- Email: [email protected]
LOW-DOSE RADIATION
840 such a period will be found only in schools with "the wisdom and courage" to provide it. Sir George reported only one but, as his correction (Sept 2., p. 513) and Professor Greenfield’s letter (Sept 16., p. 630) happily show, Nottingham is also in that category. That means that in one most important respect the situation was twice as good as Sir George first thoughtbut that is not good enough. As one whose responsibility for medical education exceeds his authority over it, I share Jacobson’s view that those "in control of today’s medical education should listen more", and listen to more of the recipients, but I am not happy with his suggestion that they should talk less. Once every ten years is not very often, perhaps not often
thrombus formation 15 leading to the occlusion of vascular grafts16 are not due to diminished prostacyclin formation. The pany,
P.G.I2
was
kindly supplied by
Dr
John E. Pike, Upjohn Com-
Kalamazoo, Michigan.
Atherosclerosis Reasearch at
Group Department of Physiology;
Atherosclerosis and Thrombosis Research Commission, Austrian Academy of Science; 2nd Department of Internal Medicine 1st Department of Surgery,
University of Vienna, A-1090 Vienna, Austria
H. SINZINGER K. SILBERBAUER
MAYA WINTER W. AUERSWALD
enough. London Hospital Medical London E1 2AD
LOW-DOSE RADIATION
College,
JOHN ELLIS
IMPLANTED VASCULAR PROSTHESES GENERATE PROSTACYCLIN
SIR,-Moncada and colleagues’have demonstrated that vascular tissue produces the potent platelet-aggregation inhibiting agent prostacyclin (P.G.Iz) in vitro. Parietal thrombus formation3and occlusionoften complicate vascular prosthetic implants in mans and animals.6 Could this be due to defective P .G.Iz formation in the cells grown in the vascular hub? We have studied eight ’Dacron’ vascular prosthetic grafts implanted from 6 weeks up to 4 months in human iliac artery. Control arterial tissue was obtained from the anastomosing area. The tissue was tested for prostacyclin activity8 and controlled morphologically. p.G.I2 activity was expressed in pg/mg tissue wet weight/min. After bioassay the dacron grafts were digested, the tissue grown into the vascular hub was removed, and the weight of the remaining synthetic material was estimated. The total weight (i.e., the weight of the tissue and the dacron) was calculated.
The human arteries generated 7.0+2.5 pg/mg P.G.Il. Incubation of the arterial tissue in platelet-rich plasma significantly enhanced p.G.Information. Prostacyclin generation of dacron graft (5.5±2.5pg/mg) was not significantly different. After endothelial desquamation the values were in the same relation. The substance liberated had the properties of prostacyclin.9-11 Thus the newly formed tissue around vascular prosthetic grafts implanted in man can generate prostacyclin, as we have found in rabbits. 12 P.G.Information between newly formed arterial wall is comparable with that produced by arteries, and the percentage of’ P.G.I generated between the layers of the vascular wall and the newly built pseudolayers of the graft are comparable too. P.G.I2 formation shows no clear-cut relation with implantationtime. Our results demonstrate that the graft cells derived from the bloodstream" generate prostacyclin in amounts which are not different from those of the vascular wall. The high thrombogeniCityl4 and frequency of parietal 1. Moncada, S., Higgs, E. A., Vane, J. R. Lancet, 1977, i, 18. 2. Moncada, S., Vane, J. R., Whittle, B. J. R. J. Physiol. 1977, 273, 20. 3. Marshall, M., Lisson, G. Vasa, 1976, 5, 122. 4. Wesolowski, S. A.: Evaluation of tissue and prosthetic vascular grafts. Ch. C. Thomas, Springfield, Illinois 1962. 5. Vollmar, J. Blood Vessels, Springer 1976, 113. 6. Eiken, O. Acta chir. scand. 1961, 121, 398. 7. Moncada, S., Herman, A. G., Higgs, E. A., Vane, J. R. Thromb. Res. 1977,
8. 9.
11, 323. Silberbauer, K., Sinzinger, H., Winter, M. Lancet, 1978, i, 1356. Moncada, S., Gryglewski, R., Bunting, S., Vane, J. R. Nature, 1976, 263, 663.
Sinzinger, H., Silberbauer, K., Wagner, O., Winter, M., Auerswald, W. Atherogenese, 1978, 3, 123. 11. Remuzzi, G., Cavenaghi, A. G., Mecca, G., Donati, M. B., DeGaetano, G.
SIR,-May I comment on the letter from Dr Stewart.’ I designed and developed the Hanford study and compiled the data from 1964 to 1976, when I was summarily dismissed. Dr Stewart and Mr Kneale came in mid-1976. They first tried to discredit my findings, of no evidence, so far, for harmful effects from low-level radiation, by alleging irregularities in the data. Failing to prove these allegations, they found, as I had shown, that there were a few types of cancer in which the "exposed" employee deaths were proportionately higher. They used these to support the conclusion of radiation-induced cancer deaths. Yet the same data revealed other types of cancers with significantly lower incidence and lower mean radiation dose, suggesting random associations, as I had demonstrated in Hanford employees with no record of occupational radiation, in siblings of Hanford employees, and in other controls who never worked in an atomic plant, where there were similar excesses and deficiencies. The table in Stewart’s letter is inaccurate: "Over 2 yr" should be 2+ yr, and the average dose for all cancer deaths (235centirad) cannot be larger than that for deaths among the "exposed" (226 centirad). The errors seem more serious than the mere switching of the two means. In column 2, in the under 2 yr group, the percentage of cancer deaths is 37.5 and non-cancer deaths 34-9 among the "exposed", an excess of 7-4. In the 2+ yr group these percentages are 88.5 and 86.7, an excess of only 2.1 1 Since the cumulative dose level will increase with years of employment the disparity should have got bigger, not smaller, if exposure to radiation induced cancer deaths. Analysts such as Anderson,’- have demonstrated other deficiencies in the Mancuso analysis, of which Stewart’s letter is a sequel. Gilbert’s analysis,3 based on the same data as those used by Mancuso et al., revealed no evidence of cancer deaths among Hanford employees attributable to occupational radiation :
*Expected deaths are calculated from age and calendar year specific U.S. mortality-rates for White males, 1945-67. s.M.R.=standardised mortality ratio. The comparison shows lower mortality from cancer among Hanford employees. Among the "2+ yr" group of employees
10.
Lancet, 1977, i, 1195. 12. Sinzinger, H., Piza-Katzer, H., Silberbauer, K., Winter, M. Int. Congr. Angiol. Prag. 1978, (in press). 13. O’Neal, R. M., Jordan, G. L., Robin, E. R., DeBakey, M. E., Halpert, B. Exp. Molec. Pathol. 1964, 3, 403. 14. Kim, S. W., Lee, R. G., Oster, H., Coleman, D., Andrade, J. D., Lentz, D. J., Olsen, D. Trans. Amer. Soc. Artif. Int. Org. 1974, 20, 449.
15. Bruck, S. Blood Vessels, Springer 1976, 117. 16. Yates, S. G., Nahagawa, Y., Berger, K., Sauvage, L. R. Surgery, 1973, 136, 12. 1. Stewart, A. M. Lancet, 1978, i, 1048. 2. Anderson, T. W. Hlth Phys. (in the press). 3. Gilbert, E. S. Testimony before the U.S. House of Representatives Committee on Interstate and Foreign Commerce, Subcommittee on Health and Environment. Washington D.C. February, 1978.
841 with rate
higher levels of occupational radiation, the cancer death is, if anything, lower than among those under 2 yr; but
the death-rate from
is much lower. In a proet al. and Dr Milham earlier, this virtue becomes a fault, showing a higher proportionate death-rate from cancer in this 2+ yr group compared with the under 2 yr group. My analyses have demonstrated the higher longevity of "exposed" Hanford employees vis-à-vis the "non-exposed" Hanford employees and all the other controls. An illustration of this is the comparative longevity of exposed and nonexposed employees with that of their siblings, the sibling nearest in age to the employee. These siblings did not work in an non-cancer causes
portionate analysis used by
Mancuso
groups would be reversed. According to Dr Gilbert, whose figures are cited by Dr Sanders, it was only among Hanford workers who were employed for more than 2 years that the S.M.R. was appreciably higher for cancers (85) than noncancers (75). Therefore, of the two explanations, the second is the more plausible. Regional Cancer Registry, Queen Elizabeth Medical Centre, Birmingham B15 2TH.
ALICE M. STEWART
CREATINE KINASE MB
atomic plant:
SIR,-In your editorial
on creatine kinase MB (MB c.K.) in brain injury (Sept. 23, p. 668) you ask, in passing, whether measurement of the enzyme adds much to the investigation of myocardial infarction. There are two important reasons for adopting this measurement, one partly theoretical and partly practical, the other highly practical. The theoretical reason is that a diagnosis may be made with greater certainty where there is a specific test for a particular condition. MB c.K. is specific to heart muscle; the other enzymes, such as aspartate transaminase, hydroxybutrate dehydrogenase, and total creatine kinase are released from a variety of tissues in a variety of conditions, several of which, such as gallbladder disease and pulmonary embolus, may present in much the same way as myocardial infarction. The wholly practical reason for adopting routine measurement of MB C.K. is that, because of its specificity, it allows the diagnosis of myocardial infarction to be made or refuted in cases where electrocardiographic changes are equivocal. In Eastbourne we have been studying the use of MB C.K. for a year. During this time the enzyme has been serially measured every 4 h in 119 consecutive patients suspected of having had an acute myocardial infarction. In 12 of these (10%) changes in the E.c.G. were equivocal or difficult to interpret. However, a confident diagnosis of myocardial infarction was made in every case by referring to the MB c.K. values. In 5 of these the E.c.G. showed left-bundle-branch block, in 3 the infarct seemed to have occurred at the site of a previous infarct, and in 4 the changes in the E.C.G. were of a minor nature. We have no doubts about the usefulness of measuring MB C.K.
acute
*The comparison is restricted to employee-sibling pairs in which or both members died between the date of employee’s hire and the off date (Oct. 1, 1972) .4
one
cut-
The comparison (besides much other evidence, including age-adjusted disability claim-rates) is compatible with the conclusion of radiation-induced cancer deaths-particularly lowlevel radiation. The Mancuso report fails to indicate limitations in the data, particularly with respect to the reliability and completeness of cumulative lifetime radiation dose, the fulcrum of the analysis and conclusion. We know that the recorded cumulative radiation dose for Hanford employees is incomplete, but not how incomplete. I designed studies to indicate the extent of this incompleteness, but these were not acted upon. The recorded cumulative lifetime dose should not be treated as meaningful quantitative data. This and other deficiencies were set out in a letter I wrote to Dr Mancuso in February, 1976 (and this letter was made available to Dr Stewart), but none of these deficiencies were touched upon in the 1977 Health Physics paper by Mancuso, Stewart, and Kneale. 5823 Soledad Rd. La Jolla, California 92037, U.S.A.
***This letter has been shown lows.-ED.L.
BARKEV S. SANDERS
to
SIR,-Iapologise for
Dr
4.
Sanders, B. S. Hlth. Phys. (in the press).
D. G. MODEL
Stewart, whose reply fol-
not detecting a typist’s error which led the average dose for exposed workers appearing in my letter as 226 centirads when the correct figure was 266. The nuclear industry is largely manned by workers who have passed pre-employment health tests, and even the more dangerous occupations are remarkably safe compared with other industries. Therefore, it is hardly surprising that Hanford workers have relatively low rates of general mortality. What is less easy to explain is why the gap between observed and expected deaths has always been narrower for cancers than other causes of death. This difference could be due to incipient cancers being harder to detect than other conditions which render workers unsuitable for employment in the industry (selective recruitment effect). Alternatively, it could be due to small doses of radiation having a cancer effect which is difficult to detect unless competing causes of death are reduced to a minimum (dose-response effect). In the first situation short-term workers would be more affected than long-term workers, and in the second situation the position of the two
to
District General Hospital, Eastbourne, East Sussex BN21 2UD
MIGRAINE: A BLOOD DISORDER?
SiR,—Iread with great interest Dr Hanington’s hypothesis (Sept. 2, p. 501) and would like to add the following comment. Tricyclic antidepressants, which are occasionally effective in migraine prophylaxis,’ are also weak monoamine-oxidase (M.A.O.) inhibitors.2 M.A.O. inhibitors are also reported to be effective in migraine.3 Lithium carbonate may be of benefit in the treatment and prophylaxis of chronic cluster headaches,4,5 and lithium increases human platelet M.A.o. activity.6 Drugs which either inhibit or enhance M.A.O. activity may have in common some form of stabilisation of mitochondrial M.A.O. The platelet abnormality in migraine which Hanington proposes could be, or include, abnormal M.A.O. activity. In view of the association between idiopathic thrombocytopenic purpura and migraine,7 it is also possible that lithium or antiCouch, J. R., Ziegler, D. K., Hassanien, R. S. Trans Am. Neurol. Ass. 1974, 99, 94. 2. Sullivan, J. L., Dackis, C., Stanfield, C Am. J. Psychiat. 1977, 134, 188. 3 Anthony, M., Lance, J W. Archs Neurol. 1969, 21, 263. 4. Lieb, J., Zeff, A. Br. J. Psychiat (in the press). 5. Kudrow, L., Headache, 1977, 17, 15. 6 Bockar, J., Roth, R , Heninger, G. Life Sci. 1974, 15, 2109. 7. Damasio, H., Beck, D., Lancet, 1978, i, 240. 1.
thrombus formation 15 leading to the occlusion of vascular grafts16 are not due to diminished prostacyclin formation. The pany,
P.G.I2
was
kindly supplied by
Dr
John E. Pike, Upjohn Com-
Kalamazoo, Michigan.
Atherosclerosis Reasearch at
Group Department of Physiology;
Atherosclerosis and Thrombosis Research Commission, Austrian Academy of Science; 2nd Department of Internal Medicine 1st Department of Surgery,
University of Vienna, A-1090 Vienna, Austria
H. SINZINGER K. SILBERBAUER
MAYA WINTER W. AUERSWALD
enough. London Hospital Medical London E1 2AD
LOW-DOSE RADIATION
College,
JOHN ELLIS
IMPLANTED VASCULAR PROSTHESES GENERATE PROSTACYCLIN
SIR,-Moncada and colleagues’have demonstrated that vascular tissue produces the potent platelet-aggregation inhibiting agent prostacyclin (P.G.Iz) in vitro. Parietal thrombus formation3and occlusionoften complicate vascular prosthetic implants in mans and animals.6 Could this be due to defective P .G.Iz formation in the cells grown in the vascular hub? We have studied eight ’Dacron’ vascular prosthetic grafts implanted from 6 weeks up to 4 months in human iliac artery. Control arterial tissue was obtained from the anastomosing area. The tissue was tested for prostacyclin activity8 and controlled morphologically. p.G.I2 activity was expressed in pg/mg tissue wet weight/min. After bioassay the dacron grafts were digested, the tissue grown into the vascular hub was removed, and the weight of the remaining synthetic material was estimated. The total weight (i.e., the weight of the tissue and the dacron) was calculated.
The human arteries generated 7.0+2.5 pg/mg P.G.Il. Incubation of the arterial tissue in platelet-rich plasma significantly enhanced p.G.Information. Prostacyclin generation of dacron graft (5.5±2.5pg/mg) was not significantly different. After endothelial desquamation the values were in the same relation. The substance liberated had the properties of prostacyclin.9-11 Thus the newly formed tissue around vascular prosthetic grafts implanted in man can generate prostacyclin, as we have found in rabbits. 12 P.G.Information between newly formed arterial wall is comparable with that produced by arteries, and the percentage of’ P.G.I generated between the layers of the vascular wall and the newly built pseudolayers of the graft are comparable too. P.G.I2 formation shows no clear-cut relation with implantationtime. Our results demonstrate that the graft cells derived from the bloodstream" generate prostacyclin in amounts which are not different from those of the vascular wall. The high thrombogeniCityl4 and frequency of parietal 1. Moncada, S., Higgs, E. A., Vane, J. R. Lancet, 1977, i, 18. 2. Moncada, S., Vane, J. R., Whittle, B. J. R. J. Physiol. 1977, 273, 20. 3. Marshall, M., Lisson, G. Vasa, 1976, 5, 122. 4. Wesolowski, S. A.: Evaluation of tissue and prosthetic vascular grafts. Ch. C. Thomas, Springfield, Illinois 1962. 5. Vollmar, J. Blood Vessels, Springer 1976, 113. 6. Eiken, O. Acta chir. scand. 1961, 121, 398. 7. Moncada, S., Herman, A. G., Higgs, E. A., Vane, J. R. Thromb. Res. 1977,
8. 9.
11, 323. Silberbauer, K., Sinzinger, H., Winter, M. Lancet, 1978, i, 1356. Moncada, S., Gryglewski, R., Bunting, S., Vane, J. R. Nature, 1976, 263, 663.
Sinzinger, H., Silberbauer, K., Wagner, O., Winter, M., Auerswald, W. Atherogenese, 1978, 3, 123. 11. Remuzzi, G., Cavenaghi, A. G., Mecca, G., Donati, M. B., DeGaetano, G.
SIR,-May I comment on the letter from Dr Stewart.’ I designed and developed the Hanford study and compiled the data from 1964 to 1976, when I was summarily dismissed. Dr Stewart and Mr Kneale came in mid-1976. They first tried to discredit my findings, of no evidence, so far, for harmful effects from low-level radiation, by alleging irregularities in the data. Failing to prove these allegations, they found, as I had shown, that there were a few types of cancer in which the "exposed" employee deaths were proportionately higher. They used these to support the conclusion of radiation-induced cancer deaths. Yet the same data revealed other types of cancers with significantly lower incidence and lower mean radiation dose, suggesting random associations, as I had demonstrated in Hanford employees with no record of occupational radiation, in siblings of Hanford employees, and in other controls who never worked in an atomic plant, where there were similar excesses and deficiencies. The table in Stewart’s letter is inaccurate: "Over 2 yr" should be 2+ yr, and the average dose for all cancer deaths (235centirad) cannot be larger than that for deaths among the "exposed" (226 centirad). The errors seem more serious than the mere switching of the two means. In column 2, in the under 2 yr group, the percentage of cancer deaths is 37.5 and non-cancer deaths 34-9 among the "exposed", an excess of 7-4. In the 2+ yr group these percentages are 88.5 and 86.7, an excess of only 2.1 1 Since the cumulative dose level will increase with years of employment the disparity should have got bigger, not smaller, if exposure to radiation induced cancer deaths. Analysts such as Anderson,’- have demonstrated other deficiencies in the Mancuso analysis, of which Stewart’s letter is a sequel. Gilbert’s analysis,3 based on the same data as those used by Mancuso et al., revealed no evidence of cancer deaths among Hanford employees attributable to occupational radiation :
*Expected deaths are calculated from age and calendar year specific U.S. mortality-rates for White males, 1945-67. s.M.R.=standardised mortality ratio. The comparison shows lower mortality from cancer among Hanford employees. Among the "2+ yr" group of employees
10.
Lancet, 1977, i, 1195. 12. Sinzinger, H., Piza-Katzer, H., Silberbauer, K., Winter, M. Int. Congr. Angiol. Prag. 1978, (in press). 13. O’Neal, R. M., Jordan, G. L., Robin, E. R., DeBakey, M. E., Halpert, B. Exp. Molec. Pathol. 1964, 3, 403. 14. Kim, S. W., Lee, R. G., Oster, H., Coleman, D., Andrade, J. D., Lentz, D. J., Olsen, D. Trans. Amer. Soc. Artif. Int. Org. 1974, 20, 449.
15. Bruck, S. Blood Vessels, Springer 1976, 117. 16. Yates, S. G., Nahagawa, Y., Berger, K., Sauvage, L. R. Surgery, 1973, 136, 12. 1. Stewart, A. M. Lancet, 1978, i, 1048. 2. Anderson, T. W. Hlth Phys. (in the press). 3. Gilbert, E. S. Testimony before the U.S. House of Representatives Committee on Interstate and Foreign Commerce, Subcommittee on Health and Environment. Washington D.C. February, 1978.
841 with rate
higher levels of occupational radiation, the cancer death is, if anything, lower than among those under 2 yr; but
the death-rate from
is much lower. In a proet al. and Dr Milham earlier, this virtue becomes a fault, showing a higher proportionate death-rate from cancer in this 2+ yr group compared with the under 2 yr group. My analyses have demonstrated the higher longevity of "exposed" Hanford employees vis-à-vis the "non-exposed" Hanford employees and all the other controls. An illustration of this is the comparative longevity of exposed and nonexposed employees with that of their siblings, the sibling nearest in age to the employee. These siblings did not work in an non-cancer causes
portionate analysis used by
Mancuso
groups would be reversed. According to Dr Gilbert, whose figures are cited by Dr Sanders, it was only among Hanford workers who were employed for more than 2 years that the S.M.R. was appreciably higher for cancers (85) than noncancers (75). Therefore, of the two explanations, the second is the more plausible. Regional Cancer Registry, Queen Elizabeth Medical Centre, Birmingham B15 2TH.
ALICE M. STEWART
CREATINE KINASE MB
atomic plant:
SIR,-In your editorial
on creatine kinase MB (MB c.K.) in brain injury (Sept. 23, p. 668) you ask, in passing, whether measurement of the enzyme adds much to the investigation of myocardial infarction. There are two important reasons for adopting this measurement, one partly theoretical and partly practical, the other highly practical. The theoretical reason is that a diagnosis may be made with greater certainty where there is a specific test for a particular condition. MB c.K. is specific to heart muscle; the other enzymes, such as aspartate transaminase, hydroxybutrate dehydrogenase, and total creatine kinase are released from a variety of tissues in a variety of conditions, several of which, such as gallbladder disease and pulmonary embolus, may present in much the same way as myocardial infarction. The wholly practical reason for adopting routine measurement of MB C.K. is that, because of its specificity, it allows the diagnosis of myocardial infarction to be made or refuted in cases where electrocardiographic changes are equivocal. In Eastbourne we have been studying the use of MB C.K. for a year. During this time the enzyme has been serially measured every 4 h in 119 consecutive patients suspected of having had an acute myocardial infarction. In 12 of these (10%) changes in the E.c.G. were equivocal or difficult to interpret. However, a confident diagnosis of myocardial infarction was made in every case by referring to the MB c.K. values. In 5 of these the E.c.G. showed left-bundle-branch block, in 3 the infarct seemed to have occurred at the site of a previous infarct, and in 4 the changes in the E.C.G. were of a minor nature. We have no doubts about the usefulness of measuring MB C.K.
acute
*The comparison is restricted to employee-sibling pairs in which or both members died between the date of employee’s hire and the off date (Oct. 1, 1972) .4
one
cut-
The comparison (besides much other evidence, including age-adjusted disability claim-rates) is compatible with the conclusion of radiation-induced cancer deaths-particularly lowlevel radiation. The Mancuso report fails to indicate limitations in the data, particularly with respect to the reliability and completeness of cumulative lifetime radiation dose, the fulcrum of the analysis and conclusion. We know that the recorded cumulative radiation dose for Hanford employees is incomplete, but not how incomplete. I designed studies to indicate the extent of this incompleteness, but these were not acted upon. The recorded cumulative lifetime dose should not be treated as meaningful quantitative data. This and other deficiencies were set out in a letter I wrote to Dr Mancuso in February, 1976 (and this letter was made available to Dr Stewart), but none of these deficiencies were touched upon in the 1977 Health Physics paper by Mancuso, Stewart, and Kneale. 5823 Soledad Rd. La Jolla, California 92037, U.S.A.
***This letter has been shown lows.-ED.L.
BARKEV S. SANDERS
to
SIR,-Iapologise for
Dr
4.
Sanders, B. S. Hlth. Phys. (in the press).
D. G. MODEL
Stewart, whose reply fol-
not detecting a typist’s error which led the average dose for exposed workers appearing in my letter as 226 centirads when the correct figure was 266. The nuclear industry is largely manned by workers who have passed pre-employment health tests, and even the more dangerous occupations are remarkably safe compared with other industries. Therefore, it is hardly surprising that Hanford workers have relatively low rates of general mortality. What is less easy to explain is why the gap between observed and expected deaths has always been narrower for cancers than other causes of death. This difference could be due to incipient cancers being harder to detect than other conditions which render workers unsuitable for employment in the industry (selective recruitment effect). Alternatively, it could be due to small doses of radiation having a cancer effect which is difficult to detect unless competing causes of death are reduced to a minimum (dose-response effect). In the first situation short-term workers would be more affected than long-term workers, and in the second situation the position of the two
to
District General Hospital, Eastbourne, East Sussex BN21 2UD
MIGRAINE: A BLOOD DISORDER?
SiR,—Iread with great interest Dr Hanington’s hypothesis (Sept. 2, p. 501) and would like to add the following comment. Tricyclic antidepressants, which are occasionally effective in migraine prophylaxis,’ are also weak monoamine-oxidase (M.A.O.) inhibitors.2 M.A.O. inhibitors are also reported to be effective in migraine.3 Lithium carbonate may be of benefit in the treatment and prophylaxis of chronic cluster headaches,4,5 and lithium increases human platelet M.A.o. activity.6 Drugs which either inhibit or enhance M.A.O. activity may have in common some form of stabilisation of mitochondrial M.A.O. The platelet abnormality in migraine which Hanington proposes could be, or include, abnormal M.A.O. activity. In view of the association between idiopathic thrombocytopenic purpura and migraine,7 it is also possible that lithium or antiCouch, J. R., Ziegler, D. K., Hassanien, R. S. Trans Am. Neurol. Ass. 1974, 99, 94. 2. Sullivan, J. L., Dackis, C., Stanfield, C Am. J. Psychiat. 1977, 134, 188. 3 Anthony, M., Lance, J W. Archs Neurol. 1969, 21, 263. 4. Lieb, J., Zeff, A. Br. J. Psychiat (in the press). 5. Kudrow, L., Headache, 1977, 17, 15. 6 Bockar, J., Roth, R , Heninger, G. Life Sci. 1974, 15, 2109. 7. Damasio, H., Beck, D., Lancet, 1978, i, 240. 1.