- Email: [email protected]
CALCIUM CARBONATE AND I.U.D. PREGNANCIES
458 noted to regard zinc as anything other than an important agent in causing anaemia. Zinc concentrations in our dialysate would have been at their highest in February when the softener was installed. However, we did not measure the concentration until late April. Thus we experienced anaemia problems when dialysing patients against dialysate zinc concentrations which were initially considerably more than 5 p.mol/1, falling to about 5 mol/1 in ten weeks. Dr Stewart and his colleagues experienced no problems dialysing patients against zinc concentrations which were initially around 5 jmol/1 and which fell to 1.5 mol/1 over one year. Both observations would be consistent with (for example) a hypothesis that anaemia problems can be initiated by zinc concentrations of about 15 p.mol/1 and sustained by concentrations around 5 mol/1. In Gallery’s home-dialysis patient2 and the two home-dialysis patients reported by us, severe anaemia problems developed when the patients were being dialysed against zinc concentrations of 20-50 p.mol/1. Thus we believe that zinc can be toxic. Because we did not measure zinc concentrations at the start of our anaemia epidemic, we are unable to set a precise limit to the toxic level, but we do not feel that the recommended concentration3 of 76 µmol/l (5 p.p.m.) is acceptable. Concentrations of 2-3 p.mol/1 seem to be safe but concentrations of more than 20 mol/1 are probably harmful. Princess Alexandra
Hospital, Ipswich Road, Woolloongabba, Queensland 4102, Australia
CALCIUM CARBONATE AND I.U.D. PREGNANCIES
SIR,-Your editorial entitled Which l.U.D.1 prompts us to
findings of a very positive correlation between calcium-carbonate coatings on copper-7 intrauterine devices (t.u.D.s) and pregnancy. Copper i.u.D.s quite often become coated with calcium carbonate after several months of use.2-4 In our first quantitative study,2 5 of the 23 copper-7s came from pregnant women, and all 5 had extensive calcium-carbonate deposits (see table). 3 other Lu.D.s removed because the comment on our
CALCIUM-CARBONATE DEPOSITS ON
COPPER-7
l.U.D. CORROSION
LAYERS
G. Row J. J. B. PETRIE
FALSE-POSITIVE MECONIUM SCREEN
SiR,—The BM meconium test is a useful screening test for cystic fibrosis. However, we have had false-positive results in
babies caused by the use of rectal glycerin suppositories. The babies presented with signs suggestive of intestinal obstruction possibly due to meconium ileus, and glycerin suppositories were inserted to speed the passage of meconium so that the BM test could be done to help confirm the diagnosis. The tests were positive but the babies were subsequently shown not to have cystic fibrosis, and we found that the glycerin suppositories themselves produce the typical blue colour on the test strip. The manufacturers (Boehringer, Mannheim) have confirmed our findings and will add to their instruction leaflet a note that glycerin suppositories may cause a falsepositive BM test. two
Department of Pædiatrics, Southmead General Hospital,
H. M. BERGER
Bristol BS10 5NB
K. H. LEE
S. J. REYNOLDS
ASPIRIN AND HEARING IMPAIRMENT
SIR,-We have had an inquiry about a case of prolonged deafness associated with aspirin use in a recent report of ours.’ On reviewing the original record we learned that this patient had had hearing impairment before receiving aspirin. While aspirin apparently increased the degree of hearing impairment, the drug should probably not be implicated in the production of what may have been permanent deafness in this patient. Boston Collaborative Drug Surveillance Boston University Medical Center, Waltham, Massachusetts 02154, U.S.A.
2. 3. 1.
Program,
JANE PORTER HERSHEL JICK
Gallery, E. D. M., Blomfield, J., Dixon, S. R. Br. med. J. 1972, iv, 331. Comty, C., Luehmann, D, Water, R., Shapiro, F. Trans. Am. Soc. artif. intern. Organs, 1974, 20, 189. Porter, J., Jick, H. Lancet, 1977, i, 587.
*Calcium
content
by
effervescence, but small
atomic
absorption; carbonate evident from
of other anions could be present too. 3 other l.V.D.S removed from pregnant women also had extensive calcium-carbonate deposits. Calcium content was not determined for 5 of the first 23 samples. amounts
seemed pregnant also had extensive calcium-carbonate deposits covering the copper wire. We have examined many I.U.D.s removed for other reasons, and in about half of these devices no calcium carbonate was found. Where calcium-carbonate had been deposited on devices removed for reasons other than pregnancy it was usually localised and should not have greatly affected the dissolution-rate of the copper. 4 or5 of the devices removed for reasons other than pregnancy did have extensive calcium-carbonate layers. This is not surprising because the plastic device even without any copper is an effective contraceptives and pregnancy-exposure risks do vary. The presence of extensive deposits on all 8 I.U.D.S removed from pregnant women does not prove that the layer contributed to the pregnancy, but it is certainly suggestive. The coating should appreciably slow the release-rate of copper. One study which attempted to determine copper loss included i.u.D.s removed from 2 pregnant women, and in both these devices the rate of copper loss was appreciably lower than average. However, variations in the composition of the corrosion layers2 and in the weight of the copper in the devices’ make such estimates only semiquantitative. Inert I.U.D.S also show calcium salt deposits,? so any I.U.D. which releases an active agent should have its efficacy limited by the build-up of calcium salts. As you noted’ women carrywoman
1. Lancet, 1977, i, 1239. 2. Lewis, K. M., Archer, R.
D., Ginsberg, A. P., Rosencwaig, A. Contraception,
1977, 15, 93. Gosden, C., Ross, A., Loudon, N. B. Br. med. J. 1977, i, 202. VanEyck, J., Lagasse, A., Thiery, M. Contraception, 1976, 13, 65. Zipper, J., Medel, M., Pastene, L., Rivera, M., Torres, L., Osorio, A., Toscanini, C. ibid. p. 7. 6. Zielske, F., Koch, F., Badura, R., Ladeburg, H. ibid. 1974, 10, 651. 7. Engineer, A. D., Dasgupta, P. R., Kar, A. B. Am. J. Obstet. Gynec. 1970, 106, 315. 3. 4. 5.
459 seem to have pregnancythose fitted with copper I.U.D.S. Uterine fluids rates similar with l.U.D.S present have calcium and carbonate concentrations necessary for saturation.89 A slow acid release at the l.U.D. surface might solve the carbonate build-up. The carbonate layer can form quickly. 1 device had about half the corrosion. layer as calcium carbonate in under 10 months; however, 3 I.U.D.S in situ for a year or more had less than 1% of the corrosion layer as calcium carbonate. There may be a slightly positive correlation between time in situ and calcium-carbonate deposition,2·3but the pregnancy-rate during the second year of copper I.U.D. use does not seem to be greater than that of the first year.
SOURCE OF AMERICAN SERRATIA
ing progesterone-releasing devices to
We thank the University of Massachusetts and its Research Council for partial support through biomedical sciences support grants.
Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, U.S.A.
RONALD D. ARCHER KENRICK M. LEWIS
Amherst Medical Associates
STEVEN J. ZWIREK
USE OF BLOOD-CULTURES
SIR,-Durbridge’ and Eisenberg2 are both doubtful of the value of blood-cultures in the diagnosis of septicaemia in adults, because the condition is usually clinically recognisable, and treatment is often started before the results of the culture are known. In geriatric practice, where patients often present in a nonspecific atypical manner, blood-cultures remain a very useful diagnostic tool. A recent survey3 showed that the test was helpful in the diagnosis of patients presenting with a non-specific malaise or "failure to thrive". The test also clarified the treatment of elderly patients with respiratory infection by identifying the causal organism when sputum cultures were negative. It is worth noting that elderly patients with significant bacteramua were characterised by the virtual absence of fever, collapse, shock, vomiting or oliguria. Patients with subacute bacterial endocarditis had only one constant sign-the cardiac murmur. Under half the patients had evidence of anaemia, polymorphonuclear leucocytosis, or uraemia. Northwick Park Hospital, Harrow, Middlesex HA1 3UJ
M.
J. DENHAM
SMOKING AND MENOPAUSE
SiR,-After the appearance of our article4 we became aware two previous publicationss.6 which described earlier menopause in smokers, and we should like to acknowledge them. HERSHEL JICK Boston Collaborative Drug Surveillance Program,
of
Boston University Medical Center, Waltham, Massachusetts 02154, U.S.A.
8. Kar, A. B.,
JANE PORTER
ALAN S. MORRISON
Engineer, A. D., Goel, R., Kamboj, V. P., Dasgupta, P. R., Chowdhury, S. R. ibid. 1968, 101, 966. 9. Moore, E. W. in Ion Exchange Electrodes (edited by R. A. Durst);chap. 7. Washington, D.C., 1969. 10. Roy, S., Azen, S. P., Mishell, D. R., Pike, M. C., Casagrande, J. Contraception, 1976, 13, 365. 1. Durbridge, T. C. Lancet, 1977, i, 1206. 2. Eisenberg, J. M. ibid. 1977, ii, 140. 3. Denham, M. J., Goodwin, G. S. Age Ageing, 1977, 6, 85. 4. Jick, H., Porter, J., Morrison, A. S. Lancet, 1977, i, 1354. 5. Bernhardt, P. Münch. med. Wschr. 1962, 104, 1826. 6. Daniell, H. W. Archs intern. Med. 1976, 136, 298.
SIR,-Dr Severn (April 2, p. 750) suggested that the greater reported incidence of Serratia marcescens as a pathogen in the U.S.A. compared with the U.K. may be due to its use in germwarfare population-vulnerability studies. This possibility has also been widely discussed in the American press. Since we have studied over 5000 S. marcescens strains from all over the world,’ our data may be helpful in examining this hypothesis. The following facts should be considered. 1. Although S. marcescens may not be an important opportunistic pathogen in the U.K., recent reports2 indicate its importance in France, Germany, Belgium, and other European countries. The experience in these countries (where, presumably, population-vulnerability studies did not take place) is similar to the American experience.’I 2. The strain that was used in the American population-vulnerability studies was S. marcescens 8 UK, a strain with a bright red pigment which has often been used as a biological indicator in aerosol experiments. This strain (obtained by us from Fort Detrick in 1969 and again in 1977) is biotype A6, serotype 08:H3, and phage type 678. These four markers form a distinct "fingerprint". Because strains of 8 UK that we preserved in 1957 and 1969 still have these characteristics, we feel that the markers are stable. 3. Biotype A6 of S. marcescens is rare;3only 20 of 2062 cultures we examined belonged to this biotype. Biotype A6 is usually isolated from the environment rather than from human infection. Only 1 of 178 strains of S. marcescens from patients in Bordeaux was biotype A6, as were only 2 of 377 strains from hospital patients in France, Germany, and Belgium. Of the American strains tested, 7 were biotype A6 but only 1 had the same serotype as strain 8 UK. S. marcescens of biotype A6 did cause a nursery outbreak in Minnesota (U.S.A.) in 1968, but the strain was of a different serotype (08:H13) from S. marcescens8UK which was used in the population-vulnerability studies. 4. Of more than 3000 U.S. strains serotyped since 1950, serotype 08 :H3 was found only 7 times. 5. Of more than 100 outbreaks of S. marcescens infection we studied in the U.S., none has been caused by a strain with characteristics of strain 8 UK. We believe that many different strains of S. marcescens cause sporadic infections and outbreaks in the U.S.’ Because not all strains of S. marcescens isolated in the U.S. are referred to us, we cannot comment on the true incidence of strain 8 UK in the U.S.A. However, we do not think that our data support the hypothesis that S. marcescens 8 UK, which was used in germ-warfare population-vulnerability studies, is an important cause of morbidity and mortality in the U.S.A. Any strains which are implicated as being related to this activity can be scientifically tested because strain 8 UK has four stable and distinct biological markers. During our investigations, we did encounter one instance in which S. marcescens 8 UK was definitely associated with intestinal colonisation of an infant. In 1957 a newborn baby in a Wisconsin nursery had red-diaper syndrome.’ The strain was shown to be serotype 08:H3 at the Center for Disease Control. An epidemiological investigation revealed that a scientist at the hospital was releasing S. marcescens 8 UK (which we confirmed to be of serotype 08:H3), as part of a research project on aerosol techniques.4 The infant was colonised by this strain, which apparently caused no harm. However, the parents (the father was a geneticist) were quite worried because originally they thought their daughter had an inborn error of metabolism. The strain was also a nuisance to a local laundry because
Farmer, J. J., Davis, B. R., Hickman, F. H., Presley, D. B., Bodey, G. P., Negut, M. H., Bobo, R. A. Lancet, 1976, ii, 455. 2. Lancet, 1977, i, 636. 3. Grimont, P. A. D., Grimont, F., Dulong de Rosnay, H. L. C., Sneath, P. H. A. J. gen. Microbiol. 1977, 98, 39. 4. Waisman, H. A., Stone, W. H. Pediatrics, 1958, 21, 8. 1.
Hospital, Ipswich Road, Woolloongabba, Queensland 4102, Australia
CALCIUM CARBONATE AND I.U.D. PREGNANCIES
SIR,-Your editorial entitled Which l.U.D.1 prompts us to
findings of a very positive correlation between calcium-carbonate coatings on copper-7 intrauterine devices (t.u.D.s) and pregnancy. Copper i.u.D.s quite often become coated with calcium carbonate after several months of use.2-4 In our first quantitative study,2 5 of the 23 copper-7s came from pregnant women, and all 5 had extensive calcium-carbonate deposits (see table). 3 other Lu.D.s removed because the comment on our
CALCIUM-CARBONATE DEPOSITS ON
COPPER-7
l.U.D. CORROSION
LAYERS
G. Row J. J. B. PETRIE
FALSE-POSITIVE MECONIUM SCREEN
SiR,—The BM meconium test is a useful screening test for cystic fibrosis. However, we have had false-positive results in
babies caused by the use of rectal glycerin suppositories. The babies presented with signs suggestive of intestinal obstruction possibly due to meconium ileus, and glycerin suppositories were inserted to speed the passage of meconium so that the BM test could be done to help confirm the diagnosis. The tests were positive but the babies were subsequently shown not to have cystic fibrosis, and we found that the glycerin suppositories themselves produce the typical blue colour on the test strip. The manufacturers (Boehringer, Mannheim) have confirmed our findings and will add to their instruction leaflet a note that glycerin suppositories may cause a falsepositive BM test. two
Department of Pædiatrics, Southmead General Hospital,
H. M. BERGER
Bristol BS10 5NB
K. H. LEE
S. J. REYNOLDS
ASPIRIN AND HEARING IMPAIRMENT
SIR,-We have had an inquiry about a case of prolonged deafness associated with aspirin use in a recent report of ours.’ On reviewing the original record we learned that this patient had had hearing impairment before receiving aspirin. While aspirin apparently increased the degree of hearing impairment, the drug should probably not be implicated in the production of what may have been permanent deafness in this patient. Boston Collaborative Drug Surveillance Boston University Medical Center, Waltham, Massachusetts 02154, U.S.A.
2. 3. 1.
Program,
JANE PORTER HERSHEL JICK
Gallery, E. D. M., Blomfield, J., Dixon, S. R. Br. med. J. 1972, iv, 331. Comty, C., Luehmann, D, Water, R., Shapiro, F. Trans. Am. Soc. artif. intern. Organs, 1974, 20, 189. Porter, J., Jick, H. Lancet, 1977, i, 587.
*Calcium
content
by
effervescence, but small
atomic
absorption; carbonate evident from
of other anions could be present too. 3 other l.V.D.S removed from pregnant women also had extensive calcium-carbonate deposits. Calcium content was not determined for 5 of the first 23 samples. amounts
seemed pregnant also had extensive calcium-carbonate deposits covering the copper wire. We have examined many I.U.D.s removed for other reasons, and in about half of these devices no calcium carbonate was found. Where calcium-carbonate had been deposited on devices removed for reasons other than pregnancy it was usually localised and should not have greatly affected the dissolution-rate of the copper. 4 or5 of the devices removed for reasons other than pregnancy did have extensive calcium-carbonate layers. This is not surprising because the plastic device even without any copper is an effective contraceptives and pregnancy-exposure risks do vary. The presence of extensive deposits on all 8 I.U.D.S removed from pregnant women does not prove that the layer contributed to the pregnancy, but it is certainly suggestive. The coating should appreciably slow the release-rate of copper. One study which attempted to determine copper loss included i.u.D.s removed from 2 pregnant women, and in both these devices the rate of copper loss was appreciably lower than average. However, variations in the composition of the corrosion layers2 and in the weight of the copper in the devices’ make such estimates only semiquantitative. Inert I.U.D.S also show calcium salt deposits,? so any I.U.D. which releases an active agent should have its efficacy limited by the build-up of calcium salts. As you noted’ women carrywoman
1. Lancet, 1977, i, 1239. 2. Lewis, K. M., Archer, R.
D., Ginsberg, A. P., Rosencwaig, A. Contraception,
1977, 15, 93. Gosden, C., Ross, A., Loudon, N. B. Br. med. J. 1977, i, 202. VanEyck, J., Lagasse, A., Thiery, M. Contraception, 1976, 13, 65. Zipper, J., Medel, M., Pastene, L., Rivera, M., Torres, L., Osorio, A., Toscanini, C. ibid. p. 7. 6. Zielske, F., Koch, F., Badura, R., Ladeburg, H. ibid. 1974, 10, 651. 7. Engineer, A. D., Dasgupta, P. R., Kar, A. B. Am. J. Obstet. Gynec. 1970, 106, 315. 3. 4. 5.
459 seem to have pregnancythose fitted with copper I.U.D.S. Uterine fluids rates similar with l.U.D.S present have calcium and carbonate concentrations necessary for saturation.89 A slow acid release at the l.U.D. surface might solve the carbonate build-up. The carbonate layer can form quickly. 1 device had about half the corrosion. layer as calcium carbonate in under 10 months; however, 3 I.U.D.S in situ for a year or more had less than 1% of the corrosion layer as calcium carbonate. There may be a slightly positive correlation between time in situ and calcium-carbonate deposition,2·3but the pregnancy-rate during the second year of copper I.U.D. use does not seem to be greater than that of the first year.
SOURCE OF AMERICAN SERRATIA
ing progesterone-releasing devices to
We thank the University of Massachusetts and its Research Council for partial support through biomedical sciences support grants.
Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, U.S.A.
RONALD D. ARCHER KENRICK M. LEWIS
Amherst Medical Associates
STEVEN J. ZWIREK
USE OF BLOOD-CULTURES
SIR,-Durbridge’ and Eisenberg2 are both doubtful of the value of blood-cultures in the diagnosis of septicaemia in adults, because the condition is usually clinically recognisable, and treatment is often started before the results of the culture are known. In geriatric practice, where patients often present in a nonspecific atypical manner, blood-cultures remain a very useful diagnostic tool. A recent survey3 showed that the test was helpful in the diagnosis of patients presenting with a non-specific malaise or "failure to thrive". The test also clarified the treatment of elderly patients with respiratory infection by identifying the causal organism when sputum cultures were negative. It is worth noting that elderly patients with significant bacteramua were characterised by the virtual absence of fever, collapse, shock, vomiting or oliguria. Patients with subacute bacterial endocarditis had only one constant sign-the cardiac murmur. Under half the patients had evidence of anaemia, polymorphonuclear leucocytosis, or uraemia. Northwick Park Hospital, Harrow, Middlesex HA1 3UJ
M.
J. DENHAM
SMOKING AND MENOPAUSE
SiR,-After the appearance of our article4 we became aware two previous publicationss.6 which described earlier menopause in smokers, and we should like to acknowledge them. HERSHEL JICK Boston Collaborative Drug Surveillance Program,
of
Boston University Medical Center, Waltham, Massachusetts 02154, U.S.A.
8. Kar, A. B.,
JANE PORTER
ALAN S. MORRISON
Engineer, A. D., Goel, R., Kamboj, V. P., Dasgupta, P. R., Chowdhury, S. R. ibid. 1968, 101, 966. 9. Moore, E. W. in Ion Exchange Electrodes (edited by R. A. Durst);chap. 7. Washington, D.C., 1969. 10. Roy, S., Azen, S. P., Mishell, D. R., Pike, M. C., Casagrande, J. Contraception, 1976, 13, 365. 1. Durbridge, T. C. Lancet, 1977, i, 1206. 2. Eisenberg, J. M. ibid. 1977, ii, 140. 3. Denham, M. J., Goodwin, G. S. Age Ageing, 1977, 6, 85. 4. Jick, H., Porter, J., Morrison, A. S. Lancet, 1977, i, 1354. 5. Bernhardt, P. Münch. med. Wschr. 1962, 104, 1826. 6. Daniell, H. W. Archs intern. Med. 1976, 136, 298.
SIR,-Dr Severn (April 2, p. 750) suggested that the greater reported incidence of Serratia marcescens as a pathogen in the U.S.A. compared with the U.K. may be due to its use in germwarfare population-vulnerability studies. This possibility has also been widely discussed in the American press. Since we have studied over 5000 S. marcescens strains from all over the world,’ our data may be helpful in examining this hypothesis. The following facts should be considered. 1. Although S. marcescens may not be an important opportunistic pathogen in the U.K., recent reports2 indicate its importance in France, Germany, Belgium, and other European countries. The experience in these countries (where, presumably, population-vulnerability studies did not take place) is similar to the American experience.’I 2. The strain that was used in the American population-vulnerability studies was S. marcescens 8 UK, a strain with a bright red pigment which has often been used as a biological indicator in aerosol experiments. This strain (obtained by us from Fort Detrick in 1969 and again in 1977) is biotype A6, serotype 08:H3, and phage type 678. These four markers form a distinct "fingerprint". Because strains of 8 UK that we preserved in 1957 and 1969 still have these characteristics, we feel that the markers are stable. 3. Biotype A6 of S. marcescens is rare;3only 20 of 2062 cultures we examined belonged to this biotype. Biotype A6 is usually isolated from the environment rather than from human infection. Only 1 of 178 strains of S. marcescens from patients in Bordeaux was biotype A6, as were only 2 of 377 strains from hospital patients in France, Germany, and Belgium. Of the American strains tested, 7 were biotype A6 but only 1 had the same serotype as strain 8 UK. S. marcescens of biotype A6 did cause a nursery outbreak in Minnesota (U.S.A.) in 1968, but the strain was of a different serotype (08:H13) from S. marcescens8UK which was used in the population-vulnerability studies. 4. Of more than 3000 U.S. strains serotyped since 1950, serotype 08 :H3 was found only 7 times. 5. Of more than 100 outbreaks of S. marcescens infection we studied in the U.S., none has been caused by a strain with characteristics of strain 8 UK. We believe that many different strains of S. marcescens cause sporadic infections and outbreaks in the U.S.’ Because not all strains of S. marcescens isolated in the U.S. are referred to us, we cannot comment on the true incidence of strain 8 UK in the U.S.A. However, we do not think that our data support the hypothesis that S. marcescens 8 UK, which was used in germ-warfare population-vulnerability studies, is an important cause of morbidity and mortality in the U.S.A. Any strains which are implicated as being related to this activity can be scientifically tested because strain 8 UK has four stable and distinct biological markers. During our investigations, we did encounter one instance in which S. marcescens 8 UK was definitely associated with intestinal colonisation of an infant. In 1957 a newborn baby in a Wisconsin nursery had red-diaper syndrome.’ The strain was shown to be serotype 08:H3 at the Center for Disease Control. An epidemiological investigation revealed that a scientist at the hospital was releasing S. marcescens 8 UK (which we confirmed to be of serotype 08:H3), as part of a research project on aerosol techniques.4 The infant was colonised by this strain, which apparently caused no harm. However, the parents (the father was a geneticist) were quite worried because originally they thought their daughter had an inborn error of metabolism. The strain was also a nuisance to a local laundry because
Farmer, J. J., Davis, B. R., Hickman, F. H., Presley, D. B., Bodey, G. P., Negut, M. H., Bobo, R. A. Lancet, 1976, ii, 455. 2. Lancet, 1977, i, 636. 3. Grimont, P. A. D., Grimont, F., Dulong de Rosnay, H. L. C., Sneath, P. H. A. J. gen. Microbiol. 1977, 98, 39. 4. Waisman, H. A., Stone, W. H. Pediatrics, 1958, 21, 8. 1.