Robert H. A. Haslam

Trisomy 9 Mosaicism with Multiple Congenital Anomalies

A nine-year-old male with developmental abnormalities was found to be mosaic for an extra No. 9 chromosome (46,XY/47,XY,+9). The clinical findings included severe mental retardation, peculiar facies, short stature, hypotonia, dextroposition with a ventricular septal defect, and patent ductus arteriosus, as well as significant abnormalities of the brain.

1677 NEUROTOXIC COMPLICATIONS OF CONTRAST CT IN CHILDREN

Computed cranial tomography (CT) has been considered a safe and accurate method for studying intracranial lesions in children. As a diagnostic adjunct, radiographic contrast material is administered intravenously (IV) to enhance and further characterize lesions such as vascular malformations. Traditional ionic contrast agents can penetrate the blood brain barrier (BBB) and exert an adverse effect due to hyperosmolality, lipid solubility and neurotoxic properties when administered intra-arterially. Contrast agents given IV are generally considered non-neurotoxic.We report 3 children with brain tumors who rapidly deteriorated following CT with infusion. All had evidence of papilledema but were alert and responsive prior to CT. A patient dose of 2-2.5 ml/kg IV Renografin-60 (diatrizoate meglumine 52% and diatrizoate sodium 8%) was used. Within 6 to 8 hours each child showed progressive lethargy, disorientation, bradycardia, hypertension and generalized seizures (2).Zamani showed that 4ml/kg IV diatrizoate meglumine-60 disrupted the BBBin some normal dogs. Focal seizures have recently been reported in adults with cerebral metastases following contrast CT. It is likely that the neurological deterioration in the reported children resulted from the osmotic effects of contrast material on cerebral tissue. As contrast enhanced CT may produce grave neurological complications in children with brain tumors, the study should be reserved for those where the probability of additional significant diagnostic yield exists.

Use of radioimmunoassay to study diphenylhydantoin pharmacokinetics in children

The detailed study of the kinetics of the anticonvulsant, diphenylhydantoin (DPH), in small children has been difficult with conventional gas chromatographic (GLC) methods. A new radioimmuno-assay (RIA) developed by Cook and Christensen (Res. Comm. Chem. Path. Pharmacol. 5: 767, 1973) was duplicated in our laboratory and some of the characteristics of the assay defined. The sensitivity of this assay allowed DPH levels to be determined accurately in 20 μl of plasma. The antibody is highly specific for DPH and the assay correlates well with GLC. In several infants being treated for seizures with a commonly used dose, plasma DPH levels were found to be low. The RIA method facilitated monitoring their plasma levels. When plasma levels were measured following an IV dose of DPH, the infants were found to metabolize the drug more rapidly than did adolescents and adults.

75 Effect of Copper on Serum. Ceruloplasmin Concentration

The effects of the oral administration of copper were studied in 1. infants with nutritionally induced cooper deficiency; 2. children receiving copper sulfate as an emetic after toxic ingestions. 1. Seven marasmic infants were rehabilitated with a high calorie-adequate protein-low copper diet. In 2 of them where initial determinations were performed, serum ceruloplasmin concentration was normal. With recovery and rapid growth, copper deficiency developed, and all 7 exhibited hypoceruloplasminemia. The intact metalloprotein was deficient both by oxidase and immunochemical assays. Apoceruloplasmin could not be detected immunochemically. Thus both the copper prosthetic group and the apoprotein were deficient. In each of the 7, ceruloplasmin levels rose after the administration of copper, 0.10–0.30 mg/kg/day. 2. Copper sulfate, 250 mg, was administered orally as an emetic to 4 children after toxic ingestions. Although vomiting occurred within 5 minutes, a rise of serum copper of 14, 22, 30 and 71 μg% was observed. Serum ceruloplaxmin concentration increased significantly in 3 of the children within 12 hours. Thus it appears that copper either stimulates de novo synthesis of ceruloplasmin or combines with apoceruloplasmin in the liver to form the metalloprotein which is then released into the peripheral blood. It is possible that in Wilsons disease this mechanism may be impaired. Because copper is corrosive and absorbed, even after prompt emesis, it does not appear to be a safe emetic, as recently advocated, particularly when the agent ingested has the same effects as toxic doses of copper. (APS)