Immunity to colon cancer assessed by antigen-induced inhibition of mixed mononuclear cell migration.

A purified preparation of mixed human peripheral blood lymphocytes and monocytes was used in an inhibition-of-migration assay for cell-mediated immunity to cancer of the colon. This preparation was reproducibly antigen-responsive and migrated with greater reliability than did a more complex cell mixture. Of 27 patients with this disease, cells from 24 showed inhibited migratio in response to colon carcinoma antigen. Uninhibited migration patterns were found in each of the 52 cancer-free controls, including eight patients with nonmalignant disease initially diagnosed as cancer of the colon, and in nine patients with surgically cured adenocarcinoma of the colon.

Diagnosis and prognosis in colon cancer based on a profile in immune reactivity.

An immunologic profile consisting of measurements of circulating carcinoembryonic antigen (CEA), tumor antigen-induced inhibition of monomuclear cell migration (IMM) and skin reactivity to purified protein derivative, streptokinase-streptodornase, and mumps was assessed as a diagnostic and prognostic tool in 16 patients with colon cancer. Preoperatively, 10 of 14 patients tested had elevated CEA, 12 of 12 showed tumor antigen-induced IMM, and 10 of 11 failed to react to 2 or more recall antigens. Potential surgical cure (7 patients) was accompanied by normal CEA in 4, absent tumor antigen-induced IMM in all 7, and increased skin-test reactivity in 6. Disseminated cancer (9 patients) was associated with elevated CEA in all 9, with absent IMM in all 7 and with suppressed skin-test reactivity in 6 of 9.

The effect of two intravenous fat emulsions and their components on bilirubin binding to albumin.

The effect of two intravenous lipid emulsions on the binding of bilirubin to albumin was investigated in vitro. Various concentrations of a soybean (Intralipid) or a safflower (Liposyn) oil emulsion in 0.48 mM albumin were assayed for changed in bilirubin displacement using Sephadex G-25 gel filtration and for alternations of albumin reserve binding capacity by a novel difference spectroscopy technique. Two major components of the emulsions, glycerol and egg phosphatides, were also assayed by difference spectroscopy. A significant enhancement of the total reserve bilirubin binding capacity of albumin was noted with concentrations of 200 to 500 mg/100 ml lipid emulsion using difference spectroscopy. Using salicylate to block secondary albumin binding sites for bilirubin, reserve bilirubin binding capacity at nonsalicylate competitive sites was shown to have increased (maximum 61%) over the range of 50 to 1000 mg/100 ml lipid emulsion. Only changes in nonsalicylate competitive binding sites could be detected at concentrations normally achieved in vivo. Egg phosphatides had little effect and glycerol decreased reserve bilirubin binding capacity. Sephadex studies were unable to detect any significant change in bilirubin retained on the column with 50 or 500 mg/100 ml lipid emulsion at any bilirubin/albumin ratio. The enhancement of reserve bilirubin binding capacity caused by lipid emulsions is mediated through changes in nonsalicylate competitive albumin binding sites. Product differences demonstrated in vitro point out the complexity of their effects on bilirubin-albumin binding and the necessity for in vivo investigations with structurally different nutritional products designed for use in newborns.

Ethotoin in seizures of childhood and adolescence.

Ethotoin is an anticonvulsant that was considered minimally effective when introduced, but due to its apparent lack of side effects, there has been renewed interest in the drug for use in generalized and psychomotor seizures. We have characterized the pharmacokinetics of ethotoin in children and have found nonlinearity. Seizures were controlled in 16 of 17 patients, and there were no side effects reported. Gingival hyperplasia due to previous phenytoin therapy improved in all cases.

Pediatric parenteral amino acid mixture in low birth weight infants.

A mixture of amino acids designed to maintain normal plasma amino acid concentrations in infants and children requiring parenteral nutrition was evaluated in 28 low birth weight (LBW) infants (birth weight, 750 to 1750 g; postnatal age, 1 to 4 weeks) who required parenteral nutrients for optimal nutritional management. Sixteen babies received only parenteral nutrients for five to 21 days. Ten of these received a typical regimen by peripheral vein (1.91 +/- 0.16 g/kg/d of amino acids and 44.7 +/- 4.4 kcal/kg/d) and six received a typical regimen through a central vein (2.39 +/- 0.11 g/kg/d of amino acids and 95.9 +/- 14.5 kcal/kg/d). Mean weight gain of the peripheral vein subgroup was 10.3 +/- 10.6 g/kg/d; mean nitrogen balance was 230 +/- 66 mg/kg/d. Both the mean rate of weight gain (17.2 +/- 5.1 g/kg/d) and the mean rate of nitrogen retention (267 +/- 49 g/kg/d) of the central vein subgroup were similar to intrauterine rates. In these two subgroups as well as the total population, plasma concentrations of all amino acids except phenylalanine were within the 95% confidence limits of the plasma concentrations observed in LBW infants fed sufficient amounts of human milk to result in a rate of weight gain similar to the intrauterine rate. However, although plasma tyrosine and cyst(e)ine concentrations were within the 95% confidence limits of the plasma concentrations goals, the LBW infant's ability to use N-acetyl-L-tyrosine and cysteine HCl appears to be even less than that of the term infant and older child. In toto, these data support the efficacy of the amino acid mixture evaluated for LBW infants. Of equal importance, they suggest that the LBW infant's ability to use parenterally delivered amino acids is not as limited as commonly thought.

Amino acid mixture designed to maintain normal plasma amino acid patterns in infants and children requiring parenteral nutrition.

A mixture of amino acids designed to maintain normal plasma amino acid concentrations of infants and children requiring parenteral nutrition was evaluated in 40 infants and children receiving only parenteral nutrients (2.39 +/- 0.26 g/kg/d of amino acids and 110.3 +/- 10.4 kcal/kg/d) for five to 21 days. The children ranged in weight from 2.0 to 12.6 kg (median weight, 3.83 kg; fifth to 95th percentile, 2.06 to 11.1 kg) and in age from 1 week to 43.6 months (median age, 2.7 months; fifth to 95th percentile, 0.2 to 25.3 months). Mean weight gain was 11.0 +/- 5.0 g/kg/d; mean nitrogen balance was 242 +/- 70 mg/kg/d. Plasma concentrations of all amino acids except tyrosine were within the normal range (ie, within the 95% confidence limits of the two-hour postprandial plasma concentrations observed in 30-day-old, healthy, normally growing, breast-fed, term infants) throughout the period of study. Mean prestudy and poststudy serum total protein, albumin, and transthyretin (prealbumin) concentrations were not significantly different. However, plasma transthyretin concentration increased in all children with low prestudy concentrations. Mean poststudy serum total bilirubin concentration of the total population was not different from the mean prestudy concentration. This was true also for the 31 children who received the parenteral amino acid mixture for more than ten days. In contrast to the expected 30% to 50% incidence of cholestasis, only one of these 31 experienced an unexplained increase in serum total bilirubin concentration during study, suggesting that normalizing plasma amino acid concentrations and/or providing taurine during parenteral nutrition may decrease the incidence of cholestasis associated with this therapy.

Comparative efficacy study of chewable aspirin and acetaminophen in the antipyresis of children.

Aspirin and acetaminophen are the most widely used antipyretics in pediatrics. Most clinicians believe the drugs to be equally effective, though clinical opinion often suggests that aspirin is more effective at higher temperatures. Fifty-nine outpatients (age range, 2-8 years), presenting with rectal temperatures of 38.8 to 40.5 degrees C, were enrolled in this double-blind trial. The children were stratified by weight and initial temperature. One dose of chewable aspirin or acetaminophen (10-15 mg/kg based on current recommendations for weight) was administered, and rectal temperatures were monitored for three hours. Of the 59 patients enrolled, 46 successfully completed the protocol. Both drugs significantly reduced temperatures in the groups studied. Age did not influence the response of the children to the antipyretic effects of either drug. Aspirin and acetaminophen appeared equally effective when initial temperatures were between 38.8 and 39.9 degrees C. However, when the initial temperature was between 40.0 and 40.5 degrees C, the duration of effect of acetaminophen was shorter than that for aspirin. This suggests that therapeutic differences in the antipyretic activities of aspirin and acetaminophen may exist at higher temperatures.

Sulfur amino acid metabolism in infants on parenteral nutrition.

In the infant on parenteral nutrition, cysteine supplementation has been suggested due to low levels of hepatic cystathionase activity limiting synthesis from methionine. We have examined the plasma concentrations of sulfur amino acids in four groups of post-surgical infants requiring parenteral nutrition receiving (A) a low methionine + cysteine + taurine formula, (B) a high methionine formula (non-steady state), (C) a high methionine formula (steady state), and (D) a high methionine + cysteine formula. Plasma methionine concentrations were above the normal reference range (2.2-4.9 micromol/dL) of normal breast-fed infants in Groups B (15.9 +/- 10.7 micromol/dL) and D (5.7 +/- 1.9 micromol/dL) and at the upper limit for Group C (4.9 +/- 1.7 micromol/dL). Total cysteine/cystine concentrations (normal reference range, 10.2-20.4 micromol/dL) were highest in Groups A (18.9 +/- 3.5 micromol/dL) and D (16.8 +/- 5.3 micromol/dL) that received cysteine HCI supplementation, and lowest in Group B (8.6 +/- 3.7 micromol/dL) that received no cysteine in non-steady state. All plasma free cystine concentrations were below the normal reference range (3.6-6.8 micromol/dL). Plasma taurine concentrations were not significantly different among the four groups and all were within the normal reference range (0.6-16.2 micromol/dL). The strikingly elevated methionine and low total cysteine/cystine values in Group B suggested the existence of a feedback loop of methionine conversion below the level of homocysteine. Equilibrium of methionine and cysteine/cystine plasma concentrations did occur, in time. Parenteral cysteine administration resulted in a greater proportion of plasma free cysteine concentration, but not cystine. The proportion of free to bound cysteine/cystine, as well as the proportion of free cystine to cysteine, was not normal during parenteral nutrition with or without cysteine HCI supplementation. Little benefit in plasma concentrations was derived from cysteine HCI supplementation to a high methionine formulation.

Assessing the validity of adjusted urinary urea nitrogen as an estimate of total urinary nitrogen in three pediatric populations.

Nitrogen excretion is a useful measurement for determining efficiency of protein utilization. Knowledge of nitrogen losses is especially important in the treatment of stressed, postsurgical, or catabolic patients, in whom optimizing the amount of nitrogen intake in the diet may spare visceral and somatic proteins and encourage anabolism. Many methods have been used to estimate total urinary nitrogen (TUN) in different patient populations. Urinary urea nitrogen (UUN) values are routinely adjusted and used by investigators who are not able to measure TUN directly by either Kjeldahl or pyrochemoluminescent methods. The rationale for the use of adjusted UUN concentrations to predict TUN is based on adult experiences. No similar experience in pediatrics has been published. We have compared TUN with adjusted UUN in a study of 250 urine samples from pediatric patients (n = 34) and normal pediatric volunteers (n = 109). Our findings suggest that adjusted UUN (determined by previously established formulas) may be of limited use in estimating TUN in neonates, infants, and critically ill pediatric patients; however, adjusted UUN may be useful in approximating TUN in healthy school-aged children. Good correlations were found between UUN and TUN for critically ill children and postsurgical neonates and infants, suggesting that these newly described regression equations (once validated) may be useful in predicting TUN from a measured UUN.

Triglyceride and fatty acid clearance in neonates following safflower oil emulsion infusion.

Fifteen neonates requiring parenteral nutrition with lipid emulsion were given a 1.0 g/kg dose of safflower oil emulsion to evaluate triglyceride (TGY) and free fatty acid clearance. The dose was infused intravenously over 4 hr, and serum was obtained at 0, 2, 4, 6, and 8 hr. Peak serum TGY averaged 592 mg/dl for the appropriate for gestational age newborns and 606 mg/dl for the small for gestational age babies. The small for gestational age neonates had significantly higher serum free fatty acids at 2 and 4 hr into the infusion than did the appropriate for gestational age infants. Peak serum free fatty acids ranged from 0.915 to 3.233 mM in the appropriate for gestational age babies and 2.518 to 3.586 mM in the small for gestational age infants. In contrast to previous work with soybean oil emulsion, we did not demonstrate differences in TGY clearance between small for gestational age and appropriate for gestational age neonates and did demonstrate a markedly elevated serum TGY in these critically ill newborns. Serum TGY and free fatty acids must be monitored in newborns administered intravenous fat emulsion to avoid the complications of iatrogenic hyperlipemia.

E-rosette formation, total T-cells, and lymphocyte transformation in infants receiving intravenous safflower oil emulsion.

There has been much concern about impaired immune function in children receiving infused lipid emulsions. Immunologic studies were carried out on 15 infants maintained on parenteral nutrition with intravenous safflower oil emulsion as part of the infusate. Significant increases in percentage rosette formation, total circulating T-cells, and mitogenesis to phytohemagglutinin and pokeweed mitogen were demonstrated after only 1 wk of lipid infusion. Additional parenteral nutrition did not further increase any immunologic parameter. These results suggest that infused safflower oil emulsion does not adversely alter cellular immune function.

Effect of intravenous L-carnitine on growth parameters and fat metabolism during parenteral nutrition in neonates.

To determine whether intravenous carnitine can improve nutritional indices, neonates requiring parenteral nutrition were randomized into carnitine treatment (n = 23) and control (n = 20) groups. Observed plasma lipid indices, carnitine and nitrogen balances, and plasma carnitine concentrations were not different in the prestudy period. Under standardized, steady-state conditions, 0.5 g/kg Intralipid was administered intravenously over 2 hr prior to carnitine administration, after infants received 7 days of 50 mumol/kg/day, and after a second 7 days of 100 mumol/kg/day of continuous intravenous L-carnitine as part of parenteral nutrition. Triglyceride (TGY), free fatty acid (FFA), acetoacetate (AA), beta-hydroxybutyrate (BOB), and plasma carnitine concentrations were measured prior to and at 2, 4, and 6 hr after the initiation of the lipid bolus. Twenty-four-hour urine collections for nitrogen and carnitine balance were obtained on days 7 and 14. Neonates receiving carnitine had significantly greater concentrations of plasma carnitine on days 7 and 14 (p less than 0.001). Greater nitrogen (p less than 0.05) and carnitine (p less than 0.001) balances and weight gain (week 2, p less than 0.05) were found in the carnitine-supplemented group when compared with controls. On day 14, (BOB + AA)/FFA ratios were significantly higher (p less than 0.05), and peak TGY concentrations and 6-hr FFA concentrations were significantly lower (p less than 0.05) in the treatment group. Carnitine supplementation was associated with modest increases in growth and nitrogen accretion possibly by enhancing the neonate's ability to utilize exogenous fat for energy.

Urinary nitrogen constituents in the postsurgical preterm neonate receiving parenteral nutrition.

Minimal information is available defining urinary nitrogen constituents in preterm neonates receiving parenteral nutrition (PN). The study objective was to evaluate 24-hour urine collections for total urinary nitrogen (TUN), urinary urea nitrogen (UUN), and the nitrogen content in creatinine, ammonia, free amino acids, protein, hippuric acid, and uric acid at baseline (days 1 to 2 of PN and days 1 to 3 after surgery) and 7 days later in eight preterm, postsurgical neonates. Calculation of undetermined nitrogen was also completed. Comparisons with historic, normal data were made for each urinary nitrogen constituent. At baseline, PN provided 59 +/- 10 nonprotein kcal/kg.day-1 and 430 +/- 54 mg/kg.day-1. At day 7, PN provided 106 +/- 23 nonprotein kcal/kg.day-1 and 432 +/- 30 mg/kg.day-1. TUN, UUN, and protein nitrogen decreased significantly from baseline at day 7 (p < .05). The percentages of TUN as amino acids, creatinine, and uric acid nitrogen were calculated. Percent amino acid nitrogen (6.0 +/- 2.3% vs 8.4 +/- 1.5%, p < .05), percent creatinine nitrogen (1.6 +/- 0.5% vs 2.9 +/- 0.8%, p < .001) and percent uric acid nitrogen (1.7 +/- 0.9% vs 3.6 +/- 2.1%, p < .05) increased significantly at day 7. The observed urinary free amino acid nitrogen fraction represented a higher percentage of TUN both at baseline and at day 7 when compared with term neonatal reference data, whereas creatinine nitrogen, uric acid nitrogen, and protein nitrogen represented a lower percentage of TUN. However, amino acid and creatinine nitrogen as a percentage of TUN were similar to levels in milk formula-fed preterm infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicities of parenteral nutrition in the critically ill patient.

Critically ill patients have unique nutritional substrate requirements. Although important advances have been made in understanding these requirements in the face of pathophysiologic and biochemical alterations induced by stress or trauma, nutrition-associated toxicities still occur. The importance of these toxicities to the critically ill patients cannot be over-stated. Many of these toxicities can be avoided by conservative use of selected nutrition substrates in specific subsets of the critically ill population. Practitioners must continue to anticipate and recognize parenteral nutrition-associated toxicities, however, as well as delineate any toxicity from the progression or exacerbation of disease.

Chromium and zinc contamination of parenteral nutrient solution components commonly used in infants and children.

Chromium and zinc contamination of components of parenteral nutrient (PN) solutions used in infants and children was studied. Solutions of amino acids, L-cysteine hydrochloride, dextrose, electrolytes, minerals, vitamins, multiple trace elements, and individual trace elements were obtained. A variety of manufacturers, lots, and expiration dates were represented when possible. The solutions were analyzed for chromium and zinc by flame atomic absorption spectrophotometry. In all amino acid products, chromium concentration was below the limit of detection and zinc concentration ranged from 0.06 to 4.97 mg/L. In the L-cysteine hydrochloride products, chromium was measurable in only two lots (0.11 and 0.23 mg/L); zinc was measurable in all lots (32-86 mg/L). Sodium and potassium salts of chloride and acetate had chromium concentrations of 0.02-0.23 mg/L and zinc concentrations of 0.35-0.56 mg/L. Phosphate salts contained chromium 0.39-0.44 mg/L and zinc 0.91-2.33 mg/L. In calcium gluconate, zinc concentration was 0.28-2.38 mg/L. In four lots of multiple trace elements, chromium was 92-104% and zinc was 100-113.5% of the labeled amount. A PN solution for a < 10-kg infant compounded from the components assayed would provide up to an additional 0.7 microgram of chromium per kilogram and 200 micrograms of zinc per kilogram. Zinc and chromium contaminants were detected in many of the products that are common components of PN solutions for infants and children; the contamination may be sufficient to result in the administration of zinc and chromium in amounts exceeding current recommendations.

Chromium and zinc concentrations in pediatric patients receiving long-term parenteral nutrition.

Serum, urine, and parenteral nutrition (PN) chromium and zinc concentrations in pediatric patients receiving long-term PN were studied. Serum, urine, and PN chromium and zinc concentrations were measured at baseline and four to six months later in four infants (less than 1 year old) and seven children (1-12 years old) receiving long-term PN. In the children, serum, urine, and PN solution zinc concentrations were measured monthly after the amino acid product was changed from a standard to a pediatric product with monthly dosages of 0, 20, 30, and 40 mg of cysteine hydrochloride per gram of amino acids. The mean +/- S.D. baseline serum chromium concentration was 4.9+/-1.9 microg/L (normal value, <0.3 microg/L); the urine chromium concentration ranged from 3.4 to 32.2 microg/L. The mean +/- S.D. prescribed chromium dosage was 0.18+/-0.05 microg/kg/day, and the dosage delivered in PN solutions was 0.41+/-0.23 microg/ kg/day. At baseline, the mean +/- S.D. serum zinc concentration was 1383+/-472 microg/L (normal range, 430 to 940 microg/L), and the prescribed and delivered zinc dosages were 177+/-10 and 238+/-145 microg/kg/ day, respectively. With 20, 30, and 40 mg of cysteine per gram of amino acids, the mean +/- S.D. serum zinc concentration was 1728+/-782, 1664+/-349, and 1685+/-268 microg/L, respectively, and the actual zinc dosages delivered were 209+/-10, 270+/-148, and 322+/-194 microg/kg/day, respectively. Serum and urine chromium concentrations were abnormally high in infants and children receiving PN solutions supplemented with normal doses of these trace elements; an escalating dosage of cysteine in the children tended to increase serum and urine zinc concentrations.

The role of taurine in infant nutrition.

The importance of taurine in the diet of pre-term and term infants has not always been clearly understood and is a topic of interest to students of infant nutrition. Recent evidence indicates that it should be considered one of the "conditionally essential" amino acids in infant nutrition. Plasma values for taurine will fall if infants are fed a taurine-free formula or do not have taurine provided in the TPN solution. Urine taurine values also fall, which is indicative of an attempt by the kidney to conserve taurine. The very-low-birth-weight infant, for a variety of reasons involving the maturation of tubular transport function, cannot maximally conserve taurine by enhancing renal reabsorption and, hence, is potentially at greater risk for taurine depletion than larger pre-term or term infants, and certainly more than older children who have taurine in their diet. Taurine has an important role in fat absorption in pre-term and possibly term infants and in children with cystic fibrosis. Because taurine-conjugated bile acids are better emulsifiers of fat than glycine-conjugated bile acids, the dietary (or TPN) intake has a direct influence on absorption of lipids. Taurine supplementation of formulas or TPN solutions could potentially serve to minimize the brain phospholipid fatty acid composition differences between formula-fed and human milk-fed infants. Taurine appears to have a role in infants, children, and even adults receiving most (> 75%) of their calories from TPN solutions in the prevention of granulation of the retina and electroencephalographic changes. Taurine has also been reported to improve maturation of auditory-evoked responses in pre-term infants, although this point is not fully established. Clearly, taurine is an important osmolyte in the brain and the renal medulla. At these locations, it is a primary factor in the cell volume regulatory process, in which brain or renal cells swell or shrink in response to osmolar changes, but return to their previous volume according to the uptake or release of taurine. While there is a dearth of clinical studies in man concerning this volume regulatory response, studies in cats, rats, and dog kidney cells indicate the protective role of taurine in hyperosmolar stress. The infant depleted of taurine may not be able to respond to hyper- or hyponatremic stress without massive changes in neuronal volume, which has obvious clinical significance. The fact that the brain content of taurine is very high at birth and falls with maturation may be a protective feature, or compensation for renal immaturity Defining an amino acid as "conditionally essential" requires that deficiency result in a clinical consequence or consequences which can be reversed by supplementation. In pre-term and term infants, taurine insufficiency results in impaired fat absorption, bile acid secretion, retinal function, and hepatic function, all of which can be reversed by taurine supplementation. Therefore, this small beta-amino acid, taurine, is indeed conditionally essential.

Clinical outcome as assessed by anthropometric parameters, albumin, and cellular immune function in high-risk infants receiving parenteral nutrition.

Twelve infants with underlying gastrointestinal tract disorders receiving 16 courses of total parenteral nutrition were retrospectively studied. Stratification according to calorie intake provided the best means for discriminating among different outcomes. Infants receiving greater than 110 calories/kg/d experienced significantly greater increases in weight, mid-arm muscle circumference, and triceps and subscapular skinfold thicknesses than did infants receiving less than 110 calories/kg/d. Catch-up growth was only seen in infants with intakes of greater than 110 calories/kg/d. In nine of these 12 infants, in vitro cellular immune parameters were assayed. Infants in both the high- and low-calorie groups experienced similar increases in transformational responses to pokeweed mitogen (PWM) and phytohemagglutinin (PHA) and in the percentage of peripheral blood T lymphocytes. No increase in serum albumin was seen regardless of calorie intake.