Phenylalanine and tyrosine metabolism in neonates receiving parenteral nutrition differing in pattern of amino acids

Tyrosine is considered to be an indispensable dietary amino acid in the neonate, yet achieving adequate parenteral tyrosine intake is difficult due to its poor solubility. Increasing the supply of phenylalanine is the most common means of compensating for low tyrosine levels. Unfortunately, plasma phenylalanine concentrations are sometimes elevated in infants receiving high phenylalanine intake. This led us to study the phenylalanine and tyrosine metabolism in 16 neonates randomized to receive total parenteral nutrition with either a high or a moderate phenylalanine-containing amino acid solution. A primed, 24-h continuous stable isotope infusion of L-[1-13C]phenylalanine and L-[3,3-2H2]tyrosine was given to enable the measurement of phenylalanine and tyrosine kinetics. Results demonstrated that 1) phenylalanine hydroxylation was significantly greater in infants receiving high phenylalanine, 2) phenylalanine oxidation and percent dose oxidized was also significantly greater in infants receiving high phenylalanine, 3) apparent phenylalanine retention was greater in neonates receiving high phenylalanine, and 4) alternate catabolites of phenylalanine and tyrosine metabolism were significantly greater in infants receiving high phenylalanine compared with moderate phenylalanine. We conclude that neonates respond to increased parenteral phenylalanine intake by increasing their hydroxylation and oxidation rates. The greater oxidation of phenylalanine in infants receiving high phenylalanine in conjunction with the urinary excretion of alternate catabolites of phenylalanine and tyrosine suggests that the high phenylalanine intake may be in excess of needs. However, the lower apparent phenylalanine retention observed in infants receiving moderate phenylalanine suggests that the total aromatic amino acid level of moderate phenylalanine may be deficient for neonatal needs.     

Manganese toxicity in children receiving long-term parenteral nutrition

BACKGROUND: In patients receiving long-term parenteral nutrition (PN), cholestatic disease and nervous system disorders have been associated with high blood concentrations of manganese. In such patients, the normal homoeostatic mechanisms of the liver and gut are bypassed and the requirement for this trace element is not known; nor has it been certain whether hypermanganesaemia causes the cholestasis or vice versa. We explored the direction of effect by serial tests of liver function after withdrawal of manganese supplements from children receiving long-term PN. We also examined the relation between blood manganese concentrations and brain lesions, as indicated by clinical examination and magnetic resonance imaging (MRI). METHODS: From a combined group of 57 children receiving PN we identified 11 with the combination of hypermanganesaemia and cholestasis; one also had a movement disorder. Manganese supplements were reduced in the first three and withdrawn in the remainder. MRI was done in two of these children. We also looked at manganese concentrations and MRI scans in six children who had received PN for more than 2 years without developing liver disease. FINDINGS: In the hypermanganesaemia/cholestasis group, four of the 11 patients died. In the seven survivors baseline whole-blood manganese was 615-1840 nmol/L, and after 4 months it had declined by a median of 643 nmol/L (p < 0.01). Over the same interval total bilirubin declined by a median of 70 mumol/L (p < 0.05). Two of these children had movement disorders, one of whom survived to have an MRI scan; this showed, with T1 weighted images, bilateral symmetrically increased signal intensity in the globus pallidus and subthalamic nuclei. Such changes were also seen in five other children--one from the hypermanganesaemia/cholestasis group and four of six in the long-term PN group without liver disease (in all of whom blood manganese was above normal). INTERPRETATION: The cholestasis complicating PN is multifactorial, but these results add to the evidence that manganese contributes. In view of the additional hazard of basal ganglia damage from high manganese levels in children receiving long-term PN, we recommend a low dose regimen of not more than 0.018 mumol/kg per 24 h together with regular examination of the nervous system.     

Lipid peroxidation and antioxidant status in adults receiving lipid-based home parenteral nutrition

BACKGROUND: Infusion of lipid emulsions rich in polyunsaturated fatty acids (PUFAs) may increase lipid peroxidation, which is counteracted mainly by superoxide dismutase (SOD) (a zinc-, copper-, and manganese-dependent enzyme), selenium-dependent glutathione peroxidase (Se-GSHPx), and alpha-tocopherol. OBJECTIVE: We investigated lipid peroxidation and antioxidant status in patients receiving home parenteral nutrition (HPN) providing variable amounts of a lipid emulsion rich in PUFAs, and alpha-tocopherol, zinc, copper, and manganese as recommended by the American Medical Association, and no selenium. DESIGN: Serum malondialdehyde, plasma alpha-tocopherol, selenium, Se-GSHPx, PUFAs, and red blood cell Se-GSHPx and SOD were evaluated in 12 patients and in 25 healthy control subjects. Malondialdehyde was also assessed in a group of 40 healthy control subjects. RESULTS: Patients had significantly higher concentrations of malondialdehyde and SOD and lower alpha-tocopherol concentrations and selenium nutritional status. Linear regression analysis showed that malondialdehyde was associated with the daily PUFA load (r=0.69, P< 0.03) and with plasma alpha-tocopherol (r=-0.59, P< 0.05), but stepwise multiple regression analysis confirmed only the association between malondialdehyde and alpha-tocopherol; plasma alpha-tocopherol was associated with the daily PUFA load (r=-0.65, P< 0.04) and with the duration of HPN (r=-0.74, P< 0.02). CONCLUSIONS: In HPN patients, the peroxidative stress due to lipid emulsions rich in PUFAs is counteracted primarily by alpha-tocopherol. The dosages of alpha-tocopherol, zinc, copper, and manganese recommended by the American Medical Association appear sufficient to sustain SOD activity but inadequate to maintain alpha-tocopherol nutritional status. HPN formulations should be supplemented with selenium.     

Effect of intradialytic parenteral nutrition on quality of life in hemodialysis patients

The purpose of this study was to determine the effect of intradialytic parenteral nutrition (IDPN) on the quality of life of malnourished patients with end-stage renal disease on high-efficiency and high-flux hemodialysis therapy. Patients, who met the Medicare eligibility requirements for IDPN, were asked to fill out and extensive questionnaire covering several measures of quality of life prior to initiating and again after completing four months of IDPN therapy. Although the IDPN improved serum albumin levels significantly, aside from improved sleep patterns, no significant improvements in quality of life could be demonstrated. The mortality rate of these enrolled patients was as high as 28% within 4 months. We concluded that the limited amount of nutrition delivered over the course of a short dialysis session may not be enough to appreciably change the lives of our malnourished patients.     

Body composition changes measured by dual-energy X-ray absorptiometry in patients receiving home parenteral nutrition

Some patients with infiltrant vesical cancer can be treated successfully with radical cysto-prostatectomy and urinary by-pass and increasingly more authors publish successful results in series of selected patients over 70- and 80-year old. Between February 1988 and July 1996, 18 radical cystectomies with orthotopic urinary by-pass were performed in the Urology Service, Policlinico Vigo, in patients over 70 (range 70-84 years), with an operative mortality rate of 11%. 8 patients (44%) developed immediate complications and 9 patients (50%) presented distant complications. Overall mortality in our series was 33.3% and survival 66.6% after a mean follow-up of 30.7 months. We believe orthotopic-continent by-pass is a valid alternative with operative mortality and complication rates similar to those of ileal ducts, with the advantage for the patient of avoiding permanent urinary stoma.     

Effect of severity of stress on whole-body protein kinetics in surgical patients receiving parenteral nutrition

A study was conducted to clarify the quantitative relationship between the alteration of protein metabolism and the severity of surgical stress to further understand the mechanisms of body nitrogen losses in surgical trauma. Twenty-one patients undergoing esophagectomy for esophageal cancer (group E), and 22 undergoing gastrectomy or colorectal operations for gastric or colorectal cancer (Group GC) were studied. All patients were fed exclusively by parenteral nutrition (PN) providing 1.5 g protein.kg-1.d-1 and 35 kcal.kg-1.d-1 before and after the operation. The measurements of whole-body protein turnover, synthesis, and breakdown were performed preoperatively and on postoperative days (PODs) .3 and 10. Urinary excretion of total nitrogen and total catecholamines was also measured. Urinary excretion of the total catecholamines of group E was twice as high as that of group GC on the POD 3 and well reflected the severity of surgical stress. Negative correlation of nitrogen retention to urinary excretion of the total catecholamines was also observed (r = 0.64; P < 0.01). The correlations between the urinary excretion of the total catecholamines and the whole-body protein flux, synthesis, and breakdown were statistically significant (r = 0.57, 0.27, and 0.57, respectively; P < 0.01 in all). Rate of elevation in breakdown according to the stress level was greater than that of synthesis. Consequently the progressive aggravation of nitrogen balance according to the severity of surgical stress was observed.     

Quality of life issues: parenteral nutrition to small bowel transplantation--a review

Parenteral nutrition (PN) has given life to patients with chronic intestinal failure who would otherwise have died. Home parenteral nutrition has improved the quality of life for many children. However, morbidity from this therapy remains significant with complications of line sepsis, lack of venous access, hepatic dysfunction, and pulmonary embolism. These complications are common in younger children. Detailed discussion must take place with the family regarding risks and benefits of PN. In those children developing complications of PN, intestinal transplantation is a logical extension of treatment. Early referral of patients for assessment is vital because significant mortality occurs when liver disease is established. Time is needed to counsel families on the potential benefits and risks of this treatment, including the physical and emotional demands made on the child and family. Overall worldwide survival for isolated small bowel transplantation is currently 50% and for combined small bowel and liver transplantation 40%. Significant complications are rejection, sepsis, and lymphoproliferative disease. Postoperative management can be complex and prolonged; child and parents require a great deal of physical and emotional support. The burden of care for parents decreases significantly after the first year. Small bowel transplantation offers a realistic alternative to PN. The choice of treatments is influenced by expected quality of life, which is just beginning to be evaluated.     

Threonine requirement of neonatal piglets receiving total parenteral nutrition is considerably lower than that of piglets receiving an identical diet intragastrically

Evidence is accumulating that the amino acid requirements for neonates receiving total parenteral nutrition (TPN) are significantly different than those for oral feeding and need to be determined. The parenteral threonine requirement was determined in 3-d-old male Yorkshire piglets (n = 25) by examining the effect of varying dietary threonine intakes [0.05-0.6 g/(kg.d)] on phenylalanine oxidation. The diet included adequate energy, total amino acids and phenylalanine, with excess tyrosine. Phenylalanine kinetics were determined from a primed, continuous intravenous infusion of L-[1-14C]phenylalanine. Phenylalanine oxidation, estimated from the rate of 14CO2 released in expired air during isotope infusion, decreased (P < 0.05) as threonine intake increased from 0.05 to 0.15 g/(kg.d) and was low and constant for threonine intakes >0.15 g/(kg.d). Using breakpoint analysis with 95% confidence interval (CI), mean requirement and safe level of parenteral threonine intake were estimated to be 0.19 and 0.21 g/(kg. d), respectively (equivalent to 13 and 14 mg/g amino acids, respectively). To compare these data with those of orally fed controls, we then repeated the experiment by infusing identical diets intragastrically to piglets (n = 25); the varying dietary threonine intakes were 0.1-1.2 g/(kg.d). Employing identical kinetics and analyses, the mean requirement and safe level of oral threonine intake were estimated to be 0.42 and 0.51 g/(kg.d), respectively (equivalent to 28 and 34 mg/g amino acids, respectively). These data demonstrate that the threonine requirement of neonates during TPN is approximately 45% of the mean oral requirement.     

Total parenteral nutrition in surgical patients

Malnutrition is common in the hospitalized surgical patient. There is a strong association between improved nutritional status and a favorable postoperative recovery, while malnutrition has an adverse effect on surgical outcome (Driscoll & Blackburn, 1990; Souba, 1997). Advances in providing parenteral nutrition have had a positive impact on nutrition care of these patients and will be reviewed in this article.     

Oxalogenesis in parenteral nutrition solution components

Oxalate has been implicated in the etiology of nephrocalcinosis in premature infants as well as in the formation of insoluble precipitates in total parenteral nutrition (TPN) intravenous tubing. Oxidation of ascorbate to oxalate, especially in the presence of catalysts such as copper and iron, has been implicated in formation of these precipitates. The purpose of this project was to measure oxalate formation in certain TPN components separately and in combination. Neonatal TPN solution components in combination were infused at 5 mL/h under simulated clinical conditions used in a neonatal intensive care unit. Aliquots were assayed at intervals for oxalate by capillary electrophoresis. Oxalate is present in one TPN mixture at concentrations up to 8 ppm. The addition of ascorbate to an aqueous solution of trace metals may promote oxalogenesis.     

Total parenteral nutrition in pregnancy]

Every minute, several million protein and RNA molecules must be transported between the cytoplasm and the nucleus of a eukaryotic cell. The characterization of mediators, receptors and accessory factors for different nuclear import and export pathways has provided a glimpse at the molecular machinery that is responsible for these trafficking events. It appears that both inbound and outbound traffic is mediated by a protein family of related transport factors that can be classified as importins and exportins.     

Reversible hyperintensity of the anterior pituitary gland on T1-weighted MR images in a patient receiving temporary parenteral nutrition

We report a patient with severe anorexia nervosa, treated with temporary total parenteral nutrition (TPN), in whom reversible hyperintensity of the anterior pituitary gland was seen on T1-weighted MR images. The anterior pituitary was isointense with white matter before TPN therapy and became markedly hyperintense after 3 months of treatment. The intensity normalized after TPN therapy was discontinued. The transient hyperintensity was also seen in the basal ganglia and dorsal brain stem. We believe the hyperintensity of the anterior pituitary may be attributed to the TPN therapy.     

Bolus intravenous infusion of amino acids or lipids does not stimulate gallbladder contraction in neonates on total parenteral nutrition

On the basolateral infoldings of the strial marginal cells in the cochlea, Na K ATPase activity is abundant. To clarify the humoral control by norepinephrine, K-NPPase activity of strial marginal cells in the cochlea was investigated in normal, reserpine, norepinephrine (NE), reserpine plus NE-treated guinea pigs using a cerium-based method. K-NPPase activity was almost completely decreased 3-20 days after reserpine administration. At 10 days after reserpinization and following NE repeated treatment, enzyme activity was detectable. These results suggested that norepinephrine might restore and regulate strial K-NPPase activity.     

Monitoring and complications of parenteral nutrition

A knowledge of the complications of parenteral nutrition is inherent in the design of any monitoring system. In the initial stages of therapy, the complications are usually of electrolyte imbalance. It must also be appreciated that the provision of nutrition to severely malnourished patients will expose underlying deficiencies, particularly of phosphates and trace elements. In long-term parenteral nutrition, the complications can be broadly divided into those associated with the line and metabolic complications. The line complications include: line blockage, sepsis, and pulmonary embolism. The most important metabolic complication is undoubtedly liver cholestasis, which may be associated with recurrent episodes of sepsis. Any department undertaking long-term parenteral nutrition should have an active nutrition team to avoid complications and audit outcome.     

Home parenteral nutrition in children: the Polish experience

BACKGROUND: Home parenteral nutrition has become routine for management of intestinal failure in patients. In Poland the main obstacle to widespread use of home parenteral nutrition is the lack of interest of commercial companies in delivering feedings and ancillaries to patients. METHODS: Twenty-five home parenteral nutrition patients aged from 4 months to more than 13 years were reviewed. The mother or both parents were trained in home parenteral nutrition techniques for 4 to 6 weeks and compounded the nutrients themselves at home. RESULTS: The mean duration of home parenteral nutrition was 10,117 patient days. Hospital stays of patients receiving parenteral feedings were significantly shorter than the duration of administration of home parenteral nutrition (p < 0.001). Eleven children are continuing the home parenteral nutrition program. Eighty-three catheters were used in these patients. The rate of catheter occlusion decreased within the observation period, and in 1997 not one case of occlusion was observed. In 1997 only three catheters were removed during 7.8 patient years, and the overall incidence of catheter-related complications was 0.38 per patient year. The overall occurrence of septicemia was one case in 516 days and of catheter infection was one in 459 days. In 1997 a catheter was infected on average of once every 1419 days. There was significant improvement in the z score for weight during therapy. The average monthly cost of nutrients and ancillary items was approximately $1200 (4200 Polish zlotys [PLN]). These costs are 1.6 to 3 times lower than those recorded in other studies. CONCLUSION: Home parenteral nutrition in children with nutrients mixed by caregivers in the home setting is a safe and appropriate method of treatment that can be used in countries where home parenteral nutrition solutions are not manufactured or where commercial home parenteral nutrition is not economically feasible.