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Cardiac Transplantation 250 THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 6, NO.6, 1993 restriction in opening the mouth, difficulty in eating and speaking and poor oral hygiene. Tongue movement is restricted in the later stages when dysphagia occurs and there is ear pain and loss of auditory acuity due to involvement of the Eustachian tubes. The biochemical changes include a decrease in the blood levels of ascorbate and iron. This typical decrease has been attributed to increased utilization of these constituents for collagen synthesis.' The diagnosis is usually obvious but in borderline cases it may be confirmed by biopsy and light microscopy. For treatment, local injection of hyaluronidase and hydrocortisone has been tried with varying results, as have injections of iron, vitamin C and placental extract. Plastic operations have also been per- formed with limited success. There appears to be a positive relation between OSMF and carcinoma.s In one study from Kerala 40% of patients with oral cancer had oral submucous fibrosis." In Bombay the reported figure was 7%.7 Studies of cell-mediated immunity suggest that OSMF may be an intermediate stage in the transforma- tion of normal to malignant cells." British doctors have proposed a ban on the import of betel leaf and nut into their country. Although such government action against these popular and culture-related substances is highly unlikely' in India, it is time that health care workers started public education programmes on the hazards of their use. REFERENCES I Canniff JP. Harvey W. Harris M. Oral submucous fibrosis: Its pathogenesis and management. Br Dent J 1986;160:429-34. 2 Rajendran R. Saga than CK. Remani P, Ankathil R. Vijayakumar T. Cell-mediated and humoral immune responses in oral submucous fibrosis. Cancer 1986;58:2628--31. 3 Anuradha CD. Shyamala Devi CS. Serum protein. ascorbic acid and iron and tissue collagen in oral submucous fibrosis-A preliminary study. Indian J Med Res 1993;98: 147-51. 4 Phatak AG. Serum proteins and immunoglobulins in oral submucous fibrosis. Indian J Otolaryngoll978;30:I-4. 5 Wahi PN. Kapur VL, Luthra UK. Srivastava Me. Submucous fibrosis of the oral cavity. I. Clinical features. Bull WHO 1966;35:789-99. 6 Jayanthi V. Probert CS. Sher KS. Mayberry JF. Oral submucous fibrosis-A preventable disease. Gut I992;33:4-{i. 7 Pindborg JJ. Kalapessi HK. Kale S. Singh B. Talarkhan BN. Frequency of oral leukoplakia and related condi- tions among 10 000 Bombayites: Preliminary report. J All India Dent Assoc 1965;37:228--9. A. G. PHATAK Sharda Research Institute Miraj Maharashtra Cardiac Transplantation It is now more than 25 years since Christiaan Barnard performed the first human heart transplant. I Much of the preliminary laboratory work had been done by Dr Shumway's group at Stanford University? and, although early results were generally poor-<>f the 166patients transplanted worldwide between 1968 and 1972, only 11% survived more than 2 years-the Stanford team con- tinued to develop and refine their programme and, by the late 1970s, were achieving results comparable with kidney transplantation. 3 The introduction of cyclosporin-based immunosuppressive protocols brought further improvement in survival" and, by the late 1980s, cardiac transplantation had become firmly established as an effective, though costly, treatment for end-stage heart failure due to myocardial disease. lHE NAnONAL MEDICAL JOURNAL OF INDIA VOL. 6, NO.6, 1993 251 The International Society for Heart Transplantation has kept an annual register of activity and survival statistics since 1981 and by the end of 1992 nearly 23000 patients had been entered on this register. The commonest indications for adult transplantation were idiopathic cardiomyopathy (50%) and ischaernic heart disease (43%). The actuarial 1-, 3- and 5-year survival statistics for adults below 65 years of age are 80%, 74% and 69% respectively. At the same time that survival statistics have been improving, so has the quality of life of the recipients due largely to better management of chronic immunosuppression. There is no doubt that initially patients tended to be over-immunosuppressed, with the result that complications from infection and renal dysfunction outweighed the benefits gained from a reduced incidence of rejection. However, with time, cyclosporin doses were reduced and immuno- suppressive protocols became more selective, so that, by one post-transplant year, the majority of patients are now maintained on azathioprine and cyclosporin without steroids.> The cost of cardiac transplantation has always been high (although not pro- hibitively so when seen in the context of other expensive new medical treatments). In Britain a careful assessment of the costs and benefits of the transplant programme at Harefield and Papworth Hospitals was undertaken in the early 1980s by an independent team of health economists. 6 This provided a basis for comparison as the technology developed and the practice extended to other units in Britain. Inevitably the cost-benefit equation will be affected by movements of components of both factors either upwards or downwards. For example, the reduction of hospital stay costs has been partially offset by additional costs incurred as a result of expanding indications to include recipients at both ends of the age spectrum or with concomitant disease such as insulin- dependent diabetes. Similarly, the substantial benefit from cyclosporin-based immunosuppression is seriously compromised by accepting patients for re-transplantation, particularly if this is done in the acute setting. The main determinants of medium-term survival after the first year are accelerated coronary artery disease in the transplanted donor heart and a higher incidence of malignancy than in the normal population. Cyclosporin- induced renal impairment and hypertension are other important causes of morbidity. The aetiology of accelerated coronary artery disease is imperfectly under- stood, but its incidence has now been documented in many centres by annual coronary angiography. However, attempts made to relate incidence to individual risk factors, such as early rejection episodes," cytomegalovirus infection," high blood cholesterol and triglyceride levels." donor heart damage and ischaemic times, \0 have been largely inconclusive. It is likely that initial damage to the coronary endothelium is antibody-mediated and that pathologically it represents a form of chronic rejection similar to the obliterative bronchiolitis which affects lung transplants. In our own series, the incidence of angiographically detectable disease, which tends to underestimate the severity and extent of the pathological process, is 24% and 43% at 3 and 5 years post-transplantation. 11 No relation- ship has been found either with recipient diagnosis or immunosuppressive protocol. Malignancy is known to occur more commonly in immunosuppressed patients and lymphoproliferative disorders and skin cancers, which are often multifocal in origin, tend to be the commonest problems.'! A high index of awareness and aggressive investigation of suspicious lesions is, therefore, important during the follow up of these patients. What of the future for cardiac transplantation now that the treatment has become established and reproducible and more generally accepted by the public and the medical profession? I think it is reasonable to expect additional refinements as a result of more effective and less toxic immunosuppressive agents. This in itself is likely to create further problems by expanding the 252 TIlE NAnONAL MEDICAL JOURNAL OF INDIA VOL. 6, NO.6, 1993 potential application of heart transplantation and hence further exacerbate the single most important limiting factor which is the shortage of donor organs. Each country has had to establish definitions and diagnoses of brain death consistent with its own legal and cultural imperatives and, having done so, has had to develop systems of procurement and distribution of donor organs which are equitable and which make the most effective use of the donor organs avail- able. However, in many developed countries, the demand for organ transplants already exceeds the potential supply of donor organs and this is particularly the case for donor hearts. It is not unreasonable, therefore, that scientists should look towards other substitutes for replacing the human heart. Mechanical devices, either in the form of ventricular assist mechanisms" or total artificial hearts.P are therefore being developed and evaluated. At the same time, immunologists are devoting increasing attention to the biological and ethical problems surrounding xenotransplantation .15 Which of these two alternatives will meet with clinical success remains to be seen. REFERENCES Barnard CN. A human cardiac transplant: An interim report of a successful operation performed at Groote Schuur Hospital. Cape Town. S Afr Med J 1967;.1:1271-4. 2 Lower RR, Stofer RC, Hurley EJ, Dong E, Cohn RB, Shumway NE. Successful homotransplantation ofthe canine heart after anoxic preservation for seven hours. Am J Surg 1962;UM:302~. 3 Jamieson SW, Reitz BA, Oyer PE, Bieber CPo Stinson EB, Shumway NE. Current management of cardiac transplant recipients. Br Heart J 1979;.1:703-8. 4 Wallwork J. Cory-Pearce R, English TAH. Cyclosporine for cardiac transplantation: U.K. trial. Transplant Proc 1983;15 (Suppl1):2559-66. 5 Miller LW. Steroid withdrawal in heart transplantation. J Heart Lung Transpianll992;11 (Part 2 Suppl):401-2. 6 Buxton M, Acheson R, Caine N, Gibson S. O'Brien B. Costs and benefits
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