Safety and efficacy of percutaneous endoscopic gastrostomy in children.

OBJECTIVES: To establish the safety and efficacy of percutaneous endoscopic gastrostomy (PEG) placement for nutritional support in children. METHODS: The charts of 70 children who underwent the procedure between 1989 and 1992 were reviewed. Three of the 70 had repeat PEG placement. Patients ranged in age from 3 months to 24 yr, and included 28 females and 42 males. In all patients, the weights at the time of insertion of the PEG, and in 64, weight after 6 months of nutritional support, were compared by Z-score, and the incidence of major and minor complications was determined. RESULTS: Forty-five of 70 patients (70%) had improved nutritional status after initiation of PEG feedings, and in three (4%), the weight was maintained despite limited oral intake. Patients with congenital heart disease (86%) and cystic fibrosis (80%) derived the greatest benefit from the enteral feedings. Major complications were noted in 13 (19%) patients and minor complications in 16 (22%). Nine of 13 (70%) major complications and four of 116 (25%) minor complications occurred in the 12 (17%) children with multi-system organ failure. The rate of major complication was significantly greater in children with multi-system organ failure than in all patients (p < 0.001) and their relative risk of complication was increased by a factor of 40. CONCLUSIONS: Our data indicate that PEG is a safe and effective modality for nutritional support in children without multi-system organ failure. Those with multi-system organ failure have an increased rate of complications and a poor response to nutritional support, suggesting that the risk of PEG may outweigh its benefit for this population.

Pediatric liver transplantation in Georgia: a paradigm for the health care crisis in the United States?

The United States health care system, felt by many to be the most technologically advanced program in the world, has many critics. Two indisputable facts that drive such criticism are 1) inequitable access and 2) rising costs out of proportion to other countries. Although Georgia is a poor state and ranks nationally near the bottom in most measures of child and adolescent care, we decided to start a pediatric liver transplant program at Egleston Children's Hospital at Emory, Atlanta. Over the past 2 1/2 years, 18 transplants have been performed in 14 patients; 10 children are presently surviving. Looking carefully at the expenses of the first 10 patients, the average cost of orthotopic liver transplantation for the eight survivors was $206,375. The hospital costs for providing care to these 10 children were over $2 million. In a state that ranks 49th out of 50 states in infant mortality and with nearly one-third of its pre-school children not immunized against preventable diseases, is this a fair and equitable distribution of our resources?

Preservation of somatostatin secretion in cystic fibrosis patients with diabetes.

Immunohistochemical studies of pancreatic tissue from patients with cystic fibrosis associated with diabetes mellitus (CFDM) show increased numbers of somatostatin secreting delta cells. To look for a possible functional correlate to this finding basal and arginine stimulated plasma somatostatin and serum C peptide concentrations in eight insulin treated patients with cystic fibrosis and eight normal male controls were measured. Mean basal somatostatin concentrations were not different in the two groups. Mean peak somatostatin concentrations were significantly higher in the group with CFDM: 11.60 pmol/l v 7.14 pmol/l in controls. Mean peak C peptide concentrations were significantly lower in the group with cystic fibrosis: 0.89 nmol/l v 4.27 nmol/l in controls. This observation provides a physiological correlate to the pathological finding of increased somatostatin content in pancreatic tissue from patients with CFDM. Selective preservation of somatostatin secretion in patients with cystic fibrosis may further complicate pancreatic endocrine insufficiencies through paracrine inhibition of insulin and glucagon secretion.

Subacute necrotizing encephalopathy: oxidative phosphorylation defects and the ATPase 6 point mutation.

Subacute necrotizing encephalopathy (SNE) or Leigh's disease is associated with various defects in oxidative phosphorylation (OXPHOS). However, the relationships between these OXPHOS defects and nuclear DNA or mitochondrial DNA (mtDNA) mutations is still unclear. We evaluated three SNE pedigrees (two singleton cases and a pedigree) biochemically for OXPHOS abnormalities and genetically for four mtDNA point mutations. There was a complex I defect in all three pedigrees that was associated with a complex III defect in two individuals. An mtDNA mutation in the ATPase, subunit 6 gene (np 8993) was present in one SNE pedigree. This mutation was maternally inherited, heteroplasmic, produced marked clinical and biochemical heterogeneity between pedigree members, and varied along the maternal lineage at levels ranging from 0% to > 95% of the total mtDNAs. These mtDNA mutations were not present in the other two pedigrees. These observations emphasize the importance of screening for OXPHOS defects and mtDNA mutations in SNE cases.

Aerosol alpha 1-antitrypsin treatment for cystic fibrosis.

In cystic fibrosis neutrophil-dominated inflammation on the respiratory epithelial surface results in a chronic epithelial burden of the destructive enzyme, neutrophil elastase. alpha 1-antitrypsin (alpha 1AT), the main inhibitor of neutrophil elastase in lung, was given in aerosol form to 12 cystic fibrosis patients. It suppressed neutrophil elastase in the respiratory epithelial lining fluid (ELF) and restored the ELF anti-neutrophil elastase capacity when ELF alpha 1AT reached 8 mumol/l. This treatment also reversed the inhibitory effect of cystic fibrosis ELF on pseudomonas killing by neutrophils, which suggests that it may augment host defence in cystic fibrosis.

Low levels of pyridoxal 5'-phosphate in patients with cystic fibrosis.

To determine the effect of cystic fibrosis on the regulation of plasma pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, we measured this compound in plasma from 56 patients with cystic fibrosis. The concentration of PLP in plasma was assayed by a radioenzymatic technique. The results of this study showed that PLP concentration was decreased significantly (6.44 +/- 5.20 ng/mL, mean +/- SD; median 4.45 ng/mL) in patients with cystic fibrosis as compared with a group of hospitalized children with neither cystic fibrosis nor hepatic disease serving as a control group (13.2 +/- 5.04 ng/mL, mean +/- SD; median 12.5 ng/mL). Additionally, 25% of the population with cystic fibrosis exhibited exceedingly low plasma PLP level (less than 2.75 ng/mL). In patients with cystic fibrosis, significant inverse linear associations were found between plasma PLP and serum levels of SGOT and SGPT (PLP v SGOT: r = -.60, P less than .03; PLP v SGPT: r = -.50, P less than .03). This study demonstrated that a deficiency of plasma PLP is a common abnormality in cystic fibrosis and that the low PLP level may be a reflection of impaired vitamin B6 metabolism associated with this disorder.

Biliary atresia: an evolving perspective.

From 1967 to 1984, 50 of our patients with extrahepatic biliary atresia had surgical exploration. Of 40 biliary drainage procedures, bile drained in 21 (52%). Thirty-four patients had portoenterostomy, three had portocholecystostomy, and the most recent six patients had a valved hepatoduodenal conduit. Successful biliary drainage was related to the presence of microscopic ducts at the porta hepatis in 20 of 21 infants. Twenty patients are alive, 12 from two to six years postoperatively (one with a liver transplant). Seven have normal serum bilirubin values. Height and weight exceed the 50th percentile in 5/15 patients studied. Multiple episodes of cholangitis have occurred in 11 patients with portoenterostomy and two with hepatoduodenal conduits. In 12 patients, hemorrhage from the stoma necessitated closure of the stoma before 1 year of age. Five of the six patients with hepatoduodenal conduit are alive two years postoperatively.

Platelet-monoamine oxidase activity in Reye's syndrome.

Platelet and liver monoamine oxidase (MAO) activity (mean +/- SD) was evaluated in patients with liver-biopsy-proven Reye's syndrome. MAO was measured by a radioenzymatic technique with [3H]tyramine as a substrate. A marked decrease in MAO activity [3.3 +/- 2.4 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] was observed in platelets on admission in all patients (n = 13) with Reye's syndrome when compared with hospitalized patients without liver disease (n = 8) [9.8 +/- 2.5 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] and with liver disease (n = 10) [9.1 +/- 2.0 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1]. Following recovery from the disease, platelet MAO approached levels that were not significantly different from those of controls. Contrastingly, reduction of hepatic MAO in Reye's syndrome was similar to that seen in patients with liver disease of different etiologies. These studies suggest that reduced platelet MAO activity is a specific abnormality in Reye's syndrome, and it may be representative of generalized impairment of mitochondrial function in these patients. Furthermore, the pattern of liver and platelet MAO activity in Reye's syndrome may allow for the differentiation of this disease from other hepatopathologic conditions.

Treatment of lower respiratory tract infections due to Pseudomonas aeruginosa in patients with cystic fibrosis.

Twenty-nine patients with cystic fibrosis received either cefsulodin or a reference agent (tobramycin or ticarcillin) in a randomized manner for treatment of pulmonary infections associated with Pseudomonas aeruginosa. Patients ranged in age from 12 to 30 years. Their infections were classified as mild (six), moderate (16), or severe (seven). Fourteen patients received cefsulodin, 14 patients were treated with tobramycin, and one patient received ticarcillin. Significant clinical improvement was noted in the majority of patients in both groups. Adverse effects and development of laboratory abnormalities were uncommon in both groups. P. aeruginosa was not permanently eradicated from the sputum of any of the patients. Resistance as measured by disk susceptibility testing may have developed during and immediately after therapy in the cefsulodin group but not in those treated with reference agents. However, this did not appear to affect the clinical outcome. Results of the nonrandomized portion of this multicenter study, in which 46 patients were treated with cefsulodin, were similar to those for the randomized group. Thus, cefsulodin was shown to be as clinically effective as the reference agents in the treatment of lower respiratory tract infections due to Pseudomonas aeruginosa in patients with cystic fibrosis.

Hypercatecholaminemia in Reye's syndrome.

To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radioenzymatic assay was used to study plasma and CSF concentration of dopamine, norepinephrine, and epinephrine in 14 patients with liver-biopsy-proven Reye's syndrome. The results (median and range) revealed significant (P less than .04, P less than .0024, and P less than .030, respectively) elevation in plasma dopamine (131, 0 to 1,193 pg/mL), norepinephrine (1,455, 20 to 5,271 pg/mL), and epinephrine (345, 7.6 to 2,504 pg/mL) at the onset of the disease when compared with the level of these neurotransmitters in a group of hospitalized patients without hepatic disorders. There was a positive correlation between plasma catecholamines and stage of coma on admission (r = .54 to .86; P less than .001 to .024). Furthermore, the concentration of dopamine, norepinephrine, and epinephrine in the CSF increased significantly during the development of cerebral edema in all patients with Reye's syndrome as compared with concentrations in a control population. Hypercatecholaminemia may contribute to the encephalopathy of Reye's syndrome.

Abnormal regulation of pyridoxal 5'-phosphate in Reye's syndrome.

Seeking to determine the effect of liver disease associated with Reye's syndrome on the regulation of plasma pyridoxal 5'-phosphate, we measured this compound in plasma from 11 patients with biopsy-proven Reye's syndrome. Its concentrations in plasma are significantly higher [37.5 (SD 6.13) micrograms/L] at the onset of the disease than after treatment [8.50 (SD 2.9) micrograms/L] or in a group of hospitalized patients with no evidence of liver disease [8.4 (SD 1.5) micrograms/L]. The concentration of pyridoxal 5'-phosphate in plasma at the time the patients entered the hospital correlated significantly with their activities of serum alanine aminotransferase.

Similarity between tyramine-induced neurotoxicity and the coma of Reye's syndrome.

The objective of the present investigation was to determine whether or not tyramine induces coma in experimental animals with impaired mitochondrial monoamine oxidase function, and whether the coma in these animals was a function of increased cerebrospinal fluid (CSF) pressure. Ten mongrel dogs were treated (orally) daily with the monoamine oxidase-inhibiting drug, phenelzine (4.5 mg/kg), over a period of 1 month. The present studies indicated that in phenelzine-treated animals with liver disease and behavioral side effects (n = 4), the i.v. administration of tyramine (1 mg/kg) caused substantial elevation in CSF pressure that exceeded 30 mm Hg (initial pressure 12.5 +/- 2.1). This was followed by substantial accumulation of tyramine, dopamine and norepinephrine concentrations in CSF of these animals. The animals became comatose soon afterward. The administration of tyramine to pretreated (n = 10) or phenelzine-treated animals without liver disease (n = 6) caused only the expected transient increase in blood pressure but with no significant effect on CSF pressure of these animals. These animals recovered fully from the experiment without any ill effect. These studies suggest that tyramine may have obvious implications in the development of intracranial hypertension in Reye's syndrome.

Yersinia enterocolitica colitis in infants: radiographic changes.

Radiographic changes of Yersinia enterocolitica colitis in 3 infants are presented. Findings included superficial aphthoid ulcers, submucosal ulcers, pancolitis (manifested by toxic megacolon), and involvement of the terminal ileum.

Total colectomy with ileo-endomuscular pull-through in the treatment of ulcerative colitis in children.

Since ulcerative colitis is primarily a mucosal disease, total colectomy with rectal mucosectomy and ileo-endomuscular pull-through (Soave) offers many theoretical advantages. The diseased colon is removed, the anal sphincteric mechanism is preserved, and permanent ileostomy is avoided, bladder and sexual function are preserved, and problems with perineal wound healing are avoided. Of critical importance is the state of rectal mucosal disease in the selection of patients for this operation. Our experience with four children in whom the operation has been performed is presented. Postoperative diarrhea has not proved to be a significant problem and continence has been maintained.

Evidence for hypertyraminemia in Reye's syndrome.

Utilizing a specific and sensitive radioimmunoassay, palsma and urine tyramine were measured in 14 consecutive patients with liver biopsy-proven Reye's syndrome. Plasma tyrosine was measured in 11 of these patients. The results revealed significant (P less than .003) elevation in plasma (3.4 +/- .52 ng/ml) (mean +/- SEM) and urine (1.00 +/- .26 mg/24 hr) tyramine as well as plasma tyrosine (204 +/- 52.5 mumole/liter) at the onset of the disease when compared to the levels of tyramine and tyrosine in a group of hospitalized patients without hepatic disorders. Furthermore, there was a positive correlation between plasma tyramine and days in coma (r = .86; P less than .001), and between plasma tyramine and tyrosine (r = 0.80; P less than .001). These data suggest that there is s substantial disturbance of tyrosine metabolism in Reye's syndrome and that the accumulation of this amino acid and its metabolite, tyramine, may contribute to the encephalopathy of this disease.