Vitamin E measurement in patients receiving intravenous lipid emulsions.

Two methods for the determination of plasma vitamin E--high-pressure liquid chromatography and spectrophotofluorometry--were compared on samples from four groups of pediatric patients: children and infants receiving lipid emulsion as part of their parenteral nutrition regimen, neonates receiving parenteral nutrition who were not receiving lipid emulsion at the time of blood sampling, and short admission surgery control subjects. In control subjects and patients not receiving lipid emulsions, both methods yielded similar results for vitamin E as alpha-tocopherol. In contrast, in patients receiving lipid emulsion, the fluorometric method yielded values ranging from 200% to 300% greater than did high-pressure liquid chromatography. The source of the discrepancy is most probably the presence of naturally occurring non-alpha-tocopherol isomers in the lipid products, which add to the fluorescent measurement but are resolved by high-pressure liquid chromatography. This study confirms clinically that fluorescent measurement of vitamin E is no longer the method of choice for monitoring tocopherol status in intensive care nurseries.

Total and direct-reacting bilirubin values by automated methods compared with liquid chromatography and with manual methods for determining delta bilirubin.

This study compares total and direct-reacting bilirubin values in 40 serum samples from patients with various diagnoses, as measured by automated methods (Beckman Synchron CX-5, Beckman Astra 8, Kodak Ektachem 700) and HPLC and by a manual method for delta bilirubin. For total bilirubin, within-run CVs were less than 6%. The Ektachem 700 method underestimated bilirubin with serum samples from patients with Crigler-Najjar syndrome and from newborns in whom unconjugated bilirubin concentrations were increased but conjugated bilirubins were not present or were present only in small amounts. The Astra 8 and Synchron CX-5 methods were inaccurate with cholestatic serum samples, in which conjugated bilirubin concentrations were increased and other compounds such as bile acids could be expected to interfere. We conclude that each automated method examined provides reasonable estimates for total and direct-reacting bilirubin values for routine clinical use. The need for each laboratory to select the appropriate bilirubin method for its particular situation is obvious.

Vitamin A sorption to polyvinyl and polyolefin intravenous tubing.

The loss of vitamin A to plastic infusion tubing from a total parenteral nutrition solution was studied using an in vitro infusion system and HPLC quantification of vitamin A. Polyolefin tubing was compared to polyvinyl chloride at varied vitamin A concentration, infusion temperature, and flow rate. Significantly enhanced recovery of vitamin A was found with the polyolefin tubing compared to that of the polyvinyl chloride under all conditions tested. After 24 hours under the varied conditions of the study, vitamin A availability ranged from 47 to 87% with polyolefin and 19 to 74% with polyvinyl chloride. These differences may be expected to result in significantly greater vitamin A delivery from polyolefin compared to polyvinyl chloride tubing to patients treated in neonatal intensive care units.

A subacute rabbit model for hepatobiliary dysfunction during total parenteral nutrition.

Total parenteral nutrition (TPN) in children is associated with the complicating syndromes of cholestasis and cholelithiasis. The causes of these syndromes are not completely clear. Gastrointestinal hypomotility associated with enteral fasting may be involved in the pathogenesis of both syndromes. We compared weanling rabbits maintained solely on TPN with chow pair-fed and free-fed controls over a 10-day period. Gastrointestinal transit time, assessed with a solid marker technique, was significantly greater in the TPN-treated animals. No difference in intestinal or biliary bacterial flora was demonstrated by aerobic or anaerobic cultures. Gallbladder bile contained a higher percentage of lithocholic acid, unconjugated bilirubin, and total calcium in the TPN-treated animals. Markers of hepatic dysfunction were elevated in the serum of the TPN-treated animals. Mild steatosis and edema were the only histologic differences in the livers of the TPN-treated animals. We conclude that gastrointestinal hypomotility associated with enteral fasting plays a role in the pathophysiologic changes leading to TPN-associated hepatobiliary dysfunction. This dysfunction may be mediated by an increase in the absolute and relative concentrations of lithocholic acid in the bile of TPN-treated animals.

The BUN/creatinine ratio in localizing gastrointestinal bleeding in pediatric patients.

Localizing the bleeding site in pediatric patients with gastrointestinal hemorrhage may require invasive and costly diagnostic procedures. A simple index to discriminate upper and lower bleeding sources would be invaluable. We evaluated the reliability of the calculated blood urea nitrogen/creatinine (BUN/Cr) ratio in segregating upper from lower gastrointestinal bleeding sites in 40 children. For upper gastrointestinal hemorrhage, the calculated BUN/Cr ratios (mg/mg) ranged from 10 to 140, with a mean value of 34. For lower gastrointestinal bleeders, the BUN/Cr ratios ranged from 3.3 to 30, with a mean value of 16. All BUN/Cr ratios greater than 30 corresponded to patients with documented upper gastrointestinal bleeding sources. Calculation of the BUN/Cr ratio in the initial evaluation of gastrointestinal bleeding may prove useful in guiding the sequence of diagnostic procedures and examinations.

The effect of tin-protoporphyrin on bilirubin conjugation and production in cholestatic rats.

Tin-protoporphyrin (SnP) is actively being investigated for treatment of exaggerated neonatal hyperbilirubinemia. Because both bilirubin conjugation and excretion are immature in the human newborn, we investigated the effect of SnP on bilirubin-conjugating mechanisms and the efficacy of SnP in suppressing serum bilirubin levels in adult rats made cholestatic by surgical bile duct ligation. Male Sprague-Dawley rats received SnP (100 mumol/kg body weight) subcutaneously either 24 h before or 24 or 48 h after bile duct ligation. Serum and urine specimens were collected 72 h after bile duct ligation and analyzed for bilirubin and its conjugates. As compared to a control group that received bile duct ligation and a sodium phosphate buffer injection, all SnP-treated animals had a significant lowering of total serum bilirubin levels. No differences in the distribution of serum bilirubin mono- and diconjugates in serum or urine samples were observed. However, the concentrations of covalently linked bilirubinprotein conjugates were significantly higher in the control cholestatic rats when compared to the SnP-treated animals. SnP effectively lowers serum bilirubin levels in rats with an impaired biliary excretory pathway for SnP. There was no adverse effect on bilirubin conjugation and no observable toxicity.

Evaluation of Arizona Health Care Cost Containment System, 1984-85.

In this article, we describe the evaluation of the Arizona Health Care Cost Containment System (AHCCCS), Arizona's alternative to the acute care portion of Medicaid. We provide an assessment of implementation of the program's innovative features during its second 18 months of operation, from April 1984 through September 1985. Included in the evaluation are assessments of the administration of the program, provider relations, eligibility, enrollment and marketing, information systems, quality assurance and member satisfaction activities, the relationship of the county governments to AHCCCS, the competitive bidding process, and the plans and their financial status.

Distribution of serum bilirubin conjugates in pediatric hepatobiliary diseases.

We used a highly specific method, alkaline methanolysis-high performance liquid chromatography, for determining the concentration and patterns of the unconjugated and esterified bilirubin fractions in the sera of pediatric patients with hepatobiliary disease. Bilirubin-protein conjugates were assayed using a new method that selectively removes bilirubin reversibly bound to protein, allowing measurement of the tightly bound bilirubin-protein conjugates by use of a diazo method. Fifty-two serum samples from children with varying bilirubin concentrations and diagnoses were studied. Whereas no conjugated pigment was detectable in the serum samples of healthy children or in individuals with Gilbert syndrome or Crigler-Najjar syndrome, bilirubin monoester and diester conjugates and bilirubin-protein conjugates were present in the sera of children with cholestatic liver disease, and accounted for 69% +/- 15% of the total bilirubin in these samples. Bilirubin fractional analysis was incapable of differentiating extrahepatic biliary obstruction from hepatocellular disease, because of overlap between the groups. The presence of bilirubin-protein conjugates in serum always coincided with detection of bilirubin monoester and diester conjugates. The distribution of bilirubin and its conjugates in sera provides a sensitive, although nonspecific, measure of hepatic disease.

Evaluation of the Arizona health care cost-containment system.

This article evaluates Arizona's alternative to the acute portion of Medicaid, the Arizona Health Care Cost-Containment System (AHCCCS), during its first 18 months of operation from October 1982 through March 1984. It focuses on the program's implementation and describes and evaluates the program's innovative features. The features of the program outlined in the original AHCCCS legislation included: Competitive bidding, prepaid capitation of providers, capitation of the State by the Health Care Financing Administration, assignment of gatekeepers, beneficiary copayment, private administration, inclusion of private and public employees and county financed long-term care. An assessment of implementation during the second 18 months of the program reporting on more recent developments and is now being prepared by SRI International.

The use of fecal alkaline phosphatase as an indicator of intestinal damage.

Fecal alkaline phosphatase excretion was evaluated as a marker for intestinal damage in rats. Animals received either intraperitoneal bleomycin or saline. Controls were pair-fed with animals in the bleomycin group throughout the study. Both groups demonstrated similar patterns of fecal alkaline phosphatase excretion. There was, however, marked daily variability of fecal enzymatic activity. Fecal alkaline phosphatase excretion was largely composed of intestinal alkaline phosphatase, which was characterized by enzymatic inhibition with L-phenylalanine. Dietary intake as well as daily fecal output and protein excretion were reduced immediately following bleomycin injections and gradually increased to baseline values by 7 days. It appeared that both the direct toxic effects of bleomycin and dietary intake influenced fecal alkaline phosphatase excretion. Routine clinical application of this assay may be limited because of the number of factors which may affect its excretion.

Cholestatic effect of intraperitoneal administration of tryptophan to suckling rat pups.

The potential cholestatic effect of amino acids and metabolites of tryptophan were evaluated by use of seven daily intraperitoneal injections to suckling and weanling rat pups. Of the amino acids present in parenteral nutrition solutions, only tryptophan (given at a dose of 4 mM/kg) produced a significant (p less than 0.01) elevation of serum cholylglycine (12.8 +/- 1.0 microM/liter) as determined by radioimmunoassay, compared to 4.9 +/- 0.4 microM/liter in saline-treated control animals. Total serum conjugates of cholic acid, as determined by radioimmunoassay, were similarly elevated, as was serum alanine aminotransferase. Tryptophan injection resulted in elevated cholylglycine concentrations only at doses of 3 mM/kg/day or higher. Animals more than 2 weeks old did not demonstrate elevation of serum cholylglycine. Injection of light-exposed tryptophan in suckling animals caused a greater elevation of cholylglycine (39.0 +/- 8.6 microM/liter) than freshly prepared tryptophan solutions (p less than 0.005). Tryptophan and its spontaneous degradation products could contribute to the cholestatic liver changes observed during parenteral nutrition therapy.

Treatment of protracted diarrhea of infancy.

Ten patients with protracted diarrhea of infancy received either 8% or 16% of 130 calories/kg/day as amino acids. Patients were treated initially with total parenteral nutrition (TPN) and subsequently with an elemental diet. Nitrogen balance was better during TPN in those who received the higher amino acid intake. No differences were noted between groups in weight gain or restoration of muscle mass. Higher levels of serum urea nitrogen and alkaline phosphatase were noted in patients with the higher amino acid intake; cholestatic liver injury developed in two of these patients. The patients receiving the higher amount of amino acid demonstrated enhanced calciuria during TPN. Other than better nitrogen balance, no clinical benefits and more undesirable side effects were observed in patients receiving 16% amino acid calories.