Warren F. Dodge

Proteinuria and hematuria in schoolchildren: Epidemiology and early natural history†

Over the past several decades screening for disease in large asymptomatic populations has increased, culminating most recently with a federal mandate for early, periodic screening, diagnosis and treatment of all children from low-income families. The present study of five consecutive examinations in over 12,000 schoolchildren shows the cumulative occurrence of proteinuria and hematuria to be surprisingly high (greater than 6%). Comparison of this large number of children with the few individuals in whom death occurs from chronic renal disease annually (less than 0.03%) suggests that the vast majority of these children with urinary abnormalities have either no renal disease or at most a self-limited condition. Observation of 512 children with proteinuria and 78 with hematuria for one to five years after initial detection and referral to their physician or clinic provides a measure of both contemporary management and early natural history. These observations suggest that there is a need to question the overall effectiveness of urinary screening and that early inclusion of roentgenographic and urologic investigations in management seems unwarranted. Rather, these children should be followed for long periods of time. Additional investigations are indicated when worsening of the abnormal findings or other evidence of renal or systemic disease occurs. If routine urinary screening is performed, it should be as one aspect of a multiphasic program by the primary physician so that it can be coupled with a clearly defined plan for follow-up and management of subjects with abnormal findings.

Tumoral Calcinosis with Hyperphosphatemia: A Report Of A Family With Incidence In Four Siblings

Four siblings with tumoral calcinosis and hyperphosphatemia have been studied for several years. In one the disease was recognized prior to its clinical appearance because of hyperphosphatemia. The hyperphosphatemia is not a result of renal insufficiency or of an abnormal parathyroid response. The hyperphosphatemia and tumors did not occur independently in our patients, and serum phosphorus determinations may be useful for screening. Recurrence after total excision of a mass is common and should be treated by early re-excision. The initial results of this treatment have been fairly good.

Population pharmacokinetic models: Effect of explicit versus assumed constant serum concentration assay error patterns upon parameter values of gentamicin in infants on and off extracorporeal membrane oxygenation

Prior authors had hypothesized (but not clearly found) an increased apparent volume of distribution (Vd) for gentamicin in neonates undergoing extracorporeal membrane oxygenation (ECMO). We chose to study the question in our own clinical setting. To develop population pharmacokinetic models of the drug, we used the nonparametric expectation and maximization population modeling method and data from 11 neonates who received gentamicin on ECMO, including 6 infants who received gentamicin both on and off ECMO for severe respiratory failure. We found an increased Vd for gentamicin on ECMO and attributed much of the difference from prior investigations to our use of an explicitly determined laboratory assay error pattern for the measured serum concentrations rather than using constant weighting of the serum level data points. For six infants, while on ECMO their median Vd was 0.748 L/kg compared with a median Vd of 0.471 L/kg after ECMO was discontinued. The median clearance of gentamicin in the six infants while undergoing ECMO was 0.239 L/h compared with 0.350 L/h after ECMO was discontinued. The median half-time (T1/2) was 9.24 h while on ECMO compared with 3.87 h when off ECMO. We conclude that while undergoing ECMO, neonates have a higher volume of distribution for gentamicin, a lower clearance, and a much longer half-life. Based on these results, for attainment of the desired peak-and-trough plasma gentamicin concentrations for infants undergoing ECMO (i.e., 5–8 and <2.0 μg/ml, respectively), we now recommend a loading dose of ∼4.3 mg/kg of gentamicin and a maintenance dose of ∼3.7 mg/kg to be given at dosing intervals of 18–24 h, followed by monitoring of serum concentrations and appropriate dose adjustments thereafter. To attain alternative goals, the model provides different loading and maintenance doses.

Defective thirst mechanism secondary to a hypothalamic lesion: studies in a child with adipsia, polyphagia, obesity, and persistent hyperosmolality.

This report details studies in a child who lacked thirst perception and had such other manifestations of hypothalamic dysfunction as polyphagia, obesity, and inadequate temperature regulation. Though no gross lesion was observed in the hypothalamus at autopsy, there was histologic evidence of degeneration of neuronal cells and a secondary inflammatory response. The accumulated data support the assumption that sustained hyperosmolality may have altered renal concentration and dilution.

Detection of bacteriuria in children

Summary Lack of a simple, inexpensive, yet accuratemethod for urine culture has prevented universal, routine office screening of girls and pregnant women for the presence of bacteriuria. The present study demonstrates a high degree of reliability for a miniature culture method (Testuria) when compared with the quantitative pour plate technique in the examination of 8,469 urine specimens. Widespread application of this screening technique will, with a minimum of expense and inconvenience, allow the majority of these females to be reliably assured that they do not have significant bacteriuria. Re-examination of the few patients in whom the single Testuria culture result is suspicious (i.e., 4 or more colonies) with a more definitive bacteriologic method is then required in order to detect those who have significant bacteriuria.

Population Pharmacokinetic Models

SummaryThe availability of personal computer programs for individualising drug dosage regimens has stimulated interest in modelling population pharmacokinetics. Appropriate use of population models requires knowledge of the distribution of their pharmacokinetic parameter values. If non-Gaussian, it is imperative not to assume that the arithmetic mean is the best measure of central tendency. This has important consequences for therapeutic drug monitoring and for individualising drug dosage regimens.Utilising a new nonparametric expectation maximisation (NPEM) population modelling program and retrospective data from 129 preterm infants who received gentamicin in our own clinical setting, we developed 2 population models. The NPEM algorithm showed that both had significant non-Gaussian distributions of their parameter values (e.g. the mean value for the volume of distribution exceeded the 75th percentile).Although the median parameter values demonstrated only slightly better predictive accuracy than the mean, its choice as the measure of central tendency was associated with excellent agreement between the goal and the subsequently observed average initial peak serum gentamicin concentrations (i.e. 6.0 vs 6.2 mg/L). In contrast, simulation using the mean parameter values predicted an average concentration 30% greater than the goal (i.e. 8.0 vs 6.0 mg/L). Thus, for this group of patients, the median proved a better measure of central tendency.

Intrarenal arteriovenous fistulas followingneedle biopsy of the kidney

Intrarenal arteriovenous fistulas following percutaneous renal biopsy have beenobserved in 3 children. One of them was severely and another mildly hypertensive prior to biopsy. In 2 of them, bilateral fistulas were demonstrated. Repeat arteriograms about a year later did not disclose any evidence of a fistula in either kidney of these two patients. Some of the manifestations of this type of distula seems to heal spontaneously in the majority of instances.

Significance of transientbacteriuria in screening programs for bacteriuria

I N 1960 Kunin and associates 1 reported the results of screening of school children for significant bacteriuria utilizing the concept of the quantitative bacterial colony count introduced by Marple 2 and extended by Kass? In subsequent years a large number of infants and children have been similarly screened. 4-8 With this has come concern about the interpretation of borderline counts, the significance of transient bacteriuria, and the possible needless treatment of otherwise healthy asymptomatic girls? The current report attempts to provide information on this point by comparison of routine annual urine culture results over 4 years for schoolgirls initially found to have persistent significant

Prolonged coma and visual loss: Unusualreaction to chlorothiazide*

Summary Chorothiazide was administered to a 7-year-old boy suffering from nephrogenic diabetes insipidus, following which he developed prolonged coma, hyperpyrexia, and cortical blindness. Though the exact mechanism of this unusual reaction is not clear, it is felt that it represents an abnormal response to the administration of chlorothiazide.

189 METABOLIC ACIDOSIS, HYPERGLYCEMIA, AND KETONURIA IN CARBAMAZEPINE OVERDOSE

Certain drugs may produce hyperglycemia by decreasing pancreatic secretion of insulin. We report a case of accidental carbamazepine overdose in a previously healthy three year old black male who presented in an unconscious state without seizures with an arterial pH of 7.28, serum glucose of 210 mg/dl, and urine glucose and ketones of 3+ and 2+, respectively. Arterial blood gases showed a pure metabolic acidosis. A diagnosis of diabetic ketoacidosis was made; the patient was given insulin, sodium bicarbonate, and intravenous hydration. Subsequent history revealed that the patient ingested an unknown amount of carbamazepine. A toxic serum carbamazepine level of 22 mcg/ml (therapeutic = 6 to 10) was found. The patient was treated with activated charcoal and general supportive care. Complete symptomatic recovery occurred by the end of 48 hours and follow up laboratory studies failed to show any evidence of hyperglycemia, ketonuria, or glycosuria.This case demonstrates a previously unreported manifestation of carbamazepine overdose in a child, i.e., metabolic acidosis, hyperglycemia and ketonuria. Carbamazepine in high dose is known to produce hyperglycemia in rats possibly by decreasing the sodium influx needed for insulin secretion (Pharmacology 24:123, 1982). We conclude that metabolic acidosis due to carbamazepine overdose should be considered in the differential diagnosis of altered metabolic states and drug overdose.