Bowel resection induced intestinal adaptation: Progress from bench to bedside

Minerva Pediatrica

Volumn 61, Issue 3, 2009, Pages 239-251

  Longshore, S W ^a,b   Wakeman, D ^a   Mcmellen, M ^a   Warner, B W ^a  

^a ST LOUIS CHILDREN S HOSPITAL   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Adaptation, physiologic; Intestine, small; Short bowel syndrome

Indexed keywords

SODIUM ION; SODIUM PROTON EXCHANGE PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; CELL PROLIFERATION; CONTROLLED STUDY; ERYTHROCYTE; INTESTINE RESECTION; LIVER DYSFUNCTION; MOUSE; NONHUMAN; REVIEW; SHORT BOWEL SYNDROME; UPREGULATION;

ADAPTATION, PHYSIOLOGICAL; ANIMALS; EVIDENCE-BASED MEDICINE; HUMANS; INTESTINAL MUCOSA; INTESTINE, SMALL; SHORT BOWEL SYNDROME;

EID: 67749135544     PISSN: 00264946     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (103)

1. Williamson RC, Bauer FL, Ross JS, Malt RA. Proximal enterectomy stimulates distal hyperplasia more than bypass or pancreaticobiliary diversion. Gastroenterology 1978;74:16-23.
2. Thompson JS, Quigley EM, Adrian TE. Smooth muscle adaptation after intestinal transection and resection. Dig Dis Sci 1996;41:1760-1767
3. Williamson RC. Intestinal adaptation (first of two parts). Structural, functional and cytokinetic changes. N Engl J Med 1978;298:1393-1402
4. Dowling RH, Booth CC. Structural and functional changes following small intestinal resection in the rat. Clin Sci 1967;32:139-149
5. Williamson RC. Intestinal adaptation (second of two parts). Mechanisms of control. N Engl J Med 1978;298:1444-1450
6. Bernal NP, Stehr W, Coyle R, Erwin CR, Warner BW. Epidermal growth factor receptor signaling regulates Bax and Bcl-w expression and apoptotic responses during intestinal adaptation in mice. Gastroenterology 2006;130:412-423 (Pubitemid 43202040)
7. O'Dwyer ST, Smith RJ, Hwang TL, Wilmore DW. Maintenance of small bowel mucosa with glutamine-enriched parenteral nutrition. JPENJ Parenter Enteral Nutr 1989;13:579-585
8. Falcone RA, Jr., Shin CE, Stern LE, Wang Z, Erwin CR, Soleimani M et al. Differential expression of ileal Na(+)/H(+) exchanger isoforms after enterectomy. J Surg Res 1999;86:192-197 (Pubitemid 29517174)
9. Hines OJ, Bilchik AJ, Zinner MJ, Skotzko MJ, Moser AJ, McFadden DW et al. Adaptation of the Na+/glucose cotransporter following intestinal resection. J Surg Res 1994;57:22-27 (Pubitemid 24243232)
10. Schulzke JD, Fromm M, Bentzel CJ, Zeitz M, Menge H, Riecken EO. Ion transport in the experimental short bowel syndrome of the rat. Gastroenterology. 1992;102:497-504.
11. Chaves M, Smith MW, Williamson RC. Increased activity of digestive enzymes in ileal enterocytes adapting to proximal small bowel resection. Gut. 1987;28:981-987 (Pubitemid 17119266)
12. Kotler DP, Levine GM, Shiau YF. Effects of luminal nutrition and metabolic status on in vivo glucose absorption. Am J Physiol. 1981;240:G432-G436.
13. Levine GM, Deren JJ, Yezdimir E. Small-bowel resection. Oral intake is the stimulus for hyperplasia. Am J Dig Dis 1976;21:542-546
14. Altmann GG, Leblond CP. Factors influencing villus size in the small intestine of adult rats as revealed by transposition of intestinal segments. Am J Anat 1970;127:15-36.
15. Warner BW, Vanderhoof JA, Reyes JD. What's new in the management of short gut syndrome in children. J Am Coll Surg 2000;190:725-736
16. Weser E, Babbitt J, Hoban M, Vandeventer A. Intestinal adaptation. Different growth responses to disaccharides compared with monosaccharides in rat small bowel. Gastroenterology 1986;91:1521-1527
17. Bines JE, Taylor RG, Justice F, Paris MC, Sourial M, Nagy E et al. Influence of diet complexity on intestinal adaptation following massive small bowel resection in a preclinical model. J Gastroenterol Hepatol 2002;17:1170-1179 (Pubitemid 36015612)
18. Sukhotnik I, Mor-Vaknin N, Drongowski RA, Coran AG, Harmon CM. Effect of dietary fat on fat absorption and concomitant plasma and tissue fat composition in a rat model of short bowel syndrome. Pediatr Surg Int 2004;20:185-191 (Pubitemid 38639389)
19. Chen WJ, Yang CL, Lai HS, Chen KM. Effects of lipids on intestinal adaptation following 60% resection in rats. J Surg Res 1995;58:253-259
20. Sukhotnik I, Hayari L, Bashenko Y, Chemodanov E, Mogilner J, Shamir R et al. Dietary palmitic acid modulates intestinal re-growth after massive small bowel resection in a rat. Pediatr Surg Int. 2008;24:1313-1321
21. Keelan M, Cheeseman CI, Clandinin MT, Thomson AB. Intestinal morphology and transport after ileal resection in rat is modified by dietary fatty acids. Clin Invest Med 1996;19:63-70. (Pubitemid 26129652)
22. Vanderhoof JA, Park JH, Herrington MK, Adrian TE. Effects of dietary menhaden oil on mucosal adaptation after small bowel resection in rats. Gastroenterology 1994;106:94-99
23. Kollman KA, Lien EL, Vanderhoof JA. Dietary lipids influence intestinal adaptation after massive bowel resection. J Pediatr Gastroenterol Nutr 1999;28:41-45
24. Wilmore DW. Indications for specific therapy in the rehabilitation of patients with the short-bowel syndrome. Best Pract Res Clin Gastroenterol 2003;17:895-906. (Pubitemid 37554709)
25. Nordgaard I, Hansen BS, Mortensen PB. Importance of colonic support for energy absorption as small-bowel failure proceeds. Am J Clin Nutr 1996;64:222-231 (Pubitemid 26250843)
26. Koruda MJ, Rolandelli RH, Settle RG, Zimmaro DM, Rombeau JL. Effect of parenteral nutrition supplemented with short-chain fatty acids on adaptation to massive small bowel resection. Gastroenterology 1988;95:715-720
27. Bartholome AL, Albin DM, Baker DH, Holst JJ, Tappenden KA. Supplementation of total parenteral nutrition with butyrate acutely increases structural aspects of intestinal adaptation after an 80% jejunoileal resection in neonatal piglets. JPEN J Parenter Enteral Nutr 2004;28:210-222
28. Tappenden KA, McBurney MI. Systemic short-chain fatty acids rapidly alter gastrointestinal structure, function, and expression of early response genes. Dig Dis Sci 1998;43:1526-1536
29. Tappenden KA, Thomson AB, Wild GE, McBurney MI. Short-chain fatty acid-supplemented total parenteral nutrition enhances functional adaptation to intestinal resection in rats. Gastroenterology 1997;112:792-802.
30. Yang H, Larsson J, Permert J, Braaf Y, Wiren M. No effect of bolus glutamine supplementation on the postresectional adaptation of small bowel mucosa in rats receiving chow ad libitum. Dig Surg 2000;17:256-260 (Pubitemid 30429730)
31. Michail S, Mohammadpour H, Park JH, Vanderhoof JA. Effect of glutamine-supplemented elemental diet on mucosal adaptation following bowel resection in rats. J Pediatr Gastroenterol Nutr 1995;21:394-398
32. Vanderhoof JA, Blackwood DJ, Mohammadpour H, Park JH. Effects of oral supplementation of glutamine on small intestinal mucosal mass following resection. J Am Coll Nutr 1992;11:223-227
33. Gu Y, Wu ZH, Xie JX, Jin DY, Zhuo HC. Effects of growth hormone (rhGH) and glutamine supplemented parenteral nutrition on intestinal adaptation in short bowel rats. Clin Nutr 2001;20:159-166 (Pubitemid 32427819)
34. Wu GH, Wu ZH, Wu ZG. Effects of bowel rehabilitation and combined trophic therapy on intestinal adaptation in short bowel patients. World J Gastroenterol 2003;9:2601-2604
35. Sukhotnik I, Lerner A, Sabo E, Krausz MM, Siplovich L, Coran AG et al. Effects of enteral arginine supplementation on the structural intestinal adaptation in a rat model of short bowel syndrome. Dig Dis Sci 2003;48:1346-1351 (Pubitemid 36793913)
36. Sukhotnik I, Mogilner JG, Lerner A, Coran AG, Lurie M, Miselevich I et al. Parenteral arginine impairs intestinal adaptation following massive small bowel resection in a rat model. Pediatr Surg Int 2005;21:460-465 (Pubitemid 40922378)
37. Czernichow B, Nsi-Emvo E, Galluser M, Gosse F, Raul F. Enteral supplementation with ornithine alpha ketoglutarate improves the early adaptive response to resection. Gut. 1997;40:67-72. (Pubitemid 27079753)
38. Dumas F, De Bandt JP, Colomb V, Le BJ, Coudray-Lucas C, Lavie S et al. Enteral ornithine alpha-ketoglutarate enhances intestinal adaptation to massive resection in rats. Metabolism 1998;47:1366-1371 (Pubitemid 28523469)
39. Scolapio JS, Camilleri M, Fleming CR, Oenning LV, Burton DD, Sebo TJ et al Effect of growth hormone, glutamine, and diet on adaptation in short-bowel syndrome: a randomized, controlled study. Gastroenterology 1997;113:1074-1081 (Pubitemid 27418959)
40. Byrne TA, Persinger RL, Young LS, Ziegler TR, Wilmore DW. A new treatment for patients with short-bowel syndrome. Growth hormone, glutamine, and a modified diet. Ann Surg 1995;222:243-254
41. Altmann GG. Influence of bile and pancreatic secretions on the size of the intestinal villi in the rat. Am J Anat 1971;132:167-177
42. Williamson RC, Bauer FL, Ross JS, Malt RA. Contributions of bile and pancreatic juice to cell proliferation in ileal mucosa. Surgery 1978;83:570-576
43. Bass BL, Fischer BA, Richardson C, Harmon JW. Somatostatin analogue treatment inhibits post-resectional adaptation of the small bowel in rats. Am J Surg 1991;161:107-111
44. Ulshen MH, Herbst CA. Effect of removal of pancreaticobiliary secretions on adaptation to short bowel in orally nourished rats. Am J Clin Nutr 1984;39:762-770
45. Secor SM, Lane JS, Whang EE, Ashley SW, Diamond J. Luminal nutrient signals for intestinal adaptation in pythons. Am J Physiol Gastrointest Liver Physiol 2002;283:G1298-G1309. (Pubitemid 35351117)
46. Carpenter G, Cohen S. Epidermal growth factor. J Biol Chem 1990;265:7709-7712
47. Ehaye-Zervas MC, Mertani H, Martini JF, Nihoul-Fekete C, Morel G, Postel-Vinay MC. Expression of the growth hormone receptor gene in human digestive tissue. J Clin Endocrinol Metab 1994;78:1473-1480 (Pubitemid 24181023)
48. Nucci AM, Finegold DN, Yaworski JA, Kowalski L, Barksdale EM, Jr. Results of growth trophic therapy in children with short bowel syndrome. J Pediatr Surg 2004;39:335-339 (Pubitemid 38338345)
49. Zhou X, Li YX, Li N, Li JS. Glutamine enhances the gut-trophic effect of growth hormone in rat after massive small bowel resection. J Surg Res 2001;99:47-52. (Pubitemid 32613958)
50. Waitzberg DL, Cukier C, Mucerino DR, Logulo AF, Torrinhas RS, de C, I. Small bowel adaptation with growth hormone and glutamine after massive resection of rat's small bowel. Nutr Hosp 1999;14:81-90. (Pubitemid 29226390)
51. Fadrique B, Lopez JM, Bermudez R, Gomez dS, I, Vazquez I, De ME. Growth hormone plus high protein diet promotes adaptation after massive bowel resection in aged rats. Exp Gerontol 2001;36:1727-1737
52. Messing B, Crenn P, Beau P, Boutron-Ruault MC, Rambaud JC, Matuchansky C. Long-term survival and parenteral nutrition dependence in adult patients with the short bowel syndrome. Gastroenterology 1999;117:1043-1050 (Pubitemid 29512662)
53. Seguy D, Vahedi K, Kapel N, Souberbielle JC, Messing B. Low-dose growth hormone in adult home parenteral nutrition-dependent short bowel syndrome patients: a positive study. Gastroenterology 2003;124:293-302. (Pubitemid 36169246)
54. Lund PK. Molecular basis of intestinal adaptation: the role of the insulin-like growth factor system. Ann N Y Acad Sci. 1998;859:18-36. (Pubitemid 29021004)
55. Vanderhoof JA, McCusker RH, Clark R, Mohammadpour H, Blackwood DJ, Harty RF et al. Truncated and native insulinlike growth factor I enhance mucosal adaptation after jejunoileal resection. Gastroenterology. 1992;102:1949-1956
56. Knott AW, Juno RJ, Jarboe MD, Profitt SA, Erwin CR, Smith EP et al. Smooth muscle overexpression of IGF-I induces a novel adaptive response to small bowel resection. Am J Physiol Gastrointest Liver Physiol 2004;287:G562-G570.
57. Gillingham MB, Dahly EM, Murali SG, Ney DM. IGF-I treatment facilitates transition from parenteral to enteral nutrition in rats with short bowel syndrome. Am J Physiol Regul Integr Comp Physiol 2003;284:R363-R371.
58. Chaet MS, Arya G, Ziegler MM, Warner BW. Epidermal growth factor enhances intestinal adaptation after massive small bowel resection. J Pediatr Surg. 1994;29:1035-1038 (Pubitemid 24265642)
59. Helmrath MA, Erwin CR, Warner BW. A defective EGF-receptor in waved-2 mice attenuates intestinal adaptation. J Surg Res 1997;69:76-80.
60. Helmrath MA, Shin CE, Fox JW, Erwin CR, Warner BW. Adaptation after small bowel resection is attenuated by sialoadenectomy: the role for endogenous epidermal growth factor. Surgery 1998;124:848-854 (Pubitemid 28520777)
61. Iskit SH, Tugtepe H, Ayyildiz SH, Kotiloglu E, Dagli TE, Yegen BC. Epidermal growth factor and bombesin act synergistically to support intestinal adaptation in rats with massive small bowel resection. Pediatr Surg Int 2005;21:436-440 (Pubitemid 40922374)
62. Thompson JS. Epidermal growth factor and the short bowel syndrome. IPEN J Parenter Enteral Nutr 1999;23:S113-S116.
63. Roberge JN, Brubaker PL. Secretion of proglucagon-derived peptides in response to intestinal luminal nutrients. Endocrinology 1991;128:3169-3174
64. Gleeson MH, Bloom SR, Polak JM, Henry K, Dowling RH. An endocrine tumour in kidney affecting small bowel structure, motility, and function. Gut 1970;11:1060.
65. Bloom SR, Polak JM. The hormonal pattern of intestinal adaptation. A major role for enteroglucagon. Scand J Gastroenterol Suppl 1982;74:93-103.
66. Washizawa N, Gu LH, Gu L, Openo KP, Jones DP, Ziegler TR. Comparative effects of glucagon-like peptide-2 (GLP-2), growth hormone (GH), and keratinocyte growth factor (KGF) on markers of gut adaptation after massive small bowel resection in rats. JPEN J Parenter Enteral Nutr 2004;28:399-409. (Pubitemid 39463823)
67. Martin GR, Wallace LE, Hartmann B, Holst JJ, Demchyshyn L, Toney K et al. Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2005;288:G431-G438. (Pubitemid 40261740)
68. Sigalet DL, Bawazir O, Martin GR, Wallace LE, Zaharko G, Miller A et al. Glucagon-like peptide-2 induces a specific pattern of adaptation in remnant jejunum. Dig Dis Sci. 2006;51:1557-1566 (Pubitemid 44379297)
69. Jeppesen PB, Hartmann B, Thulesen J, Graff J, Lohmann J, Hansen BS et al. Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon. Gastroenterology 2001;120:806-815 (Pubitemid 32193176)
70. Jeppesen PB, Sanguinetti EL, Buchman A, Howard L, Scolapio JS, Ziegler TR et al. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut 2005;54:1224-1231 (Pubitemid 41192479)
71. Michel MC, Knapp J, Ratjen H. Sensitization by dexamethasone of lymphocyte cyclic AMP formation: evidence for increased function of the adenylyl cyclase catalyst. Br J Pharmacol 1994;113:240-246 (Pubitemid 24271744)
72. Drozdowski L, Thomson AB. Intestinal hormones and growth factors: Effects on the small intestine. World J Gastroenterol 2009;15:385-406.
73. Thiesen AL, Tappenden KA, McBurney MI, Clandinin MT, Keelan M, Thomson BK et al. Dietary lipids alter the effect of steroids on the transport of glucose after intestinal resection: Part I. Phenotypic changes and expression of transporters. J Pediatr Surg. 2003;38:150-160. (Pubitemid 36160055)
74. Park JH, McCusker RH, Mohammadpour H, Blackwood DJ, Hrbek M, Vanderhoof JA. Dexamethasone inhibits mucosal adaptation after small bowel resection. Am J Physiol 1994;266:G497-G503. (Pubitemid 24115925)
75. Scott J, Batt RM, Peters TJ. Enhancement of ileal adaptation by prednisolone after proximal small bowel resection in the rat. Gut 1979;20:858-864 (Pubitemid 10206577)
76. Thiesen A, Tappenden KA, McBurney MI, Clandinin MT, Keelan M, Thomson BK et al. Dietary lipids alter the effect of steroids on the transport of fructose following intestinal resection in rats. Dig Dis Sci 2008;53:2126-2139
77. Martin del Olmo JC, Clement del RJ, Diez GM. [Behavior of thyroid function following massive intestinal resection. Experimental study]. Nutr Hosp 1991;6:227-234
78. Yuksel O, Tatlicioglu E, Poyraz A, Sahin T, Pasaoglu H, Ekinci O et al. Effects of Thyroid Hormone on the Adaptation in Short Bowel Syndrome. J Surg Res. 2008. [epub ahead of print]
79. Sukhotnik I, Shiloni E, Mogilner J, Lurie M, Hirsh M, Coran AG et al. Effect of sex and sex hormones on structural intestinal adaptation after massive small bowel resection in rats. J Pediatr Surg 2005;40:489-95. (Pubitemid 40417409)
80. Kiely JM, Noh JH, Pitt HA, Swartz-Basile DA. Impaired intestinal cell proliferation and cell death in leptin-deficient obese mice. JPEN J Parenter Enteral Nutr 2005;29:30-35
81. Sukhotnik I, Vadasz Z, Coran AG, Lurie M, Shiloni E, Hatoum OA et al. Effect of leptin on intestinal regrowth following massive small bowel resection in rat. Pediatr Surg Int 2006;22:9-15. (Pubitemid 43052193)
82. Cronk DR, Ferguson DC, Thompson JS. Malnutrition impairs postresection intestinal adaptation. JPEN J Parenter Enteral Nutr 2000;24:76-80.
83. Bertoni S, Gabella G. Hypertrophy of mucosa and serosa in the obstructed intestine of rats. J Anat 2001;199:725-734 (Pubitemid 34023822)
84. Collins J, III, Vicente Y, Georgeson K, Kelly D. Partial intestinal obstruction induces substantial mucosal proliferation in the pig. J Pediatr Surg 1996;31:415-419 (Pubitemid 26104900)
85. Georgeson K, Halpin D, Figueroa R, Vincente Y, Hardin W, Jr. Sequential intestinal lengthening procedures for refractory short bowel syndrome. J Pediatr Surg 1994;29:316-320 (Pubitemid 24068645)
86. Schmidt T, Pfeiffer A, Hackelsberger N, Widmer R, Meisel C, Kaess H. Effect of intestinal resection on human small bowel motility. Gut 1996;38:859-863 (Pubitemid 26231770)
87. Brookes SJ, Lam TC, Lubowski DZ, Costa M, King DW. Regeneration of nerve fibres across a colonic anastomosis in the guinea-pig. J Gastroenterol Hepatol 1996;11:325-334 (Pubitemid 26142925)
88. Sarna S, Condon RE, Cowles V. Enteric mechanisms of initiation of migrating myoelectric complexes in dogs. Gastroenterology 1983;84:814-822 (Pubitemid 13152632)
89. Parvadia JK, Keswani SG, Vaikunth S, Maldonado AR, Marwan A, Stehr W et al. Role of VEGF in small bowel adaptation after resection: the adaptive response is angiogenesis dependent. Am J Physiol Gastrointest Liver Physiol 2007;293:G591-G598. (Pubitemid 47435379)
90. Wildhaber BE, Yang H, Coran AG, Teitelbaum DH. Gene alteration of intestinal intraepithelial lymphocytes in response to massive small bowel resection. Pediatr Surg Int 2003;19:310-315 (Pubitemid 37046189)
91. Koga H, Yang H, Haxhija EQ, Teitelbaum DH. The role of angiotensin II type 1a receptor on intestinal epithelial cells following small bowel resection in a mouse model. Pediatr Surg Int 2008;24:1279-1286
92. Haxhija EQ, Yang H, Spencer AU, Koga H, Sun X, Teitelbaum DH. Modulation of mouse intestinal epithelial cell turnover in the absence of angiotensin converting enzyme. AmJ Physiol Gastrointest liver Physiol 2008;295:G88-G98.
93. Dekaney CM, Fong JJ, Rigby RJ, Lund PK, Henning SJ, Helmrath MA. Expansion of intestinal stem cells associated with long-term adaptation following ileocecal resection in mice. Am J Physiol Gastrointest Liver Physiol 2007;293:G1013-G1022.
94. Garrison AP, Dekaney CM, von A, Lund PK, Henning SJ, Helmrath MA. Early but not late administration of Glucagon-Like Peptide-2 following ileocecal resection augments putative intestinal stem cell expansion. Am J Physiol Gastrointest Liver Physiol 2008. [Epub ahead of print]
95. Martin CA, Bernabe KQ, Taylor JA, Nair R, Paul RJ, Guo J et al. Resection-induced intestinal adaptation and the role of enteric smooth muscle. J Pediatr Surg 2008;43:1011-1017 (Pubitemid 351814900)
96. Dodson BD, Wang JL, Swietlicki EA, Rubin DC, Levin MS. Analysis of cloned cDNAs differentially expressed in adapting remnant small intestine after partial resection. Am J Physiol 1996;271:G347-G356. (Pubitemid 26295143)
97. Erwin CR, Falcone RA, Jr., Stern LE, Kemp CJ, Warner BW. Analysis of intestinal adaptation gene expression by cDNA expression arrays. JPEN J Parenter Enteral Nutr 2000,24:311-316 (Pubitemid 30805256)
98. Erwin CR, Jarboe MD, Sartor MA, Medvedovic M, Stringer KF, Warner BW et al. Developmental characteristics of adapting mouse small intestine crypt cells. Gastroenterology 2006;130:1324-1332
99. Stern LE, Erwin CR, Falcone RA, Huang FS, Kemp CJ, Williams JL et al cDNA microarray analysis of adapting bowel after intestinal resection. J Pediatr Surg 2001;36:190-195
100. Stern LE, Falcone RA, Jr., Kemp CJ, Erwin CR, Warner BW. p21 (WAF1/CIP1) is required for the mitogenic response to intestinal resection. J Surg Res 2000;90:45-50.
101. Sheng G, Bernabe KQ, Guo J. Warner BW. Epidermal growth factor receptor-mediated proliferation of enterocytes requires p21waf1/cip1 expression. Gastroenterology 2006;131:153-164 (Pubitemid 44015760)
102. Stern LE, Huang F, Kemp CJ, Falcone RA, Jr, Erwin CR, Warner BW. Bax is required for increased enterocyte apoptosis after massive small bowel resection. Surgery 2000;128:165-170 (Pubitemid 30622479)
103. Schalamon J, Mayr JM, Hollwarth ME. Mortality and economics in short bowel syndrome. Best Pract Res Clin Gastroenterol 2003;17:931-942 (Pubitemid 37554710)