No abstract

Diabetic ketoacidosis is usually accompanied by volume depletion and prerenal azotemia. However, the case reported here and a chart review of 10 patients with diabetic ketoacidosis showed creatinine concentration to be disporportionately elevated compared to the blood urea nitrogen level on admission, compatible with true renal insufficiency. Investigation showed most of this elevation in creatinine to be artifactual and due to interference of acetoacetate in the automated methods for measuring creatinine. A manual method that excluded noncreatinine interfering chromagens showed no interference. This manual method should be used to measure creatinine in patients admitted with ketoacidosis to exclude the possibility of coexistent renal insufficiency.

Graft-versus-host disease (GVHD) remains a major obstacle to allogeneic bone marrow transplantation. We administered cyclosporin A (CsA) by continuous intravenous infusion for prophylaxis against GVHD and adjusted the dose to maintain a constant whole blood level. Forty-five patients, ranging in age from 16 to 56, mean 39.5 years, undergoing allogeneic transplantation for various hematological malignancies received CsA as a continuous intravenous infusion. CsA was started on day -1 and continued until day +22 when oral CsA was initiated. The whole blood level of CsA was determined and the dose adjusted to maintain a fixed level. Methotrexate 15 mg/m2 i.v. was given on day +1, followed by 10 mg/m2 on days +3 and +6. CsA administered as a continuous infusion was well tolerated. All patients required multiple adjustments of the infused dose of CsA to maintain the targeted whole blood level. The mean rise in creatinine was 0.89 mg/dl. There was an association between the concomitant administration of amphotericin B and CsA and the development of nephrotoxicity. Hypertension developed in 30/45 patients, and all responded to oral nifedipine. Tremors were noted in 16/45 patients. None of the patients developed serious neurological side effects. Greater than grade-I acute GVHD developed in only 13% of the patients. We conclude that administering CsA as an adjusted dose by continuous intravenous infusion is well tolerated and effective in preventing acute GVHD in patients undergoing allogeneic bone marrow transplantation.

A soluble L-a-glycerophosphate dehydrogenase, which is stimulated by FAD and is independent of added pyridine nucleotides, functions during anaerobic catabolism of glycerol and L-a-glycerophosphate by Escherichia coli. Aerobic catabolism of both glycerol and L-aglycerophosphate (L-a-GP) by Escherichia coli requires an L-a-GP dehydrogenase (E. C. 1.1.2.1) that is particulate and independent of added pyridine nucleotides. Mutants lacking this enzyme fail to grow areobically on either glycerol or La-GP (4). Glycerol or L-a-GP can also be dissimilated anaerobically by E. coli if a suitable electron acceptor such as nitrate (8) or fumarate (5) is available. We have recently found that mutants lacking the known L-a-GP dehydrogenase are unimpaired in their ability to metabolize either glycerol or L-a-GP anaerobically. This behavior is true for six independent mutants, including one with a partial deletion of the structural gene for the known dehydrogenase. Figure 1 depicts the anaerobic growth of one such mutant, strain 95, which lacks the known dehydrogenase and is totally incapable of growth aerobically on glycerol or L-a-GP (1). The medium contains L-a-GP as the principal carbon source and KNO3 as oxidant. Except for a slight lag (possibly due to residual 02 dissolved in the medium), the mutant grew as well as its wild-type parent, strain 1 [derived from E. coli K-12 Hfr Cavalli (4)]. Similar results were obtained when glycerol served as the principal carbon source.