The Henry M. Vars Award. The effect of lipid emulsions on reticuloendothelial system function in the injured animal

Use of intravenous lipid emulsions in trauma and sepsis still remains controversial. In order to examine the impact lipid emulsions have on host defense against bacterial infection during total parenteral nutrition (TPN), 56 male Sprague-Dawley rats underwent jugular cannulation and were randomly divided into three groups, each receiving one of three TPN regimens. All regimens delivered approximately 250 kcal/kg X body weight/day, of which 12.5 g were as amino acids. Group 1 received 100% of the nonprotein calories as glucose (AA + G). Group 2 was given 50% of the nonprotein calories as a longchain triglyceride emulsion (100% LCT). Group 3 received 50% of nonprotein calories as a mixed lipid system, composed of medium- and long-chain triglycerides (75% MCT/25% LCT). After 24 hr on intravenous nutrition, all animals received bilateral septic femur fractures and were continued on TPN for 3 days. On the last day, the level of bacteremia and the in vivo response to an intravenous challenge of 59Fe-labeled Escherichia coli were examined. Three days following the septic injury, animals given MCT as part of their lipid calories were not bacteremic, whereas the other groups had greater than 10(2) cfu/ml of blood. Animals receiving TPN with MCT sequestered a greater percentage of exogenously administered bacteria in the liver and sequestered less in the lung compared to animals given 100% LCT (p less than 0.05). From these data, we conclude that parenteral nutrition formulas where LCT has been partially replaced with MCT may better support host bactericidal capacity than similar regimens comprised of LCT as the sole lipid source.     

谷氨酰胺二肽对全肠外营养短肠综合征大鼠血清蛋白及肝功能的影响

目的观察谷氨酰胺二肽对Wistar大鼠短肠模型血清蛋白和肝功能的影响,及其减轻脂肪乳剂引起肝损害的作用机理。     

丙烯酰胺诱导小鼠淋巴瘤细胞tk基因突变谱的实验研究

目的为研究丙烯酰胺(AA)致基因突变的机制提供实验依据。方法挑选经AA诱导的小鼠淋巴瘤L5178Y3．2．7c-tk^ /-细胞tk基因突变子(tk-/-)，提取基因组DNA，用等位基因特异性聚合酶链反应(PCR)扩增、杂合性缺失(LOH)分析、序列分析等技术，分析其突变谱。结果AA诱导突变体tk基因LOH发生率为78．8％。LOH的发生率随AA剂量的增加呈上升趋势，染毒剂量越大，tk等位基因缺失的发生就越严重。在大集落(LC)中，AA低剂量组(150、300μg/m1)诱导LOH的发生率(25．0％、33．3％)与自发突变组和AA高剂量组(600、750μg/ml)LOH的发生率(66．7％、77．8％、85．7％)相比，差异均有统计学意义(P＜0．05)。序列分析证实，AA诱导的tk基因点突变主要为碱基置换以及1个移码，其中碱基置换主要的类型为T：G→G：T的颠换。结论AA诱导的tk基因突变谱是以功能性等位基因缺失为主的突变类型，其次是碱基置换，移码较少发生。     

Continuous v intermittent cimetidine infusion in critically ill hospitalized patients: role of TPN admixture as drug vehicle

Previous studies suggest that continuous or intermittent cimetidine infusion provides a stable and sustained therapeutic blood concentration that maintains a gastric pH greater than 4.0. Twenty-seven patients receiving cimetidine were randomized to one of five treatments. Groups 1 and 2 were given cimetidine intermittently, whereas Groups 3, 4, and 5 received the drug continuously via a total parenteral nutrient (TPN) admixture. Group 1 was given 300 mg every 8 hours, and Group 2 received 300 mg every six hours. Groups 3, 4, and 5 received 600, 900, and 1200 mg per day, respectively, as a continuous infusion in the TPN admixture. Forty-eight individually prescribed TPN admixtures were used to deliver cimetidine continuously; 23 were composed of amino acids and glucose as base nutrients, whereas 25 contained amino acids, glucose, and lipids (3-in-1 or total nutrient admixtures). Serum levels of cimetidine were measured six times in 40 h (Group 1) or 42 h (Group 2-5). A two-way analysis of variance (ANOVA) revealed statistically significant differences in the serum cimetidine concentrations between groups (p less than 0.0001), but not with respect to time interval (p = 0.8687). No significant differences were noted in mean serum cimetidine concentrations between Groups 2 and 3, despite employing half the total dose in Group 3. Equivalent daily dosages were then stratified as the percentage of subtherapeutic (less than 500 ng/ml), therapeutic (500-1250 ng/ml), and supratherapeutic (greater than 1250 ng/ml) values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability of ascorbic acid in a standard total parenteral nutrition mixture

We investigated the stability of ascorbic acid (AA) and the sum of AA plus dehydroascorbic acid (TAA) in a total parenteral nutrition (TPN) mixture that contained 1000 ml Vamin 14, 1000 ml glucose 30%, 500 ml Intralipid 20%, potassium phosphate, a multivitamin preparation (Cernevit) and trace elements. We used a spectrophotometer to measure AA and TAA. AA decreased from 42.2 (+/-0.9) mug/ml to 6.8 (+/-0.2) mug/ml in 7 days. Over the same time the concentration of TAA decreased from 42.2 (+/-0.5) mug/ml to 35.9 (+/-0.6) mug/ml, i.e. 63.3 (+/-1.2)% of the original concentration. When the solution was stored in glass bottles and saturated with nitrogen or when trace elements were omitted, the concentration decreased by only 25.2 (+/-0.2)% and 23.8 (+/-1.6)% respectively over 7 days. The influence of oxygen, lipids, trace elements and underfilling the bag was also investigated. We conclude that it is acceptable to prepare these bags in advance and to store them for 7 days at 2-4 degrees C.     

Guidewire catheter exchange with triple culture technique in the management of catheter sepsis

We report 70 total parenteral nutrition (TPN) patients who received guidewire catheter exchange for suspected sepsis during their hospitalization. To diagnose catheter-related sepsis (CRS) and catheter infection (CI), we used a system of pre- and postexchange catheter blood cultures and a catheter tip culture. There were 27 catheter exchanges with positive cultures. The rate of definite CRS/CI (eight instances) was 6.8% of catheters exchanged and 3.5% of all catheters at risk. Probable CRS/CI (11 instances) was seen in 9% of exchanged catheters and 5% of at risk catheters. Thus, 19/27 positive cultures were presumed to represent definite or probable CRS/CI. Coagulase negative Staphylococcus (SCN) was the most frequently isolated organism. Simple catheter exchange was usually effective treatment of CRS/CI when SCN was the offending organism. The salvage rate of catheters exchanged for suspected sepsis or after a positive blood culture was 84%. Only 7% of exchanged catheters had to be removed. Guidewire exchange with triple culture technique was without mechanical complications. We recommend this technique to monitor central venous catheters in patients receiving TPN since it is simple, essentially painless to perform, and easily interpreted.     

Comparison of Intravenous Glucose and Fat Calories on Host and Tumor Growth

This study was undertaken to determine if the proportions of intravenous carbohydrate and fat calories influence the relative growth of a Walker 256 carcinosarcoma and its host. Rats injected intraperitoneally with Walker 256 carcinosarcoma cells were randomized into three total parenteral nutrition (TPN) groups, G/AA in which glucose provided all nonprotein calories, G/F/AA in which the nonprotein calories were 20% fat and 80% glucose, and F/AA in which all nonprotein calories were from fat. Except for the caloric source, TPN for each group was identical. A fourth group was sham operated, fed rat food, and was not given TPN. On the 6th day after innoculation, the tumor in each rat showed a dispersed ascites form as well as a solitary mass form involving the omentum. The total number of tumor cells in the ascitic fluid and the dry weight of the mass were determined. The three TPN groups did not differ in tumor cell count, solid tumor weight, ratio of tumor cell count to final host weight, or ratio of solid tumor to final host weight. The mean ratio of ascites tumor cell count to host weight was not different between the rat food-fed group and any of the TPN groups. The mean ratio of solid tumor to host weight was less for the TPN groups than for rat food-fed animals. We conclude that TPN had no adverse effect on the growth of tumor us. host and that the source of intravenous calories (fat or carbohydrate) did not influence the relative growth of tumor and host in this TPN-tumor model. (Journal of Parenteral and Enteral Nutrition 8:657–659, 1984)     

The growth of microorganisms in total parenteral nutrition admixtures

Total nutrient admixtures (TNAs) containing glucose, amino acids, and lipid emulsion in one container and amino acid/dextrose solutions [conventional total parenteral nutrition (TPN) formulations] were studied in a controlled laboratory experiment for their ability to support the growth of microorganisms. Both TNA and conventional TPN formulations for peripheral and central venous administration with standard additives were inoculated with microorganisms to provide 10(1)-10(2) colony-forming units/ml (CFU/ml) of Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. The admixtures were stored at room temperature and samples for quantitative microbiology were taken at time 0, 6, 12, 24, 48, 72, and 96 hr. K. pneumoniae, E. coli, and P. aeruginosa were able to proliferate in central TNAs, but the growth of these organisms was retarded in conventional TPN solutions. In the peripheral formulations, K. pneumoniae and E. coli proliferated in both the TNA and conventional TPN systems, whereas P. aeruginosa grew well only in the peripheral TNA. S. epidermidis was not able to grow in any admixtures tested; however, C. albicans grew well in all admixtures, but growth was slower in the conventional central TPN. In conclusion, peripheral and central TNAs supported the growth of microorganisms significantly better than conventional TPN solutions.     

Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (A randomised double-blind study) Schloerb P and Amare M. JPEN 1993: 17: 407-413

29 patients with either haematological or solid tumours, and receiving allogeneic or autologous bone marrow transplants (BMT) were included in a double-blind, randomised study of glutamine-free versus glutamine-supplemented TPN. Patients were given isocaloric, isonitrogenous TPN after BMT until they consumed 50% of their required diet orally. Length of hospital stay was significantly (5.8 days) less in patients receiving TPN/GLN. Incidence of positive bacterial cultures, clinical infections and mortality did not differ significantly between the two groups.     

Effect of methionine-deprived nutrition on cell growth and cell kinetics in cell cultures and experimental tumors

The effect of methionine-deprived nutrition on cell growth and cell kinetics was investigated in cell cultures and in tumor-bearing rats using the total parenteral nutrition (TPN) technique. A simultaneous flow cytometric measurement of the cellular DNA content and the amount of 5-bromodeoxyuridine incorporated into cellular DNA was performed for analysis of cell kinetics. The methionine-free medium demonstrated a cytocidal effect on the growth of SLC cells after 6 hours of culturing. It decreased viability from 80% in the control medium to 23%, and it decreased the S phase and increased the G0/G1 phase of the cell cycles. The methionine-deprived medium showed a concentration-dependent inhibition in cellular growth. Methionine-deprived TPN was seen to inhibit AH109A and SLC tumor growth compared with conventional TPN and decreased the S phase and increased the G0/G1 phase of cell cycles. These results confirm that methionine deprivation blocks cells from processing into the G1 phase and recycling, and that it is effective in inhibiting tumor growth in cultures and in vivo.     

富含谷氨酰胺二肽的20种结晶氨基酸对短肠综合征大鼠免疫功能的影响

目的观察富含谷氨酰胺二肽和支链氨基酸的新型20种结晶氨基酸配制的全肠外营养液对短肠综合征大鼠免疫功能的影响。方法40只Wistar雄性大鼠随机分为谷氨酰胺二肽组、标准组、无氮组及虚拟对照组,观察各组动物之间外周血T淋巴细胞转化率、T淋巴细胞亚群(CD4 ／CDS- )以及血清肿瘤坏死因子(TNF)等免疫指标的变化。结果谷氨酰胺二肽组与标准组及无氮组相比,T淋巴细胞转化率、CD4 ／CD8 及TNF均有不同程度的增高。结论富含谷氨酰胺二肽和支链氨基酸的20种结晶氨基酸更有利于手术后创伤应激期免疫功能的恢复,增强其生存能力。     

Plasma ammonia levels in preterm infants receiving parenteral nutrition with crystalline L-amino acids

In order to investigate the severity and incidence of hyperammonemia in preterm infants receiving total parenteral nutrition (TPN) with crystalline L-amino acids having high arginine content (Travasol), we determined the plasma ammonia (PA) levels in a group of 29 preterm infants on TPN, weekly and 1 wk posttherapy. Their mean gestational age was 29.9 +/- 2.6 wk and mean birth weight 1208 +/- 262 g. Thirty five blood samples obtained from 15 preterm infants not on TPN with mean gestational age 32.2 +/- 1.9 wk and a birth weight of 1495 +/- 161 g served as a control. In the parenteral nutrition group the mean PA level (140 +/- 58 micrograms/100 ml) was significantly higher (p less than 0.001) than that in the same group one week post TPN (97 +/- 34 micrograms/100 ml) and in the control group (86 +/- 35 micrograms/100 ml). The incidence of hyperammonemia (greater than 160 micrograms/100 ml) was 30% in the TPN group versus 3% in the controls (p less than 0.01). Maximal PA level during that treatment was 405 versus 216 micrograms/100 ml 1 wk post-TPN versus 163 micrograms/100 ml in the controls. The data show a significant increase in PA levels in preterm infants receiving TPN with Travasol, possibly because of its high glycine content.     

Stability of imipenem and cilastatin sodium in total parenteral nutrient solution

The chemical stability and compatibility of imipenem-cilastatin sodium (Primaxin) in two different total parenteral nutrient (TPN) solutions was determined. TPN solutions consisted of 4.25% and 5% amino acids with 25% and 35% dextrose, respectively. Imipenem-cilastatin sodium was constituted with 10 ml of sterile water and admixed with 90 ml of TPN solution for a final concentration of 5 mg/ml of each drug. The final solutions were assayed at times 0 (immediately after admixture), 15 min, 30 min, 1, 4, 8, and 24 hr by a stability-indicating high-performance liquid chromatographic assay. Concurrently, test TPN solutions were monitored for pH changes, color changes, and precipitate formation. The potential effect of imipenem-cilastatin sodium on the stability of amino acids and other TPN additives was not evaluated. Imipenem and cilastatin sodium was stable (greater than or equal to 90% recovered) in each TPN solution at 15 min. A significant (greater than or equal to 10%) and steady decrease of imipenem recovery occurred at subsequent sampling times. Cilastatin appeared more stable than imipenem in both TPN solutions. A physical color change from colorless to dark orange appeared in each TPN solution over the 24-hr study period. Imipenem-cilastatin sodium is stable for 15 min in the TPN solutions studied; however, until the stability of the amino acids can be determined, the antibiotic should be administered through a separate line or Y-site while the TPN infusion is interrupted.     

Relative importance of amino acid infusion as a means of sparing protein in surgical patients

We performed isotopic infusions in 51 surgical patients to investigate the effectiveness of different substrates to conserve protein. All patients were initially studied in the basal state and then the effects of glucose infusion (GL, N = 13), lipid infusion (LIP, N = 11), or amino acid infusion (AA, N = 17) were determined. Ten patients receiving total parenteral nutrition (TPN) were also studied. The basal value for net protein catabolism (NPC) in GL patients was 1.53 +/- 0.4 (SEM) g/kg/day decreasing to 1.39 +/- 0.4 g/kg/day during glucose infusion (p less than 0.01). The basal NPC in the LIP group was 2.04 +/- 0.4 g/kg/day decreasing to 1.72 +/- 0.3 g/kg/day during lipid infusion (p less than 0.01). In the TPN patients the NPC was 0.79 +/- 0.46 g/kg/day whereas in the AA patients the basal value for NPC was 1.37 +/- 0.14 g/kg/day decreasing to -0.77 +/- 0.11 g/kg/day during amino acid infusion (p less than 0.0005). From our study we conclude that: (1) All substrates commonly used in intravenous feeding have the capacity to spare protein. (2) Protein sparing was more pronounced when a balanced amino acid infusion was used than with either glucose or lipid infusion alone. (3) This effect is not solely due to insulin secretion as larger insulin responses were seen with both GL and TPN patients. (4) These results may have implications for peripheral vein feeding with amino acid solutions where there is a contraindication for full TPN or the lack of resources for administering it.     

一种快速鉴定金黄色葡萄球菌的方法

本文报道用溶葡萄球菌素敏感试验快速鉴定金黄色葡萄球菌的方法。在2.0μg/ml溶葡萄球菌素浓度下,216株金黄色葡萄球菌菌株中有213株被裂解,判断为阳性结果;112株表皮葡萄球菌和141株其它球菌和杆菌均呈阴性。在模拟条件下,对13份含不同质粒谱和耐药谱金黄色葡萄球菌的血液标本的鉴定均为阳性;28份含有表皮葡萄球菌和微球菌的标本中仅1例出现假阳性结果。对53份临床标本的鉴定结果表明该方法阳性率达96.2％,无假阳性出现。     

复方氨基酸对短肠综合征大鼠肠粘膜形态结构的影响

Objective To investigate the effect of a new 20-crystalline aminoacids solution enriched with glutamine dipeptede and branch-chained animo acids(BCAA)on the morphological changes of the intestinal mucosa of SBS rats. Methods 32 male wistars rats were randomly allocated into 3 groups:12 rats in Gln-group,12 rats in Std-group,8 rats in Nitrogen-free group.Using the model of SBS rats,nutritional liquid with different aminoacids was given by central catheterization.The body weight,nitrogen balance,the total DNA and RNA of jejunalmucosal cells,jejunal mucosal thickness and villus height were measured. Results The results showed that all variable in 20AA group and 17AA group were better than no nitrogen(the second)group(P<0.05).The 20AA group had better body weight,nitrogen balance and jejunum morphology than 17AA group.Jejunal mucosalthickness and villus height,total DNA and RNA of jejunal mucosal cells in 20AA group was increased compared with 17AA group(P<0.05). Conclusions The result showed that 20AA TPN group had better nutritional support,passive nitrogen balance can be improved.It appears that 20AA TPN could be provided to maintain and support growth of the gestrointestinal mucose.     

The C-terminal heptapeptide of bombesin reduces the deleterious effect of total parenteral nutrition (TPN) on gut-associated lymphoid tissue (GALT) mass but not intestinal immunoglobulin A in vivo

BACKGROUND: Bombesin, the amphibian analog of mammalian gastrin-releasing peptide, reverses total parenteral nutrition (TPN)-induced atrophy of gut-associated lymphoid tissue and increases intestinal and respiratory immunoglobulin A (IgA) levels. Structure-activity studies suggested that the biologically active portion of bombesin is a C-terminal heptapeptide (7AA). This study investigates the effect of 7AA on lymphocytes counts of the Peyer's patches (PP), the lamina propria (LP) and the intraepithelial layer (IE). METHODS: Forty-eight male mice were randomized to receive chow (n = 13), TPN only (n = 9), TPN + 15 microg 7AA 3 times per day (n = 13) or TPN + 150 microg 7AA 3 times per day (n = 13). After 5 days of feeding, PP, LP, and IE lymphocytes were determined. Intestinal IgA levels were measured with ELISA. Groups were compared with ANOVA. RESULTS: All TPN-fed mice lost more weight than mice fed chow (p < .04). Lymphocyte counts in PP, LP, and IE were significantly lower in the TPN group than in the 3 other groups but did not differ between the groups fed chow, TPN + 15 microg 7AA 3 times per day, or TPN + 150 microg 7AA 3 times per day. Intestinal IgA levels were higher in chow-fed mice (148.4 +/- 16.9) than in mice fed TPN (98.4 +/- 14.0, p = .008), TPN + 15 microg 7AA 3 times per day (96.9 +/- 7.7, p = .003) or TPN + 150 microg 7AA 3 times per day (87.3 +/- 6.7, p = .001). CONCLUSIONS: The C-terminal heptapeptide of bombesin prevented the TPN-induced decrease in intestinal lymphocyte populations but not the reduction in intestinal IgA levels.     

The incidence of hyperglycemia in hematopoietic stem cell transplant recipients receiving total parenteral nutrition: a pilot study

OBJECTIVE: To determine whether total parenteral nutrition (TPN)-induced hyperglycemia is associated with adverse clinical outcomes. DESIGN: A retrospective cohort investigation comparing the medical records of hematopoietic stem cell transplant patients was conducted to determine clinical differences between those who received TPN and those who did not receive TPN during transplant. SUBJECTS/SETTING: Forty-eight adult patients (> or =18 years) undergoing initial autologous or allogeneic hematopoietic stem cell transplant at two urban university-affiliated hospitals were eligible for inclusion. MAIN OUTCOME MEASURES: Hyperglycemia (glucose > or =6.1 mmol/L or 110 mg/dL), presence of infection, infection duration, and in-hospital mortality. Statistical analyses performed chi 2, Student t, and Wilcoxon rank-sum tests were used to detect differences among the study participants. RESULTS: Patients had similar baseline demographic and clinical characteristics, with 63% receiving TPN during transplant. When standardized for time, TPN recipients at both institutions experienced significantly more hyperglycemia ( P <.05) after TPN initiation. TPN patients also experienced 69% of all infections and 100% of repeat positive cultures. Additionally, significantly greater differences for TPN recipients were found for length of stay and daily charges than those who did not receive TPN. No differences were found for in-hospital mortality. CONCLUSIONS: TPN is strongly associated with hyperglycemia, which may be linked to increased infections of longer duration in a profoundly immunocompromised group of patients who frequently receive TPN. The implications of these findings are limited by the small number of subjects; a larger investigation is warranted.     

谷氨酰胺强化的肠外营养对肠瘘病人腔静脉导管感染的影响

目的:观察谷氨酰胺(Gln)强化的肠外营养(PN)对肠瘘病人腔静脉导管感染(CRI)的发生率及细菌谱的影响.方法:对2002年10月至2003年12月该院收治的使用腔静脉导管进行PN的肠瘘病人进行前瞻、随机研究.对照组接受常规全肠外营养(TPN),Gln组在常规TPN中加入力肽100ml.结果:117例肠瘘病人,共进行139次腔静脉置管.对照组71例病人共进行84次腔静脉置管,细菌定植的发生率为26.2%,导管相关性血行感染(CRBSI)的发生率为6.0%.Gln组46例病人共进行55次腔静脉置管,细菌定植的发生率为12.7%,CR-BSI为1.8%.Gln组和对照组病人革兰阴性细菌感染的发生率分别为3.6%与16.7%,二者有显著性差异(P=0.037).结论:Gln强化的PN可以减少肠瘘病人CRI的发生,尤其是来源于肠道的革兰阴性菌的感染.     

Higher dextrose delivery via TPN related to the development of hyperglycemia in non-diabetic critically ill patients

The beneficial effects of total parenteral nutrition (TPN) in improving the nutritional status of malnourished patients during hospital stays have been well established. However, recent randomized trials and meta-analyses have reported an increased rate of TPN-associated complications and mortality in critically ill patients. The increased risk of complications during TPN therapy has been linked to the development of hyperglycemia, especially during the first few days of TPN therapy. This retrospective study was conducted to determine whether the amount of dextrose from TPN in the 1^st week in the intensive care unit (ICU) was related to the development of hyperglycemia and the clinical outcome. We included 88 non-diabetic critically ill patients who stayed in the medical ICU for more than two days. The subjects were 65 ± 16 years old, and the mean APACHE (Acute Physiology and Chronic Health Evaluation) II score upon admission was 20.9 ± 7.1. The subjects received 2.3 ± 1.4 g/kg/day of dextrose intravenously. We divided the subjects into two groups according to the mean blood glucose (BG) level during the 1^st week of ICU stay: < 140 mg/dl vs ≥ 140 mg/dl. Baseline BG and the amount of dextrose delivered via TPN were significantly higher in the hyperglycemia group than those in the normoglycemia group. Mortality was higher in the hyperglycemia group than in the normoglycemia group (42.4% vs 12.8%, P = 0.008). The amount of dextrose from TPN was the only significant variable in the multiple linear regression analysis, which included age, APACHE II score, baseline blood glucose concentration and dextrose delivery via TPN as independent variables. We concluded that the amount of dextrose delivered via TPN might be associated with the development of hyperglycemia in critically ill patients without a history of diabetes mellitus. The amount of dextrose in TPN should be decided and adapted carefully to maintain blood glucose within the target range.