Journal of Parenteral and Enteral Nutrition

Background: It was hypothesized that energy intake in hospitalized elderly patients could be improved by increasing the density of energy of the food and that the volume of food actually consumed, even with a higher energy content than the normal, would not change with servings of high energy-dense hospital food. Methods: Thirty-six elderly patients (52 to 96 years) of both sexes, long-term treated at two comparable wards, participated in this study. The patients were given 6 weeks of regular hospital food (RHF, 1670 kcal/d, 7.0 MJ) and 6 weeks of high-energy food (HE, 2520 kcal/d, 10.5 MJ). The volume of food was kept constant. A crossover study design was used. Food intake, energy intake, body weight, and modified functional condition (Norton scale) were measured. Results: Regardless of type of food (RHF or HE) and time of day (lunch or dinner), the food portion size (volume of food) intake was the same, approximately 80% of the portions consumed. HE led to a 40% increase in energy intake (from 25 ± 1 during RHF to 35 ± 2 kcal/kg/d, p < .0001), which resulted in a 3.4% increase in body weight (p < .001) after 3 weeks of HE. Only minimal changes in functional condition were found. The cost of HE was substantially lower (-85%) than any other mean available for improvement of energy intake. Conclusions: A significant increase in energy intake can be achieved by higher energy density in regular hospital food and that HE does not cause a decrease in the volume of the food consumed. These findings suggest that it is the volume of food rather than the energy that limits voluntary energy intake of hospital food in elderly hospitalized patients. (Journal of Parenteral and Enteral Nutrition 20:93-97, 1996)

Background: Although it has been reported that total parenteral nutrition induces an increased intestinal permeability and a decreased mucous gel layer covering the intestinal epithelium, the role of mucous gel on intestinal permeability has not been well understood. We examined the in vivo effects of N-acetyl cysteine (NAC) as mucolytic agent and colchicine as suppressant of the mucus production on the intestinal transmission of fluorescein isothiocyanate dextran 70,000 (FITC-dextran). Methods: Rats were divided into four groups. In each group, FITC-dextran (750 mg/kg) with or without NAC (3000 mg/kg) was injected into the small intestinal lumen 3 hours after intraperitoneal injection of saline or colchicine (Col, 10 mg/kg). Thirty minutes after injection of FITC-dextran, blood samples were taken from portal vein to analyze plasma fluorescein concentration by fluorescence spectrometry. Samples of small intestine were sectioned in a cryostat for fluorescence microscopy, and the identical sections were stained by periodic acid-Schiff reaction. Results: Plasma FITC-dextran level in NAC group was higher than that in control group (p<.01), that in Col+NAC group was higher than that in Col group (p < .01) and that in Col + NAC group was higher than that in NAC group (p < .05). The spaces between villi were filled with mucous gel in the control and Col groups, whereas those were not entirely filled with mucous gel in NAC and Col + NAC groups. FITC-dextran and mucous gel showed complementary distribution in all rats. The villous interstitial edema was recognized in NAC group and the villi were disrupted in Col + NAC group. Conclusions: These results suggest that intestinal permeability is possibly affected not only by the mucous gel covering the intestinal epithelium but also by mucus release from goblet cells of the small intestine. (Journal of Parenteral and Enteral Nutrition 20:98-104, 1996)

Background: The purpose was to analyze changes in the mandible and the forearm bone mineral content and oral state in patients on home parenteral nutrition due to short bowel syndrome in relation to the bone mineral values and oral findings in a normal population. Methods: The bone mineral content was measured by dual-photon absorptiometry and the dental and periodontal state were studied in 15 adults patients (12 women, and 3 men, aged 26 to 65 years). All patients were on free oral intake as a supplement to the parenteral nutrition. Results: Forty-seven percent of the patients (2 males, 2 young and 3 elderly females) showed mandibular osteoporosis (Z-scores < -2.00), and all young females showed Z-scores < 0. Moreover, 34% of the patients showed osteoporosis in the forearm bones (Z-scores < -2.00) and also radiographic signs of osteoporotic fractures of the columna. The dental and the periodontal state in the patients did not differ clearly from that of the normal Danish population of the same age. Conclusions: Such patients seem to have a high risk of developing systemic osteoporosis, including the jaws, but apparently do not show a higher risk for deterioration of the dental or periodontal state than age-matching normals from the same population. (journal of Parenteral and Enteral Nutrition 20:105-109, 1996)

Background: Fat and water soluble vitamins are an essential part of IV nutrition (IVN). However, they are unstable in solution and may adhere to the bags and tubing containing the IVN. This study has examined the safety and side-effect profile of mixed micelles (mixed bile-salt lecithin micelles) used to solubilize water and fat soluble vitamins for IV administration. Methods: Two groups of six healthy male subjects received either placebo or mixed micelles daily for 5 days by IV infusion in a randomized crossover design with a 9-day washout period separating the two treatment periods. Results: Infusion of mixed micelles resulted in a significant increase in serum glycocholic acid from a median of 26.5 μg/dL (interquartile range 18 to 38) to 115 μg/dL (70 to 155) postinfusion. Glycocholic acid may have a lytic effect on cell membranes ; however, in this study there was no evidence of hemolysis or increase in serum transaminases during mixed micelle infusion. There was no increase in reported side effects during mixed micelle infusion compared with placebo. Conclusion: Mixed micelles can be used safely for the solubilization of fat- and water-soluble vitamins and drugs that are to administered by IV injection. (Journal of Parenteral and Enteral Nutrition 20:110-112, 1996)

Background: Home parenteral nutrition (HPN) requires intensive medical case management by practitioners with expertise in the provision of nutrition support. There is expenditure of considerable time and resources for management of these patients not covered by any of the traditional reimbursement mechanisms. The costs associated with this unreimbursed input and follow-up are most often borne by the Nutrition Support Team or individual practitioners. Reimbursement by home care agencies to physicians for management of patients after discharge cannot be done because this may be construed as a "kick-back" for referral of patients to particular home care agencies. Methods: Time and costs associated with management of HPN patients after discharge from the hospital were assessed using a cost-identification analysis of 24 different factors. Daily activity logs were kept by the Nutrition Support Team members over a 2-week period. Costs of space and furnishings were calculated. Results: On average, a total of 25 h/d was spent by members of the Nutrition Support Team on our HPN patients. Variable activities accounted for 5640.1 hours of time with fixed support at 890.3 hours. This computes to a total annual personnel cost of $168,482 ($1982 per patient). If costs of furnishings and space are also included, the overall cost of all resources was $175,989 per year or $2070 per patient. Conclusion: Significant and currently nonreimbursed costs are involved in HPN patient management. These costs are most often absorbed by the Nutrition Support Team and should be considered when evaluating total costs of HPN. (Journal of Parenteral and Enteral Nutrition 20:113-119, 1996)

Background: The effects of abrupt discontinuation and tapering of total parenteral nutrition (TPN) on glucose concentration were compared in patients < 3 years of age. Methods: Serial glucose concentrations were measured over 120 minutes after abrupt discontinuation as compared with tapering (decreasing infusion rate by 50% for 1 hour before discontinuation). Serial insulin concentrations were measured after abrupt discontinuation. Results: There was a significantly greater decrease in glucose concentration from baseline at 30 minutes after abrupt discontinuation as compared with tapering. Fifty-five percent (6/11) of the patients developed hypoglycemia (glucose concentration < 40 mg/dL) after abrupt discontinuation. Age, glucose infusion rate, and serum insulin concentrations were not predictive of the development of hypoglycemia. The tapering regimen did not prevent hypoglycemia, which developed in 20% (2/ 10). Conclusion: The high incidence of hypoglycemia after TPN discontinuation in children < 3 years of age requires monitoring of serum glucose concentration when initiating intermittent TPN until tolerance is documented. (Journal of Parenteral and Enteral Nutrition 20:120-122, 1996)

Background: We previously described a patient on home parenteral nutrition (HPN) who developed glucose intolerance and neuropathy that only responded to an infusion of chromium. A patient on HPN who had neuropathy and glucose intolerance was studied. He was also on metronidazole, which could have caused the neuropathy, but the symptoms and signs persisted. Methods: Baseline clinical examination, nerve conduction studies, serum vitamin and trace element levels, and glucose tolerance were measured. Then, 250 μg of trivalent chromium as the chloride salt was infused daily for 2 weeks. The above studies were repeated. Results: The patient at baseline had peripheral neuropathy of the axonal type and was glucose intolerant. Serum chromium was raised in this patient above the reference range. Despite raised serum levels, the infusion of chromium resulted in clinical remission that was marked 4 days after starting the infusion. Normalization of nerve conduction also occurred within 3 weeks of the initial study. Conclusions: Neuropathy and glucose intolerance may occur despite increased serum chromium levels and respond to chromium infusion. The previous use of drugs such as metronidazole should not exclude chromium as a potential treatment for neuropathy in HPN patients. (journal of Parenteral and Enteral Nutrition 20:123-127, 1996)

Background: The importance of L-glutamine as metabolic fuel for enterocytes and its role in prevention of mucosal atrophy during total parenteral nutrition is well documented. No data are available to date that document whether a glutamine-free complete enteral diet, requiring full energy expenditure for hydrolysis and absorption, is associated with changes in the morphology and function of the small intestine. Our aim was to examine the effect of such a diet during a 4-week period on the morphology and function of the small intestine of rats. Methods: Three isocaloric solid rat food, containing 0%, 4%, and 8% of glutamate, respectively, were fed to three groups of rats. On the 7th and 28th days the morphology of the jejunum, the subcellular structure of enterocytes on transmission electron microscopy, enzyme activities, blood, and muscle glutamine were examined and compared in the three groups. Results: The rats on the glutamine-free diet had significantly lower mucosal wet weight, protein and DNA content, and number of intraepithelial lymphocytes on the 7th day, whereas the number of mitoses in the Lieberkuhn's crypts was significantly less on the 28th day. The height of the enterocytes and villi was 20% higher on average in the glutamine-free group. Electron microscopy revealed either early (swelling of cristae) or terminal (swelling of matrix) mitochondrial degenerative changes, homogenization of apical cytoplasm, and degeneration and fragmentation of microvilli with loss of their rootlets. The Na⁺,K⁺-ATPase activity was markedly decreased in the glutamine-free group compared with that of the other groups, most likely because of a diminished energy supply. Among brush border membrane enzymes, lactase activity decreased markedly (p < .05) in the first week. The glutamine-free diet resulted in an increase of the lung glutamine synthetase activity and decrease in muscle glutamine content by the 28th day of the diet. Conclusions: Our study shows for the first time that a complete enteral diet, deficient only in glutamine, is associated with significant early morphologic and functional changes in the small intestine. The precise effect on intracellular events and the time of onset of these changes needs to be clarified in the future. (Journal of Parenteral and Enteral Nutrition 20:128-134, 1996)

Background: Muscle protein synthesis rate is known to decrease postoperatively as a part of the catabolic response to trauma. Conventional total parenteral nutrition (TPN) in the postoperative period does not seem to counteract the decrease in protein synthesis. However, it is still unclear if ongoing TPN given continuously after surgery would inhibit this fall in muscle protein synthesis. Methods: The rate of protein synthesis in skeletal muscle was determined before and 24 hours after open cholecystectomy, used as a standardized human model of trauma. Patients (n = 14) were randomized to receive either TPN continuously throughout the postoperative period or saline as postoperative fluid therapy. The protein synthesis rate was calculated from the increase in enrichment of labeled phenylalanine in protein after an IV flooding dose of [²H₅] phenylalanine, 45 mg/kg body weight. Results: The fractional synthesis rate decreased by 31% from 1.74 ± 0.13% to 1.15 ± 0.10% per 24 hours in the saline group ( p < .02) and by 23% from 1.59 ± 0.10% to 1.22 ± 0.07% per 24 hours in the group receiving TPN (p < .01), showing no significant difference between the two groups. Conclusion: A continuous and ongoing infusion of conventional TPN started immediately after surgery did not counteract the obligatory decline of muscle protein synthesis, observed 24 hours postoperatively. (journal of Parenteral and Enteral Nutrition 20:135-138, 1996)

Background: Xylitol exerts a nitrogen-sparing effect in stress catabolic states with hyperglucagonemia, but the mechanism(s) is unknown. We examined the effects of xylitol on urea synthesis during physiologic glucagon concentrations and during hyperglucagonemia. Methods: Urea synthesis was measured independently of blood amino acid concentration by means of functional hepatic nitrogen clearance (FHNC) (ie, the linear slope of the relation between urea synthesis rate and blood α-amino nitrogen concentration during infusion of alanine). FHNC was measured on four separate occasions in each of seven healthy subjects: during constant infusion of alanine alone, alanine superimposed on a constant infusion of xylitol (blood xylitol 1 mmol/L), alanine superimposed on infusion of glucagon, and alanine superimposed on infusions of xylitol and glucagon. Results: During alanine infusion alone, plasma glucagon rose to -170 ng/L, and FHNC was (mean ± sem) 27.9 ± 1.3 L/h. Xylitol did not affect plasma glucagon and only moderately reduced FHNC to 24.3 ± 1.0 L/h (p < .05). Glucagon infusion increased plasma glucagon to -450 ng/L and FHNC twofold to 50.9 ± 6.2 L/h; this increase was totally prevented by the addition of xylitol that reduced FHNC to 27.4 ± 2.6 L/h (p < .01). Conclusions: The results show that xylitol only inhibited FHNC minimally during spontaneous glucagon levels. In contrast, xylitol completely inhibits the increase in FHNC by glucagon. This suggests that the mechanism whereby xylitol reduces nitrogen loss in stress catabolic conditions with hyperglucagonemia involves an effect on liver metabolism. The mechanism is unknown but may be related to depletion of hepatocyte adenine nucleotides. (Journal of Parenteral and Enteral Nutrition 20:139-144, 1996)

Background: Both epidemiologic and in vitro studies have indicated the inverse correlation between intake and/or blood concentrations of different carotenoids, retinol, and tocoferol with different chronic and degenerative disturbances (cancer, cardiovascular diseases, cataracts, aging). The purpose of this study was to determine the fat-soluble vitamin and carotenoid levels in men with recently diagnosed cancer of the larynx (n = 51) who had undergone total or partial laryngectomy and compare them with those of an age- and sex-matched control group (n = 51). In addition, the effects of commercial enteral formula feeding were assessed in a subgroup of these patients (n = 35). Methods: A validated high-performance liquid chromatography method was used to determine the concentrations of six carotenoids (lutein, zeaxanthin, β-cryptoxanthin, lycopene, α-carotene, and β-carotene), retinol, and α-tocopherol in serum. Commercial, rather than blender prepared, enteral formulas were supplied to the patients as the only food source for an average period of 12 days. The statistical analysis was based on non-parametric methods (Mann-Whitney and Wilcoxon). Results: The levels of all compounds analyzed were significantly lower in men with laryngeal cancer than in the control group. Retinol and tocopherol increased significantly after enteral formula feeding, although they continued to be significantly lower than those of the controls. The carotenoid levels decreased after enteral nutrition. Conclusions: The retinol and carotenoid concentrations should be monitored on a routine basis in these patients because of their relationship to this type of cancer. Moreover, it would be of interest to assess the effects of the addition of carotenoids to enteral formulas because they may offer protection from oxidative damage and potentiate the immune system. (journal of Parenteral and Enteral Nutrition 20:145-149, 1996)

Background: Small bowel motility during enteral nutriton (EN) remains poorly known. Our aim was to compare, in six healthy volunteers, the duodenojejunal motor patterns after a 750-kcal meal either ingested or infused intraduodenally at two different infusion rates: 2 kcal/min for 6 hours (6-hour EN) or 1 kcal/min for 12 hours (12-hour EN). Methods: In each volunteer, the three manometric studies were carried out in a random order with an interval of ≥ 1 week between each recording. Number of phase III (PIIIs), their characteristics, number of waves (NW), and area under the curve (AUC) were determined. Results: PIIIs were interrupted by each type of nutrition in every volunteer. In five of six during 6-hour EN and in six of six during 12-hour EN, the first PIII returned before the end of EN. The mean duration of the fed pattern was similar in the three studies. During the interruption of PIIIs after oral meal, duodenojejunal motility was characterized by uninterrupted random contractions. By contrast, in four of six during the 6-hour EN and in five of six during 12-hour EN, it was organized as regular short bursts of contractions separated by motor quiescence. In all studies during the disruption of PIIIs, NW and AUC values decreased progressively with time and were higher at the jejunum level than in the duodenum (p < .001). However, at each level of recording, NW and AUC values were similar in the three types of feeding. After the return of PIIIs, the number, duration, and propagation velocity of PIIIs, NW, and AUC values were similar in the three studies. Conclusions: EN interrupts PIIIS, but, in most cases, PIIIs reappear before the end of EN. During the interruption of PIIIs, the organization of the contractions is qualitatively different from the fed pattern observed after oral feeding. For the same caloric value of the meal, the quantitative duodenojejunal motor response is not affected by the infusion rate, and the more important jejunal, rather than duodenal motor response found after an oral meal, is observed during EN. During EN, after the return of PIIIs, despite the persistence of a nutrient infusion into the duodenum, the small bowel motor patterns are not qualitatively or quantitatively different from those recorded in fasting subjects. (journal of Parenteral and Enteral Nutrition 20:150-155, 1996)

Background: Chronically implanted catheters often become covered with a thin, white adherent covering of tissue that has been referred to as a fibrin sheath. This tissue often interferes with catheter function. Methods: To chronicle the development of this sheath, rats were implanted with silicone rubber central venous catheters. Five rats were euthanized at 3, 7, and 60 days postimplantation so that gross necropsy and histology could be performed on the catheterized vessels. Results: The coating that developed around the external portion of the catheter started as a dark red thrombus containing fibrin and progressed into vascularized, fibrous connective tissue. Conclusions: The translucent to white sheath that forms around chronically implanted catheters is not composed of fibrin and is therefore not likely to be dissolved by fibrinolytic agents such as urokinase, streptokinase, or tissue plasminogen activator. (Journal of Parenteral and Enteral Nutrition 20:156-158, 1996)

Background: The role of oral branched-chain amino acid supplements in the prevention and treatment of chronic hepatic encephalopathy is not yet established, and conflicting opinions are expressed in authoritative textbooks. We aimed to review and pool the published controlled studies by means of meta-analytical techniques. Methods: A computerized search of published papers identified nine studies, controlled against placebo, energy, alimentary proteins, or casein. Their quality score was calculated according to the protocol of Chalmers. The value of the portal-systemic encephalopathy index was chosen as main outcome, because of lack of more significant clinical outcomes. To cope with differences in trial design and data presentation, individual data were requested to authors. Results: After 18 months, we received the individual data of only two studies, thus precluding any meta-analysis. Two studies, accounting for over 60% of total enrolled patients, were in favor of branched-chain amino acids. Their quality score was much better than that of the remaining seven negative small studies, carrying a significant risk of type II error. Conclusions: Based on the results of the two largest, long-term studies, the use of oral branched-chain amino acids in the prevention and treatment of chronic encephalopathy may only be proposed for patients with advanced cirrhosis, intolerant to alimentary proteins. Large, multicenter, long-term studies, considering more important clinical outcomes, are needed to provide definite answers to an aged question. (journal of Parenteral and Enteral Nutrition 20:159-164, 1996)

Weight loss occurs in almost all patients with human immunodeficiency virus (HIV) infection, and its causes are multifactorial. One of the most common causes is anorexia, and there are presently two drugs available for these patients: megestrol acetate (Megace; Bristol-Myers Oncology Division, Princeton, NJ) and dronabinol (Marinol; Roxane Labs, Columbus, OH). A randomized, double-blind, placebo-controlled, multicenter study using megestrol acetate is reviewed here.¹ The purpose of this study was to compare the effects of different doses of the drug on weight gain and other parameters in acquired immunodeficiency syndrome (AIDS) patients who presented with weight loss. In an outpatient setting, 270 patients were evaluated for safety of the drug. Only 195 patients could be used for evaluation of both safety and efficacy. The megestrol acetate was administered at 100, 400, or 800 mg daily for 12 weeks. Patients had lost either 20% or their premorbid weight or were ≤90% of their ideal body weight. No one was included with impaired digestive or absorptive function or with severe diarrhea defined as five or more watery stools per day for ≥7 days. Weight gain was statistically better in those patients who received 800 mg of megestrol acetate compared with the placebo group. In the group receiving 800 mg of megestrol acetate, 64.2% gained ≥2.27 kg compared with the placebo group, of which 21.4% gained at least 5 pounds (p < .001). Patients receiving megestrol acetate had an increased weight gain in a dose-dependent manner (p < .001), ranging from an average of 1.9 ± 1.3, 4.2 ± 1.3, and 7.8 ± 1.3 pounds in 100, 400, and 800 mg of megestrol acetate, respectively. The placebo group lost an average of 1.6 ± 1.2 pounds. In addition to weight gain, the patients receiving the 800 mg of megestrol acetate reported improved overall feeling of well-being, appetite score, and consumed an average increase of 645.6 calories per day in contrast to a decrease of 107 calories per day in the placebo group. There were no major drug-related safety issues observed. Body composition was assessed by bioelectrical impedance and arm skinfold thicknesses. According to the skinfold thickness measurements, there was an increase in muscle mass of 1 kg in the group receiving 800 mg of the drug; all other groups lost muscle mass. All groups receiving the megestrol acetate showed increases in the triceps skinfold thicknesses in contrast to a decrease observed in the placebo group. Results of the bioelectrical impedance analyses were similar to the anthropometry measurements; the group receiving 800 mg of megestrol acetate had a mean increase of 1.14 kg lean body mass. There was no increase in total body water for any group receiving the drug therapy. The authors concluded that in patients with AIDS-related weight loss, megestrol acetate stimulates appetite and increases food intake that leads to statistically significant weight gain. These finding result in an improvement in quality of life.