- Email: [email protected]
Waking the dead
CORRESPONDENCE
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PCR amplification of DAZ gene sequences (STSs, sY277, and sY283 in Yq11) Lanes 1–6=sY277 (amplified fragment size: 275 bp); lanes 7–12=sY283 (375 bp); lanes 1 and 7, water controls; lane 2=blood from twin brother; lane 3=first blood sample from patient; lane 4=second blood sample from patient; lanes 5 and 11=unrelated male controls (blood); lane 8=lesional skin from patient; lanes 6, 9, and 12=normal female controls (blood); lane 10=blood from female control pregnant with male child.
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Srivatsa B, Srivatsa S, Johnson KL, Samura O, Lee SL, Bianchi DW. Microchimerism of presumed fetal origin in thyroid specimens from women: a casecontrol study. Lancet 2001; 358: 2034–38. van Dijk BA, Boomsma DI, de Man AJ. Blood group chimerism in human multiple births is not rare. Am J Med Genet 1996; 61: 264–68. Tanei R, Yokono H, Motoori T, Katsuoka K. Microchimerism seems uninvolved in the pathogenesis of idiopathic lichen planus. Dermatology 2000; 201: 373–74. Aractingi S, Chosidow O. Cutaneous graftversus-host disease. Arch Dermatol 1998; 134: 602–12. Lambert NC, Evans PC, Hashizumi TL, et al. Cutting edge: persistent fetal microchimerism in T lymphocytes is associated with HLA-DQA1*0501: implications in autoimmunity. J Immunol 2000; 164: 5545–48.
Sir—As Thomas Werkerle and colleagues’ comments suggest,1 surgeons like to maintain that brain death can be diagnosed with electroencephalography continued for 30 min. Many lay people are impressed by this type of test, but not neurologists and many other doctors. Who of these surgeons has ever seen the isoelectric activity of patients who are ventilated? I call on the community of transplant surgeons to study more extensively the processes about death and to exercise the necessary precision and clarity when dealing with issues pertaining to the fact of death, especially brain death. Johann Loibner Arzt für Allgemeinmedizin, 8563 Ligist, Austria 1
sample that showed typical lichenoid features (figure). However, fluorescent in-situ hybridisation of affected skin and peripheral blood lymphocytes detected no male cells. The patient (46,XX) and her twin brother (46,XY) had normal standard karyotypes. Careful precautions were taken to avoid male DNA contamination during sampling and processing of the samples. Therefore, in the absence of any other identified cause, we assume that male DNA originated from in-utero fetal blood cell transfusion from the patient’s twin. Although lichenoid skin changes are commonly seen in chronic graft-versushost disease after bone-marrow transplantation, microchimerism is not generally reported in lichen planus.3 However, we suggest the pathogenic involvement of microchimerism in this case because of the unusual clinical presentation, with features uncommon in lichen planus, but reminiscent of those noted in chronic cutaneous graftversus-host disease: involvement of the palms and soles, ulceration, poikiloderma, and retractile sclerosis.4 Moreover, the twins had the same heterozygous HLA-DQA1*0505 allele, very similar to the DQA1*0501 allele associated with persistence of fetal microchimerism.5 Thus, as in other inflammatory diseases, microchimerism may be associated with unusual presentations of lichen planus. We thank P Levillain and E Menet for histological analysis, N Raymond and F Brizard for fluorescence in-situ hybridisation analysis, D Bois for HLA typing, and P Amati-Bonneau for DNA extraction. This work was supported by grant ARS 2.13 from Fondation de la Recherche Médicale.
*Pierre Vabres, Marie-Claire Malinge, Marc Larrègue, Dominique Bonneau *Service de Dermatologie, Centre Hospitalier Universitaire, Poitiers, BP 577, 86021 Poitiers Cedex, France; and Service de Génétique, Centre Hospitalier Universitaire, Angers, France (e-mail: [email protected])
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Waking the dead Sir—Thomas Wekerle and colleagues (Dec 1, p 1907)1 place great emphasis on the documentation of protracted electrocerebral silence in the diagnosis of brain death, recognising that its declaration for transplantation purposes is an especially sensitive issue. Since electroencephalographic recording is discouraged by the UK’s protocol for the certification of death in that context, our Austrian colleagues are presumably to some extent unhappy with UK practice. It is therefore apparent that, contrary to what our Department of Health would have the general public believe, there is no European consensus on this matter. There is certainly no worldwide consensus.2 To be fair to people asked to register as potential organ donors, the Department of Health’s promotional literature should make it clear that there is continuing controversy about the diagnosis of what might be termed neurological death—the terms brain death and brain-stem death having been officially abandoned in this context—and specific consent before the crucial apnoea test should be made mandatory in light of its potential to exacerbate the brain damage or even to prove fatal.3 David W Evans 27 Gough Way, Cambridge, CB3 9LN, UK (e-mail: [email protected]) 1
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Wekerle T, Asari R, Bodingbauer M, Mühlbacher F. Waking the dead. Lancet 2001; 358: 1907. Potts M, Byrne PA, Nilges RG, eds. Beyond brain death: the case against brain based criteria for human death. Dordrect: Kluwer Academic Publishers, 2000. Coimbra CG. Implications of ischaemic penumbra for the diagnosis of brain death. Braz J Med Biol Res 1999; 32: 1479–87.
Werkerle T, Asari R, Bodingbauer M, Mühlbacher F. Waking the dead. Lancet 2001; 358: 1907.
Drug resistance and influenza pandemics Sir—Hiroshi Suzuki and colleagues (Dec 1, p 1910)1 emphasise the usefulness of amantadine as an intervention in influenza pandemics. They discuss misconceptions about development of drug resistance. 100 mg amantadine is generally well tolerated in ambulatory adults, but, unlike rimantadine, it is associated with substantial toxic effects to the central nervous system in institutionalised elderly patients,2 and in those with renal insufficiency. Furthermore, unlike the less well tolerated 200 mg dose, prophylactic or therapeutic effectiveness in pandemic influenza has not been rigorously established for the lower dose. The issue of drug resistance development needs more precise investigation. Little is known about the epidemiological importance of the emergence of drug-resistant influenza viruses, although the available evidence suggests important differences between the M2 protein inhibitors, such as amantadine, and the neuraminidase inhibitors zanamivir and oseltamivir for resistance emergence and transmission.2 The effects of large-scale antiviral administration during a pandemic could be assessed if we knew more about the dynamics of drug resistance and the spread of resistant virus. Mathematical models allow insights into this issue and the effects of interventions. We have developed a model for a closed population, which has been used to explore the effects of wide use of amantadine treatment, prophylaxis, or both, and the potential for development of drug resistance.3 An important
THE LANCET • Vol 359 • May 25, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
1
2
PCR amplification of DAZ gene sequences (STSs, sY277, and sY283 in Yq11) Lanes 1–6=sY277 (amplified fragment size: 275 bp); lanes 7–12=sY283 (375 bp); lanes 1 and 7, water controls; lane 2=blood from twin brother; lane 3=first blood sample from patient; lane 4=second blood sample from patient; lanes 5 and 11=unrelated male controls (blood); lane 8=lesional skin from patient; lanes 6, 9, and 12=normal female controls (blood); lane 10=blood from female control pregnant with male child.
3
4
5
Srivatsa B, Srivatsa S, Johnson KL, Samura O, Lee SL, Bianchi DW. Microchimerism of presumed fetal origin in thyroid specimens from women: a casecontrol study. Lancet 2001; 358: 2034–38. van Dijk BA, Boomsma DI, de Man AJ. Blood group chimerism in human multiple births is not rare. Am J Med Genet 1996; 61: 264–68. Tanei R, Yokono H, Motoori T, Katsuoka K. Microchimerism seems uninvolved in the pathogenesis of idiopathic lichen planus. Dermatology 2000; 201: 373–74. Aractingi S, Chosidow O. Cutaneous graftversus-host disease. Arch Dermatol 1998; 134: 602–12. Lambert NC, Evans PC, Hashizumi TL, et al. Cutting edge: persistent fetal microchimerism in T lymphocytes is associated with HLA-DQA1*0501: implications in autoimmunity. J Immunol 2000; 164: 5545–48.
Sir—As Thomas Werkerle and colleagues’ comments suggest,1 surgeons like to maintain that brain death can be diagnosed with electroencephalography continued for 30 min. Many lay people are impressed by this type of test, but not neurologists and many other doctors. Who of these surgeons has ever seen the isoelectric activity of patients who are ventilated? I call on the community of transplant surgeons to study more extensively the processes about death and to exercise the necessary precision and clarity when dealing with issues pertaining to the fact of death, especially brain death. Johann Loibner Arzt für Allgemeinmedizin, 8563 Ligist, Austria 1
sample that showed typical lichenoid features (figure). However, fluorescent in-situ hybridisation of affected skin and peripheral blood lymphocytes detected no male cells. The patient (46,XX) and her twin brother (46,XY) had normal standard karyotypes. Careful precautions were taken to avoid male DNA contamination during sampling and processing of the samples. Therefore, in the absence of any other identified cause, we assume that male DNA originated from in-utero fetal blood cell transfusion from the patient’s twin. Although lichenoid skin changes are commonly seen in chronic graft-versushost disease after bone-marrow transplantation, microchimerism is not generally reported in lichen planus.3 However, we suggest the pathogenic involvement of microchimerism in this case because of the unusual clinical presentation, with features uncommon in lichen planus, but reminiscent of those noted in chronic cutaneous graftversus-host disease: involvement of the palms and soles, ulceration, poikiloderma, and retractile sclerosis.4 Moreover, the twins had the same heterozygous HLA-DQA1*0505 allele, very similar to the DQA1*0501 allele associated with persistence of fetal microchimerism.5 Thus, as in other inflammatory diseases, microchimerism may be associated with unusual presentations of lichen planus. We thank P Levillain and E Menet for histological analysis, N Raymond and F Brizard for fluorescence in-situ hybridisation analysis, D Bois for HLA typing, and P Amati-Bonneau for DNA extraction. This work was supported by grant ARS 2.13 from Fondation de la Recherche Médicale.
*Pierre Vabres, Marie-Claire Malinge, Marc Larrègue, Dominique Bonneau *Service de Dermatologie, Centre Hospitalier Universitaire, Poitiers, BP 577, 86021 Poitiers Cedex, France; and Service de Génétique, Centre Hospitalier Universitaire, Angers, France (e-mail: [email protected])
1862
Waking the dead Sir—Thomas Wekerle and colleagues (Dec 1, p 1907)1 place great emphasis on the documentation of protracted electrocerebral silence in the diagnosis of brain death, recognising that its declaration for transplantation purposes is an especially sensitive issue. Since electroencephalographic recording is discouraged by the UK’s protocol for the certification of death in that context, our Austrian colleagues are presumably to some extent unhappy with UK practice. It is therefore apparent that, contrary to what our Department of Health would have the general public believe, there is no European consensus on this matter. There is certainly no worldwide consensus.2 To be fair to people asked to register as potential organ donors, the Department of Health’s promotional literature should make it clear that there is continuing controversy about the diagnosis of what might be termed neurological death—the terms brain death and brain-stem death having been officially abandoned in this context—and specific consent before the crucial apnoea test should be made mandatory in light of its potential to exacerbate the brain damage or even to prove fatal.3 David W Evans 27 Gough Way, Cambridge, CB3 9LN, UK (e-mail: [email protected]) 1
2
3
Wekerle T, Asari R, Bodingbauer M, Mühlbacher F. Waking the dead. Lancet 2001; 358: 1907. Potts M, Byrne PA, Nilges RG, eds. Beyond brain death: the case against brain based criteria for human death. Dordrect: Kluwer Academic Publishers, 2000. Coimbra CG. Implications of ischaemic penumbra for the diagnosis of brain death. Braz J Med Biol Res 1999; 32: 1479–87.
Werkerle T, Asari R, Bodingbauer M, Mühlbacher F. Waking the dead. Lancet 2001; 358: 1907.
Drug resistance and influenza pandemics Sir—Hiroshi Suzuki and colleagues (Dec 1, p 1910)1 emphasise the usefulness of amantadine as an intervention in influenza pandemics. They discuss misconceptions about development of drug resistance. 100 mg amantadine is generally well tolerated in ambulatory adults, but, unlike rimantadine, it is associated with substantial toxic effects to the central nervous system in institutionalised elderly patients,2 and in those with renal insufficiency. Furthermore, unlike the less well tolerated 200 mg dose, prophylactic or therapeutic effectiveness in pandemic influenza has not been rigorously established for the lower dose. The issue of drug resistance development needs more precise investigation. Little is known about the epidemiological importance of the emergence of drug-resistant influenza viruses, although the available evidence suggests important differences between the M2 protein inhibitors, such as amantadine, and the neuraminidase inhibitors zanamivir and oseltamivir for resistance emergence and transmission.2 The effects of large-scale antiviral administration during a pandemic could be assessed if we knew more about the dynamics of drug resistance and the spread of resistant virus. Mathematical models allow insights into this issue and the effects of interventions. We have developed a model for a closed population, which has been used to explore the effects of wide use of amantadine treatment, prophylaxis, or both, and the potential for development of drug resistance.3 An important
THE LANCET • Vol 359 • May 25, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.