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Showing papers in "Journal of Parenteral and Enteral Nutrition in 2001"


Journal ArticleDOI
TL;DR: The data suggest choline is a required nutrient for long-term home TPN patients and suggests choline deficiency is a significant contributor to the development of TPN-associated liver disease.
Abstract: Background Previous studies have shown that plasma free choline concentrations are significantly decreased in many long-term home total parenteral nutrition (TPN) patients. Furthermore, low choline status has been associated with both hepatic morphologic and hepatic aminotransferase abnormalities. A preliminary pilot study suggested choline-supplemented TPN may be useful in reversal of these hepatic abnormalities. Methods Fifteen patients (10 M, 5 F) who had required TPN for > or =80% of their nutritional needs were randomized to receive their usual TPN (n = 8), or TPN to which 2 g choline chloride had been added (n = 7) for 24 weeks. Baseline demographic data were similar between groups. Patients had CT scans of the liver and spleen, and blood for plasma free and phospholipid-bound choline, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma glutamyl transferase (GGT), bilirubin, serum lipids, complete blood count (CBC), and chemistry profile obtained at baseline, and weeks 2, 4, 6, 12, 16, 20, 24, and 34. CT scans were analyzed for Hounsfield unit (HU) densities. Results There were no significant differences in any measured parameters after 2 weeks. However, at 4 weeks, a significant difference in liver HU between groups was observed (13.3+/-5.0 HU [choline] vs 5.8+/-5.2 HU [placebo], p = .04). This significant trend continued through week 24. Recurrent hepatic steatosis and decreased HU were observed at week 34, 10 weeks after choline supplementation had been discontinued. A significant increase in the liver-spleen differential HU was also observed in the choline group (10.6+/-6.2 HU [choline] vs 1.3+/-3.3 HU [placebo], p = .01). Serum ALT decreased significantly (p = .01 to .05) in the choline group vs placebo at weeks 6,12, 20, and 24. Serum AST was significantly decreased in the choline group by week 24 (p = .02). The serum alkaline phosphatase was significantly reduced in the choline group at weeks 2, 12, 20, 24, and 34 (p = .02 to 0.07). Total bilirubin was normal in these patients and remained unchanged during the study. Serum GGT tended to decrease more in the choline group, but the greater decrease was not statistically significant. Conclusions Choline deficiency is a significant contributor to the development of TPN-associated liver disease. The data suggest choline is a required nutrient for long-term home TPN patients.

207 citations


Journal ArticleDOI
TL;DR: Improvements in enteral nutrition provision and the time to reach the goal rate in group II support the adoption of the proposed feeding protocol for critically ill patients.
Abstract: Background : The purpose of this study was to compare gastrointestinal tolerance to two enteral feeding protocols in critically ill patients. Methods: A prospective, randomized controlled trial, that involved 96 consecutive patients expected to stay in the intensive care unit for ≥3 days and who had no contraindications to enteral feeding. The patients were randomized to either the current protocol (group I; gastric residual volume threshold, 150 mL, optional prokinetic) or proposed feeding protocol (group II; gastric residual volume threshold 250 mL, mandatory prokinetic). Gastrointestinal intolerance was recorded as episodes of high gastric residual volume, emesis, or diarrhea. The time to reach the goal rate of feeding and the percentage of nutritional requirements received during the study period were also recorded. Results: Nineteen of 36 patients (19/36 = 0.53) in group I had one or more episodes of high gastric residual volume, compared with 10 of 44 patients (10/44 = 0.23) in group II (p < .005). ...

177 citations


Journal ArticleDOI
TL;DR: The requirements for L- arginine for the proliferation of CD3 stimulated T lymphocytes vary widely, and have to be taken into account when studying the mechanism of how L-arginine enhances cellular proliferation.
Abstract: Background: Dietary supplementation of L-arginine as a mechanism to enhance cellular immune response (T lymphocytes), has slowly gained approval, and appears especially important during critical illness. Despite its clinical use, little is known as to the direct effects of L-arginine on the different T lymphocyte subpopulations. Methods: Lymphocytes were harvested from spleens of C57 Bl/6 mice, and proliferation was induced with anti-CD3 in the presence of different concentrations of L-arginine ranging from 0 to 1000 μmol/L. Flow cytometry was used to evaluate the effect of L-arginine on T lymphocyte subpopulations. Interleukin-2 production was measured by ELISA and gene expression by RT-PCR. Results: L-Arginine at or greater than 100 μmol/L significantly enhanced anti-CD3 stimulated T lymphocyte proliferation (p =.01). L-Arginine was essential for adequate T lymphocyte (CD3+) cellular maturation (p =.01). Proliferation of Helper T cells (CD4+) was not dependent on L-arginine. In contrast, Cytotoxic T cells (CD8+) showed a dose dependent proliferation in response to L-arginine (p =.01). Of the CD8+ cells, an increase in the CD45RA negative CD8 positive (memory) T cell subpopulation was observed with the addition of L-arginine. In addition, the number of cell surface CD8 receptors (CD8R) and CD3 receptors (CD3R) increased in the presence of L-arginine (p =.01, p =.04). Interleukin-2 receptor (IL-2R) expression was not up-regulated by L-arginine. L-Arginine modestly increased IL-2 production and had pronounced effects on its disappearance from the culture media (p <.0001). Interleukin-2 mRNA expression was not dependent on L-arginine. Conclusions: The requirements for L-arginine for the proliferation of CD3 stimulated T lymphocytes vary widely, and have to be taken into account when studying the mechanism of how L-arginine enhances cellular proliferation. L-Arginine may increase cellular proliferation by increasing specific receptor expression and the utilization of interleukin-2.

137 citations


Journal ArticleDOI
TL;DR: Prescribing sip feed supplements in the medicine prescription chart during hospital stay reduces weight loss and support other evidence for a reduction in mortality noted in elderly patients on nutritional supplementation.
Abstract: Background: To determine whether oral protein energy supplements, prescribed during hospitalization to elderly medical admissions, affect nutritional status and if baseline nutritional state influences this status. We also considered the effects on mortality, length of hospital stay, functional recovery, and institutionalization. Methods: A prospective randomized controlled trial with no placebo. Consenting patients were stratified in 3 nutritional categories, and patients from each stratum were randomized into treatment or control. Observers were blinded to randomization. The participants were emergency admissions from home to a Medicine for the Elderly Unit in a Scottish hospital. The inclusion criteria were as follows: no known malignancy, the ability to swallow, and nonobesity (BMI < 75th percentile). The intervention was a prescription of 120 mL sip feed, 3 times daily (540 kcal, 22.5 g protein per day) throughout hospitalization, using the medicine prescription chart. The trial was powered to detect...

123 citations


Journal ArticleDOI
TL;DR: Critically ill patients fed a high-protein diet enriched with arginine, fiber, and antioxidants had a significantly lower catheter-related sepsis rate than patients feeding a standard high- protein diet.
Abstract: Background: This study was designed to evaluate the effects of a high-protein formula enriched with arginine, fiber, and antioxidants compared with a standard high-protein formula in early enteral nutrition in critically ill patients. Methods: For this study, 220 patients were enrolled in a prospective, multicenter, single-blind, randomized trial in 15 Spanish intensive care units (ICUs). The primary endpoints were the incidence density rates of nosocomial infections, ICU and hospital length of stay, ICU and in-hospital mortality, and mortality at 6-month follow-up. Results: The patients in the control and study groups had similar baseline characteristics. The study group had a lower incidence of catheter-related sepsis (0.4 episodes/1000 ICU days) than the control group (5.5 episodes/1000 ICU days), with a relative risk (RR) of 0.07 (95% confidence interval [CI] 0.01 to 0.54, p < .001). There were no differences in the incidence of ventilator-associated pneumonia, surgical infection, bacteremia, or urina...

117 citations




Journal ArticleDOI
TL;DR: The case of a 61-year-old man with stage III squamous cell carcinoma of the tongue in whom a PEG tube was placed to circumvent anticipated difficulties in swallowing after radiation therapy and review of the literature indicate that "pull" procedures for placement of gastrostomy tubes may induce metastasis by direct implantation of tumor cells because of contact between the Gastrostomy tube and tumor cells.
Abstract: Background: Patients with head and neck cancer often need a percutaneous endoscopic gastrostomy to provide adequate nutrition because of inability to swallow after tumor radiation therapy. However, metastasis of the original tumor to the gastrostomy exit site may occur. Methods: We describe the case of a 61-year-old man with stage III (T2 N1) squamous cell carcinoma of the tongue in whom a PEG tube was placed to circumvent anticipated difficulties in swallowing after radiation therapy. We also compare this case with similar cases in the literature. Results: Soreness and erythema near the gastrostomy site reported by the patient were diagnosed as cellulitis, and two courses of antibiotic treatment were prescribed. However, a biopsy showed that the original squamous cell carcinoma had metastasized to the gastrostomy exit site. The "pull" method of tube placement had been used in this patient and in all 19 cases of metastasis reported in the literature. Conclusions: Metastatic cancer should be considered in ...

73 citations


Journal ArticleDOI
TL;DR: Results indicate that provision of metabolizable nutrients to the hypoperfused intestine exacerbate hypoxia and potentially lead to intestinal ischemia, and care must be taken to ensure intestinal perfusion is adequate to allow for nutrient metabolism and prevent further compromise.
Abstract: Background: Provision of enteral nutrients shortly after traumatic injury has become the preferred method of nutrition support provided to patients. However, traumatic shock results in splanchnic hypoperfusion, which may cause persistent intestinal hypoxia. This study tested the hypothesis that delivery of enteral nutrients to the hypoperfused jejunum increases oxidative demand beyond that available, thereby exacerbating intestinal hypoxia. Methods: Wistar-Furth rats (186 ± 4 g; n = 24) were randomized to receive intestinal hypoxia (superior mesenteric artery occlusion) or serve as normoxic controls (sham laparotomy). Within the jejunum of each rat, 4 6-cm loops were randomized to receive luminal perfusions with 1 of 4 substrates: mannitol (an osmotic control); glucose (undergoes active transport via the sodium-glucose co-transporter [SGLT-1] and is metabolized); 3-o-methylglucose (3-o-mg; uses SGLT-1 but is not metabolized); or fructose (does not use SGLT-1 but is metabolized). After in situ perfusions, jejunal tissue was removed for analysis of nutrient transport and barrier function in modified Ussing chambers. Tissue homogenate was used to determine concentration of ATP, lactate, pyruvate, and protein. Also, jejunal tissue was stained with hematoxylin and eosin for qualitative analysis of ischemia and necrosis. Results: Transmural resistance was lower (p <.001) in the hypoxia groups, irrespective of substrate, indicating increased mucosal permeability. When compared with the normoxic controls, glucose transport was impaired (p <.001) in the hypoxic groups; however, glutamine transport was unaffected. The degree of intestinal hypoxia, assessed by jejunal lactate concentration, was higher (p <.001) in the glucose and fructose groups, than the control mannitol and 3-o-mg groups. Conclusions: The observation that 3-o-mg did not differ from the mannitol control indicates that SGLT-1 activation alone does not exacerbate hypoxia. Rather, these results indicate that provision of metabolizable nutrients to the hypoperfused intestine exacerbate hypoxia and potentially lead to intestinal ischemia. Although early enteral nutrition is an important intervention after trauma, care must be taken to ensure intestinal perfusion is adequate to allow for nutrient metabolism and prevent further compromise.

63 citations


Journal ArticleDOI
TL;DR: HEN provides well-tolerated long-term nutritional support in many patients, however, because of their likelihood of being old and the nature of the underlying disease, these patients as a group tend to have a modest prognosis.
Abstract: Background: The aims of this study were to prospectively analyze the 1-month mortality and long-term outcome of home enteral nutrition (HEN) patients in order to determine the benefits of this treatment. Methods: Between 1990 and 1996, 417 patients, aged 64 ± 25 years, were discharged on HEN and followed up until December 31, 1998, when outcome was assessed, which allowed us to determine survival probabilities and conditions associated with survival. Results: The mean duration of HEN was 242 ± 494 days, with a 24- to 103-month follow-up. Probabilities of being alive at 1 month, 1 year, and 5 years were 80%, 41.7%, and 25%, respectively. Factors associated with death were dementia, neurologic disease, head and neck cancer, AIDS, and age over 70 years. A total of 5.5% of patients remained dependent on HEN, 32.6% resumed full oral nutrition, 20.2% of patients died during the first month on HEN, and 35% died after more than 1 month on HEN (219 ± 257 days). A total of 6.7% of patients stopped HEN for other rea...

62 citations


Journal ArticleDOI
TL;DR: The incidence and implications of cardiovascular disease risk factors in organ transplant recipients, strategies for clinical management, and future research directions are discussed.
Abstract: Organ transplantation has become a common and effective approach to the management of patients with organ failure. The improvement in long-term survival has resulted in the emergence of cardiovascular disease as the primary cause of death in renal transplant patients and a significant complication in other organ recipients. A number of factors explain this trend, including a high incidence of hypertension, posttransplant diabetes, hyperlipidemia, and obesity risk factors that are mediated by direct effects of immunosuppressive medications. Weight gain posttransplant affects ~50% of patients and represents a significant problem because of the potential synergism between obesity and immunosuppressive medication-induced effects on cardiovascular disease risk factor development. This review discusses the incidence and implications of cardiovascular disease risk factors in organ transplant recipients, strategies for clinical management, and future research directions. (Journal of Parenteral and Enteral Nutriti...


Journal ArticleDOI
TL;DR: The study shows that the lower weight seen in transplant men and women than in controls was due to lower FFM, which was partially offset by higher FM in men but not in women, and the higher weights in posttransplant than in pretransplant patients were due to higher FM and % FM.
Abstract: Background: Bioelectrical impedance analysis (BIA) can be valuable in evaluating the fat-free (FFM) and fat masses (FM) in patients, provided that the BIA equation is valid in the subjects studied. The purpose of the clinical evaluation was to evaluate the applicability of a single BIA equation to predict FFM in pre- and posttransplant patients and to compare FFM and FM in transplant patients with healthy controls. Methods: Pre- and posttransplant liver, lung, and heart patients (159 men, 86 women) were measured by two methods—50-kHz BIA-derived FFM (FFMBIA) by Xitron instrument and DXA-derived FFM (FFMDXA) by Hologic QDR-4500 instrument—and compared with healthy controls (196 men, 129 women), aged 20 to 79 years. Results: The high correlation coefficient (r = .974), small bias (0.3 ± 2.3 kg), and small SEE (2.3 kg) suggest that BIA using the GENEVA equation is able to predict FFM in pre- and posttransplant patients. The study shows that the lower weight seen in transplant men and women than in controls w...

Journal ArticleDOI
TL;DR: This observational study suggests guidelines suggesting the use of a chest radiograph to confirm catheter position may need to be re-assessed, after 9 patients receiving home parenteral nutrition were compared.
Abstract: Background: Central vein catheter position is a vital element in promoting longevity and minimizing adverse events associated with long-term parenteral nutrition. Traditionally, position has been verified using a chest radiograph. However, this mode of assessment has limitations as the catheter is placed in a dynamic system subject to forces from changes in posture and diaphragmatic movement. Methods: We compared the reported position using a chest x-ray compared with assessment using transesophageal echocardiology (TOE) in 9 patients receiving home parenteral nutrition. The x-ray was reported by a radiologist unaware of the study. Results: There were discordant results in 7 of the 9 cases with catheter tip placed in the right atrium or impinging in the tricuspid valve which was not evident from the chest x-ray. TOE offered greater information of catheter tip position and relationship to adjacent anatomy. Conclusions: Further work is required but this observational study suggests guidelines suggesting the use of a chest radiograph to confirm catheter position may need to be re-assessed.

Journal ArticleDOI
TL;DR: The appropriateness of posttransplant nutrition support depends on the prevalence of malnutrition among patients with a specific type of organ failure and the benefits when nutrition support is given.
Abstract: Timely nutrition assessment and intervention in organ transplant recipients may improve outcomes surrounding transplantation. A pretransplant nutrition assessment should include a variety of parameters including physical assessment, history, anthropometric measurements, and laboratory tests. Malnutrition compromises posttransplant survival; prolonged waiting times worsen outcomes when patients are already malnourished. Severe obesity may decrease graft function and survival in kidney transplant recipients. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by organ failure. Enteral tube feeding is indicated for patients with functional gastrointestinal tracts who are not eating adequately. Parenteral nutrition is rarely needed pretransplant except in cases of intestinal failure. When determining pretransplant nutrient requirements, nutritional status, weight, age, gender, metabolic state, stage and type of organ failure, malabsorption, induced losses, goals, and comorbid conditions must be considered. During the acute posttransplant phase, adequate nutrition is required to help prevent infection, promote wound healing, support metabolic demands, replenish lost stores, and perhaps mediate the immune response. Nutrient recommendations reflect posttransplant metabolic changes. The appropriateness of posttransplant nutrition support depends on the prevalence of malnutrition among patients with a specific type of organ failure and the benefits when nutrition support is given. Organ transplantation complications including rejection, infection, wound healing, renal insufficiency, hyperglycemia, and surgical complications require specific nutritional requirements and therapies. Many potential applications of nutrition in the pre- and posttransplant phases exist and require further study.

Journal ArticleDOI
TL;DR: Diagnostic test characteristics of 4 techniques for tip localization for enteral feeding, including auscultation, aspiration with inspection or pH determination of aspirated material, and a recently developed electromagnetic technique are compared.
Abstract: Background: Benefits of enteral feeding are diminished by aspiration pneumonia and mechanical complications of misplaced feeding tubes. To avoid complications, clinicians determine the location of the tip before feeding. This study compares diagnostic test characteristics of 4 techniques for tip localization. Methods: A prospective, blinded trial was conducted on the wards and critical care units of four acute-care hospitals. Patients requiring at least 3 days of enteral feeding were studied. Four observers at each institution used a randomly assigned technique to determine a tube's tip location. Methods included auscultation, aspiration with inspection or pH determination of aspirated material, and a recently developed electromagnetic technique. Results were compared with radiographic determination. Success rates were compared using sensitivity, specificity, and likelihood ratios. Results: The 4 methods agreed with the radiograph in (mean, 95% confidence interval): 84 (80 to 88)%, 50 (45 to 55)%, 56 (51 ...

Journal ArticleDOI
TL;DR: The decreased killing capacity of neutrophils after exposure to medium-chain fatty acid-containing emulsions and the absence of this effect with LCT suggest that lipid emulsion influence the elimination of C. albicans depending on the triglyceride chain length.
Abstract: BACKGROUND: To test the hypothesis that structurally different lipid emulsions have distinct immune-modulating properties, we analyzed the elimination of Candida albicans by neutrophils after exposure to various emulsions. METHODS: Neutrophils from 8 volunteers were incubated in physiologic 5 mmol/L emulsions containing long-chain- (LCT), medium-chain- (MCT), mixed LCT/MCT-, alpha-tocopherol-enriched LCT/MCT (LCT/MCT-E), or structured lipids (SL). After washing, the neutrophils were incubated with C. albicans. Phagocytosis was measured as the number of yeast-associated neutrophils relative to the total neutrophil count. Killing was expressed as the percentage of Candida survival relative to the initial yeast cell count. RESULTS: No significant differences in yeast-neutrophil association could be demonstrated after neutrophil incubation in various lipid emulsions or medium, after correction for non-specific adhesion. However, although Candida survival after 1 hour incubation with non-lipid-exposed neutrophils amounted to 53% +/- 11% and was not influenced by LCT (60% +/- 11%), LCT/MCT (78% +/- 7%), LCT/MCT-E (72% +/- 12%), and SL (67% +/- 6%), pure MCT (70% +/- 13%) significantly impaired the killing capacity of neutrophils. CONCLUSIONS: The decreased killing capacity of neutrophils after exposure to medium-chain fatty acid-containing emulsions and the absence of this effect with LCT suggest that lipid emulsions influence the elimination of C. albicans depending on the triglyceride chain length.

Journal ArticleDOI
TL;DR: The parenteral structured triglyceride emulsion improves the nitrogen balance and is cleared faster from the blood, compared with the emulsion of the physical mixture of medium- and long-chain triglycerides, in moderately catabolic patients.
Abstract: BACKGROUND: Most postoperative patients lose net protein mass, which reflects loss of muscle tissue and organ function. Perioperative parenteral nutrition may reduce the loss of protein, but in general, with conventional lipid emulsions a waste of protein still remains. METHODS: We compared the effects on nitrogen balance of an emulsion containing structured triglycerides, a new type of synthesized triglycerides, with an emulsion of a physical mixture of medium- and long-chain triglycerides as part of parenteral feeding in moderately catabolic patients. The first 5 days after placement of an aortic prosthesis patients received total parenteral nutrition (TPN) providing 0.2 g of nitrogen per kg body weight per day; energy requirement was calculated using Harris and Benedict's equation, adding 300 kcal per day for activity. Twelve patients were treated with the structured triglyceride emulsion and 13 patients with the emulsion of the physical mixture of medium- and long-chain triglycerides. The design was a randomized, double-blind parallel study. RESULTS: In the patients who completed the study, the mean cumulative nitrogen balance over the first 5 postoperative days was -8+/-2 g in 10 patients on the structured triglyceride emulsion and -21+/-4 g in 9 patients on the emulsion of the physical mixture of medium- and long-chain triglycerides; the mean difference was 13 g of nitrogen (95% confidence interval 4 to 22, p = .015) in favor of the structured triglyceride emulsion. On the first postoperative day serum triglyceride and plasma medium-chain free fatty acid levels increased less during infusion of the structured triglyceride emulsion than with the physical mixture emulsion. CONCLUSIONS: The parenteral structured triglyceride emulsion improves the nitrogen balance and is cleared faster from the blood, compared with the emulsion of the physical mixture of medium- and long-chain triglycerides, in moderately catabolic patients.


Journal ArticleDOI
TL;DR: It is concluded that multivitamins protect Intralipid against lipid peroxidation, but light-dependent hydrogen peroxide production and ascorbate loss occur.
Abstract: Background: Infusion of parenteral solutions containing peroxides may be detrimental to premature infants. Intralipid frequently contains lipid peroxides and undergoes further peroxidation when exposed to light. Peroxidation is inhibited by ascorbate, and we have proposed that administration of peroxides could be minimized by mixing multivitamins with the Intralipid. In contrast, others have reported that multivitamins generate peroxides and have advised against mixing them with lipid. Our objective was to assess whether light-dependent reactions in parenteral solutions containing MVI Pediatric (MVIP) generate hydrogen peroxide and establish whether addition of multivitamins to Intralipid is beneficial or detrimental. Results: We were unable to make accurate peroxide measurements in MVIP using the ferrous oxidation of xylenol orange (FOX) assay, even though others have used it for this purpose, because of interference by ascorbate. Therefore oxygen release on adding catalase was measured to assay for hydrogen peroxide. Freshly reconstituted solutions contained 250 to 500 μmol/L hydrogen peroxide, and this increased dramatically in ambient light. This is presumably due to light-dependent, riboflavin-catalyzed reduction of oxygen by ascorbic acid. The rate of peroxide generation was less for MVIP diluted in Intralipid than in dextrose solution. Conclusions: Taken together with our previous findings, we conclude that multivitamins protect Intralipid against lipid peroxidation, but light-dependent hydrogen peroxide production and ascorbate loss occur. These latter changes are less than for multivitamins in other total parenteral nutrition solutions, so there is an advantage in mixing multivitamins with Intralipid. However, prevention of ascorbate loss and hydrogen peroxide formation in any multivitamin solution requires protection of the delivery system from light.

Journal ArticleDOI
TL;DR: This pilot study indicates both verbal and visual memory may be impaired in patients who require long-term TPN and both may be improved with choline supplementation.
Abstract: Background: Previous investigations have demonstrated that choline deficiency, manifested in low plasma-free choline concentration and hepatic injury, may develop in patients who require long-term total parenteral nutrition (TPN). Preliminary studies have suggested lecithin or choline supplementation might lead to improved visual memory in the elderly and reverse abnormal neuropsychological development in children. We sought to determine if choline-supplemented TPN would lead to improvement in neuropsychological test scores in a group of adult, choline-deficient outpatients receiving TPN. Methods: Eleven subjects (8 males, 3 females) who received nightly TPN for more than 80% of their nutritional needs for at least 12 weeks before entry in the study were enrolled. Exclusion criteria included active drug abuse, mental retardation, cerebral vascular accident, head trauma, hemodialysis or peritoneal dialysis, (prothrombin time [PT] >2× control), or acquired immune deficiency syndrome (AIDS). Patients were ra...

Journal ArticleDOI
TL;DR: Results show that L-arginine supplementation and NO synthesis improve hepatic injury and have a protective role in the transplanted liver graft, which may be mediated by low-level cNOS-derived NO.
Abstract: Background A major problem complicating liver transplantation is the preservation injury that results from cold storage and subsequent ischemia/reperfusion injury after organ revascularization. The L-arginine-nitric oxide (NO) pathway has been recognized to play critical roles during infection, inflammation, organ injury, and transplant rejection. Recent data indicates that NO synthesis has beneficial effects in several models of liver injury. The purpose of this study is to examine the role of the L-arginine-NO pathway on preservation injury in an experimental model of rat liver transplantation. Methods Orthotopic liver transplantation was performed in syngeneic (LEW to LEW) rats. Liver preservation injury was determined by measuring serum liver function tests 6 to 48 hours after transplantation. In some experiments, rats received L-arginine supplementation 0 to 24 hours after transplantation. In other experiments, NO synthase inhibitors (L-NAME or L-NIL) were injected at the time of isograft revascularization. Results L-Arginine supplementation decreased hepatic transaminase levels at all time points examined (6-48 hours). L-Arginine produced a significant improvement in liver preservation injury by 12 hours after reperfusion. The NO synthase inhibitor L-NAME caused a significant increase in liver injury 24 hours after injection. The inducible NO synthase (iNOS)-specific inhibitor L-NIL had no significant effect on liver injury. Conclusions The results show that L-arginine supplementation and NO synthesis improve hepatic injury and have a protective role in the transplanted liver graft. The protective effect may be mediated by low-level cNOS-derived NO.

Journal ArticleDOI
TL;DR: The whole-blood manganese concentration, the MRI intensity in the globus pallidus and the T1 value, an objective index of theMRI intensity, may be useful indices of the in vivoManganese level in the body.
Abstract: Background: Recently, there have been reports that magnetic resonance imaging (MRI) reveals high-intensity T1-weighted images (HI) in the basal ganglia (especially in the globus pallidus) of patients receiving total parenteral nutrition (TPN). This finding is presumably due to excess administration of manganese. We investigated the reversibility and reproducibility of these changes by means of an on-off manganese administration study. We also investigated the temporal relationships between the intensity of T 1-weighted images (MRI intensity) and the whole-blood and plasma manganese concentrations to evaluate the potential for the MRI intensity to serve as an index of the in vivo manganese level. Methods: Eleven adult patients undergoing home parenteral nutrition received TPN solutions containing manganese (0 or 20 μmol/d) according to an on-off design. The whole-blood and plasma manganese concentrations were determined at the same time the brain MRI was performed. Results: Both the whole-blood manganese c...

Journal ArticleDOI
TL;DR: Erythromycin does not facilitate transpyloric passage of feeding tubes in critically ill children and the distal migration of duodenal feeding tubes further into the small bowel is also not enhanced by erystromycin.
Abstract: Background: Erythromycin enhances gastric emptying and has been suggested to facilitate nasoenteric feeding tube placement in adults. Our primary objective was to evaluate the effect of erythromycin on the transpyloric passage of feeding tubes in critically ill children, and second, to evaluate the effect of erythromycin on the distal migration of duodenal feeding tubes. Methods: Seventy-four children were randomly assigned to receive erythromycin lactobionate (10 mg/kg) IV or equal volume of saline placebo 60 minutes before passage of a flexible weighted tip feeding tube. Abdominal radiographs were obtained 4 hours later to assess tube placement. If the tube was proximal to the third part of the duodenum, two additional doses of erythromycin/placebo were administered 6 hours apart. Those receiving additional doses had repeat radiographs 14 to 18 hours after tube placement. Results: The number of postpyloric feeding tubes was similar in the erythromycin and placebo treated groups 4 hours after tube insert...

Journal ArticleDOI
TL;DR: The site of resection, time postresection, and growth factors treatment differentially influence ATB0 and PEPT 1 mRNA expression, and enhanced sodium-dependent brush border neutral amino acid transport with GH plus EGF administration is independent of increased AtB0 mRNA expression in rabbit small intestine after enterectomy.
Abstract: Background: Sucessful intestinal adaptation after massive enterectomy is dependent on increased efficiency of nutrient transport. However, midgut resection (MGR) in rabbits induces an initial decrease in sodium-dependent brush border neutral amino acid transport, whereas parenteral epidermal growth factor (EGF) and growth hormone (GH) reverse this downregulation. We investigated intestinal amino acid transporter B° (ATB°) and oligopeptide transporter 1 (PEPT 1) mRNA expression after resection and in response to EGF and/or GH. Methods: Rabbits underwent anesthesia alone (control) or proximal, midgut, and distal resections. Full-thickness intestine was harvested from all groups on postoperative day (POD) 7, and on POD 14 from control and MGR rabbits. A second group of MGR rabbits received EGF and/or GH for 7 days, beginning 7 days after resection. ATB° and PEPT 1 mRNA levels were determined by Northern blot analysis. Results: In control animals, ileal ATB° mRNA abundance was three times higher than jejunal ...

Journal ArticleDOI
TL;DR: The accumulation of hepatic TG in burned animals is due to inhibition of VLDL-TG secretion and to increased synthesis of hepatics TG, indicating fatty acids are not channeled to TG because of impaired oxidation.
Abstract: Background: The primary goal of this study was to investigate hepatic fatty acid (FA) metabolism after severe thermal injury. Methods: Sixteen pigs were divided into control (n = 8) and burn (n = 8, with 40% full thickness total body surface area burned) groups. Catheters were inserted in the right common carotid artery, portal vein, and hepatic vein for blood sampling. Flow probes were placed around the hepatic artery and portal vein for blood flow measurements. Animals were given pain medication and sedated until the tracer study on day 4 after burn. The pigs were infused for 4 hours with U-13C16-palmitate in order to quantify hepatic FA kinetics and oxidation. Results: Liver triglyceride (TG) content was elevated from 162 ± 16 (control) to 297 ± 28 μmol TG/g dry liver wt. (p < .05). Hepatic FA uptake and oxidation were similar between the 2 groups, as were malonyl-coenzyme A (CoA) levels and activities of acetyl-CoA carboxylase and adenosine monophosphate (AMP)-activated protein kinase. In contrast, in...

Journal ArticleDOI
TL;DR: Serum phosphorus concentrations are lower in thermally injured patients compared with multiple trauma patients despite receiving a significantly greater intake of phosphorus during nutrition support, and renal phosphorus regulation does not significantly contribute to the profound hypophosphatemia observed in thermALLY injured patients when compared with several trauma patients during nutritionSupport.
Abstract: To compare phosphorus intake and renal phosphorus regulation between thermally injured patients and multiple trauma patients, 40 consecutive critically ill patients, 20 with thermal injury and 20 with multiple trauma, who required enteral tube feeding were evaluated. Phosphorus intakes were recorded for 14 days from the initiation of tube feeding which was started 1 to 3 days postinjury. Serum for determination of phosphorus concentrations was collected at days 1, 3, 7, and 14 of the study period. A 24-hour urine collection was obtained during the first and second weeks of nutrition support for urinary phosphorus excretion, fractional excretion of phosphorus, renal threshold phosphate concentration, and phosphorus clearance. Average total daily phosphorus intake during the 14-day study for thermally injured patients and multiple trauma patients was 0.99+/-0.26 mmol/kg/d vs 0.58+/-0.21 mmol/kg/d, respectively, p < .001. Serum phosphorus concentration on the third day of observation was significantly lower in the thermally injured group than those with multiple trauma (1.9+/-0.8 mg/dL vs 3.0+/-0.8 mg/dL, p < or = .01). A trend toward hypophosphatemia in the thermally injured group persisted by the seventh day of feeding (2.7+/-1.2 mg/dL vs 3.3+/-0.6 mg/dL, p < or = .04). Differences in urinary phosphorus excretion was not statistically significant between the thermally injured and multiple trauma groups (271+/-213 mg/d vs 171+/-181 mg/d for week 1, and 320+/-289 mg/d vs 258+/-184 mg/d for week 2, respectively). Urinary phosphorus clearance, fractional excretion of phosphorus, or renal threshold phosphate concentrations were also not significantly different between thermally injured and multiple trauma patients. During nutrition support, serum phosphorus concentrations are lower in thermally injured patients compared with multiple trauma patients despite receiving a significantly greater intake of phosphorus. Renal phosphorus regulation does not significantly contribute to the profound hypophosphatemia observed in thermally injured patients when compared with multiple trauma patients during nutrition support.

Journal ArticleDOI
TL;DR: Patients should be carefully monitored when receiving long-term parenteral nutrition includingManganese, even when the manganese dose is small and the frequency of receiving a manganae supplement is low.
Abstract: Background and Methods: The administration of trace elements is thought to be needed in patients receiving long-term parenteral nutrition. Recently, manganese intoxication or deposition was documented in such patients. We report two cases of manganese intoxication during intermittent parenteral nutrition including manganese. Manganese had been administered for 4 years at a frequency of one or two times per week in one case and for 5 years at a frequency of one or two times per month in the other case. Both cases showed mild symptoms with headache and dizziness. One case had mild hepatic dysfunction and the other did not. The whole-blood manganese level increased in one case, but not in the other case. T1-weighted magnetic resonance images revealed symmetrical high-intensity areas in basal ganglia and thalamus in both cases. After the administration of manganese was stopped, these symptoms all disappeared and the magnetic resonance images abnormalities gradually improved in both patients. Mild long-term ma...

Journal ArticleDOI
TL;DR: Patients developing infections had slightly higher SG levels than noninfected patients early in admission, but these SG values were far below levels considered a risk for infective complications.
Abstract: Objective: To determine the relationship between hyperglycemia and infectious complications in nutritional studies of trauma patients. Methods: Retrospective review of serum glucose values in two published randomized, prospective studies of patients receiving either enteral or parenteral feeding (trial 1) or isonitrogenous, isocaloric enteral diets (trial 2). Trial 2 also included patients prospectively followed who received little or no enteral feeding. Results: Patients randomized to enteral or parenteral feeding in trial 1 exhibited no significant differences in the highest recorded serum glucose (SG) until the fourth or fifth day after protocol entry. SG tended to be higher in infected than noninfected patients in the first 4 hospital days, but SG was far below values considered to increase the risk for infection (SG > 220 mg/dL). In trial 2, glucose levels tended to be slightly higher in infected than in noninfected patients within the first 5 days reaching statistical significance by day 5. Unfed co...

Journal ArticleDOI
TL;DR: Supplemental arginine in enteral feeding is readily absorbed, and mainly metabolized into ornithine, presumably by the arginase enzyme.
Abstract: BACKGROUND Some studies have suggested that the addition of arginine to enteral feeding solutions may improve outcome in critically ill patients, but the mechanism is incompletely explained. In particular, the availability and utilization of arginine administered enterally is not well defined. METHODS This prospective, randomized, double-blind, placebo-controlled study performed in a Department of Medicosurgical Intensive Care included 51 patients likely requiring long-term enteral feeding. Thirty-seven patients (57 +/- 7 years, SAPS II 33 +/- 6) completed the 7-day study, of whom 20 received the formula enriched with free arginine (6.3 g/L) and 17 received an isocaloric and isonitrogenous control solution. Arginine absorption was assessed from plasma arginine concentrations in serial samples. Three pathways of arginine utilization were explored: (1) the production of nitric oxide, assessed by the plasma concentration of nitrite/nitrate (NOx) and citrulline, and 24-hour urinary excretion of NOx; (2) the protein turnover, estimated by the phenylalanine concentrations; and (3) the activity of arginase, reflected by the ornithine concentration. RESULTS The plasma concentrations of arginine and ornithine increased in the group fed with the enriched formula (from 55 +/- 9 micromol/L to 102 +/- 9 micromol/L and from 57 +/- 7 to 135 +/- 11 micromol/L, respectively, p < .05), but not with the control formula. There was no difference between groups in either NO production or phenylalanine concentration. CONCLUSIONS Supplemental arginine in enteral feeding is readily absorbed, and mainly metabolized into ornithine, presumably by the arginase enzyme.