176
Round the World
Letters
to
the Editor
United States THE LAW AND UNANSWERED
QUESTIONS exhaustion has settled of when the relative JUST quiet we are over the medical uproar, malpractice temporarily faced with a new legal intervention or interpretation with profound medical implications. Recent years have been punctuated by judicial decisions on persons in custodial care; in particular, the Supreme Court’s rather illiberal attitude to the criminal has been counterbalanced by perhaps undue liberality towards the " believed-to-be insane " in custodial care. The cases have been brought by legal groups and individuals on behalf of various types of confined persons, and have resulted in some improvements at very great public cost, but there are still an enormous number of deficiencies. Recently the Supreme Court ruled that a State may not confine involuntarily with mere custodial care any mentally ill patient who is not dangerous and who can function outside in the community. The suit was brought on behalf of a 15-year-confined patient who in 1957- was admitted to hospital, at his father’s request, as a paranoid schizophrenic, and who himself admits that he had no insight into his condition when admitted. After years of litigation he has won his release and compensation for his deprivation of liberty. However, his success and the implications stemming from it seem to have frightened even his own lawyer, who has been anxious to make it clear that no-one is talking about the precipitous wholesale release of thousands of mental patients tomorrow, and that there must be adequate planning for such discharges. But the large-scale release of patients is exactly what is being talked about, and many people are asking what is meant by adequate planning, and how it can be done in overcrowded, understaffed facilities, and under the threat of being mulcted for heavy damages if a mentally ill patient who is not dangerous and can function outside is held in custodial care. Who is to say that a mentally ill patient is not dangerous ? It is precisely this that has outraged public opinion, as murderers now judged non-dangerous are released and then commit further murders. Of immediate concern is the question of whether a non-dangerous mentally ill patient can be involuntarily confined in hospital if adequate treatment is offered. That in turn raises the question as to what is adequate treatment, and how it can be offered to a non-responsive patient. Another vital question, especially for those who have to provide the facilities, is whether patients have a legal right to treatment at all. Has every patient a right to releaseindeed, is there really warrant for holding against their will even violent mentally ill people ? It can be argued that the much talked of right " to treatment, and indeed the " right " to good health, are illusions, and that good health is a privilege won by hard work. In many illnesses, mental and physical, a point is reached beyond which " treatment " brings no return, and indeed becomes wasteful. Has a patient at this stage any " right " to " adequate treatment " ? And what rights has the public ? With increasing numbers of the mentally retarded and the mentally ill being released, there will undoubtedly be an increase in incidents of one kind and another, and public emotions may well be stretched to breaking-point. Some people see in this difficult situation the failure of democracy and of our legislative bodies. The courts, in their clumsy fashion, are trying to sort out the failures of the legislative bodies to act with foresight, to see that the Civil Servants carry out their duties, and to provide the financial means for them to do so. The courts are usurping the functions that the legislatures have neglected. "
LIVER TRANSPLANTATION FOR WILSON’S DISEASE
SiR,-We have reported before on the early course of patients after liver transplantation for Wilson’s disease. 1,2 The indication for operation in the first was liver failure. This boy, whois now aged recipient 17 years, will be six years post-transplantation on July 15. He is the longest survivor in the world after liver replacement. With the provision of a new liver, a decoppering process was demonstrated, mainly by a prolonged cupriuresis. However, the potential usefulness of the
two
metabolic observations in the context of Wilson’s disease and its treatment was reduced by certain atypical features of the case. Although the copper concentration in the native liver was very high, the serum caErulopIasmin concentration was low normal and the corneas had no evidence of Kayser-Fleischer rings. The second patient is now four years two months -
post-transplantation. He was first diagnosed as having Wilson’s disease at the age of 11 years. By the age of 14 years, he had progressively deteriorating BIOCHEMICAL FINDINGS BEFORE AND AFTER TRANSPLANTATION
hepatic and neurological function. Although he had ascites, transplantation was recommended more because of the serious neurological impairment than because of liver failure. He had crippling dystonia, dysarthria, and choreoathetosis. There were prominent Kayser-Fleischer rings. Liver-function tests included a serum-bilirubin of 2-9 mg. per 100 ml., a prothrombin-time of 44%, and serum protein and albumin concentrations of 5’7 and 2-9 g. per 100 ml., respectively. He showed no response to D-penicillamine and triethyltetramine dihydrochloride. On March 23, 1971, orthotopic hepatic transplantation was carried out. Postoperatively, immunosuppression included cyclophosphamide (for which azathioprine was later substituted), prednisone, and a three-month course of heterologous antilymphocyte globulin. Presently, his liver function is normal (see accompanying table). As previously reportedhis liver removed at transplantation had a markedly increased copper content (see table). Biopsies of the homograft at twelve, thirteen, and seventeen months after transplant showed tissue-copper levels of 48, 30, and 45 fig. per g. wet weight, respectively. In the most recent biopsy at forty-two months, the tissue-copper level was 27 jjtg. per g. wet weightonly slightly above normal (see table). All the homograft biopsies appeared normal histologically. 1.
2.
DuBois, R. S., Giles, G., Rodgerson, D. O., Lilly, J., Martineau, G., Halgrimson, C. G., Schroter, G., Starzl, T. E., Sternlieb, I., Sheinberg, I. H. Lancet, 1971, i, 505. Groth, C. G., DuBois, R. S., Corman, J., Gustafsson, A., Iwatsuki, S., Rodgerson, D. O., Halgrimson, C. G., Starzl, T. E. Transplant. Proc. 1973, 5, 829.
177 copper excretion was 540 g. per 24 hours before In the early postoperative period this patient had markedly increased urinary excretion of copper, but after five months a decrease toward normal was noted. At the present time, the urinary copper excretion is 87 g. per day, which is
Urinary
operation.
still slightly elevated.
Initially, caeruloplasmin was virtually absent in the serum of this patient, but within three months after transplantation it increased dramatically and now remains normal (see table). The serum-copper concentration, which was low preoperatively, rapidly increased early postoperatively, then fell to normal. Postoperatively, the patient’s neurological dysfunction has gradually improved and now he has no neurological impairment. The Kayser-Fleischer rings have completely disappeared over a period of two and a half years as determined by several slit-lamp examinations. The complete correction, in our second patient, of all the classical clinical manifestations and biochemical abnormalities of Wilson’s disease has not been reported with other forms of therapy.33 These observations lend support to the contention that this genetic disorder is liver-based. With the provision of a normal liver, excess body-copper is eliminated over a period of years. This work was supported by research grants from the Veterans Administration; by grants AI-AM-08898 and AM-07772 of the National Institutes of Health; and by grants RR-00051 and RR-0069 from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of
Health. Departments of Surgery and Pediatrics, University of Colorado Medical Center, Denver, Colorado 80220, U.S.A.
ROBERT W. BEART, JR. CHARLES W. PUTNAM K. A. PORTER THOMAS E. STARZL.
SULPHONE RESISTANCE IN LEPROSY SIR,—The salutary paper by Dr Pearson and his colleagues (July 12, p. 69) confirms a growing suspicion that sulphone-resistant leprosy bacilli may be shown to be appearing with disturbing frequency wherever the investigation of clinical relapse can be supplemented by mouse footpad inoculation. Several instances are known to have arisen in England, in addition to the one reported by Adams and Waters.4 The financial and other constraints which, in most countries, have hitherto made monotherapy in leprosy almost obligatory, must now be reviewed in the light of the findings reported. For patients with lepromatous leprosy, treatment with more than one leprostatic drug should henceforth be the ideal to strive for, if not actually
mandatory.
FUTURE OF CHEMICAL PATHOLOGY SiR,-We read with interest but some alarm your editorial of June 14 (p. 1327) on the future of chemical pathology in this country. Chemical pathology is indeed at the crossroads and a change of direction is vital, but changes are taking place. We have now reached the point where chemical pathology can break loose from the other pathological sciences and can become an exciting and
important subject in its own right. Perhaps fortunately, economic disaster and manpower problems have led many of us to re-examine the whole philosophy of clinical biochemistry. Two types of individual are needed. The professional biochemist is necessary to cope with the complex machinery, automation, and the highly sophisticated apparatus now available, as well as to develop new methodologies, but equally the medically qualified biochemist is necessary both in the laboratory and at the bedside. His presence in the laboratory is vital so that only clinically useful and relevant tests are performed and he has a full role to play in development. His presence at the bedside is necessary to advise on biochemical problems such as fluid balance, intravenous nutrition, hyperlipidasmia, and metabolic disease, to help interpret biochemical results for the clinician, and to advise on appropriate tests. To maintain credibility he will require both a clinical and a biochemical training. This might be best fulfilled by the M.R.C.P. and an M.sc. in clinical biochemistry, together with a certain number of years spent in a chemical pathology department. Rotation of junior staff through general pathology has outlived its usefulness as a means of training, although it may have a role in recruitment. It is - surely more relevant to establish rotations through clinical medicine. The chemical pathology department of the future will probably be controlled in parallel by a top-grade biochemist and a chemical pathologist, the latter also having responsibility for metabolic clinics, being involved in intensive care, acting as a secondary referral service, and controlling a small number of investigative beds. In the district general hospital the chemical pathologist has a vital clinical role to play. You imply that a change to this type of approach is rare. We suggest that the change is already taking place, albeit slowly; that most of us are aware of the need for change; and that the subject of chemical pathology will. shortly become one of the most exciting, rewarding, and intellectually stimulating specialties in clinical medicine. University Department of Chemical Pathology and Human Metabolism, General Hospital, Southampton.
Basingstoke District General Hospital, Basingstoke.
K. G. M. M. ALBERTI G. F. BATSTONE M. NATTRASS. H. PLATT.
While Dr Pearson and his colleagues state that " the long duration of treatment before relapse is very striking ", and cite one patient who relapsed after only 5 years of
intermittent treatment, it should be known that, in
a
Nigerian patient, relapse due to dapsone-resistant organisms occurred after 52 months of regular treatment at a dose of 50 mg. twice weekly.5 Fortunately, no case of relapse due to sulphone-resistant organisms has so far failed to respond to clofazimine.6s Leprosy Study Centre, 57A Wimpole Street, London W1M 7DF. 3.
S. G. BROWNE.
Beam, A. G. in The Metabolic Basis of Inherited Disease (edited by J. B. Stanbury, J. B. Wyngaarden, and D. J. Fredrickson); p. 1033. New York, 1972. 4. Adams, A. H. D., Waters, M. F. R. Br. med. J. 1966, ii, 892. 5. Browne, S. G. Int. J. Leprosy, 1969, 37, 296. 6. Browne, S. G. Trans. St. John’s Hosp. derm. Soc. 1973, 59, 225.
SiR,—Your editorial raises complex issues and implies that there must be a reversal of "the retreat from the wards " and renewal of what many practised in the 1950s-clinical collaboration based upon the laboratory. My view, shared I think by almost all academic heads in the U.K. at a meeting this year, is that we do require medically qualified clinical biochemists and that, yes, recruitment is possible; indeed many in my own department have science qualifications. The bottlenecks ahead are money, permission for establishment, and space. For the past decade or so in Scotland we have approached staffing on a combined basis. In this way either medical or non-medical graduates can be in administrative charge of the whole of or sections of a large department. Teaching
Round the World
Letters
to
the Editor
United States THE LAW AND UNANSWERED
QUESTIONS exhaustion has settled of when the relative JUST quiet we are over the medical uproar, malpractice temporarily faced with a new legal intervention or interpretation with profound medical implications. Recent years have been punctuated by judicial decisions on persons in custodial care; in particular, the Supreme Court’s rather illiberal attitude to the criminal has been counterbalanced by perhaps undue liberality towards the " believed-to-be insane " in custodial care. The cases have been brought by legal groups and individuals on behalf of various types of confined persons, and have resulted in some improvements at very great public cost, but there are still an enormous number of deficiencies. Recently the Supreme Court ruled that a State may not confine involuntarily with mere custodial care any mentally ill patient who is not dangerous and who can function outside in the community. The suit was brought on behalf of a 15-year-confined patient who in 1957- was admitted to hospital, at his father’s request, as a paranoid schizophrenic, and who himself admits that he had no insight into his condition when admitted. After years of litigation he has won his release and compensation for his deprivation of liberty. However, his success and the implications stemming from it seem to have frightened even his own lawyer, who has been anxious to make it clear that no-one is talking about the precipitous wholesale release of thousands of mental patients tomorrow, and that there must be adequate planning for such discharges. But the large-scale release of patients is exactly what is being talked about, and many people are asking what is meant by adequate planning, and how it can be done in overcrowded, understaffed facilities, and under the threat of being mulcted for heavy damages if a mentally ill patient who is not dangerous and can function outside is held in custodial care. Who is to say that a mentally ill patient is not dangerous ? It is precisely this that has outraged public opinion, as murderers now judged non-dangerous are released and then commit further murders. Of immediate concern is the question of whether a non-dangerous mentally ill patient can be involuntarily confined in hospital if adequate treatment is offered. That in turn raises the question as to what is adequate treatment, and how it can be offered to a non-responsive patient. Another vital question, especially for those who have to provide the facilities, is whether patients have a legal right to treatment at all. Has every patient a right to releaseindeed, is there really warrant for holding against their will even violent mentally ill people ? It can be argued that the much talked of right " to treatment, and indeed the " right " to good health, are illusions, and that good health is a privilege won by hard work. In many illnesses, mental and physical, a point is reached beyond which " treatment " brings no return, and indeed becomes wasteful. Has a patient at this stage any " right " to " adequate treatment " ? And what rights has the public ? With increasing numbers of the mentally retarded and the mentally ill being released, there will undoubtedly be an increase in incidents of one kind and another, and public emotions may well be stretched to breaking-point. Some people see in this difficult situation the failure of democracy and of our legislative bodies. The courts, in their clumsy fashion, are trying to sort out the failures of the legislative bodies to act with foresight, to see that the Civil Servants carry out their duties, and to provide the financial means for them to do so. The courts are usurping the functions that the legislatures have neglected. "
LIVER TRANSPLANTATION FOR WILSON’S DISEASE
SiR,-We have reported before on the early course of patients after liver transplantation for Wilson’s disease. 1,2 The indication for operation in the first was liver failure. This boy, whois now aged recipient 17 years, will be six years post-transplantation on July 15. He is the longest survivor in the world after liver replacement. With the provision of a new liver, a decoppering process was demonstrated, mainly by a prolonged cupriuresis. However, the potential usefulness of the
two
metabolic observations in the context of Wilson’s disease and its treatment was reduced by certain atypical features of the case. Although the copper concentration in the native liver was very high, the serum caErulopIasmin concentration was low normal and the corneas had no evidence of Kayser-Fleischer rings. The second patient is now four years two months -
post-transplantation. He was first diagnosed as having Wilson’s disease at the age of 11 years. By the age of 14 years, he had progressively deteriorating BIOCHEMICAL FINDINGS BEFORE AND AFTER TRANSPLANTATION
hepatic and neurological function. Although he had ascites, transplantation was recommended more because of the serious neurological impairment than because of liver failure. He had crippling dystonia, dysarthria, and choreoathetosis. There were prominent Kayser-Fleischer rings. Liver-function tests included a serum-bilirubin of 2-9 mg. per 100 ml., a prothrombin-time of 44%, and serum protein and albumin concentrations of 5’7 and 2-9 g. per 100 ml., respectively. He showed no response to D-penicillamine and triethyltetramine dihydrochloride. On March 23, 1971, orthotopic hepatic transplantation was carried out. Postoperatively, immunosuppression included cyclophosphamide (for which azathioprine was later substituted), prednisone, and a three-month course of heterologous antilymphocyte globulin. Presently, his liver function is normal (see accompanying table). As previously reportedhis liver removed at transplantation had a markedly increased copper content (see table). Biopsies of the homograft at twelve, thirteen, and seventeen months after transplant showed tissue-copper levels of 48, 30, and 45 fig. per g. wet weight, respectively. In the most recent biopsy at forty-two months, the tissue-copper level was 27 jjtg. per g. wet weightonly slightly above normal (see table). All the homograft biopsies appeared normal histologically. 1.
2.
DuBois, R. S., Giles, G., Rodgerson, D. O., Lilly, J., Martineau, G., Halgrimson, C. G., Schroter, G., Starzl, T. E., Sternlieb, I., Sheinberg, I. H. Lancet, 1971, i, 505. Groth, C. G., DuBois, R. S., Corman, J., Gustafsson, A., Iwatsuki, S., Rodgerson, D. O., Halgrimson, C. G., Starzl, T. E. Transplant. Proc. 1973, 5, 829.
177 copper excretion was 540 g. per 24 hours before In the early postoperative period this patient had markedly increased urinary excretion of copper, but after five months a decrease toward normal was noted. At the present time, the urinary copper excretion is 87 g. per day, which is
Urinary
operation.
still slightly elevated.
Initially, caeruloplasmin was virtually absent in the serum of this patient, but within three months after transplantation it increased dramatically and now remains normal (see table). The serum-copper concentration, which was low preoperatively, rapidly increased early postoperatively, then fell to normal. Postoperatively, the patient’s neurological dysfunction has gradually improved and now he has no neurological impairment. The Kayser-Fleischer rings have completely disappeared over a period of two and a half years as determined by several slit-lamp examinations. The complete correction, in our second patient, of all the classical clinical manifestations and biochemical abnormalities of Wilson’s disease has not been reported with other forms of therapy.33 These observations lend support to the contention that this genetic disorder is liver-based. With the provision of a normal liver, excess body-copper is eliminated over a period of years. This work was supported by research grants from the Veterans Administration; by grants AI-AM-08898 and AM-07772 of the National Institutes of Health; and by grants RR-00051 and RR-0069 from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of
Health. Departments of Surgery and Pediatrics, University of Colorado Medical Center, Denver, Colorado 80220, U.S.A.
ROBERT W. BEART, JR. CHARLES W. PUTNAM K. A. PORTER THOMAS E. STARZL.
SULPHONE RESISTANCE IN LEPROSY SIR,—The salutary paper by Dr Pearson and his colleagues (July 12, p. 69) confirms a growing suspicion that sulphone-resistant leprosy bacilli may be shown to be appearing with disturbing frequency wherever the investigation of clinical relapse can be supplemented by mouse footpad inoculation. Several instances are known to have arisen in England, in addition to the one reported by Adams and Waters.4 The financial and other constraints which, in most countries, have hitherto made monotherapy in leprosy almost obligatory, must now be reviewed in the light of the findings reported. For patients with lepromatous leprosy, treatment with more than one leprostatic drug should henceforth be the ideal to strive for, if not actually
mandatory.
FUTURE OF CHEMICAL PATHOLOGY SiR,-We read with interest but some alarm your editorial of June 14 (p. 1327) on the future of chemical pathology in this country. Chemical pathology is indeed at the crossroads and a change of direction is vital, but changes are taking place. We have now reached the point where chemical pathology can break loose from the other pathological sciences and can become an exciting and
important subject in its own right. Perhaps fortunately, economic disaster and manpower problems have led many of us to re-examine the whole philosophy of clinical biochemistry. Two types of individual are needed. The professional biochemist is necessary to cope with the complex machinery, automation, and the highly sophisticated apparatus now available, as well as to develop new methodologies, but equally the medically qualified biochemist is necessary both in the laboratory and at the bedside. His presence in the laboratory is vital so that only clinically useful and relevant tests are performed and he has a full role to play in development. His presence at the bedside is necessary to advise on biochemical problems such as fluid balance, intravenous nutrition, hyperlipidasmia, and metabolic disease, to help interpret biochemical results for the clinician, and to advise on appropriate tests. To maintain credibility he will require both a clinical and a biochemical training. This might be best fulfilled by the M.R.C.P. and an M.sc. in clinical biochemistry, together with a certain number of years spent in a chemical pathology department. Rotation of junior staff through general pathology has outlived its usefulness as a means of training, although it may have a role in recruitment. It is - surely more relevant to establish rotations through clinical medicine. The chemical pathology department of the future will probably be controlled in parallel by a top-grade biochemist and a chemical pathologist, the latter also having responsibility for metabolic clinics, being involved in intensive care, acting as a secondary referral service, and controlling a small number of investigative beds. In the district general hospital the chemical pathologist has a vital clinical role to play. You imply that a change to this type of approach is rare. We suggest that the change is already taking place, albeit slowly; that most of us are aware of the need for change; and that the subject of chemical pathology will. shortly become one of the most exciting, rewarding, and intellectually stimulating specialties in clinical medicine. University Department of Chemical Pathology and Human Metabolism, General Hospital, Southampton.
Basingstoke District General Hospital, Basingstoke.
K. G. M. M. ALBERTI G. F. BATSTONE M. NATTRASS. H. PLATT.
While Dr Pearson and his colleagues state that " the long duration of treatment before relapse is very striking ", and cite one patient who relapsed after only 5 years of
intermittent treatment, it should be known that, in
a
Nigerian patient, relapse due to dapsone-resistant organisms occurred after 52 months of regular treatment at a dose of 50 mg. twice weekly.5 Fortunately, no case of relapse due to sulphone-resistant organisms has so far failed to respond to clofazimine.6s Leprosy Study Centre, 57A Wimpole Street, London W1M 7DF. 3.
S. G. BROWNE.
Beam, A. G. in The Metabolic Basis of Inherited Disease (edited by J. B. Stanbury, J. B. Wyngaarden, and D. J. Fredrickson); p. 1033. New York, 1972. 4. Adams, A. H. D., Waters, M. F. R. Br. med. J. 1966, ii, 892. 5. Browne, S. G. Int. J. Leprosy, 1969, 37, 296. 6. Browne, S. G. Trans. St. John’s Hosp. derm. Soc. 1973, 59, 225.
SiR,—Your editorial raises complex issues and implies that there must be a reversal of "the retreat from the wards " and renewal of what many practised in the 1950s-clinical collaboration based upon the laboratory. My view, shared I think by almost all academic heads in the U.K. at a meeting this year, is that we do require medically qualified clinical biochemists and that, yes, recruitment is possible; indeed many in my own department have science qualifications. The bottlenecks ahead are money, permission for establishment, and space. For the past decade or so in Scotland we have approached staffing on a combined basis. In this way either medical or non-medical graduates can be in administrative charge of the whole of or sections of a large department. Teaching
