bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Cholestyramine and Parenteral Nutrition on Hepatic Metabolism of Lidocaine: A Study Using Isolated Rat Liver Perfusion
Authors: Zaman Nuzhat , Tam Yun K. , Jewel Lawrence D. , Coutts Ronald T.
Published: May 2008

Background:The effect of an oral bile salt binder, cholestyramine, on parenteral nutrition‐related hepatic dysfunction and lidocaine metabolism was studied in rats.Methods:Rats were randomly assigned to one of three treatment groups: the PN group received infusions of dextrose and amino acids; the PNC group was treated the same as the PN group, but also received oral cholestyramine; CF group animals were fed rat food and water. Lidocaine metabolism was studied in livers isolated from animals after 7 days of parenteral nutrition.Results:No differences in liver function test values of PN and PNC groups were detected compared with group fed rat food. However, lidocaine metabolism was found to be significantly reduced in both the PN and PNC groups. Significant reductions were observed in the hepatic extraction ratio (23% and 15%) and in intrinsic clearance (61% and 53%) in PN and PNC animals, respectively(p<.05). Material balance at steady state showed that recovery of lidocaine was threefold higher in the PN group and twofold higher in the PNC group than the rat food group (p<.05). Metabolite‐to‐drug ratios were determined for each lidocaine metabolite and this revealed significant reductions inN‐dealkylation (64% and 57%) and aryl methyl hydroxylation (92% and 86%) in PN and PNC animals, respectively(p<.05).Conclusions:Histologic fmdings suggest that cholestyramine feeding prevented liver dysfunction, possibly through interruption of secondary bile salt reabsorption. However, lidocaine metabolism was still impaired after cholestyramine ingestion; the impairment mechanism remains unknown.(Journal of Parenteral and Enteral Nutrition20:349–356, 1996)
Estimation of CO2 Production in Enterally Fed Preterm Infants Using an Isotope Dilution Stable Tracer Technique
Authors: Kien C. Lawrence , McClead Richard E.
Published: May 2008

Background: Estimates of the rate of CO., production may be useful in preterm infants, but assessment of the rate of respiratory excretion of CO2 (Vco2) may not always be practical in infants requiring constant care. We hypothesized that the rate of dilution of 13CO2 (Raco2) would be a valid index of CO2 production in preterm infants. Methods: Twelve studies of Raco2 and VCO2 were performed in six enterally fed preterm infants. Raco2 was measured using a 2‐hour, primed, constant, orogastric infusion of NaH13CO3 with formula and an assessment of the plateau 13C enrichment of expired CO2. VCO2 was measured over two 10‐minute intervals during the infusion using a flow‐through system. Energy expenditure was estimated from these data and the food quotient. Results: Mean (± SD) rate of CO2 production using Raco2 (348 ± 32 μmol/kg/min) was 114% of that estimated using VCO2 (304 ± 51 μmol/kg/min). The ratio of VCO2/RaCO2 is equal to the fractional recovery of tracer CO2 in the expired air during the course of the tracer infusion. In studies of short duration, this ratio is generally less than 100% because of isotope exchange. For five pairs of studies performed on consecutive days, each individual value of Raco2 on day 2 was multiplied by the mean of the individual ratios of VCO2/RaCO2, on day 1 (0.78); corrected Raco2 was 306 ± 19 μmol/kg/min compared with 307 ± 59 μmol/kg/min for Vco2. Conclusions: Thus, Raco2, particularly when corrected for isotope recovery, may be a useful index of group mean CO2 production and energy expenditure in preterm infants. (journal of Parenteral and Enteral Nutrition 20:389–393, 1996)
The Metabolism of [75Se]Selenite in Patients With Short Bowel Syndrome
Authors: Rannem Terje , Hylander Ellinor , Ladefoged Karin , Staun Michael , Tjellesen Lone , Jarnum Stig
Published: May 2008

Background

Patients on home parenteral nutrition (HPN) require significantly higher amounts of selenium compared with controls. The purpose of the present study was to investigate if selenium deficiency of patients with short bowel syndrome is caused by selenium malabsorption or by excessive intestinal or renal loss.

Methods

The metabolism of [75Se]selenite was investigated in eight selenium‐depleted short bowel patients on HPN and in six control subjects. The isotope was given orally, and in a subsequent study as bolus injection or as 12‐hour IV infusion.

Results

The fractional intestinal absorption of selenium was significantly reduced in the patients (2% to 58%, median 20%) when compared with the reference group (79% to 91%, median 82%) (p < .001). Within the group of patients we found a positive significant correlation between fractional selenium absorption and the length of the remaining small intestine (r = 0.95, p < .05). After parenteral [75Se]selenite administration, the patients showed a significantly higher fecal loss and a significantly reduced urinary excretion of 75Se when compared with the controls. Bolus injection vs 12‐hour infusion of [75Se]selenite did not affect the cumulative fecal or urinary 75Se excretion in the HPN patients.

Conclusions

Reduced intestinal selenium absorption is probably the most important cause of the selenium deficiency reported in patients with short bowel syndrome, but increased endogenous intestinal selenium loss and low selenium intake may also contribute. Despite the renal counterregulation, which results in a low urinary selenium excretion, HPN patients need a supply of selenium with their parenteral nutrition.
Use of Cholecystokinin to Prevent the Development of Parenteral Nutrition‐Associated Cholestasis
Authors: Teitelbaum Daniel H. , Han‐Markey Theresa , Drongowski Robert A. , Coran Arnold G. , Bayar Bilge , Geiger James D. , Uitvlugt Neal , Schork M. Anthony
Published: May 2008

Background: Neonates are at high risk for the development of parenteral nutrition‐associated cholestasis when receiving a prolonged course of total parenteral nutrition (TPN). Although this cholestasis is of unknown etiology, it may result from a lack of gastrointestinal hormone formation, including cholecystokinin, which normally occurs after enteral feedings. Methods: Two groups of neonates were studied. The treatment group consisted of 21 consecutive, prospectively enlisted neonates receiving TPN for > 14 days. The nontreatment group consisted of 21 infants from the 2 years preceding the study who were matched to the treatment group by gestational age, diagnosis, and duration of TPN. The major outcome determinant was direct bilirubin. Cholestasis was defined as a direct bilirubin >2.0 mg/dL and was considered severe if the direct bilirubin was >5.0 mg/dL after other causes were ruled out. Results: The mean direct bilirubin levels in the nontreated group progressively rose over time, whereas the mean direct bilirubin in the treated group remained level. The incidence of infants with a direct bilirubin >2.0 mg/dL was 24% and 43% in the CCK+ and CCK‐ groups, respectively, and was not significant (p =.14). The percentage of infants with a direct bilirubin >5.0 mg/dL was 9.5% and 38% in the treatment and nontreatment groups, respectively, and was significant, p =.015. Conclusions: Levels of direct bilirubin were lower in the treated compared with the nontreated group. These findings suggest that cholecystokinin prophylaxis in high‐risk neonates may help prevent the development of parenteral nutrition‐associated cholestasis. (journal of Parenteral and Enteral Nutrition 21:100–103, 1997)
Nutrition Support in Clinical Practice: Review of Published Data and Recommendations for Future Research Directions
Authors: Klein Samuel , Kinney John , Jeejeebhoy Khursheed , Alpers David , Hellerstein Mark , Murray Michael , Twomey Patrick
Published: May 2008

In the last 30 years, marked advances in enteral feeding techniques, venous access, and enteral and parenteral nutrient formulations have made it possible to provide nutrition support to almost all patients. Despite the abundant medical literature and widespread use of nutritional therapy, many areas of nutrition support remain controversial. Therefore, the leadership at the National Institutes of Health, The American Society for Parenteral and Enteral Nutrition, and The American Society for Clinical Nutrition convened an advisory committee to perform a critical review of the current medical literature evaluating the clinical use of nutrition support; the goal was to assess our current body of knowledge and to identify the issues that deserve further investigation. The panel was divided into five groups to evaluate the following areas: nutrition assessment, nutrition support in patients with gastrointestinal diseases, nutrition support in wasting diseases, nutrition support in critically ill patients, and perioperative nutrition support. The findings from each group are summarized in this report.

This document is not meant to establish practice guidelines for nutrition support. The use of nutritional therapy requires a careful integration of data from pertinent clinical trials, clinical expertise in the illness or injury being treated, clinical expertise in nutritional therapy, and input from the patient and his/her family. (Journal of Parenteral and Enteral Nutrition21:133–156, 1997)
A Double‐Blind Randomized Trial Comparing Outpatient Parenteral Nutrition With Intravenous Hydration: Effect on Resumption of Oral Intake After Marrow Transplantation
Authors: Charuhas Paula M. , Fosberg Karin L. , Bruemmer Barbara , Aker Saundra N. , Leisenring Wendy , Seidel Kristy , Sullivan Keith M.
Published: May 2008

Background: Outpatient parenteral nutrition (PN) is often given to marrow transplant recipients after high‐dose chemoradiotherapy until the resumption of adequate oral intake; however, it may adversely prolong resumption of oral calorie intake by contributing to early satiety. Methods: A double‐blind, randomized study compared standard PN (final concentration 25% dextrose, 5% amino acids) with a hydration solution (5% dextrose) during the first 28 days of outpatient treatment. Patients were eligible for the study if they were ≥2 years of age, <65 days posttransplant, had <70% oral caloric intake at hospital discharge, and required ≤10 U insulin/L PN. Solutions were provided until the patient's oral intake met ≥85% caloric requirements for 3 consecutive days. Results: Two hundred fifty‐eight marrow transplant recipients (128, PN and 130, hydration solution) were studied. Age, donor type, and diagnoses were similar in the two groups. Time to resumption of ≥85% oral caloric intake was 6 days sooner in the hydration group than in the PN group (median 10 vs 16 days, respectively; p =.049). When adjusting for sex, age, donor type, total body irradiation, previous oral intake, acute graft‐versus‐host disease, and prednisone therapy, the hydration group resumed oral intake sooner than the PN group (relative risk = 1.51; 95% confidence interval [CI] 1.04 to 2.19; P =.029). The percentage of weight change from pretransplant values, adjusted for the above covariates and the number of weeks of treatment, indicated that the hydration solution group lost weight (4.63%) compared with the PN group (1.27%) after 4 weeks of therapy (p =.004). Rates of hospital readmissions, relapse of malignancy, and survival did not differ between the two treatment groups. Conclusions: We conclude that outpatient PN delays resumption of oral intake and that its replacement with hydration solution does not result in adverse patient outcome. (Journal of Parenteral and Enteral Nutrition 21:157–161, 1997)
Enhanced Growth of Small Bowel in Transgenic Mice Expressing Human Insulin‐Like Growth Factor
Authors: Ney Denise M.
Published: May 2008

Insulin‐like growth factor 1 (IGF‐1) plays an important role in the regulation of intestinal growth and maturation, whereas the direct effects of growth hormone (GH) on intestinal growth are less clear. In this study the authors utilize a transgenic mouse model to assess the extent to which longterm excess of IGF‐1 in a background of GH deficiency stimulates small bowel growth.

IGF‐1 transgenic mice that overexpress an IGF‐1 transgene driven by the mouse metallothionein I promotor were compared with wild‐type littermates and GH transgenic mice. The IGF‐1 transgenics showed elevation of circulating IGF‐1, undetectable levels of plasma GH, and a decrease in pituitary GH messenger RNA (mRNA) caused by negative feedback effects of IGF‐1 excess. Growth of small bowel, abundance and localization of mRNAs for the IGF‐1 transgene, and IGF binding protein 3 (IGFBP‐3) were assayed to determine whether enterotrophic effects of excess IGF‐1 correlate with local overexpression of IGF‐1 in small bowel.

Small bowel length and mass were greater in IGF‐1 transgenic than in wild‐type mice. Villus height, crypt depth, and crypt cell mitoses were greater in IGF‐1 transgenics than wild‐type mice. Jejunal dissacharidase activities were not different among the IGF‐1 transgenics and wild‐type mice. The IGF‐1 transgene was expressed strongly in villus epithelial cells and at much lower, but significant levels in crypt epithelial cells, lamina propria, and smooth muscle layers. IGFBP‐3 was strongly expressed and localized in the lamina propria.Regional expression of IGF‐1 and IGFBP‐3 correlated with the increase in mucosal mass in IGF‐I transgenics.

Effects of IGF‐I overexpression on intestinal length and mucosal mass were similar to effects of GH overexpression, although IGF‐I transgenics showed greater small bowel growth relative to somatic growth compared with GH transgenics. Excess of IGF‐I increased crypt cell proliferation, whereas excess of GH did not increase crypt cell proliferation but did stimulate jejunal sucrase activity. These observations suggest that GH has greater differentiative actions, whereas IGF‐I exerts primarily mitogenic actions in small bowel.
Effect of an Elemental vs a Complex Diet on Polyamine Metabolism in Rat Isolated Enterocytes
Authors: Guihot Gwénaële , Colomb Virginie , Jobert‐Giraud Agathe , Morel Marie‐Thérèse , Corriol Odile , Duée Pierre‐Henri , Ricour Claude , Blachier François
Published: May 2008

Background: Polyamines play an important role in the proliferation and differentiation of enterocytes. Ornithine decarboxylase (ODC) is the rate‐limiting enzyme for polyamine biosynthesis. Elemental diets, providing easily absorbable nutrients such as free amino acids, are used in clinical practice to treat growth failure and malnutrition. They are very different from complex diets normally consumed. Little information is available about the influence of elemental diets on metabolic capacities of enterocytes. This study was undertaken in rats to assess the effects on polyamine metabolism of an elemental diet compared with a complex diet. Methods: Rats were fed the elemental diet (group ED) or the control diet (group C) for 14 days. The dietary intakes were isocaloric and isonitrogenous in groups C and ED. Villous enterocytes were then isolated and metabolic capacities or enzyme activities were assessed. Results: Both the enterocyte capacity to decarboxylate ornithine through ODC (measured in viable enterocytes) and ODC activity (measured in homogenates) were severely decreased in group ED. The polyamine content in enterocytes, however, was maintained at a similar level in both groups. This coincided with a decrease in the main enzymatic activity responsible for putrescine catabolism (ie, diamine oxidase activity) in group ED. Conclusions: Although nutrition manipulation was shown to alter polyamine biosynthesis in this study, the polyamine homeostasis was probably maintained at least in part, through down‐regulation of diamine oxidase. (Journal of Parenteral and Enteral Nutrition 21:259–265, 1997)
Stopping Enteral Feeding for Arbitrary Gastric Residual Volume May Not Be Physiologically Sound: Results of a Computer Simulation Model
Authors: Lin Henry C. , Van Citters Gregg W.
Published: May 2008

Background: During tube feeding, it is a common practice to check gastric residual volume frequently for indications of pathologic impairment of gastric emptying. The volume threshold standards for holding feedings are applied nonselectively, disregarding slowing of gastric emptying by nutrient‐triggered intestinogastric inhibitory feedback. We developed a computer simulation model considering this feedback to test the hypothesis that gastric residual volume increases with slower gastric emptying and faster formula delivery but reaches a plateau volume (equilibrium between input and output) at volumes commonly seen in the postprandial stomach. Methods: A computer simulation model using Microsoft Excel 4.0 calculated the cumulative gastric residual volume over time when the input volume into the stomach is 125 mL/h (endogenous secretions) + 0 to 125 mL/h (formula delivery rate) and the output volume out of the stomach is equal to gastric emptying rates that varied between 0% and 50%/h. The model simulated nasogastric feeding with nine different rates of gastric emptying and six different rates of formula delivery. Measurements consisted of the cumulative gastric residual volume at the end of each hour for a minimum of 48 hours. Results: (1) Gastric residual volumes 1.5 to 6 times the commonly applied “stop feeding” threshold volume of 150 mL are encountered at gastric emptying rates of 20% to 50%/h; (2) gastric residual volume stabilizes to a plateau of 225 to 900 mL between 3 and 13 hours after start of formula delivery at these rates; and (3) at 0% gastric emptying, gastric residual volume does not reach a plateau. Conclusions: At gastric emptying rates expected with nutrient‐triggered inhibitory feedback and at formula delivery rates common in nutrition support, gastric residual volume reaches a plateau rapidly and at volumes commonly encountered in normal postprandial stomachs. On the basis of the results of this model, the current practice of stopping enteral feeding when gastric residual volume exceeds an arbitrarily selected volume threshold may not be physiologically sound. Clinical studies are needed to verify this model. (journal of Parenteral and Enteral Nutrition 21:286–289, 1997)
Comparison of Bone Marrow Toxicity of Medium‐Chain and Long‐Chain Triglyceride Emulsions: An In Vitro Study in Humans
Authors: Beau Philippe , Mannant Paul Régis , Pelletier Daniele , Brizard André
Published: May 2008

Background: In this study, we evaluated the in vitro bone marrow toxicity of two lipid emulsions containing either long‐chain triglycerides (LCT) or a mixture of medium‐chain triglycerides (MCT) and LCT. Methods: Bone marrow cells were obtained from six healthy subjects and were cultured for 14 days after a 24‐hour preincubation with various concentrations (from 0 to 10 mg/mL) of LCT‐ and LCT/MCT‐based lipid emulsions. Results: Compared with controls (no preincubation with lipid emulsion), both lipid emulsions significantly inhibited by 50% to 70% colony formation of all the human bone marrow cells cultured from a triglyceride concentration of 0.5 mg/mL (p <.05). Erythroid burst‐forming unit (BFU‐E) formation was significantly more inhibited with LCT/MCT emulsion than with LCT emulsion (p <.05). The inhibition of granulocyte‐macrophage colony‐forming unit (GM‐CFU) and mixed granulocyte‐erythrocyte‐monocytemegakaryocyte colony‐forming unit (GEMM‐CFU) formation did not significantly differ with the two emulsions. Conclusions: Both LCT‐ and LCT/MCT‐based lipid emulsions strongly inhibit colony formation by human bone marrow cells. BFU‐E colony formation is more sensitive to LCT/MCT inhibition than to LCT. (Journal of Parenteral and Enteral Nutrition 21:343–346, 1997)
Insulin Resistance and the Alterations of Glucose Transporter‐4 in Adipose Cells From Cachectic Tumor‐Bearing Rats
Authors: Yoshikawa Takaki , Noguchi Yoshikazu , Satoh Shinobu , Doi Chiharu , Okamoto Takahide , Nomura Katsutoshi , Makino Tatsuo , Tsuburaya Akira , Matsumoto Akihiko
Published: May 2008

Background: Insulin resistance may play an important role in cancer cachexia; however, its mechanisms remain to be clarified. Methods: Cellular mechanisms of insulin resistance in tumor‐bearing rats (TBR) were investigated in isolated adipose cells by measuring 3‐O‐[14C]methyl glucose transport activity and glucose transporter‐4 (GLUT4) protein in low‐density microsomes at a basal state and in the plasma membrane at an insulin‐stimulated state. Results: The insulin‐stimulated glucose transport activity in adipose cells from TBR was significantly lower than that of control rats (CTR) (0.51 ± 0.25 and 2.27 ± 0.11 fmol/cell/min, respectively). The amount of GLUT4 in low‐density microsomes at a basal state and in plasma membrane at an insulin‐stimulated state was less in TBR than in CTR. Conclusions: These data suggest that the insulin resistance seen in the adipose cells of these tumor‐bearing rats was caused in part by both a decreased amount of GLUT4 protein in a basal state and a decreased translocation of GLUT4 in response to insulin stimulation. (Journal of Parenteral and Enteral Nutrition 21:347–349, 1997)
Advances in Nutrition and Gastroenterology: Summary of the 1997 A.S.P.E.N. Research Workshop
Authors: Klein Samuel , Alters David H. , Grand Richard J. , Levin Marc S. , Lin Henry C. , Mansbach Charles M. , Burant Charles , Reeds Peter , Rombeau John L.
Published: May 2008

Background: The 1997 A.S.P.E.N. Research Workshop was held at the annual meeting in San Francisco, on January 26, 1997. The workshop focused on advances in clinical and basic research involving the interface between nutrient and luminal gastroenterology. Methods: Presentations on the genetic regulation of gastrointestinal development, the molecular biology of small intestinal adaptation, the effect of nutrition support on intestinal mucosal mass, the relationship between nutrition and gastrointestinal motility, nutrient absorption, and gastrointestinal tract substrate metabolism were made by the preeminent leaders in the field. Results: The investigators presented an insightful analysis of each topic by reviewing data from their own laboratories and the published literature. Conclusions: This workshop underscored the important interactions between nutrition and luminal gastroenterology at the basic science, metabolic/ physiologic, and clinical levels. The integration of presentations from the different disciplines provided a unique interaction of information and ideas to advance our understanding of nutrition and gastrointestinal tract. (Journal of Parenteral and Enteral Nutrition 22:3–13, 1998)
Effect of Parenteral Medium‐ and Long‐Chain Triglycerides on Lymphocytes Subpopulations and Functions in Patients With Acquired Immunodeficiency Syndrome: A Prospective Study
Authors: Gelas Patrick , Cotte Laurent , Poitevin‐Later Françoise , Pichard Claude , Leverve Xavier , Barnoud Didier , Leclercq Pascale , Touraine‐Moulin Françoise , Trépo Christian , Boulétreau Paul
Published: May 2008

Background: Total parenteral nutrition (TPN) may offer significant clinical benefit in malnourished patients with acquired immunodeficiency syndrome (AIDS). However, the immunologic effect of parenteral lipids remains unknown in these severely immunodepressed patients. Methods: We undertook a prospective randomized double‐blind multicenter study comparing the effects of two IV lipid emulsions used during TPN: long‐chain triglycerides (LCT) or balanced emulsion of long‐ and medium‐chain triglycerides (LCT/MCT). Thirty‐three AIDS patients requiring TPN for wasting and reduced oral intake were allocated randomly to receive a ternary TPN mixture consisting of 1.5 g/kg/d proteins, 18 kcal/kg/d lipids, and 12 kcal/kg/d carbohydrates for 6 days. The following tests were performed at days 0 and 7: immunoglobulins, complement fractions, lymphocyte subpopulations count, and lymphocyte proliferation with mitogens. Results: Patients were all severely malnourished (weight loss: — 14.0 ± 1.3 kg). No clinical or biological differences were observed between the groups at baseline. At day 7, both groups reported a significant increase in weight. Patients in the LCT group exhibited a significant decrease in phytohemagglutinin A response (p =.04) compared with baseline. Patients in the LCT/ MCT group exhibited a lower level of IgM (p =.03) and a significant increase in C3 fraction (p =.03) compared with baseline. They also showed a tendency to have a higher CD4/CD8 lymphocyte ratio (p =.07), whereas other immunological parameters remained unchanged. Conclusions: Parenteral ternary mixture containing LCT or LCT/MCT are clinically well tolerated in AIDS patients over 6 days. With 2 g/kg/d of lipids, LCT seems to induce significant abnormalities in lymphocyte function. Such abnormalities are not observed with LCT/MCT. (Journal of Parenteral and Enteral Nutrition 22:67–71, 1998)
Urinary 3‐Methylhistidine Excretion: Association With Total Body Skeletal Muscle Mass by Computerized Axial Tomography
Authors: Zimian Wang  , Deurenberg Paul , Matthews Dwight E. , Heymsfield Steven B.
Published: May 2008

Background: The urinary excretion of endogenous 3‐methylhistidine (3‐MH) has been proposed as a predictor of skeletal muscle mass (SM). In this study, we report the relationship between 24‐hour urinary 3‐MH excretion and SM. Methods: Total body SM was measured by multiscan computerized axial tomography (CT) in a sample of 10 healthy adult men who followed a meat‐free diet for 7 days. 3‐MH was measured during the last 3 days of the meat‐free diet protocol on consecutive 24‐hour urine collections. Results: The 3‐MH excretion was 216.3 ± 44.7 μmol/d (mean ± SD) and was found well associated with SM (in kilograms), SM = 0.0887 × 3‐MH + 11.8; r =.88, p <.001. Compared with CT, the previous 3‐MH‐SM prediction equation suggested by Lukaski et al underestimated SM by an average of 8.9 kg in the 10 healthy men. This difference was caused by the Burkinshaw‐Cohn neutron activation model, which underestimated SM and was used as the reference in the Lukaski method. Conclusions: Twenty‐four‐hour urinary 3‐MH excretion can be applied for estimating SM in healthy adult men on a meat‐free diet. (Journal of Parenteral and Enteral Nutrition 22:82–86, 1998)
Parenteral Feeding Alters the Fatty Acid Composition of Serum Phospholipids of Rabbits
Authors: Moss R. Lawrence , Enomoto T. Miko , Haynes Allan , Fry Donald E. , Glew Robert H.
Published: May 2008

Background: Cholestatic liver disease develops in 30% to 70% of neonates receiving total parenteral nutrition (TPN). We analyzed the fatty acid composition of serum phospholipids from control and TPN‐fed rabbits to determine if TPN altered the fatty acid profile. Methods: Eleven male New Zealand White rabbits aged 9 to 11 weeks received TPN, whereas 11 other rabbits were offered standard laboratory rabbit chow ad libitum. After 14 days on the prescribed diet, serum samples were analyzed for their phospholipid fatty acid content by gas chromatography. Results: The proportions of palmitolenic (16:2n7), α‐linolenic (18:3n3), arachidic (20:0), and eicosaenoic (20:1n9) acids were significantly lower in the serum phospholipids of the TPN‐fed animals compared with the control group. The proportion of docosahexaenoic acid (22:6n3), a fatty acid that is critical to the development of the nervous system, was increased two‐ to threefold. Conclusions: The differences in proportions of fatty acids observed between control and TPN‐fed animals indicate that fatty acid elongation and desaturation pathways are perturbed in rabbits on TPN. (Journal of Parenteral and Enteral Nutrition 22:98–101, 1998)
Inorganic Phosphorus Reduces Hypercalciuria During Total Parenteral Nutrition By Enhancing Renal Tubular Calcium Absorption
Authors: Berkelhammer Charles , Wood Richard J. , Sitrin Michael D.
Published: May 2008

Background: Increasing the inorganic phosphorus content of total parenteral nutrition (TPN) formulas has been shown to decrease TPN‐induced hypercalciuria in experimental animals and humans. The mechanism of this effect, however, has been uncertain. Methods: By using a randomized cross‐over design, seven patients on cyclic TPN were given otherwise identical formulas providing either 15 or 45 mmol/d of inorganic phosphorus. Urinary calcium excretion, serum ultrafilterable calcium, filtered calcium load, fractional calcium excretion, urinary cyclic adenosine 5′‐monophosphate (cAMP), and serum levels of ionized calcium, parathyroid hormone (PTH), and vitamin D metabolites were determined at the end of each study period. Results: Urinary calcium excretion was significantly lower when the patients received the higher inorganic phosphorus formula. Increasing the inorganic phosphorus in the TPN formula did not change ultrafilterable calcium or filtered calcium load, but significantly reduced fractional calcium excretion. No differences in serum levels of ionized calcium, PTH, 25‐hydroxyvitamin D, 1,25‐dihydroxyvitamin D, or urinary cAMP were observed between treatments. Conclusions: These results demonstrate that increasing the inorganic phosphorus content of the TPN formula decreases urinary calcium excretion by increasing renal tubular calcium resorption. This effect is not due to alterations in the PTH‐1,25‐dihydroxyvitamin D axis, but likely reflects a direct action of inorganic phosphorus on the renal tubules. (Journal of Parenteral and Enteral Nutrition 22:142–146, 1998)
Review: The Role of Cytokines in the Catabolic Consequences of Infection and Injury
Authors: Chang Hernan R. , Bistrian Bruce
Published: May 2008

During infection and injury a series of metabolic events are activated that leads to a state of negative nitrogen balance and significant loss of lean body mass. This process is characterized by marked anorexia, net whole body protein breakdown, and liver anabolism. This host response initially is beneficial to the body because it helps it to fight disease and enhance healing. However, if such imbalance is maintained for long periods, it will invariably produce significant loss of lean body mass that may lead to a series of untoward clinical events. The role of the proximate cytokines, tumor necrosis factor (TNF), interleukin‐1 (IL‐1), and interleukin‐6 (IL‐6) as well as glucocorticoids as important mediators of many pathophysiological manifestations of infection and injury has been studied extensively. However, the involvement of other mediators, at least in skeletal muscle proteolysis during sepsis has been hypothesized, because blockade of glucocorticoids, TNF, IL‐1, and IL‐6 reduces but does not normalize protein breakdown rates nor does the direct application of these mediators to skeletal muscle in vitro enhance proteolysis. Furthermore other studies have suggested that the lymphokine, interferon‐gamma (IFN‐γ, type II interferon or immune interferon), produces fever and enhances thermogenesis, body weight loss, and skeletal muscle depletion in rodents in a manner similar to that seen with TNF and IL‐1. Cytokines appear to be major components of the host metabolic response during infection and injury. However, neither all the cytokines involved nor the exact mechanisms underlying their metabolic effects are completely understood. The regulation of muscle protein synthesis and breakdown, which largely determines the development of cachexia, appears to depend on the delicate balance between a number of regulatory substances including cytokines, glucocorticoids, catecholamines, insulin, and insulin‐like growth factors. (Journal of Parenteral and Enteral Nutrition 22:156–166, 1998)
Use of Intravenous Lipids in Critically Ill Patients With Sepsis Without and With Hepatic Failure
Authors: Druml Wilfred , Fischer Margot , Ratheiser Klaus
Published: May 2008

Background: Fat is the preferred energy fuel both in patients with sepsis and with hepatic failure. Thus lipid emulsions should serve as an ideal nutritional substrate in parenteral nutrition. However, previous studies have generated conflicting results on the utilization of artificial lipids in these disease states, and systematic studies in critically ill patients with combined organ dysfunctions and additional complications are lacking. We compared the elimination, hydrolysis, and oxidation of a 20% lipid emulsion in critically ill patients on respiratory support with sepsis and with sepsis plus hepatic failure and in healthy control subjects. Setting: Medical critical care unit of a university hospital. Subjects and Methods: Eight critically ill patients with sepsis, 8 patients with sepsis and decompensated chronic hepatic failure, and 10 healthy volunteers were investigated. Elimination and hydrolysis was evaluated during constant IV infusion of 4.5 mg · kg body wt−1 · min−1 of triglycerides during 120 minutes. Concentrations of plasma triglycerides, free fatty acids, and glycerol were measured, and elimination parameters were analyzed from plasma curves of triglycerides by using a two‐compartment model. Resting energy expenditure and substrate oxidation were measured by indirect calorimetry. Results: In patients with sepsis without and with hepatic failure the rise in plasma triglycerides was blunted and the clearance of triglycerides was enhanced by 20% and 40% (p < 05), respectively, compared with healthy controls. Basal free fatty acid concentrations were elevated, and the rise of free fatty acids and glycerol was comparable to healthy subjects. Energy expenditure was increased and lipid oxidation (as fraction of total energy expenditure) was slightly elevated in both patient groups; the rise in lipid oxidation during lipid infusion was comparable to controls. No side effects or impairment of gas exchange was seen. Conclusions: In a clinically relevant dosage range, the utilization of an IV lipid emulsion, the elimination and hydrolysis of triglycerides, and the lipid oxidation is not impaired in ventilated critically ill patients with sepsis or sepsis and chronic hepatic failure. Lipid emulsions thus are efficiently metabolized in critically ill patients with combined organ dysfunctions and associated sepsis. (Journal of Parenteral and Enteral Nutrition 22:217–223, 1998)
Growth Hormone Increases and IGF‐I Reduces the Response to Escherichia coli Infusion in Injured Pigs K UNNEBERG, L BALTESKARD, M MJAALAND, ET AL Eur J Surg 1997;163:779–788
Authors: Svanberg Elisabeth
Published: May 2008

The aim of the present study was to evaluate whether treatment with growth hormone or its main mediator insulin‐like growth factor I (IGF‐I) alters the response to infusion of E coli in injured pigs. The pigs underwent surgery (2.5 h) consisting of a midline thoraco‐laparotomy with dissection to place flow probes around the ascending aorta, portal vein, common hepatic artery and right renal and femoral arteries, and insertion of catheters into the pulmonary artery, jugular veins, carotid arteries and portal, hepatic right renal and right femoral arteries. Following surgery, one control group received an infusion of E coli for a total of 130 minutes and one control group received saline instead of the E coli infusion as a nonseptic control. One study group received GH as a bolus injection (16U) prior to the E coli infusion, and one group received IGF‐I as a constat infusion (1.3 mg/h). Hemodynamic measurements were performed, as well as blood chemistry measurements; blood gases, plasma concentrations of glucose, lactate, free fatty acids and alanine. GH treatment increased plasma concentration of free fatty acids and fat oxidation rates. IGF‐I treatment lowered blood glucose and reduced carbohydrate oxidation. Lactate concentrations were higher and arterial pH was lower in the septic animals than in nonseptic controls. In GH treated septic animals, Pco2 was higher and Po2 lower in aorta and portal vein while renal artery flow was reduced. Cardiac output was higher, and accompanied by higher heart rate and lower stroke volume in GH treated animals and septic controls as compared to IGF‐I treated animals. Noradrenaline concentrations were higher in the GH treated group than in the IGF‐I treated group, while dopamine concentrations were higher in the IGF‐I treated group, while dopamine concentrations were higher in the IGF‐I treated animals.
Gut‐Trophic Effects of Keratinocyte Growth Factor in Rat Small Intestine and Colon During Enteral Refeeding
Authors: Estívariz Concepción F. , Jonas Carolyn R. , Gu Li H. , Díaz Emma E. , Wallace Timothy M. , Pascal Robert R. , Farrell Catherine L. , Ziegler Thomas R.
Published: May 2008

Background: Keratinocyte growth factor (KGF) induces proliferation of gut epithelium in rat models, but KGFnutrient interactions have not been studied. An experimental model of fasting‐induced gut atrophy followed by different levels of enteral refeeding was used to investigate the influence of nutrient availability on the gut‐trophic effects of exogenous KGF. Methods: After a 3‐day fast, rats were enterally refed either ad libitum or at 25% of ad libitum intake for 3 subsequent days. Either intraperitoneal KGF (5 mg/kg/d) or saline was given in each dietary regimen. Wet weight, DNA, and protein content were measured as indices of full‐thickness cellularity in duodenum, jejunum, ileum, and colon. Villus height in small bowel segments and crypt depth in all gut tissues were measured as specific indices of mucosal growth. Results: Refeeding at 25% of ad libitum intake significantly decreased full‐thickness cellularity and mucosal growth indices in duodenum, jejunum, and ileum. In the colon, only protein content fell significantly and crypt depth was maintained. KGF administration during 25% refeeding did not alter full‐thickness indices in any small bowel segment or affect jejunal mucosal growth. In contrast, KGF normalized duodenal villus height (p <.01) and duodenal and ileal crypt depth (p <.05) only in the 25%refed model. KGF significantly increased ileal villus height in both ad libitum and 25%‐refed rats (by 43% and 48%, respectively, p <.05) and markedly increased colonic cellularity and mucosal crypt depth with both levels of refeeding (p <.01). Conclusions: Rat small bowel growth is more sensitive than colon to the level of enteral refeeding after a 3‐day fast. KGF administration does not affect jejunal growth, but specifically prevents atrophy of duodenal and ileal mucosa during hypocaloric, hyponitrogenous refeeding. In ileum and colon, some KGFmediated growth responses are independent of the level of enteral refeeding. Thus gut‐trophic effects of KGF and KGF interactions with the level of nutrient intake are tissue‐specific. (Journal of Parenteral and Enteral Nutrition 22:259–267, 1998)
Pharmacologic Levels of Heparin Do Not Destabilize Neonatal Parenteral Nutrition
Authors: Silvers Karen M. , Darlow Brian A. , Winterbourn Christine C.
Published: May 2008

Background: Calcium and heparin are known to destabilize the lipid emulsion of total parenteral nutrition (TPN). However, these observations were made over long periods of time, using 5 to 10 times the amount of heparin used in a neonatal intensive care unit. We investigated the effects of lower heparin concentrations with lipid‐to‐nutrient ratios normally administered to premature infants. Methods: Lipid emulsion stability was assessed over 30 minutes by measuring viscosity at 10 mmol/L calcium after the addition of 0, 0.5, 1, and 5 IU heparin/mL. This was done at a range of lipid‐to‐nutrient ratios in clinical use. The effect of varying calcium concentration and different multivitamin preparations on emulsion stability also was observed. Results: Heparin caused an immediate increase in viscosity of pure Intralipid 20% (Intralipid; Kabi Pharmacia AB, Stockholm, Sweden), which eventually separated into two phases. Although changes in viscosity were observed at 1:1 lipid‐to‐nutrient ratios, no effect was seen at a 1:9 ratio. With the 1:1 ratio, the multivitamin preparations, MVI Pediatric (Rhone‐Poulec Rorer, Montreal, Canada) and Vitlipid (Kabi Pharmacia AB), reduced the increase in viscosity. Conclusions: Heparin and calcium destabilize Intralipid. This is unlikely to cause problems for most infants receiving TPN, provided low heparin concentrations are used. In all cases, especially where the lipid ratio is high, the risk of the lipid phase separating out can be further minimized by (1) the addition of multivitamin preparations containing detergent or an emulsifying agent and (2) by having the shortest possible delivery tube between the point of mixing the lipid and amino acid solutions of TPN and entry into the infant. (Journal of Parenteral and Enteral Nutrition 22:311–314, 1998)
Effects of Xylitol on Urea Synthesis in Patients With Cirrhosis of the Liver
Authors: Pedersen Ellen , Hamberg Ole , Borg Birgit , Haaber Anne , Enemark Helle , Vilstrup Hendrik
Published: May 2008

Background: In individuals with cirrhosis the normal inhibiting effect of glucose on urea synthesis is lost, probably because of very high concentrations of glucagon. In agreement, glucose does not prevent the inducing effect of glucagon on urea synthesis in normal humans. In contrast, the sugar alcohol, xylitol, prevents the increasing effect of glucagon in normal humans. We, therefore, examined the effect of xylitol on urea synthesis in individuals with cirrhosis and hyperglucagonemia. Methods: Urea synthesis, calculated as urinary excretion rate corrected for accumulation in total body water and intestinal loss, was measured during infusion of alanine (2 mmol/[h·kg body wt]) and during infusion of alanine superimposed on infusion of xylitol (0.12 g/[h·kg body wt]) in 8 individuals with biopsy‐proven alcoholic cirrhosis. The functional hepatic nitrogen clearance (FHNC), ie, urea synthesis expressed independent of changes in plasma amino acid concentration, was calculated as the slope of the linear relation between the urea synthesis rate and the plasma amino acid concentration. Results: All individuals had elevated basal plasma glucagon concentration (261 ± 61 ng/L; mean ± SEM) and a markedly increased response to alanine infusion (1037 ± 226 ng/L). This was not changed by xylitol. Neither the basal urea synthesis rate (13.2 ± 2.5 mmol/h) nor the alanine‐stimulated urea synthesis rate (76.8 ± 3.64 mmol/h) was changed by xylitol. FHNC during the infusion of alanine alone was 10.5 ± 0.9 L/h and did not change during the concomitant infusion of xylitol (10.1 ± 1.1 L/h). Conclusions: Xylitol reduces neither urea synthesis nor FHNC. The data do not support an important role of xylitol as a nitrogen‐sparing agent in cirrhosis. (Journal of Parenteral and Enteral Nutrition 22:320–325, 1998)
Interrelationship Between Circulating Leptin Concentrations, Hunger, and Energy Intake in Healthy Subjects Receiving Tube Feeding
Authors: Stratton Rebecca J. , Stubbs R. James , Elia Marinos
Published: May 2008

Background: Tube feeding is an unphysiological route of nutrient delivery, and yet there is a lack of controlled trials examining its effects on appetite, food intake, and factors involved in their control. This study aimed to investigate the relationship between diurnal tube feeding, hunger, food intake, and circulating concentrations of leptin (a putative satiety factor). Methods: Six healthy lean men received a continuous nasogastric infusion (9:00 AM to 9:00 PM) of colored water (2 days), liquid feeding (4.2 kJ/mL, energy provision 1x the initial predicted basal metabolic rate; 3 days), and colored water (2 days). Measurements of hunger (visual analog scales), weighed food intake, and fasting circulating leptin concentrations were made while the subjects were allowed free access to isoenergetically dense food items. Results: Three days of diurnal nasogastric feeding (mean, 6.9 MJ/d) significantly increased total energy intake (to 19.4 MJ/d; p <.001; analysis of variance [ANOVA]), suppressing oral energy intake by only 17%, with no significant effect on mean daily hunger. Higher levels of energy intake led to a universal rise in circulating leptin concentrations (2.82 to 4.23 ng/mL; p <.004; ANOVA) that was not significantly related to subsequent breakfast energy intake, first rated hunger of the day, timing of morning food consumption, or subsequent mean daily oral energy intake or hunger. Conclusions: This study suggests that 3 days of diurnal tube feeding (equivalent to basal metabolic rate) failed to suppress hunger and reduced food intake by only 17%. The rise in circulating leptin concentrations, associated with tube feeding and the increase in total energy intake, failed to predict subsequent hunger or oral energy intake. (Journal of Parenteral and Enteral Nutrition 22:335–339, 1998)
Insulin Secretion and Sensitivity in Children on Cyclic Total Parenteral Nutrition
Authors: Lienhardt Anne , Rakotoambinina Benjamin , Colomb Virginie , Souissi Sihem , Sadoun Evelyne , Goulet Olivier , Robert Jean‐Jacques , Ricour Claude
Published: May 2008

Background: Some children receiving total parenteral nutrition (TPN) have abnormal glucose tolerance. Methods: Insulin secretion and sensitivity were studied in 12 patients, aged 5.7 to 19.4 years, receiving cyclic nocturnal TPN. Insulin secretion was measured during an IV glucose tolerance test (IVGTT; 0.5 g/kg) followed by a hyperglycemic clamp (plasma glucose at 10 mmol/L). Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamp (insulin infusion = 1 mU/kg/min). Results: Patients with normal glucose tolerance receiving TPN had an insulin response to IVGTT similar to that of normal children of the same age. Insulin levels of TPN patients were higher than those in healthy young adults during the hyperglycemic clamp. Whole body glucose disposal was greater in younger than in older children (range, 7.1 to 25.2 mg/kg/min), and this inverse correlation with age was statistatically significan (p <.01). Two patients with abnormal glucose tolerance showed a decreased capacity to release insulin, whereas insulin sensitiv ity was unchanged in one of these two patients. Two patients treated with prednisone or octreotide had insulin levels similar to those of normal TPN children. Conclusions: The insulin response to sustained hyperglycemia was stronger in children with norma glucose tolerance on cyclic TPN. Patients with a limited capacity to release insulin, either constitutional or acquired, may not be able to produce enough insulin in these conditions and develop glucose intolerance during TPN. Insulin sensitivity was not a key factor in the alteration of glucose tolerance. (Journal of Paren. teral and Enteral Nutrition 22:382–386, 1998)
A Comparison of Parenteral and Enteral Feeding in Neonatal Piglets, Including an Assessment of the Utilization of a Glutamine‐Rich, Pediatric Elemental Diet
Authors: Bertolo Robert F. P. , Pencharz Paul B. , Ball Ronald O.
Published: May 2008

Background: The amino acid requirement profile for infants is different than that for adults and needs to be established; this profile also is different for infants receiving total parenteral nutrition. We used the neonatal piglet as a model for the infant to address (1) the metabolic and physiologic changes due to route of feeding and (2) the adequacy of the amino acid pattern in a pediatric elemental diet. Methods: Diets differed only in their amino acid pattern (modified human milk [MHM] and a commercial pediatric elemental diet [PED]) and were fed continuously for 8 days. Control piglets were fed MHM diet via gastric catheters (IG) and were compared with pigs fed MHM diet via venous catheters (IV) or to pigs IG‐fed PED. Results: MHM‐IV piglets experienced enlarged livers and gut atrophy, and lower nitrogen retention and body protein content. Higher glutamine (and lower glutamate) in PED‐IG, compared with MHM‐IG, produced no apparent advantage with respect to gut growth or histology. Proline, histidine, and lysine may have been limiting, and isoleucine and valine excessive, in the PED‐IG diet as indicated by plasma concentrations, compared with sow‐fed piglets; however, imbalances in the amino acid profile were not excessive because nitrogen retention was not different between MHM‐IG or PED‐IG pigs. Conclusions: Therefore, the amino acid profile of MHM needs to be modified to improve nitrogen retention during parenteral feeding and the profile of oral PED could be improved to normalize plasma amino acid concentrations. (Journal of Parenteral and Enteral Nutrition 23:47–55, 1999)