- Email: [email protected]
THE ANION GAP
710 The polyomavirus was JC, a virus previously associated with progressive multifocal leucoencephalopathy and recovered from diseased brain. This is only the third time that JC virus has been isolated from the urine of a patient without neurological disease; the other two had renal transplants and were also investigated by us. The titre of JC heemagglutination-inhibition antibody in maternal serum was 1/1280 at 36 weeks and 1/2560 at 39 weeks’ pregnancy and 5 days post partum. Titres were 1/2560 in the cord blood and 1/1280 in the baby’s serum on day 6. Serum BK antibody levels in the mother and baby were almost identical with the JC antibody titres. Mother and baby went abroad immediately after delivery and are temporarily lost to
follow-up. A polyomavirus has since been cultured from the urine of a second pregnant woman and papovavirus particles have been observed in the urine of three others. Department of Experimental Pathology, St Mary’s Hospital Medical School, London W2 1NY
D. V. COLEMAN R. A. DANIEL
Virus Reference Laboratory, Central Public Health Laboratory, London NW9
S. D. GARDNER A. M. FIELD P. E. GIBSON
THE ANION GAP
SIR,-Your excellent editorial on the anion gapl pays just tribute to the unrivalled paper by Emmett and Narins2 on the clinical value of this calculation. Apart from this aspect I wish to make a plea for the maintenance of this concept in the study of electrolyte balance. Since the sum of cations equals the sum of anions-law of electroneutrality-any discrepancy must be explained. Van Slyke et al. found that the "base" bound by the total plasma-protei ns at pH 7-4’was 0.24 meq/1 for every g/l of protein, thus accounting normally for about 16 meq/1 of anions. The binding of ions to protein is, however, complicated.4 Both normal and abnormal plasma-proteins may contribute to the anions which are not usually measured. Increased protein may reduce the anion gap by attracting cations5 but paraproteins may actually be cationic.6 Greater knowledge of the net charges of normal and abnormal proteins is needed but a very low anion gap may be a useful pointer to
troneutrality. SI units should not be permitted to obscure the importance of the concept of electrolyte balance which has proved to be useful both in diagnosis and in the principles underlying fluid therapy. Department of Chemical Pathology, University of the Witwatersrand Medical School, Johannesburg 2001, South Africa
H. B. STEIN
ALUMINIUM AND ALZHEIMER’S DISEASE
SIR,-There is renewed interest in the neurotoxicity of aluminium compounds, in particular in the aetiology of Alzheimer’s disease. Crapper and co-workers have reportedl,2 that 29% of samples from various regions of the brains of patients dying with Alzheimer’s dementia had raised concentrations of aluminium (>4 t-tg/g dry tissue). We have measured aluminium in 274 brain samples from ten Alzheimer demented (three presenile and seven senile) and nine non-neurological patients. Brains were obtained 3-24 h post mortem and stored at —70°C. Alzheimer’s disease was confirmed histopathologically by assessing the degree of neurofibrillary degeneration in the frontal cortex and hippocampus. Samples of brain (0-3-lg), mainly from the frontal cortex, temporal cortex, hippocampus, corpus callosum, and cerebellum, were analysed for aluminium by atomic-absorption spectroscopy using a dry-ashing procedure.3 Similar numbers of the diseased and the control samples were used from each brain region. ALUMINIUM CONCENTRATIONS IN BRAIN TISSUE
unsuspected multiple myeloma. Without both Cl- and HCO-3 determinations the anion gap be calculated. I agree it is a pity that some laboratories do not report te Cl- in the "routine electrolyte set". Dr Zilva7 is worried about the workload resulting from routine Clrequests. Since most large laboratories possess an automated multichannel analyser perhaps she will one day be persuaded to include the Cl- estimation in her repertoire. Finally, I welcome your "punch line" that electrical charges require expression as meq and not mmol, an important condemnation of SI units in electrolyte studies. The routine set of electrolytes is fortunately univalent, but how is one to record the net cation equivalence of the normal plasma proteins in SI units? Gamble’s8 cation-anion diagrams may involve "a number of assumptions"9 in determining the net equivalence of proteins,4 but they are still useful in providing an insight into the composition of sera based on the law of elec-
cannot
...
1. Lancet, 1977, i, 785. 2. Emmett, M., Narins, R. G. Medicine, 1977, 56, 38. 3. Van Slyke, D. D., Hastings, A. B., Hiller, A., Sendroy Jr.
J. J. biol. Chem. 1928, 79, 769. 4. Van Leeuwen, A. M.Acta med. scand. 1964, 176, (suppl. 422), 1. 5. Gutman, A. B., Gutman, E. B., Jillson, R., Williams, R. D. J. clin. Invest. 1936, 15, 475. 6. Murray, T., Long, W., Narins, R. G. New Engl.J. Med. 1975, 292, 574. 7. Zilva, J. F. Lancet, 1977, i, 948. 8. Gamble, J. L. Chemical Anatomy, Physiology and Pathology of Extracellular Fluid. Cambridge, Mass., 1954. 9. Latner, A. L. Cantarow and Trumper’s Clinical Biochemistry; p. 349. Phila-
delphia, 1975.
*[J-g aluminium/g dry tissueis.E.M.; no. of samples in parentheses. There was no significant difference in aluminium concentration between nine normal brains and ten brains from patients with dementia, in the material as a whole or in the regions rich in neurofibrillary degeneration (hippocampus and frontal and temporal cortex). 21% of senile-dementia samples have raised aluminium concentrations as defined previously,’ but so did 21% of age-matched control samples. This suggests that high aluminium levels are related to age rather than dementia. In contrast to the findings of Crapper et al. we found only a small number of samples with raised aluminium in the presenile dementia but this could be due to the limited number of samples and brain regions investigated in this group. The density of neurofibrillary tangles in the brains of Alzheimer patients is 6-40 times that in brains from mentally normal age-matched controls.4 Crapper et al. suggested that the increase in aluminium concentration correlates well with the extent of neurofibrillary degeneration.2 When we compared all the samples from brains of age 70 years or more we found that 1. 2. 3. 4.
Crapper, D. R., Krishnan, S. S., Dalton, A. J. Science, 1973, 180, 511. Crapper, D. R., Krishnan, S. S., Quittkat, S. Brain, 1976, 99, 67. McDermott, J. R., Whitehill, I. Analyt. chim. Acta, 1976, 85, 195. Ball, M. J.Neuropath. appl. Neurobiol.1976, 2, 395.
follow-up. A polyomavirus has since been cultured from the urine of a second pregnant woman and papovavirus particles have been observed in the urine of three others. Department of Experimental Pathology, St Mary’s Hospital Medical School, London W2 1NY
D. V. COLEMAN R. A. DANIEL
Virus Reference Laboratory, Central Public Health Laboratory, London NW9
S. D. GARDNER A. M. FIELD P. E. GIBSON
THE ANION GAP
SIR,-Your excellent editorial on the anion gapl pays just tribute to the unrivalled paper by Emmett and Narins2 on the clinical value of this calculation. Apart from this aspect I wish to make a plea for the maintenance of this concept in the study of electrolyte balance. Since the sum of cations equals the sum of anions-law of electroneutrality-any discrepancy must be explained. Van Slyke et al. found that the "base" bound by the total plasma-protei ns at pH 7-4’was 0.24 meq/1 for every g/l of protein, thus accounting normally for about 16 meq/1 of anions. The binding of ions to protein is, however, complicated.4 Both normal and abnormal plasma-proteins may contribute to the anions which are not usually measured. Increased protein may reduce the anion gap by attracting cations5 but paraproteins may actually be cationic.6 Greater knowledge of the net charges of normal and abnormal proteins is needed but a very low anion gap may be a useful pointer to
troneutrality. SI units should not be permitted to obscure the importance of the concept of electrolyte balance which has proved to be useful both in diagnosis and in the principles underlying fluid therapy. Department of Chemical Pathology, University of the Witwatersrand Medical School, Johannesburg 2001, South Africa
H. B. STEIN
ALUMINIUM AND ALZHEIMER’S DISEASE
SIR,-There is renewed interest in the neurotoxicity of aluminium compounds, in particular in the aetiology of Alzheimer’s disease. Crapper and co-workers have reportedl,2 that 29% of samples from various regions of the brains of patients dying with Alzheimer’s dementia had raised concentrations of aluminium (>4 t-tg/g dry tissue). We have measured aluminium in 274 brain samples from ten Alzheimer demented (three presenile and seven senile) and nine non-neurological patients. Brains were obtained 3-24 h post mortem and stored at —70°C. Alzheimer’s disease was confirmed histopathologically by assessing the degree of neurofibrillary degeneration in the frontal cortex and hippocampus. Samples of brain (0-3-lg), mainly from the frontal cortex, temporal cortex, hippocampus, corpus callosum, and cerebellum, were analysed for aluminium by atomic-absorption spectroscopy using a dry-ashing procedure.3 Similar numbers of the diseased and the control samples were used from each brain region. ALUMINIUM CONCENTRATIONS IN BRAIN TISSUE
unsuspected multiple myeloma. Without both Cl- and HCO-3 determinations the anion gap be calculated. I agree it is a pity that some laboratories do not report te Cl- in the "routine electrolyte set". Dr Zilva7 is worried about the workload resulting from routine Clrequests. Since most large laboratories possess an automated multichannel analyser perhaps she will one day be persuaded to include the Cl- estimation in her repertoire. Finally, I welcome your "punch line" that electrical charges require expression as meq and not mmol, an important condemnation of SI units in electrolyte studies. The routine set of electrolytes is fortunately univalent, but how is one to record the net cation equivalence of the normal plasma proteins in SI units? Gamble’s8 cation-anion diagrams may involve "a number of assumptions"9 in determining the net equivalence of proteins,4 but they are still useful in providing an insight into the composition of sera based on the law of elec-
cannot
...
1. Lancet, 1977, i, 785. 2. Emmett, M., Narins, R. G. Medicine, 1977, 56, 38. 3. Van Slyke, D. D., Hastings, A. B., Hiller, A., Sendroy Jr.
J. J. biol. Chem. 1928, 79, 769. 4. Van Leeuwen, A. M.Acta med. scand. 1964, 176, (suppl. 422), 1. 5. Gutman, A. B., Gutman, E. B., Jillson, R., Williams, R. D. J. clin. Invest. 1936, 15, 475. 6. Murray, T., Long, W., Narins, R. G. New Engl.J. Med. 1975, 292, 574. 7. Zilva, J. F. Lancet, 1977, i, 948. 8. Gamble, J. L. Chemical Anatomy, Physiology and Pathology of Extracellular Fluid. Cambridge, Mass., 1954. 9. Latner, A. L. Cantarow and Trumper’s Clinical Biochemistry; p. 349. Phila-
delphia, 1975.
*[J-g aluminium/g dry tissueis.E.M.; no. of samples in parentheses. There was no significant difference in aluminium concentration between nine normal brains and ten brains from patients with dementia, in the material as a whole or in the regions rich in neurofibrillary degeneration (hippocampus and frontal and temporal cortex). 21% of senile-dementia samples have raised aluminium concentrations as defined previously,’ but so did 21% of age-matched control samples. This suggests that high aluminium levels are related to age rather than dementia. In contrast to the findings of Crapper et al. we found only a small number of samples with raised aluminium in the presenile dementia but this could be due to the limited number of samples and brain regions investigated in this group. The density of neurofibrillary tangles in the brains of Alzheimer patients is 6-40 times that in brains from mentally normal age-matched controls.4 Crapper et al. suggested that the increase in aluminium concentration correlates well with the extent of neurofibrillary degeneration.2 When we compared all the samples from brains of age 70 years or more we found that 1. 2. 3. 4.
Crapper, D. R., Krishnan, S. S., Dalton, A. J. Science, 1973, 180, 511. Crapper, D. R., Krishnan, S. S., Quittkat, S. Brain, 1976, 99, 67. McDermott, J. R., Whitehill, I. Analyt. chim. Acta, 1976, 85, 195. Ball, M. J.Neuropath. appl. Neurobiol.1976, 2, 395.