1030 LIGHT CHAINS IN CEREBROSPINAL FLUID IN MULTIPLE SCLEROSIS
SIR,-Within the plaques of patients with multiple sclerosis (M.s.) Dr Esiri (Sept. 3, p. 478) found more cells with light chains than heavy chains. This accords with our cerebrospinalfluid (c.s.F.) studies in M.s. Since Cohen and Bannister’ established that lymphocytic cells obtained from the c.s.F. of a patient with M.s. do synthesise IgG, IgA, and a relatively greater amount of kappa light polypeptide chains, c.s.F. examination for light polypeptide chains has become a useful diagnostic test in m. S. 2-4 Using the radial immunodiffusion technique, Link and Zetterva112 found increased ratios of c.s.F. kappa/lambda chains in 54% of M.s. patients with oligoclonal gammopathy in the corresponding c.s.F. protein electrophoretograms and no abnormalities in the concentration of c.s.F. lambda chains. Double ring formation in a single radial immunodiffusion of kappa and not of light chains of type lambda was reported in c.s.F. of 57% of M.s. patients.3 Besides increased C.S.F. ratios of kappa/lambda chains in patients with M.s. Anthony and I have also observed, in 15% of M.s. patients studied, a relative increase in the c.s.F. concentration of lambda chains and/or a relative decrease in the amount of c.s.F. kappa chains.4 In some patients in our series of 160 with various neurological disorders, including M.s. and subacute sclerosing panencephalitis (S.S.P.E.), changes in the serum ratio of kappa/lambda chains were also established, a finding confirmed for S.S.P.E. by
Bollengier et al.5 In c.s.F. immunoelectrophoretograms6 in 21 consecutive M.s. patients, antisera to Fab fragments of IgG and to kappa or lambda chains were simultaneously used. Anodal and cathodal elongation of the precipitate of the c.s.F. light chains, compared with the precipitation arc of Fab fragments of IgG, was found in 95% of patients (see figure). Under normal conditions, the precipitate of the c.s.F. light polypeptide chains is .
died
c.s.F. immunoelectrophoresis, no simultaneous inin the concentration of both the c.s.F. kappa and lambda chains was established. Increased C.s.F. concentration of kappa chains was observed in 2 M.S. patients in whom no definite bands were seen in the gammaglobulin field of the c.s.F. protein and in 1 patient with normal c.s.F. IgG concentration. In our patients with inflammatory central nervous system afflictions and in malignant lymphoproliferative disorders’ increased c.s.F. concentration of lambda chains was more frequently established than in patients with M.S. The absence of simultaneous increases of the c.s.F. concentration of both kappa and lambda chains and the number of our M.S. patients who had increased c.s.F. concentration of kappa chains argue against a predominantly infectious xtiology for M.s. Proliferation of one clone (or a very limited number of clones) of immunocompetent cells in the c.s.F. parenchyma of M.S. patients, manifested by increased C.S.F. concentration of one of the light chains and probably also of a single subgroup of IgG,9 are more suggestive of a malignant lymphoproliferative process than of an infectious, inflammatory C.N.s. affliction.
by
crease
Department of Neurology, Indiana University Medical Center, Indianapolis, Indiana 46202, U.S.A.
OLDRICH J. KOLAR
SERUM-FERRITIN IN DIAGNOSIS OF HÆMOCHROMATOSIS
SIR,-Dr Halliday and colleagues (Sept. 24, p. 621) note patients with increased iron stores had serum-ferritin concentrations that fluctuated widely. They suggest that this was due to the fact that these patients had a daily that three of their
alcohol intake of 100 g ethanol.
either absent or shorter in both the cathodal and anodal ends when compared with the precipitation arc of the Fab fragments of IgG. Cathodal and anodal elongation of the precipitation arc of the c.s.F. kappa or lambda light chains reflects their increased c.s.F. concentration. In 19 of the M.s. patients studied, the c.s.F. immunoelectropherogram indicated raised concentration of kappa chains and, in 1 patient, increased c.s.F. concentration of lambda chains. In our M.s. patients stu1. Cohen, S., Bannister, R. Lancet, 1967, i, 366. 2. Link, H., Zettervall, O. Clin. exp. Immunol. 1970, 6, 435. 3. Iwashita, H., Grunwald, F., Bauer, H. J. Neurol. 1974, 207, 45. 4. Kolar, O., Anthony, E. Z. Neurol. 1971, 200, 6. 5. Bollengier, F., Karcher, D., Rabinovitch, N. Ann. Microbiol. Inst. Pasteur, 6.
1977, 128A, 89. Kolar, O. J., Ross, A. T., Herman, J. T. Neurology, 1970, 20, 1052.
Serial serum-ferritin values, in five patients with idiopathic heeoiochrotnatosis, determined during venesection therapy.
C.S.F. immunoelectrophoretogram in a 23-year-old female with M.S.
(pH 8.8;
ionic
strength 0.05)
In the upper groove, rabbit antiserum to Fab fragments of IgG (Behring Diagnostics, Somerville, New Jersey) and, in the lower groove, rabbit antiserum to kappa chains (Meloy, Springfield, Virginia) were used. Relative to the precipitation arc of the Fab fragments of IgG (1) there is anodal and cathodal elongation of the precipitate of the kappa chains (3). Note increased concentration of glycoproteins with electrophoretic mobility of gammagiobulins (2).
We have found’ widely varying serum-ferritin values in five with primary hasmochromatosis who did not have excessive intake of alcohol but were undergoing venesection therapy. Serum aspartate aminotransferase levels were normal
patients
7. 8.
Kolar, O. Unpublished. Palmer, D. L., Minard, B. J., Cawley, L. P.New Engl. J.Med. 1976, 294,
1.
Leyland, M. J., Brown, P. J., Bomford, A., Walker, J.Hœmat.1977, 36, 441.
447. R.
J., Williams, R. Br.
1031 in all. Serum-ferritin was measured at each venesection (see figure). In all patients the serum-ferritin concentration rose after venesection began, to between two and eight times the pre-venesection level. In two patients serum-ferritin fell progressively after that, with continuing depletion of body-iron stores. The other three patients had unexplained wide fluctuations in serum-ferritin during the first five to nine months of venesection. The only patient who reached iron deficiency had a final phase in which serum-ferritin progressively fell to low
concentrations over a period of about three months. This is another example of a situation where serum-ferritin does not accurately reflect body-iron stores.2 We cannot say whether these fluctuations are due to differential rates of clearance of ferritin from serum or whether ferritin with altered immunoreactivity is released into the circulation during venesection. Department of Hæmatology, University of Liverpool,
M. J. LEYLAND P. J. BROWN R. J. WALKER
Liverpool, L69 3BX Walton Liver
Hospital, Liverpool
Unit,
A. BOMFORD ROGER WILLIAMS
King’s College Hospital, London
HUMANISM IN MEDICINE
SiR,-Dr Agnew’s paper (Sept. 17, p. 596) is based on no data, and, in my view, was most inappropriate. In California,_ obstetrics is under tremendous pressure to be "more humanistic," meaning to provide home deliveries under unsatisfactory conditions. While obstetricians have made efforts to accommodate this view, providing alternate birth centres for low-risk pregnancies, this has not been enough and the State government is sponsoring a bill which will legalise lay midwives, presumably to provide cheap and humanistic delivery. These people will be poorly trained and nothing more than birth attendants, yet they will be allowed to manage labours at home and even in hospitals. There have been excesses of scientism in low-risk pregnancies, but I canobstetrics, not accept that humanism is the most important feature of care when a pregnancy has more than a low risk. Our urgent needs are to improve perinatal-mortality rates, reduce the incidence of cerebral palsy, and keep maternal-mortality rates low. These cannot be met by the humanistic approach and discarding modern techniques. It may be a sign of my age, but I detect a strong movement in our house-officers and students away from the science of obstetrics and towards the humanistic aspects, all which should please Dr Agnew. No one can argue against humanistic medicine but it must not be allowed to destroy the availability of scientific care.
In his Kamofsy memorial lecture, delivered to the American Society of Clinical Oncology in 1976, Dr E. J. Freireich asked
"Who took the ’clinical’ out of ’clinical research’?", and he left the impressionthat we are not only forgetting the humanism but also tending to rely too much on magic "significant differences". The recent award of the Nobel peace prize indicates that some ordinary people can think humanely. Perhaps prizes should be awarded for humanity in medicine. Dr Agnew has rightly named Mother Teresa and Dr Cicely Saunders for their outstanding contributions to medical humanism. Another might be Eva den Hertog of the Salvation Army, a dedicated nurse and medical social worker known in many African and Asian countries, particularly Bangladesh where she has striven to create happiness among the victims of politico-military genocide and natural disaster.2 An award for medical humanism should be instituted now; why not an international Lancet award for medical humanism? me
Radiotherapy Department, Academic Hospital, Free University,
A. B. M. F. KARIM
Amsterdam, Netherlands
ROYAL MEDICAL BENEVOLENT FUND CHRISTMAS APPEAL SiR,-Every year members of the medical profession help provide the beneficiaries of the Royal Medical Benevolent Fund with a little extra for Christmas. In 1976 over £16 000 was raised and distributed. We know, from the letters of thanks we receive, how much these gifts mean to the recipients.
We do like to distribute gifts in good time for Christmas. Would all individuals, societies, and groups who have not yet done so send their contributions as soon as possible to the Director, Royal Medical Benevolent Fund, 24 King’s Road, Wimbledon, London SW19 8QN.
particularly for
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, School of Medicine, University of California, Davis, U.S.A.
SIR,-Dr Agnew’s wish for
ROBERT C. GOODLIN
more
humanism in medicine
deserves the attention of all of us. We are right to pursue scientific medicine; but we should also stress the "art of healing", and we seem to be failing to serve our patients in that respect. The verdicts of patients visiting doctors and hospitals over a decade might throw some light on the question-Are we better healers? Scientifically, perhaps we are, but we need to know if our patients are really comforted by our presence and endeavours. Unless we can satisfy society, society is likely to mould us to the way it wishes. After all, medicine is nothing but one of society’s responses to its environment.1 J., Rowe, J., Mezey, S., Waterbury, L., Wright, J., Halliday, J. W., Isselbacher, K., Powell, L. New Engl. J. Med. 1976, 294, 302. 1. Rhodes, P. Value of Medicine. London, 1977.
THOMAS HOLMES SELLORS, President Medical Benevolent London SW19 8QN
Royal
Fund,
GEOFFREY BATEMAN Hon. Treasurer
SENIOR-REGISTRAR TRAINING POSTS
SIR,-The specialty advisory committees of the Joint Com-
Higher Medical Training (J.C.H.M.T) have now inof the senior registrar (or equivalent) training in medicine and allied specialties put forward for considposts eration and they hope to deal with the remainder soon. Posts approved for training are listed in the Second Report of the ].CH.M.T. and supplements (available from the ].C.H.M.T., price £ 1.50). mittee
on
spected
most
Employing authorities have been asked to state, in advertisements for senior-registrar posts, that they have been approved (if this is the case) for training by the J.C.H.M.T. This is an additional safeguard to applicants who may not have access to a copy of the second report. Absence of a positive statement of approval in any advertisement does not necessarily mean that the post has been turned down by the J.C.H.M.T. It may be a perfectly satisfactory post that has not yet been inspected or it may be a post that has only minor training deficiencies which are being put right. However, if the advertisement does not include a positive statement of approval by the J.C.H.M.T., applicants should, in their own interests, carefully scrutinise the further particulars of the post provided by the employing authority and, if neces-
2. Wands,
2.
H. Moved with Compassion: Eva den Midst of Despair. London, 1977.
Maule,
Hertog’s World of Hope in the
SIR,-Within the plaques of patients with multiple sclerosis (M.s.) Dr Esiri (Sept. 3, p. 478) found more cells with light chains than heavy chains. This accords with our cerebrospinalfluid (c.s.F.) studies in M.s. Since Cohen and Bannister’ established that lymphocytic cells obtained from the c.s.F. of a patient with M.s. do synthesise IgG, IgA, and a relatively greater amount of kappa light polypeptide chains, c.s.F. examination for light polypeptide chains has become a useful diagnostic test in m. S. 2-4 Using the radial immunodiffusion technique, Link and Zetterva112 found increased ratios of c.s.F. kappa/lambda chains in 54% of M.s. patients with oligoclonal gammopathy in the corresponding c.s.F. protein electrophoretograms and no abnormalities in the concentration of c.s.F. lambda chains. Double ring formation in a single radial immunodiffusion of kappa and not of light chains of type lambda was reported in c.s.F. of 57% of M.s. patients.3 Besides increased C.S.F. ratios of kappa/lambda chains in patients with M.s. Anthony and I have also observed, in 15% of M.s. patients studied, a relative increase in the c.s.F. concentration of lambda chains and/or a relative decrease in the amount of c.s.F. kappa chains.4 In some patients in our series of 160 with various neurological disorders, including M.s. and subacute sclerosing panencephalitis (S.S.P.E.), changes in the serum ratio of kappa/lambda chains were also established, a finding confirmed for S.S.P.E. by
Bollengier et al.5 In c.s.F. immunoelectrophoretograms6 in 21 consecutive M.s. patients, antisera to Fab fragments of IgG and to kappa or lambda chains were simultaneously used. Anodal and cathodal elongation of the precipitate of the c.s.F. light chains, compared with the precipitation arc of Fab fragments of IgG, was found in 95% of patients (see figure). Under normal conditions, the precipitate of the c.s.F. light polypeptide chains is .
died
c.s.F. immunoelectrophoresis, no simultaneous inin the concentration of both the c.s.F. kappa and lambda chains was established. Increased C.s.F. concentration of kappa chains was observed in 2 M.S. patients in whom no definite bands were seen in the gammaglobulin field of the c.s.F. protein and in 1 patient with normal c.s.F. IgG concentration. In our patients with inflammatory central nervous system afflictions and in malignant lymphoproliferative disorders’ increased c.s.F. concentration of lambda chains was more frequently established than in patients with M.S. The absence of simultaneous increases of the c.s.F. concentration of both kappa and lambda chains and the number of our M.S. patients who had increased c.s.F. concentration of kappa chains argue against a predominantly infectious xtiology for M.s. Proliferation of one clone (or a very limited number of clones) of immunocompetent cells in the c.s.F. parenchyma of M.S. patients, manifested by increased C.S.F. concentration of one of the light chains and probably also of a single subgroup of IgG,9 are more suggestive of a malignant lymphoproliferative process than of an infectious, inflammatory C.N.s. affliction.
by
crease
Department of Neurology, Indiana University Medical Center, Indianapolis, Indiana 46202, U.S.A.
OLDRICH J. KOLAR
SERUM-FERRITIN IN DIAGNOSIS OF HÆMOCHROMATOSIS
SIR,-Dr Halliday and colleagues (Sept. 24, p. 621) note patients with increased iron stores had serum-ferritin concentrations that fluctuated widely. They suggest that this was due to the fact that these patients had a daily that three of their
alcohol intake of 100 g ethanol.
either absent or shorter in both the cathodal and anodal ends when compared with the precipitation arc of the Fab fragments of IgG. Cathodal and anodal elongation of the precipitation arc of the c.s.F. kappa or lambda light chains reflects their increased c.s.F. concentration. In 19 of the M.s. patients studied, the c.s.F. immunoelectropherogram indicated raised concentration of kappa chains and, in 1 patient, increased c.s.F. concentration of lambda chains. In our M.s. patients stu1. Cohen, S., Bannister, R. Lancet, 1967, i, 366. 2. Link, H., Zettervall, O. Clin. exp. Immunol. 1970, 6, 435. 3. Iwashita, H., Grunwald, F., Bauer, H. J. Neurol. 1974, 207, 45. 4. Kolar, O., Anthony, E. Z. Neurol. 1971, 200, 6. 5. Bollengier, F., Karcher, D., Rabinovitch, N. Ann. Microbiol. Inst. Pasteur, 6.
1977, 128A, 89. Kolar, O. J., Ross, A. T., Herman, J. T. Neurology, 1970, 20, 1052.
Serial serum-ferritin values, in five patients with idiopathic heeoiochrotnatosis, determined during venesection therapy.
C.S.F. immunoelectrophoretogram in a 23-year-old female with M.S.
(pH 8.8;
ionic
strength 0.05)
In the upper groove, rabbit antiserum to Fab fragments of IgG (Behring Diagnostics, Somerville, New Jersey) and, in the lower groove, rabbit antiserum to kappa chains (Meloy, Springfield, Virginia) were used. Relative to the precipitation arc of the Fab fragments of IgG (1) there is anodal and cathodal elongation of the precipitate of the kappa chains (3). Note increased concentration of glycoproteins with electrophoretic mobility of gammagiobulins (2).
We have found’ widely varying serum-ferritin values in five with primary hasmochromatosis who did not have excessive intake of alcohol but were undergoing venesection therapy. Serum aspartate aminotransferase levels were normal
patients
7. 8.
Kolar, O. Unpublished. Palmer, D. L., Minard, B. J., Cawley, L. P.New Engl. J.Med. 1976, 294,
1.
Leyland, M. J., Brown, P. J., Bomford, A., Walker, J.Hœmat.1977, 36, 441.
447. R.
J., Williams, R. Br.
1031 in all. Serum-ferritin was measured at each venesection (see figure). In all patients the serum-ferritin concentration rose after venesection began, to between two and eight times the pre-venesection level. In two patients serum-ferritin fell progressively after that, with continuing depletion of body-iron stores. The other three patients had unexplained wide fluctuations in serum-ferritin during the first five to nine months of venesection. The only patient who reached iron deficiency had a final phase in which serum-ferritin progressively fell to low
concentrations over a period of about three months. This is another example of a situation where serum-ferritin does not accurately reflect body-iron stores.2 We cannot say whether these fluctuations are due to differential rates of clearance of ferritin from serum or whether ferritin with altered immunoreactivity is released into the circulation during venesection. Department of Hæmatology, University of Liverpool,
M. J. LEYLAND P. J. BROWN R. J. WALKER
Liverpool, L69 3BX Walton Liver
Hospital, Liverpool
Unit,
A. BOMFORD ROGER WILLIAMS
King’s College Hospital, London
HUMANISM IN MEDICINE
SiR,-Dr Agnew’s paper (Sept. 17, p. 596) is based on no data, and, in my view, was most inappropriate. In California,_ obstetrics is under tremendous pressure to be "more humanistic," meaning to provide home deliveries under unsatisfactory conditions. While obstetricians have made efforts to accommodate this view, providing alternate birth centres for low-risk pregnancies, this has not been enough and the State government is sponsoring a bill which will legalise lay midwives, presumably to provide cheap and humanistic delivery. These people will be poorly trained and nothing more than birth attendants, yet they will be allowed to manage labours at home and even in hospitals. There have been excesses of scientism in low-risk pregnancies, but I canobstetrics, not accept that humanism is the most important feature of care when a pregnancy has more than a low risk. Our urgent needs are to improve perinatal-mortality rates, reduce the incidence of cerebral palsy, and keep maternal-mortality rates low. These cannot be met by the humanistic approach and discarding modern techniques. It may be a sign of my age, but I detect a strong movement in our house-officers and students away from the science of obstetrics and towards the humanistic aspects, all which should please Dr Agnew. No one can argue against humanistic medicine but it must not be allowed to destroy the availability of scientific care.
In his Kamofsy memorial lecture, delivered to the American Society of Clinical Oncology in 1976, Dr E. J. Freireich asked
"Who took the ’clinical’ out of ’clinical research’?", and he left the impressionthat we are not only forgetting the humanism but also tending to rely too much on magic "significant differences". The recent award of the Nobel peace prize indicates that some ordinary people can think humanely. Perhaps prizes should be awarded for humanity in medicine. Dr Agnew has rightly named Mother Teresa and Dr Cicely Saunders for their outstanding contributions to medical humanism. Another might be Eva den Hertog of the Salvation Army, a dedicated nurse and medical social worker known in many African and Asian countries, particularly Bangladesh where she has striven to create happiness among the victims of politico-military genocide and natural disaster.2 An award for medical humanism should be instituted now; why not an international Lancet award for medical humanism? me
Radiotherapy Department, Academic Hospital, Free University,
A. B. M. F. KARIM
Amsterdam, Netherlands
ROYAL MEDICAL BENEVOLENT FUND CHRISTMAS APPEAL SiR,-Every year members of the medical profession help provide the beneficiaries of the Royal Medical Benevolent Fund with a little extra for Christmas. In 1976 over £16 000 was raised and distributed. We know, from the letters of thanks we receive, how much these gifts mean to the recipients.
We do like to distribute gifts in good time for Christmas. Would all individuals, societies, and groups who have not yet done so send their contributions as soon as possible to the Director, Royal Medical Benevolent Fund, 24 King’s Road, Wimbledon, London SW19 8QN.
particularly for
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, School of Medicine, University of California, Davis, U.S.A.
SIR,-Dr Agnew’s wish for
ROBERT C. GOODLIN
more
humanism in medicine
deserves the attention of all of us. We are right to pursue scientific medicine; but we should also stress the "art of healing", and we seem to be failing to serve our patients in that respect. The verdicts of patients visiting doctors and hospitals over a decade might throw some light on the question-Are we better healers? Scientifically, perhaps we are, but we need to know if our patients are really comforted by our presence and endeavours. Unless we can satisfy society, society is likely to mould us to the way it wishes. After all, medicine is nothing but one of society’s responses to its environment.1 J., Rowe, J., Mezey, S., Waterbury, L., Wright, J., Halliday, J. W., Isselbacher, K., Powell, L. New Engl. J. Med. 1976, 294, 302. 1. Rhodes, P. Value of Medicine. London, 1977.
THOMAS HOLMES SELLORS, President Medical Benevolent London SW19 8QN
Royal
Fund,
GEOFFREY BATEMAN Hon. Treasurer
SENIOR-REGISTRAR TRAINING POSTS
SIR,-The specialty advisory committees of the Joint Com-
Higher Medical Training (J.C.H.M.T) have now inof the senior registrar (or equivalent) training in medicine and allied specialties put forward for considposts eration and they hope to deal with the remainder soon. Posts approved for training are listed in the Second Report of the ].CH.M.T. and supplements (available from the ].C.H.M.T., price £ 1.50). mittee
on
spected
most
Employing authorities have been asked to state, in advertisements for senior-registrar posts, that they have been approved (if this is the case) for training by the J.C.H.M.T. This is an additional safeguard to applicants who may not have access to a copy of the second report. Absence of a positive statement of approval in any advertisement does not necessarily mean that the post has been turned down by the J.C.H.M.T. It may be a perfectly satisfactory post that has not yet been inspected or it may be a post that has only minor training deficiencies which are being put right. However, if the advertisement does not include a positive statement of approval by the J.C.H.M.T., applicants should, in their own interests, carefully scrutinise the further particulars of the post provided by the employing authority and, if neces-
2. Wands,
2.
H. Moved with Compassion: Eva den Midst of Despair. London, 1977.
Maule,
Hertog’s World of Hope in the
