Rifampin relieves pruritus in children with cholestatic liver disease.

Chronic cholestatic liver disease in children frequently results in severe intractable pruritus. Current forms of therapy, including cholestyramine, are usually ineffective. Therefore, a 6-wk, double-blind, crossover study was designed to test the ability of rifampin to relieve pruritus in children with chronic cholestasis. Rifampin proved effective in alleviating pruritus in all five children tested compared with a placebo-treated group. After the 6-wk study period, rifampin was continued for 6 mo, and its effectiveness was maintained. No complications resulted from rifampin use. This study and a similar study in older patients with primary biliary cirrhosis suggest that a highly effective form of therapy is available for treatment of severe pruritus in patients with chronic cholestasis. These patients must be carefully selected and frequently monitored.

Chest pain and dysphagia in adolescents caused by diffuse esophageal spasm.

Five adolescents, 13-18 years of age, underwent esophageal manometric studies because of chronic symptoms suggestive of esophageal dysfunction. Four of five patients had episodic nonexertional midchest pain; two patients experienced intermittent dysphagia. The manometric findings for these adolescents were consistent with a primary motility disorder known as diffuse esophageal spasm, a condition not previously reported in this age group. This represents approximately 1% of all pediatric patients undergoing esophageal manometry at our institution for the past 5 years. They have been followed for at least 2 years and three have experienced gradual resolution of their symptoms with normalization of manometric findings. Our report emphasizes two main points: (a) Diffuse esophageal spasm may cause chest pain and dysphagia in adolescents; and (b) the clinical history and esophageal manometric findings establish the diagnosis of diffuse esophageal spasm.

Measurement of plasma prednisolone level to evaluate a prednisone treatment failure in an adolescent with Crohn's disease.

A 14-year-old boy experienced multiple hospitalizations because of symptoms due to Crohn's disease involving the stomach, duodenum, and ileum. He maintained that oral corticosteroids were not effective for control of his symptoms. However, i.v. corticosteroids always relieved his symptoms. To resolve the question of noncompliance versus altered corticosteroid absorption or metabolism, our patient underwent an oral prednisone absorption study. Prednisolone, the active metabolite of prednisone, was measured in his plasma using a high-pressure liquid chromatography technique. The results led to the discovery of an elaborate deception by the patient and his subsequent need for psychotherapy. This report documents the importance of measuring plasma prednisolone concentrations to diagnose noncompliance, especially in adolescents who are overly concerned about their body image.

Evoked potential abnormalities in children with chronic cholestasis.

To assess the effect of chronic cholestasis and vitamin E deficiency on nervous system function, we did multimodality evoked potential testing of 17 children (mean age = 47 months) who had chronic liver disease. Evoked potential testing was repeated periodically in 11 patients 1 to 33 months after the initial study. Eight children had abnormal delays of the P100 peak of the visual evoked potential, and these children each had significantly higher total serum bile acid levels than did children who had normal visual evoked potentials (p = 0.002). Bilateral brainstem auditory evoked potential abnormalities consistent with conductive hearing losses were initially present in six patients. However, persistent conductive losses were found in four patients, all of whom had arteriohepatic dysplasia. Four children had mildly abnormal somatosensory evoked potentials that were due solely to a mild peripheral neuropathy. Biochemical measures of vitamin E status were not consistently associated with either normal or abnormal visual, brainstem auditory or somatosensory evoked potentials or a combination of evoked potential abnormalities, and an abnormality of one evoked potential type was not associated with an abnormality of any other. A similar lack of relationship between evoked potential results and plasma vitamin A measurement was noted. Following marked improvement in or resolution of cholestasis in four patients, the visual evoked potential became normal, but other evoked potentials did not change. Visual evoked potential improvement was greatest in two patients who underwent orthotopic liver transplantation. This is the first report that demonstrates frequent, potentially reversible visual system abnormalities that are associated with cholestasis and cannot be attributed solely to vitamin E and/or A deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of vitamin E deficiency on neurologic function in patients with cystic fibrosis.

We evaluated neurologic function in 18 patients, ages 5 to 26 years, with cystic fibrosis. Eight were deficient in vitamin E. Sural nerve conduction latency was increased and nerve action potential amplitude decreased in the vitamin E-deficient group in comparison with the vitamin E-sufficient group. Two vitamin E-deficient patients had absent deep tendon reflexes; findings of clinical neurologic examinations were otherwise normal. We recommend early supplementation with vitamin E for patients with cystic fibrosis who have pancreatic insufficiency, to prevent neurologic dysfunction.

Support for a conservative approach to mixed intrahepatic and extrahepatic biliary hypoplasia.

This report describes the pitfalls in the diagnosis of extrahepatic biliary atresia in an infant with paucity of the interlobular bile ducts.

Application of a new test for vitamin E deficiency to cystic fibrosis.

Cystic fibrosis patients with pancreatic insufficiency are at risk for the development of vitamin E deficiency. We report here the outcome of screening 13 cystic fibrosis patients with conventional descriptive measures of vitamin E status and a new functional test. The results were compared with those from age appropriate controls. Nine patients were found to be vitamin E sufficient based upon normal plasma vitamin E levels, the ratio of plasma vitamin E to total plasma lipids, and normal levels of in vitro erythrocyte malondialdehyde formation, the new functional measure of vitamin E status. Four patients considered vitamin E deficient, based upon low plasma vitamin E levels and plasma vitamin E to total plasma lipid ratios, demonstrated increased erythrocyte malondialdehyde formation in vitro when compared to age-matched controls. Since limited reference data in children are available to define normal plasma vitamin E levels and plasma vitamin E to total plasma lipid ratios, we suggest that for cystic fibrosis patients the functional in vitro malondialdehyde formation test may be a better measure of vitamin E status than static plasma levels.

Characterization of vitamin E status in cholestatic children by conventional laboratory standards and a new functional assay.

In the present study, the clinical application of a new functional test for vitamin E deficiency was evaluated. Erythrocytes from cholestatic children at risk for vitamin E deficiency and appropriate controls were incubated in vitro with hydrogen peroxide and the malondialdehyde generated and released into the supernatant quantitated. The results of these incubations were compared with fasting plasma vitamin E levels, the ratio of plasma vitamin E to plasma lipid levels, and, in some instances, hydrogen peroxide hemolysis tests. Malondialdehyde formation was less than 6% in controls and vitamin E-sufficient cholestatic children. However, cholestatic vitamin E-deficient children had a mean malondialdehyde formation of 41%. The results also suggest that for children less than 4 months of age, a ratio of plasma vitamin E to total plasma lipids less than 0.6 mg/g may be sufficient to provide protection from in vitro peroxidation. The authors suggest that this functional assay of vitamin E status be included in the evaluation of individuals with the potential for vitamin E deficiency.

Erythrocyte lipid alterations in pediatric cholestatic liver disease: relationship to serum bile acids.

Chronic pediatric cholestatic liver disease is accompanied by an elevated erythrocyte membrane cholesterol/phospholipid molar ratio. Since bile acids are known to affect erythrocyte membrane integrity, we sought to determine what relationship existed between serum bile acid concentrations and the observed alterations in erythrocyte membrane lipids. Ten children with chronic cholestasis (2 months-3 1/2 yrs) were evaluated a total of twenty-two times. For all studies a reliable correlation between erythrocyte membrane cholesterol and phospholipid was noted (r = 0.88, p less than 0.001). When total serum bile acids exceeding 100 mumol/L were excluded, a strong relationship between serum bile acids and erythrocyte cholesterol/phospholipid molar ratio was noted (r = 0.61, p less than 0.03). The results suggest that with mild to moderate cholestasis changes in serum bile acids influence erythrocyte membrane lipid composition with parallel increases in cholesterol and phospholipid.

Erythrocyte malondialdehyde release in vitro: a functional measure of vitamin E status.

The definition for a sufficient vitamin E level has often been based on population studies that established the normal range of values for fasting plasma or serum vitamin E and more recently for vitamin E to total lipid ratios. These endpoints for vitamin E replacement strategies may not be readily achievable, particularly in the cholestatic patient for whom it is often impossible to reach and sustain normal levels even with massive doses of vitamin E. Vitamin E is believed to function as an antioxidant in vivo protecting membranes from lipid peroxidation. Malondialdehyde (MDA), a product of polyunsaturated fat peroxidation, was measured as the thiobarbiturate derivative in the supernatant following incubation of erythrocytes in hydrogen peroxide. The two different incubation conditions described here and the subsequent measurement of MDA appear to provide a sensitive functional assessment of vitamin E status. The clinical utility of this assay, which requires just 1.5 to 2.0 ml of whole blood, was demonstrated by comparing the percent of total MDA released from individuals regarded as vitamin E sufficient by conventional methods with vitamin E deficient subjects. The release of MDA from erythrocytes from vitamin E deficient subjects was clearly greater (44.1 +/- 18.8% vs 2.0 +/- 1.8%) than for control subjects (p less than 0.001).

Erythrocyte lipid alterations in pediatric cholestatic liver disease: spur cell anemia of infancy.

Spur cell anemia of liver disease is a hemolytic process characterized by spiculated erythrocytes and an elevated red cell membrane cholesterol/phospholipid (C/PL) molar ratio. This form of anemia is associated almost exclusively with adults in the advanced stages of alcoholic cirrhosis. We were therefore surprised to identify two unrelated infants with cholestatic liver disease and hemolytic anemia who had spiculated erythrocytes as the major abnormal cell form on peripheral smear. Erythrocyte membrane cholesterol and phospholipid determinations from these patients were compared with six infants with extrahepatic biliary atresia and target-shaped erythrocytes and with five normal adults. Erythrocyte C/PL molar ratio distinguished target cells from normal erythrocytes (p less than 0.01). The spur cell patients' erythrocyte C/PL molar ratios were clearly greater than either target cell patients or normal controls (1.30 vs. 1.02 vs. 0.84). Both patients' spur cell anemia resolved and target cells became the major abnormal erythrocyte form. These studies identify a transient form of spur cell anemia associated with infantile cholestatic liver disease. The factors leading to the formation of spur cell anemia in infancy require further investigation.

Oral rehydration of infants in a large urban U.S. medical center.

A prospective randomized study of 100 well-nourished infants with acute gastroenteritis resulting in dehydration and acidosis was carried out at the Jackson Memorial Hospital, Miami from 1981 to 1983. Patients were randomly assigned to receive either standard intravenous therapy or oral rehydration. Infants in the latter group first received solution A containing 75 mEq/L sodium, 30 mEq/L potassium, 75 mEq/L chloride [corrected], 30 mEq/L bicarbonate, and 2 gm/dL glucose [corrected]. After ad libitum feeding for six hours, solution B containing 50 mEq/L sodium, 30 mEq/L potassium, 50 mEq/L chlorine, 30 mEq/L bicarbonate, and 3 gm/dL [corrected] glucose was given. With three exceptions (6%), oral rehydration was comparable to the intravenous regimen in clinical estimates of improvement, although the oral group had more stools in the first day. The oral group had faster correction of acidosis and a sustained rise in serum potassium concentration, whereas in the intravenous group the potassium concentration showed first a drop with a later increase, but levels were at all times below those in the oral group. Although potassium was given from the beginning of oral rehydration, and at a higher concentration than recommended by the World Health Organization, no hyperkalemia occurred. We concluded that oral therapy is safe, less expensive for patients, and more convenient for the medical and nursing staffs.