- Email: [email protected]
Total Knee Replacement
1002
there is quite a degree of cross-immunity Babesia and other blood protozoa,and tests are open to
16 between serological
misinterpretation.
It is too soon to try to estimate the extent of human infection with Babesia spp. throughout the world; by its very nature it is a zoonosis and interhuman transmission is impossible except by abnormal routes such as blood-transfusion. Thus the infection is acquired by the bite of ticks which have fed on one of the many mammals harbouring the organism, but no disease is likely to follow unless the natural immunity of man has been upset. Probably such factors operate in the more primitive countries, and in these places the physician should be aware that, for instance, a failure of a patient to respond to malaria therapy is not necessarily due to a drug-resistant strain of P. falciparum: it may be due to an infection with Babesia which is untouched by antimalarial drugs. H. E. SHORTT,1’ the nonagenarian protozoologist, has lately emphasised the diversity of possible sources of infection and the danger that human cases will escape diagnosis.
Total Knee
Replacement
outstanding success of CHARNLEY’S lowarthroplasty of the hip18 has stimulated orthopaedic surgeons in many countries to look again at replacements for other joints-particularly the knee, which is second only to the hip as a site of crippling arthritis. Arthroplasties of the knee were attempted from the early years of this century although these pioneering efforts met THE friction
with little success.19 At present, interest is concentrated on two basic patterns of total knee replacement, the hinge and the gliding joint. The hinges, introduced by WALLDIUS in 195320 21 and SHIERS in 1954, 22 -" are anchored to the femur and tibia by intramedullary stems, with or without methyl-methacrylate cement. The gliding joints are a more recent development and, as in CHARNLEY’S low-friction arthroplasty, a metal surface articulates with one of high-density polyethylene. In general, the components of the gliding joints are cemented to the bone ends, but they are not fixed to each other and depend for their stability on the integrity of the joint ligaments. They have the theoretical attraction that, being less constrained than the hinge, they allow a little rotary movement as well as flexion and so resemble more closely the function of the normal knee-joint. 16. Cox, F. E. G. Parasitology, 1972, 65, 389. 17. Shortt, H. E. Trans. R. Soc. trop. Med. Hyg. 1975, 69, 519. 18. Charnley, J. J. Bone Jt Surg, 1972, 54B, 61. 19. Blundell Jones G. Chap 8, p. 210-249 in Modern Trends in Orthopædics (edited by A. Graham Apley); chap. 8, p. 210. London, 1972. 20. Walldius, B. Acta orthop. scand. 1953, 23, 121. 21. Walldius, B. ibid. 1960, 30, 137. 22. Shiers, L. G. P. J. Bone Jt Surg. 1954, 36B, 553. 23. Shiers, L. G. P. ibid. 1960, 42B, 31.
At
a
in 1974 300 different artificial said to be available.24 While this
symposium
knee-joints
were
may have been a slight exaggeration, a glance through the advertising pages of a current orthopaedic journal reveals at least 25 different models on offer. When many treatments are advocated for a disease, this usually indicates that none is satisfactory ; and yet there is little evidence of dissatisfaction in the publications of the innovators. Comparison of models often reveals variations so small that one wonders whether the "invention" was prompted more by the creative ambition of the developer than by deficiencies in pre-existing implants-certainly a suspicion strengthened by the rapidity with which publications and advertisements appear after small-scale clinical trials. The short-term results are of little interest. What matters is that the artificial joint should continue to function for many years. CHARNLEY indicated the correct way of doing things. He painstakingly subjected his new hipjoint to thorough clinical trial before making it public; and even then he managed for several years to limit its sale and use to those who visited his unit in Wrightington for a period of instruction in its application. It is unfortunate that many of the new knee-joints have not been subjected to a similar disciplined introduction, which might have avoided the present confusion regarding their relative merits. Eventually some comparisons may be possible from the publications of large series with adequate follow-up. Some information is already available for the hinge arthroplasties which have been in use for up to twenty years. SHIERS25 reports a success-rate of about 75% and WALLDIUS26 "very good" results in 79%. These are impressive figures, although they do not match the success of the lowfriction arthroplasty of the hip and the complications of the unsuccessful cases can be very serious. ARDEN and KAMDAR, 27 in a series of 193 Shiers arthroplasties, report 7 deaths and 21 cases of deep infection leading to amputation in 3 cases and chronic discharge in 13. The prosthesis became loose in 21 cases. Many of the early reports of the gliding types of prosthesis suggest a lower complication-rate COVENTRY et al. 28 for example, had only 30 complications in 317 geometric arthroplasties and most of these were remediable, but GUNSTON29 had 5 failures in 43 cases of his polycentric arthroplasty, 4 requiring fusion. FREEMAN et al." reported 26 complications in the first 69 cases with 24. Total Knee Replacement. Report of a Conference held in London, September, 1974. London and New York: Mechanical Engineering Publications Ltd for the Institute of Mechanical Engineers. 1975. Pp. 192. £15. 25. Shiers, L. G. P. ibid. p. 44. 26. Walldius, B. ibid. p. 34. 27. Arden, G. P., Kamdar, B. A. ibid. p. 118. 28. Coventry, M. B., Upshaw, J. E., Riley, L. H., Finerman, G. A. M., Turner, R. H. Clin. Orthop. 1973, 94, 171. 29. Gunston, F. H. ibid. p. 128. 30. Freeman, M. A. R., Swanson, S. A. V., Todd, R. C. ibid. p. 153.
1003
prosthesis and, although patients required removal of
their
most were
minor, 5
the prosthesis with or fibrous arthrodesis ankylosis. The subsequent and late complications durability of the gliding prosthesis are not known but already problems are emerging. They are not self-clearing joints like the hip, and debris can accumulate to produce serious wear of the polyethylene component. The time has surely come to call a halt to the development of new knee-joints until we have taken stock of existing models. Although brilliant results have been reported, the high complication-rate and the uncertainty about long-term results suggest that their use, for the present, should be restricted to the severely crippled for whom no other treatment is available. Knee-joint replacement is not an operation for the young and vigorous, or for those with arthritis confined to one knee. The patient should be made aware that if the operation fails he may end up with a stiff knee or even no knee at all. There is insufficient information to recommend a best buy in knees but, since the hinge type may be more appropriate for the very unstable and disorganised joint while the gliding type may be better in more stable knees, the surgeon who decides to undertake these procedures should become familiar with one example of each type. Experience with knee arthroplasties raises another matter. At present it is open to any orthopxdic surgeon to devise an artificial joint, and there is no experimental animal other than man in whom it can be tried. Each operation of this kind must, in the early stages at least, be regarded as a clinical experiment. While most work of this nature has been conducted worthily, this is a heavy responsibility for one surgeon or group to bear alone and there is always a risk that enthusiasm may hamper judgment. A case can be made for the appointment of a body comparable to the Committee on Safety of Medicines who would scrutinise and approve new designs before trial. This committee could receive notice of complications of these implants and issue early warnings. Joint replacement has been a major advance in medicine: perhaps the best way to maintain progress is to adopt a more restrained and coordinated approach to new
developments.
CYPROTERONE ACETATE CYPROTERONE
(1, 2-K methylene-6-chlor-4, acetate) was de6-pregnadiene-17&agr;-ol-3, in the mid-1960s a as veloped progestagen.l During early toxicity trials, however, it was given to pregnant ACETATE
20 dione-17ot
and caused feminisation of male fetuses.2 This chance discovery led to more intensive investigation of its properties and it was eventually released as a potent
rats
drug with both antiandrogenic and progestational activity. Cyproterone acetate is thought to be active as an antiandrogen for three reasons: it competes with testosterone for target-organ receptor binding sites; it blocks testosterone (and oestrogen) synthesis in the gonad; and its progestational activity blocks the rise in gonadotrophins that would be expected to follow any fall in plasma-testosterone. This third reason is important because a pure antiandrogen which has no progestational activity-such as the parent compound cyproterone---competes with androgens at the receptor sites and causes a compensatory rise in gonadotrophin secretion. This stimulates testosterone production and effectively over-
the block.3 Since its introduction cyproterone acetate has been used in the treatment of male hypersexuality and’deviationism,4-7 precocious puberty in boys and girls irrespective of ætiology, 8-11 and prostatic carcinoma, 12-14 and also for suppressing signs of virilisation in women. 1 15 In most of these conditions the drug was said to be beneficial, but very few controlled trials have been performed. In at least one double-blind cross-over study in hypersexual patients cyproterone acetate was not significantly better than a placebo.16 Because it causes a reversible block of spermatogenesis, there were hopes that it might be useful as a male contraceptive, but unfortunately the accompanying loss of libido renders it unsuitable. There is still possibility that these two effects can be separated and trials with low doses are continuing. 17 Similarly, the drug is being assessed for use in combined contraceptive preparations for women. Most workers agree that cyproterone acetate reduces libido in 75-80% of hypersexual males (the effects being equivalent to those of surgical castration) and that the decrease in libido is maintained. However, there may be little to choose between cyproterone acetate and ethinyl oestradiol or a tranquilliser such as benperidol.’8 19 There is variation in the extent to which underlying psychiatric disease improves along with the fall in libido but most patients find social integration easier on treatment. In boys with precocious puberty cyproterone acetate leads to a fall in plasma-testosterone, a decrease in frequency of masturbation, partial regression of secondary sexual characteristics, and an improvement in adult height prognosis (as inferred from increasing height velocity as related to bone age). In girls there is a de-
comes
3. 4. 5.
Vosbeck, K., Keller, P. J. Hormone Met. Res. 1971, 3, 273. Laschet, U., Laschet, L. Klin. Wschr. 1967, 6, 116. Laschet, U., Laschet, L., Fetzner, H. R., Glaesel, H. U., Mall, G., Naab, M. Acta endocr., Copenh. 1976, suppl. 119, p. 54. 6. Cooper, A. J., Ismail, A. A. A., Phanjoo, A. L., Love, D. L. Br. J. Psychiat. 1972, 120, 59. 7. Davies, T. S. J. int. med. Res. 1974, 2, 159. 8. Helge, H., Weber, B., Hammerstein, J., Neumann, F. Acta pœdiat. scand. 1969, 58, 672. 9. Rager, K., Huenges, R., Gupta, D., Bierich, J. R. Acta endocr, Copenh. 1972, 5, 10. 10. Bossi, E., Zurbrugg, R. P., Joss, E. E. Acta pœdiat. scand. 1973, 62, 405. 11. Kauli, R., Pertzelan, A., Prager-Lewin, R., Grünebaum, M., Laron, Z. Archs Dis. Childh. 1976, 51, 202. 12. Scott, W. W., Schirmer, H. K. A. Trans. Am. Ass. genitourin. Surg. 1966, 58, 54. 13. Geller, J., Vazakas, G., Fruchtman, B., Newman, H., Nakao, K., Loh, A. Surgery Gynec. Obstet. 1968, 127, 748. 14. Wein, A. J., Murphy, J. J. J. Urol. 1973, 109, 68. 15. Hammerstein, J., Cupceancu, B. Dt. med. Wschr. 1969, 16, 829. 16. Jensen, I. A., Braudborg, G., Dein, E. Acta psychiat. scand. 1973, suppl. 243,
p. 66. Petry, R., Mauss, J., Rausch-Stroomann, J. G., Vermeulen, A. Hormone Met. Res. 1972, 4, 386. 18. Bancroft, J. H. J. J. int. med. Res. 1975, 3, suppl. 4, p. 20. 19. Matthews, R. ibid. p. 22. 17.
1. Neumann, F., Gräf, K J. J. int. med. Res. 1975, 3, suppl. 4, p. 1. 2. Neumann, F., Hamada, H. Symp. der Deutschen Gesellschaft fur Endok; p. 301. Berlin, 1964.
there is quite a degree of cross-immunity Babesia and other blood protozoa,and tests are open to
16 between serological
misinterpretation.
It is too soon to try to estimate the extent of human infection with Babesia spp. throughout the world; by its very nature it is a zoonosis and interhuman transmission is impossible except by abnormal routes such as blood-transfusion. Thus the infection is acquired by the bite of ticks which have fed on one of the many mammals harbouring the organism, but no disease is likely to follow unless the natural immunity of man has been upset. Probably such factors operate in the more primitive countries, and in these places the physician should be aware that, for instance, a failure of a patient to respond to malaria therapy is not necessarily due to a drug-resistant strain of P. falciparum: it may be due to an infection with Babesia which is untouched by antimalarial drugs. H. E. SHORTT,1’ the nonagenarian protozoologist, has lately emphasised the diversity of possible sources of infection and the danger that human cases will escape diagnosis.
Total Knee
Replacement
outstanding success of CHARNLEY’S lowarthroplasty of the hip18 has stimulated orthopaedic surgeons in many countries to look again at replacements for other joints-particularly the knee, which is second only to the hip as a site of crippling arthritis. Arthroplasties of the knee were attempted from the early years of this century although these pioneering efforts met THE friction
with little success.19 At present, interest is concentrated on two basic patterns of total knee replacement, the hinge and the gliding joint. The hinges, introduced by WALLDIUS in 195320 21 and SHIERS in 1954, 22 -" are anchored to the femur and tibia by intramedullary stems, with or without methyl-methacrylate cement. The gliding joints are a more recent development and, as in CHARNLEY’S low-friction arthroplasty, a metal surface articulates with one of high-density polyethylene. In general, the components of the gliding joints are cemented to the bone ends, but they are not fixed to each other and depend for their stability on the integrity of the joint ligaments. They have the theoretical attraction that, being less constrained than the hinge, they allow a little rotary movement as well as flexion and so resemble more closely the function of the normal knee-joint. 16. Cox, F. E. G. Parasitology, 1972, 65, 389. 17. Shortt, H. E. Trans. R. Soc. trop. Med. Hyg. 1975, 69, 519. 18. Charnley, J. J. Bone Jt Surg, 1972, 54B, 61. 19. Blundell Jones G. Chap 8, p. 210-249 in Modern Trends in Orthopædics (edited by A. Graham Apley); chap. 8, p. 210. London, 1972. 20. Walldius, B. Acta orthop. scand. 1953, 23, 121. 21. Walldius, B. ibid. 1960, 30, 137. 22. Shiers, L. G. P. J. Bone Jt Surg. 1954, 36B, 553. 23. Shiers, L. G. P. ibid. 1960, 42B, 31.
At
a
in 1974 300 different artificial said to be available.24 While this
symposium
knee-joints
were
may have been a slight exaggeration, a glance through the advertising pages of a current orthopaedic journal reveals at least 25 different models on offer. When many treatments are advocated for a disease, this usually indicates that none is satisfactory ; and yet there is little evidence of dissatisfaction in the publications of the innovators. Comparison of models often reveals variations so small that one wonders whether the "invention" was prompted more by the creative ambition of the developer than by deficiencies in pre-existing implants-certainly a suspicion strengthened by the rapidity with which publications and advertisements appear after small-scale clinical trials. The short-term results are of little interest. What matters is that the artificial joint should continue to function for many years. CHARNLEY indicated the correct way of doing things. He painstakingly subjected his new hipjoint to thorough clinical trial before making it public; and even then he managed for several years to limit its sale and use to those who visited his unit in Wrightington for a period of instruction in its application. It is unfortunate that many of the new knee-joints have not been subjected to a similar disciplined introduction, which might have avoided the present confusion regarding their relative merits. Eventually some comparisons may be possible from the publications of large series with adequate follow-up. Some information is already available for the hinge arthroplasties which have been in use for up to twenty years. SHIERS25 reports a success-rate of about 75% and WALLDIUS26 "very good" results in 79%. These are impressive figures, although they do not match the success of the lowfriction arthroplasty of the hip and the complications of the unsuccessful cases can be very serious. ARDEN and KAMDAR, 27 in a series of 193 Shiers arthroplasties, report 7 deaths and 21 cases of deep infection leading to amputation in 3 cases and chronic discharge in 13. The prosthesis became loose in 21 cases. Many of the early reports of the gliding types of prosthesis suggest a lower complication-rate COVENTRY et al. 28 for example, had only 30 complications in 317 geometric arthroplasties and most of these were remediable, but GUNSTON29 had 5 failures in 43 cases of his polycentric arthroplasty, 4 requiring fusion. FREEMAN et al." reported 26 complications in the first 69 cases with 24. Total Knee Replacement. Report of a Conference held in London, September, 1974. London and New York: Mechanical Engineering Publications Ltd for the Institute of Mechanical Engineers. 1975. Pp. 192. £15. 25. Shiers, L. G. P. ibid. p. 44. 26. Walldius, B. ibid. p. 34. 27. Arden, G. P., Kamdar, B. A. ibid. p. 118. 28. Coventry, M. B., Upshaw, J. E., Riley, L. H., Finerman, G. A. M., Turner, R. H. Clin. Orthop. 1973, 94, 171. 29. Gunston, F. H. ibid. p. 128. 30. Freeman, M. A. R., Swanson, S. A. V., Todd, R. C. ibid. p. 153.
1003
prosthesis and, although patients required removal of
their
most were
minor, 5
the prosthesis with or fibrous arthrodesis ankylosis. The subsequent and late complications durability of the gliding prosthesis are not known but already problems are emerging. They are not self-clearing joints like the hip, and debris can accumulate to produce serious wear of the polyethylene component. The time has surely come to call a halt to the development of new knee-joints until we have taken stock of existing models. Although brilliant results have been reported, the high complication-rate and the uncertainty about long-term results suggest that their use, for the present, should be restricted to the severely crippled for whom no other treatment is available. Knee-joint replacement is not an operation for the young and vigorous, or for those with arthritis confined to one knee. The patient should be made aware that if the operation fails he may end up with a stiff knee or even no knee at all. There is insufficient information to recommend a best buy in knees but, since the hinge type may be more appropriate for the very unstable and disorganised joint while the gliding type may be better in more stable knees, the surgeon who decides to undertake these procedures should become familiar with one example of each type. Experience with knee arthroplasties raises another matter. At present it is open to any orthopxdic surgeon to devise an artificial joint, and there is no experimental animal other than man in whom it can be tried. Each operation of this kind must, in the early stages at least, be regarded as a clinical experiment. While most work of this nature has been conducted worthily, this is a heavy responsibility for one surgeon or group to bear alone and there is always a risk that enthusiasm may hamper judgment. A case can be made for the appointment of a body comparable to the Committee on Safety of Medicines who would scrutinise and approve new designs before trial. This committee could receive notice of complications of these implants and issue early warnings. Joint replacement has been a major advance in medicine: perhaps the best way to maintain progress is to adopt a more restrained and coordinated approach to new
developments.
CYPROTERONE ACETATE CYPROTERONE
(1, 2-K methylene-6-chlor-4, acetate) was de6-pregnadiene-17&agr;-ol-3, in the mid-1960s a as veloped progestagen.l During early toxicity trials, however, it was given to pregnant ACETATE
20 dione-17ot
and caused feminisation of male fetuses.2 This chance discovery led to more intensive investigation of its properties and it was eventually released as a potent
rats
drug with both antiandrogenic and progestational activity. Cyproterone acetate is thought to be active as an antiandrogen for three reasons: it competes with testosterone for target-organ receptor binding sites; it blocks testosterone (and oestrogen) synthesis in the gonad; and its progestational activity blocks the rise in gonadotrophins that would be expected to follow any fall in plasma-testosterone. This third reason is important because a pure antiandrogen which has no progestational activity-such as the parent compound cyproterone---competes with androgens at the receptor sites and causes a compensatory rise in gonadotrophin secretion. This stimulates testosterone production and effectively over-
the block.3 Since its introduction cyproterone acetate has been used in the treatment of male hypersexuality and’deviationism,4-7 precocious puberty in boys and girls irrespective of ætiology, 8-11 and prostatic carcinoma, 12-14 and also for suppressing signs of virilisation in women. 1 15 In most of these conditions the drug was said to be beneficial, but very few controlled trials have been performed. In at least one double-blind cross-over study in hypersexual patients cyproterone acetate was not significantly better than a placebo.16 Because it causes a reversible block of spermatogenesis, there were hopes that it might be useful as a male contraceptive, but unfortunately the accompanying loss of libido renders it unsuitable. There is still possibility that these two effects can be separated and trials with low doses are continuing. 17 Similarly, the drug is being assessed for use in combined contraceptive preparations for women. Most workers agree that cyproterone acetate reduces libido in 75-80% of hypersexual males (the effects being equivalent to those of surgical castration) and that the decrease in libido is maintained. However, there may be little to choose between cyproterone acetate and ethinyl oestradiol or a tranquilliser such as benperidol.’8 19 There is variation in the extent to which underlying psychiatric disease improves along with the fall in libido but most patients find social integration easier on treatment. In boys with precocious puberty cyproterone acetate leads to a fall in plasma-testosterone, a decrease in frequency of masturbation, partial regression of secondary sexual characteristics, and an improvement in adult height prognosis (as inferred from increasing height velocity as related to bone age). In girls there is a de-
comes
3. 4. 5.
Vosbeck, K., Keller, P. J. Hormone Met. Res. 1971, 3, 273. Laschet, U., Laschet, L. Klin. Wschr. 1967, 6, 116. Laschet, U., Laschet, L., Fetzner, H. R., Glaesel, H. U., Mall, G., Naab, M. Acta endocr., Copenh. 1976, suppl. 119, p. 54. 6. Cooper, A. J., Ismail, A. A. A., Phanjoo, A. L., Love, D. L. Br. J. Psychiat. 1972, 120, 59. 7. Davies, T. S. J. int. med. Res. 1974, 2, 159. 8. Helge, H., Weber, B., Hammerstein, J., Neumann, F. Acta pœdiat. scand. 1969, 58, 672. 9. Rager, K., Huenges, R., Gupta, D., Bierich, J. R. Acta endocr, Copenh. 1972, 5, 10. 10. Bossi, E., Zurbrugg, R. P., Joss, E. E. Acta pœdiat. scand. 1973, 62, 405. 11. Kauli, R., Pertzelan, A., Prager-Lewin, R., Grünebaum, M., Laron, Z. Archs Dis. Childh. 1976, 51, 202. 12. Scott, W. W., Schirmer, H. K. A. Trans. Am. Ass. genitourin. Surg. 1966, 58, 54. 13. Geller, J., Vazakas, G., Fruchtman, B., Newman, H., Nakao, K., Loh, A. Surgery Gynec. Obstet. 1968, 127, 748. 14. Wein, A. J., Murphy, J. J. J. Urol. 1973, 109, 68. 15. Hammerstein, J., Cupceancu, B. Dt. med. Wschr. 1969, 16, 829. 16. Jensen, I. A., Braudborg, G., Dein, E. Acta psychiat. scand. 1973, suppl. 243,
p. 66. Petry, R., Mauss, J., Rausch-Stroomann, J. G., Vermeulen, A. Hormone Met. Res. 1972, 4, 386. 18. Bancroft, J. H. J. J. int. med. Res. 1975, 3, suppl. 4, p. 20. 19. Matthews, R. ibid. p. 22. 17.
1. Neumann, F., Gräf, K J. J. int. med. Res. 1975, 3, suppl. 4, p. 1. 2. Neumann, F., Hamada, H. Symp. der Deutschen Gesellschaft fur Endok; p. 301. Berlin, 1964.