230
respiratory and gastrointestinal tracts with cytokines may be the cause of death in SIDS. We thank the
Norwegian Research Council
release of various for Science and the
Humanities, Anders Jahre’s Foundation, and the Norwegian SIDSParents Association for financial support. Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology; and Institute of Forensic Medicine, Rikshospitalet, N-0027 Oslo, Norway, and Department of Oral Surgery and Oral Medicine, University of Oslo, Oslo
PER S. THRANE TORLEIV O. ROGNUM PER BRANDTZAEG
confirm or deny close linkage with markers on distal 4p). In a second family requesting testing the clinical diagnosis of HD has been doubted by some, since most affected members show very slight and very slow intellectual deterioration and the major clinical feature is mild chorea. Nonetheless there have been two cases with juvenile onset, and postmortem examination of one affected individual showed very mild but definite involvement of the caudate. It is important to obtain pathological confirmation of the diagnosis whenever possible, even if family structure and clinical features seem typical for HD. to
Department of Medical Genetics, Churchill Hospital, Oxford OX3 7LJ, UK
Stoltenberg L, Brandtzaeg P, Saugstad OD, Rognum TO. Tracheal wall shows local IgM immune response in SIDS. 1st World Congress in Paediatric Pathology, September 1989: B21-22 (abstr). 2. Forsyth KD, Weeks SC, Koh L, Skinner J, Bradley J. Lung immunoglobulins in the sudden infant death syndrome. Br Med J 1989; 298: 23-26. 3. Brandtzaeg P. Mucosal and glandular distribution of immunoglobulin components: immunohistochemistry with cold ethanol-fixation technique. Immunology 1974;
R. S. SHIWACH R. H. LINDENBAUM A. MICIAK
1.
MJ, Tyler A. Lazarou L, Meredith L, Harper PS. Problems m genetic prediction for Huntington’s disease. Lancet 1989; ii: 601-05. Folstein SE, Leigh RJ, Parhad IM, Folstein MF. The diagnosis of Huntington’s disease. Neurology 1986; 36: 1279-83.
1. Morris 2.
26: 1101-14.
Brandtzaeg P, Rognum TO. Evaluation of tissue preparation methods and paired immunofluorescence staining for immunocytochemistry of lymphomas. Histochem J 1983; 15: 655-89. 5. Rognum TO, Saugstad OD, Oyasaeter S, Olaisen B. Elevated levels of hypoxanthine in vitreous humor indicate prolonged cerebral hypoxia m victims of sudden infant death syndrome. Pediatrics 1988; 82: 615-18. 6. Valdes Dapena M. Sudden infant death syndrome: morphology update for forensic pathologists. Forensic Sci Int 1986; 30: 177-86. 7. Takashima S, Mito T, Becker LE. Neuronal development in medullary reticular formation in sudden infant death syndrome and premature infants. Neuropediatrics 1985; 16: 76-79. 8 Schneider PM, Wendler C, Riepert T, et al. Possible association of sudden infant death (SID) with partial complement C4 deficiency revealed by post-mortem DNA typing of HLA class II and III genes. Eur J Ped (in press). 9. Walter JS, Meyers P, Krueger JM. Microinjection of interleukin-1 into brain: separation of sleep and fever responses. Physiol Behav 1989; 45: 169-76. 10. Guntheroth WG. Interleukin-1 as intermediary causing prolonged sleep apnea and SIDS during respiratory infections. Med Hypoth 1989; 28: 121-23. 4.
Predicting Huntington’s disease SIR,-Setting up predictive testing for Huntington’s disease (HD) within the Oxford region, we have had 115 applicants so far and have met most of the difficulties described by Morris et aP plus a few additional ones. Testing post-mortem. An individual in his early sixties, from an informative family, requested predictive testing. He died, not from HD, shortly after giving blood for DNA but before being informed of the result. The widow and grown-up children have asked us to proceed with presymptomatic testing. This seems a reasonable request. Testing in prison. An individual from an informative family
requested predictive testing, although serving a long prison sentence. We saw no ethical difficulties in agreeing to this request. A bad result might argue in favour of early release. Testing the father. 4 people asking for the test thought their "official" father was not their biological one; in at least one case this suspicion was confirmed by DNA analysis. In some HD families proof of non-paternity will result in a risk reduction from nearly 50%
very low levels. Testing the wrong disorder. The misdiagnosis rate for HD may be as high as 15%. In two of thirty-eight families who had requested presymptomatic diagnosis and where there was an
Prenatal SIR,-Although comment
we
(Oct 7,
p
agree with Dr Dallapiccola and Dr Novelli’s 871) on our paper (Aug 19, p 419) that it is
possible to measure triose phosphate isomerase (TPI) activity on trophoblasts or cultured amniocytes, we have great reservations about the application of these techniques to prenatal diagnosis. Clark et al,l who also used these techniques, drew attention to the need for a marker in addition to enzyme activity; they suggested enzyme instability. In our case the red-cell enzyme activity in the was very close to the heterozygote values. This finding meant that the use of enzyme activities, even in the red cell with a narrower normal range than reported for trophoblast and cultured amniocytes, would make assignment of a homozygous or heterozygous state to a specific fetus rather difficult. Hence, we used the further, and perhaps more definitive, evidence of a metabolic block-ie, the increase in dihydroxyacetone phosphate (DHAP). This provides convincing evidence of a functional enzyme block associated with the homozygous state. However, in nucleated cells such as amniocytes and trophoblasts it is likely that the DHAP may not be such a reliable marker owing to the presence of glycerol-3phosphate dehydrogenase which would metabolise the DHAP.
affected child
We would therefore caution against the use of enzyme activity in
amniocyte or trophoblastic material until there is more evidence for a metabolic block, since such a major decision for the parents depends on the results. We would rather rely on the more sound assays on red cells in the second trimester until DNA analysis is available, which will surely follow soon. Department of Haematological Medicine,
King’s College School of Medicine and Dentistry, London SE5 9PJ, UK 1. Clark
ACL, Szobolotzky MA. Triose phosphate diagnosis. J Pediatr 1985; 106: 417-20.
A. J. BELLINGHAM A. N. LESTAS isomerase
deficiency: prenatal
Griseofulvin-induced neuropathy
to
autosomal dominant pattern of transmission and a clinical diagnosis of HD, the neuropathological findings seemed incompatible with HD or there were unusual features, clinical and neuropathological. In a large family with dominant transmission of presenile dementia and chorea through at least three generations, experienced neurologists diagnosed HD several times. However, necropsy on three closely related affected individuals revealed a differing pattern of involvement of pons, substantia nigra, inferior olive, and cerebellum, with normal caudate, putamen, and cerebral cortex. These neuropathological changes are not uniformly characteristic of any reported type of olivopontocerebellar atrophy (and there are insufficient samples of DNA from affected individuals, at present,
diagnosis of triose phosphate deficiency
isomerase
SIR,-A 76-year-old woman was treated with griseofulvin 500 mg daily for 4 months in 1987 and 6 months in 1988 for fungal nail infection. The second treatment was discontinued after paraesthesia developed in all fingers, followed by numbness of the feet and a sensation of "walking on cottonwool". Her general health was excellent. She had a history of treated hypothyroidism. Alcohol consumption was about 5 units per week. 4 months after the onset of neurological symptoms ankle jerks were absent and she had bilateral loss of vibration sense at the hallux. Nerve conduction studies showed a severe but very distal motor and sensory neuropathy (table). Laboratory investigations, including cerebrospinal fluid examination, were negative. 4 months later her sensory symptoms had resolved and there were no neurological signs. Nerve conduction had substantially improved
(table).
231
NERVE CONDUCTION STUDIES*
Neither leukaemias nor gastric cancer occurred in any of 49 controls given equivalent volumes of water. There were only 2 controls with tumours, both mammary with latent periods of about 16 months. Previous work with bracken extracts and mice have produced a majority of lymphocytic leukaemias but the myeloid system is similarly responsive and the spectrum includes rarer varieties; gastric malignancies have been both squamous and glandular.6 The sporulation of bracken is regional and influenced by several factors, but one good sized frond can yield 1-0 g of the brown powder, enough to produce leukaemias in 5 susceptible mice. School of
*Results of second examination marked
in
parentheses. tall values reduced except these so
SAP = sensory action potential (orthodromic), SCV = sensory conduction velocity, CMAP=compound muscle action potential, MCV=motor conduction velocity. R =right.
DML=distal
motor
latency,
It seems likely that the neuropathy was caused by griseofulvin. The Committee on Safety of Medicines (CSM) has reports of 5 cases of "neuropathy" and 6 cases of "paraesthesia" occurring in association with griseofulvin treatment (CSM, personal communication), but none seem to have been well documented. I thank Dr S. M. Wood, Principal Medical Officer, Committee on Safety of Medicines for permission to quote CSM data, and Dr D. L. Higson of Glaxo Laboratories for making available data held by the company.
Mersey Regional Department of Neurology, Hospital, Liverpool L9 1AE, UK
Biological Sciences, University College of North Wales, Bangor, Gwynedd LL57 2UW, UK
IA, Mason J. Carcinogenic activity of bracken. Nature 1965; 208: 913-14. 1968; 28: 2252-61. possible links with bracken. Br J Cancer (in press). 4. Villalobos-Salazar J, Meneses A, Rojas JL, et al. Bracken derived carcinogens as affecting animal health and human health in Costa Rica. In: Taylor JA, ed. Bracken toxicity and carcinogenicity as related to animal and human health: International Bracken Group special publication. Aberystwyth: University College of Wales, 1. Evans
2. Evans IA. The radiomimetic nature of bracken toxin. Cancer Res 3. Galpin OP, Whitaker CJ, Kassab J. Gastric cancer in Gwynedd:
1989: 40-51.
S, Hirayama T. Epidemiology of cancer of the oesophagus in Miye, Nara and Wakayama Prefecture with special reference to the role of the bracken fern. Proc Jap Cancer Assoc (34th annual meeting, Osaka, 1975): 211. Evans IA. Bracken carcinogenicity. In. James GV, ed. Reviews on environmental health: Int Quart Sci Rev vol VII. Tel Aviv: Freund Publishing House, 1987:
5. Kamon
6.
161-99.
Myxoedematous Munchausen?
Walton
B. R. F. LECKY
Bracken and leukaemia SIR,-From their study of cancer near potential sites of nuclear installations Paula Cook-Mozaffari (Nov 11, p 1145) and her colleagues conclude that there are "systematic differences between districts near existing or potential installations and other districts with respect to some important, unrecognised risk factors". Such factors are probably environmental; one such factor, long recognised, is bracken (Pteridium aquilinum), which itself has radiomimetic properties.1,2 Nuclear power plants, actual or potential, are likely to be sited in terrain where bracken is
indigenous. Bracken is carcinogenic in a wide variety of animal species, it affects different organs and tissues, and the younger the animal when exposed the greater is the susceptibility. There is now growing evidence from different countries that human beings are not exempt. In the UK a questionnaire-based case-control study on 101 histologically confirmed stomach cancer cases revealed a significant correlation with exposure to bracken in childhood.3 In Costa Rica gastric cancer incidence is three times greater in the mountainous, bracken-infested regions than in the bracken-free lowla..Tlds.4 Young bracken crozier (the most toxic growth stage), consumed as a delicacy, could be one factor contributing to the higher than average incidence of oesophageal cancer in some parts of Japan;5 and Japan has a very high incidence of stomach cancer. The hazard to man could be directly by consumption of bracken crozier or inhalation of spores or indirectly via milk, buttermilk, and dairy products. Long-term contamination of restricted water supplies, such as small wells and springs, in remote rural areas would be expected to increase the risk. Bracken spores entering the respiratory tract would be trapped in the mucous stream and eventually reach the stomach. An experiment in which spores suspended in water were administered by oral gavage without anaesthesia to young weanling mice (both sexes, two strains) gave the following results. Of 98 mice, most of which received 200 mg of spores, malignant disease developed in 53. Leukaemias, mainly lymphocytic with fewer granulocytic types, accounted for 28 of these. The shortest latent period was 4-5 months and many developed in less than a year; these were clearly not the spontaneous leukaemias of old age. Gastric tumours, with a much longer latent period (18 months to 2 years), were found in 6 mice; the significance is enhanced by the generally acknowledged difficulty in producing experimental stomach malignancies.
I. ANTICE EVANS O. P. GALPIN
SIR,-A 40-year-old woman presented to the accident-andemergency department with a false name, age, and address. She complained of a 1 week history of a swollen, painful left calf, and a one hour history of bright red haemoptysis with severe left-sided pleuritic pain. She was obese and dyspnoeic, clutching her left chest. She had many abdominal and pelvic scars with venous cutdown sites over peripheral and central veins. She said she had been involved in a road-traffic accident some years earlier. Chest radiography revealed prominent pulmonary arteries and an area of increased shadowing at the left base. She was in sinus tachycardia with striking right-axis deviation, findings consistent with acuteon-chronic pulmonary thromboembolic disease. She was treated with intravenous heparin. A ventilation-perfusion scan was normal. On the following morning she was recognised by a doctor and it emerged that she had been admitted five times before over a 3-year period with an identical history, giving different names and addresses every time. Her birthday was always the day after admission. After questioning she discharged herself. However, she attended the casualty department of a nearby hospital two hours later, with the same history. Two days after her discharge, thyroid function test results indicated profound primary hypothyroidism, samples having been taken when the woman had been admitted. Free thyroxine was 4-9 pmol/1 (normal 18’5-25’C), free triiodothyronine was 1 -11 pmol/1 (2’6-8’0), and thyrotropin was 46-5
mU/1 (03-40). A pattern of repeated hospital admission with simulated acute illness and false personal details -is typical of Munchausen’s syndrome. However, our patient was severely hypothyroid, and several neuropsychiatric manifestations of hypothyroidism are
recognised, including depression, memory impairment, dementia, florid hypochondriacal states. Frank psychosis ("myxoedematous madness") was described by Asher in 1949.1 His account of Munchausen’s syndrome came two years later.2 Perhaps Asher would have described this case as "myxoedematous Munchausen". Of importance to clinicians is the fact that organic illness may be overlooked in patients with Munchausen syndrome. When this patient next attends, we shall try to treat her with thyroxine. and
Department of Medicine St Thomas’s Hospital, London SE1, UK
S. J. D. BRECKER* N.
J. B. TREPTE
*Present address: Cardiac Department, London Chest Hospital, London E2 9JX, UK. 1. Asher RJ. "Myxoedematous madness". Br Med J 1949; ii: 555. 2. Asher R. Munchausen’s syndrome. Lancet 1951; i: 339-41.
respiratory and gastrointestinal tracts with cytokines may be the cause of death in SIDS. We thank the
Norwegian Research Council
release of various for Science and the
Humanities, Anders Jahre’s Foundation, and the Norwegian SIDSParents Association for financial support. Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology; and Institute of Forensic Medicine, Rikshospitalet, N-0027 Oslo, Norway, and Department of Oral Surgery and Oral Medicine, University of Oslo, Oslo
PER S. THRANE TORLEIV O. ROGNUM PER BRANDTZAEG
confirm or deny close linkage with markers on distal 4p). In a second family requesting testing the clinical diagnosis of HD has been doubted by some, since most affected members show very slight and very slow intellectual deterioration and the major clinical feature is mild chorea. Nonetheless there have been two cases with juvenile onset, and postmortem examination of one affected individual showed very mild but definite involvement of the caudate. It is important to obtain pathological confirmation of the diagnosis whenever possible, even if family structure and clinical features seem typical for HD. to
Department of Medical Genetics, Churchill Hospital, Oxford OX3 7LJ, UK
Stoltenberg L, Brandtzaeg P, Saugstad OD, Rognum TO. Tracheal wall shows local IgM immune response in SIDS. 1st World Congress in Paediatric Pathology, September 1989: B21-22 (abstr). 2. Forsyth KD, Weeks SC, Koh L, Skinner J, Bradley J. Lung immunoglobulins in the sudden infant death syndrome. Br Med J 1989; 298: 23-26. 3. Brandtzaeg P. Mucosal and glandular distribution of immunoglobulin components: immunohistochemistry with cold ethanol-fixation technique. Immunology 1974;
R. S. SHIWACH R. H. LINDENBAUM A. MICIAK
1.
MJ, Tyler A. Lazarou L, Meredith L, Harper PS. Problems m genetic prediction for Huntington’s disease. Lancet 1989; ii: 601-05. Folstein SE, Leigh RJ, Parhad IM, Folstein MF. The diagnosis of Huntington’s disease. Neurology 1986; 36: 1279-83.
1. Morris 2.
26: 1101-14.
Brandtzaeg P, Rognum TO. Evaluation of tissue preparation methods and paired immunofluorescence staining for immunocytochemistry of lymphomas. Histochem J 1983; 15: 655-89. 5. Rognum TO, Saugstad OD, Oyasaeter S, Olaisen B. Elevated levels of hypoxanthine in vitreous humor indicate prolonged cerebral hypoxia m victims of sudden infant death syndrome. Pediatrics 1988; 82: 615-18. 6. Valdes Dapena M. Sudden infant death syndrome: morphology update for forensic pathologists. Forensic Sci Int 1986; 30: 177-86. 7. Takashima S, Mito T, Becker LE. Neuronal development in medullary reticular formation in sudden infant death syndrome and premature infants. Neuropediatrics 1985; 16: 76-79. 8 Schneider PM, Wendler C, Riepert T, et al. Possible association of sudden infant death (SID) with partial complement C4 deficiency revealed by post-mortem DNA typing of HLA class II and III genes. Eur J Ped (in press). 9. Walter JS, Meyers P, Krueger JM. Microinjection of interleukin-1 into brain: separation of sleep and fever responses. Physiol Behav 1989; 45: 169-76. 10. Guntheroth WG. Interleukin-1 as intermediary causing prolonged sleep apnea and SIDS during respiratory infections. Med Hypoth 1989; 28: 121-23. 4.
Predicting Huntington’s disease SIR,-Setting up predictive testing for Huntington’s disease (HD) within the Oxford region, we have had 115 applicants so far and have met most of the difficulties described by Morris et aP plus a few additional ones. Testing post-mortem. An individual in his early sixties, from an informative family, requested predictive testing. He died, not from HD, shortly after giving blood for DNA but before being informed of the result. The widow and grown-up children have asked us to proceed with presymptomatic testing. This seems a reasonable request. Testing in prison. An individual from an informative family
requested predictive testing, although serving a long prison sentence. We saw no ethical difficulties in agreeing to this request. A bad result might argue in favour of early release. Testing the father. 4 people asking for the test thought their "official" father was not their biological one; in at least one case this suspicion was confirmed by DNA analysis. In some HD families proof of non-paternity will result in a risk reduction from nearly 50%
very low levels. Testing the wrong disorder. The misdiagnosis rate for HD may be as high as 15%. In two of thirty-eight families who had requested presymptomatic diagnosis and where there was an
Prenatal SIR,-Although comment
we
(Oct 7,
p
agree with Dr Dallapiccola and Dr Novelli’s 871) on our paper (Aug 19, p 419) that it is
possible to measure triose phosphate isomerase (TPI) activity on trophoblasts or cultured amniocytes, we have great reservations about the application of these techniques to prenatal diagnosis. Clark et al,l who also used these techniques, drew attention to the need for a marker in addition to enzyme activity; they suggested enzyme instability. In our case the red-cell enzyme activity in the was very close to the heterozygote values. This finding meant that the use of enzyme activities, even in the red cell with a narrower normal range than reported for trophoblast and cultured amniocytes, would make assignment of a homozygous or heterozygous state to a specific fetus rather difficult. Hence, we used the further, and perhaps more definitive, evidence of a metabolic block-ie, the increase in dihydroxyacetone phosphate (DHAP). This provides convincing evidence of a functional enzyme block associated with the homozygous state. However, in nucleated cells such as amniocytes and trophoblasts it is likely that the DHAP may not be such a reliable marker owing to the presence of glycerol-3phosphate dehydrogenase which would metabolise the DHAP.
affected child
We would therefore caution against the use of enzyme activity in
amniocyte or trophoblastic material until there is more evidence for a metabolic block, since such a major decision for the parents depends on the results. We would rather rely on the more sound assays on red cells in the second trimester until DNA analysis is available, which will surely follow soon. Department of Haematological Medicine,
King’s College School of Medicine and Dentistry, London SE5 9PJ, UK 1. Clark
ACL, Szobolotzky MA. Triose phosphate diagnosis. J Pediatr 1985; 106: 417-20.
A. J. BELLINGHAM A. N. LESTAS isomerase
deficiency: prenatal
Griseofulvin-induced neuropathy
to
autosomal dominant pattern of transmission and a clinical diagnosis of HD, the neuropathological findings seemed incompatible with HD or there were unusual features, clinical and neuropathological. In a large family with dominant transmission of presenile dementia and chorea through at least three generations, experienced neurologists diagnosed HD several times. However, necropsy on three closely related affected individuals revealed a differing pattern of involvement of pons, substantia nigra, inferior olive, and cerebellum, with normal caudate, putamen, and cerebral cortex. These neuropathological changes are not uniformly characteristic of any reported type of olivopontocerebellar atrophy (and there are insufficient samples of DNA from affected individuals, at present,
diagnosis of triose phosphate deficiency
isomerase
SIR,-A 76-year-old woman was treated with griseofulvin 500 mg daily for 4 months in 1987 and 6 months in 1988 for fungal nail infection. The second treatment was discontinued after paraesthesia developed in all fingers, followed by numbness of the feet and a sensation of "walking on cottonwool". Her general health was excellent. She had a history of treated hypothyroidism. Alcohol consumption was about 5 units per week. 4 months after the onset of neurological symptoms ankle jerks were absent and she had bilateral loss of vibration sense at the hallux. Nerve conduction studies showed a severe but very distal motor and sensory neuropathy (table). Laboratory investigations, including cerebrospinal fluid examination, were negative. 4 months later her sensory symptoms had resolved and there were no neurological signs. Nerve conduction had substantially improved
(table).
231
NERVE CONDUCTION STUDIES*
Neither leukaemias nor gastric cancer occurred in any of 49 controls given equivalent volumes of water. There were only 2 controls with tumours, both mammary with latent periods of about 16 months. Previous work with bracken extracts and mice have produced a majority of lymphocytic leukaemias but the myeloid system is similarly responsive and the spectrum includes rarer varieties; gastric malignancies have been both squamous and glandular.6 The sporulation of bracken is regional and influenced by several factors, but one good sized frond can yield 1-0 g of the brown powder, enough to produce leukaemias in 5 susceptible mice. School of
*Results of second examination marked
in
parentheses. tall values reduced except these so
SAP = sensory action potential (orthodromic), SCV = sensory conduction velocity, CMAP=compound muscle action potential, MCV=motor conduction velocity. R =right.
DML=distal
motor
latency,
It seems likely that the neuropathy was caused by griseofulvin. The Committee on Safety of Medicines (CSM) has reports of 5 cases of "neuropathy" and 6 cases of "paraesthesia" occurring in association with griseofulvin treatment (CSM, personal communication), but none seem to have been well documented. I thank Dr S. M. Wood, Principal Medical Officer, Committee on Safety of Medicines for permission to quote CSM data, and Dr D. L. Higson of Glaxo Laboratories for making available data held by the company.
Mersey Regional Department of Neurology, Hospital, Liverpool L9 1AE, UK
Biological Sciences, University College of North Wales, Bangor, Gwynedd LL57 2UW, UK
IA, Mason J. Carcinogenic activity of bracken. Nature 1965; 208: 913-14. 1968; 28: 2252-61. possible links with bracken. Br J Cancer (in press). 4. Villalobos-Salazar J, Meneses A, Rojas JL, et al. Bracken derived carcinogens as affecting animal health and human health in Costa Rica. In: Taylor JA, ed. Bracken toxicity and carcinogenicity as related to animal and human health: International Bracken Group special publication. Aberystwyth: University College of Wales, 1. Evans
2. Evans IA. The radiomimetic nature of bracken toxin. Cancer Res 3. Galpin OP, Whitaker CJ, Kassab J. Gastric cancer in Gwynedd:
1989: 40-51.
S, Hirayama T. Epidemiology of cancer of the oesophagus in Miye, Nara and Wakayama Prefecture with special reference to the role of the bracken fern. Proc Jap Cancer Assoc (34th annual meeting, Osaka, 1975): 211. Evans IA. Bracken carcinogenicity. In. James GV, ed. Reviews on environmental health: Int Quart Sci Rev vol VII. Tel Aviv: Freund Publishing House, 1987:
5. Kamon
6.
161-99.
Myxoedematous Munchausen?
Walton
B. R. F. LECKY
Bracken and leukaemia SIR,-From their study of cancer near potential sites of nuclear installations Paula Cook-Mozaffari (Nov 11, p 1145) and her colleagues conclude that there are "systematic differences between districts near existing or potential installations and other districts with respect to some important, unrecognised risk factors". Such factors are probably environmental; one such factor, long recognised, is bracken (Pteridium aquilinum), which itself has radiomimetic properties.1,2 Nuclear power plants, actual or potential, are likely to be sited in terrain where bracken is
indigenous. Bracken is carcinogenic in a wide variety of animal species, it affects different organs and tissues, and the younger the animal when exposed the greater is the susceptibility. There is now growing evidence from different countries that human beings are not exempt. In the UK a questionnaire-based case-control study on 101 histologically confirmed stomach cancer cases revealed a significant correlation with exposure to bracken in childhood.3 In Costa Rica gastric cancer incidence is three times greater in the mountainous, bracken-infested regions than in the bracken-free lowla..Tlds.4 Young bracken crozier (the most toxic growth stage), consumed as a delicacy, could be one factor contributing to the higher than average incidence of oesophageal cancer in some parts of Japan;5 and Japan has a very high incidence of stomach cancer. The hazard to man could be directly by consumption of bracken crozier or inhalation of spores or indirectly via milk, buttermilk, and dairy products. Long-term contamination of restricted water supplies, such as small wells and springs, in remote rural areas would be expected to increase the risk. Bracken spores entering the respiratory tract would be trapped in the mucous stream and eventually reach the stomach. An experiment in which spores suspended in water were administered by oral gavage without anaesthesia to young weanling mice (both sexes, two strains) gave the following results. Of 98 mice, most of which received 200 mg of spores, malignant disease developed in 53. Leukaemias, mainly lymphocytic with fewer granulocytic types, accounted for 28 of these. The shortest latent period was 4-5 months and many developed in less than a year; these were clearly not the spontaneous leukaemias of old age. Gastric tumours, with a much longer latent period (18 months to 2 years), were found in 6 mice; the significance is enhanced by the generally acknowledged difficulty in producing experimental stomach malignancies.
I. ANTICE EVANS O. P. GALPIN
SIR,-A 40-year-old woman presented to the accident-andemergency department with a false name, age, and address. She complained of a 1 week history of a swollen, painful left calf, and a one hour history of bright red haemoptysis with severe left-sided pleuritic pain. She was obese and dyspnoeic, clutching her left chest. She had many abdominal and pelvic scars with venous cutdown sites over peripheral and central veins. She said she had been involved in a road-traffic accident some years earlier. Chest radiography revealed prominent pulmonary arteries and an area of increased shadowing at the left base. She was in sinus tachycardia with striking right-axis deviation, findings consistent with acuteon-chronic pulmonary thromboembolic disease. She was treated with intravenous heparin. A ventilation-perfusion scan was normal. On the following morning she was recognised by a doctor and it emerged that she had been admitted five times before over a 3-year period with an identical history, giving different names and addresses every time. Her birthday was always the day after admission. After questioning she discharged herself. However, she attended the casualty department of a nearby hospital two hours later, with the same history. Two days after her discharge, thyroid function test results indicated profound primary hypothyroidism, samples having been taken when the woman had been admitted. Free thyroxine was 4-9 pmol/1 (normal 18’5-25’C), free triiodothyronine was 1 -11 pmol/1 (2’6-8’0), and thyrotropin was 46-5
mU/1 (03-40). A pattern of repeated hospital admission with simulated acute illness and false personal details -is typical of Munchausen’s syndrome. However, our patient was severely hypothyroid, and several neuropsychiatric manifestations of hypothyroidism are
recognised, including depression, memory impairment, dementia, florid hypochondriacal states. Frank psychosis ("myxoedematous madness") was described by Asher in 1949.1 His account of Munchausen’s syndrome came two years later.2 Perhaps Asher would have described this case as "myxoedematous Munchausen". Of importance to clinicians is the fact that organic illness may be overlooked in patients with Munchausen syndrome. When this patient next attends, we shall try to treat her with thyroxine. and
Department of Medicine St Thomas’s Hospital, London SE1, UK
S. J. D. BRECKER* N.
J. B. TREPTE
*Present address: Cardiac Department, London Chest Hospital, London E2 9JX, UK. 1. Asher RJ. "Myxoedematous madness". Br Med J 1949; ii: 555. 2. Asher R. Munchausen’s syndrome. Lancet 1951; i: 339-41.
