- Email: [email protected]
RIVAL TO THE WITCH DOCTOR
259 the vessels of both retinas which was threatening to make him completely blind. This appears to have gone into remission since the cyclophosphamide was withdrawn, and he has enough residual vision to read large print, though both retinas show ischxmic changes. A second living-donor recipient developed a spastic paraplegia with sphincter disturbance, homonymous hemianopia, and ataxic speech. This atypical demyelinating disease reminiscent of multiple sclerosis (but judged not to be by our neurological colleagues) has also largely remitted since withdrawal of cyclophosphamide. A third patient developed a florid malabsorption syndrome with gross steatorrhoea and a normal jejunal biopsy. He is now quite normal on azathioprine and prednisone alone. Finally 2 patients died of overwhelming infections in the face of continuing and uncontrolled graft
rejection. We are impressed by the apparent usefulness of cyclophosphamide as an adjuvant immunosuppressive in rejection uncontrolled by conventional therapy, but the appearance of these somewhat bizarre illnesses has caused
the use of this triple-drug regimen as a last in desperate cases. Furthermore, it may be wise to withdraw the cyclophosphamide once the rejection seems to be under control. ROBERT ULDALL ROSS TAYLOR Royal Victoria Infirmary,
of reddish-brown urine. In February, 1969, a diagnosis of paroxysmal nocturnal haemoglobinuria (P.N.H.) was established on the basis of hxmolytic anxmia, leucopenia, hxmoglobinuria, and positive acidified-serum and sucrose screening tests. Acenocoumarol (’ Sinthrome ’), ó-8 mg. daily, was given to stabilise prothrombin activity at 20-30% of the control value. In March, 1971, oxymetholone, 100 mg. daily, was added. One month later treatment was discontinued because of severe hsmaturia and subcutaneous bleeding in the limbs, with a prothrombin activity of less than 5%. At present, the patient is satisfactorily controlled with oxymetholone 50 mg. daily, and acenocoumarol 2 mg. daily-i.e., a third to a quarter the previous dose. Hsemolytic attacks are less frequent, and the anxmia is less severe. P.N.H. is a condition in which a trial with both drugs seems warranted. We do not believe that the use of oxymetholone with anticoagulants is absolutely contraindicated; individual tolerance can be tested in each patient with small doses of anticoagulants. J. C. DE OYA
us to reserve
resort
Newcastle upon Tyne NE1 4LP.
JOHN SWINNEY.
A. DEL RÍO M. NOYA A. VILLANUEVA.
Department of Internal Medicine, University of Santiago de Compostela, Spain.
RIVAL TO THE WITCH DOCTOR
SIR,-Now and then, Caucasian doctors months’ visit
CIRRHOSIS AND LYMPHOPROLIFERATIVE DISORDERS
SIR,-Dr. Heimann (July 10, p. 101) is wrong in supposing that an association between cirrhosis and lymphomata has not been previously reported. I am not familiar with the recent published work, but as long ago as 1956, Wetherley-Mein and Cottom1 noted portal fibrosis in patients with acute leukaemia. The important question, of course, is what part treatment with cytotoxic drugs and corticosteroids plays in the development of the liver damage2 and it is a pity Dr. Heimann gives no information on this point. I am particularly interested because I have records of a young man who died of acute myeloid leukxmia before could be started, and whose liver at necropsy showed the changes of portal cirrhosis. However, it is obviously unwise to draw conclusions from one case.
treatment
Dudley Road Hospital, Birmingham B18 7QH.
A. PATON.
pay
a
the wealth of material available and the few " labourers " around. I, like many others, am grateful to people like Dr. Sylvia Watkins for the selfless service rendered in Nigeria just after the civil war, but feel disturbed by some of the imaginative writing shown in her article Rival to the Witch Doctor.1 No granny ever attempts, as she writes, in Nigeria to " assist" her daughter who is in labour by cutting the vagina anteriorly with a razor blade ". As elsewhere, Nigeria has traditional or native midwives and " mid-men " (and these existed even before the British came), and a mother never " delivers " her daughter, as elsewhere. How do you bind up cuts with cobwebs, except in the imagination ? Are these cobwebs spun by spiders, or are Dr. Watkins’ spiders human beings ? She misinterprets completely It is usually a symptom of anxiety " internal heat ". neurosis. It is understandable if barren " women com" plain of internal heat". To be barren, in any part of Nigeria, is a social disaster. There is nowhere in rustic Nigeria ", as the place where Dr. Watkins worked could be justifiably described, where any woman is supposed to bear a baby every year, as Dr. Watkins alleges. In such a place, poverty is rife. Supplementary feeding is unavailable. A baby stays on the breast for as long as 3 years or more (and I should know, because I can still remember vividly, even now, being breast-fed!), and perhaps this is a good thing-no Freudian predisposition to seek erotic oral satisfaction in later life. If a woman delivered every year in those parts of the world, none of the children would survive, and the natives know this. The only Nigerian females who deliver babies every year are the elite, or the highly educated, who enter matrimonial life late and are anxious to get things over quickly-and they can afford the True enough, boys are preferred, but girls are cost. certainly not left to starve as suggested by Dr. Watkins. I do not know how anyone can get an inguinal hernia "
"
DECREASED ANTICOAGULANT TOLERANCE WITH OXYMETHOLONE IN PAROXYSMAL NOCTURNAL HÆMOGLOBINURIA
SIR,-Dr. Robinson and his co-workers3 report deanticoagulant tolerance with oxymetholone in patients requiring chronic hxmodialysis, and emphasise the need for careful monitoring whenever this combination must be employed. Dr. Longridge and his colleagues4are of the opinion that oxymetholone, even in reduced doses, is absolutely contraindicated with anticoagulant therapy (phenindione and warfarin). We have seen a man aged 35 with a 5-year history of anasmia, thrombophlebitis, and frequent nocturnal episodes of abdominal and substernal pain followed by the passage creased anxmic
1. 2.
Wetherley-Mein, G., Cottom, D. G. Br. J. Hœmat. 1956, 2, 345. Amromin, G. D., Deliman, R. M., Shanbrom, E. Gastroenterology, 1962, 42, 401. 3. Robinson, B. H. B., Hawkins, J. B., Ellis, J. E., Moore-Robinson, M. Lancet, 1971, i, 1356. 4. Longridge, R. G. M., Gillam, P. M. S., Barton, G. M. G. ibid. July 10, 1971, p. 90.
few
developing tropical countries and return perhaps without any conscious motivation, proclaiming, their expertise on some medical aspects of life in these areas. No doubt some (certainly only a small proportion) have some justifiable claims in view of the enormous experience gained in such countries in such a short time, because of to
"
1. Watkins, S. Lancet, 1971, i,
1062.
260
strangulated at will, as Dr. Watkins gleefully opines. Dr. Watkins writes, Certainly the Medicine Man has a big role to play amongst his own people. I feel sure that he would have done better than my few tablets of chlorpromazine for the patient who arrived in outpatients complaining of having ’been beaten up by witches and "
wizards ’ ". The native doctor was and is no fool. In that part of Nigeria, at least 400 miles from the part where I was born, the native doctors knew about rauwolffia before reserpine was discovered, and had used calabar seeds
before Walker introduced physostigmine to the developed world. True enough, There is nothing like a little Juju as a remedy against Juju ", but not everything in modern medicine is immediately seen to have a scientific basis. For example, how does amantadine benefit patients with Parkinson’s disease ? For nearly a century after Charlot clinicians used belladona alkaloids and antihistamines to relieve parkinsonism, without being able to explain why. Was that mumbo-jumbo ? Many witch doctors are better psychotherapists than the great ones in the Maudsley, as Lambo of Aro fame readily realises! I hope others will write facts, not fallacies, about medicine (whether modern or native ") in the developing countries. The developed world, surorisinslv.. can learn and benefit from the facts. "
"
Department of Psychiatry and Neurology, University College Hospital, Ibadan, Nigeria.
B. O. OSUNTOKUN.
The success of metaraminol in improving renal function in their patients may be due merely to the rise in central arterial blood-pressure, to which the normal response of the kidneys is a sodium diuresis. Hammersmith Hospital, London W.12.
STEPHEN WILKINSON.
INFLUENZA AND NEURAL-TUBE DEFECTS
SiR,—The suggestion by janerichthat the epidemic of neural-tube defects which peaked in the early 1930s may have been caused by exposure of prepubescent girls to the influenza epidemic in 1918 is novel. As he noted, such an explanation should be accompanied by a shift in the maternal-age distribution of affected births during the course of the epidemic. Ideally, one would examine malformation-rates specific for maternal age and calendar year, to determine whether a birth-cohort of high-risk mothers was passing through successive maternal-age groups as the epidemic waxed and waned. Lack of data on the maternal age distribution of the relevant population of births in the early years prevents us from providing such rates for our series,2 but such data as we do have seem not to support the hypothesis. The accompanying table shows mean maternal ages for affected individuals according to year of birth over the 25 MATERNAL AGE AT BIRTH FOR A SERIES OF CASES OF NEURAL-TUBE DEFECTS AND A SAMPLE OF UNAFFECTED BIRTHS
FALSE NEUROTRANSMITTERS AND HEPATIC FAILURE SIR,-Dr. Fischer and Dr. Baldessarini (July 10, p. 75) propose an interesting hypothesis to explain the neurological, cardiovascular, and renal manifestations of hepatic failure. Though their theory may account for many of the first two of these, their explanation of impaired renal function is open to criticism. They suggest that the renal failure accompanying hepatic failure is due to inadequate sympathetic tone secondary to replacement of noradrenaline in nerve terminals by false transmitter substances. However, it is unlikely that sympathetic tone has a very important role in the maintenance of renal function. Berne 1 has shown in dogs that
glomerular filtration-rate, renal plasma-flow, response to diuretics, and electrolyte excretion of a denervated kidney do not differ from those of the control innervated contralateral kidney. In man, spinal anaesthesia up to and above T (which effectively " denervates " both kidneys) is not associated with changes in renal blood-flow.2 The mechanism of the oliguria accompanying hepatic failure appears to involve cortical vasoconstriction, as was shown by Epstein et awl. using the radioactive-xenon washout technique and selective renal arteriography. The fact that this vasoconstriction was not abolished by phentolamine, in doses adequate to induce complete alphablockade, makes it unlikely that this is mediated via the sympathetic nervous system. Even if the sympathetic nervous system was playing a role here, it would do so in a way exactly opposite to that proposed by Fischer and Baldessarini. Sympathetic stimulation causes cortical vasoconstriction,4 whereas their hypothesis proposes that inadequate sympathetic activity is responsible for the reduction in cortical blood-flow. Berne, R. M. Am. J. Physiol. 1952, 171, 148. Smith, H. W., Rovenstine, E. A., Goldring, W., Chasis, H., Ranges, H. A. J. clin. Invest. 1939, 18, 319. 3. Epstein, M., Berk, D. P., Hollenberg, N. K., Adams, D. F., Chalmers, T. C., Abrams, H. L., Merrill, J. P. Am. J. Med. 1970, 49, 175. 4. Block, M. A., Wakim, K. G., Mann, F. C. Am. J. Physiol. 1952, 169, 659. 1.
2.
*
Maternal age unknown for 20
cases.
t See text for explanation. t Boston Lying-in Hospital only.
epidemic. Differences between these means The distributions of cases by maternal age in each of the 5-year periods were also examined. There was no indication of any significant shift in the distributions. One may estimate the mean maternal age that would be predicted for each time period if (a) the mean maternal age of the non-epidemic component of the disease (as measured by a rate of 2-6 per 1000 observed before the epidemic) remained unchanged at approximately 27 years, and (b) the epidemic component, as measured by the excess over this baseline rate, was contributed exclusively by a cohort of women who were around 12 years of age in 1918 and who aged as expected over the 25-year period. These figures are shown in the table. The absolute levels of these means are determined largely by the assumption of 27 years as the mean for the non-epidemic cases. Relevant to our question are not the absolute levels of these predicted means but the 3-year increase over the 25-year period. There is a considerable discrepancy between the relative constancy of the observed mean maternal ages of the cases and the predictions based on Janerich’s hypothesis. We must also examine the possibility that the increase in maternal age predicted from the hypothesis occurred, but was offset by a lowering of maternal age in the population of births at risk. We have data on this point from one of the
years of the are
small.
1. 2.
Janerich,
D. T. Lancet, 1971, i, 1165. MacMahon, B., Yen, S. ibid. p. 31.
rejection. We are impressed by the apparent usefulness of cyclophosphamide as an adjuvant immunosuppressive in rejection uncontrolled by conventional therapy, but the appearance of these somewhat bizarre illnesses has caused
the use of this triple-drug regimen as a last in desperate cases. Furthermore, it may be wise to withdraw the cyclophosphamide once the rejection seems to be under control. ROBERT ULDALL ROSS TAYLOR Royal Victoria Infirmary,
of reddish-brown urine. In February, 1969, a diagnosis of paroxysmal nocturnal haemoglobinuria (P.N.H.) was established on the basis of hxmolytic anxmia, leucopenia, hxmoglobinuria, and positive acidified-serum and sucrose screening tests. Acenocoumarol (’ Sinthrome ’), ó-8 mg. daily, was given to stabilise prothrombin activity at 20-30% of the control value. In March, 1971, oxymetholone, 100 mg. daily, was added. One month later treatment was discontinued because of severe hsmaturia and subcutaneous bleeding in the limbs, with a prothrombin activity of less than 5%. At present, the patient is satisfactorily controlled with oxymetholone 50 mg. daily, and acenocoumarol 2 mg. daily-i.e., a third to a quarter the previous dose. Hsemolytic attacks are less frequent, and the anxmia is less severe. P.N.H. is a condition in which a trial with both drugs seems warranted. We do not believe that the use of oxymetholone with anticoagulants is absolutely contraindicated; individual tolerance can be tested in each patient with small doses of anticoagulants. J. C. DE OYA
us to reserve
resort
Newcastle upon Tyne NE1 4LP.
JOHN SWINNEY.
A. DEL RÍO M. NOYA A. VILLANUEVA.
Department of Internal Medicine, University of Santiago de Compostela, Spain.
RIVAL TO THE WITCH DOCTOR
SIR,-Now and then, Caucasian doctors months’ visit
CIRRHOSIS AND LYMPHOPROLIFERATIVE DISORDERS
SIR,-Dr. Heimann (July 10, p. 101) is wrong in supposing that an association between cirrhosis and lymphomata has not been previously reported. I am not familiar with the recent published work, but as long ago as 1956, Wetherley-Mein and Cottom1 noted portal fibrosis in patients with acute leukaemia. The important question, of course, is what part treatment with cytotoxic drugs and corticosteroids plays in the development of the liver damage2 and it is a pity Dr. Heimann gives no information on this point. I am particularly interested because I have records of a young man who died of acute myeloid leukxmia before could be started, and whose liver at necropsy showed the changes of portal cirrhosis. However, it is obviously unwise to draw conclusions from one case.
treatment
Dudley Road Hospital, Birmingham B18 7QH.
A. PATON.
pay
a
the wealth of material available and the few " labourers " around. I, like many others, am grateful to people like Dr. Sylvia Watkins for the selfless service rendered in Nigeria just after the civil war, but feel disturbed by some of the imaginative writing shown in her article Rival to the Witch Doctor.1 No granny ever attempts, as she writes, in Nigeria to " assist" her daughter who is in labour by cutting the vagina anteriorly with a razor blade ". As elsewhere, Nigeria has traditional or native midwives and " mid-men " (and these existed even before the British came), and a mother never " delivers " her daughter, as elsewhere. How do you bind up cuts with cobwebs, except in the imagination ? Are these cobwebs spun by spiders, or are Dr. Watkins’ spiders human beings ? She misinterprets completely It is usually a symptom of anxiety " internal heat ". neurosis. It is understandable if barren " women com" plain of internal heat". To be barren, in any part of Nigeria, is a social disaster. There is nowhere in rustic Nigeria ", as the place where Dr. Watkins worked could be justifiably described, where any woman is supposed to bear a baby every year, as Dr. Watkins alleges. In such a place, poverty is rife. Supplementary feeding is unavailable. A baby stays on the breast for as long as 3 years or more (and I should know, because I can still remember vividly, even now, being breast-fed!), and perhaps this is a good thing-no Freudian predisposition to seek erotic oral satisfaction in later life. If a woman delivered every year in those parts of the world, none of the children would survive, and the natives know this. The only Nigerian females who deliver babies every year are the elite, or the highly educated, who enter matrimonial life late and are anxious to get things over quickly-and they can afford the True enough, boys are preferred, but girls are cost. certainly not left to starve as suggested by Dr. Watkins. I do not know how anyone can get an inguinal hernia "
"
DECREASED ANTICOAGULANT TOLERANCE WITH OXYMETHOLONE IN PAROXYSMAL NOCTURNAL HÆMOGLOBINURIA
SIR,-Dr. Robinson and his co-workers3 report deanticoagulant tolerance with oxymetholone in patients requiring chronic hxmodialysis, and emphasise the need for careful monitoring whenever this combination must be employed. Dr. Longridge and his colleagues4are of the opinion that oxymetholone, even in reduced doses, is absolutely contraindicated with anticoagulant therapy (phenindione and warfarin). We have seen a man aged 35 with a 5-year history of anasmia, thrombophlebitis, and frequent nocturnal episodes of abdominal and substernal pain followed by the passage creased anxmic
1. 2.
Wetherley-Mein, G., Cottom, D. G. Br. J. Hœmat. 1956, 2, 345. Amromin, G. D., Deliman, R. M., Shanbrom, E. Gastroenterology, 1962, 42, 401. 3. Robinson, B. H. B., Hawkins, J. B., Ellis, J. E., Moore-Robinson, M. Lancet, 1971, i, 1356. 4. Longridge, R. G. M., Gillam, P. M. S., Barton, G. M. G. ibid. July 10, 1971, p. 90.
few
developing tropical countries and return perhaps without any conscious motivation, proclaiming, their expertise on some medical aspects of life in these areas. No doubt some (certainly only a small proportion) have some justifiable claims in view of the enormous experience gained in such countries in such a short time, because of to
"
1. Watkins, S. Lancet, 1971, i,
1062.
260
strangulated at will, as Dr. Watkins gleefully opines. Dr. Watkins writes, Certainly the Medicine Man has a big role to play amongst his own people. I feel sure that he would have done better than my few tablets of chlorpromazine for the patient who arrived in outpatients complaining of having ’been beaten up by witches and "
wizards ’ ". The native doctor was and is no fool. In that part of Nigeria, at least 400 miles from the part where I was born, the native doctors knew about rauwolffia before reserpine was discovered, and had used calabar seeds
before Walker introduced physostigmine to the developed world. True enough, There is nothing like a little Juju as a remedy against Juju ", but not everything in modern medicine is immediately seen to have a scientific basis. For example, how does amantadine benefit patients with Parkinson’s disease ? For nearly a century after Charlot clinicians used belladona alkaloids and antihistamines to relieve parkinsonism, without being able to explain why. Was that mumbo-jumbo ? Many witch doctors are better psychotherapists than the great ones in the Maudsley, as Lambo of Aro fame readily realises! I hope others will write facts, not fallacies, about medicine (whether modern or native ") in the developing countries. The developed world, surorisinslv.. can learn and benefit from the facts. "
"
Department of Psychiatry and Neurology, University College Hospital, Ibadan, Nigeria.
B. O. OSUNTOKUN.
The success of metaraminol in improving renal function in their patients may be due merely to the rise in central arterial blood-pressure, to which the normal response of the kidneys is a sodium diuresis. Hammersmith Hospital, London W.12.
STEPHEN WILKINSON.
INFLUENZA AND NEURAL-TUBE DEFECTS
SiR,—The suggestion by janerichthat the epidemic of neural-tube defects which peaked in the early 1930s may have been caused by exposure of prepubescent girls to the influenza epidemic in 1918 is novel. As he noted, such an explanation should be accompanied by a shift in the maternal-age distribution of affected births during the course of the epidemic. Ideally, one would examine malformation-rates specific for maternal age and calendar year, to determine whether a birth-cohort of high-risk mothers was passing through successive maternal-age groups as the epidemic waxed and waned. Lack of data on the maternal age distribution of the relevant population of births in the early years prevents us from providing such rates for our series,2 but such data as we do have seem not to support the hypothesis. The accompanying table shows mean maternal ages for affected individuals according to year of birth over the 25 MATERNAL AGE AT BIRTH FOR A SERIES OF CASES OF NEURAL-TUBE DEFECTS AND A SAMPLE OF UNAFFECTED BIRTHS
FALSE NEUROTRANSMITTERS AND HEPATIC FAILURE SIR,-Dr. Fischer and Dr. Baldessarini (July 10, p. 75) propose an interesting hypothesis to explain the neurological, cardiovascular, and renal manifestations of hepatic failure. Though their theory may account for many of the first two of these, their explanation of impaired renal function is open to criticism. They suggest that the renal failure accompanying hepatic failure is due to inadequate sympathetic tone secondary to replacement of noradrenaline in nerve terminals by false transmitter substances. However, it is unlikely that sympathetic tone has a very important role in the maintenance of renal function. Berne 1 has shown in dogs that
glomerular filtration-rate, renal plasma-flow, response to diuretics, and electrolyte excretion of a denervated kidney do not differ from those of the control innervated contralateral kidney. In man, spinal anaesthesia up to and above T (which effectively " denervates " both kidneys) is not associated with changes in renal blood-flow.2 The mechanism of the oliguria accompanying hepatic failure appears to involve cortical vasoconstriction, as was shown by Epstein et awl. using the radioactive-xenon washout technique and selective renal arteriography. The fact that this vasoconstriction was not abolished by phentolamine, in doses adequate to induce complete alphablockade, makes it unlikely that this is mediated via the sympathetic nervous system. Even if the sympathetic nervous system was playing a role here, it would do so in a way exactly opposite to that proposed by Fischer and Baldessarini. Sympathetic stimulation causes cortical vasoconstriction,4 whereas their hypothesis proposes that inadequate sympathetic activity is responsible for the reduction in cortical blood-flow. Berne, R. M. Am. J. Physiol. 1952, 171, 148. Smith, H. W., Rovenstine, E. A., Goldring, W., Chasis, H., Ranges, H. A. J. clin. Invest. 1939, 18, 319. 3. Epstein, M., Berk, D. P., Hollenberg, N. K., Adams, D. F., Chalmers, T. C., Abrams, H. L., Merrill, J. P. Am. J. Med. 1970, 49, 175. 4. Block, M. A., Wakim, K. G., Mann, F. C. Am. J. Physiol. 1952, 169, 659. 1.
2.
*
Maternal age unknown for 20
cases.
t See text for explanation. t Boston Lying-in Hospital only.
epidemic. Differences between these means The distributions of cases by maternal age in each of the 5-year periods were also examined. There was no indication of any significant shift in the distributions. One may estimate the mean maternal age that would be predicted for each time period if (a) the mean maternal age of the non-epidemic component of the disease (as measured by a rate of 2-6 per 1000 observed before the epidemic) remained unchanged at approximately 27 years, and (b) the epidemic component, as measured by the excess over this baseline rate, was contributed exclusively by a cohort of women who were around 12 years of age in 1918 and who aged as expected over the 25-year period. These figures are shown in the table. The absolute levels of these means are determined largely by the assumption of 27 years as the mean for the non-epidemic cases. Relevant to our question are not the absolute levels of these predicted means but the 3-year increase over the 25-year period. There is a considerable discrepancy between the relative constancy of the observed mean maternal ages of the cases and the predictions based on Janerich’s hypothesis. We must also examine the possibility that the increase in maternal age predicted from the hypothesis occurred, but was offset by a lowering of maternal age in the population of births at risk. We have data on this point from one of the
years of the are
small.
1. 2.
Janerich,
D. T. Lancet, 1971, i, 1165. MacMahon, B., Yen, S. ibid. p. 31.