604 GLYCINE IN ACKEE POISONING
SIR,-Dr Tanaka’s comments’ prompted by our suggestion that administration of large amounts of glycine may be of value in human ackee poisoning,2 miss the point. It was not practicable in a short letter to review her earlier work,34nor to discuss in detail the relationships between the concentrations of unusual metabolites in plasma and urine and their effects in ackee poisoning in different spepharmacological cites. 56 It is believed that methylenecyclopropylacetyl-coenzyme A (M.c.P.A.-CoA), formed by the metabolism of hypoglycin (the toxic principle of the ackee fruit), irreversibly inhibits butyrylCoA and isovaleryl-CoA dehydrogenases,7-’J and possibly some other enzymes,’ and that the profound and varied metabolic disturbances in ackee poisoning are consequences of these pri9 6 One pathway for removal of mary inhibitions.5 M.c.p.A.-CoA in rats is conjugation with glycine to give M.c.p.A.-glycine.45 This reaction is probably catalysed by glycine N-acylase which has a very low affinity for glycine (reported Km values of 3-3or 15 mmol/1 for the beef liver enzyme’O 11). Therefore, it was a reasonable prediction that artificially boosting tissue concentrations of glycine would increase the rate of removal of M.C.P.A.-CoA and hence lessen the toxic effects.2 This worked in rats.:1 The fact that smaller concentrations of isovaleric acid and isovalerylglycine are found in human ackee poisoning than in poisoned rats4-6 does not detract from the idea that administration of glycine may also be effective in man; perhaps this treatment would give detectable amounts of M.c.p.A.-glycine in human urine. Indeed, Kreiger and Tanaka speculated that human glycine N-acylase has similar properties to the rat enzyme.12 We were pleased to learn that glycine has been used successfully in hereditary isovalericacidaemia,’2 indicating that tissue concentrations of glycine are rate-limiting for conjugation in man; we regret having overlooked this report. Department of Pharmacological Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne NE 1 7RU
H. S. A. SHERRATT S. S. AL-BASSAM
REACTIONS TO CO-TRIMOXAZOLE
SIR,-We would like to report a further case of reaction to co-trimoxazole. Our patient, like Wåhlin and Rosman’s,! had a cutaneous reaction, but she also had a systemic reaction which was reversible. A 66-year-old asthmatic woman on prednisolone had a respiratory infection. After 9 days of treatment with co-trimoxazole (320 mg of trimethoprim and 1600 mg of sulphamethoxazole daily) she had a generalised itching rash. These were discrete areas of erythema, slightly raised. She also had oliguria. When admitted she was pyrexial (40’C) and toxic. She was almost anuric. Blood-urea 45-2 mmol; (271 mg/dl) erythrocyte-sedimentation rate 14 mm/lst h; leucocytes 13 700/{jJ (polymorphs 94%, lymphocytes 6%); moderate albuminuria. The dose of prednisolone was increased. Diuretics were used, maintaining strict fluid balance. A low-protein diet was instituted. 1. Tanaka, K. Lancet, 1977, i, 370. 2. Sherratt, H. S. A., Al-Bassam, S. S. ibid. 1976, ii, 1243. 3. Tanaka, K., Isselbacher, K. J. J. biol. Chem. 1967, 242, 2966. 4. Tanaka, K., Isselbacher, K. J., Shih, V. E. Science, 1972, 175, 69. 5. Tanaka, K. J. biol. Chem. 1972, 247, 7465. 6. Tanaka, K., Kean, E. A., Johnson, B. New Engl. J. Med. 1976, 295, 461. 7. Billington, D., and others. I.R.C.S. (Biochem. Pharmac.) 1974, 2, 1714. 8. Osmundsen, H., Sherratt, H. S. A. FEBS Lett. 1975, 55, 38. 9. Sherratt, H. S. A., Osmundsen, H. Biochem. Pharmac. 1976, 25, 743. 10. Bartlett, K., Gompertz, D. Biochem. Med. 1974, 10, 15. 11. Schacter, D., Taggart, J. V. J. biol. Chem. 1954, 208, 263. 12. Krieger, I., Tanaka, K. Pediat. Res. 1976, 10, 25. 1. Wåhlin, A., Rosman, N. Lancet, 1976, ii, 1415.
Over 6 days the rash faded gradually; she became apyrexial; and her blood-urea fell to 7.3mmol/1 with good diuresis. The patient became clinically well after 10 days and has remained symptom-free since. Creatinine clearance done at this time showed: plasma-creatinine 120 mol/1 (normal 60-125), urine creatinine 71 fLmoV24 h (normal 9-18), clearance 41 ml/min (normal 75-115). When repeated after 12 weeks the figures were plasma-creatinine 105 mol/1, urine creatinine 8.9 )imo)/24 h, clearance 87 ml/min. Neither cutaneous nor renal biopsy was carried out. Cutaneous manifestations due to co-trimoxazole are now well accepted as an allergic reaction, but renal toxicity is controversial. Kalowski et al.2 observed that administration of cotrimoxazole to patients with chronic renal failure produced a deterioration in renal function which was usually reversible. Tasker et al.3 found that an adjusted dose of co-trimoxazole could be used in similar patients without any deterioration, Kalowski et al. were partly supported by Gotloib.4 We conclude that the acute episode described in this patient was due to co-trimoxazole. R. S. RAMAIAH M. A. GALLAGHER Hospital, Llangwyfan Llandyrnog, Clwyd LL16 4ND R. W. BIAGI
TRANSCENDENTAL MEDITATION AND HYPERTENSION
SIR9 Dr Pollack and his colleagues (Jan. 8, p. 71) may have missed an important point which could explain their negative results. They found significant decreases in systolic blood-pressure and pulse-rate in twenty hypertensives in the first three months after learning the transcendental meditation (TM) technique. However, these decreases were not maintained at statistically significant levels by the end of the sixmonth study. A possible reason for this is that the patients may have become irregular in the practice of TM or stopped altogether. Williams et al. demonstrated that the degree to which TMrelated effects accumulated was directly proportional to the frequency of meditation. However, Dr Pollack and his colleagues do not mention this important variable. They state that, while fourteen patients "expressed a strong desire to continue meditating," six apparently wanted to "discontinue" the practice. No data were given on how often the patients meditated, which is normally for twenty minutes in the morning and evening. If these patients did not follow the prescribed routine, the efficacy of the treatment would have been limited and would be reflected in the group means for blood-pressure and pulse-rate as a loss of significant decreases. There were decreases in mean blood-pressure and pulse-rate for months5 and 6, but these were not significant. Full participation (assuming this did not happen) in the TM programme by all participants may have made these decreases significant. It would be interesting to see the data broken down in terms of frequency and regularity of meditation. Patients might have been more irregular in their meditation in the last three months of the study because of the method of meditation training. Personal consultation with the TM teacher was maintained regularly for only the first three months. Continuous contact with the TM teacher might have encouraged a regular pattern of meditation and ensured that the technique was correct. TM teachers acknowledge the value of regular sessions to check technique in ensuring continued participation in a programme. 2.
Kalowski, S., Nanra, R. S., Mathew, T. H., Kincaid-Smith, P. ibid. 1973, i, 394. 3. Tasker, P. R. W., McGregor, G. A., de Wardener, H. E., Thomas, R. D., Jones, N. F. ibid. 1975, i, 1216. 4. Gotloib, L. ibid. 1975, ii, 365. 1. Williams, P., Francis, A., Durham, R. Perceptual Motor Skills, 1976, 43, 787.
605
Plasma-renin-activity was measured before and after the six months of meditation and showed no significant change. These data seem inconclusive; intermediate measurements were not done, and the before-and-after data may again reflect irregularity in the practice of TM. I suggest that future studies of TM should include control for fluctuations in participation which significantly affect the outcome.
branch of the left coronary as the artery of sudden death is not undeserved. But there are reasons for believing that even large branches of the coronary arteries may be occluded - at times acutely - without resulting death, at least without death in the immediate future. Even the main trunk may at times be obstructed and the patient live. It is the object of this paper to present a few facts along this line and particularly to describe some of the clinical manifestations of sudden yet more immediately fatal cases of coronary obstruction".1 of Preventive Medicine and Biostatistics,
Department
Department of Neuroscience, College of Medicine, University of Florida, Gainesville, Florida 32610, U.S.A.
University of Toronto, Toronto, Ontario, Canada
*** This letter has been shown to Dr lows.-ED. L.
SIR,-Mr Bralley wonders if
T. W. ANDERSON
JAMES A. BRALLEY
Pollack, whose reply fol-
patients meditated with the same frequency during the later part of the study as they did at the beginning. If they did not, this would help to explain why the early falls in systolic pressure were not sustained. We went to considerable lengths to encourage our patients to adhere to their twice-daily schedule of meditation, and to the best of our knowledge they did so. Even the minority of patients who intended to discontinue TM at the end of the study maintained, we believe, a high degree of compliance. The question of whether the fall in blood-pressure by the end of study was significant or not hardly seems important. As we pointed out, the mean amplitude of the blood-pressure response in our patients was not greatly different to that reported by Benson et al.’ However, only three of the twenty patients experienced blood-pressure decreases that could be regarded as clinically useful, while in another three patients blood-pressure rose. A more important issue is whether TM can be recommended as a substitute for more conventional treatment. Even using the data obtained by Benson et al., it seems unrealistic to recommend meditation, a technique requiring forty minutes of the patient’s time each day together with regular follow-up visits to a TM teacher, as a standard approach to antihypertensive management. If, as Mr Bralley points out, even enthusiastic participants tend to become less reliable in their use of this technique, routine recommendation of TM seems even less appealing. We did not mean to appear "negative" about TM. As we pointed out, most of our patients subjectively felt a sense of well-being while practising the technique, and this may be useful in enhancing compliance with other forms of treatment. our
Cardiovascular Center, New York Hospital—Cornell Medical Center, New York, N.Y. 10021, U.S.A.
SIR,-You challenge (Jan, 8, p. 80) the classical concept of thrombosis as the cause of myocardial infarction. As you point out, thrombosis is rare in subendocardial infarction and in patients dying suddenly, and it is not always found in transmural infarction-reasons enough for questioning the thrombosis
hypothesis. Since assessing the age of a coronary thrombus by its microscopical appearance is almost impossible when the thrombus is recent, the time-relationship between thrombosis and necrosis has to be studied experimentally. However, there are two important problems: we need a substance that will be incorporated into a forming thrombus, and we need to know whether the myocardial necrosis has started when this substance is injected. A forming thrombus will incorporate radioactively labelled fibrinogen but so, for at least 18 h, will already formed thrombi.’ Therefore, the studies by Erhardt et al. 2and Fulton and Sumner4 must be questioned on the basis of technique. The fact that radioactivity is found in thrombi does not exclude the possibility that they were formed after the necrosis, but it certainly weakens the argument. Deciding the onset of myocardial necrosis is also difficult. Clinically we only have electrocardiography and enzymes. Onset of pain is unreliable because the period of pain before the
onset
of necrosis is variable. The release of enzymes is also
variable,s and the enzymes must be measured frequently to pinpoint the onset of necrosis. The E.c.G. frequently shows characteristic early changes in transmural infarction but these early changes indicate ischaemia and not necrosis. Even if we could accurately decide the onset of necrosis we could not give any substance during the first hours because the patients would not be available. Thus, the early changes in the coronary arteries in acute myocardial infarction in man are very difficult to study. Your views and those of Dr Fulton (Feb. 5, p. 303) and Professor Moore (Feb. 12, p. 367) may not be contradictory since it may very well be that coronary-artery thrombosis in some follows the necrosis and in some cases is the cause of it. To settle the question we need a substance that is incorporated only into a growing thrombus, but not in one already formed. cases
ALBERT A. POLLACK
Department of Medicine, Serafimerlasarettet, S-112 83 Stockholm, Sweden
PLATELETS, LIPIDS, AND MYOCARDIAL
LEIF R. ERHARDT
INFARCTION
SIR,-Your editorial (Jan. 8, p. 80) perpetuates the myth that the concept of coronary thrombosis was introduced by Herrick in 1912.2 In fact, the importance of coronary thrombosis nised at least 20 years earlier:
was
recog-
"The blocking of one of these [coronary] vessels by a thrombus or embolus leads to a condition known as anaemic necrosis or white infarct... In medicolegal cases it is a point of primary importance to remember that this is one of the common causes of sudden death".3 Herrick’s contribution was in demonstrating that coronary
occlusion need not always be fatal: "It 1
must
be admitted, also, that the reputation of the
Benson, H., Rosner,
WILSON’S DISEASE AND CHRONIC ACTIVE HEPATITIS
SIR,-As Dr Archer and Dr Monie (Feb. 26, p. 486) point Wilson’s disease can present as chronic active hepatitis, and it is also true that all children and young adults with subacute or chronic liver damage should be screened as possible cases of Wilson’s disease. At least half of all patients with Wilson’s disease either present as liver damage or give a history out
1. Moschos, C. B., Oldewurtel, H. A., Haider, B.,
descending
B. A., Marzetta, B. R., Klemchuk, H. M. Lancet, 1974, i, 289. 2 Herrick, J. B., J. Am. med. Ass. 1912, 59, 2015. 3 Osler, W. The Principles and Practice of Medicine, Edinburgh, 1892.
Regan, T. J. Circulation, 1976, 54, 653. 2. Erhardt, L. R., Lundman, T., Mellstedt, H. Lancet, 1973, i, 387. 3. Erhardt, L. R., Unge, G., Boman, G. Am. Heart J. 1976, 91, 592. 4. Fulton, W. F. M., Sumner, D. G. Br. Heart J. 1976, 38, 880. 5. Mathey, D., Bleifeld, W., Buss, H., Hanrath, P. ibid. 1975, 37, 1161. 6. Fulton, W. F. M. Lancet, 1977, i, 303. 7. Moore, S. ibid. p. 367.
SIR,-Dr Tanaka’s comments’ prompted by our suggestion that administration of large amounts of glycine may be of value in human ackee poisoning,2 miss the point. It was not practicable in a short letter to review her earlier work,34nor to discuss in detail the relationships between the concentrations of unusual metabolites in plasma and urine and their effects in ackee poisoning in different spepharmacological cites. 56 It is believed that methylenecyclopropylacetyl-coenzyme A (M.c.P.A.-CoA), formed by the metabolism of hypoglycin (the toxic principle of the ackee fruit), irreversibly inhibits butyrylCoA and isovaleryl-CoA dehydrogenases,7-’J and possibly some other enzymes,’ and that the profound and varied metabolic disturbances in ackee poisoning are consequences of these pri9 6 One pathway for removal of mary inhibitions.5 M.c.p.A.-CoA in rats is conjugation with glycine to give M.c.p.A.-glycine.45 This reaction is probably catalysed by glycine N-acylase which has a very low affinity for glycine (reported Km values of 3-3or 15 mmol/1 for the beef liver enzyme’O 11). Therefore, it was a reasonable prediction that artificially boosting tissue concentrations of glycine would increase the rate of removal of M.C.P.A.-CoA and hence lessen the toxic effects.2 This worked in rats.:1 The fact that smaller concentrations of isovaleric acid and isovalerylglycine are found in human ackee poisoning than in poisoned rats4-6 does not detract from the idea that administration of glycine may also be effective in man; perhaps this treatment would give detectable amounts of M.c.p.A.-glycine in human urine. Indeed, Kreiger and Tanaka speculated that human glycine N-acylase has similar properties to the rat enzyme.12 We were pleased to learn that glycine has been used successfully in hereditary isovalericacidaemia,’2 indicating that tissue concentrations of glycine are rate-limiting for conjugation in man; we regret having overlooked this report. Department of Pharmacological Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne NE 1 7RU
H. S. A. SHERRATT S. S. AL-BASSAM
REACTIONS TO CO-TRIMOXAZOLE
SIR,-We would like to report a further case of reaction to co-trimoxazole. Our patient, like Wåhlin and Rosman’s,! had a cutaneous reaction, but she also had a systemic reaction which was reversible. A 66-year-old asthmatic woman on prednisolone had a respiratory infection. After 9 days of treatment with co-trimoxazole (320 mg of trimethoprim and 1600 mg of sulphamethoxazole daily) she had a generalised itching rash. These were discrete areas of erythema, slightly raised. She also had oliguria. When admitted she was pyrexial (40’C) and toxic. She was almost anuric. Blood-urea 45-2 mmol; (271 mg/dl) erythrocyte-sedimentation rate 14 mm/lst h; leucocytes 13 700/{jJ (polymorphs 94%, lymphocytes 6%); moderate albuminuria. The dose of prednisolone was increased. Diuretics were used, maintaining strict fluid balance. A low-protein diet was instituted. 1. Tanaka, K. Lancet, 1977, i, 370. 2. Sherratt, H. S. A., Al-Bassam, S. S. ibid. 1976, ii, 1243. 3. Tanaka, K., Isselbacher, K. J. J. biol. Chem. 1967, 242, 2966. 4. Tanaka, K., Isselbacher, K. J., Shih, V. E. Science, 1972, 175, 69. 5. Tanaka, K. J. biol. Chem. 1972, 247, 7465. 6. Tanaka, K., Kean, E. A., Johnson, B. New Engl. J. Med. 1976, 295, 461. 7. Billington, D., and others. I.R.C.S. (Biochem. Pharmac.) 1974, 2, 1714. 8. Osmundsen, H., Sherratt, H. S. A. FEBS Lett. 1975, 55, 38. 9. Sherratt, H. S. A., Osmundsen, H. Biochem. Pharmac. 1976, 25, 743. 10. Bartlett, K., Gompertz, D. Biochem. Med. 1974, 10, 15. 11. Schacter, D., Taggart, J. V. J. biol. Chem. 1954, 208, 263. 12. Krieger, I., Tanaka, K. Pediat. Res. 1976, 10, 25. 1. Wåhlin, A., Rosman, N. Lancet, 1976, ii, 1415.
Over 6 days the rash faded gradually; she became apyrexial; and her blood-urea fell to 7.3mmol/1 with good diuresis. The patient became clinically well after 10 days and has remained symptom-free since. Creatinine clearance done at this time showed: plasma-creatinine 120 mol/1 (normal 60-125), urine creatinine 71 fLmoV24 h (normal 9-18), clearance 41 ml/min (normal 75-115). When repeated after 12 weeks the figures were plasma-creatinine 105 mol/1, urine creatinine 8.9 )imo)/24 h, clearance 87 ml/min. Neither cutaneous nor renal biopsy was carried out. Cutaneous manifestations due to co-trimoxazole are now well accepted as an allergic reaction, but renal toxicity is controversial. Kalowski et al.2 observed that administration of cotrimoxazole to patients with chronic renal failure produced a deterioration in renal function which was usually reversible. Tasker et al.3 found that an adjusted dose of co-trimoxazole could be used in similar patients without any deterioration, Kalowski et al. were partly supported by Gotloib.4 We conclude that the acute episode described in this patient was due to co-trimoxazole. R. S. RAMAIAH M. A. GALLAGHER Hospital, Llangwyfan Llandyrnog, Clwyd LL16 4ND R. W. BIAGI
TRANSCENDENTAL MEDITATION AND HYPERTENSION
SIR9 Dr Pollack and his colleagues (Jan. 8, p. 71) may have missed an important point which could explain their negative results. They found significant decreases in systolic blood-pressure and pulse-rate in twenty hypertensives in the first three months after learning the transcendental meditation (TM) technique. However, these decreases were not maintained at statistically significant levels by the end of the sixmonth study. A possible reason for this is that the patients may have become irregular in the practice of TM or stopped altogether. Williams et al. demonstrated that the degree to which TMrelated effects accumulated was directly proportional to the frequency of meditation. However, Dr Pollack and his colleagues do not mention this important variable. They state that, while fourteen patients "expressed a strong desire to continue meditating," six apparently wanted to "discontinue" the practice. No data were given on how often the patients meditated, which is normally for twenty minutes in the morning and evening. If these patients did not follow the prescribed routine, the efficacy of the treatment would have been limited and would be reflected in the group means for blood-pressure and pulse-rate as a loss of significant decreases. There were decreases in mean blood-pressure and pulse-rate for months5 and 6, but these were not significant. Full participation (assuming this did not happen) in the TM programme by all participants may have made these decreases significant. It would be interesting to see the data broken down in terms of frequency and regularity of meditation. Patients might have been more irregular in their meditation in the last three months of the study because of the method of meditation training. Personal consultation with the TM teacher was maintained regularly for only the first three months. Continuous contact with the TM teacher might have encouraged a regular pattern of meditation and ensured that the technique was correct. TM teachers acknowledge the value of regular sessions to check technique in ensuring continued participation in a programme. 2.
Kalowski, S., Nanra, R. S., Mathew, T. H., Kincaid-Smith, P. ibid. 1973, i, 394. 3. Tasker, P. R. W., McGregor, G. A., de Wardener, H. E., Thomas, R. D., Jones, N. F. ibid. 1975, i, 1216. 4. Gotloib, L. ibid. 1975, ii, 365. 1. Williams, P., Francis, A., Durham, R. Perceptual Motor Skills, 1976, 43, 787.
605
Plasma-renin-activity was measured before and after the six months of meditation and showed no significant change. These data seem inconclusive; intermediate measurements were not done, and the before-and-after data may again reflect irregularity in the practice of TM. I suggest that future studies of TM should include control for fluctuations in participation which significantly affect the outcome.
branch of the left coronary as the artery of sudden death is not undeserved. But there are reasons for believing that even large branches of the coronary arteries may be occluded - at times acutely - without resulting death, at least without death in the immediate future. Even the main trunk may at times be obstructed and the patient live. It is the object of this paper to present a few facts along this line and particularly to describe some of the clinical manifestations of sudden yet more immediately fatal cases of coronary obstruction".1 of Preventive Medicine and Biostatistics,
Department
Department of Neuroscience, College of Medicine, University of Florida, Gainesville, Florida 32610, U.S.A.
University of Toronto, Toronto, Ontario, Canada
*** This letter has been shown to Dr lows.-ED. L.
SIR,-Mr Bralley wonders if
T. W. ANDERSON
JAMES A. BRALLEY
Pollack, whose reply fol-
patients meditated with the same frequency during the later part of the study as they did at the beginning. If they did not, this would help to explain why the early falls in systolic pressure were not sustained. We went to considerable lengths to encourage our patients to adhere to their twice-daily schedule of meditation, and to the best of our knowledge they did so. Even the minority of patients who intended to discontinue TM at the end of the study maintained, we believe, a high degree of compliance. The question of whether the fall in blood-pressure by the end of study was significant or not hardly seems important. As we pointed out, the mean amplitude of the blood-pressure response in our patients was not greatly different to that reported by Benson et al.’ However, only three of the twenty patients experienced blood-pressure decreases that could be regarded as clinically useful, while in another three patients blood-pressure rose. A more important issue is whether TM can be recommended as a substitute for more conventional treatment. Even using the data obtained by Benson et al., it seems unrealistic to recommend meditation, a technique requiring forty minutes of the patient’s time each day together with regular follow-up visits to a TM teacher, as a standard approach to antihypertensive management. If, as Mr Bralley points out, even enthusiastic participants tend to become less reliable in their use of this technique, routine recommendation of TM seems even less appealing. We did not mean to appear "negative" about TM. As we pointed out, most of our patients subjectively felt a sense of well-being while practising the technique, and this may be useful in enhancing compliance with other forms of treatment. our
Cardiovascular Center, New York Hospital—Cornell Medical Center, New York, N.Y. 10021, U.S.A.
SIR,-You challenge (Jan, 8, p. 80) the classical concept of thrombosis as the cause of myocardial infarction. As you point out, thrombosis is rare in subendocardial infarction and in patients dying suddenly, and it is not always found in transmural infarction-reasons enough for questioning the thrombosis
hypothesis. Since assessing the age of a coronary thrombus by its microscopical appearance is almost impossible when the thrombus is recent, the time-relationship between thrombosis and necrosis has to be studied experimentally. However, there are two important problems: we need a substance that will be incorporated into a forming thrombus, and we need to know whether the myocardial necrosis has started when this substance is injected. A forming thrombus will incorporate radioactively labelled fibrinogen but so, for at least 18 h, will already formed thrombi.’ Therefore, the studies by Erhardt et al. 2and Fulton and Sumner4 must be questioned on the basis of technique. The fact that radioactivity is found in thrombi does not exclude the possibility that they were formed after the necrosis, but it certainly weakens the argument. Deciding the onset of myocardial necrosis is also difficult. Clinically we only have electrocardiography and enzymes. Onset of pain is unreliable because the period of pain before the
onset
of necrosis is variable. The release of enzymes is also
variable,s and the enzymes must be measured frequently to pinpoint the onset of necrosis. The E.c.G. frequently shows characteristic early changes in transmural infarction but these early changes indicate ischaemia and not necrosis. Even if we could accurately decide the onset of necrosis we could not give any substance during the first hours because the patients would not be available. Thus, the early changes in the coronary arteries in acute myocardial infarction in man are very difficult to study. Your views and those of Dr Fulton (Feb. 5, p. 303) and Professor Moore (Feb. 12, p. 367) may not be contradictory since it may very well be that coronary-artery thrombosis in some follows the necrosis and in some cases is the cause of it. To settle the question we need a substance that is incorporated only into a growing thrombus, but not in one already formed. cases
ALBERT A. POLLACK
Department of Medicine, Serafimerlasarettet, S-112 83 Stockholm, Sweden
PLATELETS, LIPIDS, AND MYOCARDIAL
LEIF R. ERHARDT
INFARCTION
SIR,-Your editorial (Jan. 8, p. 80) perpetuates the myth that the concept of coronary thrombosis was introduced by Herrick in 1912.2 In fact, the importance of coronary thrombosis nised at least 20 years earlier:
was
recog-
"The blocking of one of these [coronary] vessels by a thrombus or embolus leads to a condition known as anaemic necrosis or white infarct... In medicolegal cases it is a point of primary importance to remember that this is one of the common causes of sudden death".3 Herrick’s contribution was in demonstrating that coronary
occlusion need not always be fatal: "It 1
must
be admitted, also, that the reputation of the
Benson, H., Rosner,
WILSON’S DISEASE AND CHRONIC ACTIVE HEPATITIS
SIR,-As Dr Archer and Dr Monie (Feb. 26, p. 486) point Wilson’s disease can present as chronic active hepatitis, and it is also true that all children and young adults with subacute or chronic liver damage should be screened as possible cases of Wilson’s disease. At least half of all patients with Wilson’s disease either present as liver damage or give a history out
1. Moschos, C. B., Oldewurtel, H. A., Haider, B.,
descending
B. A., Marzetta, B. R., Klemchuk, H. M. Lancet, 1974, i, 289. 2 Herrick, J. B., J. Am. med. Ass. 1912, 59, 2015. 3 Osler, W. The Principles and Practice of Medicine, Edinburgh, 1892.
Regan, T. J. Circulation, 1976, 54, 653. 2. Erhardt, L. R., Lundman, T., Mellstedt, H. Lancet, 1973, i, 387. 3. Erhardt, L. R., Unge, G., Boman, G. Am. Heart J. 1976, 91, 592. 4. Fulton, W. F. M., Sumner, D. G. Br. Heart J. 1976, 38, 880. 5. Mathey, D., Bleifeld, W., Buss, H., Hanrath, P. ibid. 1975, 37, 1161. 6. Fulton, W. F. M. Lancet, 1977, i, 303. 7. Moore, S. ibid. p. 367.
