Drugs

, Volume 55, Issue 4, pp 519–542 | Cite as

A Practical Guide to the Management of Distal Ulcerative Colitis

  • Sandro Ardizzone
  • Gabriele Bianchi Porto
Review Article

Summary

This article reviews the role of corticosteroids, sulfasalazine and mesalazine (5-aminosalicylic acid, mesalamine), immunosuppressive agents and alternative novel drugs for the treatment of distal ulcerative colitis.

Short cycles of traditional, rectally administered corticosteroids (methylprednisolone, betamethasone, hydrocortisone) are effective for the treatment of mild to moderately active distal ulcerative colitis. In this context, their systemic administration is limited to patients who are refractory to either oral 5-aminosalicylates, topical mesalazine or topical corticosteroids. Of no value in maintaining remission, the long term use of either or topical corticosteroids may be hazardous. A new class of topically acting corticosteroids [budesonide, fluticasone, beclomethasone dipropionate, prednisolone-21-methasulphobenzoate, tixocortol (tixocortol pivalate)] represents a valid alternative for the treatment of active ulcerative colitis, and may be useful in the treatment of refractory distal ulcerative colitis.

Although there is controversy concerning dosage or duration of therapy, oral and topical mesalazine is effective in the treatment of mild to moderately active distal ulcerative colitis.

Sulfasalazine and mesalazine remain the first-choice drugs for the maintenance therapy of distal ulcerative colitis. Evidence exists showing a trend to a higher remission rate with higher doses of oral mesalazine. Topical mesalazine (suppositories or enemas) also is effective in maintenance treatment.

For patients with chronically active or corticosteroid-dependent disease, azathioprine and mercaptopurine are effective in reducing either the need for corticosteroids or clinical relapses. Moreover, they are effective for long term maintenance remission. Cyclosporin may be useful in inducing remission in patients with acutely severe disease who do not achieve remission with an intensive intravenous regimen. Existing data suggest that azathioprine and mercaptopurine may be effective in prolonging remission in these patients.

The role of alternative drugs for the treatment of distal ulcerative colitis and its different forms is reviewed. In particular data are reported concerning the effectiveness of 5-lipoxygenase inhibitors, topical use of short chain fatty acids, nicotine, local anaesthetics, bismuth subsalicylate enema, sucralfate, clonidine, free radical scavengers, heparin and hydroxychloroquine.

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References

  1. 1.
    Cello JG. Ulcerative colitis. In: Sleisenger MH, Fordtran JS, editors. Gastrointestinal disease: pathophysiology, diagnosis, management. Philadelphia: WB Saunders, 1983: 1122–68Google Scholar
  2. 2.
    Truelove SC, Witts LJ. Cortisone in ulcerative colitis: a final report on a therapeutic trial. BMJ 1955; 2: 1041–8PubMedGoogle Scholar
  3. 3.
    Powell-Tuck J, Day DW, Buckell NA, et al. Correlation between defined sigmoidoscopic appearances and other measures of disease activity in ulcerative colitis. Dig Dis Sci 1982 Jun; 27(6): 533–7PubMedGoogle Scholar
  4. 4.
    Sutherland LR, Martin F, Greer S, et al. 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis and proctitis. Gastroenterology 1987; 92: 1894–8PubMedGoogle Scholar
  5. 5.
    Hanauer SB. Measurements of disease activity. In: Targan SR, Shanahan F, editors. Inflammatory bowel disease: from bench to beside. Baltimore: Williams & Wilkins, 1994; 424–44Google Scholar
  6. 6.
    Edwards FC, Truelove SC. The course and prognosis of ulcerative colitis. Part I: short-term prognosis. Part II: long-term prognosis. Gut 1963; 4: 299–315Google Scholar
  7. 7.
    Kirsner JB, Palmer WL, Merimen SH, et al. Clinical course of chronic non-specific ulcerative colitis. JAMA 1948; 137: 922Google Scholar
  8. 8.
    Korelitz BI, Lindner AE. Influence of corticotropin and adrenal steroids in course of ulcerative colitis. Gastroenterology 1964; 46: 671–3PubMedGoogle Scholar
  9. 9.
    Lauritsen K, Laursen LS, Bukhave K, et al. Role of eicosanoids in inflammatory bowel disease. In: Järnerot G, editor. Inflammatory bowel disease. New York: Raven Press, 1987: 89–90Google Scholar
  10. 10.
    Lauritsen K, Laursen LS, Bukhave K, et al. Effects of topical 5-aminosalicylic acid and prednisolone on prostaglandin E2 and leucotriene B2 determined by equilibrium in vivo dialysis of rectum in relapsing ulcerative colitis. Gastroenterology 1986; 91: 837–44PubMedGoogle Scholar
  11. 11.
    Haynes RC. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Gilman AG, Rall TW, Nies AS, et al., editors. The pharmacological basis of therapeutics. New York: Pergamon Press, 1990: 1431–62Google Scholar
  12. 12.
    Lennard-Jones JE, Misiewicz JJ, Connell AM, et al. Prednisolone as maintenance treatment for ulcerative colitis in remission. Lancet 1965; I: 188–9Google Scholar
  13. 13.
    Powell-Tuck J, Brown RL, Chambers TJ, et al. Acontrolled trial of alternate day prednisolone as a maintenance treatment for ulcerative colitis in remission. Digestion 1981; 22: 263–70PubMedGoogle Scholar
  14. 14.
    Lennard-Jones JE. Corticosteroids and immunosuppressive drugs. In: Allan RN, Keighley MRB, Alexander-Williams J, et al., editors. Inflammatory bowel disease. London: Churchill Livingstone, 1990: 373–89Google Scholar
  15. 15.
    Baron JH, Connell AM, Kanaghinis TG, et al. Outpatients treatment of ulcerative colitis: comparison between three doses of oral prednisone. BMJ 1962; II: 441–3Google Scholar
  16. 16.
    Powell-Tuck J, Bown RL, Lennard-Jones JE. A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis. Scand J Gastroenterol 1978; 13: 833–7PubMedGoogle Scholar
  17. 17.
    Truelove SC, Lee EG, Willoughby CP, et al. Further experience in the treatment of severe attacks of ulcerative colitis. Lancet 1978; II: 1086–8Google Scholar
  18. 18.
    Truelove SC. Treatment of ulcerative colitis with local hydrocortisone hemisuccinate sodium: report on a controlled therapeutic trial. BMJ 1958; 2: 1072–7PubMedGoogle Scholar
  19. 19.
    Margolin ML, Krumholz MP, Fochios SE, et al. Clinical trials in ulcerative colitis: II. Historical review. Am J Gastroenterol 1988; 83: 227–43Google Scholar
  20. 20.
    Ardizzone S, Bianchi Porro G. The topical treatment of distal ulcerative colitis. Eur J Gastroenterol Hepatol 1996; 8: 599–602PubMedGoogle Scholar
  21. 21.
    McIntyre PB, Macrea FA, Berghouse L, et al. Therapeutic benefits from a poorly absorbed prednisolone enema in distal colitis. Gut 1985; 26: 822–4PubMedGoogle Scholar
  22. 22.
    Cann PA, Holdsworth CD. Systemic absorption from hydrocortisone foam enemas in ulcerative colitis. Lancet 1987; I: 922–3Google Scholar
  23. 23.
    Matts SGF. Local treatment of ulcerative colitis with prednisolone-21-phosphate enema. Lancet 1960; 1: 517–9Google Scholar
  24. 24.
    Wood E, Wilson CG, Hardy JG, et al. The spreading of foam and solution enemas. Int J Pharm 1985; 25: 191–7Google Scholar
  25. 25.
    Hay DJ. Spreading characteristics of proprietary rectal steroid preparation. In: Hardy JG, Frier M, Davis SS, editors. Radionuclide imaging in drug research. London: Croom Helm, 1982: 171–80Google Scholar
  26. 26.
    Ruddell WSJ, Dickinson RJ, Dixon MF, et al. Treatment of distal ulcerative colitis (proctosigmoiditis) in relapse: comparison of hydrocortisone enemas and rectal hydrocortisone foam. Gut 1980; 21: 885–9PubMedGoogle Scholar
  27. 27.
    Somerville KW, Langman MS, Kane SP, et al. Effects of treatment on symptoms and quality of life in patients with ulcerative colitis: comparative trial of hydrocortisone acetate foam and prednisolone-21-phosphate enemas. BMJ 1985; 291: 866PubMedGoogle Scholar
  28. 28.
    Thiesen A, Thomson ABR. Older and newer topical glucocorticosteroids and the gastrointestinal tract. Aliment Pharmacol Ther 1996; 10: 487–96PubMedGoogle Scholar
  29. 29.
    Bianchi Porro G, Prantera C, Campieri M, et al. Comparative trial of methylprednisolone and budesonide enemas in active distal ulcerative colitis. Eur J Gastroenterol Hepatol 1994; 6: 125–30Google Scholar
  30. 30.
    Angus P, Snook JA, Reid M, et al. Oral fluticasone propionate in active distal ulcerative colitis. Gut 1992; 33: 711–4PubMedGoogle Scholar
  31. 31.
    Hawthorne AB, Record CO, Holdsworth CD, et al. Double blind trial of oral fluticasone propionate prednisolone in the treatment of active ulcerative colitis. Gut 1993; 34: 125–8PubMedGoogle Scholar
  32. 32.
    Hanauer SB, Kirsner JB, Barrett WE. The treatment of left-sided ulcerative colitis with tixocortol pivalate [abstract]. Gastroenterology 1986; 90: 1449AGoogle Scholar
  33. 33.
    Friedman G. Treatment of refractory proctosigmoiditis and left-sided colitis with rectally instilled non-mineralcorticoid [abstract]. Gastroenterology 1985; 88: 1388AGoogle Scholar
  34. 34.
    Kumana CR, Seaton T, Meghji M, et al. Beclomethasone dipropionate enemas for treating inflammatory bowel disease without producing Cushing’s syndrome or hypothalamic pituitary adrenal suppression. Lancet 1982 Aug; I: 579–83Google Scholar
  35. 35.
    Bansky G, Buhler H, Bernhard S, et al. Treatment of distal ulcerative colitis with beclomethasone enemas: high therapeutic efficacy without endocrine side effects: a prospective, randomized, double-blind trial. Dis Colon Rectum 1987; 30: 288–92PubMedGoogle Scholar
  36. 36.
    Van der Heide H, van den Brandt-Gradel V, Tytgat GNJ, et al. Comparison of beclomethasone dipropionate and prednisolone-21-phosphate enemas in the treatment of ulcerative proctitis. J Clin Gastroenterol 1988; 10: 169–72PubMedGoogle Scholar
  37. 37.
    Halpern Z, Sold O, Baratz F, et al. A controlled trial of beclomethasone versus betamethasone enemas in distal ulcerative colitis. J Clin Gastroenterol 1991; 13: 38–41PubMedGoogle Scholar
  38. 38.
    Mulder CJJ, Fockens P, Meijer JWR, et al. Beclomethasone dipropionate (3 mg) versus 5-aminosalicylic acid (2 gr) versus the combination of both (3 mg/2 gr) as retention enemas in active ulcerative proctitis. Eur J Gastroenterol Hepatol 1996; 8: 549–53PubMedGoogle Scholar
  39. 39.
    Danielsson A, Hellers G, Lyrenas E, et al. A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Scand J Gastroenterol 1987; 22: 987–92PubMedGoogle Scholar
  40. 40.
    Matzen P. Budesonide enema in distal ulcerative colitis: a randomized dose-response trial with prednisolone enema as positive control. Scand J Gastroenterol 1991; 26: 1225–30Google Scholar
  41. 41.
    Lamers C, Meijer, Engels L, et al. Comparative study of the topically acting glucorticosteroid budesonide and 5-aminosalicylic acid enema therapy of proctitis and proctosigmoiditis [abstract]. Gastroenterology 1991; 100: A223Google Scholar
  42. 42.
    Tarpila S, Turunen U, Seppala K, et al. Budesonide enema in active haemorrhagic proctitis — a controlled trial against hydrocortisone foam enema. Aliment Pharmacol Ther 194; 8: 591–5Google Scholar
  43. 43.
    Lofberg R, Thomsen O, Langholz E, et al. Budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Aliment Pharmacol Ther 1994; 8: 623–9PubMedGoogle Scholar
  44. 44.
    Lemann M, Galian A, Rutgeerts P, et al. Comparison of budesonide and 5-aminosalicylic acid enemas in active distal ulcerative colitis. Aliment Pharmacol Ther 1995; 9: 557–62PubMedGoogle Scholar
  45. 45.
    Bayless T, Sninsky C. Budesonide enema is an effective alternative to hydrocortisone enema in active distal ulcerative colitis [abstract]. Gastroenterology 1995; 108: A778Google Scholar
  46. 46.
    Hanauer S, Robinson M. Dose ranging study of budesonide enema in active distal ulcerative colitis [abstract]. Gastroenterology 1995; 108: A832Google Scholar
  47. 47.
    Lofberg R, Danielsson A, Suhr O, et al. Oral budesonide versus prednisolone in patients with active extensive and left-sided colitis. Gastroenterology 1996; 110: 1713–8PubMedGoogle Scholar
  48. 48.
    Keller R, Stoll R, Foerster EC, et al. Oral budesonide therapy for steroid-dependent ulcerative colitis: a pilot study. Aliment Pharmacol Ther 1997; 11: 1047–52PubMedGoogle Scholar
  49. 49.
    Marshall JK, Irvine EJ. Rectal corticosteroids versus alternative treatments in ulcerative colitis: a meta-analysis. Gut 1997; 40: 775–81PubMedGoogle Scholar
  50. 50.
    Misiewicz JJ, Lennard-Jones JE, Connell AM, et al. Controlled trial of sulphasalazine in maintenance therapy for ulcerative colitis. Lancet 1965; I: 185–8Google Scholar
  51. 51.
    Kornbluth AA, Salomon P, Sacks HS, et al. Meta-analysis of the effectiveness of current drug therapy of ulcerative colitis. J Clin Gastroenterol 1993; 16: 215–8PubMedGoogle Scholar
  52. 52.
    Das KM. Sulfasalazine therapy in inflammatory bowel disease. Gastroenterol Clin North Am 1989; 18: 1–20PubMedGoogle Scholar
  53. 53.
    Azad Khan AK, Piris J, Truelove SC, et al. An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet 1977; II: 892–5Google Scholar
  54. 54.
    Sutherland LR, May GR, Shaffer EA. Sulafasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis. Ann Intern Med 1993; 118: 540–9PubMedGoogle Scholar
  55. 55.
    Sutherland LR, Roth DE, Beck PL. Alternatives to sulfasalazine: a meta-analysis of 5-ASA in the treatment of ulcerative colitis. Inflamm Bowel Dis 1997; 3: 65–78Google Scholar
  56. 56.
    Robinson M, Hanauer S, Hoop R, et al. Mesalamine capsules enhance the quality of life for patients with ulcerative colitis. Aliment Pharmacol Ther 1994; 8: 27–34PubMedGoogle Scholar
  57. 57.
    Marshall JK, Irvine EJ. Rectal aminosalicylate therapy for distal ulcerative colitis: a meta-analysis. Aliment Pharmacol Ther 1995; 9: 293–300PubMedGoogle Scholar
  58. 58.
    Biddle WL, Miner PB. Long-term use of mesalamine enemas to induce remission in ulcerative colitis. Gastroenterology 1990; 99: 113–8PubMedGoogle Scholar
  59. 59.
    Campieri M, Gionchetti P, Belluzzi A, et al. Optimum dosage of 5-aminosalicylic acid as rectal enemas in patients with active ulcerative colitis. Gut 1991; 32: 929–31PubMedGoogle Scholar
  60. 60.
    Bianchi Porro G, Ardizzone S, Petrillo M, et al. Low Pentasa dosage versus hydrocortisone in the topical treatment of active ulcerative colitis: a randomized, double-blind study. Am J Gastroenterol 1995; 90: 736–9PubMedGoogle Scholar
  61. 61.
    Campieri M, Paoluzi P, D’Albasio G, et al. Better quality of therapy with 5-ASA colonic foam in active ulcerative colitis: a multicenter comparative trial with 5-ASA enema. Dig Dis Sci 1993; 38: 1843–50PubMedGoogle Scholar
  62. 62.
    Gionchetti P, Rizzello A, Venturi C, et al. Comparison of mesalazine suppositories in proctitis and distal proctosigmoiditis. Aliment Pharmacol Ther 1997; 11: 1053–7PubMedGoogle Scholar
  63. 63.
    Gionchetti P, Ardizzone S, Benvenuti ME, et al. A new 5-ASA rectal formulation in the treatment of distal ulcerative colitis: a randomised, 5-ASA foam enema controlled multicenter trial [abstract]. Ital J Gastroenterol Hepatol 1997; 29: A41Google Scholar
  64. 64.
    Kam C, Cohen H, Dooley C, et al. A comparison of mesalamine suspension enema and oral sulfasalazine for treatment of active distal ulcerative colitis in adults. Am J Gastroenterol 1996; 91: 1338–42PubMedGoogle Scholar
  65. 65.
    D’Albasio G, Pacini F, Camarri E, et al. Combined therapy with 5-aminosalicylic acid tablets and enemas for maintaining remission in ulcerative colitis: a randomized double-blind study. Am J Gastroenterol 1997; 92: 1143–7PubMedGoogle Scholar
  66. 66.
    Sandborn WJ. A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine and methotrexate. Am J Gastroenterol 1996; 91: 423–33PubMedGoogle Scholar
  67. 67.
    Campbell AC, Skinner JM, Hersey P, et al. Immunosuppression in the treatment of inflammatory bowel disease: 1. Changes in lymphoid subpopulations in the blood and rectal mucosa following cessation of treatment with azathioprine. Clin Exp Immunol 1974; 16: 521–33Google Scholar
  68. 68.
    Campbell AC, Skinner JM, MacLennan ICM, et al. Immunosuppression in the treatment of inflammatory bowel disease: 2. The effects of azathioprine on lymphoid cell populations in a double blind trial in ulcerative colitis. Clin Exp Immunol 1976; 24: 249–58Google Scholar
  69. 69.
    Connell WR, Kamm MA, Lennard-Jones JE, et al. Bone marrow toxicity resulting from azathioprine treatment in inflammatory bowel disease: experience from 1663 patient years of therapy [abstract]. Gut 1992; 33 Suppl. 1: S10Google Scholar
  70. 70.
    Connell WR, Kamm MA, Dickson M, et al. Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease. Lancet 1994; 343: 1249–52PubMedGoogle Scholar
  71. 71.
    Adler DJ, Korelitz BI. The therapeutic efficacy of 6-mercaptopurine in refractory ulcerative colitis. Am J Gastroenterol 1990; 85: 717–22PubMedGoogle Scholar
  72. 72.
    Ardizzone S, Molteni P, Imbesi V, et al. Azathioprine in steroid-resistant and steroid-dependent ulcerative colitis. J Clin Gastroenterol 1997; 25: 127–30Google Scholar
  73. 73.
    Hawthorne AB, Logan RFA, Hawkey CJ, et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. BMJ 1992; 305: 20–2PubMedGoogle Scholar
  74. 74.
    George J, Present DH, Pou R, et al. The long-term outcome of ulcerative colitis treated with 6-mercaptopurine. Am J Gastroenterol 1996; 91: 1711–4PubMedGoogle Scholar
  75. 75.
    Hess AD, Tutschka PJ, Santos GW. Effect of cyclosporin A on human lymphocyte response in vitro: III. CsA inhibits the production of T lymphocyte growth factors in secondary mixed lymphocyte responses but does not inhibit the response of primed lymphocytes to TCGF. J Immunol 1982; 128: 355–9PubMedGoogle Scholar
  76. 76.
    Sandborn WJ. A critical review of cyclosporin therapy in inflammatory bowel disease. Inflamm Bowel Dis 1995; 1: 48–63Google Scholar
  77. 77.
    Lichtiger S, Present DH, Korkbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 1994; 330: 1841–5PubMedGoogle Scholar
  78. 78.
    Marion JF, Present DH. 6-Mercaptopurine maintains cyclosporine induced response in patients with ulcerative colitis [abstract]. Am J Gastroenterol 1996; 91: 1975Google Scholar
  79. 79.
    Fernandez-Banares F, Bertran X, Esteve-Comas M, et al. Azathioprine is useful in maintaining long-term remission induced by intravenous cyclosporine in steroid-refractory severe ulcerative colitis. Am J Gastroenterol 1996; 91: 2498–9PubMedGoogle Scholar
  80. 80.
    Sandborn WJ, Tremaine WJ, Schroeder KW, et al. A placebo-controlled trial of cyclosporine enemas for mildly to moderately active left-sided ulcerative colitis. Gastroenterology 1994; 106: 1429–35PubMedGoogle Scholar
  81. 81.
    Miller LC, Cohen SE, Orencole SF. Interleukin-1 is structurally related to dihydrofolate reductase: effect of methotrexate on IL-1 [abstract]. Lymphokine Res 1988; 7: A272Google Scholar
  82. 82.
    Kozarek RA, Patterson DJ, Geelfand MD, et al. Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease. Ann Intern Med 1989; 110: 353–6PubMedGoogle Scholar
  83. 83.
    Oren R, Arber N, Odes S, et al. Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli Multicenter Trial. Gastroenterology 1996; 110: 1416–21PubMedGoogle Scholar
  84. 84.
    Baron TH, Russ CD, Elson CO. Low-dose oral methotrexate in refractory inflammatory bowel disease. Dig Dis Sci 1993; 38: 1851–6PubMedGoogle Scholar
  85. 85.
    Debinski HS, Kamm MA. Novel drug therapies in inflammatory bowel disease. Eur J Gastroenterol Hepatol 1995; 7: 169–81PubMedGoogle Scholar
  86. 86.
    Lauritsen K, Laursen LS, Rask-Madsen J, et al. Abbott-64077, a potent lipoxygenase inhibitor in the treatment of ulcerative colitis [abstract]. Gastroenterology 1990; 98: A185Google Scholar
  87. 87.
    Peppercorn M, Das K, Elson C, et al. Zileuton, a 5-lipoxygenase inhibitor, in the treatment of active ulcerative colitis — a double-blind, placebo-controlled trial [abstract]. Gastroenterology 1994; 106: A751Google Scholar
  88. 88.
    Hawkey CJ, Dube LM, Lorraine V, et al. A trial of zileuton versus mesalazine or placebo in the maintenance of remission of ulcerative colitis. Gastroenterology 1997; 112: 718–24PubMedGoogle Scholar
  89. 89.
    Roberts WG, Simon TJ, Berlin RG, et al. Leukotrienes in ulcerative colitis: results of a multicenter trial of a leukotriene biosynthesis inhibitor, MK-591. Gastroenterology 1997; 12: 725–32Google Scholar
  90. 90.
    Roediger WEW. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet 1980; II: 712–5Google Scholar
  91. 91.
    Scheppach W, Sommer H, Kirchner T, et al. Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology 1992; 103: 51–6PubMedGoogle Scholar
  92. 92.
    Steinhart AH, Brzezinski A, Baker JP. Treatment of refractory ulcerative proctosigmoiditis with butyrate enemas. Am J Gastroenterol 1994; 89: 179–83PubMedGoogle Scholar
  93. 93.
    Vernia P, Cittadini M, Caprilli R, et al. Topical treatment of refractory distal ulcerative colitis with 5-ASA and sodium butyrate. Dig Dis Sci 1995; 40: 305–7PubMedGoogle Scholar
  94. 94.
    Vernia P, Marcheggiano A, Caprilli R, et al. Short-chain fatty acid topical treatment in distal ulcerative colitis. Aliment Pharmacol Ther 1995; 9: 309–13PubMedGoogle Scholar
  95. 95.
    Steinhart AH, Hiruki T, Brzezinski A, et al. Treatment of left-sided ulcerative colitis with butyrate enemas: a controlled trial. Aliment Pharmacol Ther 1996; 10: 729–36PubMedGoogle Scholar
  96. 96.
    Franceschi S, Panza E, La Vecchia C, et al. Non specific inflammatory bowel disease and smoking. Am J Epidemiol 1987; 125: 445–52PubMedGoogle Scholar
  97. 97.
    Cope GE, Heatley RV. Cigarette smoking and intestinal defenses. Gut 1992; 33: 721–3PubMedGoogle Scholar
  98. 98.
    Cohen RD, Hanauer SB. Nicotine in ulcerative colitis: how does it work and how can we use it? Clin Immunother 1996; 5: 169–74Google Scholar
  99. 99.
    Pullan RD, Rhodes J, Ganesh S, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med 1994; 330: 811–5PubMedGoogle Scholar
  100. 100.
    Thomas GAO, Rhodes J, Mani V, et al. Transdermal nicotine as maintenance therapy for ulcerative colitis. N Engl J Med 1995; 332: 988–92PubMedGoogle Scholar
  101. 101.
    Sandborn WJ, Tremaine WJ, Laighton JA, et al. Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study. Aliment Pharmacol Ther 1997; 11: 663–71PubMedGoogle Scholar
  102. 102.
    Bjork S, Dahlstrom A, Johansson L, et al. Treatment of the mucosa with local anaesthetics in ulcerative colitis. Agents Actions 1992; Special Conference Issue: C60-75Google Scholar
  103. 103.
    Arlander E, Ost A, Stahlberg D, et al. Ropivicaine gel in active distal ulcerative colitis and proctitis — a pharmacokinetic and exploratory clinical study. Aliment Pharmacol Ther 1996; 10: 73–81PubMedGoogle Scholar
  104. 104.
    Campieri M, Gionchetti P, Belluzzi A, et al. 5-Aminosalicylic acid, sucralfate and placebo enemas in the treatment of distal ulcerative colitis. Eur J Gastroenterol Hepatol 1991; 3: 41–4Google Scholar
  105. 105.
    Ardizzone S, Petrillo M, Antonacci CM, et al. Sucralfate and hydrocortisone enemas in the treatment of active ulcerative proctitis — a randomized single-blind comparative study. Aliment Pharmacol Ther 1996; 10: 957–60PubMedGoogle Scholar
  106. 106.
    Lechin F, Van der Dijs B, Insausti CL, et al. Treatment of ulcerative colitis with clonidine. J Clin Pharmacol 1985; 25: 219–26PubMedGoogle Scholar
  107. 107.
    Gaffney PR, Doyle CT, Gaffney A, et al. Paradoxical response to heparin in 10 patients with ulcerative colitis. Am J Gastroenterol 1995; 90: 220–3PubMedGoogle Scholar
  108. 108.
    Evans RC, Shim Wong V, Morris AI, et al. Treatment of corticosteroid-resistant ulcerative colitis with heparin: a report of 16 cases. Aliment Pharmacol Ther 1997; 11: 1037–40PubMedGoogle Scholar
  109. 109.
    Mayer L, Sachar DB, Present DH, et al. Randomized double-blind, placebo-controlled trial of hydroxychloroquine (Plaquenil) in the treatment of ulcerative colitis [abstract]. Gastroenterology 1992; 102: A661Google Scholar
  110. 110.
    Goenka MK, Kochhar R, Tandia B, et al. Chloroquine for mild to moderately active ulcerative colitis: comparison with sulfasalazine. Am J Gastroenterol 1996; 91: 917–21PubMedGoogle Scholar
  111. 111.
    Truelove SC, Jewell DP. Intensive intravenous regimen for severe attacks of ulcerative colitis. Lancet 1974; I: 1067–70Google Scholar
  112. 112.
    Järnerot G, Ronly P, Sandberg-Gertzen H. Intensive intravenous treatment of ulcerative colitis. Gastroenterology 1985; 89: 1005–13PubMedGoogle Scholar
  113. 113.
    Järnerot G, Lennard-Jones JE, Bianchi Porro G, et al. Medical treatment of refractory distal ulcerative colitis. Gastroenterol Int 1991; 4: 93–8Google Scholar
  114. 114.
    Forbes A, Britton TC, House IM, et al. Safety and efficacy of acetarsol suppositories in unresponsive proctitis. Aliment Pharmacol Ther 1989; 3; 553–6PubMedGoogle Scholar
  115. 115.
    Ardizzone S, Petrillo M, Molteni P, et al. Coated oral 5-aminosalicylic acid (Claversal) is equivalent to sulfasalazine for remission maintenance in ulcerative colitis. J Clin Gastroenterol 1995; 21: 287–9PubMedGoogle Scholar
  116. 116.
    Ardizzone S, Molteni P, Bollani S, et al. Guidelines for the treatment of ulcerative colitis in remission. Eur J Gastroenterol Hepatol 1997; 9: 836–41PubMedGoogle Scholar
  117. 117.
    Azad Khan AK, Howes DT, Piris J, et al. Optimum dose of sulphasalazine for maintenance treatment in ulcerative colitis. Gut 1980; 21: 232–40PubMedGoogle Scholar
  118. 118.
    Travis SPL, Tysk C, de Silava HJ, et al. Optimum dose of olsalazine for maintaining remission in ulcerative colitis. Gut 1994; 35: 1282–6PubMedGoogle Scholar
  119. 119.
    Fockens P, Mulder JJ, Tytgat GNJ, et al. Comparison of the efficacy and safety of 1.5 compared with 3.0 g oral slow-release mesalazine (Pentasa) in the maintenance treatment of ulcerative colitis. Eur J Gastroenterol 1995; 7: 1025–30Google Scholar
  120. 120.
    Mesalamine Study Group. An oral preparation of mesalamine as long-term maintenance therapy for ulcerative colitis: a randomized, placebo-controlled trial. Ann Intern Med 1996; 124: 204–11Google Scholar
  121. 121.
    D’Arienzo A, Panarese A, D’Armiento FP, et al. 5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind, placebo-controlled trial. Am J Gastroenterol 1990; 85: 1079–82PubMedGoogle Scholar
  122. 122.
    D’Albasio G, Paoluzi P, Campieri M, et al. Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo controlled trial. Am J Gastroenterol. In pressGoogle Scholar
  123. 123.
    D’Albasio G, Trallori G, Ghetti A, et al. Intermittent therapy with high-dose 5-aminosalicylic acid enemas for maintaining remission in ulcerative proctosigmoiditis. Dis Colon Rectum 1990; 33: 394–7PubMedGoogle Scholar

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© Adis International Limited 1998

Authors and Affiliations

  • Sandro Ardizzone
    • 1
  • Gabriele Bianchi Porto
    • 1
  1. 1.Gastrointestinal Unit‘L. Sacco’ University HospitalMilanItaly

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