Probiotics and gastrointestinal diseases

Journal of Internal Medicine

Volumn 257, Issue 1, 2005, Pages 78-92

  Sullivan, A ^a   Nord, Carl Erik ^a  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Diarrhoea; Gastrointestinal diseases; Probiotics

Indexed keywords

ANTIBIOTIC AGENT; CLARITHROMYCIN; GENTAMICIN; MESALAZINE; OMEPRAZOLE; ORAL REHYDRATION SOLUTION; PLACEBO; PREDNISOLONE; PROBIOTIC AGENT; RIFAXIMIN; TINIDAZOLE;

ACUTE DIARRHEA; BACTERIAL STRAIN; BIFIDOBACTERIUM ANIMALIS; CLINICAL TRIAL; CLOSTRIDIUM DIFFICILE; CROHN DISEASE; DIARRHEA; ENTERITIS; ERADICATION THERAPY; FOOD INTAKE; GASTROINTESTINAL DISEASE; HELICOBACTER PYLORI; HUMAN; ILEITIS; IRRITABLE COLON; LACTOBACILLUS ACIDOPHILUS; LACTOBACILLUS CASEI; LACTOBACILLUS GASSERI; LACTOBACILLUS JOHNSONII; PEDIATRICS; PRIORITY JOURNAL; RADIATION INJURY; REVIEW; ROTAVIRUS; SACCHAROMYCES BOULARDII; TRAVELLER DIARRHEA; TUBE FEEDING;

ACUTE DISEASE; ANTI-INFECTIVE AGENTS; CHILD; DIARRHEA; ENTEROCOLITIS, PSEUDOMEMBRANOUS; GASTROINTESTINAL DISEASES; HELICOBACTER INFECTIONS; HELICOBACTER PYLORI; HUMANS; INFLAMMATORY BOWEL DISEASES; IRRITABLE BOWEL SYNDROME; PROBIOTICS;

EID: 12344289179     PISSN: 09546820     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1365-2796.2004.01410.x     Document Type: Review

References (107)

1. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet 2003; 361: 512-9.
2. Vollaard EJ, Clasener HA. Colonization resistance. Antimicrob Agents Chemother 1994; 38: 409-14.
3. Sullivan A, Nord CE. The place of probiotics in human intestinal infections. Int J Antimicrob Agents 2002; 20: 313-9.
4. Sullivan A, Nord CE. Probiotics in human infections. J Antimicrob Chemother 2002; 50: 625-7.
5. FAO/WHO. Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria. Expert Consultation Report: Córdoba, Argentina: Food and Agriculture Organization of the United Nations and World Health Organization, 1-4 October 2001.
6. Alvarez-Olmos MI, Oberhelman RA. Probiotic agents and infectious diseases: a modern perspective on a traditional therapy. Clin Infect Dis 2001; 32: 1567-76.
7. Reid G, Sanders ME, Gaskins HR et al. New scientific paradigms for probiotics and prebiotics. J Clin Gastroenterol 2003; 37: 105-18.
8. de Vrese M, Stegelmann A, Richter B, Fenselau S, Laue C, Schrezenmeir J. Probiotics - compensation for lactase insufficiency. Am J Clin Nutr 2001; 73: 421S-9S.
9. Boudeau J, Glasser AL, Julien S, Colombel JF, Darfeuille-Michaud A. Inhibitory effect of probiotic Escherichia coli strain Nissle 1917 on adhesion to and invasion of intestinal epithelial cells by adherent-invasive E. coli strains isolated from patients with Crohn's disease. Aliment Pharmacol Ther 2003; 18: 45-56.
10. Lodinova-Zadnikova R, Sonnenborn U. Effect of preventive administration of a nonpathogenic Escherichia coli strain on the colonization of the intestine with microbial pathogens in newborn infants. Biol Neonate 1997; 71: 224-32.
11. Pinchuk IV, Bressollier P, Verneuil B et al. In vitro anti-Helicobacter pylori activity of the probiotic strain Bacillus subtilis 3 is due to secretion of antibiotics. Antimicrob Agents Chemother 2001; 45: 3156-61.
12. Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C. Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect Immun 1999; 67: 302-7.
13. Girard P, Pansart Y, Lorette I, Gillardin JM. Dose-response relationship and mechanism of action of Saccharomyces boulardii in castor oil-induced diarrhea in rats. Dig Dis Sci 2003; 48: 770-4.
14. Malfertheiner P, Megraud F, O'Morain C et al. Current concepts in the management of Helicobacter pylori infection - the Maastricht 2-2000 Consensus Report. Aliment Pharmacol Ther 2002; 16: 167-80.
15. Felley C, Michetti P. Probiotics and Helicobacter pylori. Best Pract Res Clin Gastroenterol 2003; 17: 785-91.
16. Armuzzi A, Cremonini F, Bartolozzi F et al. The effect of oral administration of Lactobacillus GG on antibiotic-associated gastrointestinal side-effects during Helicobacter pylori eradication therapy. Aliment Pharmacol Ther 2001; 15: 163-9.
17. Canducci F, Armuzzi A, Cremonini F et al. A lyophilized and inactivated culture of Lactobacillus acidophilus increases Helicobacter pylori eradication rates. Aliment Pharmacol Ther 2000; 14: 1625-9.
18. Cats A, Kuipers EJ, Bosschaert MA, Pot RG, Vandenbroucke-Grauls CM, Kusters JG. Effect of frequent consumption of a Lactobacillus casei-containing milk drink in Helicobacter pylori-colonized subjects. Aliment Pharmacol Ther 2003; 17: 429-35.
19. Cremonini F, Di Caro S, Covino M et al. Effect of different probiotic preparations on anti-Helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study. Am J Gastroenterol 2002; 97: 2744-9.
20. Felley CP, Corthesy-Theulaz I, Rivero JL et al. Favourable effect of an acidified milk (LC-1) on Helicobacter pylori gastritis in man. Eur J Gastroenterol Hepatol 2001; 13: 25-9.
21. Michetti P, Dorta G, Wiesel PH et al. Effect of whey-based culture supernatant of Lactobacillus acidophilus (johnsonii) La1 on Helicobacter pylori infection in humans. Digestion 1999; 60: 203-9.
22. Mrda Z, Zivanovic M, Rasic J et al. Therapy of Helicobacter pylori infection using Lactobacillus acidophilus. Med Pregl 1998; 51: 343-5.
23. Pantoflickova D, Corthesy-Theulaz I, Dorta G et al. Favourable effect of regular intake of fermented milk containing Lactobacillus johnsonii on Helicobacter pylori associated gastritis. Aliment Pharmacol Ther 2003; 18: 805-13.
24. Sakamoto I, Igarashi M, Kimura K, Takagi A, Miwa T, Koga Y. Suppressive effect of Lactobacillus gasseri OLL 2716 (LG21) on Helicobacter pylori infection in humans. J Antimicrob Chemother 2001; 47: 709-10.
25. Sheu BS, Wu JJ, Lo CY et al. Impact of supplement with Lactobacillus- and Bifidobacterium-containing yogurt on triple therapy for Helicobacter pylori eradication. Aliment Pharmacol Ther 2002; 16: 1669-75.
26. Wendakoon CN, Thomson AB, Ozimek L. Lack of therapeutic effect of a specially designed yogurt for the eradication of Helicobacter pylori infection. Digestion 2002; 65: 16-20.
27. Sanders JW, Tribble DR. Diarrhea in the returned traveler. Curr Gastroenterol Rep 2001; 3: 304-14.
28. Oksanen PJ, Salminen S, Saxelin M et al. Prevention of travellers' diarrhoea by Lactobacillus GG. Ann Med 1990; 22: 53-6.
29. Hilton E, Kolakowski P, Singer C, Smith M. Efficacy of Lactobacillus GG as a diarrheal preventive in travelers. J Travel Med 1997; 4: 41-3.
30. de dios Pozo-Olano J, Warram JH Jr, Gomez RG, Cavazos MG. Effect of a lactobacilli preparation on traveler's diarrhea. A randomized, double blind clinical trial. Gastroenterology 1978; 74: 829-30.
31. Katelaris PH, Salam I, Farthing MJ. Lactobacilli to prevent traveler's diarrhea? N Engl J Med 1995; 333: 1360-1.
32. Black FT, Andersen PL, Orskov J, Orskov F, Gaarslev K, Laulund S. Prophylactic efficacy of lactobacilli on traveler's diarrhea. Travel Med 1989; 8: 333-5.
33. Kollaritsch H, Holst H, Grobara P, Wiedermann G. Prevention of traveler's diarrhea with Saccharomyces boulardii. Results of a placebo controlled double-blind study. Fortschr Med 1993; 111: 152-6.
34. Gill HS. Probiotics to enhance anti-infective defences in the gastrointestinal tract. Best Pract Res Clin Gastroenterol 2003; 17: 755-73.
35. Szajewska H, Kotowska M, Mrukowicz JZ, Armanska M, Mikolajczyk W. Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants. J Pediatr 2001; 138: 361-5.
36. Mastretta E, Longo P, Laccisaglia A et al. Effect of Lactobacillus GG and breast-feeding in the prevention of rotavirus nosocomial infection. J Pediatr Gastroenterol Nutr 2002; 35: 527-31.
37. Saavedra JM, Bauman NA, Oung I, Perman JA, Yolken RH. Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. Lancet 1994; 344: 1046-9.
38. Oberhelman RA, Gilman RH, Sheen P et al. A placebo-controlled trial of Lactobacillus GG to prevent diarrhea in undernourished Peruvian children. J Pediatr 1999; 134: 15-20.
39. Pedone CA, Bernabeu AO, Postaire ER, Bouley CF, Reinert P. The effect of supplementation with milk fermented by Lactobacillus casei (strain DN-114 001) on acute diarrhoea in children attending day care centres. Int J Clin Pract 1999; 53: 179-84.
40. Ciarlet M, Estes MK. Interactions between rotavirus and gastrointestinal cells. Curr Opin Microbiol 2001; 4: 435-41.
41. Boulloche J, Mouterde O, Mallet E. Traitment des diarrhe'es aigues chez le nourrisson et le jeune enfant. Ann Pediatr (Paris) 1994; 41: 457-63.
42. Costa-Ribeiro H, Ribeiro TC, Mattos AP et al. Limitations of probiotic therapy in acute, severe dehydrating diarrhea. J Pediatr Gastroenterol Nutr 2003; 36: 112-5.
43. Isolauri E, Juntunen M. Rautanen T, Sillanaukee P, Koivula T. A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children. Pediatrics 1991; 88: 90-7.
44. Kaila M, Isolauri E, Soppi E, Virtanen E, Laine S, Arvilommi H. Enhancement of the circulating antibody secreting cell response in human diarrhea by a human Lactobacillus strain. Pediatr Res 1992; 32: 141-4.
45. Guandalini S, Pensabene L, Zikri MA et al. Lactobacillus GG administered in oral rehydration solution to children with acute diarrhea: a multicenter European trial. J Pediatr Gastroenterol Nutr 2000; 30: 54-60.
46. Pant AR, Graham SM, Allen SJ et al. Lactobacillus GG and acute diarrhoea in young children in the tropics. J Trop Pediatr 1996; 42: 162-5.
47. Pearce JL, Hamilton JR. Controlled trial of orally administered lactobacilli in acute infantile diarrhea. J Pediatr 1974; 84: 261-2.
48. Rosenfeldt V, Michaelsen KF, Jakobsen M et al. Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhea. Pediatr Infect Dis J 2002; 21: 411-6.
49. Rosenfeldt V, Michaelsen KF, Jakobsen M et al. Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers. Pediatr Infect Dis J 2002; 21: 417-9.
50. Shornikova AV, Casas IA, Isolauri E, Mykkanen H, Vesikari T. Lactobacillus reuteri as a therapeutic agent in acute diarrhea in young children. J Pediatr Gastroenterol Nutr 1997; 24: 399-404.
51. Shornikova AV, Isolauri E, Burkanova L, Lukovnikova S, Vesikari T. A trial in the Karelian Republic of oral rehydration and Lactobacillus GG for treatment of acute diarrhoea. Acta Paediatr 1997; 86: 460-5.
52. Simakachorn N, Pichaipat V, Rithipornpaisarn P, Kongkaew C, Tongpradit P, Varavithya W. Clinical evaluation of the addition of lyophilized, heat-killed Lactobacillus acidophilus LB to oral rehydration therapy in the treatment of acute diarrhea in children. J Pediatr Gastroenterol Nutr 2000; 30: 68-72.
53. Shornikova AV, Casas IA, Mykkanen H, Salo E, Vesikari T. Bacteriotherapy with Lactobacillus reuteri in rotavirus gastroenteritis. Pediatr Infect Dis J 1997; 16: 1103-7.
54. Huang JS, Bousvaros A, Lee JW, Diaz A, Davidson EJ. Efficacy of probiotic use in acute diarrhea in children: a meta-analysis. Dig Dis Sci 2002; 47: 2625-34.
55. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo-controlled trials. J Pediatr Gastroenterol Nutr 2001; 33(Suppl. 2): S17-25.
56. Van Niel CW, Feudtner C, Garrison MM, Christakis DA. Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics 2002; 109: 678-84.
57. Allen S, Okoko B, Martinez E, Gregorio G, Dans L. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev 2004; 2: CD003048.
58. Bergogne-Berezin E. Treatment and prevention of antibiotic associated diarrhea. Int J Antimicrob Agents 2000; 16: 521-6.
59. Barbut F, Petit JC. Epidemiology of Clostridium difficile-associated infections. Clin Microbiol Infect 2001; 7: 405-10.
60. Thomas MR, Litin SC, Osmon DR, Corr AP, Weaver AL, Lohse CM. Lack of effect of Lactobacillus GG on antibiotic-associated diarrhea: a randomized, placebo-controlled trial. Mayo Clin Proc 2001; 76: 883-9.
61. Arvola T, Laiho K, Torkkeli S et al. Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children with respiratory infections: a randomized study. Pediatrics 1999; 104: e64.
62. Vanderhoof JA, Whitney DB, Antonson DL, Hanner TL, Lupo JV, Young RJ. Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children. J Pediatr 1999; 135: 564-8.
63. Lewis SJ, Potts LF, Barry RE. The lack of therapeutic effect of Saccharomyces boulardii in the prevention of antibiotic-related diarrhoea in elderly patients. J Infect 1998; 36: 171-4.
64. McFarland LV, Surawicz CM, Greenberg RN et al. Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo. Am J Gastroenterol 1995; 90: 439-48.
65. Surawicz CM, Elmer GW, Speelman P, McFarland LV, Chinn J, van Belle G. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study. Gastroenterology 1989; 96: 981-8.
66. D'Souza AL, Rajkumar C, Cooke J, Bulpitt CJ. Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ 2002; 324: 1361.
67. Cremonini F, Di Caro S, Nista EC et al. Meta-analysis: The effect of probiotic administration on antibiotic-associated diarrhoea. Aliment Pharmacol Ther 2002; 16: 1461-7.
68. Surawicz CM. Probiotics, antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in humans. Best Pract Res Clin Gastroenterol 2003; 17: 775-83.
69. Barbut F, Richard A, Hamadi K, Chomette V, Burghoffer B, Petit JC. Epidemiology of recurrences or reinfections of Clostridium difficile-associated diarrhea. J Clin Microbiol 2000; 38: 2386-8.
70. Wullt M, Hagslatt ML, Odenholt I. Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial. Scand J Infect Dis 2003; 35: 365-7.
71. Surawicz CM, McFarland LV, Elmer G, Chinn J. Treatment of recurrent Clostridium difficile colitis with vancomycin and Saccharomyces boulardii. Am J Gastroenterol 1989; 84: 1285-7.
72. Popoola J, Swann A, Warwick G. Clostridium difficile in patients with renal failure - management of an outbreak using biotherapy. Nephrol Dial Transplant 2000; 15: 571-4.
73. McFarland LV, Surawicz CM, Greenberg RN et al. A randomized 0placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994; 271: 1913-8.
74. Surawicz CM, McFarland LV, Greenberg RN et al. The search for a better treatment for recurrent Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis 2000; 31: 1012-7.
75. Donner CS. Pathophysiology and therapy of chronic radiation-induced injury to the colon. Dig Dis 1998; 16: 253-61.
76. Delia P, Sansotta G, Donato V et al. Prevention of radiation-induced diarrhea with the use of VSL 3, a new high-potency probiotic preparation. Am J Gastroenterol 2002; 97: 2150-2.
77. Urbancsek H, Kazar T, Mezes I, Neumann K. Results of a double-blind, randomized study to evaluate the efficacy and safety of Antibiophilus in patients with radiation-induced diarrhoea. Eur J Gastroenterol Hepatol 2001; 13: 391-6.
78. Whelan K, Gibson GR, Judd PA, Taylor MA. The role of probiotics and prebiotics in the management of diarrhoea associated with enteral tube feeding. J Hum Nutr Diet 2001; 14: 423-33.
79. Bleichner G, Blehaut H, Mentec H, Moyse D. Saccharomyces boulardii prevents diarrhea in critically ill tube-fed patients. A multicenter, randomized, double-blind placebo-controlled trial. Intensive Care Med 1997; 23: 517-23.
80. Heimburger DC, Sockwell DG, Geels WJ. Diarrhea with enteral feeding: prospective reappraisal of putative causes. Nutrition 1994; 10: 392-6.
81. Guslandi M. Probiotics for chronic intestinal disorders. Am J Gastroenterol 2003; 98: 520-1.
82. Guslandi M. Of germs in inflammatory bowel disease and of how to light them. J Gastroenterol Hepatol 2003; 18: 115-6.
83. Shanahan F. Crohn's disease. Lancet 2002; 359: 62-9.
84. Prantera C, Scribano ML, Falasco G, Andreoli A, Luzi C. Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG. Gut 2002; 51: 405-9.
85. Gionchetti P, Amadini C, Rizzello F, Venturi A, Poggioli G, Campieri M. Probiotics for the treatment of postoperative complications following intestinal surgery. Best Pract Res Clin Gastroenterol 2003; 17: 821-31.
86. Malchow HA. Crohn's disease and Escherichia coli. A new approach in therapy to maintain remission of colonic Crohn's disease? J Clin Gastroenterol 1997; 25: 653-8.
87. Guslandi M, Mezzi G, Sorghi M, Testoni PA. Saccharomyces boulardii in maintenance treatment of Crohn's disease. Dig Dis Sci 2000; 45: 1462-1.
88. Tamboli CP, Caucheteux C, Cortot A, Colombel JF, Desreumaux P. Probiotics in inflammatory bowel disease: a critical review. Best Pract Res Clin Gastroenterol 2003; 17: 805-20.
89. Ishikawa H, Akedo I, Umesaki Y, Tanaka R, Imaoka A, Otani T. Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis. J Am Coll Nutr 2003; 22: 56-63.
90. Kruis W, Schutz E, Fric P, Fixa B, Judmaler G, Stolte M. Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 1997; 11: 853-8.
91. Rembacken BJ, Snelling AM. Hawkey PM, Chalmers DM, Axon AT. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 1999; 354: 635-9.
92. Kuisma J, Mentula S, Jarvinen H, Kahri A, Saxelin M, Farkkila M. Effect of Lactobacillus rhamnosus GG on ileal pouch inflammation and microbial flora. Aliment Pharmacol Ther 2003; 17: 509-15.
93. Gionchetti P, Rizzello F, Venturi A et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 2000; 119: 305-9.
94. Mimura T, Rizzello F, Helwig U et al. Once daily high dose probiotic therapy (VSL 3) for maintaining remission in recurrent or refractory pouchitis. Gut 2004; 53: 108-14.
95. Gionchetti P, Rizzello F, Helwig U et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 2003; 124: 1202-9.
96. Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowel syndrome. Gastroenterology 2002; 123: 2108-31.
97. Mertz HR. Irritable bowel syndrome. N Engl J Med 2003; 349: 2136-46.
98. Madden JA, Hunter JO. A review of the role of the gut microflora in irritable bowel syndrome and the effects of probiotics. Br J Nutr 2002; 88(Suppl. 1): S67-72.
99. Halpern GM, Prindiville T, Blankenburg M, Hsia T, Gershwin ME. Treatment of irritable bowel syndrome with Lacteol Fort: a randomized, double-blind, cross-over trial. Am J Gastroenterol 1996; 91: 1579-85.
100. Niedzielin K, Kordecki H, Birkenfeld B. A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol 2001; 13: 1143-7.
101. Nobaek S, Johansson ML, Molin G, Ahrne S, Jeppsson B. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome. Am J Gastroenterol 2000; 95: 1231-8.
102. Maxwell PR, Mendall MA, Kumar D. Irritable bowel syndrome. Lancet 1997; 350: 1691-5.
103. Sen S, Mullan MM, Parker TJ, Woolner JT, Tarry SA, Hunter JO. Effect of Lactobacillus plantarum 299v on colonic fermentation and symptoms of irritable bowel syndrome. Dig Dis Sci 2002; 47: 2615-20.
104. O'Sullivan MA, O'Morain CA. Bacterial supplementation in the irritable bowel syndrome. A randomised double-blind placebo-controlled crossover study. Dig Liver Dis 2000: 32: 294-301.
105. Hamilton-Miller JMT. Probiotics in the management of irritable bowel syndrome; a review of clinical trials. Microb Ecol Health Dis 2001; 13: 212-6.
106. FAO/WHO. Guidelines for the Evaluation of Probiotics in Food. Working Group Report; London, Ontario, Canada; Food and Agriculture Organization of the United Nations and World Health Organization, 30 April and 1 May 2002.
107. Marteau P, Seksik P, Shanahan F. Manipulation of the bacterial flora in inflammatory bowel disease. Best Pract Res Clin Gastroenterol 2003; 17: 47-61.