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Biomedical subjects

R A Helms

Publications and source records attributed to R A Helms.

35 records · Page 2Linked to original sources

Enhanced lipid utilization in infants receiving oral L-carnitine during long-term parenteral nutrition.

Fourteen infants requiring long-term total parenteral nutrition but able to tolerate small quantities of enteral feedings were randomized into carnitine treatment and placebo control groups. All infants had received nutritional support devoid of carnitine. Plasma carnitine levels and observed plasma lipid indices were not different before supplementation. Under standardized, steady-state conditions, 0.5 g/kg fat emulsion (intralipid) was administered intravenously over 2 hours both before and after infants received 7 days of continuous nasogastric or gastric tube L-carnitine (50 mumol/kg/day) or placebo. Plasma triglyceride, free fatty acid, acetoacetate, beta-hydroxybutyrate, and carnitine concentrations were observed at 0 (start of lipid infusion), 2, and 4 hours for pre- and post-treatment periods, and in addition at 6 and 8 hours after carnitine supplementation. Infants receiving carnitine had significantly greater beta-hydroxybutyrate plasma concentrations (P less than 0.05) and carnitine (P less than 0.001) at 0, 2, 4, 6, and 8 hours, and greater plasma acetoacetate concentrations (P less than 0.05) at 2, 4, 6, and 8 hours, compared with controls. Twenty-four-hour urinary carnitine excretion was very low for both groups before supplementation; after supplementation, excretion was higher (P less than 0.05) in the carnitine group. No significant differences were found between groups for plasma triglyceride or free fatty acid concentrations at any observation period. This study demonstrated enhanced fatty acid oxidation, as evidenced by increased ketogenesis, with L-carnitine supplementation in infants receiving long-term total parenteral nutrition.

3-Hydroxybutyric Acid↗

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.

Adolescent↗

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.

Anthropometry↗

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.

Bilirubin↗

Standardized versus pharmacist-monitored individualized parenteral nutrition in low-birth-weight infants.

The clinical contribution and cost effectiveness of pharmacist involvement in peripheral-vein total parenteral nutrition (TPN) in a neonatal intensive-care unit was studied. Fourteen neonates who received a standardized TPN solution without pharmacist monitoring (Group 1) were compared with 14 neonates who received an individualized TPN solution with pharmacist monitoring (Group 2). Infants were excluded from the study if they received oral feeding, or TPN for less than five days, or were fluid-restricted. No significant difference in mean gestational age, birth weight, gestational size, age at initiation of therapy, duration of therapy, or daily amount of fluid administered was found between the two groups. The mean weight gain in Group 1 (4.9 g/day) was significantly less than in Group 2 (11.8 g/day) (p less than 0.02). The amount of protein provided to Group 2 (2.2 g/kg/day) was significantly greater than to Group 1 (1.9 g/kg/day) (p less than 0.01). The number of calories provided per day was greater for Group 2 (63 kcal/kg/day) than for Group 1 (53 kcal/kg/day) (p less than 0.001). When only those infants who received lipids were analyzed, Group 2 received significantly more lipid (2.0 g/kg/day) than group 1 (1.5 g/kg/day) (p less than 0.001). The mean daily cost was greater for Group 2; however, when cost was related to efficacy, Group-2 cost per gram of weight gain was lower than Group-1 cost. Pharmacist monitoring of an individualized program of TPN in neonates provided a greater mean daily weight gain, allowed a greater amount of nutrients to be provided, and was cost effective compared with the use of a standardized solution without pharmacist monitoring.

Body Weight↗

Natural killer activity of human lymphocytes against colon cancer cells.

A human colon cancer cell line, HCT-8, is shown to be an appropriate target cell for study of natural killer (NK) activity in man. In parallel experiments, effector cell characteristics for NK and antibody-dependent cellular cytotoxicity (ADCC) were found to be vested in a single lymphocyte subpopulation, which bore receptors for the Fc fragment of IgG, but lacked other surface receptors. The effector cell failed to adhere to glass and was inactivated by exposure to 3500 rad x-irradiation. Cells forming rosettes with SRBC and cells bearing receptors for complement were inactive in both systems. A wide distribution of NK activity was noted among individuals that correlated with the distribution of effector cell activity in ADCC (r = 0.8). Preincubation of NK effector cells with antibody-coated ADCC target cells markedly reduced NK activity. Neuraminidase treatment of effector cells led to increased NK and diminished ADCC, while trypsin treatment led to reduced NK activity and showed no effect on ADCC. Thus, NK and ADCC effector cells are highly overlapping if not identical populations, but different structures on the cell membrane may mediate the two activities.

Antibody-Dependent Cell Cytotoxicity↗

Cirrhotic hyperglobulinemia: increased rates of immunoglobulin synthesis by circulating lymphoid cells.

We have measured immunoglobulin (Ig) synthesis by circulating lymphoid cells of 20 patients with cirrhotic hyperglobulinemia (CH) and 20 age-matched controls. We used specific anti-Ig antisera to precipitate Ig synthesized from [14C] amino acid precursors in 13 controls and employed an electroimmunoassay of the "rocket" type to measure Ig elaborated by cultured cells in 4 patient-control pairs. In addition, we studied 3 patient-control pairs by absorption of elaborated Ig onto an anti-Ig-coated solid phase, bromoacetylcellulose. The synthetic index (SI; the ratio of Ig synthesis by a CH patient and a control) was elevated in every case. Mean SI by coprecipitation was 7.2 +/- 5.4 (mean +/- SD), by rocket" 7.3 +/- 3.0 for IgG and 2.2 +/- 0.8 for IgA, and by immunoabsorption 13.8 +/- 8.4 for IgG. Three cirrhotic nonhyperglobulinemic patient-control pairs showed a mean SI of 1.0 +/- 0.1. CH and control populations showed equal numbers of membrane Ig-positive B lymphocytes by immunofluorescence. We conclude that (1) peripheral blood lymphoid cells are appropriate for study of differences in Ig synthetic capacity among individuals; (2) CH is associated with increased in vitro Ig synthesis; and (3) CH lymphocytes may be an appropriate cell population for the study of control mechanisms in Ig synthesis.

B-Lymphocytes↗

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.

Adult↗

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.

Adenocarcinoma↗

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.

Fat Emulsions, Intravenous↗

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.

Fat Emulsions, Intravenous↗

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.

Carnitine↗

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)

Amino Acids↗

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.

Cardiac Surgical Procedures↗

Retinol-binding protein and prealbumin: useful measures of protein repletion in critically ill, malnourished infants.

Plasma prealbumin (PA) and retinol-binding protein (RBP) concentrations were serially measured in 25 critically ill, malnourished infants requiring parenteral nutrition to determine if these visceral protein markers are useful in assessing acute protein repletion. Significant increases in both proteins (p less than 0.05) were noted as early as 5 to 7 days after institution of parenteral nutrition and continued significantly above baseline values through 2 weeks of observation. Gestational development (in infants less than 4 weeks old) and mean protein intake influenced visceral protein responses. Appropriate for gestational age neonates had more rapid and quantitatively greater PA responses (p less than 0.05) than small for gestational age neonates. Small for gestational age neonates never exceeded baseline RBP responses. Average protein intake of less than or equal to 2 g/kg/day resulted in PA and RBP concentrations below baseline and significantly lower than infants on higher protein intakes (p less than 0.05), at the end of 2 weeks. Average calorie intake of greater than 100 cal/kg/day had no differential influence on PA or RBP when compared with infants on less calories. Prealbumin values correlated with RBP values observed simultaneously (r = 0.588, p less than 0.0001). We conclude that PA and RBP are useful measures of protein repletion in critically ill infants requiring parenteral nutrition.

Critical Care↗