Minimizing the risk of brain herniation during treatment of diabetic ketoacidemia: a retrospective and prospective study.

We studied retrospectively, 219 episodes of diabetic ketoacidemia in 119 patients aged 13 months to 30 years, to determine the trend of the concentration of sodium in serum as glucose declined during treatment of uncomplicated episodes and of episodes with complications attributable to brain swelling. Of 20 complication, 13 were minor (headache only) and 7 major (death or near death). The concentration of sodium in serum failed to rise as that of glucose declined in 82 (54%) of 164 uncomplicated episodes and in 18 (95%) of 20 complicated episodes (p less than 0.01). Hence complications were more likely to occur among patients with a failure of the concentration of sodium to rise as glucose declined. Fifty-eight episodes of diabetic ketoacidemia in 40 patients aged 1 1/2 to 20 years were then studied prospectively on a 48-hour treatment plan to provide the volume of deficit evenly, with half the deficit of sodium in the first 42 hours. Sodium concentration in serum rose in 55 (95%) of 58 episodes as that of glucose declined. No patient had a major complication. We conclude that failure of the sodium concentration measured in serum to rise as glucose concentration declines is a marker for excessive administration of free water. An expanded repair period, with repair fluid containing an average of 125 mmol/L Na+ early in therapy, will usually protect against a downward trend in the concentration of sodium in serum and therefore against a rapid decline in effective serum osmolality. This regimen may be protective against near-death episodes and brain herniation during treatment.

Intermittent non-ketotic dicarboxylic aciduria in two siblings with hypoglycaemia: an apparent defect in beta-oxidation of fatty acids.

Two siblings with intermittent hypoglycaemia, lethargy and coma associated with fatty infiltration of the liver are reported. Urine contained C6 to C14-dicarboxylic acids.

Pharmacokinetics of methicillin in patients with cystic fibrosis.

The disposition of methicillin in normal subjects and in subjects with cystic fibrosis (CF) was studied after administration of single intravenous doses of 15 mg/kg. The area under the serum concentration vs. time curve for CF patients was, on the average, only 75% of that found for normal subjects. The low concentrations in serum were caused by more rapid urinary excretion of the antibiotic, with rates of renal clearance averaging 425 ml/min per 1.73 m2 in the patients with CF and 362 ml/min per 1.73 m2 in the normal subjects. No differences were found in volumes of distribution and metabolic clearance rates of methicillin or in rates of creatinine clearance between the two groups of subjects. These data support previous findings with dicloxacillin which show that patients with CF exhibit unusually rapid, active tubular secretion of certain penicillins that may necessitate use of larger doses of these drugs in treatment of infections.

Hypophosphatasia: a developmental anomaly of alkaline phosphatase?

This report deals with quantitative and qualitative investigations of alkaline phosphatase in two unrelated infants with the severe infantile form of hypophosphatasia. Both affected infants had no detectable leukocyte alkaline phosphatase activities and both sets of parents and one sibling tended to have low but variable leukocyte enzyme activities. Normal duodenal juice alkaline phosphatase activity was present in the one patient in whom it was measured and a wide range of variation in enzymic activity was observed in the stools. There was no significant difference in the stool enzyme activity between both patients with hypophosphatasia (42.01 +/- 9.77 U) and control infants (40.55 +/- 6.29 U). However, the heterozygous parents had values significantly lower than the control adults (2.10 +/- 0.47 as compared with 19.10 +/- 4.44 U). Intestinal bacteria did not contribute significantly to the stool alkaline phosphatase activity. Enzyme activity was present in the bile of one of the patients and nearly absent in that of the other. Three "inducers" of alkaline phosphatase were given to both patients (phenobarbital, vitamin A, and corticosteroid). No clinical improvement or rise in serum alkaline phosphatase activity was observed during the trial of therapy with these agents. However, a significant increase in the activity of serum acid phosphatase was demonstrated during the course of vitamin A administration, suggesting an in vivo action of vitamin A on the lysosomes through decreasing the stability of the membrane and releasing acid phosphatase to the serum. Quantitative determination of tissue alkaline phosphatases from autopsy tissues was highly variable: no activity was found in bone, lungs, or spleen of either infant; there was a discrepancy in liver and kidney alkaline phosphatase values (zero in one patient and present in the other) and activity was present in the intestinal mucosa of both. Qualitative analysis of kidney, liver, and intestinal alkaline phosphatase revealed some differences between the patients and control subjects in heat inactivation and phenylalanine inhibition (Table 3). Starch gel electrophoresis of the liver preparation of one patient disclosed a single band which had greater mobility than that of six control subjects matched for age. Liver extracts from a premature and from full term newborns showed two bands. The single band of the patient's liver enzyme corresponded to the newborn's fast moving component. In addition, the intestinal enzyme prepared from the same patient had an extra band when compared with age-matched control subjects.

Enhanced renal excretion of dicloxacillin in patients with cystic fibrosis.

Single oral doses of 6.25 mg/kg of dicloxacillin suspension were given to ten cystic fibrosis (CF) patients and eight normal subjects. Peak serum concentrations and areas under the concentration versus time curves for dicloxacillin were variable and, on average, were 2 1/2 times lower in the CF patients. The time of occurrence of the peak serum concentration was similar in both groups and the total urinary recovery of dicloxacillin was normal or increased in the CF patients, suggesting that the intestinal absorption of the drug was unaffected by the disease. The low serum concentrations in the CF patients were caused by unusually high renal clearances of dicloxacillin which average 282 +/- 135 compared to 95 +/- 28 ml/min/1.73 sq m in the normal subjects. Creatinine clearances were also elevated in the CF patients by 55% on average, while urea clearances were normal. The serum protein binding of dicloxacillin was similar in both groups of subjects. Because the rapid excretion results in low and variable serum concentrations of the antibiotic, treatment of CF patients with dicloxacillin may warrant use of increased or more frequent doses and monitoring of serum antibiotic levels.

Colonization by Enterobacteriaceae of the respiratory tract of children with cystic fibrosis of the pancreas and their antibody response.

Of 72 patients with fibrosis, 49 harbored Enterobacteriaceae in the respiratory tract, including Escherichia coli, Klebsiella, and Enterobacter. Colonization by two to four genera was documented in 29 subjects. Staphylococcus aureus was recovered from 44 of these 49 patients. The distribution of serogroups of E. coli was similar to that seen in patients with urinary tract infection. Antibody response against the O antigens of the patients' own Enterobacteriaceae was documented in 29 of these 49 children and encountered more often in patients with severe disease. Colonization by Enterobacteriaceae in the absence of Pseudomonas aeruginosa was seen more frequently in children with the mild form of the illness.