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ANOTHER AMITRIPTYLINE SIDE-EFFECT?
590 management that seems reasonable to the others; that they should, with the cooperation of the others, be able to develop an interest and expertise in a particular condition or form of therapy; and that they should all participate, if they wish, in the organisation and administration of the division. It is only by the closest and most harmonious team-work that the best results are achieved. Scotland’s " continuing status ... as an obstetric poor relation ", to quote Mr. MacDonald, is not contributed to by team-work; the poor results are due to environmental factors causing prematurity and foetal abnormalities rather than to obstetric factors for which the obstetric service could be held responsible. University Department of Obstetrics and Gynæcology, IAN MACGILLIVRAY. Foresterhill, Aberdeen AB9 2ZD.
SiR,—Iwas interested by the letter from Mr. MacDonald, and am entirely in sympathy with his views. I am a consultant in administrative charge but have experience in both the English and Scottish systems. There is no doubt that, compared with England, Scotland has had a hierarchical and somewhat autocratic tradition in the relationships between consultants, though this is disappearing in many centres. I do not believe that it is necessary to give up all the advantages of some form of organisation between consultants in the same specialty, as has been advocated in the recent reports in England and Scotland cited in Mr. MacDonald’s letter, in order to preserve consultant clinical freedom. The divisional type of organisation has many virtues for large departments trying to provide a community service, particularly in my own sphere of orthopxdic and accident work, in which beds have to be set aside for such purposes to keep an accident service running. The preservation of this freedom is I believe quite simple but of vital importance. A consultant in administrative charge should have no clinical overseeing of his consultant colleagues. The consultant in charge is not in clinical charge of patients, who should be left to the consultant whose patients they are he is only in administrative charge. In my own department I have never seen the patient of another colleague except at his request in the ten years that I have been here; this is a matter of simple principle. It is only by seeing that all consultants have total clinical responsibility for their patients that one may expect to attract and keep worth-while colleagues. In addition, the multiple problems of administration in this type of department, with a large number of junior staff to be rotated for training purposes and holidays, and the many other administrative matters that arise, are surely to be met not by a dictat from the consultant in administrative charge but by discussion in a consultant staff committee where policy can be made. Clearly from his situation the consultant in charge is most in touch with the administrative problems, is often able to suggest solutions, and must be able to take day-to-day decisions on administrative matters. Choosing colleagues both consultant and junior involves only rotation on selection committees, and arranging junior staff to work with all consultants on a six-monthly basis (not in daily fashion) to provide training is surely not difficult. In clinical work there are occasional reasons for accepting a departmental policy-e.g, controlled trials. Special clinical problems may interest one man among a group, and his colleagues may wish to concentrate such cases under the care of this one consultant. Discussion in a consultant staff committee is the ideal mode of making such mutually agreeable arrangements.
There is no doubt that medical administrators by and large do enjoy the advantages of having a single person to consult, but this should be strongly resisted. Mr. MacDonald’s letter is very important, particularly at this time when divisional organisation may be introduced. It is, however, possible to have administrative collaboration and clinical independence, and it is essential to see that this is achieved. University Department of Orthopaedic Surgery, Clinical Research Unit, Princess Margaret Rose Orthopdæic Hospital, J. I. P. JAMES. Edinburgh 10.
DUAL ADDICTION SIR,-I have followed with interest the recent correspondence on the effects of barbiturates and other drugs, and of withdrawal from them. Dr. Merry (Jan. 13, p. 96) advisedly draws attention to the concurrent use of heroin and barbiturates. In this foundation we have observed that there is an apparent increase in the proportion of our patients (primarily heroin addicts) who also abuse barbiturates. A recent study1 lends support to this observation. Too often one may not be aware of this dual addiction, and the patient is not asked if he (or more likely she) is also using barbiturates when heroin-withdrawal treatment is being instituted. Dr. Merry draws attention to the need to ask the patient this question-and the same applies to the possibility of abuse of a variety of other drugs. Since withdrawal from barbiturates is usually a more dangerous and difficult problem in management and treatment, the patient requires continued supervision in a hospital or clinic. It should be a standard part of the clinical investigation to inquire into the history of use of other sedative or stimulant drugs. Even when the patient denies that this is so, on his admission to hospital a careful search should always be made of his clothing and other possessions, since patients will often secrete such drugs, or have their friends and relatives supply them, while they are being withdrawn from heroin or other
drug.22 Drug abuse should also be considered in the differential diagnosis of a patient who has vague or recurrent complaints, particularly insomnia, and it should be remembered that such abuse is not necessarily restricted to just one drug at a time. The Narcotic Addiction Foundation of British Columbia, Vancouver 9.
R. HALLIDAY.
DIAZEPAM FOR TREATMENT OF PHOBIAS SIR,-I read Dr. Yeung’s letter (March 2, p. 475) with some interest, but I should like to know why he goes to the trouble of giving diazepam (’Valium’) intravenously when surely a similar dose orally would have the same effect. My practice in patients with agoraphobia and other similar phobias is to give the patient a supply of 2 mg. tablets of diazepam, which I tell him to take in proportion to the anxiety he experiences or thinks he may experience in any given situation. For example, some patients find that the journey to work in the morning is a very much more stressful and anxiety-provoking experience than the journey home in the evening. In such a case the patient might take a dose of 10 mg. before the morning journey and need only, say, 4 mg. for the journey home. I certainly find intravenous diazepam useful, since it gives some guide to the dose of oral medication which may be needed. It also helps to give the patients confidence that diazepam is an active agent and really will relieve the anxiety of which they complain. However, I should like to make a plea for much more flexible drug dosage in psychiatry, particularly with patients like agoraphobics in whom there is a wide variation in anxiety throughout the day. Rigid dosage on a t.d.s. or q.d.s. basis is surely inappropriate in these cases. Bexley Hospital, MICHAEL BOTT. Bexley, Kent.
ANOTHER AMITRIPTYLINE SIDE-EFFECT? SIR,-Dr. Blackwell (Feb. 24, p. 426) discusses amitriptyline
possible cause of hysteria. Last month in this hospital I saw a 59-year-old man, who 8 months before had been treated with imipramine and diazepam in ordinary doses because of a mild depression. 2 weeks after the beginning of this therapy he had complained of parassthesia over the whole of the left side of the body. He had also had short attacks of speech disturbance. His doctor had reassured him and had not arranged any further examinations. 6 months as a
1. 2.
Cumberlidge, M. C. Can. med. Ass. J. (in the press.) Halliday, R. Br. Columbia med. J. 1967, 9, 374.
591 later he had had slight paresis of his left hand, and when I saw him he also had paresis of his left leg. Right-sided carotid angiography showed stenosis in the lower intracanalicular part of the internal carotid artery. In the next week his left-sided paresis became complete, and repeated carotid angiography showed total stenosis of the medial cerebral artery, 3 cm. from its origin. The systolic blood-pressure varied between 150 and 100 mm. Hg, and he was not on antidepressants. This short description emphasises that the diagnosis of hysteria in a similar case must be very doubtful until a neuroradiological investigation has been done. Tricyclic antidepressants with their well-known tendency to produce orthostatic hypotension may cause recurrent ischasmic attacks in persons with partial obstruction of the cerebral arteries. Lasarettet, CARL L. BRECHTER. Trelleborg, Sweden
IRON DEFICIENCY WITHOUT ANÆMIA SIR,-We wish to take issue with you over your leading article (March 2, p. 462). We feel that a very biased view of the so-called syndrome of " sideropenia " has been presented. In your leading article you outline the argument which first led to the use of the term " sideropenia ". Yet you fail to " point out the " non-sequitur in this argument, nor do you make reference to a study published in this journal which showed that in the community the association between postcricoid dysphagia and iron deficiency is probably chance.1 You then refer to the often quoted trial of Beutler et awl. In fact you describe this trial wrongly as there were not two separate treatment groups, but a cross-over design was used and every subject was given both iron and placebo tablets. At the end of the trial the benefit from the two treatments were compared on the basis of conventional clinical interviews. It MEAN CHANGES IN " FATIGUE ", GRADED ON AN ARBITRARY SEVENPOINT SCALE, IN WOMEN WITH AN INITIAL HIGH GRADE OF " " FATIGUE AND H/BMOGLOBIN LEVELS OF 13-5 ML. OR MORE, AT GIVEN, RANDOM, ORAL IRON OR A PLACEBO TABLET FOR EIGHT WEEKS.
G/100
A
negative change in the grade implies improvement.
is obvious, and Beutler et al. admit, that because of undesirable side-effects the iron tablet could not be effectively masked, and, therefore, this trial was not truly blind on the"part of all of the subjects. In fact, their " placebo " was not a placebo "3 Your leading article then refers to a study by Macfarlane et al.4 who found a prevalence of 21 % of women with " latent iron deficiency." Yet you fail to refer to the double-blind trial of iron therapy conducted by the workers, in which there was no evidence that iron therapy gave greater symptomatic benefit than an iron-free placebo.5 We have already presented the results of a community study of the effect of oral iron on symptoms,6 and we hope shortly to report the results of further larger studies. These latter included a trial which was similar to that of Beutler et awl. but 1.
Elwood, P. C., Jacobs, A., Pitman, R. G., Entwistle, C. C. Lancet, 1964, ii, 716. 2. Beutler, E., Larsh, S. E., Gurney, C. W. Ann. intern. Med. 1960, 52, 378. 3. Leyburn, P. Lancet, 1967, ii, 1135. 4. Macfarlane, B., Pinkerton, P. H., Dagg, J. H., Goldberg, A. Br.J. Hœmat.
in which we did not use a cross-over design. The table summarises some of the results and shows that at every initial level of serum-iron the beneficial effect of iron was less than that of a placebo tablet. There are serious statistical objections to the syndrome of " sideropenia " as defined in your leading article. The correlation between circulating-hxmoglobin level and serum-iron level is not unity (in our epidemiological studies r is around 0-5); hence there is a probability by chance alone of a concur" rence in an individual of a normal " level of one variate and a " low " level of the other. The surveys described in your leading article may only be estimating this probability in the very curious samples studied. Your leading article concludes with the statement that " it should not be difficult to find out whether administration of iron... really benefits the patients ... " Our experience is that it is exceedingly difficult to design and conduct trials which are bias free, based on representative samples of the community, and which use realistic indices of benefit, but anything less than this will only introduce further confusion into this difficult field. Certainly further careful scientific work should be done before this syndrome becomes established in the " art " of medicine. M.R.C. Epidemiological Research Unit A. L. COCHRANE (South Wales), Road, Cardiff.
P. C. ELWOOD.
4 Richmond
SIR,-Your generally admirable leading article is marred by confusion
over
the criteria which establish the presence of iron
deficiency (reduced total body iron), and by the use of the word sideropenia " both for the combination of iron deficiency "
"
with normal haemoglobin levels " and for " serum-iron below 50 g. per 100 ml." Since a low plasma-iron may often be found in the absence of iron deficiency, you recommend measurement also of the saturation of the total iron-binding capacity (T.i.i3.c.), and note that a saturation below 16% has been taken to indicate iron deficiency. While saturation of the T.i.B.c. below 16% is usually due to iron deficiency, Bainton and Finch2 found that the saturation was also below this level in many patients with " anaemia of infection " who were shown not to be iron deficient by the demonstration of stainable storage iron in the bonemarrow. Furthermore, they pointed out that hypochromic red cells were formed whenever delivery of iron to the marrow was curtailed by low saturation of the T.I.B.C. (" iron-deficient erythropoiesis "), whether or not this was due to true iron deficiency. Caution should therefore be exercised in the assessment of iron deficiency from measurement of plasmairon and saturation of the T.I.B.C., particularly in elderly illnesses. In hospital patients with a variety of complicating " or a low with elevated practice, plasma-iron high normal " T.I.B.C. is nearly always due to iron deficiency, but when the T.I.B.C. is low (or in the lower part of the normal range) iron deficiency can be diagnosed only from other evidence, particularly the absence of marrow-storage iron. You say also that " a low M.c.H.c. is invariably associated with a low serum-iron level ", apparently supporting the belief that the mean corpuscular haemoglobin concentration is a reliable index of iron deficiency. Red-cell hypochromia is due to impairment of haemoglobin synthesis, and in an increasing number of patients in the United Kingdom this is due to causes other than defective supply of iron to the marrow-for example, thalassemia and other sideroblastic " anxmias. This is important, because in these patients iron therapy is nearly always strongly contraindicated. "
Medical Unit, The London Hospital, London E.1.
ADAM TURNBULL.
*** We also said that " some patients with low serum-iron levels have a normal M.C.H.C. "-ED. L.
1967, 13, 794. 5.
Dagg, J. H., Morrow, J. J., Macfarlane, B., Goldberg, A. Q. Jl. Med. 1967, 36, 600. 6. Elwood, P. C., Wood, M. M. Br. J. prev. soc. Med. 1966, 20, 172.
McFarlane, D. B., Pinkerton, P. H., Dagg, J. H., Goldberg, A. Hœmat. 1967, 13, 794. 2. Bainton, D. F., Finch, C. A. Am. J. Med. 1964, 37, 62. 1.
Br. J.
SiR,—Iwas interested by the letter from Mr. MacDonald, and am entirely in sympathy with his views. I am a consultant in administrative charge but have experience in both the English and Scottish systems. There is no doubt that, compared with England, Scotland has had a hierarchical and somewhat autocratic tradition in the relationships between consultants, though this is disappearing in many centres. I do not believe that it is necessary to give up all the advantages of some form of organisation between consultants in the same specialty, as has been advocated in the recent reports in England and Scotland cited in Mr. MacDonald’s letter, in order to preserve consultant clinical freedom. The divisional type of organisation has many virtues for large departments trying to provide a community service, particularly in my own sphere of orthopxdic and accident work, in which beds have to be set aside for such purposes to keep an accident service running. The preservation of this freedom is I believe quite simple but of vital importance. A consultant in administrative charge should have no clinical overseeing of his consultant colleagues. The consultant in charge is not in clinical charge of patients, who should be left to the consultant whose patients they are he is only in administrative charge. In my own department I have never seen the patient of another colleague except at his request in the ten years that I have been here; this is a matter of simple principle. It is only by seeing that all consultants have total clinical responsibility for their patients that one may expect to attract and keep worth-while colleagues. In addition, the multiple problems of administration in this type of department, with a large number of junior staff to be rotated for training purposes and holidays, and the many other administrative matters that arise, are surely to be met not by a dictat from the consultant in administrative charge but by discussion in a consultant staff committee where policy can be made. Clearly from his situation the consultant in charge is most in touch with the administrative problems, is often able to suggest solutions, and must be able to take day-to-day decisions on administrative matters. Choosing colleagues both consultant and junior involves only rotation on selection committees, and arranging junior staff to work with all consultants on a six-monthly basis (not in daily fashion) to provide training is surely not difficult. In clinical work there are occasional reasons for accepting a departmental policy-e.g, controlled trials. Special clinical problems may interest one man among a group, and his colleagues may wish to concentrate such cases under the care of this one consultant. Discussion in a consultant staff committee is the ideal mode of making such mutually agreeable arrangements.
There is no doubt that medical administrators by and large do enjoy the advantages of having a single person to consult, but this should be strongly resisted. Mr. MacDonald’s letter is very important, particularly at this time when divisional organisation may be introduced. It is, however, possible to have administrative collaboration and clinical independence, and it is essential to see that this is achieved. University Department of Orthopaedic Surgery, Clinical Research Unit, Princess Margaret Rose Orthopdæic Hospital, J. I. P. JAMES. Edinburgh 10.
DUAL ADDICTION SIR,-I have followed with interest the recent correspondence on the effects of barbiturates and other drugs, and of withdrawal from them. Dr. Merry (Jan. 13, p. 96) advisedly draws attention to the concurrent use of heroin and barbiturates. In this foundation we have observed that there is an apparent increase in the proportion of our patients (primarily heroin addicts) who also abuse barbiturates. A recent study1 lends support to this observation. Too often one may not be aware of this dual addiction, and the patient is not asked if he (or more likely she) is also using barbiturates when heroin-withdrawal treatment is being instituted. Dr. Merry draws attention to the need to ask the patient this question-and the same applies to the possibility of abuse of a variety of other drugs. Since withdrawal from barbiturates is usually a more dangerous and difficult problem in management and treatment, the patient requires continued supervision in a hospital or clinic. It should be a standard part of the clinical investigation to inquire into the history of use of other sedative or stimulant drugs. Even when the patient denies that this is so, on his admission to hospital a careful search should always be made of his clothing and other possessions, since patients will often secrete such drugs, or have their friends and relatives supply them, while they are being withdrawn from heroin or other
drug.22 Drug abuse should also be considered in the differential diagnosis of a patient who has vague or recurrent complaints, particularly insomnia, and it should be remembered that such abuse is not necessarily restricted to just one drug at a time. The Narcotic Addiction Foundation of British Columbia, Vancouver 9.
R. HALLIDAY.
DIAZEPAM FOR TREATMENT OF PHOBIAS SIR,-I read Dr. Yeung’s letter (March 2, p. 475) with some interest, but I should like to know why he goes to the trouble of giving diazepam (’Valium’) intravenously when surely a similar dose orally would have the same effect. My practice in patients with agoraphobia and other similar phobias is to give the patient a supply of 2 mg. tablets of diazepam, which I tell him to take in proportion to the anxiety he experiences or thinks he may experience in any given situation. For example, some patients find that the journey to work in the morning is a very much more stressful and anxiety-provoking experience than the journey home in the evening. In such a case the patient might take a dose of 10 mg. before the morning journey and need only, say, 4 mg. for the journey home. I certainly find intravenous diazepam useful, since it gives some guide to the dose of oral medication which may be needed. It also helps to give the patients confidence that diazepam is an active agent and really will relieve the anxiety of which they complain. However, I should like to make a plea for much more flexible drug dosage in psychiatry, particularly with patients like agoraphobics in whom there is a wide variation in anxiety throughout the day. Rigid dosage on a t.d.s. or q.d.s. basis is surely inappropriate in these cases. Bexley Hospital, MICHAEL BOTT. Bexley, Kent.
ANOTHER AMITRIPTYLINE SIDE-EFFECT? SIR,-Dr. Blackwell (Feb. 24, p. 426) discusses amitriptyline
possible cause of hysteria. Last month in this hospital I saw a 59-year-old man, who 8 months before had been treated with imipramine and diazepam in ordinary doses because of a mild depression. 2 weeks after the beginning of this therapy he had complained of parassthesia over the whole of the left side of the body. He had also had short attacks of speech disturbance. His doctor had reassured him and had not arranged any further examinations. 6 months as a
1. 2.
Cumberlidge, M. C. Can. med. Ass. J. (in the press.) Halliday, R. Br. Columbia med. J. 1967, 9, 374.
591 later he had had slight paresis of his left hand, and when I saw him he also had paresis of his left leg. Right-sided carotid angiography showed stenosis in the lower intracanalicular part of the internal carotid artery. In the next week his left-sided paresis became complete, and repeated carotid angiography showed total stenosis of the medial cerebral artery, 3 cm. from its origin. The systolic blood-pressure varied between 150 and 100 mm. Hg, and he was not on antidepressants. This short description emphasises that the diagnosis of hysteria in a similar case must be very doubtful until a neuroradiological investigation has been done. Tricyclic antidepressants with their well-known tendency to produce orthostatic hypotension may cause recurrent ischasmic attacks in persons with partial obstruction of the cerebral arteries. Lasarettet, CARL L. BRECHTER. Trelleborg, Sweden
IRON DEFICIENCY WITHOUT ANÆMIA SIR,-We wish to take issue with you over your leading article (March 2, p. 462). We feel that a very biased view of the so-called syndrome of " sideropenia " has been presented. In your leading article you outline the argument which first led to the use of the term " sideropenia ". Yet you fail to " point out the " non-sequitur in this argument, nor do you make reference to a study published in this journal which showed that in the community the association between postcricoid dysphagia and iron deficiency is probably chance.1 You then refer to the often quoted trial of Beutler et awl. In fact you describe this trial wrongly as there were not two separate treatment groups, but a cross-over design was used and every subject was given both iron and placebo tablets. At the end of the trial the benefit from the two treatments were compared on the basis of conventional clinical interviews. It MEAN CHANGES IN " FATIGUE ", GRADED ON AN ARBITRARY SEVENPOINT SCALE, IN WOMEN WITH AN INITIAL HIGH GRADE OF " " FATIGUE AND H/BMOGLOBIN LEVELS OF 13-5 ML. OR MORE, AT GIVEN, RANDOM, ORAL IRON OR A PLACEBO TABLET FOR EIGHT WEEKS.
G/100
A
negative change in the grade implies improvement.
is obvious, and Beutler et al. admit, that because of undesirable side-effects the iron tablet could not be effectively masked, and, therefore, this trial was not truly blind on the"part of all of the subjects. In fact, their " placebo " was not a placebo "3 Your leading article then refers to a study by Macfarlane et al.4 who found a prevalence of 21 % of women with " latent iron deficiency." Yet you fail to refer to the double-blind trial of iron therapy conducted by the workers, in which there was no evidence that iron therapy gave greater symptomatic benefit than an iron-free placebo.5 We have already presented the results of a community study of the effect of oral iron on symptoms,6 and we hope shortly to report the results of further larger studies. These latter included a trial which was similar to that of Beutler et awl. but 1.
Elwood, P. C., Jacobs, A., Pitman, R. G., Entwistle, C. C. Lancet, 1964, ii, 716. 2. Beutler, E., Larsh, S. E., Gurney, C. W. Ann. intern. Med. 1960, 52, 378. 3. Leyburn, P. Lancet, 1967, ii, 1135. 4. Macfarlane, B., Pinkerton, P. H., Dagg, J. H., Goldberg, A. Br.J. Hœmat.
in which we did not use a cross-over design. The table summarises some of the results and shows that at every initial level of serum-iron the beneficial effect of iron was less than that of a placebo tablet. There are serious statistical objections to the syndrome of " sideropenia " as defined in your leading article. The correlation between circulating-hxmoglobin level and serum-iron level is not unity (in our epidemiological studies r is around 0-5); hence there is a probability by chance alone of a concur" rence in an individual of a normal " level of one variate and a " low " level of the other. The surveys described in your leading article may only be estimating this probability in the very curious samples studied. Your leading article concludes with the statement that " it should not be difficult to find out whether administration of iron... really benefits the patients ... " Our experience is that it is exceedingly difficult to design and conduct trials which are bias free, based on representative samples of the community, and which use realistic indices of benefit, but anything less than this will only introduce further confusion into this difficult field. Certainly further careful scientific work should be done before this syndrome becomes established in the " art " of medicine. M.R.C. Epidemiological Research Unit A. L. COCHRANE (South Wales), Road, Cardiff.
P. C. ELWOOD.
4 Richmond
SIR,-Your generally admirable leading article is marred by confusion
over
the criteria which establish the presence of iron
deficiency (reduced total body iron), and by the use of the word sideropenia " both for the combination of iron deficiency "
"
with normal haemoglobin levels " and for " serum-iron below 50 g. per 100 ml." Since a low plasma-iron may often be found in the absence of iron deficiency, you recommend measurement also of the saturation of the total iron-binding capacity (T.i.i3.c.), and note that a saturation below 16% has been taken to indicate iron deficiency. While saturation of the T.i.B.c. below 16% is usually due to iron deficiency, Bainton and Finch2 found that the saturation was also below this level in many patients with " anaemia of infection " who were shown not to be iron deficient by the demonstration of stainable storage iron in the bonemarrow. Furthermore, they pointed out that hypochromic red cells were formed whenever delivery of iron to the marrow was curtailed by low saturation of the T.I.B.C. (" iron-deficient erythropoiesis "), whether or not this was due to true iron deficiency. Caution should therefore be exercised in the assessment of iron deficiency from measurement of plasmairon and saturation of the T.I.B.C., particularly in elderly illnesses. In hospital patients with a variety of complicating " or a low with elevated practice, plasma-iron high normal " T.I.B.C. is nearly always due to iron deficiency, but when the T.I.B.C. is low (or in the lower part of the normal range) iron deficiency can be diagnosed only from other evidence, particularly the absence of marrow-storage iron. You say also that " a low M.c.H.c. is invariably associated with a low serum-iron level ", apparently supporting the belief that the mean corpuscular haemoglobin concentration is a reliable index of iron deficiency. Red-cell hypochromia is due to impairment of haemoglobin synthesis, and in an increasing number of patients in the United Kingdom this is due to causes other than defective supply of iron to the marrow-for example, thalassemia and other sideroblastic " anxmias. This is important, because in these patients iron therapy is nearly always strongly contraindicated. "
Medical Unit, The London Hospital, London E.1.
ADAM TURNBULL.
*** We also said that " some patients with low serum-iron levels have a normal M.C.H.C. "-ED. L.
1967, 13, 794. 5.
Dagg, J. H., Morrow, J. J., Macfarlane, B., Goldberg, A. Q. Jl. Med. 1967, 36, 600. 6. Elwood, P. C., Wood, M. M. Br. J. prev. soc. Med. 1966, 20, 172.
McFarlane, D. B., Pinkerton, P. H., Dagg, J. H., Goldberg, A. Hœmat. 1967, 13, 794. 2. Bainton, D. F., Finch, C. A. Am. J. Med. 1964, 37, 62. 1.
Br. J.