- Email: [email protected]
A very young Lancet reader
We amplified a 189 basepair (bp) fragment of the factor V gene, using as primers 5’-TGCCCAGTGCTTAACAAGACCA-3’ (nucleotides 1581-1602)2 and 5’-GACCTAACATGTTCTAGCCAGAAG-3’ (intron 10, nt 45 to nt 68)3 in intron 10. Digestion of the 189 bp fragment with Mnll resulted in three fragments of 85, 67, and 37 bp in healthy individuals and 122, 85, 67, and 37 in heterozygotes carrying the A-G mutation at position 1691 (figure). Five (2-5%) of 200 individuals studied had the A-G mutation at position 1691 as detected by Mnll digestion confirmed by direct sequencing. The 2-5% frequency found in our study is consistent with the range (3-7%) reported by others.4 Our results indicate that Rees and colleagues’ finding of no individuals with this mutation is not an accurate representation of the distribution in Saudi Arabia, and probably the Middle East as a whole. Their inclusion of African and Middle Eastern individuals within the same group is inappropriate. We believe that evaluation of the factor V mutation as a risk factor for thrombophilia in the Saudi Arabian population is justified.
blood is infective in laboratory animals during the incubation
period and clinical encephalopathy.’
phase
of
subacute
spongiform
I
*Alain Créange, Françoise Gray, Pierre Cesaro, Jean-Denis Degos *Service de Neurologie et Département de Neurosciences, Centre Hospitalier Universitaire Henri Mondor, 94010 Créteil, France
1 2
3
4
Operskalski EA, Mosley JW. Pooled plasma derivatives and Creutzfeldt-Jakob disease. Lancet 1995; 346: 1224. Créange A, Gray F, Cesaro P, et al. Creutzfeldt-Jakob disease after liver transplantation. Ann Neurol 1995; 38: 269-72. Manuelidis EE, Kim JH, Mericangas JR, Manuelidis L. Transmission to animals of Creutzfeldt-Jakob disease from human blood. Lancet 1985; ii: 896-97. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC. Creutzfeldt-Jakob disease in mice: persistent viremia and preferential replication of virus in low-density lymphocytes. Infect Immun 1983; 41: 154-61.
A very young Lancet reader
*Nduna Dzimiri, Brian Meyer Biological and Medical Research Department (MBC-03), King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
1 2
3
Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-34. Bertini RM, Koelman BPC, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67. Beauchamp NJ, Daly ME, Hampton KK, et al. High prevalence of a mutation in the factor V gene within the UK population: relationship to activated protein C resistance and familial thrombosis.
Br J Haematol 1994; 4
88: 219-22.
Dahlback B. Molecular genetics of venous thromboembolism. Ann Med 1995; 27: 187-92.
Pooled plasma derivatives and CreutzfeldtJakob disease SIR-The role of blood products in the transmission of Creutzfeldt-Jakob disease (CJD) is debatable. Operskalski and Mosley,’ in view of the absence of CJD reported in haemophilia patients, suggested that plasma products should not be a risk for prion transmission. We would draw the attention of these investigators to our recent observations about a 57-year-old woman who died from CJD 2 years after a liver transplantation.2 The liver donor had no history of neurological disease. However, and blood, albumin, during grafting, plasma, transfused. were One anticytomegalovirus immunoglobulins albumin donor developed, 3 years later, probable CJD. Our female patient’s disease began with cerebellar ataxia. Her neuropathological changes, including Kuru-type plaques and prion protein deposits (western blot analysis), predominantly involved the cerebellum. The patient was homozygous for valine at codon 129 of the PrP gene whereas the liver was homozygous for methionine. None of the known pathogenic mutation was detected in the PrP-gene-coding sequence, even in the DNA extracted from the grafted liver. Clinical, pathological, biochemical, and genetic features suggested the possibility of a transmitted CJD.
latrogenic CJD secondary
to
growth-hormone injections
hormone production from thousands of We suggest that the role of non-neural pooled pituitaries. blood tissue, including products, in the transmission of CJD should not be overlooked. For example, thousands of units of plasma are required to produce purified blood fractions, as they are for growth-hormone purification. Transmission of CJD to animals from human blood is possible.3 Finally,
has been related
482
to
Francesco Vaira, aged 2 months D Vaira
DEPARTMENT OF ERROR Monozygotic twins concordant for response to clozapine-In this letter by Vojvoda and colleagues (Jan 6, p 61) an error in dosage occurred several times. Doses of clozapine, valproate, and haloperidol should have read "once daily" (para 2, lines 10 and 15; para 3, lines 4, 8, and 11); and blood concentrations of clozapine and valproate should have read 55 Ilg/L (para 2, last line). Not
13,
quite as random as I pretended---In this commentary by Martyn (Jan 70), reference 1 referred to in the first paragraph was incorrect and
p
should have read: Schulz KF. Subverting randomization in controlled trials. JAMA 1995; 274: 1456-58. The references numbered 1 and 2 in the third paragraph are those listed in the reference list, which should have been numbered 2 and 3. The Infected metropolis-In this commentary by Horton (Jan 20, p 134), the photograph should have been accredited to The Telegraph Colour
Lzbrary.
blood is infective in laboratory animals during the incubation
period and clinical encephalopathy.’
phase
of
subacute
spongiform
I
*Alain Créange, Françoise Gray, Pierre Cesaro, Jean-Denis Degos *Service de Neurologie et Département de Neurosciences, Centre Hospitalier Universitaire Henri Mondor, 94010 Créteil, France
1 2
3
4
Operskalski EA, Mosley JW. Pooled plasma derivatives and Creutzfeldt-Jakob disease. Lancet 1995; 346: 1224. Créange A, Gray F, Cesaro P, et al. Creutzfeldt-Jakob disease after liver transplantation. Ann Neurol 1995; 38: 269-72. Manuelidis EE, Kim JH, Mericangas JR, Manuelidis L. Transmission to animals of Creutzfeldt-Jakob disease from human blood. Lancet 1985; ii: 896-97. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC. Creutzfeldt-Jakob disease in mice: persistent viremia and preferential replication of virus in low-density lymphocytes. Infect Immun 1983; 41: 154-61.
A very young Lancet reader
*Nduna Dzimiri, Brian Meyer Biological and Medical Research Department (MBC-03), King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
1 2
3
Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-34. Bertini RM, Koelman BPC, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67. Beauchamp NJ, Daly ME, Hampton KK, et al. High prevalence of a mutation in the factor V gene within the UK population: relationship to activated protein C resistance and familial thrombosis.
Br J Haematol 1994; 4
88: 219-22.
Dahlback B. Molecular genetics of venous thromboembolism. Ann Med 1995; 27: 187-92.
Pooled plasma derivatives and CreutzfeldtJakob disease SIR-The role of blood products in the transmission of Creutzfeldt-Jakob disease (CJD) is debatable. Operskalski and Mosley,’ in view of the absence of CJD reported in haemophilia patients, suggested that plasma products should not be a risk for prion transmission. We would draw the attention of these investigators to our recent observations about a 57-year-old woman who died from CJD 2 years after a liver transplantation.2 The liver donor had no history of neurological disease. However, and blood, albumin, during grafting, plasma, transfused. were One anticytomegalovirus immunoglobulins albumin donor developed, 3 years later, probable CJD. Our female patient’s disease began with cerebellar ataxia. Her neuropathological changes, including Kuru-type plaques and prion protein deposits (western blot analysis), predominantly involved the cerebellum. The patient was homozygous for valine at codon 129 of the PrP gene whereas the liver was homozygous for methionine. None of the known pathogenic mutation was detected in the PrP-gene-coding sequence, even in the DNA extracted from the grafted liver. Clinical, pathological, biochemical, and genetic features suggested the possibility of a transmitted CJD.
latrogenic CJD secondary
to
growth-hormone injections
hormone production from thousands of We suggest that the role of non-neural pooled pituitaries. blood tissue, including products, in the transmission of CJD should not be overlooked. For example, thousands of units of plasma are required to produce purified blood fractions, as they are for growth-hormone purification. Transmission of CJD to animals from human blood is possible.3 Finally,
has been related
482
to
Francesco Vaira, aged 2 months D Vaira
DEPARTMENT OF ERROR Monozygotic twins concordant for response to clozapine-In this letter by Vojvoda and colleagues (Jan 6, p 61) an error in dosage occurred several times. Doses of clozapine, valproate, and haloperidol should have read "once daily" (para 2, lines 10 and 15; para 3, lines 4, 8, and 11); and blood concentrations of clozapine and valproate should have read 55 Ilg/L (para 2, last line). Not
13,
quite as random as I pretended---In this commentary by Martyn (Jan 70), reference 1 referred to in the first paragraph was incorrect and
p
should have read: Schulz KF. Subverting randomization in controlled trials. JAMA 1995; 274: 1456-58. The references numbered 1 and 2 in the third paragraph are those listed in the reference list, which should have been numbered 2 and 3. The Infected metropolis-In this commentary by Horton (Jan 20, p 134), the photograph should have been accredited to The Telegraph Colour
Lzbrary.