Reduced plasma levels of tyrosine,precursor of brain catecholamines,and of essential amino acids in patients with severe traumatic brain injury after rehabilitation

OBJECTIVE: To investigate whether levels of plasma tyrosine and tryptophan, precursors of brain catecholamine and serotonin neurotransmitters, respectively, and other essential amino acids (EAA) may return to normal in patients with severe traumatic brain injury (TBI) after 2 months in a hospital rehabilitation center. DESIGN: Peripheral plasma concentrations of tyrosine, tryptophan, and other EAAs in subjects with severe TBI, both at admission (44+/-11d postinjury) and at discharge from the center (110+/-15d after acute event) were compared with concentrations in control subjects. SETTING: Tertiary care rehabilitation setting in Italy. PARTICIPANTS: Ten men (26.6+/-12.6y) with TBI and 6 healthy subjects (controls) matched for age, sex, voluntary loss of body weight, and sedentary lifestyle. INTERVENTIONS: Not applicable. Main Outcome Measures: Concentrations of brain neurotransmitter precursor amino acids and of EAA. RESULTS: On admission, patients had lower plasma tyrosine, leucine, valine, methionine, and phenylalanine concentrations than did control subjects. The plasma concentrations of tryptophan were similar in the 2 groups. These amino acid abnormalities were still present at discharge. CONCLUSION: The levels of plasma tyrosine and many EAA in patients with TBI did not recover by discharge (110+/-15d) from rehabilitation. Plasma tryptophan concentrations were similar in patients and controls.     

Plasma amino acid concentrations during late rehabilitation in patients with traumatic brain injury

OBJECTIVES: To investigate whether the basal plasma amino acid concentrations in patients with traumatic brain injury (TBI) have returned to levels found in healthy controls at about 17 months postinjury and to determine the effect of intake of a mixture of essential amino acids (EAA) on plasma amino acid concentrations in TBI versus healthy controls. DESIGN: Peripheral venous amino acid concentrations in subjects with TBI were compared with concentrations in healthy controls both at rest and for 1 hour after intake of 7g of EAA. SETTING: Postacute brain injury rehabilitation center. PARTICIPANTS: Six men with TBI (age +/- standard deviation, 27+/-6y; months postinjury, 17+/-4) and 6 healthy men (age, 43+/-7y). INTERVENTION: Intake of a drink consisting of 7g of EAA. MAIN OUTCOME MEASURES: Individual and total plasma amino acid concentrations. RESULTS: Total amino acid concentration was about 12% lower in TBI versus controls (P=.022). Valine was reduced by 33% in the TBI group versus controls (P=.003), whereas the other EAA did not differ between groups. After intake of the EAA drink, plasma non-EAA increased to a significantly higher level in controls versus TBI subjects (P=.017). CONCLUSIONS: Plasma total amino acid concentration is still reduced 17 months postinjury in patients with TBI versus healthy controls, mainly because of a lower valine level. This may be of importance for both brain and muscle metabolic functions, and warrant further study. Further, ingested EAA are apparently not as readily converted to non-EAA in TBI patients as in healthy controls, suggesting that in recovery from TBI, certain non-EAA may become provisionally essential.     

Evaluation of a glycine-rich amino acid solution for parenteral nutrition in endotoxemic rats

OBJECTIVE: It has been shown recently that high amounts of glycine might have some pharmacologic effects (reduction of injury and mortality in endotoxemic rats), but its effects on the nutritional status and protein metabolism during injury are still unknown. The aim of this study was to compare the nutritional effects of a glycine-rich amino acid solution for parenteral nutrition (AFD) with a standard one (Vintene) (glycine, 15 vs. 9 g/L) in endotoxemic rats. DESIGN: Laboratory investigation. SETTING: University laboratory. SUBJECTS: Male Wistar rats (198 +/- 11 g). INTERVENTIONS: Rats were operated to receive total parenteral nutrition (250 kcal/kg/day, 2 g N/kg/day) with amino acids supplied by either AFD (n = 9) or Vintene (V, n = 6). One day after surgery, corresponding to day 0 of the experiment and to the first day of full-strength total parenteral nutrition, the AFD and V group rats received an endotoxemic shock by intraperitoneal injection of lipopolysaccharide (Escherichia coli, 8 mg/kg). The rats were then studied over 3 days and compared with a healthy ad libitum-fed group (AL, n = 10). MEASUREMENTS AND MAIN RESULTS: The rats were weighed and urine was collected daily to determine nitrogen balance and 3-methylhistidine excretion. On day 3, the thymus, spleen, liver, intestinal mucosa, and muscles were weighed, and amino acids from plasma and tissues were analyzed. Lipopolysaccharide caused the classic endotoxemic shock, of similar intensity in the V and AFD groups (V and AFD not equal AL, p < .05): no weight gain, decreased nitrogen balance (day 3, AL 558 +/- 21, V 83 +/- 28, AFD 123 +/- 25 mg N/day), increased urinary 3-methylhistidine/creatinine excretion (day 3, AL 51 +/- 2, V 91 +/- 13, AFD 87 +/- 14 mumol/mmol), soleus (V -15% and AFD -26 % vs. AL) and thymus atrophy (V -36% and AFD -33%), and spleen hypertrophy (V 51% and AFD 83%). Compared with V solution, AFD has a reduced content of some essential amino acids and proline and an elevated content of glycine, aspartate, and glutamate. These differences were not reflected in tissue or plasma amino acids, except for plasma glycine, which in the AFD group was restored to the level of the AL group (AL 426 +/- 12 and AFD 379 +/- 50 vs. V 251 +/- 31 mumol/L, p < .05). CONCLUSIONS: In endotoxemic rats, the nutritional effects of a glycine-rich AFD solution are similar to those of a standard amino acid solution for parenteral nutrition.     

Branched-chain amino acids enhance the cognitive recovery of patients with severe traumatic brain injury

OBJECTIVE: To investigate whether supplementation with branched-chain amino acids (BCAAs) in patients with severe traumatic brain injury (TBI) improves recovery of cognition and influences plasma concentrations of tyrosine and tryptophan, which are precursors of, respectively, catecholamine and serotonin neurotransmitters in the brain. DESIGN: Forty patients with TBI were randomly assigned to 15 days of intravenous BCAA supplementation (19.6g/d) (n=20) or an isonitrogenous placebo (n=20). SETTING: Tertiary care rehabilitation setting in Italy. PARTICIPANTS: Forty men (mean age, 32+/-15 y) with TBI and 20 healthy subjects (controls) matched for age, sex, and sedentary lifestyle. INTERVENTION: Supplementation with BCAAs. MAIN OUTCOME MEASURES: Disability Rating Scale (DRS) and plasma concentrations of BCAAs, tyrosine, and tryptophan. RESULTS: Fifteen days after admission to the rehabilitation department, the DRS score had improved significantly in both the placebo group (P<.05 vs baseline) and in the BCAA-supplemented group (P<.01 vs baseline). The difference between the 2 groups was significant (P<.004). Plasma tyrosine concentration improved in the group given BCAA supplementation, and tryptophan concentration increased in patients receiving placebo. CONCLUSIONS: Supplemental BCAAs enhance the retrieval of DRS without causing negative effects on tyrosine and tryptophan concentration.     

Carnitine deficiency and hyperammonemia in children receiving valproic acid with and without other anticonvulsant drugs

Plasma ammonia and total and free carnitine were measured in 84 children requiring anticonvulsant drugs: 32 patients (group A) on valproic acid alone, 28 children (group B) on polytherapy including valproic acid, and 24 patients (group C) on polytherapy without valproic acid. The other anticonvulsant drugs used in groups B and C were carbamazepine and phenobarbital. Plasma ammonia concentrations were elevated in both group A and B compared with controls. Group B patients showed significantly higher hyperammonemia than group A (59.9 +/- 16.3 micrograms/dl vs. 36.7 +/- 12.4 micrograms/dl; P < 0.05). Group C patients had plasma ammonia levels similar to those of controls (31.1 +/- 14.7 micrograms/dl vs. 29.7 +/- 12.1 micrograms/dl; NS). In both group A and group B patients, plasma ammonia levels were correlated with the valproic acid dosage (r = 0.32, P < 0.01) and with serum concentrations of valproic acid (r = 0.41, P < 0.001). Moreover, a significant correlation between plasma ammonia and duration of valproic acid therapy was found in the patients as a whole (r = 0.31, P < 0.01). Plasma total and free carnitine concentrations were significantly reduced in groups A and B (total carnitine 36.9 +/- 6.9 mumol/l vs. 32.9 +/- 9.7 mumol/l; free carnitine 28.9 +/- 5.1 mumol/l vs. 25.7 +/- 4.3 mumol/l, respectively) compared with group C patients who did not receive valproic acid and in whom values were similar to controls (total carnitine 46.1 +/- 9.0 mumol/l vs. 47.7 +/- 10.1 mumol/l; free carnitine 40.1 +/- 7.1 mumol/l vs. 42.9 +/- 8.0 mumol/l, respectively). Twenty-eight patients (18 of group A and 10 of group B) were re-evaluated and showed a complete normalization of plasma ammonia, and total and free carnitine levels which were similar to controls. Our data suggest that hyperammonemia is an important problem in patients receiving valproic acid, particularly in association with other anticonvulsant drugs. This increase of plasma ammonia and the concomitant reduction of carnitine seem to be transient and completely reversible.     

Experiences with L-carnitine in the post-stress phase

A prospective randomized double blind investigation was made in 24 multiple injured patients. All patients were treated with a combined parenteral-enteral nutrition during 7 days. A group of 11 patients received as a continuous infusion over 16 h 60 mg/kg BW carnitine daily. Beside carnitine and acetylcarnitine levels in plasma and urine the following parameters were determinated to evaluate the effect of carnitine: for the metabolism of fatty acids: triglycerides, free fatty acids (FFA), alpha-hydroxy-butyrate for the metabolism of carbohydrates: glucose, insulin and lactate in plasma. Finally for amino acid metabolism: urea, creatinine, cholinesterase and kolloid osmotic pressure in plasma as well as ureanitrogen and alpha-aminonitrogen excretion in urine. In the patients receiving carnitine especially acetyl-carnitine in plasma and acetyl-carnitine excretion in urine increased, proving that the administered carnitine can pass through the mitochondrial membrane. In these patients the plasma level of FFA was markedly lower than in the group without carnitine. Simultaneously the level of the alpha-hydroxybutyrate was elevated, equivalent to an increased oxydation of fatty acids. There was no difference between the two groups in the metabolism of carbohydrates. Administration of carnitine caused a slight increase of the production of urea (PU), catabolism could not be reduced. The excretion of alpha-aminonitrogen in urine augmented after carnitine infusion. Carnitine is an AA itself and so the amount of excreted alpha-amino nitrogen will increase; additionally the reabsorption of AA in the proximal renal tubulus may be inhibited by carnitine.     

Plasma an intraerythrocyte amino-acid levels during and after haemodialysis in acute renal failure

A study is carried out on the variations of plasma and blood red cells free amino acid concentrations secondary to haemodialysis in patients suffering from acute renal failure. A reduction in plasma free amino acid pool has been observed in patients undergoing to many periodic haemosialysis, but no significant differences occur in plasma aminogram between before and after a single dyalitic procedure. Significant alterations were also observed in blood red cells aminogram, and this may be interpreted as reflex of intracellular omeostatic mechanisms for the maintenance of normal plasma free amioacid pattern.     

High-dose amino acid infusion preserves diuresis and improves nitrogen balance in non-oliguric acute renal failure

INTRODUCTION: The effects of protein-enriched diets on glomerular filtration have been described in normal subjects and in patients with chronic renal failure. In acute renal failure, the effects of administration of high rates of protein on renal function and nitrogen balance have not been studied in critically ill patients. The present study examines the effects of large doses of amino acids on the glomerular filtration rate and nitrogen balance in critically ill patients with acute renal failure. METHODS: Fourteen critically ill patients with a creatinine clearance below 50 ml/min and conserved diuresis above 2,000 ml/day received 2000 non-protein kcal/day and either 75 g (Group 1) or 150 g (Group 2) of amino acids parenterally. Renal function tests, fluid balance, sodium and nitrogen balances, and furosemide administration were assessed on day 1 (baseline day when dextrose 5% was administered) and days 2, 3 and 4. RESULTS: The two groups were comparable in terms of severity indices, sex and creatinine clearance. Group 2 was significantly older (p < 0.05). Blood urea nitrogen increased significantly in Group 1 but not in Group 2; creatinine clearance remained unchanged in the two groups. Group 2 patients had a significantly more positive cumulative nitrogen balance (-10.5 +/- 17 g/day vs. 9 +/- 8.3 g/day) (p < 0.01), less positive fluid balance (2003 +/- 1336 ml vs. -2407 +/- 1990 ml) and lower furosemide requirement (1003 +/- 288 mg vs. 649 +/- 293 mg) (p < 0.05). CONCLUSION: A high amino acid regimen administered as a part of parenteral nutrition improves nitrogen balance, reduces furosemide requirements and ameliorates water balance in acute renal failure patients with conserved diuresis.     

缺血再灌注复合内毒素血症诱导多器官功能障碍综合征时氨基酸的变化及与肿瘤坏死因子的关系

目的：观察山羊缺血再灌注复合内毒素攻击诱发多器官功能障碍综合征（ＭＯＤＳ）时血浆游离氨基酸的代谢变化及其与肿瘤坏死因子（ＴＮＦ）变化的关系。方法：以北京地区雄性成年山羊为模型，经动脉导管快速放血，造成低血容量性休克后再复苏，复苏后２４小时经门静脉持续输入内毒素诱发ＭＯＤＳ。结果：致伤后第５日支链氨基酸与芳香氨基酸比值（ＢＣＡＡ／ＡＡＡ）显著降低，伤后第３日起尿氮排出增加，第５日增加更加显著（Ｐ＜０．０５）；尿三甲基组氨酸（３Ｍｅｈｉｓ）在伤后３日和５日排出显著升高；血ＢＣＡＡ／ＡＡＡ、苯丙氨酸／酪氨酸（Ｐｈｅ／Ｔｙｒ）和尿３Ｍｅｈｉｓ的变化与ＴＮＦ变化高度相关；Ｐｈｅ／Ｔｙｒ与丙氨酸转氨酶（ＡＬＴ）变化呈正相关。结论：山羊在失血后再灌注及内毒素的双重作用下，ＴＮＦ可能介导了骨骼肌蛋白质分解代谢增强，导致氨基酸代谢紊乱和肝功能受损     

Increased hepatic amino nitrogen conversion after elective cholecystectomy in man

1. The effect of elective, uncomplicated cholecystectomy on plasma clearances of amino acids and on amino acid-stimulated urea synthesis was investigated in 10 patients, pre-operatively and on the first post-operative day, and compared with six controls treated identically apart from the surgery. 2. A mixture of amino acids was given as a prime-continuous infusion. Steady-state concentrations 75% higher than basal were attained and were maintained for 90 min. The clearances of amino acids were calculated as the ratios between amino acid infusion rate and the concentration. The urea synthesis rate was calculated as urinary excretion corrected for accumulation and intestinal loss. 3. After surgery the fasting plasma concentrations of alanine, arginine, glutamine plus glutamate, glycine, proline, lysine and threonine decreased by 20-30%, but were unchanged in the control group. The plasma clearance of alpha-amino nitrogen increased from 5.1 +/- 1.2 ml/s before surgery (mean +/- SD) to 6.1 +/- 1.1 ml/s (P less than 0.05, paired t-test) after surgery due to increased clearances of the above-mentioned amino acids. In the control group, the clearance decreased from 6.4 +/- 1.6 to 5.9 +/- 1.1 (P less than 0.05, paired t-test). The amino acid-stimulated urea synthesis rate after surgery was 37 +/- 9 mumol of N/s vs 30 +/- 6 (P less than 0.01, paired t-test) in the controls despite a lower alpha-amino nitrogen concentration (4.5 +/- 0.5 mmol/l vs 5.1 +/- 0.5 mmol/l, P less than 0.05, paired t-test). The post-operative urea synthesis rate exceeded the amino nitrogen infusion by 20%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Beta-thalassemia major and its effect on amino acid metabolism and growth in patients in the United Arab Emirates

BACKGROUND: There may be a marked reduction in essential amino acids in the serum of children with thalassemia major and this is related to decreased growth in affected children. METHODS: One hundred patients with beta-thalassemia and 50 control children selected from among those who had presented with minor disorders unrelated to hematological disease were recruited. Urine and heparinized blood were collected from fasting thalassemic patients. After deproteinization and dilution, amino acid concentrations were measured using ion-exchange chromatography. RESULTS: Isoleucine (p<0.0001), phenylalanine (p<0.05), tyrosine (p<0.0001), taurine (p<0.0001) and glutamine (p<0.01) were significantly decreased in the plasma of thalassemic patients compared to the control group. Whereas glutamate (p<0.0001), serine (p<0.05) and proline (p<0.05) were significantly higher in thalassemic patients, threonine, glycine, alanine, valine, methionine, leucine, ornithine, lysine, histidine and arginine values were not different. The essential amino acids taurine (p<0.0001), methionine (p<0.01), valine (p<0.01), phenylalanine (p<0.01) and leucine (p<0.05) were significantly decreased in urine of thalassemic patients vs. controls, but threonine and ornithine were not different. The mean urinary excretion rate of beta-aminoisobutyric acid was not different (69+/-96 in thalassemics vs. 41+/-52 in controls). However, most plasma and urinary essential amino acids were found to be lower in thalassemics. Thalassemic patients were also found to be significantly growth impaired for age, both in height and weight compared to controls. CONCLUSION: Lower plasma values of essential amino acids and a decrease in urinary amino acids occur in thalassemic patients. Growth impairment both in height and weight also occurs in thalassemic patients compared to a control population.     

Plasma precursors of brain catecholaminergic and serotonergic neurotransmitters in rehabilitation patients with ischemic stroke

Aquilani R, Verri M, Iadarola P, Arcidiaco P, Boschi F, Dossena M, Sessarego P, Scocchi M, Arrigoni N, Pastoris O. Plasma precursors of brain catecholaminergic and serotonergic neurotransmitters in rehabilitation patients with ischemic stroke. Arch Phys Med Rehabil 2004;85:779-84.

Objective

To determine levels of plasma amino acid tyrosine and tryptophan, precursors of brain catecholamine and serotonin neurotransmitters, respectively, in rehabilitative patients with ischemic stroke.

Design

Controlled, pre-post analysis, consecutive sample.

Setting

Rehabilitation center.

Participants

Twenty men with ischemic stroke (age, 68±11.3y) consecutively admitted into rehabilitation 15±10 days (range, 7-28d) after an acute cerebrovascular insult; 15 healthy sedentary subjects (controls 1); and 13 healthy hypoactive individuals who had recently had knee arthroplasty (controls 2). Both control groups were matched to stroke subjects for age, gender, and body weight.

Interventions

At 8:00 am, after overnight fasting, venous blood samples were drawn from patients to determine plasma tyrosine and tryptophan levels. A nutritional evaluation, including nitrogen balance, was made. The same procedures were repeated after 45 days of rehabilitation. Amino acid data were compared with those obtained from the controls.

Main outcome measure

Plasma concentrations of amino acids.

Results

Patients with ischemic stroke, on admission, had lower plasma tyrosine concentration than did both controls 1 (P<.0005) and controls 2 (P<.001), but a similar tryptophan level. The plasma content of tyrosine was similar between the 2 control groups. After 45 days of rehabilitation, the stroke patients’ tyrosine and tryptophan levels remained virtually unchanged, as did nutritional parameters. Nutritional intakes were adequate to meet body needs but insufficient to correct plasma tyrosine.

Conclusions

Patients experiencing a recent stroke may have low plasma tyrosine levels and, therefore, reduced brain catecholamine formation. It is possible that an imbalance of brain neurotransmitters may occur.     

Motor performance in physically well-recovered men with traumatic brain injury.

OBJECTIVE: The primary aim of this study was to compare the motor performance of physically well-recovered men with traumatic brain injury with that of healthy men. DESIGN: Cross-sectional study in a national rehabilitation centre. METHODS: Static and dynamic balance, agility and rhythm co-ordination of men with traumatic brain injury (n=34) and healthy controls (n=36) were assessed. Between-group differences in dynamic balance and agility were analysed by analysis of covariance and differences in static balance and rhythm co-ordination by logistic regression analysis. Cut-off points for clinical screening were determined by receiver operating characteristics analyses. RESULTS: Men with traumatic brain injury had impaired balance and agility compared with healthy men and in a rhythm co-ordination test they had difficulties in starting and sustaining simultaneous rhythmical movements of hands and feet. In receiver operating characteristics analyses a running figure-of-eight test (agility), tandem walking forwards (dynamic balance) and rhythm co-ordination test with fast tempo were found the most sensitive and specific for distinguishing between men with traumatic brain injury and the healthy men. CONCLUSIONS: The impairments in motor performance of physically well-recovered patients with traumatic brain injury were obvious. The results of this study extend the knowledge of problems in motor performance among patients with traumatic brain injury and provide further information for clinical rehabilitation.     

脑外伤患者血清兴奋性氨基酸水平与功能性恢复的分析

目的 探讨脑外伤患血清氨基酸水平与功能恢复的相关性。方法 采用高效液相色谱法（ＨＰＬＣ）检测了３０例脑外伤患外伤后２４ｈ内和６ｄ后的血甭中谷氨酸（ＧＬＵ）的水平,并在２４ｈ内采用格拉斯歌昏迷量表计分（ＧＣＳ０及２０ｄ后功能独立性９ＦＩＭ）的评定值进行相关性研究。结果 显示血清ＧＬＵ（２４ｈ）的水平和ＧＣＳ、ＦＩＭ得分呈良好的负相关,将２４ｙ测量的血清ＧＬＵ浓度与６ｄ血清ＧＬＵ浓度值比较,分为持     

Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome.

Plasma and urine free and acyl carnitine were measured in 19 children with nephropathic cystinosis and renal Fanconi syndrome. Each patient exhibited a deficiency of plasma free carnitine (mean 11.7 +/- 4.0 [SD] nmol/ml) compared with normal control values (42.0 +/- 9.0 nmol/ml) (P less than 0.001). Mean plasma acyl carnitine in the cystinotic subjects was normal. Four subjects with Fanconi syndrome but not cystinosis displayed the same abnormal pattern of plasma carnitine levels; controls with acidosis or a lysosomal storage disorder (Fabry disease), but not Fanconi syndrome, had entirely normal plasma carnitine levels. Two postrenal transplant subjects with cystinosis but without Fanconi syndrome also had normal plasma carnitine levels. Absolute amounts of urinary free carnitine were elevated in cystinotic individuals with Fanconi syndrome. In all 21 subjects with several different etiologies for the Fanconi syndrome, the mean fractional excretion of free carnitine (33%) as well as acyl carnitine (26%) greatly exceeded normal values (3 and 5%, respectively). Total free carnitine excretion in Fanconi syndrome patients correlated with total amino acid excretion (r = 0.76). Two cystinotic patients fasted for 24 h and one idiopathic Fanconi syndrome patient fasted for 5 h showed normal increases in plasma beta-hydroxybutyrate and acetoacetate, which suggested that hepatic fatty acid oxidation was intact despite very low plasma free carnitine levels. Muscle biopsies from two cystinotic subjects with Fanconi syndrome and plasma carnitine deficiency had 8.5 and 13.1 nmol free carnitine per milligram of noncollagen protein, respectively (normal controls, 22.3 and 17.1); total carnitines were 11.8 and 13.3 nmol/mg noncollagen protein (controls 33.5, 20.0). One biopsy revealed a mild increase in lipid droplets. The other showed mild myopathic features with variation in muscle fiber size, small vacuoles, and an increase in lipid droplets. In renal Fanconi syndrome, failure to reabsorb free and acyl carnitine results in a secondary plasma and muscle free carnitine deficiency.     

Amino acid losses and nitrogen balance during slow diurnal hemodialysis in critically ill patients with renal failure

Objective: The effects of slow diurnal hemodialysis (slow HD) on amino acid losses and nitrogen balance were studied. Design: Slow HD was conducted for 10 h during the day at the dialysate flow rate of 30 ml/min. The patients received total parenteral nutrition including 40 g of amino acids (6.08 g of nitrogen). The amino acid concentrations in plasma and dialysate were determined and the daily nitrogen balance was calculated from the urea nitrogen appearance. Patients: Six critically ill patients with renal failure were entered into the study. Results: Slow HD eliminated 48.5±4.4 mmol (6.2±0.6 g) of amino acids, representing 16% of the daily amino acid load. The estimated nitrogen balance was –2.3±1.3 g/day. Amino acid nitrogen lost in the dialysate was 1.0±0.1 g, contributing 43% of the daily negative nitrogen balance. Conclusion: The amount of amino acid losses during slow HD should be taken into consideration when designing nutritional schedules for maintaining positive nitrogen balance in critically ill patients. Received: 27 December 1995 Accepted: 3 September 1996     

TEN AMINO ACIDS ESSENTIAL FOR PLASMA PROTEIN PRODUCTION EFFECTIVE ORALLY OR INTRAVENOUSLY

When blood plasma proteins are depleted by bleeding with return of the washed red cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet protein intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. When the protein intake of such dogs is completely replaced by the growth mixture (Rose) of crystalline amino acids, plasma protein production is excellent, weight and nitrogen balance are maintained. This growth mixture consists of ten amino acids, threonine, valine, leucine, isoleucine, tryptophane, lysine, phenylalanine, methionine, histidine, arginine, and is as effective as most diet proteins in plasma protein production. The above amino acid mixture in aqueous solution may be given by vein with equally good plasma protein production and no apparent clinical disturbance even when given rapidly. Cystine may replace methionine in the above mixture with equally good plasma protein production for 7 to 10 days but at the expense of the body tissues, that is, with weight loss and a negative nitrogen balance. The addition of cystine to the protein-free, otherwise adequate diet may result in the production of considerable new plasma protein during a period as long as 1 week (cystine effect). This reaction may depend upon the amino acid constitution of the preceding diet protein in that it occurred following a liver feeding but did not occur after pancreas feeding. Arginine is required in the diet of the protein depleted dog for fabrication of plasma protein. It is apparently not needed for nitrogen balance for as long as 1 or 2 weeks. The omission of either threonine or valine from the growth mixture is quickly followed by a sharp decline in plasma protein formation and by a negative nitrogen balance. When histidine, arginine, and most of the lysine are omitted from the growth mixture, nitrogen balance and weight may be maintained for as long as 1 week but plasma protein production falls off markedly. The findings indicate that the growth mixture of amino acids should be a valuable addition to transfusion and infusion therapy in disease states associated with deficient nitrogen intake or tissue injury and accelerated nitrogen loss, including shock, burns, and major operative procedures.     

Recovery of ambulation after traumatic brain injury

OBJECTIVES: To identify variables that are predictive of independent ambulation after traumatic brain injury (TBI) and to define the time course of recovery. DESIGN: Retrospective review of consecutive admissions of patients with severe TBI over a 32-month period. SETTING: Brain injury unit in an acute, inpatient rehabilitation hospital. PARTICIPANTS: Of 264 patients screened, 116 met criteria that included the ability to participate in motor and functional evaluation on admission to acute rehabilitation, and the absence of other neurologic disorders or fractures that affect one's ability to ambulate. INTERVENTION: Inpatient rehabilitation on a specialized TBI unit by an interdisciplinary team.Main outcome measures Recovery of independent ambulation and time to recover independent ambulation. RESULTS: Of eligible patients, 73.3% achieved independent ambulation by latest follow-up (up to 5.1 mo). Patients who achieved independent ambulation were significantly younger (P<.05), had better gait scores on admission (P<.05), and tended to be less severely injured-based on duration of posttraumatic amnesia (PTA; P=.058)-than those who did not ambulate independently. There were no differences in recovery based on neuropathologic profile. Mean time to independent ambulation +/- standard deviation was 5.7+/-4.3 weeks; of those achieving independent ambulation, 82.4% did so by 2 months and 94.1% by 3 months. If not independent by 3 months postinjury, patients had a 13.9% chance of recovery. Multivariate regression analysis generated prediction models for time to independent ambulation, using admission FIM instrument scores and age (38% of variance); initial gait score, loss of consciousness, and age (40% of variance); or initial gait score and PTA (58% of variance), when restricted to just those patients with diffuse axonal injury. CONCLUSIONS: Most patients with severe TBI achieved independent ambulation; the vast majority did so within 3 months postinjury. Functional measures, injury severity measures, and age can help guide prognosis and expectations for time to recover.     

Total parenteral nutrition enriched with arginine and glutamate generates glutamine and limits protein catabolism in surgical patients hospitalized in intensive care units

OBJECTIVES: To study the effect of a parenteral nutrition solution enriched with potential precursors of glutamine, i.e., arginine and glutamate, on plasma glutamine concentrations and protein metabolism. DESIGN: Prospective, randomized, single-blind, comparative study. SETTING: Two intensive care units in two different hospitals. PATIENTS: Fifteen surgical patients. INTERVENTIONS: Patients were randomized to receive total parenteral nutrition for 5 days with the enriched glutamine precursor solution (GlnP+ group) or a conventional solution (control group), both total parenteral nutrition providing 0.25 gN/kg per day and 35 kcal/kg per day (glucose/lipids, 70%:30%). MEASUREMENTS AND MAIN RESULTS: Plasma amino acid concentrations before (T0) and after 3 hrs (T3) of perfusion, nitrogen balance (daily and cumulated), and urinary excretion of 3-methylhistidine were measured daily from day 1 to day 5. The two groups were identical for age, weight, severity score, and nitrogen and energy intakes. After a 3-hr perfusion, plasma concentrations of arginine, ornithine, and glutamine increased, and the differences (T3 - T0) were significantly higher in the GlnP+ group: arginine, 107.6+/-7.0 vs. 51.9+/-3.3 (mean over 5 days; p < .001); ornithine, 78.9+/-7.1 vs. 43.6+/-3.1 (p < .001); and glutamine, 32.4+/-8.6 vs. 6.7+/-5.0 micromol/L (p < .05), respectively. A positive correlation was found between arginine and glutamine plasma increases only in the GlnP+ group: r = .45; p < .01 (Spearman's rank-correlation test). Daily and cumulated nitrogen balances were not significantly different between the two groups but were positive (difference from 0) only in the GlnP+ group. The urinary 3-methylhistidine/creatinine ratio decreased significantly from day 1 to day 5 only in the GlnP+ group: 24.5+/-2.7 vs. 18.8+/-2.7 micromol/mmol (p < .05). CONCLUSIONS: Total parenteral nutrition enriched with arginine and glutamate promotes a better nitrogen balance, limits protein myofibrillar catabolism, and generates glutamine, with arginine (not glutamate) probably being the main contributor to the glutamine-generating effect of the solution through the formation of ornithine.     

脑外伤患者血浆一氧化氮合酶与T淋巴细胞亚群的变化

目的 :通过检测急性脑损伤患者血浆一氧化氮合酶 (NOS)与 T淋巴细胞亚群 (CD 4 /CD 8)含量变化 ,探讨其临床意义。方法 :采用酶法检测 NOS,应用单克隆抗体 APAAP法检测 45例脑损伤患者的 T淋巴细胞亚群。结果 :脑损伤患者血浆中 NOS与 CD 8细胞含量均较对照组升高 ,中、重型组差异有显著性 (P<0 .0 5或 P<0 .0 1) ;而脑损伤患者的 CD 4 较对照组下降 ,中、重型组差异有显著性 (P<0 .0 5或 P<0 .0 1)。 NOS与CD 8间呈正相关关系 (r=0 .36 7,P<0 .0 1)。CD 4 /CD 8比值与对照组比较差异均显著 (P均 <0 .0 1)。结论 :血浆中 NOS、CD 8升高水平与脑损伤程度有关 ,临床检测 NOS与 T淋巴细胞亚群的含量有助于评价脑损伤患者的病情及预后