Scientific Poster Exchange
060 Temporal Response Of Arginine But Not Nitric Oxide In Plasma And Exudate Of An Inflammatory Site For Rats Receiving Parenteral Nutrition With Citrulline Or Ornithine Substituted For Arginine. Bruce Grossie, PhD, Jinny Edwards, BS, RD, Rayna Rogiers, BS, Deema Hussein, MS. Texas Woman’s University, Denton, TX, USA.
Background: As the precursor of nitric oxide (NO), arginine may have a significant impact on the host inflammatory response. Recent data from my laboratory shows that the concentration of the stable end products of nitric oxide synthesis (nitrate/nitrite, NOx) in the exudate of a subcutaneous inflammatory site (implanted sponge) decreased rapidly over time. The exudate arginine concentration is also often decreased. Results from my laboratory have also shown that after 4 days of parenteral nutrition (PN), the plasma arginine concentration for rats receiving PN with citrulline substituted for arginine (PNcit) was significantly higher than rats receiving PN with arginine (PNarg); the plasma arginine was lower when ornithine was substituted for arginine (PNorn). The impact of modified PN on the arginine and NO concentration of the exudate of an inflammatory site, however, has not been evaluated. This study was designed to test the hypothesis that PNcit- and PNorn-induced changes in plasma arginine concentrations will result in corresponding changes in the arginine and NOx concentration of an inflammatory exudate.
Methods: Male Sprague Dawley rats (n=3-6/final group) with a subcutaneous inflammatory site were given isonitrogenous/isocaloric PN for 24 or 96 hours and the plasma and exudate concentration of arginine and NOx were compared. PNarg, PNcit, or PNorn was administered through a central venous catheter; the inflammatory site was implanted at catheter implant. The amino acid profile of plasma and exudate was determined by HPLC; the NOx concentration measured by a nitrate reductase/Griess reagent assay. Data was analyzed with a one-way ANOVA using SPSS.
Results: The arginine concentration (μM) of plasma and exudate is shown in the table. The plasma arginine concentration after 24 hours was not affected for PNcit rats but was significantly lower for PNorn rats. After 96 hours, however, the plasma arginine concentration for PNcit rats was significantly greater than that for rats receiving PNarg: PNorn decreased the concentration. The exudate arginine concentration after 24 hours was significantly greater for PNcit rats than for PNarg rats and significantly lower for PNorn rats. At 96 hours, the arginine concentration in the exudate of all PN rats was lower as compared to that at day 1. Neither time of administration or the amino acid composition of PN affected the concentration of NOx (μM) in the plasma and exudates.
Temporal change in the plasma and exudate arginine concentration (μM)
Conclusions: These results suggest that a decrease, but not an increase, in plasma arginine concentration will affect the exudate arginine concentration of an inflammatory site. The results demonstrate, however, that the arginine concentration will not affect the innate nitric oxide synthesis of the host or inflammatory site.
061 Effect of Glutamine Dipeptide and Antioxidant Nutrients on the Intestinal Proliferation of Malnourished Rats submitted to Trauma. Claudia C. Alves, RD, Camila G. Marques, RD, Letcia De Nardi, RD, Paula M. Toth, RB, Raquel S. Torrinhas, MB, ngela F. Logullo, MD, Joaquim Gama-Rodrigues, PhD, Dan L. Waitzberg, PhD. Faculdade de Medicina, Universidade de So Paulo, Brazil. Malnutrition and catabolic states may decrease intestinal proliferation. Glutamine is an energy source for enterocytes. Antioxidant nutrients are useful in these states by decreasing cell membrane peroxidation. A new supplement Intestamin (Fresenius-Kabi) containing vitamins C/E, beta carotene, selenium, zinc, tributyrin and dipeptide forms of glutamine (alanyl-glutamine and glycyl- glutamine) was designed to improve intestinal rehabilitation in trauma.
Objective – to determine the intestinal proliferation in malnourished and traumatized rats after Intestamin feeding. Material and Methods – Malnourished Lewis isogenic adult rats (n=24) were submitted to gaslrostomy (G) and a standard dorsal skin lesion. The rats were divided in groups according to their diet (isocaloric and isonitrogenous): a) C: standard laboratory oral diet (OD) + saline by G; b) OPl: OD + Intestamin by G; c) AaI: OD + essential amino acids 6.7% by G and d) AaGli: OD + essential amino acids 6.7%, alanine and glycine by G. On day 6, samples of the distal and proximal small intestine were collected and submitted to histopathologically analysis.
Results – There were no statistically significant alterations among the variables studied in the intestinal tissue (Table). Table – Histological analysis of the distal and proximal small intestine of malnourished mice with Intestamin supplementation. (Statistical tests: Friedman and Student-Newman Keuls, p <0.05).
Distal Small Intestine
Conclusion – Supplementation with Intestamin did not modify the intestinal proliferation in malnourished rats subjected to trauma.
062 Glutamine-Supplemented Total Parenteral Nutrition Attenuates Plasma Interleukin-6 in Surgical Patients with Lower Disease Severity. Ming-Tsan Lin, MD, PhD.1, Ming-Hsun Wu, MD1, Sung-Ling Yeh, PhD2, Po-Huang Lee, MD, PhD.1, Wei-Jao Chen, MD, PhD.1 1Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan Republic of China, 2Institute of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan Republic of China.
Objective: Previous reports have shown that decrease in plasma glutamine (Gln) level following major surgery may contribute to the state of immunosuppression. Gln supplementation improves the depletion of body Gln pool, and may have indirect effect on reducing proinflammatory mediator release. This study was designed to evaluate whether the effect of Gln dipeptide-enriched total parenteral nutrition (TPN) on postoperative cytokine alteration were dependent on the severity of patients undergoing surgery.
Methods: Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous (0.228 g nitrogen/ kg/day) and isoenergetic (30 kcal/kg/day) TPN for 6 days. Control group (Conv) using conventional TPN solutionreceived 1.5 g amino acids/kg/day, whereas the test group received 0.972 g amino acids/ kg/day and 0.417 g of L-alanyl-L-glutamine (Ala-Gln)/kg/day. Blood samples were collected on day 1 and day 6 postoperatively for plasma interleukin (IL)-2, IL-6, IL-8 and interferon-γ (IFN-γ) analysis. Results: Plasma IL-2 and IFN-γ were not detectable. IL-6 concentrations were significantly lower on the 6th postoperative day in the Ala-Gin group than those in the Conv group in patients with APACHE II < 6, whereas no difference was noted in patients with APACHE II ≥ 6. There was no difference in IL-8 levels between the two groups. There was no difference in cumulative nitrogen balance on day 5 after operation between the two groups (Ala-Gin -3.2 1.6 g vs. Conv -6.5 2.7 g). Nevertheless, a singinficant inverse correlation was observed between plasma IL-6 levels and cumulative nitrogen balance on day 5 postoperatively in the Ala-Gin group.
Conclusion: TPN supplemented with Gln dipeptide had no effect on plasma IL-8 levels after surgery. Nevertheless, Gln supplementation had beneficial effect on decreasing IL-6 production in patients with low admission illness severity, and reducing IL-6 may improve nitrogen balance after surgery when Gln was used.
063 The Influence Of Early Glutamine Enhanced Tube Feeding (gtf) On Incidence Of Sepsis And Hospital Length Of Stay Following Cardiac Surgery. Elamin M. Elamin, MD, MSc1, Seif Mohsin, MD2, Syed Wasti, MD, MPH1. 1Southern Illinois University, Springfield, IL, USA, 2University of Illinois, Peoria, IL, USA.
Background: Translocation of gram-negative bacteria from the gut to the blood and alterations of the immune system, are known complication after cardiac surgery. The etiology is thought to be due to the brief, but measurable, hypotension that occurs during placement on the heart-lung machine. The role of glutamine in altering post-cardiac surgery septic complications and possible increase in length of hospital stay is not known.
Study Design: In a retrospective study the records of 679 adult subjects who underwent cardiac surgery and received enteral feeding before the 5th postoperative day were reviewed. Data was collected on demographic information, preexisting conditions, and markers of Systemic Inflammatory Response Syndrome (SIRS)/MODS during the 28 postoperative periods or until death.
Results: Few [2.0% (14/679)] patients underwent cardiac surgery and received enterai feeding before the 5th postoperative day. Of the eligible subjects 21.5% (3/14) received GTE with the remaining 78.5% (11/14) received none Glutamine enhanced tube-feeding (NGTF). There was statistically significant decrease in MODS between the two groups over the first 7 days (GTE= 4.67 to 0.67 while NGTE= 4.55 to 3.73), Figure 1. In addition, there was statistically significant decrease in median duration of hospital stay in the GTE group comparing to the NGTF group (12 days compared to 26 days). However due to the small sample size for the GTE group\, the Westenberg- Mood Median Test and the group x day interaction were not significant (p>.5) and (p>0.18) respectively.
Figure 1, Decrease of MODS after Glutamine enhanced tube feeding (GTF).
Conclusion: This pilot study demonstrated a trend for early decrease of the MODS and length of hospital stay with early post- cardiac surgery GTF. A larger prospective study will be conducted to further examine these results.
064 Role Of Arginine In The Immunomodulatory Effects Of Crucial: Study In A Rat Head-injury (hi) Model. Djamel Hamani, MS, Christine Charrueau, PhD, PharmD, Marie-Jos Butel, PhD, Valerie Besson, PhD, PharmD, Ioannis Nicolis, PhD, Servane Le Plenier, Catherine Marchand- Verrecchia, PhD, Jean-Claude Chaumeil, PhD, PharmD, Luc Cynober, PhD, PharmD, Christophe Moinard, PhD. Facult de Pharmacie, Paris, France.
Introduction: The presence of arginine in immune-enhancing diets is controversial. The aim of this study was to define the role of arginine in the immunomodulatory effects of Crucial in HI rats.
Materials and methods: 34 male Sprague-Dawley rats were randomized into 5 groups: AL (ad libitum), HI (Head-Injured), HIS (HI+SondalisHP), HISA (HI+SondalisHP+Arg in equimolar concentration to Arg in Crucial), and HIC (HI+Crucial). Isocaloric (290 kcal/kg/ d) and isonitrogenous (3.29 g/kg/d) diets were administered continuously over 4 days. After sacrifice, the thymus was removed and weighed. The density of CD25 receptors on blood lymphocytes was evaluated (by flow cytometry) at basal state and following stimulation with Concanavalin A (ConA), and production of IL2 was measured by ELISA. Mesenteric lymph nodes, liver and spleen were removed and cultured for studying bacterial translocation and enterobacterial dissemination.
Results: In response to ConA stimulation, CD25 density and IL2 secretion were significantly increased only in HISA and HIC groups. Moreover, only Crucial has couteracled thymus atrophy induced by HI (AL : 0.490.02, HI : 0.270.03 and HIC 0.460.02 g). Head injury- induced bacterial dissemination (spleen and liver) was blunted only in the HISA group (p<0.05).
Conclusion: Arginine contributes to a large extent to the immunomodulatory effects of Crucial, and seems to be able to limit bacterial dissemination
065 Bioelectrical Impedance Analysis: Population Reference Values for Phase Angle by Age and Sex. M. Cristina G. Barbosa e Silva, PhD1, Alusio J. D. Barros, PhD2, Jack Wang, MS3, Steven B. Heymsfield, MD3, Richard N. Pierson, Jr., PhD3. 1Universidade Ctolica de Pelotas, Pelotas, Brazil, 2Universidade Federal de Pelotas, Pelotas, Brazil, 3St. Luke’s-Roosevelt Hospital Center, Columbia University, New York, NY, USA.
Background: Phase angle (PA) is an indicator based on reactance and resistance obtained from bioelectrical impedance analysis (BIA). Although its biologic meaning is still not very clear, PA has been interpreted as an indicator of membrane integrity and of water distribution between the intra- and extra cellular spaces. It also seems to have an important prognostic role in several clinical conditions. The lack of PA reference values has limited its use in clinical and epidemiological situations. The aim of this study is to estimate population PA averages and standard deviations that could be used as reference values.
Method: 1967 healthy adults, aged 18-94 years, were submitted to BIA (model 101, RJL systems) under standard conditions. PA was calculated directly from reactance and resistance. Comparisons between sexes and age groups were done using unpaired two-tailed t- tests and analysis of variance.
Results: Phase angle is smaller in women and decreases with age (all p < 0.001). Phase angle mean was 6.93 overall, 7.48 for men and 6.53 for women. There was a significant and decreasing linear trend in phase angle with age, in both sexes. Phase angle decreased from 7.90 (youngest group) to 6.19 (oldest group) in men, and from 7.04 (youngest group) to 5.64 (oldest group) in women.
Conclusions: PA differs between sex and age categories. The use of these reference values will help assessing the predictive role of phase angle in clinical and epidemiological applications.
066 Comparison of Phase Angle between Normal Individuals and Chemotherapy Patients using Age and Sex Reference Values. M. Cristina G. Barbosa e Silva, PhD1, Aluisio J. D. Barros, PhD2, M. Cecilia F. Assuno, PhD2, Silvana I. Paiva2. 1Universidade Catlica de Pelotas, Pelotas, Brazil, 2Universidade Federal de Pelotas, Pelotas, Brazil.
Background: Phase angle (PA) is an indicator based on reactance and resistance obtained from bioelectrical impedance analysis (BIA). It seems to have an important prognostic role in several clinical conditions, as HIV patients, cirrhosis of the liver and lung cancer patients. PA seems to change with age and sex, and it becomes difficult to compare its crude values that come from different age sample. The use of standardized PA (SPA), obtained from reference values, make comparisons possible even when the clinical status and age are very different among groups, and may be useful in clinical and epidemiological situations. The aim of this study is to compare the mean phase angle between normal volunteers and chemotherapy patients, who are much older than then volunteers, and to illustrate the use of SPA.
Method: A sample of 52 healthy adults, aged 19-47 years, and 53 chemotherapy patients, aged 21-84 years, were submitted to BIA (BIA Quantum, RJL systems) under standard conditions. PA was calculated directly from reactance and resistance. SPA was obtained by subtracting the age/sex specific mean from the individual values and then dividing it by the age/sex specific standard deviation (sd). The age and sex specific PA reference values were obtained from a population (1967 subjects) previously studied. Comparisons between healthy and chemotherapy groups were done using unpaired two-tailed t-tests and analysis of variance.
Results: PA was significantly lower (p<0.001) in chemotherapy patients (PA = 5.19) than in healthy subjects (PA = 6.36), but this effect is confounded by age, since this group was significantly older. Using SPA, the difference between normal individuals (SPA = - 1.09 sd) and chemotherapy patients (SPA = - 1.51 sd) was 0.42 sd (p = 0,005).
Conclusions: SPA can be used to compare healthy and cancer subjects, even when the mean age between the groups is very different. PAS may be useful to identify groups of greater risk, despite of difference of sex and age of the sample in clinical and epidemiological studies.
067 Use of Bioelectrical Impedance Analysis (BIA) and Biochemical Markers to Predict Nutritional Status and Degree of Liver Disease in HIV Mono-infected and HIV/HCV Co-infected Patients. Claudia A. Barber, MFCS, RD, LDN, Sharon Kimmel, Ph.D, Margaret L. Hoffman- Terry, M.D. Lehigh Valley Hospital and Health Network, Allentown, PA, USA.
Background: Drug cocktails have dramatically slowed HIV disease progression and decreased HIV wasting. HIV patients now survive long enough to become ill from their hepatitis C (HCV) induced liver disease and co-morbidities, such as diabetes mellitus and obesity. Patients co-infected with HIV/HCV are at greater nutritional risk because of poor liver function, which results in decreasing muscle mass. Is it possible to use biochemical parameters with bioelectric impedance analysis (BIA) to measure muscle mass, in order to predict nutritional status in HIV mono-infected versus HIV/HCV co-infected patients?
Methods: We analyzed BIA results and biochemical parameters available on all clinic patients that have been seen 09/02- 04/04.
Results: The sample size included 378 patients who had at least one BIA during the time frame in which we analyzed data. The demographics of the patients that we analyzed included: mean age of 41 years; 61% were male; 22% were African-American; 32% were Caucasian; and 46% were Latino. Of the 378 patients, 75% (282 patients) were mono-infected with HIV and 25% (96 patients) were co- infected with HCV and HIV. Out of the co-infected patients, 42% (40) had liver biopsy results indicating that 77.5% (31) patients had mild-moderate liver disease and 22.5% (9) patients had moderate- severe liver disease. Univariate analysis, with covariates as appropriate, were performed on the following body compartments: total body water (TBW), intracellular water (ICW), and extracellular water (ECW); body cell mass (BCM) and percent of total body weight, fat and percent of total body weight; and ICW/ECW ratio. The following biochemical parameters were analyzed: albumin, liver function enzymes such as AST and ALT, HIV viral load, glucose, and lipid panel consisting of cholesterol, HDL, LDL, cholesterol/ HDL ratio, and triglycerides. Statistically significant differences (SSD, p< 0.001) between mono/co-infected patients for BIA results are shown in Table 1 and SSD of BIA results between liver disease are shown in Table 2. Table 3 shows SSD (p=0.003) for biochemical parameters among mono/co-infected patients.
Conclusions: Co-infected patients, in general, had higher glucose, AST, ALT, TBW, ICW, ECW, and BCM than monoinfected. However co-infected patients with moderate-severe liver disease had greater fat, greater extracellular and less intracellular water, and a lower body cell mass indicating lower muscle mass. Using body composition testing such as the BIA may help with detection of liver disease, especially in the late stage. The BIA may serve as a practical and noninvasive tool in the clinical setting for health professionals.
Table 1. BIA Results Among Mono/co-infected Patients
Table 2. BIA Results and Stages of Liver Disease
Table 3. Biochemical Parameters Among Mono/co-infected Patients
068 Effects Of Nutritional Support In Patients With Colorectal Cancer During Chemotherapy. Renata Dobrila-Dintinjana, MD1, Iris Dipalo, MD1, Bozica Magdic, MD1, Davor Stimac, Prof.1, Marij\an Dintinjana, MD2. 1University hospital Rijeka, Rijeka, Croatia, 2Private Practice Ambulance, Rijeka, Croatia.
Background: cancex cachexia occur in significant number of patients (pts) with cancer. Benefit of nutritional support still remain unclear.
Rationale: to examine does nutritional support (counseling, oral liquids, megestrol acetate) has influence on nutritional status and symptoms prevalence in patients with colorectal cancer during chemotherapy.
Methods: We rectospectivelly (group A) examined data of 173 pts who were treated in 3 years period without nutritional counseling. Prospectivelly (group B-215 pts), we offered to our pts individualised nutritional counseling, liquid supplementation, and megestrol acetate. Dietary intake (Nottingham Screening Tool Score) and body weight (Body Mass Indeks) were monitored before, during and after chemotherapy. The nutritional plan was modified when necessary.
Results: during 6 years period we were treating 388 pts with colorectal cancer. Baseline, in the both groups about 55% of pts were moderately or severe malnoutrished.
In group A during chemotherapy 140 (80,9%) of pts decreased in weight gaine 2-5 kg and 77 (44,5%) were severe malnoutrished on the end of chemotherapy. In group B, 184 (85,6%) of pts gain weight. The effect of nutritional support were most expressed in the group receiving Megestrol acetat and nutritional counseling after 4 weeks of therapy. Average gain weight was 1,5 kg (0,6-2,8).
069 The Influence Of Early Supplementation Of Parenteral Nutrition On Quality Of Life And Body Composition In Patients With Advanced Cancer. Edward Shang, MD, Meike Roessler, Stefan Post, MD, Georg Kaehler, MD. University Hospital Mannheim, Mannheim, Germany.
Background: Based on current evidence, most organizations, i.e. the American Society for Parenteral and Enteral Nutrition (ASPEN) recommend the use of an artificial nutrition for carcinoma patients. Despite the general recommendation for parenteral nutrition, data for early supplementary nutrition (PNS) in patients with an advanced malignoma can only be found rudimentary. In addition to the effect PNS has on the body composition it is also quite interesting in connection with the quality of life for these patients.
Methods: Evaluation of prospective controlled and randomized data of 152 consecutive patients suffering from advanced carcinoma and receiving intensified artificial nutrition. Patients are randomized into two groups with one group receiving intensified oral enterai nutrition (PN-), and the other group receiving intensified oral enterai nutrition plus parenteral supplementary nutrition (PN+). The body weight, body mass index (BMI), and caloric intake are measured, hemoglobin (g/dl) and albumin (g/l) are identified in the serum, body composition is identified via body impedance analysis (BlA) and quality of life (QL) is determined via EORTC QLQ-C30 sheets every 6 weeks.
Results: No significant differences were evident between the two groups in reference to age, sex, medical diagnosis, weight, BMI, and QL. The analysis of variance showed an significantly positive influence of the PNS in reference to body weight, BMI, body composition, albumin, quality of life and loss of appetite. The cumulative survival rate was significantly higher in the PN+ group compared to the PN- group (p < .0001).
Conclusion: To sum it up, a PNS significantly improves the quality of life for palliative treated patients with carcinomas. In contrast to a purely intensified oral enteral nutrition, the body composition, body weight loss as well as protein could be stabilized for a long period of time. To detect change in body composition as well as signs of deficiency, the BIA measuring method showed very significant advantages over the BMI and body weight curve measuring methods. Not only because of the positive influence of a PNS in connection with body composition and quality of life but also in reference to the higher survival rate in the PNS group – although afflicted with much bias – more prospective, randomized studies will be conducted to confirm and strengthen these very positive findings.
070 Randomized Study Of Early Enterai Immunonutriton With Gut- Specific Nutritients. Lidija Kompan, MD, PhD1, Stig B.S. Bengmark, MD, PhD2, Irena Vovk, PhD3, Drago Kompan, PhD4.
1Clinical centre Ljubljana, Ljubljana, Slovenia, 2Departments of Hepatology and Surgery, London, United Kingdom, 3National Institue of Chemistry, Ljubljana, Slovenia, 4University of Ljubljana, Ljubljana. Slovenia.
Objective: To assess four different nutritional supplements with gut specific activity. The primary endpoint was to determine whether they influence intestinal permeability (IP), the secondary was their influence on clinical outcome.
Materials and Methods: Multiply injured patients with Injury Severity Score (ISS) of >18 were studied in a 20 bed surgical intensive care unit (ICU). Intragastric tube feeding was started at the latest 24 hours following injury. Patients were randomly allocated into four groups: group A complete diet including 15.5 g of glutamine/ L, group B diet with 22 g of soluble fibres/ L, group C fed with small peptide diet and group D standard diet supplemented with Synbiotic 2000, consisting 4×10 billion lactic acid bacteria of four different strains and 4×2.5 g of four bioactive soluble fibres. On days 2, 4 and 7 after admission IP was evaluated by measuring lactulose-mannitol (L/M) excretion.
Results: 100 multiple injured patients were studied; seven (1 group A, 2 B, 3 C, and 1 group D) died during their treatment in ICU. No differences were observed in length of ICU stay or days on mechanical ventilation. Patients group A coincidently started on enteral nutrition later than the others, yet in first 24 hours they received more feed. Patients group D had the highest gastric retention volume and received the least amount of feed of ail.
IP showed uniform growth till day 7, except group D, which exhibited significant (p<0.05) drop on day 7; L/M index in group D on day 4 was 0.439 and dropped to 0.128 day 7. Group A showed a rise: day 2 0.061 was significantly (p<0.02) lower than day 4 0.223 and increased to 0.515 day 7 (Figure 1). 34 patients showed signs of pneumonia (12 group A, 11 group B, 10 group C and 1 group D), one patient group A suffered urinary tract infection, 2 intravascular catheter infections (1 Group A, 1 group B), 7 wound infections (3 Group A, 1 Group B, 1 group C and 1 group D), 3 had positive hemocultures (1 group A, 2 group B). The difference in pneumonia rate was significant between patients group C and D p< 0.03.
Discussion: Our study did not identify difference in mortality, ICU stay, days of mechanical ventilation. However, those supplemented with Synbiotic, in spite of some intolerance problems, suffered significantly less pneumonia in comparison to those on peptide diet. IP showed uniform growth till day 7, except at those supplemented with Synbiotic. Also the patients on glutamine, showed significant rise in IP. This has been observed before and attributed to dose, yet we were not able to find any correlation between dose and IP.
It is difficult to add immunonutritients to diets, because intolerance problems prevent achievement of sufficient amount. The patients fed with glutamine, peptide diet and those fed with high soluble fibre content had supplements mixed into the diet. Sachets with Synbiotics were mixed with fluids and administered separately. Therefore some of its influence could be attributed to the administration protocol.
071 Phenytoin Binding to Enteral Formulas in an Equilibrium Dialysis Model as Analyzed using HPLC. Mark Klang, MS, RPh, BCNSP, Michelle Chan. Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Introduction: Phenytoin (PHT) binds to enteral feeding formula administered through feeding tubes. Unpredictable absorption has been documented clinically following concomitant administration of PHT and nutrition formulas. Binding of PHT to the intact protein in enteral nutrition, has been suggested as a cause of reduced absorption. This equilibrium dialysis model looks at the rate of dissolution of PHT crushed tablets or suspension in either gastric or intestinal environments. The effect of the nutrition formulas on dissolution will be compared to an equal volume of water.
Methods: A mixture was prepared containing 50 mg PHT / 25 ml de- ionized triple filtered water, using either a crushed tablet or 2 ml of suspension. The mixture was set on vortex for 10 seconds before 5 ml samples were removed. This was combined in a 5 cm dialysis (<3500 mw) pouch with 5 ml of water, standard enteral formula (SE), high protein formula (HP) or peptide based (PB) formula. Packets were placed in beakers containing 200 mL's of either USP simulated gastric fluid (SG) pH 1.2 or USP simulated intestinal fluid (SI) pH 6.8. Beakers were placed in an incubated (37 C) shaker for 3 hours. 5 ml samples were withdrawn at 30, 90, 120 and 180 minutes. The samples were analyzed by HPLC using an Agilient 1100, @ 1 ml/hr, SB- CN Zorbax 4.6X150 5 μm at 50C. Mobile phase consisted of ACN: Methanol: Acetic Acid: Triethylamine: water (150:125:1.0:0.6:725). Each sample was tested in triplicate along with a bracketed internal standard. Based upon initial linear curve values were converted into meg/ml concentration.
Results: All values were normalized against the values of PHT combined with an equal volume of water. Results are reported as the comparative total percent available of PHT after combination with the nutrition formulas after 3 hours. Both tablet and suspension formulations were compared in either SG or SI.
Discussion: All samples combined with Standard Enteral formula (SE) showed reduced availability. Highest loss occurred when the PHT tablet formulation was mixed with gastric fluid. PHT is least soluble in an acidic milieu. Surprisingly, the High Protein formul\a did not show increased loss of PHT when combined in most samples. This suggests that the loss of PHT is not solely due to direct protein-binding controlled scenario. This idea is reinforced by the Peptide Based product, which contains no intact protein, yet demonstrates reduced release of PHT. Earlier literature suggested the tablet formulation may be superior or equal in binding to enteral formulas. This report does not support that concept. Further studies will be needed to determine the exact mechanism of this interaction.
072 Effects of a Synthetic Protease Inhibitor on Gut Ischemia- reperfusion-induced Changes in Gut-associated Lymphoid Tissue and Organ Vascular Permeability. Kazuhiko Fukatsu, MD1, Tomoyuki Moriya, MD2, Etsuko Hara, MT1, Chikara Ueno, MD3, Yoshinori Maeshima, MD3, Hidetaka Mochizuki, MD3, Hoshio Hiraide, MD1. 1National Defense Medical College Research Institute, Tokorozawa, Japan, 2Chiba University Department of Surgery I, Chiba, Japan, 3National Defense Medical College Department of Surgery I, Tokorozawa-city, Japan.
Background: Gut hypoperfusion causes remote organ injury and impairs gut barrier function, resulting in MOF. In addition, our previous study revealed that gut ischemia-reperfusion (I/R) affects gut-associated lymphoid tissue (GALT), a center of mucosal immunity, reducing GALT cell number and changing its phenotype. We hypothesized that gabexate mesilate (GM), a synthetic protease inhibitor, would reverse I/R-induced changes in GALT and organ vascular permeability.
Methods: Male ICR mice were randomized to control and GM groups. After IV cannulation, the mice underwent 60 minutes of I/R. Control mice received normal saline infusions at 0.3 ml/h for 3 hours (1 hour during ischemia and 2 hours after reperfusion), while GM mice received 10 mg/kg/h of GM. Survival at 24 h after reperfusion was monitored (n=39). Lymphocyte numbers in Peyer’s patches (PP), lamina propria (LP) cells, and intraepithelial (IE) spaces in the small intestine were determined at 24 h (n=20). The lymphocytic phenotypes (αβTCR, γδTCR, CD4, CD8, and B220 as a B cell marker) were also determined using flowcytometry. Another set of mice were assessed for organ vascular permeability at 4 h using the Evans blue technique (n=7).
Results: Survival rates at 24 h were 65% (11/17) in the GM and 59% (13/22) in the control group. GM treatment significantly increased total the IE lymphocyte number and the absolute number of γδTCR+, CD8+ and B220+ cells in IE spaces and γδTCR+ cells in the LP, as compared with controls. GM significantly reduced pulmonary vascular permeability.
Conclusion: Despite the lack of a marked effect on survival at 24 h, GM treatment after onset of gut ischemia reduces GALT cell loss and lung injury, suggesting a possible therapeutic option for gut hypoperfusion.
GALT lymphocyte numbers (x 10^sup 6^)
073 Intestinal Bacterial Flora in Patients on Long Term Home Enteral Nutrition. Lidia Santarpia, MD1, Lucia Alfonsi, MD1, Ida Torre, MD2, Francesca Pennino, MD2, Rossella Bonifacio, MD1, Vincenzo Corcione, MD3, Fabrizio Pasanisi, MD1, Franco Contaldo, MD1. 1Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy, 2Department of Hygiene and Preventive Medicine, Federico II University, Naples, Italy, 3Clinical Nutrition, Nola Civil Hospital, Naples, Italy.
Only few studies are available on the long term effects of Total Enteral Nutrition on intestinal bacterial flora. The aim of this study was to evaluate the possible effects of long term HEN on intestinal bacterial flora and its relation with anthropometric, some routine and inflammatory biochemical parameters. Eighteen patients (11 F, 7 M, 52.9 19.9 yrs; 53.8 9.8 kg; 20.4 3.2 kg/m2) on long term HEN (>6 months) and 18 healthy controls (10 F, 8 M, 48.6 17.5 yrs; 67.8 11.0 kg; 24.8 3.6 kg/m2) selected among relatives living with the patients were recruited.
Baseline diseases were: 5 Amiotrophic Lateral Sclerosis, 4 Cerebellar Ataxia, 3 Alzheimer Disease, 2 post surgery dysphagia, 1 Multiple Sclerosis, 1 neonatal cerebral disease; 14 received fiber enriched formulas and 4 standard EN formulas. Controls were 5 parents, 7 sons, 4 consorts and 2 germans. Selected anthropometric parameters, routine biochemical variables and serum TNFα, IL1β and IL6 were measured. Fecal bacteria were identified according to standard methods and numbered (Log CFU/g feces). U- Mann Whitney Test was used for statistical analysis.
Patients’ body weight (p< 0.0001), BMI (p< 0.001) and serum albumin (3.5 05 g/dL vs 4.2 0.3; p< 0.0001), cholesterol (151 30 mg/dL vs 185 32; p< 0.01), lymphocytes (1844 743/mm3 vs 2441 835 p< 0.05) and haemoglobin (12.8 2.0 g/dL vs13.8 1.0; p< 0.05) were significantly lower than in controls; whereas white blood cells (9378 5278/mm3 vs 7794 2477; p< 0.01), platelet count (301 218/ mm3 vs 240 vs 54 p< 0.01), IL6 (11.0 pg/mL 14.8 vs 6.2 3.3; p< 0.01) and ferritin (344 ng/mL 459 vs 110 79; p< 0.01) were significantly higher. Moreover serum albumin was inversely related to white blood cells (r = - 0.50; p = 0.03) and platelet count (r = - 0.53; p = 0.02) and ferritin to cholesterol (r = - 0.51; p =0.03) and cholinesterase (r = - 0.49; p =0.04). The number of aerobes and anaerobes species did not differ among patients and controls: Escherichia Coli and Staphylococci among aerobes and Clostridi, Bacteroides and Prevotellae among anaerobes being the most frequent germs in both groups.
Total bacterial number was significantly higher in patients compared to controls. Lactobacilli have been isolated mostly in controls, while Peptostreptococci only in patients. Anaerobes were in significantly higher concentration in patients receiving fiber enriched than in those receiving standard EN formulas (p< 0.05).
In conclusion, in our experience, TEN does not reduce the number of the species of the intestinal flora. Fiber enriched EN formulas seem to positively and significantly influence intestinal bacterial flora. Long term Home EN patients were slightly undernourished compared to controls. The nutritional and phlogistic parameters measured were inversely related.
074 The Effects Of Probiotics On Glutation Reductase, Glutathione- s-transferase And Pentose Phosphate Pathway Regulating Enzymes After Abdominal Irradiation In Rats. Seher Demirer, Associated proffesor1, Nuray Nuriye Ulusu, Associated proffesor2, Belma Aslim, Proffesor3, Ilknur Kepenekci, Fellow surgeon4, Ulusoy Cemal, Resident4, Meltem Nalca Andreiu, Associated proffesor5, Aydmtug Semih, Proffesor1. 1Ankara University School of Medicine Department of Surgery Nutrition Team, Ankara, Turkey, 2Hacettepe University School of Medicine Department of Biochemistry, Ankara, Turkey, 3Gazi University Faculty of Science, Ankara, Turkey, 4Ankara University School of Medicine Department of Surgery, Ankara, Turkey, 5Ankara University School of Medicine Department of Radiation Oncology, Ankara, Turkey. Radiation is an important aspect of multimodal cancer therapy. Radiation induced acute intestinal injury after abdominal and pelvic irradiation is a common and serious problem. Probiotics are defined as living microorganisms that belong to the normal enteric flora and when administered in adequate amounts, confer a health benefit on the host. The best known are iactobacillus and bifidobacteria which are widely used in yoghurts and other dairy products.
The aim of this study was to evaluate the protective effect of probiotics on the activities of glutathione-S-transferase, glutathione reductase and pentose phosphate pathway regulating enzymes after abdominal radiotherapy. Glutathione is an antioxidant which plays important roles in phase-II detoxification of carcinogens. The levels of reduced glutathione are maintained by glutathione-depleting as well as regenerating enzymes such as glutathione-S-transferase and glutathione reductase, respectively. Pentose phosphate pathway performs a variety of functions: Production of ribose-5-phosphate for nucleotide synthesis; generation of NADPH for the biosynthetic reactions and also the protection of the cells against oxygen radical injury. Also it is known that glucose-6-phosphate dehydrogenase plays a critical role in cell growth and cell death. 6-phosphogluconate dehydrogenase is the second enzyme in the pentose phosphate pathway and responsible for the production of 50% of NADPH formed by the pentose phosphate pathway. 27 Wistar Albino rats were divided into 3 groups. Lactobacillus bulgaricus strain isolated from yoghurt was used as probiotic. The first group consisting of 7 rats did’nt receive radiotherapy but only probiotics (Group1). Remaining 20 rats were subjected to a single dose of 1100 rads of X radiation to the abdomen and further divided into two groups. 10 rats received probiotics (Group 2), and 10 rats received placebo (Group 3) for 7 days after radiotherapy. All rats were sacrified on postradiation day 8. We removed jejunal. ileal and colonie segments and the effects of probiotics in irradiated intestinal and colonic segments were examined using the activities of these enzymes. Radioactivity treatment increased the activity of the jejenum glutathione-S- transferase in group 3. This found to be significant (p <0.05). After probiotic treatment glutathione-S-transferase levels were return to the same level as the first group. We thought that probiotic treatment could increase the antioxidant defence mechanism by an unknown mechanism and normalized the enzyme activity. There was not any significant change in the glutathione reductase and glutathione-S-transferase enzyme activities in the colon and ileum. Glucose-6-phosphat dehydrogenase showed a significant (p<0.05) increase in group 3. The increase was seen in group 2 but this increase was not found to be significant (p>0.05). This may be show that the probiotic tr\eatment normalized the enzyme activity. 6- phosphogluconate mean value was increased approximately two times in the second and third group but this increase was not found significant. There was no change in the activity of 6- phosphogluconatc dehydrogenase enzyme in the jejunum. These results support the idea that probiotics may have some beneficial effect against radiation induced intestinal injury. But randomized studies with higher numbers of animals are needed for better clarification of the role of probiotics on radiation enteritis.
075 Does the Maximum Change in Hydrogen Production with the Lactose Breath Hydrogen Test Reveal the Severity of the Lactose Intolerance? Jose Beauchamp, RD, M.Sc., Selina Lai, RD, Margaret Boland, MD, David Mack, MD. Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada.
Background: A positive lactose breath hydrogen test (LBHT) requires a minimum rise of 20 parts per million (ppm) of hydrogen above baseline. The aim of this study was to evaluate if there was a relationship between the maximum change in hydrogen production following ingestion of lactose with the LBHT and the degree of lactose intolerance.
Methods: From January 2001 to February 2004, 211 patients were screened for lactose intolerance with the LBHT in the Division of Gastroenterology at the Children’s Hospital of Eastern Ontario, Canada. A total of 44 patients (21%) had a positive LBHT. Patients were given a dose of lactose of either 1 gram/kilogram to a maximum of 25 grams (group A) or to a maximum of 50 grams (group B). Patients with a positive LBHT were assigned to a phase of the lactose-free diet based on the maximum change in hydrogen production (see table below).
Results: Of the 44 positive LBHT, 26 patients were in group A and 18 patients were in group B. The median change in hydrogen was 43.5 ppm for group A and 56.5 ppm for group B. A Spearman’s correlation test indicated a negative relationship between the maximum change in hydrogen production and the successful phase of the lactose-free diet for both groups; however, this relationship was not statistically significant for either group. The correlation was – 0.240 (p-value=0.237) and -0.127 (p-value=0.627) for groups A and B respectively.
Conclusion: The LBHT gives a clear indication of lactose intolerance but the maximum change in hydrogen production does not correlate with the ability of patients to tolerate lactose. Therefore, we cannot allocate a specific phase of the lactose-free diet according to the maximum change in hydrogen production.
Lactose-free diet phase according to maximum change in hydrogen production
076 Influence of Preoperative Feeding on the Healing of Colonic Anastomosis in Malnourished Rats. Carolina G. Goncalves, MD1, Antonio C. Campos, MD, PhD1, Julio C. Coelho, MD, PhD1, Anne K. Groth, MD1, Marcelo Ferreira, MD1, Danilo Aedo, BSc1, Michael M. Meguid, M.D., PhD2. 1 Federal University of Parana, Curitiba, Brazil, 2 SUNY Upstate Medical University, Syracuse, NY, USA.
Malnutrition influences the healing of gastrointestinal anastomosis. We hypothesized that the healing of colonic anastomosis is decreased by malnutrition and it might be improved by pre- operative re-feeding. To test our hypothesis we studied fifty-six adult male Wistar rats, weighing 327 38 g. The rats were housed in individual cages and after one week of acclimation were randomly divided into 4 groups that were subjected to two colonie anastomoses: i. Control rats (C21), fed regular chow diet ad libitum for 21 days; ii. Malnourished pairfed rats (MPF), fed 50% of the average of the in Healing of Colonic Anastomosis in Rats gested food by the control rats for 21 days; iii. Malnourished pair-fed (MPFR) and re-fed rats that were fed 50% diet for 21 days and then re-fed with regular chow diet ad libitum for 1 week before the surgical procedure; iv. Control re-fed rats (CRF), fed ad libitum for 28 days. On the 21 or 28 days the rats were anesthetized and subjected to 2 colonic transections, one at 6 cm distal to the ileo cecal valve and another 10 cm distal from the first transection. Colon continuity was restored by 2 end-to-end, single layer, everted anastomosis with 8 interrupted sutures (6-0 nylon). After the operation, the rats were kept in individual cages and had free access to water and rat chow. The rats were killed on operative day 5, and the 2 colonic anastomoses of each animal were resected and stored in 0.9% saline and 10% formalin for tensile strength and histologic (collagen densitometry) studies, respectively. Student’s t-test and Kruskal Wallis tests were used for statistical analysis.
Results: Total rupture strength was significantly lower in the malnourished group (MNS) compared to the control (C21) group (0.57 0.02 vs. 0.093 0.04 (kgf/mm^sup 2^, p<0,05)), and the collagen densitometry analysis demonstrated lesser percent area of type I (mature) in the MNS group compared to controls (C21) (4.02 1.16 vs. 5.82 1.32 (kgf/mm^sup 2^, p<0,05)), while in the malnourished re- fed rats (MPFR) the rupture strength was increased compared to the MNS group (0.79 0.05 vs. 0.57 0.02(kgf/mn^sup 2^, p<0,05)) but still decreased when compared to the control rats (CRF) (0.79 0.05 vs. 0.91 0.06 (kgf/mm^sup 2^, p<0,05)) .The mature collagen was also decreased when compared to controls (4.77 1.71 vs. 6.81 2.61).
Conclusions: Malnutrition decreases the total rupture strength and the percentage area of mature collagen deposition at the anastomosis site on PO day 5. Pre-operative re-feeding for 7 days increases the tensile strength and the percentage area of mature collagen but not in enough proportion as to reach the control values.
077 Hyperglycemia in Hematopoietic Stem Cell Transplant (HSCT) Patients: the Joint Effects of Total Parenteral Nutrition (TPN) and Obesity (Body Mass Index ≥30). Patricia Sheean, M.S., R.D., Carol Braunschweig, Ph.D., R.D. University of Illnois at Chicago, Chicago, IL, USA. The benefits of TPN provision for obese hospitalized patients with temporary gastrointestinal compromise are unknown. Because obesity and TPN are each independently associated with hyperglycemia, we hypothesized exposure to either (or both) would lead to higher incidence rates of hyperglycemia and result in increased morbidity and mcrtality. The purpose of this retrospective cohort investigation was to: 1) determine the incidence of hyperglycemia in patients undergoing initial HSCT (N=311), without diabetes, stratified by TPN exposure and obesity, and 2) evaluate the impact of TPN exposure on clinical outcomes (infections, blood product support, length of stay, mortality). Medical records at 2 hospitals were reviewed for clinical outcomes and hyperglycemia (glucose ≥ 110 mg/dL). Chi square, Student’s t and Wilcoxon rank-sum tests were used to detect differences between obese (BMI ≥ 30) and TPN (yes/no) groups. Discrepancies between groups and disease severity were addressed by: 1) comparing admission demographics, medical and surgical histories, nutritional status, glucose, white cell count, and Karnofsky scores for TPN vs. non-TPN and obese vs. lean patients, and 2) discerning the temporality of outcomes with regard to TPN exposure before and after TPN initiation. To this end, standardized time frames were created using the mean hospital days prior to TPN initiation (“before TPN” = 12 days) and the mean hospital days of TPN exposure (“after TPN” = 12 days) to determine and compare the proportion of hyperglycemic days in non-TPN patients; actual TPN infusion days were used to calculate proportion of hyperglycemic days for TPN patients. No differences in baseline characteristics were found between TPN and non-TPN groups. Obese patients were more likely to be female (p=.04) and African American (p=0.003). Comparisons were made within (i.e., obese TPN vs. lean TPN, etc.), and across (i.e., obese TPN vs. obese non-TPN, etc.) groups. Generally, TPN administration and obesity were independently and jointly associated with significantly greater hyperglycemia and increased morbidity. Specifically: a) no differences were detected across groups “before” for hyperglycemia, infections or blood product support, b) within those exposed to TPN, significantly more hyperglycemia occurred “after TPN” vs. “before TPN” in both obese and lean; c) within the lean TPN patients, significantly more infections (p=0.003), red cell (p=0.001) and platelet transfusions (p=0.0001) occurred “after TPN” vs. “before TPN”; d) compared to their TPN counterparts, non-TPN patients (both obese and lean) had significant reductions in hyperglycemia (p<0.0001), infections (p=0.02), red cell (p=0.001) and platelet transfusions (p=.008) "after": and e) among non-TPN patients, obese patients had significantly more hyperglycemic events than lean patients "after." Additionally, TPN patients had longer hospital stays (p<0.0001), more repeat positive cultures (p=0.006), and greater in-hospital mortality (p=0.001) than non-TPN recipients, and separately. TPN and obese patients experienced prolonged engraftment time (p<0.05). Overall, TPN administration in HSCT patients was associated with significantly worse glycemic control, greater morbidity and rendered lean patients "metabolically obese." These findings have enormous implications for current parenteral feeding practices.
The incidence of hyperglycemie days, stratified by TPN and obesity (n=311)
078 Effects of Adequate Nutrition Support, Acute Hyperglycemia and Acute Hyperinsulinemia on the Systemic Inflammatory Response and Hepatic Oxidative Stress in Rats. Pei-Ra Ling, M.D., Bruce R. Bistrian, M.D, Ph.D. Beth Israel Deaconess Medical Center, Boston, MA, USA. The purpose of this study was to compare the effects of adequate nutrition support (NS) (200 kcal/kg.day, n=8), acute hyperglycemia (HG) (glucose infusion rate 8.4 g/kg.hr, glucose- target 300 mg/dl, n=9), and acute hyperinsulinemia (HI\) (insulin infusion rate 7.5. mU/kg.min, glucose-target 100-120 mg/dl, n=10) for 3 hours on the systemic inflammatory response and hepatic oxidative stress in rats. Non-fasted animals were used as controls (Con, n=9). At the end of 3 hours, serum levels of glucose, insulin, tumor necrosis factor (TNF). interleukin 1 (IL-1), and alpha-1 acid glycoprotein (AGP) were measured. Malondialdehyde (MDA) and total glutathione (TGSH) were determined in the liver.
NS significantly increased glucose concentration (range from 133 – 156 mg/dl). and slightly increased insulin levels as compared to Con. HG significantly increased serum levels of TNF, IL-1 and AGP and the content of MDA in the liver and significantly decreased hepatic total glutalhione content compared to Con and NS. HI significantly increased MDA but not other markers compared to Con. However, the levels of TNF appeared to be comparable between HI and NS, while the levels of MDA were comparable between HI and HG. These results demonstrate that 1) adequate nutrition support producing mild hyperglycemia pad no impact on inflammation; 2) hyperinsulinemia without hyperglycemia induced by the same amount of glucose infusion as NS increased MDA but not other markers; 3) severe hyperglycemia with hyperinsulinemia induced by glucose over- feeding induced a full systemic inflammatory response and hepatic oxidative stress. Thus, both substantial hyperglycemia (glucose >150 mg/dl) and severe hyperinsulinemia (insulin > 112 μU/ml) can produce hepatic oxidative stress, while a full-blown systemic inflammatory response occurs when both are present.
079 ENCORE PRESENTATION Infectious Complications in Patiets Receiving Home Parenteral Nutrition is Associated with Blood Glucose Control. John K. Siepler, Pharm.D., Reid A. Nishikawa, Pharm.D., Tom Diamantidis, Pharm.D., Craig Petersen, Rod Okamoto, BS, RPh. Nutrishare, Inc, Elk Grove, CA, CA, USA.
Background: A reduction in infectious complications was demonstrated in critically ill patients with strictly controlled blood glucose(BG). We wanted to determine if there was an association between BG control and infectious complications in patients on long-term home parenteral nutrition (HPN).
Methods: A retrospective review of outpatient BG determinations in HPN patients from one homecare provider were collected for a six month period. BG determinations were obtained in the morning after HPN was tapered off. Mean BG values were calculated for each patient. Patient demographic data and HPN calorie provisions were recorded. Catheter related blood stream infections (CRBSI) and antibiotic use(ABX) were recorded and compared to mean BG. Logistic regression was used to determine a relationship between BG and CRBSI or ABX. MiniTab V. 14 was used for statistical analysis with p<0.05 being significant.
Results: There were 131 patients who met the inclusion criteria. The mean age was 4119 years with 84(64%) being female. The mean weight, duration of HPN, and total caloric delivery were 5611kg, 85.6 years, and 2920cal/kg respectively. There were 681 BGs obtained with a mean value of 9317mg/dl. There were 35 patients (26.7%) with a CRBSI (2.1 4.6/1,000cath days). ABX use was 9.925.2 days/episode of CRBSI. The mean BG was nearly identical in those patients with or without a CRBSI (92.8 mg/dl vs 92.6 mg/dl). Despite the lack of a difference in the mean BG, there was a association between BG and CRBSI. Patients whose mean BG was >90mg/dl had an increased incidence of CRBSI and ABX use. This relationship was not present for those patients whose >100mg/dl. (see below for RR and 95%CI).
Conclusions: We have demonstrated that patients whose mean BG was below 90mg/dl but not below 100 for the first 9 months of 2004 had a lower rate of CI and ABX use. These results are consistent with data in critically ill patients, but a randomized trial controlling BG should be conducted before one can say that tight BG control will reduce CI rate and ABX use. (CI=n/1,000cath days, ABX= Antibiotic days). (Statistical comparisons are for patients with BG > 90 with those <90 and those >100 with those <100)
HPN Complications & Blood Glucose
080 Autopsy Tissue Selenium Levels In Eight Home Parenteral Nutrition (HPN) Patients. Lyn Howard, MB, FRCP1, Christopher Ashley, MD1, David Lyon, PhD2, Alan Shenkin, PhD3. 1 Medicine, Division of GI and Nutrition, Albany Medical College, Albany, NY, USA, 2 Biochemistry, Royal Infirmary, Glasgow, United Kingdom, 3 Clinical Chemistry, Royal Liverpool University Hospital, Liverpool, United Kingdom.
Background: Parenteral trace element requirements are not precisely known. Plasma values are not reliable indicators in patients receiving daily intravenous trace elements. To better define Se needs the element was measured in autopsy materials from 8 patients with short bowel due to Crohn’s disease (4) and mesenteric ischemia (4).
Method: Se concentrations were determined by inductively coupled MASS spectrometry in heart, muscle, liver and kidney tissue of the 8 HPN patients (P) and compared to previously reported values from 45 age matched control subjects (C).
Results: Patient characteristics, mean (range) age 46 yrs (29- 69); HPN duration 14 yrs (2-20); jejunal length 60 cm (0-90). Patients received 600 μm of parenteral Se per week Se values μg/g dry weight Mean (SD)
90% of individual tissue values fell within the mean 2 SD for controls. In the 2 younger subjects muscle and kidney values were low. Neither of these subjects complained of muscle cramps when alive and glutathione peroxidase activity was not measured.
Conclusion: These results suggest most long term HPN patients achieve normal tissue Se levels with 600 μg of parenteral Se per week. Younger subjects appear to require somewhat higher amounts to achieve the higher tissue levels of their age matched controls.
081 When all else fails: The Role of Intestinal Transplantation. Geoffrey J. Bond, MD1, George Mazariegos, MD2, Rakesh Sindhi, MD2, Kareem Abu-Elmagd, MD1. 1 Intestinal Rehabilitation and Transplant Center, Pittsburgh, PA, USA, 2 Children’s Hospital, Pittsburgh, PA, USA.
Purpose: Intestinal transplantation has progressed significantly since it’s inception in the 1960′s. Early results were universally poor, and it wasn’t until the introduction of Tacrolimus in the 1990′s that intestinal transplantation became systematically achievable. Now it has progressed from an “experimental” stage to a clinical reality. It offers those patients suffering terminal complications of parenteral nutrition (PN) an alternative therapy for their intestinal failure. So successful, intestinal and multivisceral transplantation has become the Medicare accepted standard of care for this group of patients, with outcomes approaching those of other solid organ transplants. We present the largest single center experience with this procedure, in adults and in children, that has allowed the majority of these patients to regain their previous lifestyles and become PN free. In particular, recent novel immunosuppression strategies have allow for dosage minimization that augers well for improved long term outcomes in adults and especially in children.
Methods: Over the last 14 years, 286 patients received 307 intestinal containing allografts, almost a third of those performed world-wide. Of these 151 (53%) were adults and 48% were female. The majority of patients suffer from short gut syndrome, the children mostly from congenital or neonatal afflictions, the adults from thrombotic or acquired diseases. The types of transplants included isolated intestine (n=137, 45%, mostly adults), liver/intestine (n=104, 34%, mostly children), and multivisceral (n=66, 21%, mostly adults). Historically, immunosuppression began with tacrolimus and steroids, and later the addition of further immunosuppressants as developed throughout the 1990′s. This led to an overall enhanced level of immunosuppression, with concomitant infectious complications. Recently, a tolerogenic protocol of preconditioning induction and post-transplant steroid-free monotherapy with delayed dosing minimization has been utilized. This has allowed for patients to be on single drug therapy as little as once a week.
Results: Patient and graft survival continues to improve. Over the entire experience, greater than 60% of patients are still alive. The recent one-year patient and graft survival is greater than 95% and 90% respectively. Greater than 96% of patients become PN free and are able to return to unrestricted enterai diet. Infectious complications (CMV, EBV/PTLD) have markedly decreased, in part due to monitoring and treatment strategies, but also due to the lowered overall levels of immunosuppression. The majority of recent patients (since July 2001) are off steroids and on tacrolimus monotherapy at spaced doses, from once a day to as little as once a week.
Conclusion: Intestinal transplantation, once considered experimental at best, has with ‘perseverance and experience, proved itself to be a lifesaving therapy for patients with endstage intestinal failure. Recent immunosuppression protocols offer long- term benefits to the patients, especially the chance for the children to be steroid-free. Continued progress is being made, to the extent where intestinal transplantation may be a consideration even before terminal complications arise. Until that date, intestinal transplantation should be considered for those with intestinal failure in whom all other modalities of treatments have failed.
082 Catheter-related Sepsis during Long-term TPN for Chronic Intestinal Pseudoobstruction -The Role of Bacterial Translocation and the Prospects of Synbiotics. Akio Kubota, MD, PhD, Hisayoshi Kawahara, MD, PhD, HIroomi Okuyama, MD, PhD, Hiroshi Nakai, MD, Hideki Yoshida, MD, Yuichi Takama, MD, Yuki Kiyohara, MD, Shinobu Ida, MD, PhD. Osaka Medical Center for Maternal and Child Health, Osaka, Japan.
Ba\ckground/Purpose: Hypoganglionosis (HG) is a kind of chronic intestinal pseudoobstruction (CIP), which is characterized by intractable non-mechanical ileus manifested in the neonatal period and histologicaliy hypogenetic myenteric plexus. On the other hand, congenital CIP including HG which depends on long-term total patenterai nutrition (TPN) is called intestinal failure, and its long-term prognosis is extremely poor. We have experienced seven cases of HG, and five of them died of catheter-related sepsis (CRS) and hepatic failure associated with intractable stagnant enteritis and long-term TPN. In this study, we investigated whether bacterial translocation (BT) from bacterial overgrowth in the stagnant intestine is responsible for CRS on long-term TPN, and whether synbiotics is prospective effective in suppression of bacterial overgrowth in the stagnant intestine and prevention of BT in cases of HG on long-term TPN.
Methods/Materials: Six cases of HG which had been on TPN from the neonatal period for more than one year are included this study. CRS was defined when the culture of catheter tip or blood withdrawn through the catheter were identical with that of stool or intestinal microbes. As synbiotics therapy. Lactobacillus casei Shirota 3×10^sup 9^ bacteria, Bifidobacterium breve Yakult 3×10^sup 9^ bacteria and Galacto-oligosaccharide 3 gram per day were administered perorally.
Results: case 1-3 died of sepsis and hepatic failure caused by stagnant enteritis at age of 1.8 – 2.2 years, all of them were dependent on TPN whole their lives. case 4 had been on and off TPN since her birth, and at age of 10 years, he died of sepsis and hepatic failure after surgical repair to intractable intestinal stagnation. case5 (17 year-old) has been totally or partially dependent on PN since her birth, at present she is a candidate for small bowel transplantation (SBT). case 6 (10 year-old) is on HPN, and he can eat small amount of low-residual diet. The incidence of CRS (number of episodes per 1,000 catheter-day) in case 1 – 3, 4, 5 and 6 were 5.1 – 5, 0.9, 1.1 and 0.6, respectively. The incidence of CRS caused by BT in case 1 – 3, 4, 5 and 6 were 1.1 – 1.7, 0.5, 1.1 and 0.4, respectively. In surviving cases, cases 5 and 6, synbiotics have been administered for 2 years, and for these two years, both cases have not had CRS or BT. After commencement of synbiotics therapy, abdominal distention or bowel dilatation on X-ray were attenuated obviously.
Conclusion: All the cases of HG experienced episodes of CRS during TPN, and in each case at least one of them was caused by BT. There was a tendency that the severer clinical symptom the higher the incidence of CRS and BT. Synbiotics therapy is suggested to be effective in suppression of intestinal bacteria overgrowth and eventually prevent BT during long-term TPN for CIP.
083 Noninvasive Measurement of Transit Time in Short Bowel Syndrome. Charlene W. Compher, PhD, Stephen Rubesin, MD, Bruce Kinosian, MD, Julie Madaras, BA, David Metz, MD. University of Pennsylvania, Philadelphia, PA, USA.
Background: Patients with short bowel syndrome (SBS) have rapid transit lime (TT), relative to normal controls, a factor that compromises nutrient absorption. The purpose of this study was to establish a clinically-feasible, noninvasive method with acceptable accuracy for TT measurement.
Hypothesis: Measurement of TT by radiography of serial stool samples following the ingestion of radio-opaque plastic rings will measure TT with accuracy.
Method: Patients with SBS obtained measurement of TT by 3 methods during admission to the General Clinical Research Center. The first method timed the first appearance of bluegreen color in ostomy effluent or stool after the ingestion of blue food dye, both in the fasted state and just prior to the morning meal. The second employed radiographic examination of frozen, timed, serial ostomy effluent or stool samples for 48 hours after taking a Sitzmark capsule just prior to the morning meal. The third method was lactulose-breath hydrogen testing of oral-cecal or oral-colonic transit, after an overnight fast, with termination of the test shortly after blue food dye (added to the 10 g lactulose dose) appeared in ostomy effluent or stool. If bacterial overgrowth or nonfermentation was obtained, the breath hydrogen test was repeated after several weeks to confirm the finding. Data are presented as median (SEM) due to the non- normal data distribution.
Results: Six subjects with age 65 (SEM 3.4) years, 62 (SEM 19) months of home parenteral nutrition due to SBS as a result of infarction (3), IBD (2) or cancer resection (1) were studied. TT was longer in subjects with a colonie segment than in those with SB ostomies. Feeding a solid meal shortened the median TT by 15 minutes relative to fasting, and lactulose shortened median TT by 25 minutes. The Sitzmark procedure measured a longer post-meal TT but required collection of serial stool samples for > 48 hrs, an arduous task for patients at home. Breath hydrogen testing did not reveal TT in most subjects, due to bacterial overgrowth or nonfermentation of lactulose. Individual data are presented below.
Conclusions: The appearance of color in stool or ostomy effluent after ingestion of blue food dye is more informative of TT than breath hydrogen testing, and more convenient than 48 hour stool collections.
Table 1. Individual Transit Time Data. Median (SEM).
084 A New Graduated Dosing Regimen For Phosphorus Replacement In Patients Receiving Nutrition Support. Kaleb A. Brown, PharmD1, Roland N. Dickerson, PharmD1, Laurie Morgan, RN2, Katy Alexander, MS, RD2, Gayle Minard, MD1, Rex O. Brown, Pharm.D.1. 1 University of Tennessee Health Science Center, Memphis, TN, USA, 2 Regional Medical Center at Memphis, Memphis, TN, USA.
Background: We have previously reported use of a graduated dos