- Email: [email protected]
Increasing incidence of CNS primary lymphoma in south-east Scotland
895
that would almost double the amount of MTHF formed (from z 156 to 0-246 ug/1 plasma per min), equivalent to that provided by the single 4 mg dose prescribed in the MRC study (0-242 ug/1 per min). We support Scott and colleagues’ view of the value of a low-dose arm in the trial of primary prevention of NTD now underway in China. However, it seems unlikely that it is PteGlu rather than MTHF which is preventing NTD. Small doses of PteGlu, albeit in combination with other vitamins, or increases in food folate, both of which would result in almost all the vitamin appearing in the circulation as MTHF, have been associated with the prevention of NTD in the intervention studies of Smithells et al6,7 and the retrospective observations of Bower and Stanley.8 We would urge caution on synthetic MTHF. PteGlu is readily converted to the natural [6R] diastereoisomer of MTHF in vivo, but commercial MTHF is a mixture of natural and unnatural [6S] diastereoisomers. The effect of circulating [6S]-MTHF on the developing embryo should be established before MTHF supplementation is considered. An alternative might be the provision of a food rich in [6R]-MTHF. Our experiments suggest that pure orange juice may be a suitable source of this. The increase in plasma MTHF 21h after ingestion of 500 ml orange juice, containing 152-8 gg total Lactobacillus casei active folate (98’7 Ilg MTHF), was 10-4 ug/1 (unpublished), almost identical to the increase in plasma MTHF 21 h after 200 ng PteGlu.’ M. D. LUCOCK University Department of Paediatrics and Child Health,
JENNIFER WILD
Leeds General Infirmary, Leeds LS2 9NS, UK
R. HARTLEY M. I. LEVENE
Department of Chemical Pathology, University of Leeds
C.
J. SCHORAH
1. Lucock M, Wild J, Smithells RW, Hartley R. In vivo characterisation of the absorption and biotransformation of pteroylmonoglutamic acid in man: a model for future studies. Biochem Med Metab Biol 1989; 42: 30-42. 2. Lucock MD, Hartley R, Smithells RW. A rapid and specific HPLC-electrochemical method for the determination of endogeneous 5-methyltetrahydrofolic acid in plasma using solid phase sample preparation with internal standardization. Biomed
Chromatogr 1989; 3: 58-63. 3. Davis RE, Nicol DJ, Kelly A. An automated method for the measurement of folate activity. J Clin Pathol 1970; 23: 47-53. 4. Lucock M, Wild J, Smithells RW, Hartley R. Biotransformation of pteroylmonoglutamic acid during absorption: implications of Michaelis-Menten kinetics Eur J Clin Nutr 1989; 43: 631-35. 5. Czeizel A, Fritz G. Ethics of a randomized trial of periconceptual vitamins. JAMA 1989; 262: 1633-34. 6. Smithells RW, Sellar MJ, Hams R, et al. Further experience of vitamin supplementation for prevention of NTD recurrence. Lancet 1983; i: 1027-31. 7. Smithells RW, Sheppard S, Wild J, Schorah CJ. Prevention of neural tube defect recurrences in Yorkshire: final report. Lancet 1989; ii: 498-99. 8. Bower D, Stanley FJ. Dietary folate as a nsk factor for neural-tube defects: evidence from a case-control study in Western Australia. Med J Austr 1989; 150: 613-18.
SIR,-While 4 mg folic acid daily until 12 weeks of pregnancy may reduce the incidence of NTD there may be damaging effects. There is inadequate information on the safety of folic acid at this high dose in early pregnancy. After a single 5 mg dose substantial amounts of unmetabolised folic acid appear in plasma.’ In contrast to the major natural folate 5-methyltetrahydrofolic acid, folic acid inhibits dihydropteridine reductase (DHPR)DHPR is a key enzyme in the maintenance of tetrahydrobiopterin levels, and the lowered levels of dopamine, noradrenaline, and serotonin and folates in the central nervous system of children with inherited DHPR deficiency lead to gross neurological damage and death if untreated.3 High-dose folic acid may therefore damage neural tissue
during early embryonic development. Haematology Department, General Hospital,
Birmingham B4 6NH, Aston
University, Birmingham
UK
R.
J. LEEMING
J. A. BLAIR S. E. BROWN
1. Ratanasthien K, Blair JA, Leeming RJ, Cooke WT, Melikian V. Folates in human serum. J Clin Pathol 1974; 27: 875-79. 2. Brown SE. The biosynthesis of tetrahydrobiopterin in the rat. PhD thesis, Aston University, Birmingham, 1981. 3 Smith I, Leeming RJ, Cavanagh NPC, Hyland K. Neurological aspects of biopterin metabolism. Arch Dis Child 1986; 61: 130-37.
SiR,—Dr Taguchi (Aug 24, p 506) draws attention to the very prevalence of NTD in Japan at 0-4 to 06 per 1000 births and speculates that this is because of the widespread practice of eating fresh vegetables, fruit, and fish with rice at every meal, giving a folic acid intake far above minimum daily requirements. Might a similar explanation account for the very low incidence of NTD in Hong Kong? When I worked in Hong Kong in the 1980s I was impressed by the virtual absence of spina bifida (anencephaly did occur, but usually as part of syndromes of multiple congenital anomalies). A study from Tsan Yuk Hospital (University of Hong Kong) of the low
incidence of NTD defects amongst all deliveries in 1961-80
(123 491 births) showed incidences of anencephaly, spina bifida, and encephalocele of 083. 0,12, and 0-06 per 1000 births,
respectively.1 Between 1984 and 1990 at the Prince of Wales Hospital in the New Territories (about 30 000 births) there were 15 cases of anencephaly, 2 of encephalocele, 3 ofmeningomyelocele (all in South Asian babies), and 2 of meningocele (Dr T. F. Fok, personal communication). The southern Chinese diet typically contains a lot of green vegetables, fresh fruit, and rice, thereby providing a substantial amount of folic acid. Cooking vegetables by rapid stir-frying or by brief steaming would be expected to preserve folic acid content better than western cooking practices where vegetables are often overcooked in boiling water. Apparently in north China spina bifida is as common as it used to be in many western countries (Prof Michael Laurence, personal communication). In these regions diet is influenced by season, and fresh vegetables are scarce for much of the year. Some Chinese medical opinion has linked this high incidence of spina bifida with a much lower folic acid intake.2 Department of Child Health, University of Wales College of Medicine, Cardiff CF4 4XN, UK
D. P. DAVIES
A, Woo JSK, Poon IML, Ma H-K. Neural-tube defects in Hong Kong Chinese. Lancet 1981; ii: 468-69. 2. Ye H. The strategy of risk approach in perinatal care in Shuniyi county, Beijing. Paper read at symposium of Paediatrics in China and Africa (Royal Society of Medicine,
1. Ghosh
London, June, 1986).
Increasing incidence of CNS primary lymphoma in south-east Scotland SIR,-Primary (non-Hodgkin) lymphoma of the central nervous system (NHL-CNS), previously termed reticulum cell sarcoma and cerebral microglioma, is a non-Hodgkin lymphoma predominantly of B-cell origin.1.2 We have noted an abrupt rise in the frequency of confirmed diagnosis of NHL-CNS in south-east Scotland (catchment population 1-2 million) over the past 2 years. We have reviewed brain tumour diagnoses made in this department over
the past decade.
Pathology reference files and case-notes from the department of clinical neurosciences from January, 1981, to July, 1991, were studied to identify cases of NHL-CNS, defined as follows: (a) the patient presented with a neurological complaint, (b) the complaint proved to be due to a brain tumour confirmed as lymphoma by biopsy or necropsy, and (c) the work-up at the time of presentation disclosed no evidence of lymphoma except in the brain, leptomeninges, spinal cord, or eye.2 Cases of glioma and primary intracranial neoplasm during the same period were also analysed. 21 patients with NHL-CNS were identified. 15 (8 men and 7 women) were not immunocompromised and the other 6 (all male) had cerebral AIDS. Patients with AIDS presented earlier than non-immunocompromised patients (median 36 vs 60 years). Over the decade the annual number of cases of both primary intracranial neoplasm (median 173, range 145-183) and glioma (median 69, range 61-86) seen in our department remained fairly steady. The frequency of NHL-CNS has risen sharply with 15 cases presenting in the past 18 months (figure). It is unlikely that the increased use of computed tomographic scanning accounts for our finding since this tool has been available for much longer than 10 years, and over the past decade the annual number of cases of glioma and primary intracranial neoplasm have remained constant. Although immunocytochemical techniques
896
haemorrhage within the abdominal cavity. Her history of travel to a malaria-endemic country suggested investigation for malaria as a cause of the splenic rupture. Blood (typed Fya-b-) taken from the femoral vein showed a 1-8% P ovale infection with rings, trophozoites, schizonts, and multiple invasion. No other species of plasmodium was seen. DNA analysis of the blood sample using the P falciparum-specific Pfmdrprimer confirmed the absence of P falciparum.’ Histological examination of the lungs, brain, and kidney showed no important abnormalities. The liver showed slight sinusoidal congestion with prominence of Kupffer cells containing malarial pigment. The spleen contained areas of focal haemorrhage and frank haemorrhage within the subcapsular space and loss of the capsule. Expansion of sinusoids with prominent phagocytosis of red cells and malarial pigment was seen. P ovale as the cause of imported malaria in the UK is increasing. For example, statistics provided by the malaria reference laboratory (London School of Hygiene and Tropical Medicine) show that imported P ovale has risen from 2 7 % of all cases in 1986 to 7’1 % in Number of cases of NHL-CNS number of cases of glioma.
expressed
as
percentage of
have facilitated diagnostic classification, it is unlikely, in view of the skills available in our neuropathology department, that these lesions were previously misdiagnosed. Nor can an age shift in the at-risk population be the whole explanation.3 An increase in the frequency of NHL-CNS has also been recently noted elsewhere in the UK (Glasgow,4 Leeds5) and in the USA (Boston2). The rising frequency of NHL-CNS has implications for aetiology, epidemiology, and management. A diagnosis of NHLCNS is not encoded in the International Classification of Diseases 9th edition. Accurate national statistics are therefore very difficult to obtain from the Scottish Cancer Register or the Information and Statistics Division of the Scottish Health Service (J. A. Clarke, personnal communication). We therefore recommend the initiation of a national tumour register for NHL-CNS.
Department of Clinical Neurosciences, Western General Hospital, Edinburgh EH4 2XU, UK
MICHAEL G. O’SULLIVAN IAN R. WHITTLE ANNA GREGOR JAMES W. IRONSIDE
TL, Britt RH, Colby TV. Primary lymphoma of the central nervous system: clinicopathological study of experience at Stanford. J Neurosurg 1984; 60: 94-103. 2. Hochberg FH, Miller DC. Primary central nervous system lymphoma. J Neurosurg 1988; 68: 835-53. 3. Baumgartner JE, Rachlin JR, Beckstead JH, et al. Primary central nervous system lymphoma: natural history and response to radiation therapy in 55 patients with 1990; 73: 206-11. acquired immunodeficiency syndrome. Neurosurg J 4. Adams JH, Howatson AG. Cerebral lymphomas: a review of 70 cases. J Clin Pathol 1990; 43: 544-47. 5. Murphy JK, O’Brien CJ, Ironside JW. Morphologic and immunophenotypic characterisation of primary brain lymphomas using paraffin-embedded tissue. Histopathology 1989; 15: 449-60. 1. Helle
Spontaneous splenic rupture due to Plasmodium ovale malaria SiR,—Splenomegaly is characteristic of malaria, irrespective of the infecting species of plasmodium. In acute infections the spleen may enlarge to 500 g, and during repeated attacks can double this size. However, non-traumatic or spontaneous splenic rupture is P vivax has been the species in the few reported cases, the explanation being a rapid splenic enlargement during the acute stage, and therefore a greater risk of splenic rupture in P vivax malaria. We report what is, as far as we are aware, the first case of fatal splenic rupture due to infection with P ovale in the UK. A 51-year-old West-Indian woman, a long-time resident in the UK, took a nineteen day holiday to Ghana after the necessary vaccinations at a central London clinic. She was not advised to take antimalarial prophylactic drugs. Five days after her return she felt unwell and a week after this visited her doctor because of fever and headache and was prescribed pain killers. The following day she was found dead in bed. Necropsy done three hours later revealed no evidence of injury either superficially to the skin overlying the spleen or on deep dissection. On internal examination, the only major abnormality was a ruptured spleen with widespread rare.
1990. The reason is uncertain but may relate to an increase in Africans travelling to West Africa where the heaviest transmission of P ovale in sub-Saharan Africa takes place. Thus in the 2 years 1989-90, 69% of all cases of P ovale were imported from West African countries.2 The absolute requirement for visitors to malaria-endemic regions is that appropriate advice should be given about protection against mosquito bites and malaria chemoprophylaxis. Travellers should be made aware of the symptoms of malaria, and general practitioners the possibility of malaria in such a traveller. We thank Dr D. Warhurst for the DNA analysis.
Departments of Haematology and Forensic Medicine, London Hospital Medical London E1 2AD, UK
College,
CHRISTINE A. FACER D. ROUSE
1 Warhurst DC, Awad El Kanem FM, Miles MA. Simplified preparation of malarial blood samples for polymerase chain reaction. Lancet 1991; 337: 303-07. 2. Bradley DJ, Warhurst DC, Blaze M, Smith V. Malaria imported into the United Kingdom 1989 and 1990. Commun Dis Rep 1991; 1: R45.
Reduction of coma by quinine loading dose in falciparum cerebral malaria StR,—Increasing Plasmodium falciparum resistance to chloroquine and severity of cerebral malaria have become a major problem in Yaounde, Cameroon.’ On the basis of pharmacokinetic indices in cerebral malariaaquinine infusion regimen (8 mg of quinine base/kg body weight over 1 h followed by 8 mg of base/kg over 7 h, then 8 mg/kg over 8 h three times daily for 3 days) was randomly allocated to 10 patients; 10 others received a standard regimen used in Cameroon (8 mg of base/kg over 8 h, three times daily for 3 days). Thick blood films were obtained every 3 h for the first 12 h and every 12 h thereafter. They were stained with Giemsa and examined for parasites. All patients were African. They all had cerebral malaria and fulfilled the definition proposed by Warrell et al3-unrousable coma according to the Glasgow coma scale that was not attributable to other causes of encephalopathy, and P falciparum mono specific COMPARISON BETWEEN TREATMENT GROUPS ON ADMISSION AND AFTER START OF TREATMENT
*Non-parametnc Mann-Whitney U test corrected for ties. iv intravenous, NS not significant. =
=
that would almost double the amount of MTHF formed (from z 156 to 0-246 ug/1 plasma per min), equivalent to that provided by the single 4 mg dose prescribed in the MRC study (0-242 ug/1 per min). We support Scott and colleagues’ view of the value of a low-dose arm in the trial of primary prevention of NTD now underway in China. However, it seems unlikely that it is PteGlu rather than MTHF which is preventing NTD. Small doses of PteGlu, albeit in combination with other vitamins, or increases in food folate, both of which would result in almost all the vitamin appearing in the circulation as MTHF, have been associated with the prevention of NTD in the intervention studies of Smithells et al6,7 and the retrospective observations of Bower and Stanley.8 We would urge caution on synthetic MTHF. PteGlu is readily converted to the natural [6R] diastereoisomer of MTHF in vivo, but commercial MTHF is a mixture of natural and unnatural [6S] diastereoisomers. The effect of circulating [6S]-MTHF on the developing embryo should be established before MTHF supplementation is considered. An alternative might be the provision of a food rich in [6R]-MTHF. Our experiments suggest that pure orange juice may be a suitable source of this. The increase in plasma MTHF 21h after ingestion of 500 ml orange juice, containing 152-8 gg total Lactobacillus casei active folate (98’7 Ilg MTHF), was 10-4 ug/1 (unpublished), almost identical to the increase in plasma MTHF 21 h after 200 ng PteGlu.’ M. D. LUCOCK University Department of Paediatrics and Child Health,
JENNIFER WILD
Leeds General Infirmary, Leeds LS2 9NS, UK
R. HARTLEY M. I. LEVENE
Department of Chemical Pathology, University of Leeds
C.
J. SCHORAH
1. Lucock M, Wild J, Smithells RW, Hartley R. In vivo characterisation of the absorption and biotransformation of pteroylmonoglutamic acid in man: a model for future studies. Biochem Med Metab Biol 1989; 42: 30-42. 2. Lucock MD, Hartley R, Smithells RW. A rapid and specific HPLC-electrochemical method for the determination of endogeneous 5-methyltetrahydrofolic acid in plasma using solid phase sample preparation with internal standardization. Biomed
Chromatogr 1989; 3: 58-63. 3. Davis RE, Nicol DJ, Kelly A. An automated method for the measurement of folate activity. J Clin Pathol 1970; 23: 47-53. 4. Lucock M, Wild J, Smithells RW, Hartley R. Biotransformation of pteroylmonoglutamic acid during absorption: implications of Michaelis-Menten kinetics Eur J Clin Nutr 1989; 43: 631-35. 5. Czeizel A, Fritz G. Ethics of a randomized trial of periconceptual vitamins. JAMA 1989; 262: 1633-34. 6. Smithells RW, Sellar MJ, Hams R, et al. Further experience of vitamin supplementation for prevention of NTD recurrence. Lancet 1983; i: 1027-31. 7. Smithells RW, Sheppard S, Wild J, Schorah CJ. Prevention of neural tube defect recurrences in Yorkshire: final report. Lancet 1989; ii: 498-99. 8. Bower D, Stanley FJ. Dietary folate as a nsk factor for neural-tube defects: evidence from a case-control study in Western Australia. Med J Austr 1989; 150: 613-18.
SIR,-While 4 mg folic acid daily until 12 weeks of pregnancy may reduce the incidence of NTD there may be damaging effects. There is inadequate information on the safety of folic acid at this high dose in early pregnancy. After a single 5 mg dose substantial amounts of unmetabolised folic acid appear in plasma.’ In contrast to the major natural folate 5-methyltetrahydrofolic acid, folic acid inhibits dihydropteridine reductase (DHPR)DHPR is a key enzyme in the maintenance of tetrahydrobiopterin levels, and the lowered levels of dopamine, noradrenaline, and serotonin and folates in the central nervous system of children with inherited DHPR deficiency lead to gross neurological damage and death if untreated.3 High-dose folic acid may therefore damage neural tissue
during early embryonic development. Haematology Department, General Hospital,
Birmingham B4 6NH, Aston
University, Birmingham
UK
R.
J. LEEMING
J. A. BLAIR S. E. BROWN
1. Ratanasthien K, Blair JA, Leeming RJ, Cooke WT, Melikian V. Folates in human serum. J Clin Pathol 1974; 27: 875-79. 2. Brown SE. The biosynthesis of tetrahydrobiopterin in the rat. PhD thesis, Aston University, Birmingham, 1981. 3 Smith I, Leeming RJ, Cavanagh NPC, Hyland K. Neurological aspects of biopterin metabolism. Arch Dis Child 1986; 61: 130-37.
SiR,—Dr Taguchi (Aug 24, p 506) draws attention to the very prevalence of NTD in Japan at 0-4 to 06 per 1000 births and speculates that this is because of the widespread practice of eating fresh vegetables, fruit, and fish with rice at every meal, giving a folic acid intake far above minimum daily requirements. Might a similar explanation account for the very low incidence of NTD in Hong Kong? When I worked in Hong Kong in the 1980s I was impressed by the virtual absence of spina bifida (anencephaly did occur, but usually as part of syndromes of multiple congenital anomalies). A study from Tsan Yuk Hospital (University of Hong Kong) of the low
incidence of NTD defects amongst all deliveries in 1961-80
(123 491 births) showed incidences of anencephaly, spina bifida, and encephalocele of 083. 0,12, and 0-06 per 1000 births,
respectively.1 Between 1984 and 1990 at the Prince of Wales Hospital in the New Territories (about 30 000 births) there were 15 cases of anencephaly, 2 of encephalocele, 3 ofmeningomyelocele (all in South Asian babies), and 2 of meningocele (Dr T. F. Fok, personal communication). The southern Chinese diet typically contains a lot of green vegetables, fresh fruit, and rice, thereby providing a substantial amount of folic acid. Cooking vegetables by rapid stir-frying or by brief steaming would be expected to preserve folic acid content better than western cooking practices where vegetables are often overcooked in boiling water. Apparently in north China spina bifida is as common as it used to be in many western countries (Prof Michael Laurence, personal communication). In these regions diet is influenced by season, and fresh vegetables are scarce for much of the year. Some Chinese medical opinion has linked this high incidence of spina bifida with a much lower folic acid intake.2 Department of Child Health, University of Wales College of Medicine, Cardiff CF4 4XN, UK
D. P. DAVIES
A, Woo JSK, Poon IML, Ma H-K. Neural-tube defects in Hong Kong Chinese. Lancet 1981; ii: 468-69. 2. Ye H. The strategy of risk approach in perinatal care in Shuniyi county, Beijing. Paper read at symposium of Paediatrics in China and Africa (Royal Society of Medicine,
1. Ghosh
London, June, 1986).
Increasing incidence of CNS primary lymphoma in south-east Scotland SIR,-Primary (non-Hodgkin) lymphoma of the central nervous system (NHL-CNS), previously termed reticulum cell sarcoma and cerebral microglioma, is a non-Hodgkin lymphoma predominantly of B-cell origin.1.2 We have noted an abrupt rise in the frequency of confirmed diagnosis of NHL-CNS in south-east Scotland (catchment population 1-2 million) over the past 2 years. We have reviewed brain tumour diagnoses made in this department over
the past decade.
Pathology reference files and case-notes from the department of clinical neurosciences from January, 1981, to July, 1991, were studied to identify cases of NHL-CNS, defined as follows: (a) the patient presented with a neurological complaint, (b) the complaint proved to be due to a brain tumour confirmed as lymphoma by biopsy or necropsy, and (c) the work-up at the time of presentation disclosed no evidence of lymphoma except in the brain, leptomeninges, spinal cord, or eye.2 Cases of glioma and primary intracranial neoplasm during the same period were also analysed. 21 patients with NHL-CNS were identified. 15 (8 men and 7 women) were not immunocompromised and the other 6 (all male) had cerebral AIDS. Patients with AIDS presented earlier than non-immunocompromised patients (median 36 vs 60 years). Over the decade the annual number of cases of both primary intracranial neoplasm (median 173, range 145-183) and glioma (median 69, range 61-86) seen in our department remained fairly steady. The frequency of NHL-CNS has risen sharply with 15 cases presenting in the past 18 months (figure). It is unlikely that the increased use of computed tomographic scanning accounts for our finding since this tool has been available for much longer than 10 years, and over the past decade the annual number of cases of glioma and primary intracranial neoplasm have remained constant. Although immunocytochemical techniques
896
haemorrhage within the abdominal cavity. Her history of travel to a malaria-endemic country suggested investigation for malaria as a cause of the splenic rupture. Blood (typed Fya-b-) taken from the femoral vein showed a 1-8% P ovale infection with rings, trophozoites, schizonts, and multiple invasion. No other species of plasmodium was seen. DNA analysis of the blood sample using the P falciparum-specific Pfmdrprimer confirmed the absence of P falciparum.’ Histological examination of the lungs, brain, and kidney showed no important abnormalities. The liver showed slight sinusoidal congestion with prominence of Kupffer cells containing malarial pigment. The spleen contained areas of focal haemorrhage and frank haemorrhage within the subcapsular space and loss of the capsule. Expansion of sinusoids with prominent phagocytosis of red cells and malarial pigment was seen. P ovale as the cause of imported malaria in the UK is increasing. For example, statistics provided by the malaria reference laboratory (London School of Hygiene and Tropical Medicine) show that imported P ovale has risen from 2 7 % of all cases in 1986 to 7’1 % in Number of cases of NHL-CNS number of cases of glioma.
expressed
as
percentage of
have facilitated diagnostic classification, it is unlikely, in view of the skills available in our neuropathology department, that these lesions were previously misdiagnosed. Nor can an age shift in the at-risk population be the whole explanation.3 An increase in the frequency of NHL-CNS has also been recently noted elsewhere in the UK (Glasgow,4 Leeds5) and in the USA (Boston2). The rising frequency of NHL-CNS has implications for aetiology, epidemiology, and management. A diagnosis of NHLCNS is not encoded in the International Classification of Diseases 9th edition. Accurate national statistics are therefore very difficult to obtain from the Scottish Cancer Register or the Information and Statistics Division of the Scottish Health Service (J. A. Clarke, personnal communication). We therefore recommend the initiation of a national tumour register for NHL-CNS.
Department of Clinical Neurosciences, Western General Hospital, Edinburgh EH4 2XU, UK
MICHAEL G. O’SULLIVAN IAN R. WHITTLE ANNA GREGOR JAMES W. IRONSIDE
TL, Britt RH, Colby TV. Primary lymphoma of the central nervous system: clinicopathological study of experience at Stanford. J Neurosurg 1984; 60: 94-103. 2. Hochberg FH, Miller DC. Primary central nervous system lymphoma. J Neurosurg 1988; 68: 835-53. 3. Baumgartner JE, Rachlin JR, Beckstead JH, et al. Primary central nervous system lymphoma: natural history and response to radiation therapy in 55 patients with 1990; 73: 206-11. acquired immunodeficiency syndrome. Neurosurg J 4. Adams JH, Howatson AG. Cerebral lymphomas: a review of 70 cases. J Clin Pathol 1990; 43: 544-47. 5. Murphy JK, O’Brien CJ, Ironside JW. Morphologic and immunophenotypic characterisation of primary brain lymphomas using paraffin-embedded tissue. Histopathology 1989; 15: 449-60. 1. Helle
Spontaneous splenic rupture due to Plasmodium ovale malaria SiR,—Splenomegaly is characteristic of malaria, irrespective of the infecting species of plasmodium. In acute infections the spleen may enlarge to 500 g, and during repeated attacks can double this size. However, non-traumatic or spontaneous splenic rupture is P vivax has been the species in the few reported cases, the explanation being a rapid splenic enlargement during the acute stage, and therefore a greater risk of splenic rupture in P vivax malaria. We report what is, as far as we are aware, the first case of fatal splenic rupture due to infection with P ovale in the UK. A 51-year-old West-Indian woman, a long-time resident in the UK, took a nineteen day holiday to Ghana after the necessary vaccinations at a central London clinic. She was not advised to take antimalarial prophylactic drugs. Five days after her return she felt unwell and a week after this visited her doctor because of fever and headache and was prescribed pain killers. The following day she was found dead in bed. Necropsy done three hours later revealed no evidence of injury either superficially to the skin overlying the spleen or on deep dissection. On internal examination, the only major abnormality was a ruptured spleen with widespread rare.
1990. The reason is uncertain but may relate to an increase in Africans travelling to West Africa where the heaviest transmission of P ovale in sub-Saharan Africa takes place. Thus in the 2 years 1989-90, 69% of all cases of P ovale were imported from West African countries.2 The absolute requirement for visitors to malaria-endemic regions is that appropriate advice should be given about protection against mosquito bites and malaria chemoprophylaxis. Travellers should be made aware of the symptoms of malaria, and general practitioners the possibility of malaria in such a traveller. We thank Dr D. Warhurst for the DNA analysis.
Departments of Haematology and Forensic Medicine, London Hospital Medical London E1 2AD, UK
College,
CHRISTINE A. FACER D. ROUSE
1 Warhurst DC, Awad El Kanem FM, Miles MA. Simplified preparation of malarial blood samples for polymerase chain reaction. Lancet 1991; 337: 303-07. 2. Bradley DJ, Warhurst DC, Blaze M, Smith V. Malaria imported into the United Kingdom 1989 and 1990. Commun Dis Rep 1991; 1: R45.
Reduction of coma by quinine loading dose in falciparum cerebral malaria StR,—Increasing Plasmodium falciparum resistance to chloroquine and severity of cerebral malaria have become a major problem in Yaounde, Cameroon.’ On the basis of pharmacokinetic indices in cerebral malariaaquinine infusion regimen (8 mg of quinine base/kg body weight over 1 h followed by 8 mg of base/kg over 7 h, then 8 mg/kg over 8 h three times daily for 3 days) was randomly allocated to 10 patients; 10 others received a standard regimen used in Cameroon (8 mg of base/kg over 8 h, three times daily for 3 days). Thick blood films were obtained every 3 h for the first 12 h and every 12 h thereafter. They were stained with Giemsa and examined for parasites. All patients were African. They all had cerebral malaria and fulfilled the definition proposed by Warrell et al3-unrousable coma according to the Glasgow coma scale that was not attributable to other causes of encephalopathy, and P falciparum mono specific COMPARISON BETWEEN TREATMENT GROUPS ON ADMISSION AND AFTER START OF TREATMENT
*Non-parametnc Mann-Whitney U test corrected for ties. iv intravenous, NS not significant. =
=