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ORAL PAPAIN IN GLUTEN INTOLERANCE
1022 medicine was changed without due notice being given to prescribers. We also stated (albeit as a footnote) that such cases could, "if repeated, seriously undermine [prescribers’] faith in brand names generally". Brand names must indeed always ensure consistent bioavailability if their use is to be advocated on those grounds. Nevertheless, it would be misleading to suggest that the O.H.E. paper argued that bioavailability considerations were the only justification for the use of brand names. Apart from the several economic arguments in their favour, brand identification helps to ensure manufacturer accountability for aspects of product manufacture and performance which go beyond bioavailability alone. Office of Health Economics, 130 Regent Street, London W1R 5FE
G. TEELING-SMITH
that
a
resulting relapse would provide a further opportunintc
the effect of oral papain. However, xylose remained normal and the patient has been symptom-free ever since, despite his gluten-containing diet. A duodenal biopsy done in May, 1976, revealed normal morphology. It would therefore appear that the patient had acquired or transient gluten intolerance rather than creliac disease. Other possibilities, such as giardiasis, cannot entirely be excluded, but appear less likely in view of the good clinical response to the glutenfree diet. We feel that further trials with oral crude papain as an
test
absorption
adjunct to a gluten-free diet in the treatment of gluten-intolerance are justified. We thank Mr 0. Bode, Department of Pharmacy, University of the formulation of enterically coated tablets of crude
Sydney for papain.
Departments of Biochemistry and Medicine, University of Sydney, Sydney, New South Wales 2006, U.S.A.
M. MESSER P. E. BAUME
ORAL PAPAIN IN GLUTEN INTOLERANCE
SIR,—Many patients with wheat-gluten intolerance, cceliac disease, show
e.g.,
delayed response to a gluten-free diet. Although symptomatic improvement is usually rapid, it is often 6-12 months before absorption tests or jejunal morphology improve, particularly in adults. A suboptimal response is usually ascribed to deviation from a strict gluten-free diet,’ the effect of which would be the ingestion of small amounts of gluten which might retard, though not necessarily prevent, improvement. The oral administration of an enzyme which could destroy the effect of such small amounts of gluten, might therefore improve the initial response to the gluten-free diet. Studies in which gluten was predigested in vitro with proteases, and then fed to coeliac patients, showed that of various commercially available enzymes, only crude papain abolished the harmful action of gluten; pepsin and trypsin or pancreatin or purified papain were ineffective.2 3 crude papain, the dried and powdered latex of the unripe pawpaw (Carica papaya), contains a mixture of enzymes including papain, chymopapain, papaya peptidase, and glutamine cyclotransferase.4s The biochemical mechanism by which it abolishes the effect of gluten in cœliac disease is unknown, but it has been suggested that N-glutaminyl peptides liberated from gluten by the proteases of crude papain are detoxified by glutamine cyclotransferase.3 All four enzymes are active at pH 7 and should therefore be able to act within the small intestine. The crude enzyme, orally administered, was once popular in Asia as an anthelmintic and in the U.S.A. as a treatment for chronic dyspepsia; no deleterious effects were mentioned.6 Papain was also given to children with diarrha:a.6 More recently it has been proposed for postoperative inflammation and oedema, and it is still widely used as a meat tenderiser. We have tested the effect of oral papain on an adult with intestinal malabsorption and partial villous atrophy who was regarded as having cceliac disease. He was put on a gluten-free diet in April, 1973, yet, despite rapid symptomatic improvement and some gain in weight, steatorrhoea continued and xylose absorption had improved only slightly after 6 months on the diet. In October, 1973, the patient began taking six 330 mg enteric-coated tables of crude papain (Sigma Chemical Co., St. Louis, U.S.A.), with every meal. No side-effects were noted, but he reported a lower incidence of loose stools. After 4 weeks of therapy his absorption had improved to normal. The patient then agreed to abandon the gluten-free diet in the expectation 1.
TESTING FOR HYDATID DISEASE
a
Townley, R R W, Anderson, C. M., Ergebnisse d. inn. Medizin, N.F., 26, Springer-Verlag, 1967. 2. Krainick, H. G., Mohn, G. Helv. pædiat. Acta, 1959, 14, 124. 3. Messer, M., Anderson, C. M., Hubbard, L. Gut, 1964, 5, 295. 4. Glazer, A N., Smith, E. L. in The Enzymes (edited by P. D. Boyer); vol. III, p. 501. New York, 1971. 5. Messer, M., Ottesen, M. Biochim. biophys. Acta, 1964, 92, 409. 6. Hwang, K., Ivy, A. C. Ann. N.Y. Acad. Sci. 1951, 54, 161.
SIR,-Your editorial (Sept. 11, p. 553) on hydatid immunofailed to mention one of the most significant advances of the past 10 years. The presentation would have been more balanced if you had considered the immunoelectrophoresis (I.E.P.) test introduced by Capron et al. in France;’ this is the only test, using currently available antigens, that is absolutely specific for hydatid disease. The diagnostic criterion for the I.E.P. test is qualitative-the demonstration of the Echinococcus granulosus specific "arc-5", one of several antigen-antibody precipitation bands which may be demonstrable in the serum of patients with hydatid disease. Using this criterion, no false-positive reactions have been reported in persons without hydatid disease.2-6 Specificity is a unique and important advantage of the I.E.P. test because neoplasms and other space-filling lesions of the lungs and liver that may resemble false-positive hydatid disease clinically are associated with reactions in other tests for hydatid disease.67 You seem to advocate the complement-fixation (c.F,) test, although this test, even under ideal conditions, is less sensitive and less specific than many others, all of which (except for the I.E.P. test) are limited by non-specificity.’-" Although the c.F, test is useful for the postoperative evaluation of patients with hydatids because of the relatively rapid decline in antibody titre, 12 I.E.P. is useful for the same purpose,2and, because of its other advantages, would be the test of choice. At least until methods for isolating and purifying E, granulosus specific antigens 13 proceed to the point that such antigens can be adapted for use in simpler and more rapid serological tests, the I.E.P. test using whole hydatid cyst fluid as antigen should be included among those tests used for diagnosing hydatid disease.
diagnosis
Parasitic Diseases Branch, Bureau of Epidemiology, Center for Disease Control, Atlanta, Georgia 30333, U.S.A.
1.
PETER M. SCHANTZ
Capron, A., Vernes, A., Biquet, J. in Le kyste hydatique du foie; p. 27. Lyon, 1967.
2. 3. 4.
Capron, A., Yarzabal, L., Vernes, A., Fruit, J. Path. Biol. 1970, 18, 357. Quilici, M., Assadourian, Y., Ranque, P. med. trop., 1971, 31, 207. Yarzabal, L. A., Leiton, J., Lopez-Lemes, M. H. Am. J. trop. Med Hyg. 1974, 23, 662. 5. Varela-Diaz, V. M., Coltorti, E. A., Prezioso, V., Lopez-Lemes, M. H. Gui santes, J. A., Yarzabal, L. A. ibid. 1975, 24, 312. 6. Yarzabal, L. A., Schantz, P. M., Lopez-Lemes, M. H. ibid. 1975, 24, 843 7. Kagan, I. G. Bull. Wld Hlth Org. 1968, 39, 25. 8. Sorice, F., Pauluzzi, S., Castagnari, L., Telu, A. Boll. Ist. sieroter milan., 1965, 44, 22. 9. Zanussi, C., Sorice, F., Castagnari, L. ibid. 1966, 45, 102. 10. Garabedian, G. A. Ann. trop. Med. Parsit. 1971, 65, 385. 11. Lass, N., Laver, Z., Lengy, J. Ann. Allergy, 1973, 31, 430. 12. Matossian, R. M., Araj, G. F. J. Hyg. Camb, 1975, 75, 333. 13. Bout, D., Fruit, J., Capron, A. Ann. Immun. Inst. Pasteur, 1974 125c,775.
G. TEELING-SMITH
that
a
resulting relapse would provide a further opportunintc
the effect of oral papain. However, xylose remained normal and the patient has been symptom-free ever since, despite his gluten-containing diet. A duodenal biopsy done in May, 1976, revealed normal morphology. It would therefore appear that the patient had acquired or transient gluten intolerance rather than creliac disease. Other possibilities, such as giardiasis, cannot entirely be excluded, but appear less likely in view of the good clinical response to the glutenfree diet. We feel that further trials with oral crude papain as an
test
absorption
adjunct to a gluten-free diet in the treatment of gluten-intolerance are justified. We thank Mr 0. Bode, Department of Pharmacy, University of the formulation of enterically coated tablets of crude
Sydney for papain.
Departments of Biochemistry and Medicine, University of Sydney, Sydney, New South Wales 2006, U.S.A.
M. MESSER P. E. BAUME
ORAL PAPAIN IN GLUTEN INTOLERANCE
SIR,—Many patients with wheat-gluten intolerance, cceliac disease, show
e.g.,
delayed response to a gluten-free diet. Although symptomatic improvement is usually rapid, it is often 6-12 months before absorption tests or jejunal morphology improve, particularly in adults. A suboptimal response is usually ascribed to deviation from a strict gluten-free diet,’ the effect of which would be the ingestion of small amounts of gluten which might retard, though not necessarily prevent, improvement. The oral administration of an enzyme which could destroy the effect of such small amounts of gluten, might therefore improve the initial response to the gluten-free diet. Studies in which gluten was predigested in vitro with proteases, and then fed to coeliac patients, showed that of various commercially available enzymes, only crude papain abolished the harmful action of gluten; pepsin and trypsin or pancreatin or purified papain were ineffective.2 3 crude papain, the dried and powdered latex of the unripe pawpaw (Carica papaya), contains a mixture of enzymes including papain, chymopapain, papaya peptidase, and glutamine cyclotransferase.4s The biochemical mechanism by which it abolishes the effect of gluten in cœliac disease is unknown, but it has been suggested that N-glutaminyl peptides liberated from gluten by the proteases of crude papain are detoxified by glutamine cyclotransferase.3 All four enzymes are active at pH 7 and should therefore be able to act within the small intestine. The crude enzyme, orally administered, was once popular in Asia as an anthelmintic and in the U.S.A. as a treatment for chronic dyspepsia; no deleterious effects were mentioned.6 Papain was also given to children with diarrha:a.6 More recently it has been proposed for postoperative inflammation and oedema, and it is still widely used as a meat tenderiser. We have tested the effect of oral papain on an adult with intestinal malabsorption and partial villous atrophy who was regarded as having cceliac disease. He was put on a gluten-free diet in April, 1973, yet, despite rapid symptomatic improvement and some gain in weight, steatorrhoea continued and xylose absorption had improved only slightly after 6 months on the diet. In October, 1973, the patient began taking six 330 mg enteric-coated tables of crude papain (Sigma Chemical Co., St. Louis, U.S.A.), with every meal. No side-effects were noted, but he reported a lower incidence of loose stools. After 4 weeks of therapy his absorption had improved to normal. The patient then agreed to abandon the gluten-free diet in the expectation 1.
TESTING FOR HYDATID DISEASE
a
Townley, R R W, Anderson, C. M., Ergebnisse d. inn. Medizin, N.F., 26, Springer-Verlag, 1967. 2. Krainick, H. G., Mohn, G. Helv. pædiat. Acta, 1959, 14, 124. 3. Messer, M., Anderson, C. M., Hubbard, L. Gut, 1964, 5, 295. 4. Glazer, A N., Smith, E. L. in The Enzymes (edited by P. D. Boyer); vol. III, p. 501. New York, 1971. 5. Messer, M., Ottesen, M. Biochim. biophys. Acta, 1964, 92, 409. 6. Hwang, K., Ivy, A. C. Ann. N.Y. Acad. Sci. 1951, 54, 161.
SIR,-Your editorial (Sept. 11, p. 553) on hydatid immunofailed to mention one of the most significant advances of the past 10 years. The presentation would have been more balanced if you had considered the immunoelectrophoresis (I.E.P.) test introduced by Capron et al. in France;’ this is the only test, using currently available antigens, that is absolutely specific for hydatid disease. The diagnostic criterion for the I.E.P. test is qualitative-the demonstration of the Echinococcus granulosus specific "arc-5", one of several antigen-antibody precipitation bands which may be demonstrable in the serum of patients with hydatid disease. Using this criterion, no false-positive reactions have been reported in persons without hydatid disease.2-6 Specificity is a unique and important advantage of the I.E.P. test because neoplasms and other space-filling lesions of the lungs and liver that may resemble false-positive hydatid disease clinically are associated with reactions in other tests for hydatid disease.67 You seem to advocate the complement-fixation (c.F,) test, although this test, even under ideal conditions, is less sensitive and less specific than many others, all of which (except for the I.E.P. test) are limited by non-specificity.’-" Although the c.F, test is useful for the postoperative evaluation of patients with hydatids because of the relatively rapid decline in antibody titre, 12 I.E.P. is useful for the same purpose,2and, because of its other advantages, would be the test of choice. At least until methods for isolating and purifying E, granulosus specific antigens 13 proceed to the point that such antigens can be adapted for use in simpler and more rapid serological tests, the I.E.P. test using whole hydatid cyst fluid as antigen should be included among those tests used for diagnosing hydatid disease.
diagnosis
Parasitic Diseases Branch, Bureau of Epidemiology, Center for Disease Control, Atlanta, Georgia 30333, U.S.A.
1.
PETER M. SCHANTZ
Capron, A., Vernes, A., Biquet, J. in Le kyste hydatique du foie; p. 27. Lyon, 1967.
2. 3. 4.
Capron, A., Yarzabal, L., Vernes, A., Fruit, J. Path. Biol. 1970, 18, 357. Quilici, M., Assadourian, Y., Ranque, P. med. trop., 1971, 31, 207. Yarzabal, L. A., Leiton, J., Lopez-Lemes, M. H. Am. J. trop. Med Hyg. 1974, 23, 662. 5. Varela-Diaz, V. M., Coltorti, E. A., Prezioso, V., Lopez-Lemes, M. H. Gui santes, J. A., Yarzabal, L. A. ibid. 1975, 24, 312. 6. Yarzabal, L. A., Schantz, P. M., Lopez-Lemes, M. H. ibid. 1975, 24, 843 7. Kagan, I. G. Bull. Wld Hlth Org. 1968, 39, 25. 8. Sorice, F., Pauluzzi, S., Castagnari, L., Telu, A. Boll. Ist. sieroter milan., 1965, 44, 22. 9. Zanussi, C., Sorice, F., Castagnari, L. ibid. 1966, 45, 102. 10. Garabedian, G. A. Ann. trop. Med. Parsit. 1971, 65, 385. 11. Lass, N., Laver, Z., Lengy, J. Ann. Allergy, 1973, 31, 430. 12. Matossian, R. M., Araj, G. F. J. Hyg. Camb, 1975, 75, 333. 13. Bout, D., Fruit, J., Capron, A. Ann. Immun. Inst. Pasteur, 1974 125c,775.