Gold in the treatment of rheumatoid arthritis

  • R. C. Butler


Published trials of gold treatment in rheumatoid arthritis have been reviewed. There is clear evidence that a six-month course of gold injections will reduce symptoms and signs of synovitis and improve patient well-being to a greater extent than placebo. This advantage will persist for one year after injections have been stopped, but can no longer be demonstrated after a further year. There is no compelling evidence that treatment for longer than six months is of value. Evidence that gold alters the outcome in rheumatoid arthritis is scanty, and the contention that gold retards radiological deterioration rests largely on a single prospective study in 27 patients. The undoubted short-term and equivocal longer-term benefits of gold therapy are achieved at a high price in terms of toxicity; even when long-term treatment is attempted, only a minority of patients will remain on treatment after three years. The place of gold salts in the treatment of rheumatoid arthritis needs to be reassessed.


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  1. 1.
    Forestier, J. ‘Rheumatoid arthritis and its treatment by gold salts’, Lancet 2 (1934) 646–8.CrossRefGoogle Scholar
  2. 2.
    Hartfall, S. J., Garland, H. G. and Goldie, W. ‘Gold treatment of arthritis. A review of 900 cases’, Lancet 2 (1937) 784–8 and 838–42.Google Scholar
  3. 3.
    Jessop, J. D. and Johns, R. G. S. ‘Serum gold determination in patients with rheumatoid arthritis receiving sodium aurothiomalate’, Ann. Rheum. Dis. 32 (1973) 228–32.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Gottlieb, N. L., Smith, P. M. and Smith, E. M. ‘Pharmacodynamics of 197-Au and 195-Au labelled aurothiomalate in blood’, Arthritis Rheum. 17 (1974) 171–83.PubMedCrossRefGoogle Scholar
  5. 5.
    Mascarthenas, B. R., Granda, J. L. and Freyberg, R. H. ‘Gold metabolism in patients with rheumatoid arthritis treated with gold compounds reinvestigated’, Arthritis Rheum. 15 (1972) 391–402.CrossRefGoogle Scholar
  6. 6.
    Gottlieb, N. L., Smith, P. M. and Smith, E. M. ‘Gold excretion correlated with clinical course during chrysotherapy in rheumatoid arthritis’, Arthritis Rheum. 15 (1972) 582–92.PubMedCrossRefGoogle Scholar
  7. 7.
    Gerber, R. C., Paulus, H. E., Jennrich, R. I. et al. ‘Gold kinetics following aurothiomalate therapy: use of a whole body radiation counter’, J. Lab. Clin. Med. 83 (1974) 778–89.PubMedGoogle Scholar
  8. 8.
    Pedersen, S. M. and Graabaek, P. M. ‘Gold in erythrocytes, whole blood, and plasma during long-term chrysotherapy’, Ann. Rheum. Dis. 39 (1980) 576–9.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Graham, G. G., Haavisto, T. M., McNaught, P. J., Browne, C. D. and Champion, G. D. ‘The effect of smoking on the distribution of gold in blood’, J. Rheumatol. 9 (1982) 527–31.PubMedGoogle Scholar
  10. 10.
    Lewis, D., Capell, H. A., McNeil, C. J., Iqbal, M. S., Brown, D. H. and Smith, W. E. ‘Gold levels produced by treatment with auranofin and sodium aurothiomalate’, Ann. Rheum. Dis. 42 (1983) 566–70.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Gerber, R. C., Paulus, H. E., Bluestone, R. et al. ‘Kinetics of aurothiomalate in serum and synovial fluid’, Arthritis Rheum. 15 (1972) 625–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Gottlieb, N. L., Smith, P. M., and Smith, E. M. ‘Tissue gold concentration in a rheumatoid arthritic receiving chrysotherapy’, Arthritis Rheum. 15 (1972) 16–22.PubMedCrossRefGoogle Scholar
  13. 13.
    Penneys, N. S., McCreary, S. and Gottlieb, N. L. ‘Intracellular distribution of radiogold: localisation to large granule membranes’, Arthritis Rheum. 19 (1976) 927–32.PubMedCrossRefGoogle Scholar
  14. 14.
    Vernon-Roberts, B., Dore, J. L., Jessop, J. D. and Henderson, W. J. ‘Selective concentration and localisation of gold in macrophages of synovial and other tissues during and after chrysotherapy in rheumatoid patients’, Ann. Rheum. Dis. 35 (1976) 477–86.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Blocka, K., Furst, D. E., Landaw, E. et al. ‘Single dose pharmacokinetics of auranofin in rheumatoid arthritis’, J. Rheumatol. 9 (suppl. 8) (1982) 110–19.Google Scholar
  16. 16.
  17. 17.
    Ellman, P., Lawrence, J. S. and Thorold, G. P. ‘Gold therapy in rheumatoid arthritis’, Br. Med. J. 2 (1940) 314–16.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Fraser, T. N. ‘Gold treatment in rheumatoid arthritis’, Ann. Rheum. Dis. 4 (1945) 71–5.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Research Subcommittee of the Empire Rheumatism Council, ‘Gold therapy in rheumatoid arthritis. Report of a multicentre controlled trial’, Ann. Rheum. Dis. 19 (1960) 95–119.CrossRefGoogle Scholar
  20. 20.
    Research Subcommittee of the Empire Rheumatism Council, ‘Gold therapy in rheumatoid arthritis. Final report of a multicentre controlled trial’, Ann. Rheum. Dis. 20 (1961) 315–34.CrossRefGoogle Scholar
  21. 21.
  22. 22.
    Cooperating Clinics Committee of the American Rheumatism Association ‘A controlled trial of gold salt therapy in rheumatoid arthritis’, Arthritis Rheum. 16 (1973) 353–8.Google Scholar
  23. 23.
    Waine, H., Baker, F. and Mettier, S. R. ‘Controlled evaluation of gold therapy in rheumatoid arthritis’, Calif. Med. 66 (1947) 295–6.PubMedCentralGoogle Scholar
  24. 24.
    Freyberg, R. H. ‘Gold therapy for rheumatoid arthritis’, in Hollander, J. L., McCarty, D. J. (eds). Arthritis and Allied Conditions, 8th edition (Philadelphia: Lea and Febiger, 1972 ) 455–82.Google Scholar
  25. 25.
    See notes 19 and 20.Google Scholar
  26. 26.
    Cats, A. ‘A multicentre controlled trial of the effects of different dosage of gold therapy, followed by a maintenance dosage’, Agents and Actions, 6 (1976) 355–63.PubMedCrossRefGoogle Scholar
  27. 27.
    See note 20.Google Scholar
  28. 28.
    Sigler, J. W., Bluhm, G. B., Duncan, H., Sharp, J. T., Ensign, D. C. and McCrum, W. R. ‘Gold salts in the treatment of rheumatoid arthritis. A double-blind study’, Ann. Intern. Med. 80 (1974) 21–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Rothermich, N. O., Philips, V., Bergen, W. and Thomas, M. H. ‘Chrysotherapy. A prospective study’, Arthritis Rheum. 19 (1976) 1321–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Griffin, A. J., Gibson, T., Hutson, G. and Taylor, A. ‘Maintenance chrysotherapy in rheumatoid arthritis: a comparison of two dose schedules’, Ann. Rheum. Dis. 40 (1981) 250–3.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    See note 29.Google Scholar
  32. 32.
    Sagransky, D. M. and Greenwald, R. A. ‘Efficacy and toxicity of retreatment with gold salts: a retrospective review of 25 cases’, J. Rheumatol. 7 (1980) 474–8.PubMedGoogle Scholar
  33. 33.
    Evers, A. E. and Sundstrom, W. R. ‘Second course of gold therapy in the treatment of rheumatoid arthritis’, Arthritis Rheum. 26 (1983) 1071–5.PubMedCrossRefGoogle Scholar
  34. 34.
    See note 29.Google Scholar
  35. 35.
    Rothermich, N. O., Philips, V., Bergen, W. and Thomas, M. H. ‘Follow-up study of chrysotherapy’, Arthritis Rheum. 22 (1979) 423.PubMedCrossRefGoogle Scholar
  36. 36.
    Srinivasan, R., Miller, B. L. and Paulus, H. E. ‘Long-term chrysotherapy in rheumatoid arthritis’ Arthritis Rheum. 22 (1979) 105–10.PubMedCrossRefGoogle Scholar
  37. 37.
    See note 26.Google Scholar
  38. 38.
    See note 29.Google Scholar
  39. 39.
    Furst, D. E., Levine, S., Srinivasan, R., Metzger, A. L., Bangert, R. and Paulus, H. E. ‘A double-blind trial of high versus conventional dosages of gold salts for rheumatoid arthritis’, Arthritis Rheum. 20 (1977) 1473–80.PubMedCrossRefGoogle Scholar
  40. 40.
    Sharp, J. T., Lidsky, M. D., Duffy, J., Thompson, H. K., Person, B. D., Masri, A. F. and Andrianakos, A. A. ‘Comparison of two dosage schedules of gold salts in the treatment of rheumatoid arthritis. Relationship of serum gold levels to therapeutic response’, Arthritis Rheum. 20 (1977) 1179–87.PubMedCrossRefGoogle Scholar
  41. 41.
    See note 39.Google Scholar
  42. 42.
    Lorber, A., Atkins, C. J., Chang, C. C., Lee, Y. B., Starrs, J. and Bory, R. A. ‘Monitoring serum gold values to improve chrysotherapy in rheumatoid arthritis’, Ann. Rheum. Dis. 32 (1973) 133–9.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    McKenzie, J. M. M. ‘Report on a double-blind trial comparing small and large doses of gold in the treatment of rheumatoid disease’, Rheumatol. Rehabil. 20 (1981) 198–202.PubMedCrossRefGoogle Scholar
  44. 44.
    Katz, W. A., Alexander, S., Bland, J. H. et al. ‘The efficacy and safety of auranofin compared to placebo in rheumatoid arthritis’, J. Rheumatol. 9 (suppl. 8) (1982) 173–8.Google Scholar
  45. 45.
    Ward, J. R., Williams, H. J., Egger, M. J. et al. ‘Comparison of auranofin, gold sodium thiomalate and placebo in the treatment of rheumatoid arthritis’, Arthritis Rheum. 26 (1983) 1303–15.PubMedCrossRefGoogle Scholar
  46. 46.
    Huskisson, E. C., Gibson, T. G., Balme, H. W. et al. ‘Trial comparing D-penicillamine and gold in rheumatoid arthritis. Preliminary report’, Ann. Rheum. Dis. 33 (1974) 532–5.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Currey, H. L. F., Harris, J., Mason, R. M. et al. ‘Comparison of azathioprine, cyclophosphamide and gold in the treatment of rheumatoid arthritis’, Br. Med. J. 3 (1974) 763–6.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Dwosh, I. L., Stein, H. B., Urowitz, M. H., Smythe, H. A., Hunter, T. and Ogryzlo, M. A. ‘Azathioprine in early rheumatoid arthritis. Comparison with gold and chloroquine’, Arthritis Rheum. 20 (1977) 685–92.PubMedCrossRefGoogle Scholar
  49. 49.
    Pullar, T., Hunter, J. A., Capell, H. A. ‘Sulphasalazine in rheumatoid arthritis: a double-blind comparison of sulphasalazine with placebo and sodium aurothiomalate’, Br. Med. J. 287 (1983) 1102–4.CrossRefGoogle Scholar
  50. 50.
    See note 20.Google Scholar
  51. 51.
    See note 22.Google Scholar
  52. 52.
    See note 26.Google Scholar
  53. 53.
    See note 28.Google Scholar
  54. 54.
    Sharp, J. T., Lidsky, M. D., Collins, L. C. and Moreland, J. ‘Methods of scoring the progression of radiologic changes in rheumatoid arthritis. Correlation of radiologic, clinical and laboratory abnormalities’, Arthritis Rheum. 14 (1971) 706–20.PubMedCrossRefGoogle Scholar
  55. 55.
    Iannuzzi, L., Dawson, N., Zein, N. and Kushner, I. ‘Does drug therapy slow radiographic deterioration in rheumatoid arthritis?’, New Engl. J. Med. 309 (1983) 1023–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Luukainen, R., Isomaki, H. and Kajander, R. ‘Effect of gold treatment on the progression of erosions in RA patients’, Scand. J. Rheumatol. 6 (1977) 123–7.CrossRefGoogle Scholar
  57. 57.
    Luukainen, K., Kajander, R. and Isomaki, H. ‘Effect of gold on progression of erosions in rheumatoid arthritis. Better results with early treatment’, Scand. J. Rheumatol. 6 (1977) 189–92.CrossRefGoogle Scholar
  58. 58.
    Luukainen, R. ‘Chrysotherapy in rheumatoid arthritis’, Scand. J. Rheumatol. 9 (suppl. 9) (1980) 1–56.Google Scholar
  59. 59.
    Rasker, J. J. and Cosh, J. A. ‘Radiological study of cervical spine and hand in patients with rheumatoid arthritis of 15 years’ duration: an assessment of the effects of corticosteroid treatment’, Ann. Rheum. Dis. 37 (1978) 529–35.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Scott, D. L., Grindulis, K. A., Struthers, G. R., Coulton, B. L., Popert, A. J. and Bacon, P. A. ‘Progression of radiological changes in rheumatoid arthritis’, Ann. Rheum. Dis. 43 (1984) 8–17.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Phials, R. S., Masi, A. T. and Larsen, R. A. ‘Preliminary criteria for clinical remission in rheumatoid arthritis’, Arthritis Rheum. 24 (1981) 1308–15.CrossRefGoogle Scholar
  62. 62.
    Karten, I., O’Brien, W. M., Becker, M. H. and McEwen, C. ‘Articular erosions in rheumatoid arthritis’, J. Chronic Dis. 25 (1972) 449–56.PubMedCrossRefGoogle Scholar
  63. 63.
    Sharp, J. T., Lidsky, M. D., Duffy, J. ‘Clinical responses during gold therapy for rheumatoid arthritis. Changes in synovitis, radiologically detectable erosive lesions, serum proteins and serologic abnormalities’, Arthritis Rheum. 25 (1982) 540–9.PubMedCrossRefGoogle Scholar
  64. 64.
    See note 45.Google Scholar
  65. 65.
    Duthie, J. J. R., Brown, P. E., Truelove, L. H., Baragar, F. D. and Lawrie, A. J. ‘Course and prognosis in rheumatoid arthritis. A further report’ Ann. Rheum. Dis. 23 (1964) 193–204.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Short, C. L. ‘Long remissions in rheumatoid arthritis’, Medicine, 43 (1964) 401–6.PubMedGoogle Scholar
  67. 67.
    See notes 18 and 19.Google Scholar
  68. 68.
    Girdwood, R. H. ‘Death after taking medicaments’, Br. Med. J. 1 (1974) 501–5.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    See note 26.Google Scholar
  70. 70.
    Research Subcommittee of the Empire Rheumatism Council, ‘Relation of toxic reactions in gold therapy to improvement in rheumatoid arthritis’, Ann. Rheum. Dis. 20 (1961) 335–40.CrossRefGoogle Scholar
  71. 71.
    Halla, J. T., Hardin, J. G. and Linn, J. E. Postinjection nonvasomotor reactions during chrysotherapy. Constitutional and rheumatic symptoms following injections of gold salts’, Arthritis Rheum. 20 (1977) 1188–91.PubMedCrossRefGoogle Scholar
  72. 72.
    See notes 26 and 39.Google Scholar
  73. 73.
    See notes 29 and 39.Google Scholar
  74. 74.
    See note 29.Google Scholar
  75. 75.
    Lawrence, J. S. ‘Comparative toxicity of gold preparations in treatment of rheumatoid arthritis’, Ann. Rheum. Dis. 35 (1976) 171–3.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Kean, W. F. and Anastassiades, T. P. ‘Long-term chrysotherapy. Incidence of toxicity and efficacy during sequential time periods’, Arthritis Rheum. 22(1979)495–501.PubMedCrossRefGoogle Scholar
  77. 77.
    Penneys, N. S., Ackerman, A. B. and Gottlieb, N. L. ‘Gold dermatitis’, Arch. Dermatol. 109 (1974) 372–6.PubMedCrossRefGoogle Scholar
  78. 78.
    Klinefelter, H. F. ‘Reinstitution of gold therapy in rheumatoid arthritis after mucocutaneous reactions’, J. Rheumatot. 2 (1975) 21–7.Google Scholar
  79. 79.
    Silverberg, D. S., Kidd, E. G., Schnitka, T. K. et al. ‘Gold nephropathy’, Arthritis Rheum. 13 (1970) 812–25.PubMedCrossRefGoogle Scholar
  80. 80.
    Bourke, B. E., Woodrow, D. F. and Scott, J. T. ‘Proteinuria in rheumatoid arthritis–drug-induced or amyloid?’, Ann. Rheum. Dis. 40 (1981) 240–4.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Tornroth, T. and Skrifvars, B. ‘Gold nephropathy prototype of membranous glomerulonephritis’, Am. J. Pathol. 75 (1974) 573–86.PubMedCentralGoogle Scholar
  82. 82.
    Petras, R., Tubbs, R., Gephardt, G., McMahon, J., Vidt, D. and Valenzuela, R. ‘Membranous glomerulonephritis associated with gold therapy’, (abstr.) Am. J. Clin. Pathol. 78 (1982) 267.Google Scholar
  83. 83.
    Vaamonde, C. A. and Hunt, F. R. ‘The nephrotic syndrome as a complication of gold therapy’, Arthritis Rheum. 13 (1970) 826–34.PubMedCrossRefGoogle Scholar
  84. 84.
    Newton, P., Swinburn, W. R. and Swinson, D. R. ‘Proteinuria with gold therapy: when should gold be permanently stopped?’, Br. J. Rheumaol. 22 (1983) 11–17.CrossRefGoogle Scholar
  85. 85.
    McCarty, D. J., Brill, J. M. and Harrop, D. ‘Aplastic anaemia secondary to gold salt therapy’, JAMA 179 (1962) 655–7.CrossRefGoogle Scholar
  86. 86.
    Kay, A. G. L. ‘Myelotoxicity of gold’, Br. Med. J. 1 (1976) 1266–8.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    See note 39.Google Scholar
  88. 88.
    See note 71.Google Scholar
  89. 89.
    Stein, H. B. and Urowitz, M. B. ‘Gold induced enterocolitis’ J. Rheumatol. 3 (1976) 21–6.PubMedGoogle Scholar
  90. 90.
    Favreau, M., Tannenbaum, H. and Lough, J. ‘Hepatic toxicity associated with gold therapy’, Ann. Intern. Med. 87 (1977) 717–9.PubMedCrossRefGoogle Scholar
  91. 91.
    Winterbauer, R. H., Wilski, K. R. and Wheelis, R. F. ‘Diffuse pulmonary injury associated with gold treatment’, New Engl. J. Med. 294 (1979) 919–21.CrossRefGoogle Scholar
  92. 92.
    Skrifvars, B., Tornroth, T. and Falck, H. M. ‘Granulomatous glomerulonephritis in a patient with rheumatoid arthritis treated with gold salts’, Scand. J. Rheumatol. 8 (1979) 234–40.PubMedCrossRefGoogle Scholar
  93. 93.
    Schlumpf, U., Meyer, M., Ulrich, J. and Friede, R. L. ‘Neurologic complications induced by gold treatment’, Arthritis Rheum. 26 (1983) 825–31.PubMedCrossRefGoogle Scholar
  94. 94.
    Heuer, M. A. and Morris, R. W. ‘Smith, Kline and French worldwide clinical experience with auranofin: a review’, in Capell, H. A., Cole, D. S., Manghani, K. K. and Morris, R. W. (eds) Auranofin ( Amsterdam: Excerpta Medica, 1983 ) 474–503.Google Scholar
  95. 95.
    Wooley, P. M., Griffin, J., Panayi, G. S., Batchelor, J. R., Welsh, K. I. and Gibson, T. J. ‘HLA-DR antigens and toxic reactions to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis’, New Engl. J. Med. 303 (1980) 300–2.PubMedCrossRefGoogle Scholar
  96. 96.
    Gran, J. T., Husby, G. and Thorsby, E. ‘HLA-DR antigens and gold toxicity’, Ann. Rheum. Dis. 42 (1983) 63–6.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Bretza, J., Wells, I. and Novey, H. S. ‘Association of IgE antibodies to sodium aurothiomalate and adverse reactions to chrysotherapy for rheumatoid arthritis’, Am. J. Med. 74 (1983) 945–50.PubMedCrossRefGoogle Scholar
  98. 98.
    See notes 19, 20 and 22.Google Scholar
  99. 99.
    McConkey, B., Davies, P., Crockson, R. A., Crockson, A. P., Butler, M., Constable, T. J. and Amos, R. S. ‘Effects of gold, dapsone and prednisone on serum C-reactive protein and haptoglobin and the erythrocyte sedimentation rate in rheumatoid arthritis’, Ann. Rheum. Dis. 38 (1979) 141–4.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Dixon, J. S. ‘Biochemical and clinical changes in rheumatoid arthritis: their relation to the action of antirheumatoid drugs’, Sem. Arthritis Rheum. 12 (1982) 191–207.CrossRefGoogle Scholar
  101. 101.
    Lorber, A., Simon, T., Leeb, J., Peter, A. and Wilcox, S. ‘Chrysotherapy. Suppression of immunoglobulin synthesis’, Arthritis Rheum. 21 (1978) 785–91.PubMedCrossRefGoogle Scholar
  102. 102.
    Klinefelter, H. F. and Achurra, A. ‘Effect of gold salts and antimalarials on the rheumatoid factor in rheumatoid arthritis’, Scand. J. Rheumatol. 2 (1973) 177–82.PubMedCrossRefGoogle Scholar
  103. 103.
    Gottlieb, N. L., Kiem, I. M., Penneys, N. S. and Schultz, D. R. ‘The influence of chrysotherapy on serum proteins and immunoglobulin levels rheumatoid factor and anti-epithelial antibody titres’, J. Lab. Clin. Med. 86 (1975) 962–72.PubMedGoogle Scholar
  104. 104.
    Highton, J., Panayi, G. S., Shepherd, P., Griffin, J. and Gibson, T. ‘Changes in immune function in patients with rheumatoid arthritis following treatment with sodium aurothiomalate’, Ann. Rheum. Dis. 40 (1981) 254–62.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Lipsky, P. E. ‘The mechanisms of action of slow-acting agents in rheumatoid arthritis’, in Panayi, G. S. (ed.) Scientific Basis of Rheumatology ( Edinburgh: Churchill Livingstone, 1982 ) 272–90.Google Scholar
  106. 106.
    See note 14.Google Scholar
  107. 107.
    Nakamuru, H. and Igarashi, M. ‘Localisation of gold in synovial membrane of rheumatoid arthritis treated with sodium aurothiomalate: studies by electron microscope and electron probe X-ray microanalysis’, Ann. Rheum. Dis. 36 (1977) 209–15.CrossRefGoogle Scholar
  108. 108.
    Ghadially, F. N., Oryschak, A. F. and Mitchell, D. M. ‘Ultrastructural changes produced in rheumatoid synovial membrane by chrysotherapy’, Ann. Rheum. Dis. 35 (1976) 67–72.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Persellin, R. H. and Ziff, M. ‘The effect of gold on lysosomal enzyme of the peritoneal macrophage’, Arthritis Rheum. 9 (1966) 57–65.PubMedCrossRefGoogle Scholar
  110. 110.
    Lipsky, P. E., Ugai, K. and Ziff, M. ‘Alterations in human monocyte structure and function induced by incubation with gold sodium thiomalate’, J. Rheumatol. 6 (suppl. 5) (1979) 130–6.Google Scholar
  111. 111.
    Ugai, K., Ziff, M. and Lipsky, P. E. ‘Gold-induced changes in the morphology and functional capabilities of human monocytes’, Arthritis Rheum. 22 (1979) 1352–60.PubMedCrossRefGoogle Scholar
  112. 112.
    Scheinberg, M. A., Santos, L. M. B. and Finkelstein, A. E. ‘The effect of auranofin and sodium aurothiomalate on peripheral blood monocytes’, J. Rheumatol. 9 (1982) 366–9.PubMedGoogle Scholar
  113. 113.
    Jessop, J. D., Vernon-Roberts, B. and Harris, J. ‘Effects of gold salts and prednisolone on inflammatory cells. I. Phagocytic activity of macrophages and polymorphs in inflammatory exudates studies by a “skin-window”technique in rheumatoid and control patients’, Ann. Rheum. Dis. 32 (1973) 294–300.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Vernon-Roberts, B., Jessop, J. D. and Dore, J. ‘Effects of gold salts and prednisolone on inflammatory cells. II. Suppression of inflammation and phagocytosis in the rat’, Ann. Rheum. Dis. 32 (1973) 301–7.CrossRefGoogle Scholar
  115. 115.
    Ghaffar, A., McBride, W. H. and Cullen, R. T. ‘Interaction of tumour cells and macrophages in vitro: modulation by Corynebacterium parvum and gold salt,’ J. Reticulo-endothelial Soc. 20 (1976) 283–9.Google Scholar
  116. 116.
    Lipsky, P. E. and Ziff, M. ‘Inhibition of antigen and mitogen-induced human lymphocyte proliferation by gold compounds’, J. Clin. Invest. 59 (1977) 455–66.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Lies, R. B., Cardin, C. and Paulus, H. E. ‘Inhibition by gold of human lymphocyte stimulation. An in vitro study’, Ann. Rheum. Dis. 36 (1977) 216–18.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Harth, M., Stiller, C. R. and Sinclair, N. R. St C., ‘Effects of a gold salt on lymphocyte responses’, Clin. Exp. Immunol. 27 (1977) 357–64.PubMedPubMedCentralGoogle Scholar
  119. 119.
    See note 116.Google Scholar
  120. 120.
    Salmeron, G. and Lipsky, P. E. ‘Modulation of human immune responsiveness in vitro by auranofin’, J. Rheumatol. 9 (suppl. 8) (1982) 25–31.Google Scholar
  121. 121.
    See note 104.Google Scholar
  122. 122.
    Percy, J. S., Davis, P., Miller, C. L. and Russell, A. ‘Sequential observations of in vitro responses of lymphocytes to phytohaemagglutinin in patients receiving gold therapy for rheumatoid arthritis’, J. Rheumatol. 6 (suppl. 5) (1979) 117–19.Google Scholar
  123. 123.
    Lorber, A., Jackson, W. H. and Simon, T. M. ‘Effects of chrysotherapy on cell mediated immune response’, J. Rheumatol. 9 (suppl. 8) (1982) 37–45.Google Scholar
  124. 124.
    Coughlan, R. J., Richter, M. B. and Panayi, G. S. ‘Changes in mononuclear cell function in patients with rheumatoid arthritis following treatment with auranofin’, in Capell, H. A., Cole, D. S., Manghani, K. K. and Morris, R. W. (eds) Auranofin ( Amsterdam: Excerpta Medica, 1982 ) 71–9.Google Scholar
  125. 125.
    Adam, M. and Kuhn, K. ‘Investigations on the reaction of metals with collagen in vivo. I. Comparison of the reaction of gold thiosulphate with collagen in vivo and in vitro’, Eur. J. Biochem. 3 (1968) 407–10.PubMedCrossRefGoogle Scholar
  126. 126.
    Schultz, D. R., Volanakis, J. E., Arnold, P. J., Gottlieb, N. L., Sakai, K. and Stround, R. M. ‘Inactivation of C 1 in rheumatoid synovial fluid, purified Cl and Cl esterase by gold compounds’, Clin. Exp. Immunol. 17 (1974) 395–406.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Burge, J. J., Fearon, D. T. and Austen, K. F. ‘Inhibition of the alternative pathway of complement by gold thiomalate in vitro’, J. Immunol. 120 (1978) 1625–30.PubMedGoogle Scholar
  128. 128.
    Hasselbacher, P. ‘Inhibition of complement by gold sodium thiomalate’, J. Rheumatol. 8 (1981) 57–61.PubMedGoogle Scholar
  129. 129.
    Gerber, D. A. ‘Inhibition of heat-aggregation of human gammaglobulin by histidine, gold thiomalate and penicillamine’, (abstr.) Arthritis Rheum. 14 (1971) 383.Google Scholar
  130. 130.
    Lorber, A., Bovy, R. A. and Chang, C. C. ‘Relationship between serum gold content and distribution to serum immunoglobulins and complement’, Nature New Biol. 236 (1972) 250–2.CrossRefGoogle Scholar
  131. 131.
    Rohozkova, D. and Steven, F. S. ‘Gold-containing drugs and the control of proteolytic enzymes’, Br. J. Pharmacol. 79 (1983) 181–9.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Davis, P., Johnston, C., Miller, C. L. and Wong, K. ‘Effects of gold compounds on the function of phagocytic cells. II. Inhibition of superoxide radical generation by tripeptide-activated polymorphonuclear leucocytes’, Arthritis Rheum. 26 (1983) 82–6.PubMedCrossRefGoogle Scholar
  133. 133.
    Leibfarth, J. H. and Persellin, R. H. ‘Mechanisms of action of gold’, Agents and Actions 11 (1981) 458–72.PubMedCrossRefGoogle Scholar
  134. 134.
    See notes 19 and 20.Google Scholar
  135. 135.
    See note 22.Google Scholar
  136. 136.
    Freiman, J. A., Chalmers, T. C., Smith, H. and Kuebler, R. R. ‘The importance of beta, the type II error and sample size in the design and interpretation of the randomised control trial. Survey of 71 “negative” trials’, New Engl. J. Med. 299 (1978) 690–4.PubMedCrossRefGoogle Scholar
  137. 137.
    See note 22.Google Scholar
  138. 138.
    See note 26.Google Scholar
  139. 139.
    See note 61.Google Scholar
  140. 140.
    See note 65.Google Scholar
  141. 141.
    See note 66.Google Scholar
  142. 142.
    Silman, A. and Davies, P. ‘Is the incidence of seropositive rheumatoid arthritis decreasing?’ (abstr.) Ann. Rheum. Dis. 40 (1981) 517–18.Google Scholar
  143. 143.
    See note 36.Google Scholar
  144. 144.
    See note 68.Google Scholar
  145. 145.
    See note 95.Google Scholar
  146. 146.
    Rosenthal, M. ‘Loss of efficacy of antirheumatic drugs in rheumatoid arthritis’, J. Rheumatol. 7 (1980) 586–7.PubMedGoogle Scholar
  147. 147.
    Fries, J. F. ‘Towards an understanding of patient outcome measurement’, Arthritis Rheum. 26 (1983) 697–704.PubMedCrossRefGoogle Scholar
  148. 148.
    Bacon, P. A. ‘Assessment in rheumatic diseases’, in Panayi, G. S. (ed.) Scientific Basis of Rheumatology ( Edinburgh: Churchill Livingstone, 1982 ) 242–59.Google Scholar
  149. 149.
    Dixon, J. S., Bird, H. A., Pickup, M. E. and Wright, V. ‘A human model screening system for the detection of specific antirheumatic activity’, Sem. Arthritis Rheum. 12 (1982) 185–90.CrossRefGoogle Scholar
  150. 150.
    Kirwan, J. R. and Currey, H. L. F. ‘Rheumatoid arthritis: disease-modifying antirheumatic drugs’, Clinics Rheum. Dis. 9 (1983) 581–99.Google Scholar

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© D. H. Goddard and R. C. Butler 1984

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  • R. C. Butler

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