Isolated congenital malabsorption of folic acid in a male infant: insights into treatment and mechanism of defect.

An instructive case of isolated congenital folate malabsorption provides insight into the understanding of this rare disease. Folate loading tests with both timed serum and cerebrospinal fluid folate determinations suggest that both of the two mechanisms involved in gastrointestinal folate absorption are defective in this condition.

Oral versus intravenous corticosteroids in children hospitalized with asthma.

BACKGROUND: Previous studies have demonstrated that in the emergency treatment of an asthma exacerbation, corticosteroids used in conjunction with beta-agonists result in lower hospitalization rates for children and adults. Furthermore, orally administered corticosteroids have been found to be effective in the treatment of outpatients with asthma. However, similar data in inpatients is lacking. OBJECTIVE: The purpose of this study was to determine the efficacy of oral prednisone versus intravenous methylprednisolone in equivalent doses for the treatment of an acute asthma exacerbation in hospitalized children. METHODS: We conducted a randomized, double-blind, double-placebo study comparing oral prednisone at 2 mg/kg/dose (maximum 120 mg/dose) twice daily versus intravenous methylprednisolone at 1 mg/kg/dose (maximum 60 mg/dose) four times daily in a group of patients 2 through 18 years of age hospitalized for an acute asthma exacerbation. All patients were assessed by a clinical asthma score 3 times a day. The main study outcome was length of hospitalization; total length of stay and time elapsed before beta-agonists could be administered at 6-hour intervals. Duration of supplemental oxygen administration and peak flow measurements were secondary outcome measures. RESULTS: Sixty-six patients were evaluated. Children in the prednisone group had a mean length of stay of 70 hours compared with 78 hours for the methylprednisolone group (P =.52). Children in the prednisone group were successfully weaned to beta-agonists in 6-hour intervals after 59 hours compared with 68 hours for the methylprednisolone group (P =.47). Patients receiving prednisone required supplemental oxygen for 30 hours compared with 52 hours for the methylprednisolone group (P =.04). CONCLUSION: There was no difference in length of hospital stay between asthmatic patients receiving oral prednisone and those receiving intravenous methylprednisolone. Because hospitalization charges are approximately 10 times greater for intravenous methylprednisolone compared with oral prednisone, the use of oral prednisone to treat inpatients with acute asthma would result in substantial savings.

Granulomatous hepatitis in three children due to cat-scratch disease without peripheral adenopathy. An unrecognized cause of fever of unknown origin.

OBJECTIVE: To report the clinical experience of three patients with fever of unknown origin ultimately diagnosed as having cat-scratch granulomatous hepatitis in the absence of peripheral adenopathy. DESIGN: Case-control study. SETTING: Referral center at university-based referral practice. PATIENTS: Three children with fever of unknown origin. Follow-up following presentation was 6 months for each patient. MEASUREMENT AND RESULTS: All three patients with fever of unknown origin were diagnosed radiographically to have multiple hepatic defects. The defects were shown histologically to be granulomatous. Two of the three patients had Warthin-Starry staining bacilli in the granulomas consistent with a diagnosis of Afipia felis. All three had positive cat-scratch skin test results. CONCLUSIONS: Cat-scratch disease in the absence of peripheral adenopathy is a heretofore unrecognized cause of fever of undetermined origin and may account for a small, but significant, percentage of children presenting with it.

Polycystic kidneys, pancreatic cysts, and cystadenomatous bile ducts in the oral-facial-digital syndrome type I.

Oral-facial-digital syndrome type I is a group of X-linked dominant conditions, lethal in utero in male individuals. Internal anomalies are less well documented than are external findings. We report a case of typical phenotype and absent family history of kidney disease in a 15-year-old white girl (46,XX) who died of renal failure and massive cerebral hemorrhage. At necropsy, the kidneys were greatly enlarged but of fairly normal shape. The cortex was replaced by thin-walled spherical cysts, 0.5 to 2.0 cm in diameter; the majority of the smaller cysts were located deep in the cortex, and the medulla contained lesser numbers of larger cysts. No distal urinary tract obstruction was present. Microdissection revealed cysts and diverticula located in all segments of the nephrons and collecting ducts. Uninvolved nephrons showed diffuse hypertrophy. These findings were correlated with immunoperoxidase stains using peanut lectin, Lotus tetragonolobus agglutinin, antibodies to cytokeratins, stage-specific embryonic antigen-1, Tamm-Horsfall protein, and epithelial membrane antigen. Other visceral anomalies included biliary cystadenomatous proliferation in the liver and pancreatic cysts. The renal changes are similar to those of autosomal dominant (adult-type) polycystic disease.

Marked transient alkaline phosphatemia following pediatric liver transplantation.

An isolated marked transient rise in serum alkaline phosphatase levels in otherwise healthy children is a well-documented occurrence. However, in children undergoing liver transplantation, elevated alkaline phosphatase values raise the possibility of biliary obstruction, rejection, or both. During a 6-year period, 6 of 278 children undergoing liver transplantation exhibited a similar phenomenon as an isolated abnormality. None had rejection, biliary obstruction, or other allograft dysfunction during a long follow-up. Eventually and without intervention, the alkaline phosphatase levels returned to normal. These instructive cases suggest that caution be used in advocating invasive procedures if elevated alkaline phosphatase levels are an isolated abnormality, and close observation with noninvasive testing is recommended.

Varicella in pediatric orthotopic liver transplant recipients.

From May 1981 to May 1984, 90 pediatric patients underwent liver transplantation and 65 patients survived as of May 1986. Two of the nonsurvivors died with complications related to clinical varicella. Of these 67 patients (65 survivors and two nonsurvivors who died of varicella-related causes), 51 patients were determined to be varicella susceptible. Clinical disease developed in no patients with serologic evidence or clinical history of varicella prior to transplantation. Eighteen susceptible patients were exposed and received zoster immune globulin and varicella did not develop. Clinical disease developed in eight patients despite zoster immune globulin, although one patient received it 96 hours after exposure. Six patients received no zoster immune globulin and clinical varicella developed. In all, varicella developed in 14 patients. Thirteen were admitted to the hospital and treated with intravenous acyclovir. Of those treated, two died of causes related to complications of varicella. The remaining patients treated with acyclovir had mild disease. The one patient not treated with acyclovir also had mild disease. We conclude that patients contracting varicella after liver transplantation while receiving maintenance immunosuppressive agents should be treated with intravenous acyclovir. Generally, when treated with acyclovir while receiving maintenance immunosuppressive drugs, these patients have mild clinical disease. Patients recently treated with high-dose prednisone and cyclosporine may have severe clinical disease resulting in death.

Kawasaki disease and perineal rash.

During the past several years, we treated seven children with Kawasaki disease who developed a distinctive but rarely described perineal rash. This rash began three to four days from onset of the illness and desquamated in all instances by days 5 to 7. The presence of this rash may facilitate early diagnosis of Kawasaki disease and, hence, may influence the initiation of early treatment.

Changes in life-style after liver transplantation.

Sixty-five pediatric patients who received liver transplants between May 1981 and May 1984 were observed for as many as 5 years and examined for changes in life-style. Children were less frequently hospitalized, spent less time hospitalized, required fewer medications, and generally had excellent liver and renal function after hepatic transplantation as compared with their pretransplantation status. Most children were in age-appropriate and standard school classes or were only 1 year behind. Cognitive abilities remained unchanged. Children improved in gross motor function and patients' behavior significantly improved according to parents' perceptions. Enuresis was more prevalent, however, than in the population of children who had not received liver transplants. Parental divorce rates were no greater than those reported for other families with chronically ill children. Overall, objective changes in life-style as well as parents' perceptions of behavior of children appear to be improved after liver transplantation.

Improvement of cerebral CT abnormalities following liver transplantation in a patient with Wilson disease.

Cerebral CT performed in patients with Wilson disease (hepatolenticular degeneration) often reveals abnormalities of the putamen, globus pallidus, thalamocapsular region, cerebral cortex, dentate nucleus, and brain stem. We report a patient with Wilson disease who demonstrated rapid reversal of CT abnormalities following orthotopic liver transplantation.

Choosing a pediatric recipient for orthotopic liver transplantation.

Between March 3, 1981, and June 1, 1984, 216 children were evaluated for orthotopic liver transplantation. Of the 216 patients, 117 (55%) had received at least one liver transplant by June 1, 1985. Fifty-five (25%) died before transplantation. The 117 patients who received transplants were grouped according to severity of disease and degree of general decompensation at the time of transplantation. The severity of a patient's medical condition with the possible exception of deep hepatic coma, did not predict outcome following orthotopic liver transplantation. Seventy variables were assessed at the time of the evaluation. Twenty-three of the 70 variables were found to have prognostic significance with regard to death from progressive liver disease before transplantation. These 23 variables were incorporated into a multivariate model to provide a means of determining the relative risk of death among pediatric patients with end-stage liver disease. This information may allow more informed selection of candidates awaiting liver transplantation.

Pediatric liver transplantation: patient evaluation and selection, infectious complications, and life-style after transplantation.

Liver transplantation is an increasingly accepted treatment for children with end-stage liver disease. Evaluation of the patient and appropriate patient selection for transplantation will become increasingly important issues as more and more children come to transplantation and compete for available organs. Numerous complications occur after transplantation, including infections. We have summarized our experience with bacterial, fungal, and viral infections in these patients and emphasize the need for continued improvement in immune suppressive drugs and regimens to minimize such complications. And finally, information presented on 65 pediatric patients followed 2 to 5 years suggests that, despite numerous complications and often prolonged hospitalization for transplantation, life-style after transplantation appears to be significantly improved.

Linear growth following pediatric liver transplantation.

The linear growth of 29 patients was evaluated from two to 41/2 years after liver transplantation. All patients received cyclosporine and low-dose prednisone. Eight patients (28%) displayed acceleration of linear growth velocity and were above the fifth percentile at the end of the evaluation period. Four patients (14%) grew normally prior to transplantation and continued to grow normally after the surgical procedure. Only four patients (14%) dropped from higher levels to below the fifth percentile. Thirteen patients (45%) were less than the fifth percentile before and after surgery; ten of these 13 patients have attained normal or accelerated growth velocity. Good linear growth has been achieved in more than three fourths of patients who underwent liver transplantation.

Hepatic infarction and acute liver failure in children with extrahepatic biliary atresia and cirrhosis.

Acute hepatic failure developed in four patients (aged 7 to 13 months) who had extrahepatic biliary atresia treated initially by portoenterostomy. Two were stable outpatients with minimal jaundice, while the other two were hospitalized for metabolic or nutritional complications. Postmortem examination in each patient revealed massive acute hepatic infarction with few surviving hepatocytes. In all cases, the hepatic failure had been preceded by an episode of hypotension and/or hypovolemia. The exact pathogenesis of the infarction remains unclear but it may be related to decreased hepatic blood flow secondary to biliary obstruction. The only effective treatment for these patients is intensive supportive care and urgent liver transplantation.

Cyclosporine absorption following orthotopic liver transplantation.

Blood concentrations of cyclosporine were determined in adult and pediatric patients following orthotopic liver transplantation to quantitate cyclosporine blood clearance and oral absorption. Seventeen bioavailability studies were performed following transplantation surgery in nine children and seven adults. The intravenous cyclosporine study was performed following an average dose of 2.1 mg/kg. The patients were again studied when they received the same intravenous dose plus an oral dose of cyclosporine of 8.6 mg/kg or an oral dose alone. Blood samples were collected and analyzed for cyclosporine using high-performance liquid chromatography. Cyclosporine blood clearance ranged from 29 to 203 mL/min (1.9-21.5 mL/min/kg) in children and from 253 to 680 mL/min (3.2-7.6 mL/min/kg) in adults. The mean cyclosporine clearance value was 9.3 mL/min/kg in the pediatric patients and 5.5 mL/min/kg in the adults. Cyclosporine bioavailability was less than 5% in six studies on five pediatric patients in the immediate postoperative period. The bioavailability varied from 8% to 60% in adult liver transplant patients (mean, 27%). We conclude that: cyclosporine clearance is highly variable between patients, pediatric patients clear the drug more rapidly than adults and therefore need a higher cyclosporine dose on a body weight basis, cyclosporine is poorly and variably absorbed in liver transplant patients, and cyclosporine blood concentration monitoring is essential following orthotopic liver transplantation.