Journal of Parenteral and Enteral Nutrition

This study evaluated the safety of triple vs single-lumen catheters in intravenous nutrition. Patients who were judged likely to benefit from a triple-lumen catheter were randomized to receive either a single-lumen catheter, with additional peripheral or central venous access as needed, or a triple-lumen catheter. All patients were at increased risk of catheter-related infection because of one or more of the following conditions: >60 years of age, breakdown of skin integrity, severe underlying illness, diagnosis of acute pancreatitis, recent head or neck surgery, or presence of a preexisting infection. Patients were excluded who had neutropenia, were immuno-suppressed, had body burns >40%, or had contaminated wounds in the subclavicular area. Of 204 patients entered between June 1989 and November 1991, 177 completed the required ≥7 days of therapy. Seventy-eight of these patients were randomized to a single-lumen catheter and 99 to a triple-lumen catheter. Catheters were inserted and maintained by the Nutrition Support Team. Dressings were monitored daily and changed weekly using a bio-occlusive dressing. When parameters were met for a possible septic episode, simultaneous peripheral and central catheter blood cultures were obtained using the Isolator method. Catheter-related sepsis was considered present if the colony count from a central catheter lumen was ≥5 times that of the peripheral blood. The incidence of catheter-related sepsis for single-lumen catheters was 2.6% (2 of 78) compared with 13.1% for triple-lumen catheters (13 of 99) (p < .01). No correlation was found with the number of insertion attempts, catheter days, or patient's age. We conclude that triple-lumen catheters should not be routinely used for intravenous nutrition because of an increased risk for central catheter-related sepsis. (Journal of Parenteral and Enteral Nutrition 16: 403-407, 1992)

The objective of this study was to evaluate body composition as measured by bioelectric impedance analysis using splints and body positions differing from the standard supine position. Forty-three patients, randomized into two groups of different body positions, and 101 healthy volunteers were prospectively studied. Resistance and reactance of body tissues were measured by bioelectric impedance analysis. Body composition is described by a three-compartment model composed of body fat, body cell mass, and extra cellular mass. The patients were measured in the standard supine position and then randomized into two groups. They were then remeasured with the appropriate splinting device or position change. Volunteers were measured in the standard supine position and all four alternative positions. There was a statistically significant difference demonstrated in whole body resistance, whole body reactance, body cell mass, and the ratio of extracellular mass to body cell mass in some body positions. The percentage of change with different body positions and splints, when compared with the standard supine position, was generally below 2%, a clinically insignificant difference. We conclude that the reliability of resistance and reactance as measured by bioelectric impedance analysis is clinically valid using any of the tested body positions and/or splints. The three-compartment model may be a useful concept to measure body composition changes in both healthy and sick persons. (Journal of Parenteral and Enteral Nutrition 16: 408-412, 1992)

Glutathione (GSH) is a potent endogenous antioxidant that protects major organs from oxidant injury. However, present nutrition regimens may inadequately support tissue stores of this tripeptide during critical illness. To determine whether GSH reserves can be enhanced in vivo with intravenous (IV) supplements, rats underwent central venous catheterization, were given chow and water ad libitum during a 2-day recovery period, and were then randomized to receive one of three treatments as an IV bolus: (1) dextrose, (2) glutathione (GSH), or (3) glutathione monoethyl ester. GSH monoethyl ester is transported into cells more easily than is GSH. Tissue and plasma samples were analyzed for GSH at 2 and 4 hours after drug administration. Liver, renal, and ileal mucosal GSH were significantly increased in the GSH-monoethyl ester rats compared with dextrose-treated animals. In addition, plasma GSH was dramatically increased after monoester injection. In contrast, GSH administration depressed liver GSH stores and did not significantly affect GSH concentration in the other organs analyzed. Plasma GSH concentration was elevated 2 hours after GSH administration. We conclude that: (1) the monoethyl ester of glutathione can be used in vivo to enhance tissue and plasma GSH concentration and (2) IV GSH administration does not significantly increase tissue GSH levels and may paradoxically depress hepatic GSH in normal rats. Because the malnourished and critically ill are likely to have depleted GSH stores, nutrition strategies that include the provision of GSH monoester may lend additional support to those organs that are at risk for injury from oxygen free radicals during catabolic states. (Journal of Parenteral and Enteral Nutrition 16:413-418, 1992)

The incidence of gastroesophageal reflux (GER) in critically ill patients as well as the effect of a nasogastric tube (NGT) and body position as risk factors for GER were determined. Seventy patients with orotracheal intubation receiving enteral nutrition through a NGT for more than 48 hours were prospectively studied with two randomly assigned body positions: supine or semirecumbent. Detection of GER was achieved by scintigraphy after labeling gastric contents with 500 μCi of technetium-99m sulfur colloid administered through the NGT. In 50 patients scintigraphy was performed after subjects had remained in the randomized position for 2 hours with the NGT pinched. Twenty additional patients were studied after the NGT had been removed.

In 50 patients with NGT, GER was present in 74% (37 of 50) and was higher in the supine position (81%, 21 of 26) than in the semirecumbent position (67%, 16 of 24), but this difference was not statistically significant (p = .26). In 20 patients without NGT, the incidence of GER was 35% (7 of 20) and it was also higher in the supine (50%, 6 of 12) than in the semirecumbent position (12%, 1 of 8, p = .16). There was a statistically significant difference between GER in patients with and without NGT (74% vs 35%, p = .0002). These data show that there is a high incidence of GER in patients with orotracheal intubation and NGT. The presence of a NGT is a risk factor for GER. Semirecumbency does not prevent GER, but there is less incidence than in the supine position. (Journal of Parenteral and Enteral Nutrition 16:419-422, 1992)

When given as a dietary supplement, arginine enhances lymphocyte mitogenesis and improves nitrogen balance. The purpose of this study was to evaluate arginine's ability to mediate these same effects when given as the sole nitrogen source with minimum additional calories. Thirty patients were randomized to receive 20 g/day arginine hydrochloride or a mixed amino acid solution (Travasol) by intravenous infusion for 7 days after abdominal operations. Mean patient age, body weight, gender ratios, and preoperative degree of weight loss were similar between groups. Mean plasma arginine and ornithine levels rose to 228 ± 50 μmol/L and 191 ± 76 μmol/L in the arginine group during infusion. Mean nitrogen balance was -8.8 g/day and -9.2 g/day in the arginine and Travasol groups, respectively. Mean lymphocyte stimulation indices to concanavalin A and phytohemagglutinin fell on postoperative day 1 in both groups. No significant differences in patterns of lymphocyte mitogenesis changes were noted between groups. The mean total number of circulating T cells increased in the arginine group at postoperative day 7. Thus, parenteral arginine infusion in postoperative patients provided comparable nitrogen balance to a balanced amino acid solution but did not increase peripheral blood lymphocyte mitogenesis. When arginine is given parenterally as the sole nitrogen source with minimal additional calories to postoperative patients, no enhancement of mitogen-stimulated lymphocyte proliferation could be demonstrated. (Journal of Parenteral and Enteral Nutrition 16:423-428, 1992)

Supplemental L-arginine has been shown to enhance thymic and T-cell responses in rodents. We examined the ability of supplemental dietary L-arginine to induce T-cell function in athymic nude mice that lack a normally developed T-cell system. Groups of male nude (nu/nu) mice (Balb/c background) 7 to 8 weeks old were given for 2 weeks 1.2% arginine hydrochloride solution for drinking, whereas controls received acidified tap water. All mice ingested a standard laboratory chow. In the first experiment, the arginine-supplemented animals had significantly greater number of T cells in the spleen (assessed by the number of Thy 1.2-positive lymphocytes) and these cells had enhanced mitogenic responses to mitogenic stimulation (phytohemagglutinin and concanavalin A). In vivo delayed-type hypersensitivity responses to 2,4-dinitro-1-difluorobenzene were also significantly increased after the 2 weeks of arginine supplementation. In a second experiment, mice maintained under the same conditions were skin grafted with rat tail skin. Animals were observed for 100 days for rejection but no significant difference was noted in skin graft survival. We conclude that dietary arginine can increase extrathymic T-cell maturation and function, but cannot induce in vivo allogeneic graft recognition in athymic nude mice. (Journal of Parenteral and Enteral Nutrition 16:429-432, 1992)

The production of short-chain fatty acids and ammonia was measured in 16.6% fecal homogenates from 50 subjects incubated at 37°C for 6 and 24 hours. All 50 homogenates produced ammonia and short-chain fatty acids of any chain length (C2-C5). Incubation for 24 hours with dietary fiber (ispaghula husk or wheat bran), albumin, or glucose (10 mg/ mL) increased the short-chain fatty acid production (43.6 ± 2.8, 45.4 ± 2.0, 60.3 ± 3.2, and 65.8 ± 3.1 mmol/L, respectively) compared with controls (21.4 ± 1.3 mmol/L). The degradation of different substrates was associated with the production of different amounts of ammonia and short-chain fatty acids. Ispaghula, wheat bran, albumin, and glucose were fermented to acetate (>2 mmol/L; 24-hour incubations) in 86%, 96%, 98%, and 98% of the homogenates, to propionate in 80%, 76%, 100%, and 68%, and to butyrate in 32%, 94%, 88%, and 54% of the homogenates, respectively. Isobutyrate, valerate, and isovalerate were produced from albumin in all (100%) of the homogenates, but only in 2 to 4% of the homogenates incubated with ispaghula or glucose. Ammonia was always (100%) produced after the addition of albumin and always (98%) consumed (assimilated) when glucose was fermented. Surgery (sigmoid or right- or left-sided colonic resection) did not change the pattern of ammonia and short-chain fatty acid production from these substrates.

This study suggests that the different colonic flora from a large number of subjects share general biochemical characteristics, which metabolize different substrates to specific patterns of ammonia and short-chain fatty acids. (Journal of Parenteral and Enteral Nutrition 16:433-439, 1992)

Male Sprague-Dawley rats housed in individual metabolic cages received total parenteral nutrients via chronic indwelling internal jugular catheters to determine whether supplementing parenteral nutrition with glutamine would accelerate recovery of small-bowel morphology after abdominal radiation. After recovering from catheter insertion for 3 days they received either 1000 cGy gamma radiation to the abdomen only or no radiation and immediately thereafter received iso-nitrogenous and isocaloric intravenous solutions containing either 0% or 2% glutamine at 1.58 mL/h for the next 5 days. Intestinal segments were then assayed for whole-bowel deoxyribose nucleic acid content and villus height. Irradiation caused a 40% decrement in these parameters, which were not restored by glutamine supplementation. Therefore, intravenous glutamine supplementation failed to accelerate recovery of small-bowel morphology in this model of combined surgical and radiation injury. (Journal of Parenteral and Enteral Nutrition 16:440-444, 1992)

The effect of meal ingestion (9 kcal/kg of body weight, 53% carbohydrate, 30% fat, 17% protein, as a liquid formula) on energy expenditure and oxidation rate of carbohydrate, fat, and protein was assessed by indirect calorimetry and urinary nitrogen excretion before and for 3 hours after eating in stable cirrhotic patients and control subjects of comparable age. Postprandial modifications of substrate and hormone levels were also studied. Compared with basal values, the mean ± SD resting energy expenditure during the first 3 hours after meal ingestion increased similarly in cirrhotic patients (+0.32 ± 0.12 kcal/min) and control subjects (+0.31 ± 0.08 kcal/min). Dietary induced thermogenesis was equivalent to 10% of the energy contained in the meal in both groups. Before eating, the carbohydrate oxidation rate was lower and fat oxidation higher in cirrhotic patients than in the control subjects. After eating, glucose oxidation increased whereas fat and protein oxidation rates were reduced in both groups. As a consequence the amount of fat oxidized in the postprandial period remained higher in cirrhotic patients than in the control subjects. After meal ingestion, serum glucose levels increased whereas plasma free fatty acid and glycerol levels decreased in both groups. The substrates, however, remained significantly higher in cirrhotic patients than in control subjects, despite the higher postprandial insulin increment in the patients group, thus suggesting the presence of insulin resistance. Because the postprandial glucose oxidation rate was normal, the low insulin-mediated glucose uptake observed in cirrhotic patients seems to reflect a defect in the nonoxidative disposal of the glucose ingested. These alterations in endogenous and exogenous nutrient use may account for the wasting in energy stores frequently observed in cirrhotic patients. (Journal of Parenteral and Enteral Nutrition 16:445-450, 1992)

This study was undertaken to clarify differences in the effects of lipid emulsions containing either long-chain or medium-chain triglycerides (MCT) on glucose metabolism during total parenteral nutrition (TPN). Glucose kinetics were assessed in beagle dogs using primed, constant infusions of [ ¹⁴C]- and [6-³H]glucose. The rate of appearance of glucose, the percent of VCO₂ derived from the oxidation of glucose, the rate of glucose oxidation, and the percent of glucose uptake oxidized were measured at the end of 72 hours of each of the two TPN regimens, ie, TPN in which soybean oil served as long-chain triglyceride comprising 40% of nonprotein calories (L-TPN), and TPN in which tricaprylin emulsion served as MCT (M-TPN). Glucose intake was 5.9 ± 0.5 mg/kg per minute in L-TPN and 5.8 ± 0.2 mg/kg per minute in M-TPN. There was no significant difference in the rate of glucose appearance between L-TPN and M-TPN. The rate of glucose oxidation was higher with M-TPN than with L-TPN (p <.05). Not only the percent of VCO₂ derived from the oxidation of glucose but also the percent of glucose uptake oxidized tended to be higher during M-TPN than during L-TPN. These findings suggest that the glucose metabolism of dogs receiving L-TPN is different from that of dogs receiving M-TPN. ( Journal of Parenteral and Enteral Nutrition 16:451-454, 1992)

One hundred and forty silicone catheters were inserted in 127 patients for long-term intravenous access with a cumulative follow-up time of 21,125 catheter-days (58 patient-years). Fifty-six patients had acquired immunodeficiency syndrome (AIDS); 44 were not AIDS patients and were receiving ambulatory home parenteral nutrition, whereas the remaining 27 did not have AIDS and were receiving home antibiotic therapy. Patients had a mean of 1.1 catheters inserted, and the rate of Hickman catheter-related sepsis was 0.18 per 100 catheter days or 0.6 septic episodes per patient year of treatment. Catheter-related sepsis was higher in AIDS patients (p < .01) and in patients receiving parenteral nutrition (p < .05) compared with those receiving antibiotic therapy. Prior catheter infection and AIDS were the most significant predictors of catheter infection (p < .01). Staphylococcus aureus was the most commonly isolated pathogen (61%) in AIDS patients. Fever (p < .001) and relative leukocytosis (p < .02) were the most common signs of infection. Only 14 infected catheters (37.8%) were salvaged by antibiotic therapy after the initial infection episode, and 6 of these catheters (42.9%) had recurrent multiple infections. In addition, inflammatory bowel disease was found to be a risk factor for venous thrombosis (p = .018). We conclude that because immunocompromised patients have a high risk of infection, catheter-related sepsis in these patients should be treated by catheter removal and antibiotics. (Journal of Parenteral and Enteral Nutrition 16:455-459, 1992)

Pediatric amino acid products contain lower concentrations of methionine and require the addition of L-cysteine HCl just before infusion. Reports of a potential interaction between cysteine and copper, a routine addition to parenteral nutrition solutions, have appeared in the literature. This study serially evaluated cysteine/cystine and copper concentrations pre- and postfilter (0.22 μm) in two parenteral nutrition formulations prescribed for normal fluid (NF) or fluid-restricted (FR) pediatric patients. Solutions were infused via a peristaltic pump in vitro for 24 hours. Pre- and postfilter samples were obtained immediately after the infusion began (time 0) and at 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours during the infusion. At 24 hours pre- and postfilter, cysteine/cystine were quantitated at 87.3% and 85% of the initial concentrations, respectively, for the NF solution and 92% and 91.5% for the FR solution. Pre- and postfilter copper was quantitated at 87.5% and 92.5% of the initial concentrations, respectively, for the NF solution and 88.2% and 95.2% for the FR solution. The 24 hour area under the curve for cysteine/cystine was 88.4% for the NF solution and 96.4% for the FR solution. For copper, the area under the curve for the NF solution was 99% and 96.7% for the FR solution. There was no visual evidence of incompatibility or precipitation. We conclude that copper-containing parenteral nutrition solutions with L-cysteine HCl added immediately before infusion are relatively stable after compounding and infusion over 24 hours. (Journal of Parenteral and Enteral Nutrition 16:460-463, 1992)

We studied 21 patients with Guillain-Barré syndrome who demonstrated multiple nutritional risk factors upon admission to an intensive care unit: ventilator dependence (71.4%), adynamic ileus (23.8%), significant weight loss in the 2 weeks before admission (53.0%), antecedent viral illness with gastrointestinal sequelae (43.0%), cranial nerve deficits impairing oral intake and gastrointestinal motility (60%), and depressed serum transferrin (85.7%). Patients are hypermetabolic and hypercatabolic because of endocrine, infectious, and inflammatory components of the disease. High-energy (40 to 45 nonprotein kcal/kg), high-protein (2.0 to 2.5 g/kg) nutrition support appears to exert a favorable effect on visceral protein repletion, nitrogen balance, and resistance to pulmonary infection. Immediate attainment of positive energy balance in these hypermetabolic patients, ideally assessed by indirect calorimetry and followed by high-energy, high-protein feedings, may promote positive nitrogen balance early and attenuate muscle wasting in Guillain-Barré syndrome. (Journal of Parenteral and Enteral Nutrition 16:464-472, 1992)

A simple and noninvasive method to redirect malpositioned Silastic central venous catheters is described. A syringe is connected to the catheter hub, and burst injections of saline cause the tip of the catheter to flip into the correct intravascular position. The present technique has been applied to more than 30 pediatric patients with excellent results. A detailed description of the technique and case examples are presented. (Journal of Parenteral and Enteral Nutrition 16:473-476, 1992)

Rapid advances in molecular biology have yielded important new techniques for understanding the cellular mechanisms of normal homeostasis and disease. In particular, molecular laboratory methodologies have become important investigative tools for nutritional studies. Detection techniques for specific DNAs, RNAs, and proteins allow direct examination of cellular regulation of protein expression in health and illness. Construction of transgeneic models by recent techniques of inserting foreign genes into experimental animals has provided novel models for studies of cellular metabolism. In addition, molecular biology has had impact on clinical nutrition and therapy. Molecular techniques not only allow for early diagnosis of many inborn genetic errors of metabolism, recombinant technology has also provided for large-scale production of proteins and hormones of potential therapeutic value. The possibility for direct gene therapies is also nearing reality. Hence, understanding the language of molecular biology and the recent developments in this field is not only of research interest, but is also of clinical relevance.(Journal of Parenteral and Enteral Nutrition 16:477-486, 1992)

Several investigators, including the authors, have demonstrated that patients receiving long-term total parenteral nutrition (TPN) have low plasma choline levels.^1-3 In the present study, 15 patients who were receiving home TPN were randomly chosen from a group of long-term TPN patients found to have low levels of plasma free choline on initial screening.³

The patients received TPN for 7.0 ± 1.1 years (range, 1.5 to 12.5 years). Their TPN consisted of 2 to 3 liters of 15% to 25% dextrose solution with 3.5% to 4.25% amino acids, electrolytes, trace elements, and vitamins. Patients received 20.1 ± 2.2 kcal/kg per day actual body weight. Parenteral lipid supplied was 22 ± 5% of daily intravenous caloric intake (Intralipid 20%, Kabi-Vitrum, Alameda, CA).

Patients received either lecithin supplementation (20 g/12 hours in 2.5 tablespoons of soybean oil-based liquid) or placebo (2.5 tablespoons of oil) for 6 weeks in a double-blind fashion. Patients were evaluated at baseline and at 2 and 6 weeks. Laboratory measurements included plasma and red blood cell free choline, plasma and red blood cell phospholipid-bound choline, transaminases, alkaline phosphatase, bilirubin, cholesterol, high and low density lipoproteins, carnitine (total and free), and methionine. Free and phospholipid-bound choline levels were measured in bottles of Intralipid. Liver imaging was carried out by computed tomography (CT) scanning. Limited noncontrast CT scans of the liver and spleen were performed at 120 kV, 120 mA with a 3.0-second scan time. Multiple representative sections were examined and a mean CT number in Hounsfield units was determined by two methods, determination of the mean absolute liver CT number and the liver spleen differential, obtained by subtracting the average spleen CT number from the average liver CT number to correct for interscan variability. Data were analyzed statistically by comparing percent changes in blood tests at 2 and 6 weeks and absolute changes in Hounsfield units.

The full 6-week study was completed in 10 of the 15 patients. Eight of 15 subjects had fatty livers at baseline. Lecithin supplementation led to an increase in plasma free choline of 53.4% ± 15.4% at 2 weeks (p < .04), whereas the placebo group had no change at 2 weeks. A significant (p < .02) decrease in liver fat, indicated by the change in Hounsfield units was seen at 2 weeks in the lecithin-supplemented group (7.5 ± 1.7 units). No significant changes were seen in the placebo group.

The authors concluded that hepatic steatosis in many patients receiving long-term TPN is caused by plasma free choline deficiency and may be reversed with lecithin supplementation.

The purpose of this study is to document the effect that various definitions of diarrhea have on its reported incidence in tube-fed patients. Following a group of 29 patients who were tube-fed for at least 5 days (median duration of feeding, 13 days), the investigators prospectively monitored the occurrence of diarrhea according to each of eight definitions: ≥1, ≥2, ≥3, ≥4 liquid stools/ day; ≥3 stools/day; ≥4 stools/day; ≥4 stools/day for 2 days; and ≥5 stools/day. None of the definitions incorporated measurements of either stool weights or volumes. Because treatment with antibiotics and the presence of hypoalbuminemia have been associated with diarrhea in some reports, the investigators took those into account. Sixty-six percent of the patients (19 patients) were treated with antibiotics and only 7% (2 patients) had serum albumin levels <26 g/L; the mean serum albumin level of the remaining 27 patients was 34 g/L. Only 10% (3 patients) were in critical care units. Because duration of monitoring would be expected to correlate positively with incidence, and is often not reported in studies of tube-feeding-associated diarrhea, the authors reported both the incidence of diarrhea and the percent of days with diarrhea. It is also noteworthy that 31% (9 patients) of the patients received kaolin-pectin for treatment of diarrhea, which probably affected the percent of days with diarrhea.

The more lenient definitions of diarrhea resulted in higher incidence rates and higher percentages of days with diarrhea. The most lenient definition (≥1 liquid stool/day) was associated with an incidence rate of 72%, and 26% of days with diarrhea, whereas the most rigorous definitions (≥4 liquid stools/day and ≥5 stools/day) resulted in 21% incidence and 1.7% of days with diarrhea. The number of days patients were monitored correlated positively with the incidence of diarrhea, but very weakly with the percent of days with diarrhea. Thus, the use of percent of days with diarrhea as the method of reporting reduced the effect of varying durations of monitoring. Antibiotic treatment correlated positively with percent of days with diarrhea, but not with incidence. Serum albumin levels did not correlate with diarrhea, but this may have been caused by the largely normal albumin levels in this population.

The aims of this study were: (1) to investigate the effect of an intravenous infusion of the dipeptide glycylglutamine on organ fluxes of amino acids in postabsorptive and briefly starved human subjects and (2) to investigate the effect of starvation on the metabolism of glycylglutamine. Studies were carried out on 17 male subjects who were matched for age and weight. The postabsorptive group (N = 8) was fasted overnight (12 to 14 hours), whereas the briefly starved group (N = 9) was fasted for 84 to 86 hours before the experiment. On the day of the experiment, all subjects underwent catheterization of the hepatic, renal, right femoral, and antecubital veins and the right and left femoral arteries. During a 30-minute equilibration period, primed, constant infusions of indocyanine green dye and p-aminohippurate were begun to assess hepatic, muscle (right lower extremity), and renal plasma flow. After a 45-minute saline infusion control period, the dipeptide glycylglutamine (100 μmol/kg per hour) was infused during a 120-minute experimental period. Blood was sampled every 15 minutes during the study, and plasma concentrations of the dipeptide and individual amino acids were determined. At the end of each experiment, urine was collected for dipeptide and amino acid analysis. The arterial concentration of glycylglutamine reached a steady-state level after 60 minutes of infusion. Amino acid and dipeptide balances across organs were calculated as the product of the arterial-venous concentration differences and the respective plasma flow. A negative balance indicated net release; a positive balance indicated net uptake.

The arterial concentrations of glycylglutamine during the experimental period were similar in both postabsorptive and starved subjects (265 ± 18 and 241 ± 13 μmol/ L, respectively). The infusion of glycylglutamine resulted in significantly increased arterial concentrations of glycine and glutamine in both postoperative and starved subjects. Less than 1% of the glycylglutamine infused into postabsorptive and starved subjects was recovered in urine. Starvation had no effect on organ plasma flow to the lower extremity, kidney, or splanchnic bed. Starvation decreased renal clearance of glycylglutamine approximately 45% us the postabsorptive group but did not have an effect on muscle and splanchnic tissue clearance. Focusing on the lower extremity (muscle bed), the infusion of glycylglutamine in the postabsorptive patient abolished net glycine release (—6 ± 2 to 3 ± 2 μmol/min) and increased net uptake of serine (3 ± 0.4 to 5 ± 0.9 μmol/min). Infusion in the starved patient decreased net muscle release of glutamine, glycine, alanine, and serine (-17 ± 2 to -12 ± 2, -7 ± 1 to -3 ± 0.4, -27 ± 3 to -23 ± 2, and -3 ± 0.7 to -2 ± 0.4 μmol/min, respectively) compared with the saline control period. Focusing on the kidney, starvation increased net uptake of glutamine (41 ± 5 to 79 ± 1 μmol/min) and increased net production of glutamate (-18 ± 3 to -32 ± 5 μmol/min). The infusion of glycylglutamine in starved subjects significantly decreased net glutamine uptake (-79 ± 1 to 17 ± 9 μmol/min) in the kidney, which became a net producer of glycine (5 ± 4 to -30 ± 4 μmol/min). Focusing on the splanchnic bed, starvation significantly increased net uptake of glycine, serine, threonine, methionine, isoleucine, and leucine and increased net splanchnic release of glutamate. In'the postabsorptive subject, the infusion of glycylglutamine markedly increased the net uptake of glutamine and glycine (71 ± 9 to 141 ± 16 and 16 ± 5 to 33 ± 5 μmol/min, respectively). There was a similar trend in starved patients, although the magnitude of the change was less. During starvation, net alanine uptake did not increase significantly (104 ± 18 to 132 ± 12 μmol/ min), and the infusion of glycylglutamine did not affect net alanine uptake. The infusion did increase net uptake of serine and threonine in the postabsorptive subject (22 ± 4 to 31 ± 5 and 14 ± 2 to 19 ± 2 μmol/min, respectively) but had no similar effect on the starved subject.