- Email: [email protected]
O.37 Preventive enteral administration of ornithinealpha-ketoglutarate improves intestinal mucosal repair after transient ischemia in rats
0.34 Perioperative TPN in malnourished patients with gastrointestinal cancer: a randomized clinical trial
0.35 Increased rates of gluconeogenesis from alanine in weight-losing lung cancer patients
F. Bozzetti, C. Gavazzi, L. Cozzaglio, R. Mice~i, N. Rossi, L. Mariani and S. Piacenza Istituto Nazioinale Tumori, Milano, Italy,
S.
H a l f w e r k , P. C. Dagnelie, J. W. O. van den Berg, C. H. K. Hordijk-Luijk, J. L. D. Wattimena, G. R. Swart and J. H. P. Wilson Institute of Internal Medicine II, Erasmus University of Rotterdam, The Netherlands.
Aim of the study: To evaluate the impact of TPN on post-operative morbidity and mortality in malnourished patients affected by gastrointestinal cancer.
Introduction: Cancer cachexia is characterized by increased loss of muscle mass and body protein. One of the suggested mechanisms of this phenomenon involves elevated utilization of muscle-derived amino acids, alanine especially, for hepatic glucose synthesis (gluconeogenesis). Gluconeogenesis from alanine has never been quantitatively assessed in patients with specific tumour types. Aim o f the study: To compare gluconeogenesis from alanine in lung cancer patients with/without weight loss and healthy subjects. Methods: We studied weight-stable (WS, n = 8) and weight-losing (WL, n = 5) lung cancer patients, without liver metastases or metabolic disease. Healthy subjects were included as controls (n = 10). After an overnight fast, turnover measurements were performed in steady state (60-90 minutes) using a primed-constant infusion of [6,6-2H2]-glucese and [3-13C]-alanine. Results: WL patients had lost an average of 15% (range 8-22%) of preillness weight over the previous 6 months. Alanine flux and gluconeogenesis from alanine were markedly elevated in WL lung cancer patients when compared with WS patients and healthy controls (Table 1). Glucose flux was also significantly higher in WL patients than in control subjects. Table 1 : Turnover rates (mmol/kg.h) in lung cancer patients and controls (mean _+SEM).
Patients and methods: Ninety malnourished patients (weight loss _>10% of usual weight), affected by gastric or colon-rectum cancer, were stratified by tumour localization and age (_65 years), and were randomized in two groups. TPN group (43 patients) received TPN through a central venous catheter for 10 days before surgery and up to onset of bowel movements. Non-protein calories were planned as 150% of resting energy expenditure, with lipids accounting for 30% of non-protein calories and Kcal:N ratio of 150:1. Control group (CTR; 47 patients) followed a standard oral diet before surgery, and received a hypocaloric parenteral nutrition post-operatively. Morbidity (mild and severe complications) and hospital mortality were recorded for each patient. Severe complications were those requiring admission to ICU or a second surgical procedure.
Results: On the whole, post-operative complications were 57 in 27 patients of CTR group and 25 in 16 patients of TPN group. The frequency of patients with mild and severe complications was 32% and 25% in CTR group, 25% and 12% in TPN group. The difference between the two groups was statistically significant at the MannWhitney test (P = 0.013). Such difference was mainly due to non-infectious complications. Five patients in the CTR group died after severe complications whereas none in TPN group (P = 0.035 at the Fisher's exact test).
Control(n = 10) Ca-WS(n = 8) Ca-WL (n = 5) Glucose 0.46 -+0.06 0.57 ± 0.03 0.68 -+0.4~ Alanine 0.39 -+0.03 0.32 +_0.04 0.52 _+0.05ab Gluconeogenesisfrom alanine 0.25_+0.04 0.24-+ 0.04 0.41 _+0.05ab Note: a) Significantlydifferentfrom controls;b) from WS (P < 0.05, t-test).
Conclusions: Perioperative TPN in malnourished patients, affected by gastrointestinal cancer reduces post-operative morbidity and mortality. Data on morbidity are in agreement with the findings observed by the Maastricht Trial 1 in a subset of cancer patients with weight loss _>10%.
Conclusions: Weight loss in lung cancer patients is accompanied by elevated glucose and alanine flux, and increased gluconeogenesis from alanine. In contrast, values observed in WS patients are not different from those in healthy subjects. Aberrant gluconeogenesis may contribute to loss of muscle protein and body weight in lung cancer.
Reference: 1. Von Meyenfeldt M F, et al. Clin Nutr 1992; 11 : 180-186.
Session 6 - GASTROINTESTINAL
0.36 Combined growth hormone (GH) and epidermal growth factor (EGF) administration upregulates H*-coupied oligopeptide transporter PEPT1 gene expression in rabbit jejunum after small bowel resection T. R. Ziegler, R lannoli, L. H. Gu, J. H. Miller, C. K. Ryan and H. C.
SYSTEM
Treatmentgroup
Jejunum
Ileum
Control-saline GH EGF GH + EGF 1"= P< 0.01 vs control.
100 _+14 117-+16 147-+19 220 -+51 t
100 -+ 18 71 -+4 98+_19 105 _+11
Conclusions: PEPT1 mRNA is abundantly expressed in rabbit small
Sax Emory University School of Medicine, Atlanta, GA, USA and University of Rochester Medical Center, Rochester, New York, USA.
intestine. PEPT1 gene expression in residual rabbit jejunum and ileum is differentially regulated by SBR itself and by post-SBR hormonal treatment. Administration of GH or EGF alone have no effect on gut PEPT1 mRNA levels. However, combined treatment with GH + EGF synergistically upregulates expression of this major peptide transporter mRNA in residual jejunum, but not in ileum. These data represent the first in vivo demonstration of growth factor-stimulated peptide transporter gene expression, and suggest a possible therapeutic role for combined GH + EGF as a method to enhance oligopeptide transport in proximal small intestine after massive SBR.
Background and purpose: In a rabbit model of massive small bowel resection (SBR), post-operative administration of GH plus EGF significantly upregulated brush-border amino acid transport in residual small intestine. To investigate amino acid transport capacity ir this animal model at the molecular level, we determined jejunal and ileal mRNA expression of the H+-coupled oligopeptide transporter PEPTI. Methods: Adult rabbits underwent 70% mid-jejunoileal SBR. After recovery, either saline (control), GH (0.2mg/kg/day, i.m.), EGF (l .5 #g/kg/hr s.c.) or GH + EGF was given for 7 days. Animals without SBR or hormonal therapy served as unresected controls. Total RNA extracted from full-thickness intestine was used for Northern blotting. PEPT1 mRNA levels were determined using a full-length rabbit PEPT1 cDNA probe, normalized to 18S mRNA expression. Results: Expression of the 2.9kb PEPT1 mRNAtranscript was similar in jejunum versus ileum. SBR significantly decreased PEPT1 mRNA in jejunum versus unresected controls (to 52 +__17% of unresected; P = 0.032). In contrast, SBR was associated with a non-significant increase in ileal PEPT1 expression (to 144 _+16% of unresected; NS). PEPT1 mRNA expression after SBR and hormonal therapy is shown below (mean +_ SEM, as a % of SBR controls).
0.37 Preventive enteral administration of ornithine alpha-ketoglutarate improves intestinal mucosal repair after transient ischemia in rats F. Raul, B. Duranton, E Gosse, M. Galluser, C. Bergmann and R.
Schleiffer CJF INSERM 95-09, IRCAD, 67000-Strasbourg, France. The polyamines are involved in repair processes after intestinal ischemia. The objective of the present work was to investigate whether the preventive enteral administration of a polyamine precursor like ornithine alphaketoglutarate (OKG) has a beneficial effect on the morphological and 10
venous correction of nutritional deficiencies in patients under parenteral nutrition (PN). Bone mass evolution under PN had given contradictory results. The aim of this study was to assess the role played in bone loss by intestinal malabsorption and PN, and to evaluate the change of bone, fat and non-fat (i.e. lean body) masses under PN. Methods: Bone mass as well as fat and non-fat masses, were measured using X-ray absorptiometry (LUNAR DPX). Bone mass was expressed as Z score at the lumbar spine and femoral neck. We studied 75 patients (mean _+SD: 47 _+16 years; 41 men, 34 women) with intestinal malabsorption syndrome including 71 short bowel syndrome. Fortythree patients were under PN since more than one year (56 (12-92) months) (median (range)) and among them 28 underwent a second DPX 17 (3-23) months after the first one. Twenty-one patients were under PN since less than one year (6 (1-11) months) and 11 had not been under PN. Results: No correlation was found between bone mass and remnant small bowel length or PN duration, but Z score at lumbar spine was correlated to the duration of the malabsorption syndrome (P < 0.01 ). Bone mass was not significantly different in patients under PN when compared to those without PN. Z score at femoral neck and lean body mass were significantly (P < 0.05) lower in patients with intestinal malabsorption syndrome existing before PN (n = 47), as compared to those without intestinal malabsorption syndrome before PN (n = 28); body fat mass was similar in these two groups. In the subgroup of 28 patients under long-term PN who had a second DPX, body fat mass increased (P < 0.05) whereas bone mass and lean body mass remained unchanged. Conclusion: In the overall population bone loss was related to the presence and duration of the malabsorption syndrome but not to PN per se. Long-term PN is associated with a gain in body fat mass and avoid a further decrease in ~ither lean or bone masses.
functional recovery, of the intestinal mucosa after transient mesenteric vascular occlusion. Methods: Male Wistar rats, weighing 330-350g, received intragastrically, 17 h and 1 h 30 before surgery either distilled water (group H20, n = 18), or under isonitrogenous conditions an amino-acid solution in distilled water, either OKG (1 g/kg, n = 18) or L-lysine (0.68 g/kg, n = 18). Intestinal ischemia was produced in anesthetized rats by occluding the superior mesenteric artery for 90 minutes with a microbulldog clamp. At the end of the ischemic period the clamp was removed, allowing reperfusion and the abdomen was closed. At 0 h, 4 h and 24h after ischemia/reperfusion (I/R), the mid jejuno-ileum was resected. Intestinal morphology, polyamine content and hydrolase activities were determined. Results: In all grc,ups at the end of the ischemic period the villi were smashed with preservation of the crypts. Rats treated with OKG exhibited a restoration of small villi by 4 h of I/R, the villi remained extensively denuded in the other groups. By 24 h only rats treated with OKG showed a complete recovery of normal mucosal architecture. The amount of the polyamine putrescine was significantly enhanced in the mucosa of rats treated with OKG as compared to the two other groups (OKG: 388 + 44*; lysine: 165 _+ 13 and H20:137 _+23 nmol/gmucosa, *P < 0.01). At a functional level, by 4h of I/R aminopeptidase activity remained significantly higher in rats treated with OKG as compared to the two other groups (P< 0.05). By 24 h, aminopeptidase activity was normalized in rats treated with OKG (450 + 29 mU/mg prot.) whereas an important deficit remained in rats receiving either H20 or lysine (respectively 235 + 23 and 320 _+34 mU/mg prot.). Conclusions: OKG administration to rats did not prevent ischemic damage of the intestinal mucosa, but accelerated the repair of the mucosa during reperfusion. OKG favoured the restitution of normal vilus architecture and the functional recovery of the intestine. We hypothesize that OKG-triggered metabolites might mediate the restitution process and contribute to the healing of the intestinal mucosa by minimizing cell injury.
0.38 Protein-sparing therapy after major abdominal surgery: results of a prospective multicenter randomized study
0.40 Effect of the manipulation of dietary Iipids on mucosal fatty acid (FA) profile and intracolonic leukotriene (LT) release in experimental colitis
M. Malerba, G. B. Doglietto, R. Bellantone, E Pace//i, A. Sgadari, L. Gaflitelli, F. Crucitti and Protein Sparing Therapy Study Groups Members Department of General Surgery, Catholic University, Rome, Italy.
Bertran, J. Ma~6, F. Fernandez-Bahares, R. Bartolf, E. Navarro, E. Castell& J. M. Hernandez, C. Pastor, E. Cabre and M. A. Gassull Department of Gastroenterology, Research Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.
X.
Objective: This study was undertaken to test the hypothesis that postoperative protein-sparing therapy (PST) decreases the incidence of serious complications after major abdominal surgery in normonourished or mildly malnourished patients. Methods: On the basis of previous studies performed on our surgical population, we anticipated a 20 per cent incidence rate of major postoperative complications in the control group. Detecting a reduction of this rate by half (to 10 per cent) in the PST group, at the level of statistical significance of 0.05 and power of 0.90 with a two-tailed test proportion, would require there to be 335 patients in each group. Six hundred and seventy-eight patients undergoing major abdominal surgery were randomly assigned to receive either protein-sparing therapy (PST group) or conventional therapy (control group). The patients were monitored for nutritional parameters and for post-operative complications and mortality. Results: Despite enhanced nutritional results in PST patients compared to controls, the rate of major post-operative complications were similar in the two groups (PST group, 19.5 per cent; control group, 20.9 per cent; P = 0.66), as were the overall post-operative mortality rates (4.7 per cent and 3.5 per cent, respectively; P = 0.43). There was no difference between the PST group and control group concerning both major infectious and non-infectious complications (7.7 vs 5 per cent and 15.1 vs 17.4 per cent respectively; P = 0.42). Conclusions: The present study indicates that routine post-operative protein-sparing therapy for normonourished or mildly malnourished patients undergoing major abdominal surgery is not clinically justified.
Membrane cell FA modulate the inflammatory response by inducing changes in eicosanoid synthesis. This has been the basis for using fish oil to treat Inflammatory Bowel Disease. Besides, it has been claimed that the primary therapeutic effect of enteral nutrition in Crohn's disease lies on the type of fat used in enteral formulas. 1 Aim: To assess how changes in colonic FA profile of rats fed diets rich in different FA modify the intracolonic release of LTB4/LTB 5, in an experimental model of chronic colitis. Methods: 180 S-D female rats were fed n6 FA (linoleate), n3 FA (eicosapentaenoate), n9 FA (oleate) or MCT diets. After 1 month, TNB colitis was induced. At 72h, and at 2rid and 4th week, 15 rats of each group were sacrificed and the FA colonic mucosal profile (capillary column GLC) and macro- and microscopic damage scores were assessed. The LTB4/LTB 5 release (HPLC + EIA) in intracolonic dialysis fluid was measured immediately before sacrifice. Twenty-four rats with a sham-colitis (6 fed each diet) were used as controls. Results: a) The percentage of mucosal n6, n3, and n9 FA increased in rats fed n6, n3, and n9 FA diets, respectively, b) The mucosal FA pattern in rats fed the MCT diet was similar to that observed in the n9 diet group, c) At 72 h and 2 weeks, the LTB4 release increased similarly in all groups, whereas the LTB 5 release was higher in rats fed the n3 than those the n9, n6, and MCT diets (72 h: 132 _+26 vs 37 +_5 vs 24 _+4 vs 63_+ 10pg/ml; P< 0.001.2 weeks: 88_+ 10 vs 42_+ 17 vs 31 _+6 vs 41 _+ 4pg/ml; P < 0.01). d) At 4 weeks, the release of LTB4 and LTB 5 returned to control values, e) As a consequence, the LTB4/LTB 5 ratio was lower with the n3 diet. f) Despite these changes, there were no differences in the macro- and microscopic damage scores among the dietary groups. Conclusions: 1) Dietary lipid manipulation results in changes of colonic FA profile in experimental colitis. 2) Feeding n3 FA diet is associated to increased LTB5 release. 3) Changes in leukotriene release do not seem to account for the putative anti-inflammatory effect of oleic acid.
0.39 R o l e o f parenteral nutrition in bone, lean and fat mass variations during intestinal malabsorption syndrome M. T k o u b 1, P. Crenn 1, M. Cohen-Solal 2, M. C. De Vernejoul2 and B.
Messing 1 1Gastro-Enterology-Nutrition and INSERM U290, 2Rheumatology and INSERM U349, Groupe Hospitalier Lariboisi~re, Paris, France.
Reference:
Intestinal malabsorption syndrome induces nutritional deficiencies leading especially to bone disorders and decreased bone mass despite intra-
1. Gut 1994; 35 (Supp[ 1): $65-68. 11
0.35 Increased rates of gluconeogenesis from alanine in weight-losing lung cancer patients
F. Bozzetti, C. Gavazzi, L. Cozzaglio, R. Mice~i, N. Rossi, L. Mariani and S. Piacenza Istituto Nazioinale Tumori, Milano, Italy,
S.
H a l f w e r k , P. C. Dagnelie, J. W. O. van den Berg, C. H. K. Hordijk-Luijk, J. L. D. Wattimena, G. R. Swart and J. H. P. Wilson Institute of Internal Medicine II, Erasmus University of Rotterdam, The Netherlands.
Aim of the study: To evaluate the impact of TPN on post-operative morbidity and mortality in malnourished patients affected by gastrointestinal cancer.
Introduction: Cancer cachexia is characterized by increased loss of muscle mass and body protein. One of the suggested mechanisms of this phenomenon involves elevated utilization of muscle-derived amino acids, alanine especially, for hepatic glucose synthesis (gluconeogenesis). Gluconeogenesis from alanine has never been quantitatively assessed in patients with specific tumour types. Aim o f the study: To compare gluconeogenesis from alanine in lung cancer patients with/without weight loss and healthy subjects. Methods: We studied weight-stable (WS, n = 8) and weight-losing (WL, n = 5) lung cancer patients, without liver metastases or metabolic disease. Healthy subjects were included as controls (n = 10). After an overnight fast, turnover measurements were performed in steady state (60-90 minutes) using a primed-constant infusion of [6,6-2H2]-glucese and [3-13C]-alanine. Results: WL patients had lost an average of 15% (range 8-22%) of preillness weight over the previous 6 months. Alanine flux and gluconeogenesis from alanine were markedly elevated in WL lung cancer patients when compared with WS patients and healthy controls (Table 1). Glucose flux was also significantly higher in WL patients than in control subjects. Table 1 : Turnover rates (mmol/kg.h) in lung cancer patients and controls (mean _+SEM).
Patients and methods: Ninety malnourished patients (weight loss _>10% of usual weight), affected by gastric or colon-rectum cancer, were stratified by tumour localization and age (_
Results: On the whole, post-operative complications were 57 in 27 patients of CTR group and 25 in 16 patients of TPN group. The frequency of patients with mild and severe complications was 32% and 25% in CTR group, 25% and 12% in TPN group. The difference between the two groups was statistically significant at the MannWhitney test (P = 0.013). Such difference was mainly due to non-infectious complications. Five patients in the CTR group died after severe complications whereas none in TPN group (P = 0.035 at the Fisher's exact test).
Control(n = 10) Ca-WS(n = 8) Ca-WL (n = 5) Glucose 0.46 -+0.06 0.57 ± 0.03 0.68 -+0.4~ Alanine 0.39 -+0.03 0.32 +_0.04 0.52 _+0.05ab Gluconeogenesisfrom alanine 0.25_+0.04 0.24-+ 0.04 0.41 _+0.05ab Note: a) Significantlydifferentfrom controls;b) from WS (P < 0.05, t-test).
Conclusions: Perioperative TPN in malnourished patients, affected by gastrointestinal cancer reduces post-operative morbidity and mortality. Data on morbidity are in agreement with the findings observed by the Maastricht Trial 1 in a subset of cancer patients with weight loss _>10%.
Conclusions: Weight loss in lung cancer patients is accompanied by elevated glucose and alanine flux, and increased gluconeogenesis from alanine. In contrast, values observed in WS patients are not different from those in healthy subjects. Aberrant gluconeogenesis may contribute to loss of muscle protein and body weight in lung cancer.
Reference: 1. Von Meyenfeldt M F, et al. Clin Nutr 1992; 11 : 180-186.
Session 6 - GASTROINTESTINAL
0.36 Combined growth hormone (GH) and epidermal growth factor (EGF) administration upregulates H*-coupied oligopeptide transporter PEPT1 gene expression in rabbit jejunum after small bowel resection T. R. Ziegler, R lannoli, L. H. Gu, J. H. Miller, C. K. Ryan and H. C.
SYSTEM
Treatmentgroup
Jejunum
Ileum
Control-saline GH EGF GH + EGF 1"= P< 0.01 vs control.
100 _+14 117-+16 147-+19 220 -+51 t
100 -+ 18 71 -+4 98+_19 105 _+11
Conclusions: PEPT1 mRNA is abundantly expressed in rabbit small
Sax Emory University School of Medicine, Atlanta, GA, USA and University of Rochester Medical Center, Rochester, New York, USA.
intestine. PEPT1 gene expression in residual rabbit jejunum and ileum is differentially regulated by SBR itself and by post-SBR hormonal treatment. Administration of GH or EGF alone have no effect on gut PEPT1 mRNA levels. However, combined treatment with GH + EGF synergistically upregulates expression of this major peptide transporter mRNA in residual jejunum, but not in ileum. These data represent the first in vivo demonstration of growth factor-stimulated peptide transporter gene expression, and suggest a possible therapeutic role for combined GH + EGF as a method to enhance oligopeptide transport in proximal small intestine after massive SBR.
Background and purpose: In a rabbit model of massive small bowel resection (SBR), post-operative administration of GH plus EGF significantly upregulated brush-border amino acid transport in residual small intestine. To investigate amino acid transport capacity ir this animal model at the molecular level, we determined jejunal and ileal mRNA expression of the H+-coupled oligopeptide transporter PEPTI. Methods: Adult rabbits underwent 70% mid-jejunoileal SBR. After recovery, either saline (control), GH (0.2mg/kg/day, i.m.), EGF (l .5 #g/kg/hr s.c.) or GH + EGF was given for 7 days. Animals without SBR or hormonal therapy served as unresected controls. Total RNA extracted from full-thickness intestine was used for Northern blotting. PEPT1 mRNA levels were determined using a full-length rabbit PEPT1 cDNA probe, normalized to 18S mRNA expression. Results: Expression of the 2.9kb PEPT1 mRNAtranscript was similar in jejunum versus ileum. SBR significantly decreased PEPT1 mRNA in jejunum versus unresected controls (to 52 +__17% of unresected; P = 0.032). In contrast, SBR was associated with a non-significant increase in ileal PEPT1 expression (to 144 _+16% of unresected; NS). PEPT1 mRNA expression after SBR and hormonal therapy is shown below (mean +_ SEM, as a % of SBR controls).
0.37 Preventive enteral administration of ornithine alpha-ketoglutarate improves intestinal mucosal repair after transient ischemia in rats F. Raul, B. Duranton, E Gosse, M. Galluser, C. Bergmann and R.
Schleiffer CJF INSERM 95-09, IRCAD, 67000-Strasbourg, France. The polyamines are involved in repair processes after intestinal ischemia. The objective of the present work was to investigate whether the preventive enteral administration of a polyamine precursor like ornithine alphaketoglutarate (OKG) has a beneficial effect on the morphological and 10
venous correction of nutritional deficiencies in patients under parenteral nutrition (PN). Bone mass evolution under PN had given contradictory results. The aim of this study was to assess the role played in bone loss by intestinal malabsorption and PN, and to evaluate the change of bone, fat and non-fat (i.e. lean body) masses under PN. Methods: Bone mass as well as fat and non-fat masses, were measured using X-ray absorptiometry (LUNAR DPX). Bone mass was expressed as Z score at the lumbar spine and femoral neck. We studied 75 patients (mean _+SD: 47 _+16 years; 41 men, 34 women) with intestinal malabsorption syndrome including 71 short bowel syndrome. Fortythree patients were under PN since more than one year (56 (12-92) months) (median (range)) and among them 28 underwent a second DPX 17 (3-23) months after the first one. Twenty-one patients were under PN since less than one year (6 (1-11) months) and 11 had not been under PN. Results: No correlation was found between bone mass and remnant small bowel length or PN duration, but Z score at lumbar spine was correlated to the duration of the malabsorption syndrome (P < 0.01 ). Bone mass was not significantly different in patients under PN when compared to those without PN. Z score at femoral neck and lean body mass were significantly (P < 0.05) lower in patients with intestinal malabsorption syndrome existing before PN (n = 47), as compared to those without intestinal malabsorption syndrome before PN (n = 28); body fat mass was similar in these two groups. In the subgroup of 28 patients under long-term PN who had a second DPX, body fat mass increased (P < 0.05) whereas bone mass and lean body mass remained unchanged. Conclusion: In the overall population bone loss was related to the presence and duration of the malabsorption syndrome but not to PN per se. Long-term PN is associated with a gain in body fat mass and avoid a further decrease in ~ither lean or bone masses.
functional recovery, of the intestinal mucosa after transient mesenteric vascular occlusion. Methods: Male Wistar rats, weighing 330-350g, received intragastrically, 17 h and 1 h 30 before surgery either distilled water (group H20, n = 18), or under isonitrogenous conditions an amino-acid solution in distilled water, either OKG (1 g/kg, n = 18) or L-lysine (0.68 g/kg, n = 18). Intestinal ischemia was produced in anesthetized rats by occluding the superior mesenteric artery for 90 minutes with a microbulldog clamp. At the end of the ischemic period the clamp was removed, allowing reperfusion and the abdomen was closed. At 0 h, 4 h and 24h after ischemia/reperfusion (I/R), the mid jejuno-ileum was resected. Intestinal morphology, polyamine content and hydrolase activities were determined. Results: In all grc,ups at the end of the ischemic period the villi were smashed with preservation of the crypts. Rats treated with OKG exhibited a restoration of small villi by 4 h of I/R, the villi remained extensively denuded in the other groups. By 24 h only rats treated with OKG showed a complete recovery of normal mucosal architecture. The amount of the polyamine putrescine was significantly enhanced in the mucosa of rats treated with OKG as compared to the two other groups (OKG: 388 + 44*; lysine: 165 _+ 13 and H20:137 _+23 nmol/gmucosa, *P < 0.01). At a functional level, by 4h of I/R aminopeptidase activity remained significantly higher in rats treated with OKG as compared to the two other groups (P< 0.05). By 24 h, aminopeptidase activity was normalized in rats treated with OKG (450 + 29 mU/mg prot.) whereas an important deficit remained in rats receiving either H20 or lysine (respectively 235 + 23 and 320 _+34 mU/mg prot.). Conclusions: OKG administration to rats did not prevent ischemic damage of the intestinal mucosa, but accelerated the repair of the mucosa during reperfusion. OKG favoured the restitution of normal vilus architecture and the functional recovery of the intestine. We hypothesize that OKG-triggered metabolites might mediate the restitution process and contribute to the healing of the intestinal mucosa by minimizing cell injury.
0.38 Protein-sparing therapy after major abdominal surgery: results of a prospective multicenter randomized study
0.40 Effect of the manipulation of dietary Iipids on mucosal fatty acid (FA) profile and intracolonic leukotriene (LT) release in experimental colitis
M. Malerba, G. B. Doglietto, R. Bellantone, E Pace//i, A. Sgadari, L. Gaflitelli, F. Crucitti and Protein Sparing Therapy Study Groups Members Department of General Surgery, Catholic University, Rome, Italy.
Bertran, J. Ma~6, F. Fernandez-Bahares, R. Bartolf, E. Navarro, E. Castell& J. M. Hernandez, C. Pastor, E. Cabre and M. A. Gassull Department of Gastroenterology, Research Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.
X.
Objective: This study was undertaken to test the hypothesis that postoperative protein-sparing therapy (PST) decreases the incidence of serious complications after major abdominal surgery in normonourished or mildly malnourished patients. Methods: On the basis of previous studies performed on our surgical population, we anticipated a 20 per cent incidence rate of major postoperative complications in the control group. Detecting a reduction of this rate by half (to 10 per cent) in the PST group, at the level of statistical significance of 0.05 and power of 0.90 with a two-tailed test proportion, would require there to be 335 patients in each group. Six hundred and seventy-eight patients undergoing major abdominal surgery were randomly assigned to receive either protein-sparing therapy (PST group) or conventional therapy (control group). The patients were monitored for nutritional parameters and for post-operative complications and mortality. Results: Despite enhanced nutritional results in PST patients compared to controls, the rate of major post-operative complications were similar in the two groups (PST group, 19.5 per cent; control group, 20.9 per cent; P = 0.66), as were the overall post-operative mortality rates (4.7 per cent and 3.5 per cent, respectively; P = 0.43). There was no difference between the PST group and control group concerning both major infectious and non-infectious complications (7.7 vs 5 per cent and 15.1 vs 17.4 per cent respectively; P = 0.42). Conclusions: The present study indicates that routine post-operative protein-sparing therapy for normonourished or mildly malnourished patients undergoing major abdominal surgery is not clinically justified.
Membrane cell FA modulate the inflammatory response by inducing changes in eicosanoid synthesis. This has been the basis for using fish oil to treat Inflammatory Bowel Disease. Besides, it has been claimed that the primary therapeutic effect of enteral nutrition in Crohn's disease lies on the type of fat used in enteral formulas. 1 Aim: To assess how changes in colonic FA profile of rats fed diets rich in different FA modify the intracolonic release of LTB4/LTB 5, in an experimental model of chronic colitis. Methods: 180 S-D female rats were fed n6 FA (linoleate), n3 FA (eicosapentaenoate), n9 FA (oleate) or MCT diets. After 1 month, TNB colitis was induced. At 72h, and at 2rid and 4th week, 15 rats of each group were sacrificed and the FA colonic mucosal profile (capillary column GLC) and macro- and microscopic damage scores were assessed. The LTB4/LTB 5 release (HPLC + EIA) in intracolonic dialysis fluid was measured immediately before sacrifice. Twenty-four rats with a sham-colitis (6 fed each diet) were used as controls. Results: a) The percentage of mucosal n6, n3, and n9 FA increased in rats fed n6, n3, and n9 FA diets, respectively, b) The mucosal FA pattern in rats fed the MCT diet was similar to that observed in the n9 diet group, c) At 72 h and 2 weeks, the LTB4 release increased similarly in all groups, whereas the LTB 5 release was higher in rats fed the n3 than those the n9, n6, and MCT diets (72 h: 132 _+26 vs 37 +_5 vs 24 _+4 vs 63_+ 10pg/ml; P< 0.001.2 weeks: 88_+ 10 vs 42_+ 17 vs 31 _+6 vs 41 _+ 4pg/ml; P < 0.01). d) At 4 weeks, the release of LTB4 and LTB 5 returned to control values, e) As a consequence, the LTB4/LTB 5 ratio was lower with the n3 diet. f) Despite these changes, there were no differences in the macro- and microscopic damage scores among the dietary groups. Conclusions: 1) Dietary lipid manipulation results in changes of colonic FA profile in experimental colitis. 2) Feeding n3 FA diet is associated to increased LTB5 release. 3) Changes in leukotriene release do not seem to account for the putative anti-inflammatory effect of oleic acid.
0.39 R o l e o f parenteral nutrition in bone, lean and fat mass variations during intestinal malabsorption syndrome M. T k o u b 1, P. Crenn 1, M. Cohen-Solal 2, M. C. De Vernejoul2 and B.
Messing 1 1Gastro-Enterology-Nutrition and INSERM U290, 2Rheumatology and INSERM U349, Groupe Hospitalier Lariboisi~re, Paris, France.
Reference:
Intestinal malabsorption syndrome induces nutritional deficiencies leading especially to bone disorders and decreased bone mass despite intra-
1. Gut 1994; 35 (Supp[ 1): $65-68. 11