hemodialysis temporarily reduces, but does not normalize, both the serum SO4 and the AG of such patients.

Effect of hypercalcemia on the anion gap.

It has been assumed, but not documented, that hypercalcemia induces an appreciable reduction in the serum anion gap (AG) because it represents an increase in the level of unmeasured cations. To test this question, we retrospectively compared the data of 59 hypercalcemic patients with malignancy [group 1, serum Ca 13.3 +/- SE 0.3 mg/dl] with those of 108 patients whose hypercalcemia was of parathyroid origin (group 2, serum Ca 12.1 +/- 0.1 mg/dl), and those of 51 control subjects (group 3, serum Ca 9.5 +/- 0.1 mg/dl). The AG of group 2 subjects (8.7 +/- 0.3 mEq/l) was significantly lower than that of the other two groups (p less than 0.001 for both) despite their higher serum albumin and lower serum Ca in comparison to group 1. The AGs of group 1 (11.1 +/- 0.4 mEq/l) and group 3 (11.1 +/- 0.3 mEq/l) were identical. There was no statistically significant correlation between the AG and serum Ca in the hypercalcemic patients. The major finding that the association of hypercalcemia with reduced AG is seen in hyperparathyroidism, but not in malignancy-related hypercalcemia, is not explained by differences in serum albumin, renal function, or acid-base status. Overlap of values between groups limits the diagnostic usefulness of the AG in an individual patient. Nevertheless, in the absence of multiple myeloma, the finding of an AG of 5 mEq/l or less in a hypercalcemic patient may be a helpful clue suggesting that malignancy is not the etiology.

Influence of magnesium sulfate-induced hypermagnesemia on the anion gap: role of hypersulfatemia.

Although hypermagnesemia purportedly lowers the anion gap (AG), we have shown previously that increases in the serum concentration of the unmeasured cation (UC) Mg due to therapeutic infusion of MgSO4 are not associated with AG reduction. To assess our hypothesis that increases in serum SO4 (unmeasured anion, UA) offset the effect of elevated serum Mg on the AG, we prospectively studied 11 patients receiving MgSO4 intravenously for toxemia of pregnancy. After 6 h of MgSO4 infusion, serum Mg increased by 2.1 +/- 0.2 (SE) mEq/l (p less than 0.001) without a significant decrease in the AG. Concomitantly, serum SO4 increased by 1.4 +/- 0.2 mEq/l. Comparison of the renal handling of SO4 versus Mg showed a higher fractional excretion of the former, probably accounting in part for the smaller increment of serum SO4 than of Mg. Comparison of the change in serum SO4 minus that of Mg indicated that, on the average, 70% of the observed 1.0 +/- 0.7 mEq/l reduction in AG was accounted for by the observed changes in the two pertinent unmeasured ions. A small decrement in serum Ca probably was a quantitatively minor factor tending to obviate a greater decrease in AG. We conclude that hypersulfatemia attenuates the reduction in AG that would otherwise accompany MgSO4-induced hypermagnesemia.

Severe hypermagnesemia without reduction in the anion gap.

The serum anion gap (AG) is usually calculated by the equation: AG = Na - (Cl + HCO3), reflecting the difference between the total level of unmeasured anions (all anions other than chloride and bicarbonate) and that of unmeasured cations (all cations other than sodium). Thus, several recent reviews have cited hypermagnesemia as a cause of a reduction in the AG. Whether this might occur depends in part on the nature of the accompanying anion (if the etiology of the hypermagnesemia is an exogenous load of magnesium), as well as on the presence of concomitant changes in endogenous unmeasured anions. In the present paper, we describe an unusual patient whose severe hypermagnesemia was not associated with AG reduction. Although multiple factors, including lactic acidosis, might have countervailed the effect of her hypermagnesemia on the AG, there is no actual substantiation in the literature of an association between increased serum Mg and AG lowering. In conclusion, the finding of a normal AG has no documented negative predictive value, and the finding of a low AG has no documented positive predictive value for the diagnosis of hypermagnesemia.

Anthracycline antibiotics. Interaction with DNA and nucleosomes and inhibition of DNA synthesis.

We report studies of the interaction of four anthracycline antibiotics, iremycin (IM), daunomycin (DM), aclacinomycin A (AM), and violamycin B1 (VM), with naked DNA, nucleosomal core particles, and 175 base pair (bp) nucleosomes lacking histone H1. In all cases the binding strength increases in the order IM less than DM approximately AM less than VM. The binding substrates increased in affinity for the drugs in the following order: core particles less than 175-bp nucleosomes less than DNA. The apparent DNA length increment per drug bound decreases in the progression IM greater than DM greater than AM greater than VM, the same serial order as is characterized by increasing binding affinity. Dichroism amplitude measurements show that for all drugs the long-wavelength absorbance transition moment is tilted by 26-29 degrees relative to the plane perpendicular to the helix axis; this angle probably corresponds to the long axis tilt of the intercalated chromophore. Finally, it was found that the ability of the drugs to inhibit DNA synthesis by Escherichia coli DNA polymerase I increases in the same order as their binding affinity.

Unfolding of 175-base-pair nucleosomes.

Calf thymus nucleosomes containing 175 base pairs of DNA unfold in two steps as the salt concentration is lowered, as detected by electric dichroism measurements. The transition midpoints are at 2.9 and 1.1 mM ionic strength at 7 degrees C with at most a small dependence on temperature. We identify the product of the 2.9 mM transition as an expanded disklike structure similar to the product of the 1.0--1.3 mM unfolding transition of 146-base-pair nucleosomes. The product of the 1.1 mM transition in 175-base-pair nucleosomes is elongated into a more asymmetric particle.