422
Noticeboard AIDS without HIV? The first international meeting to examine details of sporadic of unexplained severe immunosuppression in adults without serological or virological evidence of human immunodeficiency virus, the association that attracted much attention at the VIII International Conference on AIDS last month (see Lancet Aug 1, pp 273 and 280), will be held at the World Health Organisation headquarters in Geneva on Sept 28-30.1 It will examine the information to be obtained in an urgent retrospective survey of such cases now being conducted by WHO in selected countries in Africa, Latin America, Asia, and Europe, and by the US Centers for Disease Control in North America. Recommendations for further research and public health guidelines will be formulated at the conference. Meanwhile, the CDC, together with the US National Institutes of Health, has held a meeting of investigators and public-health officials on August 14 to review findings. As of August 5 the CDC had received reports of 14 cases other than the 21 described in published reports." There is no indication of an epidemiological linkage between the cases, nor is it known whether they represent a single syndrome. One suggestion is that the CD4 depletion is a response to some infection and the deficiency is being recognised now because of the increased availability of T-cell phenotyping. The CDC is requesting health-care providers to report patients who have CD4 cell counts below 300 cells/1 or less than 20% on more than one determination, no serological evidence of HIV infection, and no defmed immunodeficiency or therapy associated with T-cell depletion. cases
Programme on AIDS. Unexplained CD4 T-lymphocyte depletion in persons without evidence of HIV infection. Weekly Epidemiol Rec 1992; 69: 237-40. 2. US Centers for Disease Control. Unexplained CD4 + T-lymphocyte depletion m persons without evident HIV infection-United States. MMWR 1992; 41: 541-45. 3. US Centers for Disease Control. Update: CD4+ T-lymphocytopenia in persons without evident HIV infection—United States. MMWR 1992; 41: 578-79. 1. Global
Undue optimism
over
human
myoblast transfer
A neurophysiologist’s claims of the benefit of myoblast transfer to patients with Duchenne’s muscular dystrophy were seriously questioned by his peers at the First International Congress of the Cell Transplant Society 6 weeks ago. The controversy over his work has extended beyond the conference; the institute at which he works is being investigated by the Food and Drug Administration.! Dr Peter Law’s work was one of four phase I human myoblast transfer studies set up in 1990. At the meeting Law said that 5 of the 11boys in his study in Memphis showed patches of dystrophinpositive fibres and some structural improvement in treated muscle 3 months after injection (see Lancet 1990; 336: 114 for his first patient), and 3 showed an increase in muscle strength. Prof George Karparti, from Montreal, reported a few dystrophin-positive muscle fibres in 2 of 8 boys 3 months after transfer, but there was no difference between treated and control muscle after 2 years. Dr Jacques Tremblay of Quebec had injected myoblasts crossmatched with host muscle so, unlike the other 3 studies, no cyclosporin was given. 7 of 9 boys showed dystrophin in treated muscle a month later. Increase in absolute muscle strength was unimpressive (and not permanent), or absent. Furthermore, despite cross-matching, antibodies to the newly formed muscle fibres developed. Work by Dr Helen Blau and Dr Robert Miller in San Francisco confirmed by polymerase chain reaction that the small number of dystrophin-positive cells found at site of injection contained donor dystrophin. They also reported that cyclosporin alone, without myoblast transfer, increased muscle strength. In his phase II uncontrolled studies Law has treated 21 boys aged 6-14 years and he claims that the 13 in whom the effect on muscle strength has been assessed have shown a 43% increase in power.2 Data from only 3 of the responders in the phase I study have been published, and only 2 of these had been treated double blind. His work was also said to be flawed because it did not identify the origin
of dystrophin; it did not take into account the factors that can confound assessment of muscle strength (eg, natural history of disease, growth of child, psychological effects, cyclosporin); it lacked controls (in the phase II study); and it has used percentage rather than absolute change in assessment of effect on strength. There are also concerns about forging ahead without adequate assessment of long-term safety. Tremblay has found that 3 of the 1000 clones of cultured human myoblasts tested were positive on an in-vitro tumorigenicity test.3 In addition he warns of the possibility that should rejection of transplanted muscle cell occur when immunosuppressive drugs are withdrawn after 6 months (as is done in Law’s phase II study), host muscle could also be lost because of fusion between host and donor muscle cells. Law now works at Cell Therapy Foundation, which he set up after leaving the University of Tennessee at Memphis. Two of the allegations in the preliminary report obtained by Sciencel are that there is data selection and that experiments are being conducted on more subjects than Law’s review board gave permission for. 1. Thompson L. Cell transplant results under fire. Science 1992; 257: 472-74 2. Law PK, Goodwin TG, Fang Q, et al. Feasibility, safety, and efficacy of
transfer therapy on Duchenne muscular dystrophy boys. Cell
myoblast Transplant 1992, 1:
235-44.
3
Tremblay JP, Roy B, Goulet M. Human myoblast transplantation: a simple assay for tumorigenicity. Neuromusc Disorders 1991; 1: 341-43.
Consulting about children with
HIV
The recent VIIIth International Conference on AIDS in Amsterdam raised disquieting issues about the difficulties faced by HIV-infected children and those who care for them. For instance, an Italian studyl showed that of a cohort of perinatally infected children, 23 % were now attending primary school-the researchers concluded that urgent guidelines were needed for those responsible for the psychological support, welfare provision, and schooling of these children. The UK Department of Health has now issued guidance to Local Authority Social Service departments about the services for children who are both infected and affected by HIV.2 The draft document has been written within the existing framework set out by the Children Act 19893 and the Community Care Act 1990. The report highlights four key issues. Because of the risk of stigma associated with HIV infection, a breach in confidentiality may have especially distressing consequences to the child and family. Disclosure of HIV status must be made only with the full informed consent of the child and/or the child’s parents. A family-centred approach is essential since children are often the first members of a family to be diagnosed with HIV infection. Coordination and liaison with other agencies is necessary to provide consistent and seamless care and, finally, the staff providing such care must also be given support and training in what can be an exceptionally stressful working environment. Consultation will take two months, after which formal guidelines will be drawn up and published by the Department of Health. M, Tovo PA, Galli L, Gabiano C. HIV-1 perinatally infected children approaching adolescent age. VIII International Conference on AIDS, Amsterdam,
1. De Martino
1992. POC 4683.
Department of Health. Consultation document Children and HIV: guidance for local authorities. 1992. Copies available from the AIDS Unit, Room 221, Friars House, 157-168 Blackfriars Road, London SE1 8EU, UK 3. Noticeboard A child in time. Lancet 1991; 338: 1007-08. 2.
Ashworth and the doctors Media coverage of the results of the Ashworth Hospital inquiry have focused mainly on the committee’s accusations both that some nurses had behaved in brutal, racist, harrassing, and negligent ways towards patients, and that the Prison Officers Association wielded an inappropriate amount of power in the hospital.1 But what about the clinicians? The report reminds us that since nursing staff spend more time with patients than do the other professions it is unsurprising that there were relatively more examples of cruel and thoughtless behaviour attributed to nurses. In the words of the report, "The evidence suggested that many medical staff ascribed little value to patients lives". The committee were able to hear evidence on specific patient issues from only a handful of the
Noticeboard AIDS without HIV? The first international meeting to examine details of sporadic of unexplained severe immunosuppression in adults without serological or virological evidence of human immunodeficiency virus, the association that attracted much attention at the VIII International Conference on AIDS last month (see Lancet Aug 1, pp 273 and 280), will be held at the World Health Organisation headquarters in Geneva on Sept 28-30.1 It will examine the information to be obtained in an urgent retrospective survey of such cases now being conducted by WHO in selected countries in Africa, Latin America, Asia, and Europe, and by the US Centers for Disease Control in North America. Recommendations for further research and public health guidelines will be formulated at the conference. Meanwhile, the CDC, together with the US National Institutes of Health, has held a meeting of investigators and public-health officials on August 14 to review findings. As of August 5 the CDC had received reports of 14 cases other than the 21 described in published reports." There is no indication of an epidemiological linkage between the cases, nor is it known whether they represent a single syndrome. One suggestion is that the CD4 depletion is a response to some infection and the deficiency is being recognised now because of the increased availability of T-cell phenotyping. The CDC is requesting health-care providers to report patients who have CD4 cell counts below 300 cells/1 or less than 20% on more than one determination, no serological evidence of HIV infection, and no defmed immunodeficiency or therapy associated with T-cell depletion. cases
Programme on AIDS. Unexplained CD4 T-lymphocyte depletion in persons without evidence of HIV infection. Weekly Epidemiol Rec 1992; 69: 237-40. 2. US Centers for Disease Control. Unexplained CD4 + T-lymphocyte depletion m persons without evident HIV infection-United States. MMWR 1992; 41: 541-45. 3. US Centers for Disease Control. Update: CD4+ T-lymphocytopenia in persons without evident HIV infection—United States. MMWR 1992; 41: 578-79. 1. Global
Undue optimism
over
human
myoblast transfer
A neurophysiologist’s claims of the benefit of myoblast transfer to patients with Duchenne’s muscular dystrophy were seriously questioned by his peers at the First International Congress of the Cell Transplant Society 6 weeks ago. The controversy over his work has extended beyond the conference; the institute at which he works is being investigated by the Food and Drug Administration.! Dr Peter Law’s work was one of four phase I human myoblast transfer studies set up in 1990. At the meeting Law said that 5 of the 11boys in his study in Memphis showed patches of dystrophinpositive fibres and some structural improvement in treated muscle 3 months after injection (see Lancet 1990; 336: 114 for his first patient), and 3 showed an increase in muscle strength. Prof George Karparti, from Montreal, reported a few dystrophin-positive muscle fibres in 2 of 8 boys 3 months after transfer, but there was no difference between treated and control muscle after 2 years. Dr Jacques Tremblay of Quebec had injected myoblasts crossmatched with host muscle so, unlike the other 3 studies, no cyclosporin was given. 7 of 9 boys showed dystrophin in treated muscle a month later. Increase in absolute muscle strength was unimpressive (and not permanent), or absent. Furthermore, despite cross-matching, antibodies to the newly formed muscle fibres developed. Work by Dr Helen Blau and Dr Robert Miller in San Francisco confirmed by polymerase chain reaction that the small number of dystrophin-positive cells found at site of injection contained donor dystrophin. They also reported that cyclosporin alone, without myoblast transfer, increased muscle strength. In his phase II uncontrolled studies Law has treated 21 boys aged 6-14 years and he claims that the 13 in whom the effect on muscle strength has been assessed have shown a 43% increase in power.2 Data from only 3 of the responders in the phase I study have been published, and only 2 of these had been treated double blind. His work was also said to be flawed because it did not identify the origin
of dystrophin; it did not take into account the factors that can confound assessment of muscle strength (eg, natural history of disease, growth of child, psychological effects, cyclosporin); it lacked controls (in the phase II study); and it has used percentage rather than absolute change in assessment of effect on strength. There are also concerns about forging ahead without adequate assessment of long-term safety. Tremblay has found that 3 of the 1000 clones of cultured human myoblasts tested were positive on an in-vitro tumorigenicity test.3 In addition he warns of the possibility that should rejection of transplanted muscle cell occur when immunosuppressive drugs are withdrawn after 6 months (as is done in Law’s phase II study), host muscle could also be lost because of fusion between host and donor muscle cells. Law now works at Cell Therapy Foundation, which he set up after leaving the University of Tennessee at Memphis. Two of the allegations in the preliminary report obtained by Sciencel are that there is data selection and that experiments are being conducted on more subjects than Law’s review board gave permission for. 1. Thompson L. Cell transplant results under fire. Science 1992; 257: 472-74 2. Law PK, Goodwin TG, Fang Q, et al. Feasibility, safety, and efficacy of
transfer therapy on Duchenne muscular dystrophy boys. Cell
myoblast Transplant 1992, 1:
235-44.
3
Tremblay JP, Roy B, Goulet M. Human myoblast transplantation: a simple assay for tumorigenicity. Neuromusc Disorders 1991; 1: 341-43.
Consulting about children with
HIV
The recent VIIIth International Conference on AIDS in Amsterdam raised disquieting issues about the difficulties faced by HIV-infected children and those who care for them. For instance, an Italian studyl showed that of a cohort of perinatally infected children, 23 % were now attending primary school-the researchers concluded that urgent guidelines were needed for those responsible for the psychological support, welfare provision, and schooling of these children. The UK Department of Health has now issued guidance to Local Authority Social Service departments about the services for children who are both infected and affected by HIV.2 The draft document has been written within the existing framework set out by the Children Act 19893 and the Community Care Act 1990. The report highlights four key issues. Because of the risk of stigma associated with HIV infection, a breach in confidentiality may have especially distressing consequences to the child and family. Disclosure of HIV status must be made only with the full informed consent of the child and/or the child’s parents. A family-centred approach is essential since children are often the first members of a family to be diagnosed with HIV infection. Coordination and liaison with other agencies is necessary to provide consistent and seamless care and, finally, the staff providing such care must also be given support and training in what can be an exceptionally stressful working environment. Consultation will take two months, after which formal guidelines will be drawn up and published by the Department of Health. M, Tovo PA, Galli L, Gabiano C. HIV-1 perinatally infected children approaching adolescent age. VIII International Conference on AIDS, Amsterdam,
1. De Martino
1992. POC 4683.
Department of Health. Consultation document Children and HIV: guidance for local authorities. 1992. Copies available from the AIDS Unit, Room 221, Friars House, 157-168 Blackfriars Road, London SE1 8EU, UK 3. Noticeboard A child in time. Lancet 1991; 338: 1007-08. 2.
Ashworth and the doctors Media coverage of the results of the Ashworth Hospital inquiry have focused mainly on the committee’s accusations both that some nurses had behaved in brutal, racist, harrassing, and negligent ways towards patients, and that the Prison Officers Association wielded an inappropriate amount of power in the hospital.1 But what about the clinicians? The report reminds us that since nursing staff spend more time with patients than do the other professions it is unsurprising that there were relatively more examples of cruel and thoughtless behaviour attributed to nurses. In the words of the report, "The evidence suggested that many medical staff ascribed little value to patients lives". The committee were able to hear evidence on specific patient issues from only a handful of the
