989 to be able to cure the younger patient of his disease. No major progress will occur if the suggestions of Dr Burge and his colleagues are adopted.
In
short, our ultimate aim is
Royal Marsden Hospital, Downs Road, Sutton, Surrev
been considered presumptuous by some who believe that it prophesies a course of events which need not necessarily occur.
Meanwhile, there
are
patients
in whom the
H. MACD. CLINK I. D. C. DOUGLAS
SIR,-Dr Burge and his colleagues state: "Until a major advance in treatment of acute myeloid leukaemia occurs, treatment should be limited ...". No advance, either major or minor, in the treatment of acute myeloid leukaemia, or any other disease, occurs spontaneously. Intellectual, experimental, and clinical work are needed to secure advance. of Haematology, Hospital,
St. Orsola University 40138 Bologna, Italy.
MICHELE BACCARANI
THYROID FUNCTION AFTER TREATMENT OF HYPERTHYROIDISM
StR,—!t is only two years since Dr Toft, Dr Irvine, and their colleagues’ believed that the plasma-thyroid-stimulatinghormone (T.S.H.) level could not be used as an indication of impending overt hypothyroidism. My colleagues and J2 found their conclusion surprising, and it is a pleasure to find a different message in their recent interesting paper (Sept. 27, p. 576). After studying their patients for a longer time, they now conclude that those with a normal plasma-T.s.H. need not be seen so often as those similarly treated euthyroid patients with a raised plasma-T.s.H. Your leading article on the same subject (p. 590) ends with an exhortation to follow patients "carefully and clinically, or check for binding abnormalities or seek specialist advice." It is surprising that Dr Toft and his colleagues and your leader are concerned with a routine follow-up of these patients since you do not appear to believe that any hazard exists while the patients are clinically euthyroid with normal plasma-thyroid-hormone levels, although they have a raised plasma-T.s.H. If a raised plasma-T.s.H. level is a simple re-adjustment of the pituitary/thyroid axis with no clinical significance, the patients could be told to report if symptoms occurred. A simple routine test of thyroid function, such as measurement of the ankle reflex, could be done to confirm objectively the diagnosis of myxmdema before starting life-long replacement treatment. This would eliminate work in the outpatient and biochemical departments. Richard Asher often said that nothing appears to achieve existence until it is labelled and that a condition springs into being as soon as a name is given to it. We believe3 that a clearcut condition affecting patients does exist and has the following five criteria: (11 The patients are clinically euthyroid. (2) Plasma-thyroid-hormone levels are normal. ...
(3) Thyroid disease is present-usually autoimmune thyroiditis indicated by the presence of thyroid antibodies, or previous partial thyroid ablaton by irradiation or surgery. (4) The basal plasma-T.s.H. level is raised or there is an exaggerated response to thyrotrophin-releasing hormones. 3i Plasma-lipids are often raised, and this change is associated with degenerative arterial disease.
Evered and his colleagues4 call this condition subclinical hypothyroidism and do not include the fifth criterion, which is certainly not a constant finding. However, the condition is neither subclinical nor hypothyroid and had already been called premyxoedema in 1967.5 The term premyxoedema has 1 Toft, A. D., Barnes, E. W., Hunter, W. M., Seth, J., Irvine, W. J Lancet, 1973, ii, 644. 2 Fowler, P. B. S., Ikram, H., Banim, S ibid. p. 801. 3 Ikram, H , Banim, S., Fowler, P. B. S. ibid p. 1405. 4 Evered, D., Ormston, B. J., Smith, P. A., Hall, R., Bird, T. Br. med.J. 1973, 1,657 Fowler, P. B. S., Swale, J. Lancet, 1967, i, 1077.
of
generally acceptable name so that it can be known to exist. Charing Cross Hospital, London W6 8RF.
Division
development
coronary-artery disease may be preventable, and I make a plea that the condition from which they suffer should be given a
P. B. S. FOWLER
IMMUNOSUPPRESSIVE EFFECT OF PREGNANCY-ASSOCIATED
ALPHA2-MACROGLOBULIN SIR,-The non-specific suppressive properties of pregnancyassociated -macroglobulin/2-glycoprotein (P.A.M.) have been shown by several in-vitro methods of immunological assessment, 1-4 Dr Than and his colleagues (Sept. 13, p. 515) reported that the glycoprotein, at concentrations below 130 .g/ml, can cause considerable reductions in lymphocyte proliferation initiated by allogeneic cells or phytohaemagglutinin. However, work in this laboratory has indicated that significant reduction in transformation occurs only when the serum-protein is incorporated into leucocyte cultures at levels above 200 llg/Ml.4 Maximum inhibition was achieved at approximately 400 g/ml, and further additions of the protein caused little change in lymphocyte reactivity. Hence the large range in concentrations that have been found in late pregnancy (872 + 584 ug/ml)s do not rule out its possible role as an immunosuppressive factor. Kasakurawas unable to demonstrate that heat treatment of pregnancy plasma (known to destroy the macroglobulin) altered its ability to reduce transformation in mixed leucocyte cultures. However, the concentration of plasma in his cultures was only 20% v/v, and therefore there was probably too little glycoprotein to produce significant inhibition. Nevertheless, the total non-specific immunosuppressive effect of pregnancy plasma cannot be accounted for by this compound alone,4 and studies7 have indicated that a low-molecular-weight lipid may also be involved. The ability of the x-macroglobulin to inhibit transformation has been investigated. Stimulation of lymphocytes by allogeneic cells, concanavalin A, phytohaemagglutinin, and P.P.D. was reduced by 56%, 57%, 64%, and 51% respectively, when 400 .g/ml glycoprotein was introduced into the cultures. Transformation inhibition
was much less evident, however, with Escherichia coli lipopolysaccharide (16% inhibition) or goat antihuman F(ab’)2 serum (5% inhibition). The former group of agents are often regarded as preferential stimulators of T lymphocytes, whereas the lipopolysaccharide and antiserum may selectively stimulate B cells.9 Perhaps the suppressive properties of this pregnancy-associated protein are directed primarily against the cell-mediated immune response. Reduced lymphocyte reactivity has been demonstrated in women receiving contraceptive steroids9 and in patients with cancer.lo The level of the glycoprotein is raised in both these groups,"but it is generally lower than in pregnancy.
Department of Biochemistry, University of Strathclyde, 204
George Street, Glasgow G1 1XW.
W. H. STIMSON
1. Stimson, W. H. Lancet, 1972, i, 684. 2. Von Schoultz, B., Stigbrand, T., Tärnvik, A. FEBS Lett. 1973, 38, 23. 3. Than, G. N., Csaba, I. F., Szabó, D. G., Paál, M., Ambrus, M, Bajtai, G. IRCS med. Sci. 1975, 3, 309. 4. Stimson, W. H. Behring Inst. Mitt. 1975, 57, 42 5. Stimson, W. H.J. Reprod. Fert. 1975, 43, 579. 6. Kasakura, S. Nature, 1973, 246, 496. 7. Stimson, W. H., Blackstock, J. C. Behring Inst. Mut. 1975, 57, 92. 8. Dimitrui, A., Dy, M., Thomson, N., Bona, C. Clin. exp. Immun 1974, 18,
141. 9. Davis, J. C., Hipkm, L. J. Lancet, 1974, ii, 217. 10. Robinson, E., Sher, S., Mekori, T. Cancer Res. 1974, 11. Stimson, W. H. Lancet, 1975, i, 777.
34, 1548.
In
short, our ultimate aim is
Royal Marsden Hospital, Downs Road, Sutton, Surrev
been considered presumptuous by some who believe that it prophesies a course of events which need not necessarily occur.
Meanwhile, there
are
patients
in whom the
H. MACD. CLINK I. D. C. DOUGLAS
SIR,-Dr Burge and his colleagues state: "Until a major advance in treatment of acute myeloid leukaemia occurs, treatment should be limited ...". No advance, either major or minor, in the treatment of acute myeloid leukaemia, or any other disease, occurs spontaneously. Intellectual, experimental, and clinical work are needed to secure advance. of Haematology, Hospital,
St. Orsola University 40138 Bologna, Italy.
MICHELE BACCARANI
THYROID FUNCTION AFTER TREATMENT OF HYPERTHYROIDISM
StR,—!t is only two years since Dr Toft, Dr Irvine, and their colleagues’ believed that the plasma-thyroid-stimulatinghormone (T.S.H.) level could not be used as an indication of impending overt hypothyroidism. My colleagues and J2 found their conclusion surprising, and it is a pleasure to find a different message in their recent interesting paper (Sept. 27, p. 576). After studying their patients for a longer time, they now conclude that those with a normal plasma-T.s.H. need not be seen so often as those similarly treated euthyroid patients with a raised plasma-T.s.H. Your leading article on the same subject (p. 590) ends with an exhortation to follow patients "carefully and clinically, or check for binding abnormalities or seek specialist advice." It is surprising that Dr Toft and his colleagues and your leader are concerned with a routine follow-up of these patients since you do not appear to believe that any hazard exists while the patients are clinically euthyroid with normal plasma-thyroid-hormone levels, although they have a raised plasma-T.s.H. If a raised plasma-T.s.H. level is a simple re-adjustment of the pituitary/thyroid axis with no clinical significance, the patients could be told to report if symptoms occurred. A simple routine test of thyroid function, such as measurement of the ankle reflex, could be done to confirm objectively the diagnosis of myxmdema before starting life-long replacement treatment. This would eliminate work in the outpatient and biochemical departments. Richard Asher often said that nothing appears to achieve existence until it is labelled and that a condition springs into being as soon as a name is given to it. We believe3 that a clearcut condition affecting patients does exist and has the following five criteria: (11 The patients are clinically euthyroid. (2) Plasma-thyroid-hormone levels are normal. ...
(3) Thyroid disease is present-usually autoimmune thyroiditis indicated by the presence of thyroid antibodies, or previous partial thyroid ablaton by irradiation or surgery. (4) The basal plasma-T.s.H. level is raised or there is an exaggerated response to thyrotrophin-releasing hormones. 3i Plasma-lipids are often raised, and this change is associated with degenerative arterial disease.
Evered and his colleagues4 call this condition subclinical hypothyroidism and do not include the fifth criterion, which is certainly not a constant finding. However, the condition is neither subclinical nor hypothyroid and had already been called premyxoedema in 1967.5 The term premyxoedema has 1 Toft, A. D., Barnes, E. W., Hunter, W. M., Seth, J., Irvine, W. J Lancet, 1973, ii, 644. 2 Fowler, P. B. S., Ikram, H., Banim, S ibid. p. 801. 3 Ikram, H , Banim, S., Fowler, P. B. S. ibid p. 1405. 4 Evered, D., Ormston, B. J., Smith, P. A., Hall, R., Bird, T. Br. med.J. 1973, 1,657 Fowler, P. B. S., Swale, J. Lancet, 1967, i, 1077.
of
generally acceptable name so that it can be known to exist. Charing Cross Hospital, London W6 8RF.
Division
development
coronary-artery disease may be preventable, and I make a plea that the condition from which they suffer should be given a
P. B. S. FOWLER
IMMUNOSUPPRESSIVE EFFECT OF PREGNANCY-ASSOCIATED
ALPHA2-MACROGLOBULIN SIR,-The non-specific suppressive properties of pregnancyassociated -macroglobulin/2-glycoprotein (P.A.M.) have been shown by several in-vitro methods of immunological assessment, 1-4 Dr Than and his colleagues (Sept. 13, p. 515) reported that the glycoprotein, at concentrations below 130 .g/ml, can cause considerable reductions in lymphocyte proliferation initiated by allogeneic cells or phytohaemagglutinin. However, work in this laboratory has indicated that significant reduction in transformation occurs only when the serum-protein is incorporated into leucocyte cultures at levels above 200 llg/Ml.4 Maximum inhibition was achieved at approximately 400 g/ml, and further additions of the protein caused little change in lymphocyte reactivity. Hence the large range in concentrations that have been found in late pregnancy (872 + 584 ug/ml)s do not rule out its possible role as an immunosuppressive factor. Kasakurawas unable to demonstrate that heat treatment of pregnancy plasma (known to destroy the macroglobulin) altered its ability to reduce transformation in mixed leucocyte cultures. However, the concentration of plasma in his cultures was only 20% v/v, and therefore there was probably too little glycoprotein to produce significant inhibition. Nevertheless, the total non-specific immunosuppressive effect of pregnancy plasma cannot be accounted for by this compound alone,4 and studies7 have indicated that a low-molecular-weight lipid may also be involved. The ability of the x-macroglobulin to inhibit transformation has been investigated. Stimulation of lymphocytes by allogeneic cells, concanavalin A, phytohaemagglutinin, and P.P.D. was reduced by 56%, 57%, 64%, and 51% respectively, when 400 .g/ml glycoprotein was introduced into the cultures. Transformation inhibition
was much less evident, however, with Escherichia coli lipopolysaccharide (16% inhibition) or goat antihuman F(ab’)2 serum (5% inhibition). The former group of agents are often regarded as preferential stimulators of T lymphocytes, whereas the lipopolysaccharide and antiserum may selectively stimulate B cells.9 Perhaps the suppressive properties of this pregnancy-associated protein are directed primarily against the cell-mediated immune response. Reduced lymphocyte reactivity has been demonstrated in women receiving contraceptive steroids9 and in patients with cancer.lo The level of the glycoprotein is raised in both these groups,"but it is generally lower than in pregnancy.
Department of Biochemistry, University of Strathclyde, 204
George Street, Glasgow G1 1XW.
W. H. STIMSON
1. Stimson, W. H. Lancet, 1972, i, 684. 2. Von Schoultz, B., Stigbrand, T., Tärnvik, A. FEBS Lett. 1973, 38, 23. 3. Than, G. N., Csaba, I. F., Szabó, D. G., Paál, M., Ambrus, M, Bajtai, G. IRCS med. Sci. 1975, 3, 309. 4. Stimson, W. H. Behring Inst. Mitt. 1975, 57, 42 5. Stimson, W. H.J. Reprod. Fert. 1975, 43, 579. 6. Kasakura, S. Nature, 1973, 246, 496. 7. Stimson, W. H., Blackstock, J. C. Behring Inst. Mut. 1975, 57, 92. 8. Dimitrui, A., Dy, M., Thomson, N., Bona, C. Clin. exp. Immun 1974, 18,
141. 9. Davis, J. C., Hipkm, L. J. Lancet, 1974, ii, 217. 10. Robinson, E., Sher, S., Mekori, T. Cancer Res. 1974, 11. Stimson, W. H. Lancet, 1975, i, 777.
34, 1548.
