- Email: [email protected]
THE ANION GAP
513
topenia
and anaemia. However, the anaemia
was never
fully
controlled, unlike the thrombocytopenia. The only accompaniment to both the onset and the improvement in the headache was a change in platelet-count: the coincidence was striking.
Migraine headaches have been associated with serotonin metabolism since Sicuteri et at.’ found an increase in the urinary excretion of 5-hydroxyindoleacetic acid (5-H.I.A.A.) during migraine attacks. This finding has been confirmed by somebut not by others.3° The disparity may be linked to the heterogeneity of patient types usually included in studies of migraine. Furthermore, plasma-serotonin decreases during a migraine attack, and during such attacks the urinary excretion of serotonin is increased even though 5-H.I.A.A. excretion remains normal. Since serotonin constricts large arteries and veins and dilates of arterioles, and capillaries, a fall in circulating serotonin could explain the extracranial vasodilatation found during attacks and the capillary constriction which causes the typical pallor of the migrainous patient. But what causes the fall in serotonin? One important store of serotonin is the platelets, and the platelets have received special attention in studies of migraine. They aggregate more readily in the presence of serotonin; their serotonin content falls during a migraine attack and free serotonin decreases. It has been suggested that free serotonin is more rapidly picked up from the circulation, more quickly metabolised, and excreted at an accelerated rate.8 It has also been proposed that during migraine attacks there is a primary depression of platelet monoamine-oxidase activity which might be linked to abnormal metabolism of serotonin, in the absence of changes in platelet-count.9 On the other hand, ultrastructural studies of platelets of migraine patients have not demonstrated any abnormality. 10 In thrombocytopenia changes in serotonin content and metabolism can be expected-indeed patients do have a decreased serum-serotonin when platelet-counts fall below 100 000.11 It is likely that circulating serotonin levels in my patient became very low during the thrombocytopenic crisis and possibly abruptly. I suggest that the rate of lowering of serotonin level may also be a factor in the sudden onset of a migraine attack. Sudden changes in platelet-count might be related to variation of serotonin level and thus contribute to the production of migraine, in the absence of other clinical
signs. Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, U.S.A.
HANNA DAMASIO
THE ANION GAP
SiR,-Your editorial on the anion gap (April 9, p. 785) drew attention to and condensed the valuable review by Emmett and Narins.12 Because Dr Patel and Dr Wright (May 14, p. 1054) found an increased anion gap in 51% of 94 patients aged 65-90 they suggested that anion-gap results were less valuable in the
we found an increased anion gap in 31 % of hundred consecutive acutely ill inpatients aged 65-93 years and in 20% of fifty consecutive outpatients aged 65-86 years. Males constituted 60% of both our groups of patients all of whom were patients of a large general teaching hospital. We suggest that the high frequency of increased anion gap in the series investigated by Dr Patel and Dr Wright is more apparent than real, since they calculated the anion gap by the formula (Na++K+) - (Cl-+HCO ), which has a reference range of 11-19 meq/l,"but they interpreted their results according to the reference range of 8-16 meq/1 which belongs to the other formula, (Na+) - (Cl-+HCO3-), as cited in your editorial. Experience of more than 10 years’ routine reporting of the anion gap and discussion with clinical colleagues at the bedside has convinced the staff of this laboratory of the value of this calculation in patient management.
elderly. However, a
Division of Clinical Chemistry, Institute of Medical and Veterinary Frome Road, Adelaide, South Australia 5000
A. PRIOR P. J. PHILLIPS R. W. PAIN
Science,
Hb G NORFOLK ASSOCIATED WITH MALIGNANT MYELOSCLEROSIS
SIR,-It is now usual to perform haemoglobin electrophoron patients presenting with a haematological malignancy. We have investigated an 81-year-old man who presented with esis
malignant myelosclerosis. On electrophoresis haemoglobin band was detected which migrated
an abnormal between HbA and HbS. The HbF level was less than 1% and the HbA2 level was 2.5%. The abnormal haemoglobin was identified as HbG Norfolk &agr;85(F6) Asp-Asn, and a slowly migrating band Gz was also present (04%). The association between leukxmia and abnormal hoemoglobin production is established. However, this association is most commonly seen in erythraemic myelosis.2·3 The most common abnormality is an imbalance in the synthesis of either the a or the j3 chains. However, structural haemoglobin variants have been found (White, J. M., personal communication). Also, there are occasional changes in the HbA2 and HbF levels. These are not confined to leukaemia, but are commonly found in many conditions associated with dyshæmopoiesis.4 The finding of an abnormal haemoglobin in this patient suggested that the abnormality resided within the erythroid line. However, when it was found to be HbG Norfolk, it was realised that this was a fortuitous finding. Family studies confirmed this. Both of the affected relatives are hsematologically normal. Three cases of HbG Norfolk have been described. The first was found during a survey to assess the frequency of the fast moving Hb Norfolk (&agr;2Gly→Asp&bgr;2).5 The characterisation of HbG Norfolk in the other two was described by Lorkin et al.6 One of these cases was in an English child from Swindon who had leukaemia, and it was also present in the father unassociated with any other haematological abnormality.
cases
We thank Prof. H.
Lehmann,
F.R.S., for
identifying
the abnormal
haemoglobin as G Norfolk. 1. 2. 3. 4.
Sicuteri, F., Testi, A., Anselmi, B. Int. Archs Allergy, 1961, 19, 55. Curan, D. A., Hinterberger, H., Lance, J. W. Brain, 1965, 88, 999. Curzon, G. et al. J. Neurol. Neurosurg. Psychiatry, 1966, 29, 85. Anthony M., Lance, J. W. in Modern Topics in Migraine (edited by J. Pearce); p. 107. London, 1975.
5. Anthony, M. Paper read at sixth international Migraine Symposium, held in London, in 1974. 6. Hilton, B. P., Cumings, J. N. J. Neurol. Neurosurg. Psychiat. 1972, 35, 505. 7. Anthony M., Hinterberger, H., Lance J. W. Res. clin. Stud. Headache, 1969,
2, 29. 8. Sommerville,
B. W. Neurology, 1976, 26, 41. 9 Sicuteri, F., Buffoni, F., Anselmi, B., Del Bianco, Headache, 1972, 3, 245. 10. Grammeltvedt, A., Headache, 1975, 14, 226. 11. Bigelow, F. S. J. Lab. clin. Med. 1954, 43, 759. 12. Emmett, M., Narins, R. Medicine, 1977, 56, 38.
P. L. Res. Clin. Stud.
King’s College Hospital Medical School, University of London, Department of Hæmatology, Denmark Hill, London SE5 8RX
D. R. HIGGS
B. FROST J. C. SHARP
13. Thomas, D. W., Pain, R. W., Duncan, B. M. Lancet, 1973, ii, 848. 1 Lubin, J., Rosen, S., Rylwin, A. M. Arch. intern. Med. 1976,136, 141. 2. White, J. C., and others. Br. J. Hœmat. 1960, 6, 171. 3. Rosenzweig, A. I., and others. Acta hœmat. 1968, 39, 91. 4. Bradley, T. B., Ranney, H. M. Progr. Hœmat. 1974, 8, 77. 5. Huntsman, R. G., Hall, M., Lehmann, H., Sukumaran, P. K. Br. med. J. 1963, i, 720. 6. Lorkin, P. A., Huntsman, R. G., Ager, J. A. M., Lehmann, H., Vella, F., Darbre, P. D. Biochim. biophy. Acta. 1975, 379, 22.
topenia
and anaemia. However, the anaemia
was never
fully
controlled, unlike the thrombocytopenia. The only accompaniment to both the onset and the improvement in the headache was a change in platelet-count: the coincidence was striking.
Migraine headaches have been associated with serotonin metabolism since Sicuteri et at.’ found an increase in the urinary excretion of 5-hydroxyindoleacetic acid (5-H.I.A.A.) during migraine attacks. This finding has been confirmed by somebut not by others.3° The disparity may be linked to the heterogeneity of patient types usually included in studies of migraine. Furthermore, plasma-serotonin decreases during a migraine attack, and during such attacks the urinary excretion of serotonin is increased even though 5-H.I.A.A. excretion remains normal. Since serotonin constricts large arteries and veins and dilates of arterioles, and capillaries, a fall in circulating serotonin could explain the extracranial vasodilatation found during attacks and the capillary constriction which causes the typical pallor of the migrainous patient. But what causes the fall in serotonin? One important store of serotonin is the platelets, and the platelets have received special attention in studies of migraine. They aggregate more readily in the presence of serotonin; their serotonin content falls during a migraine attack and free serotonin decreases. It has been suggested that free serotonin is more rapidly picked up from the circulation, more quickly metabolised, and excreted at an accelerated rate.8 It has also been proposed that during migraine attacks there is a primary depression of platelet monoamine-oxidase activity which might be linked to abnormal metabolism of serotonin, in the absence of changes in platelet-count.9 On the other hand, ultrastructural studies of platelets of migraine patients have not demonstrated any abnormality. 10 In thrombocytopenia changes in serotonin content and metabolism can be expected-indeed patients do have a decreased serum-serotonin when platelet-counts fall below 100 000.11 It is likely that circulating serotonin levels in my patient became very low during the thrombocytopenic crisis and possibly abruptly. I suggest that the rate of lowering of serotonin level may also be a factor in the sudden onset of a migraine attack. Sudden changes in platelet-count might be related to variation of serotonin level and thus contribute to the production of migraine, in the absence of other clinical
signs. Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, U.S.A.
HANNA DAMASIO
THE ANION GAP
SiR,-Your editorial on the anion gap (April 9, p. 785) drew attention to and condensed the valuable review by Emmett and Narins.12 Because Dr Patel and Dr Wright (May 14, p. 1054) found an increased anion gap in 51% of 94 patients aged 65-90 they suggested that anion-gap results were less valuable in the
we found an increased anion gap in 31 % of hundred consecutive acutely ill inpatients aged 65-93 years and in 20% of fifty consecutive outpatients aged 65-86 years. Males constituted 60% of both our groups of patients all of whom were patients of a large general teaching hospital. We suggest that the high frequency of increased anion gap in the series investigated by Dr Patel and Dr Wright is more apparent than real, since they calculated the anion gap by the formula (Na++K+) - (Cl-+HCO ), which has a reference range of 11-19 meq/l,"but they interpreted their results according to the reference range of 8-16 meq/1 which belongs to the other formula, (Na+) - (Cl-+HCO3-), as cited in your editorial. Experience of more than 10 years’ routine reporting of the anion gap and discussion with clinical colleagues at the bedside has convinced the staff of this laboratory of the value of this calculation in patient management.
elderly. However, a
Division of Clinical Chemistry, Institute of Medical and Veterinary Frome Road, Adelaide, South Australia 5000
A. PRIOR P. J. PHILLIPS R. W. PAIN
Science,
Hb G NORFOLK ASSOCIATED WITH MALIGNANT MYELOSCLEROSIS
SIR,-It is now usual to perform haemoglobin electrophoron patients presenting with a haematological malignancy. We have investigated an 81-year-old man who presented with esis
malignant myelosclerosis. On electrophoresis haemoglobin band was detected which migrated
an abnormal between HbA and HbS. The HbF level was less than 1% and the HbA2 level was 2.5%. The abnormal haemoglobin was identified as HbG Norfolk &agr;85(F6) Asp-Asn, and a slowly migrating band Gz was also present (04%). The association between leukxmia and abnormal hoemoglobin production is established. However, this association is most commonly seen in erythraemic myelosis.2·3 The most common abnormality is an imbalance in the synthesis of either the a or the j3 chains. However, structural haemoglobin variants have been found (White, J. M., personal communication). Also, there are occasional changes in the HbA2 and HbF levels. These are not confined to leukaemia, but are commonly found in many conditions associated with dyshæmopoiesis.4 The finding of an abnormal haemoglobin in this patient suggested that the abnormality resided within the erythroid line. However, when it was found to be HbG Norfolk, it was realised that this was a fortuitous finding. Family studies confirmed this. Both of the affected relatives are hsematologically normal. Three cases of HbG Norfolk have been described. The first was found during a survey to assess the frequency of the fast moving Hb Norfolk (&agr;2Gly→Asp&bgr;2).5 The characterisation of HbG Norfolk in the other two was described by Lorkin et al.6 One of these cases was in an English child from Swindon who had leukaemia, and it was also present in the father unassociated with any other haematological abnormality.
cases
We thank Prof. H.
Lehmann,
F.R.S., for
identifying
the abnormal
haemoglobin as G Norfolk. 1. 2. 3. 4.
Sicuteri, F., Testi, A., Anselmi, B. Int. Archs Allergy, 1961, 19, 55. Curan, D. A., Hinterberger, H., Lance, J. W. Brain, 1965, 88, 999. Curzon, G. et al. J. Neurol. Neurosurg. Psychiatry, 1966, 29, 85. Anthony M., Lance, J. W. in Modern Topics in Migraine (edited by J. Pearce); p. 107. London, 1975.
5. Anthony, M. Paper read at sixth international Migraine Symposium, held in London, in 1974. 6. Hilton, B. P., Cumings, J. N. J. Neurol. Neurosurg. Psychiat. 1972, 35, 505. 7. Anthony M., Hinterberger, H., Lance J. W. Res. clin. Stud. Headache, 1969,
2, 29. 8. Sommerville,
B. W. Neurology, 1976, 26, 41. 9 Sicuteri, F., Buffoni, F., Anselmi, B., Del Bianco, Headache, 1972, 3, 245. 10. Grammeltvedt, A., Headache, 1975, 14, 226. 11. Bigelow, F. S. J. Lab. clin. Med. 1954, 43, 759. 12. Emmett, M., Narins, R. Medicine, 1977, 56, 38.
P. L. Res. Clin. Stud.
King’s College Hospital Medical School, University of London, Department of Hæmatology, Denmark Hill, London SE5 8RX
D. R. HIGGS
B. FROST J. C. SHARP
13. Thomas, D. W., Pain, R. W., Duncan, B. M. Lancet, 1973, ii, 848. 1 Lubin, J., Rosen, S., Rylwin, A. M. Arch. intern. Med. 1976,136, 141. 2. White, J. C., and others. Br. J. Hœmat. 1960, 6, 171. 3. Rosenzweig, A. I., and others. Acta hœmat. 1968, 39, 91. 4. Bradley, T. B., Ranney, H. M. Progr. Hœmat. 1974, 8, 77. 5. Huntsman, R. G., Hall, M., Lehmann, H., Sukumaran, P. K. Br. med. J. 1963, i, 720. 6. Lorkin, P. A., Huntsman, R. G., Ager, J. A. M., Lehmann, H., Vella, F., Darbre, P. D. Biochim. biophy. Acta. 1975, 379, 22.