The effect of enriched branched chain amino acid solution on amino acid metabolism during perioperative total parenteral nutrition support

A prospective, randomized clinical study was performed in patients underwent subtotal gastrectomy or hemicolectomy. Patients were randomly divided into two groups receiving standard amino acid solution (23% BCAA) or a solution enriched with branched chain amino acid (41% BCAA). Preoperative postprandial plasma amino acid levels were used as base line. The amino acid concentrations in plasma between control group (A) and study group (B) were compared during perioperative period. The dynamics of postoperative plasma amino acid profile of the two groups were similar except that plasma BCAA concentrations were very high in group B. In both groups, the levels of plasma glutamine, alanine, tyrosine, lysine, threonine, arginine, asparagine, and cystine decreased, whereas the levels of plasma methionine, phenylalanine, and tryptophan increased. The solution of 41% BCAA was not found to be superior to standard 23% BCAA in normalizing the disorder of plasma amino acid spectrum during the period of TPN support. The differences of urinary amino acid excretion including 3-MHIS and nitrogen balance between the two groups were not statistically significant. Also the results showed more severe disorder of plasma amino acid profile caused by 41% BCAA solution than by standard solution of 23% BCAA.     

Dehydroascorbic acid and oxidative stress in haemodialysis patients.

BACKGROUND: The amount of dehydroascorbic acid contained within total ascorbic acid (oxidized as well as non-oxidized forms) in plasma, hereafter referred to as the dehydroascorbic acid fraction, may be a measure of oxidative stress during haemodialysis. In the present study, we determined this fraction in chronic haemodialysis patients. METHODS: Using high performance liquid chromatography, dehydroascorbic acid and total ascorbic acid levels were measured in 80 maintenance haemodialysis patients for a period of > 2 years as well as in 49 controls, to examine a possible association of these compounds with clinical parameters and/or drugs taken by the patients. RESULTS: Dialysis patients who had an increased plasma urate level (P < 0.05) and had been taking allopurinol (P < 0.05) or NSAID (non-steroid anti-inflammatory drugs) (P < 0.01), and dialysis patients who were younger (< or = 55 years), as compared with older dialysis patients (P < 0.01), were found to have a lower dehydroascorbic acid fraction by multivariate analysis. Mean plasma dehydroascorbic acid levels and dehydroascorbic acid fractions were significantly lower in the younger haemodialysis patients (4.8 +/- 0.7 micromol/l and 28.4 +/- 3.9%) than in healthy younger controls (13.3 +/- 1.1 micromol/l and 41.1 +/- 1.8%) (P < 0.0001 and P < 0.01, respectively). Moreover, a correlation was found between plasma dehydroascorbic acid fraction and plasma lipid peroxide (r = 0.66, P < 0.01) in patients who had not been taking allopurinol and/or NSAID. CONCLUSION: We found that dehydroascorbic acid fraction was related to patients' age, plasma urate level and to taking allopurinol or NSAID. Dehydroascorbic acid fraction may be another indirect index of oxidative stress.     

Ammonium chloride and alpha-ketoglutaric acid increase glutamine availability in the early phase of induced acute metabolic acidosis

BACKGROUND: Glutamine deficiency in critical illness is associated with increased morbidity and mortality. We hypothesized that ammonium chloride (NH(4)Cl) and alpha-ketoglutaric acid (alpha-KGA) infusions could increase glutamine availability possibly through de novo synthesis in the liver. METHODS: Anesthetized post-absorptive pigs were allocated to four groups (n = 8). The study groups received either a 4-h intravenous infusion of alpha-KGA, 11.4 micromol/kg/min and NH(4) (+), 9.7 micromol/kg/min (group 1), or alpha-KGA, 2.85 micromol/kg/min and NH(4) (+), 46.3 micromol/kg/min (group 2), or alpha-KGA, 11.4 micromol/kg/min (group 3), or isotonic saline (control group). Plasma concentrations of glutamine and glutamine exchange in liver, intestine and skeletal muscle were investigated. RESULTS: Plasma glutamine concentrations in group 1 (58% increase) were greater (P < 0.05) compared with the control group (14% decrease) and group 3 (13% decrease), and in group 2 (91% increase) compared with the control group, group 3 (P < 0.0001) and group 1 (P < 0.05). Intestinal glutamine extractions in group 2 were significantly greater (P < 0.01) compared with all other groups. Neither the liver nor the hind leg increased its release of glutamine. Arterial pH decreased (all P < 0.001) to 7.39 +/- 0.01 in the control group, 7.30 +/- 0.01 in group 1, 7.19 +/- 0.01 in group 2 and 7.35 +/- 0.01 in group 3. CONCLUSION: Infusions of alpha-KGA and NH(4)Cl, to a pH range of 7.20-7.30, did not enhance hind leg or hepatic glutamine release. The increased plasma concentrations of glutamine were effects of NH(4)Cl, not alpha-KGA, and caused either by de novo synthesis or decreased degradation.     

Treatment of hyperhomocysteinemia in children on dialysis by folic acid

Adult patients with renal failure have a high total homocysteine concentration in plasma. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. Folic acid lowers the homocysteine concentrations in plasma in hyperhomocysteinemia. Whether this results in a reduced risk for cardiovascular diseases remains to be proven by intervention studies. In the present study we investigated: (1) if homocysteine concentrations are elevated in the plasma of children with renal failure and (2) the influence of folic acid administration on the plasma homocysteine concentration. The plasma homocysteine concentration was measured in 21 children, 9 on hemodialysis and 12 on peritoneal dialysis, before and 4 weeks after treatment with 2.5 mg folic acid daily. Healthy children (234) constituted the control group. In controls the median homocysteine concentration was 9.1 μmol/l (range 4.3–20.0 μmol/l). The median plasma homocysteine concentration in patients before folic acid treatment was 20.0 μmol/l (Q1-Q3 13.7–26.0; Q, quartile). After 4 weeks of folic acid treatment the median plasma homocysteine concentration was 12.0 μmol/l [Q1-Q3 9.8–14.3 (P<0.0001 Wilcoxon signed rank test)]. There was no significant difference between hemodialysis and peritoneal dialysis patients. Children with renal failure treated with hemodialysis or peritoneal dialysis have elevated plasma homocysteine concentrations, but this is significantly reduced after administration of 2.5 mg folic acid daily for 4 weeks. It is suggested that folic acid be added to the treatment of children with renal failure, although a beneficial effect still has to be proven. The required dose needs further study. Received: 16 February 1998 / Revised: 2 November 1998 / Accepted: 4 November 1998     

The nutritional/metabolic and hormonal effects of 8 weeks of continuous ambulatory peritoneal dialysis with a 1% amino acid solution

Circulating intermediary metabolites, hormones and plasma amino acids (AA) were measured at intervals over 24 hours in seven non-diabetic patients with chronic renal failure treated by continuous ambulatory peritoneal dialysis (CAPD), before and after an 8-week period during which a 1% amino acid dialysis solution replaced two of the four dextrose exchanges. Mean 24-hour concentrations of plasma total and essential amino acid were higher following the AA dialysate (total pre: 2893 +/- 185; total post: 3357 +/- 244; p less than 0.05; essential pre: 751 +/- 47; essential post: 1064 +/- 57 mumol/l; p less than 0.001). Mean 24-hour concentrations of the branched chain amino acids leucine, isoleucine and valine were higher following the AA dialysate (valine pre: 201 +/- 18; valine post: 321 +/- 19; p less than 0.001; leucine pre: 102 +/- 6; leucine post: 127 +/- 9; p less than 0.01; isoleucine pre: 67 +/- 5; isoleucine post: 85 +/- 7 mumol/l; p less than 0.05). Serum albumin increased with use of the AA dialysate (pre: 36 +/- 1; 2 weeks, 40 +/- 1; 4 weeks, 40 +/- 1; 6 weeks, 41 +/- 1; 8 weeks, 38 +/- 2 g/l). 24-hour profiles and mean 24-hour concentrations of blood glucose, serum insulin, serum triglyceride, plasma non-esterified fatty acids (NEFA), plasma 3-hydroxybutyrate and plasma alanine were unchanged after the AA period. Plasma bicarbonate decreased with use of the amino acid solution (pre: 21 +/- 1; 2 weeks, 18 +/- 1; 4 weeks, 18 +/- 1; 6 weeks, 16 +/- 1; 8 weeks, 16 +/- 1 mmol/l). Use of a 1% amino acid solution over an 8-week period in CAPD patients improves the plasma amino acid profile but results in a metabolic acidosis. The other endocrine and metabolic abnormalities of uremia remain unchanged.     

Effects of methionine loading on plasma and erythrocyte sulphur amino acids and sulph-hydryls before and after co-factor supplementation in haemodialysis patients.

BACKGROUND: Hyperhomocysteinaemia, which is potentially atherogenic, is common in chronic haemodialysis (HD) patients but the reason for this is not yet known. The methionine (Met) loading test (MLT) is used to test the capacity of homocysteine (Hcy) disposal by the trans-sulphuration pathway and thus may provide information on the metabolism of sulphur amino acids. The availability of vitamin B(6) and folic acid, as co-factors for Hcy metabolism may affect the response to MLT. In the present study, we compared the effect of Met loading on plasma and erythrocyte (RBC) sulphur amino acids and sulph-hydryls before and after co-factor supplementation in healthy subjects and HD patients. METHODS: In 10 HD patients and 10 healthy subjects the effect of Met loading, 0.1 g/kg BW, on plasma and RBC methionine metabolites was studied over 7 h, before and after 4 weeks supplementation with high daily doses of vitamin B(6) (200 mg) and folic acid (15 mg). RESULTS: MLT before vitamin supplementation in HD patients, compared to the healthy subjects, caused significantly greater increases in plasma Hcy levels (43+/-12 vs 15+/-5 micromol/l), cysteinesulphinic acid (CSA) (1.34 vs 0.36 micromol/l) and gamma-glutamylcysteine (0.98+/-0.83 vs -01+/-0.42 micromol/l) and no decline in plasma cysteine (Cys) (0.5+/-33.9 vs -31+/-26 micromol/l), but no significant differences in plasma taurine, cysteinylglycine, and glutathione concentrations. In RBCs there was a small increase in Hcy levels and a more marked increase in Tau levels, with no difference between the healthy subjects and HD patients. Vitamin supplementation in pharmacological doses failed to correct the abnormal responses to MLT in the HD patients. CONCLUSIONS: Oral methionine loading in HD patients leads to higher accumulation of Hcy and other Met metabolites in plasma and RBCs than in healthy subjects, indicating impaired metabolism of sulphur amino acids via the trans-sulphuration pathway. Supplementation with high doses of vitamin B(6) and folic acid does not correct this impairment, suggesting that it most probably is not due to lack of these co-factors.     

Sustained reduction of hyperhomocysteinaemia with folic acid supplementation in predialysis patients.

BACKGROUND: Moderate hyperhomocysteinaemia, as occurs in chronic renal failure patients, is an established independent risk factor for atherosclerotic arterial occlusive accidents, the incidence of which is abnormally high in such patients. Folic acid supplementation has been shown to reduce plasma homocysteine level in end-stage renal disease patients treated with haemodialysis or peritoneal dialysis, but its long-term effects in predialysis patients had not been assessed. METHODS: We prospectively treated a total of 78 predialysis patients with folic acid for at least 1 year (range 12-74 months) together with oral pyridoxine and vitamin B12 supplements. Of the patients, 67 received 5 mg folic acid three times per week, whereas the other 11 patients who were treated with recombinant erythropoietin received 5 mg/day. Plasma fasting total homocysteine concentration was determined at baseline, after 3 months and at the end of follow-up. RESULTS: Mean (+/-SD) plasma total homocysteine level decreased from 21.2+/-6.4 micromol/l at baseline to 14.2+/-4.6 at 3 months and remained at 12.8+/-3.7 micromol/l at the end of follow-up (average duration 2.8 years), whereas plasma creatinine rose from 268+/-129 to 399+/-234 micromol/l. Mean plasma folate concentration rose from 19+/-12 to 47+/-13 nmol/l and mean plasma vitamin B12 rose from 237+/-119 to 347+/-191 pmol/l from baseline to end of follow-up. CONCLUSIONS: Moderate folic acid supplementation (2.15 mg/day) allows a substantial (40% as a mean) and sustained (up to 6 years) reduction of plasma total homocysteine level in predialysis uraemic patients without any detectable side effect. Folic acid supplementation may thus contribute to lower the risk of accelerated atherosclerosis in such patients.     

Amino acid kinetics during the anhepatic phase of liver transplantation

Alanine and glutamine are interorgan nitrogen/carbon carriers for ureagenesis and gluconeogenesis, which are mainly but not necessarily only hepatic. The liver is central to alanine and glutamine metabolism, but most organs can produce and use them. We studied amino acid kinetics after liver removal to depict initial events of liver failure and to provide a model to study extrahepatic gluconeogenesis and nitrogen disposal in humans. We measured amino acid kinetics with [5,5,5-(2)H(3)]leucine and [3-(13)C]alanine or [1,2-(13)C(2)]glutamine tracers in 21 subjects during and after the anhepatic phase of liver transplantation: 12 were at 7 months posttransplantation, and 7 were healthy control subjects. Anhepatic leucine kinetics, including proteolysis, was unchanged. Alanine plasma and whole-body contents increased 3x and 2x, with a halved metabolic clearance and a doubled production, 2% greater than disposal. Free whole-body glutamine decreased 25% but increased 50% in plasma. Glutamine clearance was halved, and the production decreased by 25%, still 2% greater than disposal. Liver replacement decreased alanine and glutamine concentrations, leaving leucine unchanged. Liver removal caused doubled alanine fluxes, minor changes in glutamine, and no changes in leucine. The initial events after liver removal are an accumulation of three-carbon compounds, an acceleration of alanine turnover, and limited nitrogen storage in alanine and glutamine.     

Folate, vitamin B12, and sulfur amino acid levels in patients with renal failure

We examined the plasma profile of sulfur amino acids (SAA) in patients with chronic renal failure (CRF) and looked for any correlation with serum folate (FA) and/or vitamin B₁₂. Group 1 comprised 9 patients with CRF and glomerular filtration rate (GFR) >20 ml/min per 1.73 m², 9 patients with GFR<20 ml/min per 1.73 m² comprised group 2, and 14 patients on hemodialysis group 3. The control group comprised 16 healthy children. Homocysteine (Hcy), methionine (Met), cysteine (Cys), and serine (Ser) were measured with gas chromatography. FA and vitamin B₁₂ were measured using enzymatic immunoassay. Median SAA concentrations were significantly lower in controls than in the three groups of patients. Hcy concentrations were 0.8 μmol/l in controls versus 5 μmol/ (group 1), 9 μmol/l (group 2), and 20 μmol/l (group 3). Met concentrations were 26 μmol/l in controls versus 26 μmol/l (group 1), 66 μmol/l (group 2), and 281 μmol/l (group 3). Cys concentrations were 10 μmol/ in controls versus 98 μmol/l (group 1), 54 μmol/l (group 2), and 122 μmol/l (group 3). Ser concentrations were 88 μmol/ in controls versus 153 μmol/l (group 1), 239 μmol/l (group 2), and 240 μmol/l (group 3). The median concentrations of FA were lower in controls than in groups 2 and 3: 5.5 ng/ml versus 8 ng/ml and 15 ng/ml, respectively. Vitamin B₁₂ concentrations did not differ between groups. Vitamin levels did not correlate with SAA. The only difference between patients with Hcy levels in the lower and upper quartile was in Met concentration (38 vs. 263 μmol/l, P<0.02) and GFR (P<0.01). In conclusion, patients with CRF had higher SAA concentrations than healthy children. FA concentrations are higher in CRF patients than in healthy children but did not correlate with concentrations of SAA. Received: 3 January 2000 / Revised: 21 September 2000 / Accepted: 11 October 2000     

Difference in the homocysteine-lowering effect of folic acid in haemodialysis patients with and without occlusive vascular disease.

BACKGROUND: Hyperhomocysteinaemia has been identified as an independent cardiovascular risk factor and is found in more than 85% of patients on maintenance haemodialysis. Previous studies have shown that folic acid can lower circulating homocysteine in dialysis patients. We evaluated prospectively the effect of increasing the folic acid dosage from 1 to 6 mg per dialysis on plasma total homocysteine levels of haemodialysis patients with and without a history of occlusive vascular artery disease (OVD). METHODS: Thirty-nine stable patients on high-flux dialysis were studied. Their mean age was 63 +/-11 years and 17 (43%) had a history of OVD, either coronary and/or cerebral and/or peripheral occlusive disease. For several years prior to the study, the patients had received an oral post-dialysis multivitamin supplement including 1 mg of folic acid per dialysis. After baseline determinations, the folic acid dose was increased from 1 to 6 mg/dialysis for 3 months. RESULTS: After 3 months, plasma homocysteine had decreased significantly by approximately 23% from 31.1 +/- 12.7 to 24.5 +/- 9 micromol/l (P = 0.0005), while folic acid concentrations had increased from 6.5 +/- 2.5 to 14.4+/-2.5 microg/l (P < 0.0001). However, the decrease of homocysteine was quite different in patients with and in those without OVD. In patients with OVD, homocysteine decreased only marginally by approximately 2.5% (from 29.0 +/- 10.3 to 28.3 +/- 8.4 micromol/l, P = 0.74), whereas in patients without OVD there was a significant reduction of approximately 34% (from 32.7+/-14.4 to 21.6+/-8.6 micromol/l, P = 0.0008). Plasma homocysteine levels were reduced by > 15% in three patients (18%) in the group with OVD compared with 19 (86%) in the group without OVD (P = 0.001), and by > 30% in none of the patients (0%) in the former group compared with 13 (59%) in the latter (P = 0.001). CONCLUSIONS: These results indicate that the homocysteine-lowering effect of folic acid administration appears to be less effective in haemodialysis patients having occlusive vascular disease than in those without evidence of such disease.     

Kinetic study during amino acid infusion in catabolic patients. Comparison between two solutions

The equilibrium kinetic of two different amino acid solutions was investigated in ten catabolic patients (Parentamin, Pierrel; HBC, Baxter). Plasma amino acid pattern was determined on arterial samples before TPN and several times over 48 hours of TPN. Nitrogen balance was measured from 24 hours urine collection. Three different cinetic trends were found: a fast modification (diminution or increase), a slow adaptation, or no modification of plasmatic levels, however each amino acid reached a steady state plateau. The adequacy of the infusion of each amino acid was evaluated comparing its steady-state plasma level to the after lunch level in healthy man. This made possible to approximate metabolic needs of each of the infused amino acids and to identify the inadequacy of some metabolic pathways to synthetized non essential amino acids lacking in solutions. This made possible to identify amino acids infused in excess or in defect, and those infused in dose adapt to the metabolic needs of such patients.     

腹腔感染合并急性肾功能衰竭患者连续静脉-静脉血液滤过治疗前后血浆氨基酸水平变化

目的 探讨腹腔感染合并急性肾功能衰竭患者连续静脉-静脉血液滤过(CVVH)治疗前后血浆氨基酸水平变化和氨基酸丢失量.方法 回顾性分析2008年9月至2009年9月南京军区南京总医院收治的10例腹腔感染合并急性肾功能衰竭患者的临床资料.采用AV600S聚砜膜行24 h CVVH治疗,分别采集CVVH治疗前、治疗12 h和24 h血浆,连续收集24 h滤液.高压液相色谱测定血浆和滤液氨基酸浓度,并计算滤液氨基酸丢失量.采用配对t检验或Wilcoxon秩和检验,一元线性回归分析变量之间的关系.结果 10例患者中死亡6例,其中3例死于脓毒性休克,3例死于MODS.CVVH治疗24 h后血浆各种氨基酸水平显著下降,其中组氨酸、异亮氨酸、半胱氨酸和谷氨酰胺分别由(22.1±10.3)、(20.0±7.6)、(10.3±4.7)、(122.3±72.2)μmoL/L下降至(5.6±3.4)、(6.4±2.5)、(2.9±2.4)、(42.5±33.6)μmol/L.血浆总氨基酸水平呈下降趋势,CVVH治疗12 h和24 h分别下降52%和59%.滤液氨基酸24 h平均丢失量为(9631±1089)mg/d,其中非必需氨基酸和必需氨基酸丢失量分别为(5072±618)mg/d和(3747±654)mg/d,两者比较,差异有统计学意义(t=4.52,P＜0.05).CVVH治疗12 h后滤液氨基酸丢失量和血浆氨基酸水平之间呈正相关(r=0.68,P＜0.05).结论 腹腔感染患者接受CVVH治疗时,氨基酸可以经滤液丢失,因此,为CVVH患者制定营养方案时,滤液额外丢失的氨基酸需要考虑在内,尤其要适当增加非必需氨基酸的含量.     

The effect of metabolic acidosis on amino acid and keto acid metabolism in chronic renal failure

The effect of metabolic acidosis (MA) on amino acid and keto acid metabolism was studied in fourteen patients with chronic renal failure (CRF) under the low protein diet (0.6-0.8 g/kgBW). The comparative study of five patients with renal tubular acidosis was carried out. Each patient was investigated before [MA(+)period] and after correction with sodium bicarbonate administration lasting 10 days [MA(-)period]. The correction of MA improved nitrogen balance and elevated plasma branched-chain amino acids (BCAA), keto acids (BCKA), glutamine and alanine concentrations. No effect was however, observed in change of plasma insulin and glucagon. Oral administration of the keto-analogues of BCKA [0.1 g/kgBW of alpha-ketoisovalerates (KIV) and alpha-keto-isocaproic acid (KIC)] is made for the purpose of investigating the change in the metabolic conversion rate to amino acids. As a result, MA (+) suppressed an increase in plasma KIV and KIC concentrations. Moreover, an increase in plasma valine and leucine concentrations were suppressed by MA (+). These results suggested that MA stimulates BCKA oxidation and suppresses the protein sparing effect of leucine and KIC, and accelerates the catabolism in CRF under the low protein diet. The correction of MA is ineffective in severe renal failure (serum creatinine above 10.0 mg/dl), because the other uremic factors appear to be affecting protein and amino acid metabolism. Therefore, it might be concluded that MA should be corrected at an earlier stage of CRF.     

Muscle and plasma amino acids after injury: hypocaloric glucose vs. amino acid infusion

This study examines the effect of three different hypocaloric diets on the patterns of muscle and plasma amino acids in patients undergoing total hip replacement. Group I (seven patients) received 90 g/day of glucose, Group II (seven patients) received 70 g/day of amino acids, Group III (eight patients) received both 90 g of glucose and 70 grams of amino acids per day. Utilizing the percutaneous biopsy technique of Bergström, free amino acid patterns in muscle and plasma were analyzed pre- and postoperatively (day 4). The postoperative pattern of amino acids was characterized by elevated levels in muscle and plasma of the branched chain amino acids, phenylalanine, tyrosine and methionine. There was a marked decrease in muscle glutamine and smaller decreases in the basic amino acids in both muscle and plasma. Muscle:plasma concentration ratios increased for the neutral amino acids, decreased for glutamine and the basic amino acids and were unchanged for the acidic amino acids. The patterns seen after hip replacement are almost identical to those seen after colectomy or accidental injury. There was little effect of diet on amino acid concentrations in muscle. In plasma, concentrations of leucine, isoleucine, valine and proline were higher in Group II in the absence of glucose intake, than in the other groups. Lysine was lower in Group I with no amino acid intake than in the other groups. Thus, there is a unique amino acid pattern associated with operative trauma which is relatively unaffected by hypocaloric, intravenous nutrition.     

Factors influencing the concentrations of the large neutral amino acids in the brain and in the CSF of dogs after portacaval anastomosis.

Portal-systemic shunting of blood is associated with hyperammonemia, an increased glutamine concentration in brain, an altered plasma neutral amino acid pattern, and high levels of several of the large neutral amino acids in brain. Since some of these amino acids are precursors for neurotransmitters and for other potentially neuroactive substances, high CNS levels of these amino acids may contribute to the development of encephalopathy. In order to determine the relative importance of changes in brain glutamine levels and changes in competition among the neutral amino acids for blood-brain transport, we measured the concentrations of the large neutral amino acids in plasma, cisternal cerebrospinal fluid and in brain tissue from various regions of dogs after end-to-side portacaval shunt. Although the changes in CSF amino acid levels correlated partially with altered amino acid plasma competitor ratios, better correlations were observed with the elevation of CSF glutamine. These results suggest a model of blood-brain amino acid transport in which a high level of glutamine in brain extracellular fluid competes with other neutral amino acids for efflux from brain, thus raising brain amino acid levels after portal-systemic shunting.     

The analgesic efficacy of preoperative high dose (40 mg x kg(-1)) oral acetaminophen after bilateral myringotomy and tube insertion in children

BACKGROUND: The purpose of this study was to measure the plasma levels and analgesic effectiveness of a dose of 40 mg x kg(-1) of preoperative oral acetaminophen. METHODS: Thirty children aged 55 (17-72) months undergoing bilateral myringotomy and tube insertion (BMT) received acetaminophen 40 mg x kg(-1) p.o. preoperatively. Plasma levels were measured, at 29 (10-51) min and at 60 min in the postanaesthesia care unit (PACU). Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), for all subjects and the Poker Chip Tool (PCT) a self-report scale for subjects aged > 4 years, were used. After discharge, 24-h analgesic efficacy was evaluated using an observer Visual Analogue Scale (VAS) score and further acetaminophen use was recorded. RESULTS: Plasma concentrations were 259 (60-391) micromol x l(-1) and 250 (135-450) micromol x l(-1), respectively. All 60 min plasma concentrations were > or = 70 micromol x l(-1) (ED50 for adenotonsillectomy) and less than 800 micromol x l(-1) (associated with toxicity). Twenty-six subjects (87%) had adequate analgesia (CHEOPS < or = 8). The PCT was only understood in the PACU by 13 of the 21 children > 4 years (62%). The median worst 24-h observer VAS was 0.5 (0-5.5) (27 subjects). No further analgesic was required after discharge in 16/28 (57%). A higher plasma level was associated with fewer doses of acetaminophen after discharge (r = -0.36, P=0.05). CONCLUSIONS: No relationship was evident between age, the 60 min plasma acetaminophen level and the CHEOPS carried out at the same time. Acetaminophen 40 mg x g(-1) p.o. results in 60 min plasma levels of 250 (135-450) micromol x l(-1). The in-hospital analgesic efficacy was 87% (CHEOPS < 9, no further analgesics) and the 24-h efficacy was 57% (need for further acetaminophen).     

Amino acid and lipid profiles following pig‐to‐primate liver xenotransplantation

As outcomes in clinical liver transplantation steadily improve, demand continues to exceed supply, leading to a substantial disparity in organ availability. The translation of porcine liver xenotransplantation (LXT) into a clinical reality aims to address this dilemma. Our laboratory has previously established an applicable model of α‐1,3‐galactosyltransferase knockout (GalT‐KO) pig‐to‐primate LXT with continuous human coagulation factor infusion and costimulation blockade. This report aims to further investigate the post‐LXT lipid and amino acid metabolism profile in our longest surviving recipients (25 and 29 days). Experimental samples and control samples, consisting of pre‐transplant porcine and baboon serum and plasma, were analyzed for standard lipid profiles and for amino acid levels. Lipid profiles of LXT recipients remained stable following xenotransplantation compared to donor porcine baseline levels. Amino acid concentrations also remained similar to baseline controls, with the exception of a 3‐fold increase in l ‐ornithine and more than a 10‐fold decrease in l ‐arginine post‐transplant when compared to both porcine and baboon baseline levels. The observed changes in l ‐arginine are consistent with prior studies investigating the effects of graft preservation injury following liver transplantation. These results indicate that the porcine liver can maintain most biochemical profiles stably post‐operatively in baboons and suggest that arginine supplementation post‐LXT may potentially be useful for further prolongation of xenograft survival.     

Amino acid and carnitine supplementation in haemodialysed children

Plasma carnitine, amino acids and lipids levels were studied in ten uraemic children treated with haemodialysis and given amino acid supplementation with and without carnitine. As carnitine is synthesised from lysine and methionine and has a significant influence on lipid metabolism, the relationship between these was examined. Amino acid supplementation (0.25 g/kg body weight) was started with the intention of improving the plasma amino acid pattern in these children and increasing the concentration of lysine, which is the substrate for carnitine synthesis. Amino acids were administered i. v. during dialysis and carnitine (25 mg/kg body weight i. v.) was administered after dialysis three times a week. Concentrations of most essential amino acids were decreased in these patients. The first period of amino acid supplementation did not increase plasma levels of the essential amino acids, with the exception of tyrosine (P<0.01). After the second period of supplementation, methionine was increased (P<0.01), isoleucine was decreased (P<0.01), but tyrosine normalised and was significantly lower than after the first period (P<0.05). Thus overall amino acid supplementation did not improve amino acid levels; it was inconsistently associated with a further decrease in highdensity lipoprotein-cholesterol and an increase in total protein levels. Lysine concentrations after amino acid supplementation remained low. Paradoxically, before carnitine supplementation a positive correlation between free carnitine and triglycerides was observed. The plasma carnitine concentration, initially very low, was excessively high after carnitine supplementation. After carnitine administration no amelioration of any of the other biochemical indices was observed. Carnitine supplementation was associated with a significant reduction of total protein levels (P<0.01). In children with end-stage renal disease on haemodialysis, neither amino acid nor carnitine supplementation appear to result in significant improvements in plasma levels of essential amino acids or lipids.     

The effect of intravenous amino acids on plasma amino acid concentration during total parenteral nutrition in infants with necrotizing enterocolitis

Plasma aminograms of infants receiving total parenteral nutrition as part of the treatment for necrotizing enterocolitis were studied. Their ages varied from 2 to 60 days and their mean birth mass was 1 621 g (range 760-2 550 g). The intravenous administration of amino acids produced changes in plasma amino acid levels corresponding to the concentration of individual amino acid levels in the solution employed: higher levels of amino acids in the infusate produced increased plasma levels, whereas low plasma levels were obtained for amino acids not present or present in small amounts according to the solution used. The infants did not appear to suffer in any way, but the long-term effects still have to be evaluated. Pending further knowledge in this regard it is suggested that plasma amino acid levels should be maintained as near to normal values as possible. This could probably be achieved by the use of amino acid solutions specially formulated according to the amino acid profile of breast milk or the plasma amino acid profile of normal infants.     

Short-term enteral glutamine does not enhance protein accretion in burned children: a stable isotope study

OBJECTIVE: Glutamine is a nonessential amino acid that, in recent years, has been found to play important roles in several metabolic and immunologic processes. It has been theorized that, in a stressed state, it may become "conditionally essential" because the patient's ability to manufacture glutamine may not be adequate to meet their needs under this condition. We chose to evaluate the ability of 48 hours of enteral glutamine to enhance immediate nitrogen accretion in stressed pediatric burn patients. METHODS: Nine children with serious burns who were tolerating tube feedings were enrolled in a human studies committee-approved protocol in which they received 48 hours of enteral feedings with glutamine replacing 20% of essential and nonessential amino acids and 48 hours of isonitrogenous, isocaloric standard enteral feedings. This interval was chosen to help ensure that the study periods were comparable from a metabolic perspective. At the end of each period, protein kinetics were determined by a primed constant infusion of L-[1-(13)C] leucine tracer. The order of the studies was randomized. Seven children completed both phases of the study. Results were compared by paired t test and are presented as mean +/- standard error of the mean. RESULTS: During the glutamine feeding period, the leucine flux and leucine oxidation rate were significantly lower than those in the conventional feeding period. This reflects a reduction in total leucine intake from 80 +/- 11 to 62 +/- 10 micromol/kg per hour. However, there was no significant difference in the net balance of leucine accretion into proteins between these 2 dietary periods, which indicated that enriched glutamine feeding for 48 hours did not result in an immediate whole body protein gain in this group of pediatric patients. In addition, plasma glutamine concentration showed a moderate increase after 48 hours of supplementation but did not reach significance. CONCLUSION: Rapid protein accretion does not occur with short-term enteral glutamine supplementation. Several days of glutamine supplementation may be required to restore plasma glutamine levels and stimulate protein synthesis.