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SCREENING FOR VITAMIN-B12 DEFICIENCY
309
normal sea-level values in about 3 months2 and that the increased sensitivity to hypoxia persists for weeks or even months. Would the native in time become imadapted to his original life? If so, he would probably reacclimatise quite quickly.
Annotations A BASELINE FOR CRIMINAL ABORTIONS?
THOSE who support the spirit of the Abortion Act -and even, perhaps, some of those who do notmust hope that it will be seen to bring about a reduction in maternal mortality and illegitimacy and relieve distress not measurable in statistical terms. It is far too early to say whether any of these objectives have been achieved, but in any assessment of the effect on the incidence of self-induced or back-street abortions a reliable baseline would be helpful. Goodhart 12 suggests that previous estimates of the number of illegal abortions done in the U.K. were much too large: more specifically he now claims that the oft-cited figure of around 100,000 illegal abortions a year before the Abortion Act came into operation is about five times too high. Such a claim merits careful evaluation, because if it is correct the interpretation of abortion statistics will be more difficult than it is
Lastly, Goodhart looks to Aberdeen for support. In city there was a sympathetic attitude to abortion long before the 1967 Act, and Baird 14 has suggested that criminal abortion has almost disappeared. Thus, that
many of the 70 or so abortions done in Aberdeen each year might otherwise be done illegally, again producing an abortion-rate on a national scale of far less than 100,000. But Aberdeen is not typical: the city has a better family-planning service that most other
places in Britain, and tubal ligation is offered to and accepted by many women post partum. Goodhart’s paper is useful in eliminating some of the wilder guesses in excess of 100,000, and in stimulating a more critical attitude to these statistics, but his own estimate of 15,000 to 20,000 seems unrealistic. In evaluating the effects of the Abortion Act it seems wiser to accept a higher figure. If we do, and remove from the notifications (45,000 a year) some arbitrary figure for patients coming from overseas and for those who would not have turned elsewhere had a legal termination been refused, we seem to be left with a number of women who continue to have recourse to the illegal operator. As Sir George Godber says on p. 312, " Something is radically wrong if the very women whose safety we hoped to achieve are still seeking illicit and dangerous intervention rather than a service which the N.H.S. could provide."
already. There are three ways of interpreting the statement that 30 maternal deaths in 100,000 abortions seems improbably low. The numerator might be too small (if death certificates understate the true position); the rate could be exactly right, merely unsurprising; or, as Goodhart believes, the denominator could be too large. Most people now agree that the mortality figures for abortions are more or less right, especially since they tally with the data from the confidential inquiries into maternal deaths. In countries such as Japan, Czechoslovakia, and Hungary with longer experience of the workings of a liberal law on abortion, the death-rate for legally terminated pregnancies has been less than 5 per 100,000 operations; in England and Wales there were 3 deaths among at least
25,000 (Diggory’s estimate 13) legal terminations in 1967, and 6 such deaths were notified in 1968 when many more abortions were done. Thus 100,000 a year is compatible with 30 maternal deaths if criminal abortion is taken to be ten times more risky than termination in proper surroundings and by experienced operators. In fact, it may be wrong to concentrate too much on maternal lives saved when justifying the Abortion Act since, of 100,000 pregnant women, about 20 would be expected to die as a result of pregnancy. Hospital inpatient statistics are of little value since no-one knows what proportion of women undergoing illegal intervention will eventually present at hospital with complications. An opinion poll carried out for the Abortion Law Reform Association three years ago had a responserate of only 60%, and so the estimate of 31,000 illegal abortions a year for 1946-65 is not very conclusive.
illegal abortions
12. 13.
Goodhart, C. B. J. biosoc. Sci. 1969, 1, 235. Diggory, P. L. C. Lancet, 1969, i, 873.
SCREENING FOR VITAMIN-B12 DEFICIENCY
VITAMIN-BI2 deficiency may give rise to hamatelogical, neurological, and mental abnormalities either singly or in combination. The commonest cause of vitamin-B12 deficiency in Western countries is pernicious anaemia, and the diagnosis can often be suspected on clinical grounds; but, in the vast majority of cases, whether it is suspected clinically or not, there are associated changes in the peripheral blood, such as anisopoikilocytosis and macrocytosis of the red cells, hypersegmentation of neutrophil nuclei, and megaloblastic changes in the bone-marrow. Less commonly, gastrectomised patients and those with disease involving the terminal ileum may develop vitamin-Bl2 deficiency. Dietary deficiency is a rare cause of vitamin-B12 deficiency and is seen only in strict vegans. Very occasionally the mental abnormalities may dominate the clinical picture in pernicious anaemia and the hasmatological changes may be slight or not apparStrachan and Henderson 15 reported 3 cases of ent. this kind among their psychiatric patients in Aberdeen. The incidence of pernicious anaemia in psychiatric patients is about the same as that in the general population 16 and it accounts for under 1 % of psychiatric illness,17 Nevertheless, because it is a treatable form of mental illness, early diagnosis is important. Henderson et
a1.l7 have put forward the view that occult vitamin-
Bl2 deficiency is a commoner cause of mental illness than is generally believed and they advocate screening all psychiatric patients for pernicious anxmia; for this purpose they propose the immunofluorescence 14. 15. 16. 17.
Baird, D. Eugen. Rev. 1966, 58, 195. Strachan, R. W., Henderson, J. G. Q. Jl Med. 1965, 34, 303. Shulman, R. Br. med. J. 1967, ii, 266. Henderson, J. G., Strachan, R. W., Beck, J. S., Dawson, A. A., Daniel, M. Lancet, 1966, ii, 809.
310
detecting antibodies in serum to gastric parietal cells, preferring this method for screening method for
purposes
to
the direct estimation of the
serum-
vitamin-Bl2 concentration. Antibodies to gastric parietal cells are not found in all patients with pernicious anxmia (the overall incidence is about 80%); and they may also be found in a substantial number of patients without pernicious anxmia, the number increasing with age. Thus, the test will be positive in most but not all cases of pernicious anaemia and it will also give many false-positive results. Despite these shortcomings Henderson et a1.17 prefer the antibody test to the direct estimation of vitamin B12 in serum, claiming that it is quicker and simpler. More recently Swanson Beck et a1,18 have presented evidence that the antibody test is also more economical to carry out.
THE YEAR OF THE DEPARTMENT
THE new Department of Health and Social Security into being on Nov. 1, 1968, so its first annual report 25 covers a year punctuated by this coordinating event. One of the first priorities has been the integration of research and the development of central planning ; and early steps have been taken to create the necessary machinery. Moreover, the year was marked by unprecedented activity in the way of proposals for radical reconstruction and change in the social services -notably the earnings-related national superannuation scheme, the Seebohm and Todd reports, and the green-paper on the administrative structure of the medical and related services. During the year E90-5 million was spent on hospital building (in terms of advances to hospital boards on capital accounts), compared with E75’3 million in 1966-67. The estimate for 1968-69 is E101 million. Building schemes to the value of S124 million were started in 1967-68, compared with E108 million in 1966-67. The total value of work in progress at Sept. 30, 1968, was E320 million, an increase of 25% over the corresponding figure for 1967. Total N.H.S. hospital revenue expenditure rose from S675 million in 1966-67 to E731 million in 1967-68; and about twothirds of this increase was accounted for by changes in the rates of pay and insurance of staff, by rises in the price of commodities and services, and by the first full year of selective employment tax. On Dec. 31, 1968, 534,890 patients were waiting for admission to N.H.S. hospitals as inpatients. This modest reduction of 6-4% over 1967 is no matter for loud cheers, but some satisfaction lies in the fact that this is the first fall recorded since 1962. The largest waiting-lists continued to be those in surgical and gynaecological departments. For the second year running, however, general surgery showed a small reduction and other specialties to improve were E.N.T., ophthalmology, urology, plastic surgery, and thoracic surgery. On the other hand, waiting-lists for traumatic and orthopaedic surgery, cardiology, dentistry, and In gynaecology, neurosurgery increased further. where pressure on resources has long been sustained, a small decrease was recorded for the second year in succession. In the medical specialties lists fell by about 1-3%. The ratio of numbers awaiting admission came
patients with positive tests for antibodies gastric parietal cells, further tests to confirm the diagnosis of pernicious anxmia are carried out (for example, serum-vitamin-Bl2 assay, gastric-juice analysis for acid content, and tests for vitamin-Bl2 absorption). But only a small proportion of psychiatric patients in whom antibodies to gastric parietal cells were detected were later found to have pernicious anxmia 1’ and the value of the suggested screening test (in preference to a careful blood-count and film examination followed by assay of vitamin B12 in serum) has been questioned. I 9 20 Furthermore Shulman 16 21 22 has expressed doubt about the causal link between reduced levels of vitamin B12 in serum and the psychiatric state of the patient. He described 10 patients with reduced levels of vitamin Bl2 in serum: 4 recovered or improved without B12 therapy, 5 with advanced senile dementia showed no response to vitamin-Bl2 injections, and 1 patient with an acute confusional On those
to
died. He concluded 16 that there was no evidence support the routine screening of psychiatric patients for pernicious anaemia, and he suggested that psychiatrists should be alert to the possibility of Bl2 deficiency in three situations: anaemic or post-gastrectomy patients, those with unexplained fatigue, and those with confusional states or dementia of unknown origin. Hxmatological changes, with or without anaemia, can be detected in the vast majority of patients with pernicious anxmia, and a hxmoglobin estimation with a careful examination of a blood-film by an experienced hxmatologist should be carried out in the first place. Further tests, including serum-B12 assay, can then establish the diagnosis; if special tests are to be used for screening then serum-vitarnin-B12 assay would seem preferable to the indirect method of testing for antibodies to gastric parietal cells. Swanson Beck et a1,18’I have calculated that the indirect method is substantially cheaper than the direct estimation of vitamin B12 in serum using Lactobacillus leichmannii, but other factors should probably be considered as well, such as the need for specialised equipment (fluorescence microscope, cryostat), the supply of normal stomach tissue, and also the skill required in reading the immunofluoresstate
to
18. Beck, J. S., Dawson, A. A., Henderson, J. G., J. clin. Path. 1969, 22, 317. 19. Hansen, T., Rafaelson, O. J., Rødbro, P. Lancet, 20. Varadi, S. ibid. 21. Shulman, R. Br. J. Psychiat. 1967, 113, 241. 22. Shulman, R. ibid. p. 252.
results. But even the estimation of the serumvitamin-Bl2 concentration by microbiological methods is not specific, in that patients with folate deficiency may have reduced serum-Bl2 levels as a consequence of folate deficiency and this state is not necessarily a true B12 deficiency. 23 Because mentally disturbed patients may not eat well, dietary folate deficiency may develop. A simple, rapid, and specific test for vitaminB12 deficiency remains to be devised. It might be possible to automate a radioisotope method for estimating B12 in serum.24 cence
Strachan,
R. W.
1966, ii, 965.
23. Johnson, S., Swaminathan, S. P., Baker, J. J. clin. Path. 1962, 15, 274. 24. Raven, J. L., Robson, M. B., Walker, P. L., Barkhan, P. ibid. 1969, 22, 205. 25. Annual report of the Department of Health and Social Security for the year 1968. Cmnd. 4100. H.M. Stationery Office, 1969. 40s.
normal sea-level values in about 3 months2 and that the increased sensitivity to hypoxia persists for weeks or even months. Would the native in time become imadapted to his original life? If so, he would probably reacclimatise quite quickly.
Annotations A BASELINE FOR CRIMINAL ABORTIONS?
THOSE who support the spirit of the Abortion Act -and even, perhaps, some of those who do notmust hope that it will be seen to bring about a reduction in maternal mortality and illegitimacy and relieve distress not measurable in statistical terms. It is far too early to say whether any of these objectives have been achieved, but in any assessment of the effect on the incidence of self-induced or back-street abortions a reliable baseline would be helpful. Goodhart 12 suggests that previous estimates of the number of illegal abortions done in the U.K. were much too large: more specifically he now claims that the oft-cited figure of around 100,000 illegal abortions a year before the Abortion Act came into operation is about five times too high. Such a claim merits careful evaluation, because if it is correct the interpretation of abortion statistics will be more difficult than it is
Lastly, Goodhart looks to Aberdeen for support. In city there was a sympathetic attitude to abortion long before the 1967 Act, and Baird 14 has suggested that criminal abortion has almost disappeared. Thus, that
many of the 70 or so abortions done in Aberdeen each year might otherwise be done illegally, again producing an abortion-rate on a national scale of far less than 100,000. But Aberdeen is not typical: the city has a better family-planning service that most other
places in Britain, and tubal ligation is offered to and accepted by many women post partum. Goodhart’s paper is useful in eliminating some of the wilder guesses in excess of 100,000, and in stimulating a more critical attitude to these statistics, but his own estimate of 15,000 to 20,000 seems unrealistic. In evaluating the effects of the Abortion Act it seems wiser to accept a higher figure. If we do, and remove from the notifications (45,000 a year) some arbitrary figure for patients coming from overseas and for those who would not have turned elsewhere had a legal termination been refused, we seem to be left with a number of women who continue to have recourse to the illegal operator. As Sir George Godber says on p. 312, " Something is radically wrong if the very women whose safety we hoped to achieve are still seeking illicit and dangerous intervention rather than a service which the N.H.S. could provide."
already. There are three ways of interpreting the statement that 30 maternal deaths in 100,000 abortions seems improbably low. The numerator might be too small (if death certificates understate the true position); the rate could be exactly right, merely unsurprising; or, as Goodhart believes, the denominator could be too large. Most people now agree that the mortality figures for abortions are more or less right, especially since they tally with the data from the confidential inquiries into maternal deaths. In countries such as Japan, Czechoslovakia, and Hungary with longer experience of the workings of a liberal law on abortion, the death-rate for legally terminated pregnancies has been less than 5 per 100,000 operations; in England and Wales there were 3 deaths among at least
25,000 (Diggory’s estimate 13) legal terminations in 1967, and 6 such deaths were notified in 1968 when many more abortions were done. Thus 100,000 a year is compatible with 30 maternal deaths if criminal abortion is taken to be ten times more risky than termination in proper surroundings and by experienced operators. In fact, it may be wrong to concentrate too much on maternal lives saved when justifying the Abortion Act since, of 100,000 pregnant women, about 20 would be expected to die as a result of pregnancy. Hospital inpatient statistics are of little value since no-one knows what proportion of women undergoing illegal intervention will eventually present at hospital with complications. An opinion poll carried out for the Abortion Law Reform Association three years ago had a responserate of only 60%, and so the estimate of 31,000 illegal abortions a year for 1946-65 is not very conclusive.
illegal abortions
12. 13.
Goodhart, C. B. J. biosoc. Sci. 1969, 1, 235. Diggory, P. L. C. Lancet, 1969, i, 873.
SCREENING FOR VITAMIN-B12 DEFICIENCY
VITAMIN-BI2 deficiency may give rise to hamatelogical, neurological, and mental abnormalities either singly or in combination. The commonest cause of vitamin-B12 deficiency in Western countries is pernicious anaemia, and the diagnosis can often be suspected on clinical grounds; but, in the vast majority of cases, whether it is suspected clinically or not, there are associated changes in the peripheral blood, such as anisopoikilocytosis and macrocytosis of the red cells, hypersegmentation of neutrophil nuclei, and megaloblastic changes in the bone-marrow. Less commonly, gastrectomised patients and those with disease involving the terminal ileum may develop vitamin-Bl2 deficiency. Dietary deficiency is a rare cause of vitamin-B12 deficiency and is seen only in strict vegans. Very occasionally the mental abnormalities may dominate the clinical picture in pernicious anaemia and the hasmatological changes may be slight or not apparStrachan and Henderson 15 reported 3 cases of ent. this kind among their psychiatric patients in Aberdeen. The incidence of pernicious anaemia in psychiatric patients is about the same as that in the general population 16 and it accounts for under 1 % of psychiatric illness,17 Nevertheless, because it is a treatable form of mental illness, early diagnosis is important. Henderson et
a1.l7 have put forward the view that occult vitamin-
Bl2 deficiency is a commoner cause of mental illness than is generally believed and they advocate screening all psychiatric patients for pernicious anxmia; for this purpose they propose the immunofluorescence 14. 15. 16. 17.
Baird, D. Eugen. Rev. 1966, 58, 195. Strachan, R. W., Henderson, J. G. Q. Jl Med. 1965, 34, 303. Shulman, R. Br. med. J. 1967, ii, 266. Henderson, J. G., Strachan, R. W., Beck, J. S., Dawson, A. A., Daniel, M. Lancet, 1966, ii, 809.
310
detecting antibodies in serum to gastric parietal cells, preferring this method for screening method for
purposes
to
the direct estimation of the
serum-
vitamin-Bl2 concentration. Antibodies to gastric parietal cells are not found in all patients with pernicious anxmia (the overall incidence is about 80%); and they may also be found in a substantial number of patients without pernicious anxmia, the number increasing with age. Thus, the test will be positive in most but not all cases of pernicious anaemia and it will also give many false-positive results. Despite these shortcomings Henderson et a1.17 prefer the antibody test to the direct estimation of vitamin B12 in serum, claiming that it is quicker and simpler. More recently Swanson Beck et a1,18 have presented evidence that the antibody test is also more economical to carry out.
THE YEAR OF THE DEPARTMENT
THE new Department of Health and Social Security into being on Nov. 1, 1968, so its first annual report 25 covers a year punctuated by this coordinating event. One of the first priorities has been the integration of research and the development of central planning ; and early steps have been taken to create the necessary machinery. Moreover, the year was marked by unprecedented activity in the way of proposals for radical reconstruction and change in the social services -notably the earnings-related national superannuation scheme, the Seebohm and Todd reports, and the green-paper on the administrative structure of the medical and related services. During the year E90-5 million was spent on hospital building (in terms of advances to hospital boards on capital accounts), compared with E75’3 million in 1966-67. The estimate for 1968-69 is E101 million. Building schemes to the value of S124 million were started in 1967-68, compared with E108 million in 1966-67. The total value of work in progress at Sept. 30, 1968, was E320 million, an increase of 25% over the corresponding figure for 1967. Total N.H.S. hospital revenue expenditure rose from S675 million in 1966-67 to E731 million in 1967-68; and about twothirds of this increase was accounted for by changes in the rates of pay and insurance of staff, by rises in the price of commodities and services, and by the first full year of selective employment tax. On Dec. 31, 1968, 534,890 patients were waiting for admission to N.H.S. hospitals as inpatients. This modest reduction of 6-4% over 1967 is no matter for loud cheers, but some satisfaction lies in the fact that this is the first fall recorded since 1962. The largest waiting-lists continued to be those in surgical and gynaecological departments. For the second year running, however, general surgery showed a small reduction and other specialties to improve were E.N.T., ophthalmology, urology, plastic surgery, and thoracic surgery. On the other hand, waiting-lists for traumatic and orthopaedic surgery, cardiology, dentistry, and In gynaecology, neurosurgery increased further. where pressure on resources has long been sustained, a small decrease was recorded for the second year in succession. In the medical specialties lists fell by about 1-3%. The ratio of numbers awaiting admission came
patients with positive tests for antibodies gastric parietal cells, further tests to confirm the diagnosis of pernicious anxmia are carried out (for example, serum-vitamin-Bl2 assay, gastric-juice analysis for acid content, and tests for vitamin-Bl2 absorption). But only a small proportion of psychiatric patients in whom antibodies to gastric parietal cells were detected were later found to have pernicious anxmia 1’ and the value of the suggested screening test (in preference to a careful blood-count and film examination followed by assay of vitamin B12 in serum) has been questioned. I 9 20 Furthermore Shulman 16 21 22 has expressed doubt about the causal link between reduced levels of vitamin B12 in serum and the psychiatric state of the patient. He described 10 patients with reduced levels of vitamin Bl2 in serum: 4 recovered or improved without B12 therapy, 5 with advanced senile dementia showed no response to vitamin-Bl2 injections, and 1 patient with an acute confusional On those
to
died. He concluded 16 that there was no evidence support the routine screening of psychiatric patients for pernicious anaemia, and he suggested that psychiatrists should be alert to the possibility of Bl2 deficiency in three situations: anaemic or post-gastrectomy patients, those with unexplained fatigue, and those with confusional states or dementia of unknown origin. Hxmatological changes, with or without anaemia, can be detected in the vast majority of patients with pernicious anxmia, and a hxmoglobin estimation with a careful examination of a blood-film by an experienced hxmatologist should be carried out in the first place. Further tests, including serum-B12 assay, can then establish the diagnosis; if special tests are to be used for screening then serum-vitarnin-B12 assay would seem preferable to the indirect method of testing for antibodies to gastric parietal cells. Swanson Beck et a1,18’I have calculated that the indirect method is substantially cheaper than the direct estimation of vitamin B12 in serum using Lactobacillus leichmannii, but other factors should probably be considered as well, such as the need for specialised equipment (fluorescence microscope, cryostat), the supply of normal stomach tissue, and also the skill required in reading the immunofluoresstate
to
18. Beck, J. S., Dawson, A. A., Henderson, J. G., J. clin. Path. 1969, 22, 317. 19. Hansen, T., Rafaelson, O. J., Rødbro, P. Lancet, 20. Varadi, S. ibid. 21. Shulman, R. Br. J. Psychiat. 1967, 113, 241. 22. Shulman, R. ibid. p. 252.
results. But even the estimation of the serumvitamin-Bl2 concentration by microbiological methods is not specific, in that patients with folate deficiency may have reduced serum-Bl2 levels as a consequence of folate deficiency and this state is not necessarily a true B12 deficiency. 23 Because mentally disturbed patients may not eat well, dietary folate deficiency may develop. A simple, rapid, and specific test for vitaminB12 deficiency remains to be devised. It might be possible to automate a radioisotope method for estimating B12 in serum.24 cence
Strachan,
R. W.
1966, ii, 965.
23. Johnson, S., Swaminathan, S. P., Baker, J. J. clin. Path. 1962, 15, 274. 24. Raven, J. L., Robson, M. B., Walker, P. L., Barkhan, P. ibid. 1969, 22, 205. 25. Annual report of the Department of Health and Social Security for the year 1968. Cmnd. 4100. H.M. Stationery Office, 1969. 40s.