A report of accidental ethylene glycol ingestion in 2 siblings.

We describe a case of 2 siblings aged 2 1/2 and 3 1/2 yrs accidentally poisoned by ethylene glycol ingestion. We found estimating the level of ethylene glycol in plasma by calculation of osmolar gap too insensitive to be of value and advocate the availability of a specific method. In our study only one of the 2 children had a toxic level of ethylene glycol but assay by conventional assay and by proton magnetic resonance spectroscopy (1HMRS) of toxic metabolites viz glycolate, glyoxylate and oxalate showed both to be excreting grossly elevated levels. This indicates the desirability of assaying the toxic metabolites of the glycol as well as the parent compound in assessing ingestions.

Corticotropin deficiency: a rare cause of hyponatremia mimicking SIADH.

We describe 2 patients presenting with severe chronic hyponatremia in whom clinical and biochemical features strongly suggested the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Both, however, were proven to have a primary pituitary deficiency of corticotropin. Their short synacthen tests were only mildly abnormal but associated with low basal ACTH levels. The diagnosis of ACTH deficiency was made more convincingly by their dramatic response to glucocorticoid replacement therapy. In patients in whom no cause for SIADH can be found, a trial of maintenance cortisol therapy is warranted to exclude this eminently treatable condition.

Nitromethane interferes in assay of creatinine by the Jaffé reaction.

A patient who ingested a methanol/nitromethane mixture (model airplane fuel) showed an apparent plasma creatinine concentration of 8.0 mmol/L by the Jaffé reaction when the actual creatinine concentration, as measured by a specific enzymatic method, was 0.09 mmol/L. This effect was due to nitromethane in the plasma. Interference by nitromethane with the determination of creatinine by reaction with alkaline picrate (the Jaffé reaction) has not previously been reported. When nitromethane was added to plasma, the apparent creatinine measured was linearly related to the amount of nitromethane added. Comparison of spectral changes occurring during creatinine/picrate and nitromethane/picrate reactions show substantial similarity, suggesting a similar structure for the products. Although the findings are of interest for both their toxicological and analytical implications, the main interest lies with their suggestion of a model system for future investigation of the Jaffé reaction.

Evidence that the oral glucose-tolerance test does not provide a uniform stimulus to pancreatic islets in pregnancy.

Fifty consecutive pregnant patients referred for a glucose-tolerance test were classified on the basis of increasing (n = 20) or decreasing (n = 28) hematocrit after an oral 75-g glucose load. (The hematocrit did not change in the other two patients.) Patients with increasing hematocrit, a response previously seen in patients with the dumping syndrome, showed significantly flatter increases in glucose concentrations in plasma after the load. The mean decrease in the concentration of phosphate in plasma, measured as an index of glucose uptake by cells, was significantly less (P less than 0.05) 2 h after the load in the group with flatter glucose responses, suggesting that the flat response is ascribable to poor glucose absorption rather than to an exaggerated insulin response. These results indicate that the oral glucose-tolerance test stresses the pancreatic islets differently in different pregnant subjects, owing to individual variations in the gastrointestinal handling of the glucose load. Consequently, patients may give a "normal" result who might otherwise become hyperglycemic after normal meals. We suggest that alternative screening procedures be investigated to assess pregnant patients postprandially.

Functioning lipoadenoma of the parathyroid gland.

A lipoadenoma of the parathyroid gland was discovered at autopsy as the result of a search for the cause of terminally detected hyperparathyroidism in an elderly man who had suffered cerebral infarction. It is the only case known to the authors in which this uncommon cause of hyperparathyroidism was found at post-mortem examination after hypercalcemia and raised levels of serum immunoreactive parathormone were documented during life.

Comparison of 51Cr EDTA clearance with formulae in the measurement of glomerular filtration rate.

The need exists for a fast and accurate method of estimating glomerular filtration rate (GFR). A number of nomograms and formulae which estimate GFR on the basis of a plasma creatinine level have appeared in the literature. We examined some of these nomograms and formulae and showed that when the formula published by Cockcroft and Gault was compared with the GFR as estimated by 51Cr EDTA clearance, the coefficient of correlation was better than 0.94. We also compared creatinine clearance with the Cockcroft and Gault formula, and the Siersbaek-Nielsen nomogram. In each case, the correlation coefficient was less than that for the Cockcroft and Gault-51Cr EDTA comparison. Because of the inherent difficulties in making accurate 24 h urine collections, and problems associated with 51Cr EDTA studies, it is suggested that the formula prediction of GFR is more reliable than a GFR estimate using a 24 h collection.

Effects of subjects' sex, and intake of tobacco, alcohol and oral contraceptives on plasma phenytoin levels.

1. Steady state plasma phenytoin levels in 210 epileptic patients were studied by computerized analysis of covariance to determine whether the subject's sex, alcohol intake, tobacco smoking or use of oral contraceptives influenced the relation between plasma drug level and drug dose. 2. Sex, tobacco smoking and alcohol usage had no statistically significant effect. There was a trend towards higher phenytoin levels relative to drug dose in oral contraceptive users. 3. This finding prompted an additional study of plasma phenytoin levels in 40 oral contraceptive users and 135 aged matched non-users. Analysis of covariance again showed higher plasma phenytoin levels relative to drug dose in users of oral contraceptives (P = 0.061). 4. This finding raised the possibility that the relation between plasma phenytoin level and drug dose differed between males and females who did not use oral contraceptives. However, when the relation between plasma phenytoin levels and drug dose was compared in 159 females who did not use oral contraceptives and 101 males (both groups aged 15 to 70 years) no statistically significant difference was found.

PIP: Computerized analysis of covariance was used to study the steady state plasma phenytoin levels of 210 epileptic patients to determine whether sex, alcohol intake, tobacco smoking, or use of oral contraceptives (OCs) affected the relation between plasms drug level and drug dose. Sex, tobacco, and alcohol had no statistically significant effects. However, a trend toward higher phenytoin levels relative to drug dose in OC users prompted an additional study of plasma phenytoin levels in 40 OC users and 135 aged-matched controls (nonusers). Again, analysis of covariance showed higher plasma phenytoin levels relative to drug dose in OC users (P=.061). This finding was investigated in relation to subjects' sex; however, when the relation between plasma phenytoin levels and drug dose was compared in 159 females who did not use OCs and 101 males (both groups aged 15-70 years), no statistically significant difference was found. Therefore, the results indicate that age (beyond puberty) and sex are not significant determinants of plasma phenytoin levels relative to dose; tobacco use and moderate intake of alcohol were also unimportant considerations; however, the significance of OCs to plasma levels raises the possibility that OC use may decrease phenytoin metabolism.