早期全肠外营养及肠内、外混合营养对神经外科危重患者免疫功能的影响

目的探讨早期给予全肠外营养（TPN）及肠内营养（EN）、肠外营养（PN）混合支持对神经外科危重患者免疫功能的影响。方法采用前瞻性对照研究将神经外科危重患者按入院顺序随机分为TPN组及EN＋PN组,并对比营养支持前后两组CD3、CD4、CD8、CD4／CD8、CD3／CD25、IgA、IgG、IgM、血清白蛋白的变化。结果给予神经外科危重患者两种营养支持均可提高其CD3、CD4、CD8及CD3＋／CD25＋比值（P〈0．05,P〈0．01）;两种营养支持方式均可显著升高IgA、IgG、IgM、（P〈0．05）及血清白蛋白浓度（P〈0．01）。与TPN组比较,EN＋PN组CD3、CD4、CD8、CD4／CD8比值、IgA、IgG、IgM浓度及血清白蛋白水平均显著升高（P〈0．05,P〈0．01）。结论早期TPN及EN＋PN支持均可促进神经外科危重患者免疫功能的恢复及提高,EN＋PN的作用优于TPN,对于神经外科危重患者应早期给予营养支持治疗。     

Lymphocyte and granulocyte function in nutritionally depleted patients. The effect of 2 weeks of total parenteral nutrition

Parenteral nutrition has been reported to restore impaired immune function in nutritionally depleted patients. Lymphocyte and granulocyte function were studied before and after 2 weeks of total parenteral nutrition (TPN) in 9 depleted patients, 5 with gastrointestinal cancer and 4 with benign gastrointestinal disorders. The ability of purified blood lymphocytes to incorporate (14)C-labelled thymidine spontaneously and following mitogenic and antigenic stimulation was studied. Before TPN spontaneous lymphocyte activity was significantly increased and mitogen and antigen responsiveness significantly decreased in comparison to healthy controls. These abnormalities were more pronounced in patients with malignant disorders while the remaining patients showed a moderate impairment. No improvement in lymphocyte capacity was observed following 2 weeks of TPN. Granulocyte function measured as chemotaxis, phagocytosis, NBT-reduction and bactericidal capacity did not differ significantly between patients and controls and no changes were seen following nutritional treatment. These findings support the concept that the underlying disease and/or other factors rather than the secondary nutritional depletion are the main reasons for immune impairment. Furthermore, no immunomodulating effects of lipid emulsions on lymphocyte and granulocyte function, under these experimental conditions, were apparent.     

胃肠癌术后肠外营养支持加精氨酸强化对机体免疫功能的影响

目的：观察胃肠癌术后肠外营养支持加精氨酸强化对机体免疫功能的影响。方法：选择胃肠癌行根治术后病人40例，随机分为试验组和对照组。试验组采用精氨酸强化肠外营养支持，对照组应用常规的肠外营养支持。分别在术前、术后第1天及第8天检测IgG、IgA、IgM、T细胞亚群、NK细胞活性和IL－2的改变。结果：胃肠癌病人术前均有不同程度的免疫功能低下，术后第1天IgG,IgA,IgM,CD4^ ,CD4^ ,CD4^ /CD8^ ，NK细胞活性IL－2均较术前显著下降，术后第8天试验组上述指标迅速恢复，并超过术前水平，与对照组相比差异显著（P＜0．01）。结论：精氨酸强化肠外营养对胃肠癌病人后免疫功能具有明显的增强作用。     

Intestinal immune function is unaffected by parenteral nutrition in man.

Animal studies have demonstrated intestinal immunoglobulin production is decreased when luminal nutrition is withheld and nutrition is provided solely on the basis of total parenteral nutrition (TPN).

Eight normal volunteers were hospitalized in the Clinical Research Center for three weeks. The subjects received TPN as an exclusive means of nutritional support for 14 days followed by 5 days of enteral feeding with either standard or a glutamine- and arginine-supplemented formula in which the protein source was primarily free amino acids and peptides. Endoscopic jejunal biopsies obtained before and after TPN and following enteral refeeding were evaluated by immunofluorescence for the number of IgA, IgM and IgG-producing cells; T and B cells as well as intraepithelial and lamina propria lymphocytes were also counted. Serum immunoglobulins and the molecular forms of serum IgA were determined at the same intervals.

The number of intestinal IgA-, IgM- and IgG-producing cells was unaffected by TPN (676 +/? 58 vs. 643 +/? 38, 101 +/? 14 vs. 98 +/? 18, 10 +/? 1 vs. 11 +/? 2 per low power field). The total number of intestinal lymphocytes, and CD3+ lymphocytes in the intraepithelial area was unaffected by TPN (10.4 +/? 0.4 vs. 10.2 +/? 1.3, 7.3 +/? 0.8 vs. 8.6 +/? 1.6 per 100 epithelial cells). Similarly, the total number of lymphocytes and CD3+ lymphocytes in the intestinal lamina propria was unaffected by TPN (4.4 +/? 0.2 vs. 6.2 +/? 0.8, 3.3 +/? 0.7 vs. 4.5 +/? 0.8). A small, but statistically significant increase in serum IgA and IgM was seen with TPN 314 +/? 11 vs. 342 +/? 16 mg/dL and 154 +/? 25 vs. 226 +/? 47 mg/dL, although IgG remained unchanged (1262 +/? 69 vs. 1207 +/? 57 mg/dL). The proportion of polymeric and monomeric serum IgA remained unchanged after TPN (19.2 vs. 22.1% polymeric).

The use of TPN is not associated with intestinal immune dysfunction in man. A small, but statistically significant increase in serum IgM, and a borderline statistically significant increase in serum IgM were associated with TPN. The etiology and clinical significance of these observations is unclear.     

Effects of artificial nutrition on the nutritional status of cancer patients

The paper critically analyzes available data on the nutritional and metabolic effects of total parenteral nutrition (TPN) and enteral nutrition (EN) in cachectic cancer patients. Only papers dealing with adult cancer patients and providing data regarding type of tumor, duration of the nutritional support, and administration rate of calories and amino acids, validated by statistical analysis of the results, are included. The main conclusions are the following: (1) No nutritional variable worsened in cancer patients receiving TPN or EN, in conditions in which progressive deterioration of the nutritional status is the rule. (2) The nutritional variables improved by TPN and EN were body weight, fat mass, and some indicators of lean body mass (nitrogen balance and whole body potassium). Thyroxin-binding prealbumin and retinol-binding protein increased only with TPN, whereas some immunologic indexes (complement factors and lymphocytes) improved only with EN. (3) The daily regimens which improved lean body mass and visceral proteins ranged from 35 to 55 kcal/kg and from 1.2 to 2.0 g of amino acids/kg for TPN; for EN it was 35 kcal/kg and 1.3 g of amino acids/kg. However, the enteral regimen capable of improving some immune responses included at least 42 kcal/kg and 2.3 g of amino acids/kg. (4) Only three randomized studies were performed to compare TPN and EN, and conflicting results were obtained. Only TPN showed some significant advantages with regard to weight gain, nitrogen balance, maintenance of serum albumin levels and some mineral balances. However, the advantage of TPN was not clear enough to recommend its indiscriminate use. The choice between TPN and EN should always consider the functionality of the GI tract, the need for hospitalization to start a TPN regimen, and the higher cost of intravenous feeding. (5) When comparing TPN to a standard oral diet, the following variables improved with the nutritional support: body weight, nitrogen balance, 3-methylhistidine, urinary excretion, and serum levels of transferrin, cholinesterase, thyroxin-binding prealbumin, and retinol-binding protein. (6) When comparing TPN with glucose vs TPN with glucose-lipids, no major difference was found with regard to most nutritional variables. In conclusion, nutritional support alone probably has a small role in managing a limited number of advanced cancer patients dying primarily because of malnutrition or mainly suffering from nutritional deterioration. It can also have a "permissive" role in those patients potentially candidate to an oncologic treatment which cannot be delivered because of a poor nutritional status.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of medium-chain and long-chain triacylglycerols in pediatric surgical patients

Medium-chain triacylglycerols (MCTs) have been shown to provide better nutritional support than long-chain triacylglycerols (LCTs). This study compares the efficacy of MCT combined with LCT with LCT alone in pediatric patients with surgical stress. Two groups of patients (n = 19 in each) received equivalent amounts of glucose (12 g. kg. d) and amino acids (2 g. kg. d), but one group received 10% Lipofundin MCT/LCT and the other received 10% LCT (1.5 g. kg. d) in a randomized study. Total parenteral nutrition (TPN) was given for 14 d. Blood and urine samples were collected before and after TPN administration for determination of various biochemical parameters. Indirect calorimetry was also performed to determine respiratory quotients and fuel utilization. After 14 d of TPN in the MCT/LCT group, there was a significantly higher blood lymphocyte percentage, a decreasing tendency of serum asparate aminotransferase and of total and direct bilirubin (P < 0.05). These changes were not observed in the LCT group. A significantly better nitrogen balance and a higher ketogenesis from day 3 were observed in the MCT/LCT group. The MCT/LCT group showed a more marked increased utilization of fat than the LCT group, whereas carbohydrate oxidation was less in the MCT/LCT group than in the LCT group (P < 0.05). In children after surgery, MCT/LCT is more protein sparing and induces a better immune response when compared with LCT-containing lipid emulsion. A TPN regimen containing MCT/LCT is likely to result in rapid oxidation of fats for energy without compromising the respiratory system.     

Nutrition in patients undergoing orthotopic liver transplant

Thirteen patients with severe liver disease had nutritional assessment in the weeks prior to orthotopic liver transplantation. Parameters measured included height and weight, upper arm anthropometry, delayed cutaneous hypersensitivity, total lymphocyte count, serum levels of albumin and transferrin, and plasma amino acids. Weight, when expressed as a percentage of ideal body weight, was greater than 85%, considered the normal lower limit, in all but two patients. However, mean triceps skinfold and arm muscle circumference were 49 +/- 25 and 78 +/- 9% standard, respectively. Mean serum albumin was 2.7 +/- 0.6 g/dl and although mean serum transferrin level was 184 +/- 86, eight patients had levels less than normal. Seven patients were anergic to Multitest CMI (58%) and 12 patients had depressed total lymphocyte count. All these later measurements in the aggregate support a diagnosis of protein-calorie malnutrition. High preoperative levels of amino acids, especially aspartate, phenylalanine, tyrosine, and methionine, were returned to normal by transplantation. We conclude that protein-calorie malnutrition is common in the group of patients likely to require liver transplant, although individual nutritional assessment parameters may lack sensitivity and specificity in determining nutritional status.     

Intralipid-based short-term total parenteral nutrition does not impair small intestinal mucosa-related cellular immune reactivity in the healthy rat

BACKGROUND: The lipid component of total parenteral nutrition (TPN) has reportedly been associated with trophic effects on the intestinal mucosa and suppressive effects on the immune system. METHODS: We have challenged these hypotheses using a 7-day TPN rodent model comparing the effects of isocaloric, isonitrogenous lipid-based (TPN-lipid, 50% of calories as long-chain triacylglycerol) and carbohydrate-based TPN (TPN-CH, 100% of calories as carbohydrates) on mucosal morphology and immune function. Enterally fed animals were included to establish a baseline for immunologic read-outs. The study was performed in healthy, metabolically stable animals to avoid interference by septic or trauma-related stress factors. RESULTS: Both TPN regimens resulted in a significantly smaller weight gain (TPN-lipid, 29.8 +/- 4.0 g; TPN-CH, 30.3 +/- 4.4 g) compared with enterally fed reference animals (49.2 +/- 3.2 g; p = .007), with no difference in nitrogen balance between the TPN groups. Mucosal sucrase activity was significantly lower in both TPN groups (TPN-lipid, 8.8 +/- 1.0 x 10(-7) katal per gram (kat/g) of protein; CH: 11.9 +/- 1.6 x 10(-7) kat/g of protein) compared with enteral feeding (17.4 +/- 0.9 x 10(-7) kat/g of protein; ANOVA: p = .0007). Morphometric analysis of the small intestine revealed no differences between the two TPN groups although a significantly depressed villus height in the TPN-lipid group could be observed in comparison to enterally fed reference rats (TPN-lipid, 0.47 +/- 0.02; TPN-CH, 0.50 +/- 0.01; enteral, 0.56 +/- 0.02 mm; ANOVA: p = .0298). Light and electron microscopy revealed a normal surface architecture in all three groups of rats. Cellular immune reactivity was evaluated using a novel specific immunization protocol: animals were immunized against OVA 4 weeks before TPN. OVA-induced lymphoproliferative responses and phenotypic data from draining popliteal and mesenteric lymph nodes were evaluated after the different regimens. Results did not differ among the three groups. CONCLUSIONS: In healthy rodents, short-term lipid-based and carbohydrate-based TPN regimens lead to limited mucosal atrophy with preserved surface architecture compared with enteral feeding. However, peripheral and mesenteric cellular immune responsiveness after both TPN regimens remained comparable to enterally fed reference animals. Therefore, mesenteric and systemic cellular immune reactivity does not appear to be impaired by lipid-based or carbohydrate-based TPN.     

Effect of different types of total parenteral nutrition on T-lymphocyte subpopulations and NK cells

Long-chain triglycerides (LCTs) contained in total parenteral nutrition (TPN) regimens provide a considerable energy substrate in malnourished patients. Their effect on the immune system is controversial, however. In this randomized, prospective study we investigated the possible differences between the effect of TPN with LCTs or medium-chain triglycerides (MCTs) on T-lymphocyte subpopulations. Our study included 15 normal subjects, 20 patients receiving glucose-based TPN, and 40 patients receiving glucose-fat-based TPN. In the last group 20 patients received TPN that included LCTs and 20 received 50% MCTs and 50% LCTs. T-lymphocyte subpopulations, including total T cells and T-helper, T-suppressor, and NK cells, as well as the ratio of helper to suppressor T cells were determined before and 10 d after initiation of TPN. We found a significant decrease in the ratio of helper to suppressor T cells in the LCT group although no such difference was detected in the MCT-LCT group. No difference whatever was found in total T cells and helper, suppressor, and NK cells.     

Effects of surgery and nutritional support on some lymphocyte and PMN leucocyte functions in man

The purpose of the present study was to evaluate the effect on some leucocyte functions of 1) an elective surgical procedure; 2) nutritional repletion provided by parenteral alimentation (TPN). The rates of cellular proliferation and protein synthesis in lymphocyte cultures were measured by the incorporation of respectively 3H-thymidine and 3H-leucine; both measures were performed without and with additions of mitogenic agents. Random migration and chemotaxis of PMN leucocytes were measured under agarose. In 10 well-nourished patients, both lymphocyte proliferation and protein synthesis in stimulated cultures decreased after elective surgery, respectively by 50% (p < 0.01) and by 32% (p < 0.05) while random migration of PMN leucocytes was increased by 50% (p < 0.02). Stimulated lymphocyte proliferation and protein synthesis measured in 10 nutritionally depleted non-cancer patients prior to TPN were lower in comparison to the values obtained in a control population (respectively p < 0.006 and p < 0.04). These parameters rose progressively during TPN and reached the normal range after 3 weeks. Before TPN, PMN leucocyte random migration was slower in depleted patients than in control subjects; this parameter reached normal values after one week of TPN, while chemotaxis tended to decrease. Both parameters were in the normal range after 3 weeks of TPN. Conclusions 1) an elective operation depresses lymphocyte functions but stimulates PMN leucocyte random migration in well-nourished patients; 2) in depleted patients, previously depressed leucocyte responses are restored within 3 weeks of adequate nutritional support.     

Inducer and suppressor T cell subsets in protein-energy malnutrition: Analysis by monoclonal antibodies

Malnutrition results in impaired cell-mediated immune responses. We have examined various subsets of T lymphocytes reactive with monoclonal antibodies against cell-surface antigens using flourescein-triggered cell sorting technique. There was a reduction in the absolute number of T lymphocytes reactive with anti-T3. Both inducer cells identified by anti-T4 and suppressor cells identified by anti-T8 were decreased in number, particularly the former. The inducer/suppressor ratio was low. These alterations in lymphocyte subset numbers were reversed to normal following nutritional therapy for 4–8 weeks. Changes in T lymphocyte subpopulations may partly explain depressed cell-medicated immunity in malnutrition.     

Parenteral nutrition in bone marrow transplantation

Twenty-nine patients undergoing bone marrow transplantation (BMT) were randomised prospectively to evaluate the effect of parenteral nutrition (TPN) on morbidity and mortality. Fourteen patients received a standard regimen of TPN for 10 +/- 4 days (mean +/- SD). All patients had free access to oral diet, which was significantly reduced compared to pre-transplant intake. In the TPN group, serum bilirubin by day 14 and serum bilirubin and gamma glutamyl transferase by day 21 were significantly higher than in the controls (p < 0.05). These differences probably reflect the higher incidence of serious pyrexia (T > 38.5' C) and blood culture positive rates in the TPN group. Weight loss in the control group was significantly greater than that of the TPN group (p < 0.05). TPN did not affect time to grafting or incidence of graft-versus-host disease. The use of TPN in the nutritional support of patients in small BMT units requires careful consideration.     

Metabolic and thermogenic response to continuous and cyclic total parenteral nutrition in traumatised and infected patients

16 traumatised or infected patients on mechanical ventilation were randomised to continuous TPN or to cyclic TPN after a 24-h period of glucose infusion (1.25 kJ x kg BW(-1) x h(-1)). Energy supply was equivalent to 1.3 x baseline energy expenditure. Glucose, fat and amino acids were administered at a constant rate over 24 h in the continuous TPN group and over 12 h, followed by glucose (1.25 kJ x kg BW(-1) x h(-1)), in the cyclic TPN group. Nutrient-induced thermogenesis was lower during continuous than during cyclic TPN (5 +/- 4 vs. 12 +/- 7%, mean +/- SD, p < 0.05), as was the increase in CO(2) elimination (13 +/- 11 vs. 30 +/- 7%, respectively, p < 0.01). Energy balance was more positive during continuous TPN. In both groups, energy expenditure reached a plateau during the first 12 h of TPN infusion. The lower nutrient-induced thermogenesis and more positive energy balance, indicates a more efficient utilisation of nutrients during continuous than during cyclic TPN. The lower CO(2) production during continuous TPN, may be advantageous when respiratory function is compromised. The plateau in energy expenditure in response to TPN infusion may be useful as a guideline for nutritional therapy.     

老年胃肿瘤病人术后早期肠内营养的应用

目的:探讨早期肠内营养对改善老年胃肿瘤病人术后的营养免疫状况及减少并发症的作用.方法:将84例老年胃肿瘤病人随机分为肠内营养(EN)组及肠外营养(PN)组,于术后24 h开始予以相同热量及氮量营养支持,分别观察营养支持前后的营养和免疫指标及术后并发症.结果:两组的营养及免疫指标于营养支持后明显改善(P＜0.05),免疫指标EN组较PN组明显提高(P＜0.05);EN组与PN组相比,明显促进病人术后胃肠道功能恢复,减少并发症的发生及住院费用.结论:老年胃肿瘤病人术后早期肠内营养是一种安全、有效、简便、经济和理想的营养治疗方法.     

Effect of energy substrate manipulation on tumour cell proliferation in parenterally fed cancer patients

The effects of isocaloric carbohydrate-based vs. fat-based total parenteral nutrition (TPN) regimens on cancer cell proliferation and host nutritional status were evaluated in 27 patients with tumours of the gastro intestinal tract consecutively assigned to receive for 14 days: a glucose-based (A) or a lipid-based (B) TPN formula, or an oral diet (C) isocaloric and isonitrogenous to A and B. Cancer cell replication rate was evaluated by thymidine labelling index (LI) on tumour samples before and at the end of each nutritional regimen. The number of replicating cells increased by 32.2% in patients receiving regimen A. LI decreased by 24.3% in patients given regimen B. LI values were slightly increased (+15%) in patients maintained on regimen C. Nutritional status remained within normal limits. None of the LI changes observed between and within the three arms of the trial were found to be statistically significant. Thus we failed to prove that glucose consistently stimulates or lipids inhibit tumour proliferation despite a trend in this sense.     

Effects of glutamine supplementation on innate immune response in rats with gut-derived sepsis

The present study examined the effect of glutamine (Gln)-enriched diets before sepsis or Gln-containing total parenteral nutrition (TPN) after sepsis, or both, on the phagocytic activity and blood lymphocyte subpopulation in rats with gut-derived sepsis. Rats were assigned to a control group or one of four experimental groups. The control group and groups 1 and 2 were fed a semipurified diet; groups 3 and 4 had part of casein replaced by Gln. After feeding the diets for 10 d, sepsis was induced by caecal ligation and puncture (CLP); TPN was maintained for 3 d after CLP. The control group and groups 1 and 3 were infused with conventional TPN and groups 2 and 4 were supplemented with Gln in the TPN solution. All rats were killed 3 d after CLP or sham operation to examine their immune responses. The results showed that compared with the control group, the phagocytic activities of peritoneal macrophages were enhanced in groups 3 and 4, but not in groups 1 and 2. The proportion of CD3+ cells in group 1 was significantly lower (P<0.05) than that of the control group, whereas no differences were observed among the control and Gln-supplemented groups. The CD4+ cell proportion was significantly lower (P<0.05) in group 1 compared with the control group and groups 3 and 4. These findings suggest that Gln-enriched diets before CLP significantly enhanced peritoneal macrophage phagocytic activity, preserved CD4+ cells and maintained blood total T lymphocytes in gut-derived sepsis. However, parenteral Gln administration after caecal ligation and puncture had no favourable effects on modulating immune response in septic rats.     

胃癌术后应用TPN对血清IL-12 及细胞免疫功能的影响

目的：研究胃癌根治术后病人应用TPN对IL－2及细胞免疫功能的影响。方法：胃癌病人34例,随机分为实验组、对照组、实验组每天应用TPN,连续8在,对照组每天静脉输注含糖的普通液体。检测IL－12及细胞免疫指标,包括T细胞亚群（CD3^ 、CD4^ 、CD8^ ）。结果：应用TPN后实验组IL－12、CD4^ 、CD4^ ／CD8^ 均有显著提高。结论：TPN能提高胃癌术后病人血清IL－12水平,并能改善胃癌根冶术后应激体的免疫功能。     

Nutritional support after liver transplantation: a randomized prospective study

Nutritional support in patients with advanced cirrhosis is difficult due to protein, fluid and salt restrictions. Successful liver transplantation should improve nutrient tolerance. We randomly assigned 28 hypoalbuminemic cirrhotic patients to receive, immediately after liver transplantation, one of three regimens: group 1, no nutritional support (n = 10); group 2, total parenteral nutrition (TPN) (35 kcal/kg/day) with standard amino acids (1.5 g/kg/day) (n = 8); or group 3, isocaloric isonitrogenous TPN with added branched-chain amino acids (n = 10). Therapy was continued for 7 days posttransplant. Jaundice resolution was unaffected by nutritional support. Nitrogen balance favored both TPN groups. Branched-chain amino acid (BCAA) aromatic amino acid ratios were highest in group 3. Coma scores and serum ammonia levels were similar in all groups. Both TPN groups achieved respirator independence earlier; this difference was not statistically significant. Group 1 patients stayed longest in ICU; the difference was statistically significant. TPN with either standard or BCAA- enriched amino acids is tolerated well immediately after successful liver transplant. Positive nitrogen balance is achieved; large protein loads do not worsen encephalopathy. Nutritional support may improve respiratory muscle function, allowing earlier weaning from ventilatory support. A shortened length of ICU stay justifies the expense of TPN.     

The effects of different intravenous feeding regimens on the rates of synthesis of alpha1-antitrypsin after surgery

The effects of two nutritional regimens on the synthesis of alpha-1 antitrypsin were investigated postoperatively in gynaecological cancer patients. Total parenteral nutrition (TPN) or a hypocaloric amino acid mixture was administered on the day of surgery and continued for 3 days. The rate of synthesis of alpha-1 antitrypsin was estimated by a computer model from serial plasma concentrations of this protein and a reference protein, albumin. The hypocaloric amino acid mixture resulted in a more negative nitrogen balance than that produced during administration of TPN containing the same amount of nitrogen but more non-protein energy. Urinary excretion of 3-methylhistidine was significantly greater (p = 0.017) in the hypocaloric amino acid group (350 +/- 40 mumol/day; mean +/- SE) on the third postoperative day, as compared to the TPN group (240 +/- 20 mumol/day). In spite of this the synthesis of alpha-1 antitrypsin was apparently greater in the hypocaloric amino acid than in the TPN group. The accumulated plasma appearance rate of alpha-1 antitrypsin was significantly higher (p = 0.0465) in HAA group, at 70 h it was 490 +/- 40 compared to 400 +/- 20 times the pre-operative synthesis in the TPN group.