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INHIBITION OF PROSTAGLANDIN SYNTHESIS AS A TREATMENT FOR BILIARY PAIN
584 suppose that rejection and immunosuppressive therapy will be harder to manage with transplanted islet cells than with other transplanted tissues. Indeed, some
to
successful attempts have been made to circumvent these problems by encasing the implant in ’Nucleopore’ chambers 16 or storing the islets in tissue-culture for a long period to reduce their antigenicity. 17-19 This work was supported by grants from the Swedish Medical Research Council, the Swedish Diabetes Association, and the Nordic Insulin Fund. I thank Miss Eva Hansson and Miss Astrid Nordin for technical assistance.
disease was confirmed at surgery or by treated for 24 separate attacks of biliary colic with no medication other than 50 mg of indomethacin injected intravenously over 5 min. The mean duration of pain before the treatment was 36 h (range 2-85 h). Ten of the patients had a temperature of 38°C or more. The abdomen was examined by a surgeon, and blood-pressure, pulse-rate, and the patients’ symptoms were recorded before the injection and during observation periods of 30 min to 2 h after administration of the drug. Any side-effects were also recorded. in whom
X-ray
gallstone
were
RESULTS REFERENCES
relieved within 30 min of each of all 24 In 3 instances the effect was moderate, in the remaining 21 it was complete or almost complete. Pain
1. Ballinger, W., Lacy, P. E. Surgery, 1972, 72, 175. 2. Hegre, O. D., Lazarow, A. in The Diabetic Pancreas (edited by B. W. Volk and K. F. Wellman); p. 517. New York, 1977. 3. MacLaren, N. K., Huang, S. E., Fogh, J. Lancet, 1975,i, 997. 4. Ibid. 1975,ii, 909. 5. LeCompte, P. M. Archs Path. 1958, 66, 450. 6. Gepts, W. Diabetes, 1965, 14, 619. 7. Bottazzo, G. F., Flovin-Christensen, A., Doniach, D. Lancet, 1974,ii, 1279. 8. Hume, D. M., Merrill, J. P., Miller, B. F., Thorn, G. W. J. clin. Invest. 1955,
was
treatments.
DATA ON
20
PATIENTS TREATED FOR
24
ATTACKS OF PAIN
ASSOCIATED WITH GALLSTONES
34, 327. 9. Merrill, J. P. New Engl. J. Med. 1974, 290, 374. 10. Like, A. A., Rossini, A. A. Science, 1976, 193, 415. 11. Howell, S. L., Taylor, K. W. Biochem. J. 1968, 108, 17. 12. Andersson, A. Diabetologia, 1978, 14, 397. 13. Rossini, A. A., Williams, R. M., Appel, M. C., Like, A. A. Nature, 1978, 276, 182. 14. Lendrum, R., Walker, G., Gamble, D. R. Lancet, 1975, i, 880. 15. Lendrum, R., Walker, G., Cudworth, A. G., Theophanides, C., Pyke, D. A., Bloom, A., Gamble, D.R. ibid. 1976,ii, 1273. 16. Gates, R. J., Lazarus, N. R. ibid. 1977,ii, 1257. 17. Seltzer, H. Univ. Mich. med. Cent. J. 1976, 42, 12. 18. Kedinger, M., Haffen, K., Grenier, J., Eloy, R. Nature, 1977, 270, 736. 19. Andersson, A., Hellerström, C. in The Immunology of Diabetes (edited by W. J. Irvine) (in the press).
INHIBITION OF PROSTAGLANDIN SYNTHESIS AS A TREATMENT FOR BILIARY PAIN E. THORNELL J. G. KRAL
R. JANSSON J. SVANVIK
Department of Surgery, University of Göteborg, Göteborg, Sweden
with confirmed gallbladder disease were treated with intravenous indomethacin during 24 separate attacks of biliary pain. In all cases the pain was promptly relieved and there were no important side-effects. Indomethacin, an inhibitor of prostaglandin synthesis, may reduce intraluminal pressure in the gallbladder, and relieve pain.
Summary
Twenty patients
INTRODUCTION
PROSTAGLANDINS
can
contract
gallbladder
smooth
muscle1 and induce secretion into the gallbladder lumen.2 Both these effects may increase the intraluminal pressure within the
gallbladder, and this in turn can cause biliary pain.3 The high concentrations of prostaglandins in the gallbladder mucosa of patients with chronic cholecystitis4 suggest that prostaglandins may be involved in the pathogenesis of biliary pain. In this study indomethacin, an inhibitor of prostaglandin synthesis was used to treat patients with biliary pain. METHODS
Twenty consecutive patients in the hospital emergency ward
Op.=operation.
Abdominal tenderness and guarding were reduced in all patients within 15-20 min. Apart from vertigo and slight nausea in 7 treatments in males and 5 in females there were no side-effects. DISCUSSION
Intravenous indomethacin effectively relieved biliary pain during attacks of gallstone disease. Although central analgesic or placebo effects cannot be ruled out, neither mechanism seems sufficient to explain the dramatic and consistent results. Indomethacin might act by inhibiting local prostaglandin synthesis in the gallbladder. The precursor fatty acid for prostaglandin synthesis can be provided by phospholipids in gallbladder tissue or bile by the action of phospholipase Awhich is set free in the gallbladder mucosa by mechanical and chemical 6
stimuli. The results suggest that inhibition of prostaglandin synthesis might be a valuable new method for the treatment of attacks of gallstone disease. In addition new insights into the pathophysiology of cholecystitis may be provided. A double-blind study with placebo is in progress.
Requests for reprints should be addressed to E.T., Ktrurgtska Kliniken, Sahlgrenska Sjukhuset, 41345 Goteborg, Sweden. REFERENCES 1. Morton,
K.
J. M., Saverymuttu, S. H., Wood, J. H., Wood, J. R. Br. J. Pharmac. 1974, 50, 460. 2. Heintze, K., Lemesser, W., Peterson, K. U., Heidenreich, O. Prostaglandins, 1975, 9, 309. 3. Layne, J. A., Bergh, G. S. Surgery Gynec. Obstet. 1940, 70, 18. 4. Wood, J. R., Stamford, J. F. Prostaglandins, 1977, 13, 97. 5. Kunze, H., Vogt, W. Am. N.Y.Acad. Sci. 1971, 180, 123. 6. Sjödahl, R., Tagesson, C., Wetterfors, J. Surgery Gynec. Obstet. 1975, 146, 199.
to
successful attempts have been made to circumvent these problems by encasing the implant in ’Nucleopore’ chambers 16 or storing the islets in tissue-culture for a long period to reduce their antigenicity. 17-19 This work was supported by grants from the Swedish Medical Research Council, the Swedish Diabetes Association, and the Nordic Insulin Fund. I thank Miss Eva Hansson and Miss Astrid Nordin for technical assistance.
disease was confirmed at surgery or by treated for 24 separate attacks of biliary colic with no medication other than 50 mg of indomethacin injected intravenously over 5 min. The mean duration of pain before the treatment was 36 h (range 2-85 h). Ten of the patients had a temperature of 38°C or more. The abdomen was examined by a surgeon, and blood-pressure, pulse-rate, and the patients’ symptoms were recorded before the injection and during observation periods of 30 min to 2 h after administration of the drug. Any side-effects were also recorded. in whom
X-ray
gallstone
were
RESULTS REFERENCES
relieved within 30 min of each of all 24 In 3 instances the effect was moderate, in the remaining 21 it was complete or almost complete. Pain
1. Ballinger, W., Lacy, P. E. Surgery, 1972, 72, 175. 2. Hegre, O. D., Lazarow, A. in The Diabetic Pancreas (edited by B. W. Volk and K. F. Wellman); p. 517. New York, 1977. 3. MacLaren, N. K., Huang, S. E., Fogh, J. Lancet, 1975,i, 997. 4. Ibid. 1975,ii, 909. 5. LeCompte, P. M. Archs Path. 1958, 66, 450. 6. Gepts, W. Diabetes, 1965, 14, 619. 7. Bottazzo, G. F., Flovin-Christensen, A., Doniach, D. Lancet, 1974,ii, 1279. 8. Hume, D. M., Merrill, J. P., Miller, B. F., Thorn, G. W. J. clin. Invest. 1955,
was
treatments.
DATA ON
20
PATIENTS TREATED FOR
24
ATTACKS OF PAIN
ASSOCIATED WITH GALLSTONES
34, 327. 9. Merrill, J. P. New Engl. J. Med. 1974, 290, 374. 10. Like, A. A., Rossini, A. A. Science, 1976, 193, 415. 11. Howell, S. L., Taylor, K. W. Biochem. J. 1968, 108, 17. 12. Andersson, A. Diabetologia, 1978, 14, 397. 13. Rossini, A. A., Williams, R. M., Appel, M. C., Like, A. A. Nature, 1978, 276, 182. 14. Lendrum, R., Walker, G., Gamble, D. R. Lancet, 1975, i, 880. 15. Lendrum, R., Walker, G., Cudworth, A. G., Theophanides, C., Pyke, D. A., Bloom, A., Gamble, D.R. ibid. 1976,ii, 1273. 16. Gates, R. J., Lazarus, N. R. ibid. 1977,ii, 1257. 17. Seltzer, H. Univ. Mich. med. Cent. J. 1976, 42, 12. 18. Kedinger, M., Haffen, K., Grenier, J., Eloy, R. Nature, 1977, 270, 736. 19. Andersson, A., Hellerström, C. in The Immunology of Diabetes (edited by W. J. Irvine) (in the press).
INHIBITION OF PROSTAGLANDIN SYNTHESIS AS A TREATMENT FOR BILIARY PAIN E. THORNELL J. G. KRAL
R. JANSSON J. SVANVIK
Department of Surgery, University of Göteborg, Göteborg, Sweden
with confirmed gallbladder disease were treated with intravenous indomethacin during 24 separate attacks of biliary pain. In all cases the pain was promptly relieved and there were no important side-effects. Indomethacin, an inhibitor of prostaglandin synthesis, may reduce intraluminal pressure in the gallbladder, and relieve pain.
Summary
Twenty patients
INTRODUCTION
PROSTAGLANDINS
can
contract
gallbladder
smooth
muscle1 and induce secretion into the gallbladder lumen.2 Both these effects may increase the intraluminal pressure within the
gallbladder, and this in turn can cause biliary pain.3 The high concentrations of prostaglandins in the gallbladder mucosa of patients with chronic cholecystitis4 suggest that prostaglandins may be involved in the pathogenesis of biliary pain. In this study indomethacin, an inhibitor of prostaglandin synthesis was used to treat patients with biliary pain. METHODS
Twenty consecutive patients in the hospital emergency ward
Op.=operation.
Abdominal tenderness and guarding were reduced in all patients within 15-20 min. Apart from vertigo and slight nausea in 7 treatments in males and 5 in females there were no side-effects. DISCUSSION
Intravenous indomethacin effectively relieved biliary pain during attacks of gallstone disease. Although central analgesic or placebo effects cannot be ruled out, neither mechanism seems sufficient to explain the dramatic and consistent results. Indomethacin might act by inhibiting local prostaglandin synthesis in the gallbladder. The precursor fatty acid for prostaglandin synthesis can be provided by phospholipids in gallbladder tissue or bile by the action of phospholipase Awhich is set free in the gallbladder mucosa by mechanical and chemical 6
stimuli. The results suggest that inhibition of prostaglandin synthesis might be a valuable new method for the treatment of attacks of gallstone disease. In addition new insights into the pathophysiology of cholecystitis may be provided. A double-blind study with placebo is in progress.
Requests for reprints should be addressed to E.T., Ktrurgtska Kliniken, Sahlgrenska Sjukhuset, 41345 Goteborg, Sweden. REFERENCES 1. Morton,
K.
J. M., Saverymuttu, S. H., Wood, J. H., Wood, J. R. Br. J. Pharmac. 1974, 50, 460. 2. Heintze, K., Lemesser, W., Peterson, K. U., Heidenreich, O. Prostaglandins, 1975, 9, 309. 3. Layne, J. A., Bergh, G. S. Surgery Gynec. Obstet. 1940, 70, 18. 4. Wood, J. R., Stamford, J. F. Prostaglandins, 1977, 13, 97. 5. Kunze, H., Vogt, W. Am. N.Y.Acad. Sci. 1971, 180, 123. 6. Sjödahl, R., Tagesson, C., Wetterfors, J. Surgery Gynec. Obstet. 1975, 146, 199.