758
Jakob’s disease and kuru, in which the pathological changes are restricted to neuronal masses and white matter is not involved, no abnormalities of CSF are noted. In progressive multifocal yet another disease of this type, the is clearly not immune-mediated but results from the destruction of oligodendrocytes by the virus. There again, no changes are found in the CSF. Thus, there seems to be strong evidence that in AIDS
leucoencephalopathy, destruction of white
matter
encephalomyelitis (as well as in other persistent viral infections) in addition to the actual invasion by the virus there is a contemporaneous immune-mediated response that is responsible for most, perhaps all, of the disseminated, extensive demyelination noted in these conditions in both the central and the peripheral nervous systems. Many patients with post-infectious or post-vaccinal encephalomyelitis respond dramatically to corticosteroids or ACTH, whereas in others plasmapheresis with or without corticosteroid therapy is also indicated. It is clear, however, that such therapy is directed against the oedema and inflammation, and has as its additional goal the stabilisation of the blood-brain barrier and restoration of its impermeability. Loss of myelin will not respond to such therapy and therefore the response to treatment is
highly unpredictable. Despite the reservations about use of corticosteroids in patients at great risk of acquiring or already harbouring opportunistic infections, the potential therapeutic benefits should be weighed against the possible harmful effects. Several workers have reported limited success and/or the absence of harmful side-effects of corticosteroids for peripheral neuropathy in AIDS.5,6 Plasmapheresis has also been used. Furthermore this form of therapy has also been used safely in AIDS patients with toxoplasma thrombotic encephalitis7 thrombocytopenic purpura,8 disseminated tuberculosis,9 and pneumocystis pneumonia.10 It is curious that there are no reported instances of the use of such therapy in AIDS encephalomyelitis. In such cases with neuropathy in which secondary infections can reasonably be excluded by appropriate examinations, and in patients whose infection is being treated by suitable drugs, consideration should be given to corticosteroid or ACTH therapy. Department of Neurology, Harvard Medical School and Neurological Unit, Beth Israel Hospital, Boston, Mass 02215, USA
CHARLES M. POSER
1. Pumarola-Sune T, Navia B, Cordo-Cardo C, et al. HIV antigen in the brains of patients with AIDS dementia complex Ann Neurol 1987; 21: 490-96. 2. Poser C. AIDS encephalomyelitis. Lancet 1987; ii: 1886-87. 3. Poser C. Notes on the pathogenesis of subacute sclerosing panencephalitis. J Neurol Sci 1990; 95: 219-24. 4. Oger J, Kastrukoff L, Li D, et al. Multiple sclerosis: in relapsing patients, immune functions vary with disease activity as assessed by MRI Neurology 1988; 38: 1739-44. 5. Lipkin W, Parry G, Kiprov D, et al. Inflammatory neuropathy in homosexual men with lymphadenopathy. Neurology 1985; 35: 1479-83. 6. Comblith D, McArthur J, Kennedy P, et al. Inflammatory demyelinating peripheral neuropathies associated with human T-cell lymphotropic virus type III infection. Ann Neurol 1987; 21: 32-40. 7. Haverkos H. Assessment of therapy for toxoplasma encephalitis: the TE Study Group.
disease,",on the contrary, on page 1 we cite standard publications of progression from infection to development of AIDS and on page 22 we state that "even the most optimistic statistics [show] that 85% of those who fall ill die within five years of diagnosis". The thesis of the study is that negative reactions, by individuals, institutions, and governments, to HIV disease are in themselves a factor in the spread of the epidemic. Many examples to support this are provided from around the world. Of particular interest are chapters on the use of blood tests to detect the presence of HIV and on the implications for doctors, nurses, and others working in health care of increasing caseloads of potentially HIV-positive patients. MARTIN
The Panos Institute, 9 White Lion Street, London N1 9PD, UK
FOREMAN,
Director, AIDS and
Development Information Unit
Reconstitution of peripheral benzodiazepine receptor expression in X-linked chronic granulomatous disease by interferon-&ggr; SiR,—We have reported,’ in patients with X-linked (X-CGD) but autosomal recessive chronic granulomatous disease,
not
significantly
altered
expression
of the
neutrophil peripheral type
benzodiazepine receptor (PBZDR). We identified this receptor as an 18 kD membrane protein and suggested that it is a component of the NADPH-oxidase complex that may be involved in host defence. Interferon-gamma (IFN-y) is clinically useful in CGD, restoring partly (and in some patients totally) the normal range of bactericidal activity.2,3 Whether this is due to enhancement of oxygen dependent and/or independent antimicrobial mechanisms is still a matter of debate. Increased expression of a cytochrome b558 gene product was reported in a few cases. Nevertheless, the absence of quantitative correlation between cytochrome b558 expression and the increment of phagocyte oxidative and/or microbicidal activity leads one to speculate that other IFN-y-induced gene products could be involved in IFN-y beneficial effects.z3 We decided to investigate whether PBZDR could be a target for IFN-y action in CGD. Because of the limited amount of blood available, PBZDR
phagocyte
expression was measured, on monocyte-derived macrophages, as the specific binding of the prototypical peripheral benzodiazepine ligand (tritiated Ro 5-4864), at a single concentration of 40 nmol/1, close to the dissociation constant. In vitro, IFN-y (100 U/ml, 72 h incubation) selectively restored altered PBZDR expression in monocyte-derived macrophages from the X-CGD patients whereas it remained inactive on PBZDR expression of monocytes from fourteen normal donors (figure). IFN-y did not influence PBZDR expression in monocytes from three patients with autosomal recessive CGD, who have normal cytochrome bS58 levels, whereas this was restored to a normal level in two patients with the type III variant of the autosomal recessive form who share with X-CGD the
cytochrome b558 deficiency (data not shown).
Am J Med 1987; 82: 907-14. Jokela J, Flynn T, Henry K. Thrombotic thrombocytopenic purpura in a human immunodeficiency virus (HIV)-seropositive homosexual man. Am J Hematol 1987; 25: 341-43. 9. Masud T, Kemp E. Corticosteroids in treatment of disseminated tuberculosis in patient with HIV infection. Br Med J 1988; 296: 464-65. 10. McFadden D, Edelson J, Hyland R, et al. Corticosteroids as adjunctive therapy in treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet 1987; i: 1477-79. 8.
International perspectives
on
HIV
SiR,—Iwelcome your mention of our latest publication, The Third Epidemic: Repercussions of the Fear of AIDS (Aug 4, p 304), but I regret that its contents have been misrepresented. The use of language in relation to HIV/AIDS to which you refer occupies less than 1 page of a 320-page volume. Furthermore, I can find no trace of "arguments presented against the central dogma of HIV ...
Effect of IFN-y treatment on PBZDR expression of monocytes from normal subjects and X-CGD patients.
Jakob’s disease and kuru, in which the pathological changes are restricted to neuronal masses and white matter is not involved, no abnormalities of CSF are noted. In progressive multifocal yet another disease of this type, the is clearly not immune-mediated but results from the destruction of oligodendrocytes by the virus. There again, no changes are found in the CSF. Thus, there seems to be strong evidence that in AIDS
leucoencephalopathy, destruction of white
matter
encephalomyelitis (as well as in other persistent viral infections) in addition to the actual invasion by the virus there is a contemporaneous immune-mediated response that is responsible for most, perhaps all, of the disseminated, extensive demyelination noted in these conditions in both the central and the peripheral nervous systems. Many patients with post-infectious or post-vaccinal encephalomyelitis respond dramatically to corticosteroids or ACTH, whereas in others plasmapheresis with or without corticosteroid therapy is also indicated. It is clear, however, that such therapy is directed against the oedema and inflammation, and has as its additional goal the stabilisation of the blood-brain barrier and restoration of its impermeability. Loss of myelin will not respond to such therapy and therefore the response to treatment is
highly unpredictable. Despite the reservations about use of corticosteroids in patients at great risk of acquiring or already harbouring opportunistic infections, the potential therapeutic benefits should be weighed against the possible harmful effects. Several workers have reported limited success and/or the absence of harmful side-effects of corticosteroids for peripheral neuropathy in AIDS.5,6 Plasmapheresis has also been used. Furthermore this form of therapy has also been used safely in AIDS patients with toxoplasma thrombotic encephalitis7 thrombocytopenic purpura,8 disseminated tuberculosis,9 and pneumocystis pneumonia.10 It is curious that there are no reported instances of the use of such therapy in AIDS encephalomyelitis. In such cases with neuropathy in which secondary infections can reasonably be excluded by appropriate examinations, and in patients whose infection is being treated by suitable drugs, consideration should be given to corticosteroid or ACTH therapy. Department of Neurology, Harvard Medical School and Neurological Unit, Beth Israel Hospital, Boston, Mass 02215, USA
CHARLES M. POSER
1. Pumarola-Sune T, Navia B, Cordo-Cardo C, et al. HIV antigen in the brains of patients with AIDS dementia complex Ann Neurol 1987; 21: 490-96. 2. Poser C. AIDS encephalomyelitis. Lancet 1987; ii: 1886-87. 3. Poser C. Notes on the pathogenesis of subacute sclerosing panencephalitis. J Neurol Sci 1990; 95: 219-24. 4. Oger J, Kastrukoff L, Li D, et al. Multiple sclerosis: in relapsing patients, immune functions vary with disease activity as assessed by MRI Neurology 1988; 38: 1739-44. 5. Lipkin W, Parry G, Kiprov D, et al. Inflammatory neuropathy in homosexual men with lymphadenopathy. Neurology 1985; 35: 1479-83. 6. Comblith D, McArthur J, Kennedy P, et al. Inflammatory demyelinating peripheral neuropathies associated with human T-cell lymphotropic virus type III infection. Ann Neurol 1987; 21: 32-40. 7. Haverkos H. Assessment of therapy for toxoplasma encephalitis: the TE Study Group.
disease,",on the contrary, on page 1 we cite standard publications of progression from infection to development of AIDS and on page 22 we state that "even the most optimistic statistics [show] that 85% of those who fall ill die within five years of diagnosis". The thesis of the study is that negative reactions, by individuals, institutions, and governments, to HIV disease are in themselves a factor in the spread of the epidemic. Many examples to support this are provided from around the world. Of particular interest are chapters on the use of blood tests to detect the presence of HIV and on the implications for doctors, nurses, and others working in health care of increasing caseloads of potentially HIV-positive patients. MARTIN
The Panos Institute, 9 White Lion Street, London N1 9PD, UK
FOREMAN,
Director, AIDS and
Development Information Unit
Reconstitution of peripheral benzodiazepine receptor expression in X-linked chronic granulomatous disease by interferon-&ggr; SiR,—We have reported,’ in patients with X-linked (X-CGD) but autosomal recessive chronic granulomatous disease,
not
significantly
altered
expression
of the
neutrophil peripheral type
benzodiazepine receptor (PBZDR). We identified this receptor as an 18 kD membrane protein and suggested that it is a component of the NADPH-oxidase complex that may be involved in host defence. Interferon-gamma (IFN-y) is clinically useful in CGD, restoring partly (and in some patients totally) the normal range of bactericidal activity.2,3 Whether this is due to enhancement of oxygen dependent and/or independent antimicrobial mechanisms is still a matter of debate. Increased expression of a cytochrome b558 gene product was reported in a few cases. Nevertheless, the absence of quantitative correlation between cytochrome b558 expression and the increment of phagocyte oxidative and/or microbicidal activity leads one to speculate that other IFN-y-induced gene products could be involved in IFN-y beneficial effects.z3 We decided to investigate whether PBZDR could be a target for IFN-y action in CGD. Because of the limited amount of blood available, PBZDR
phagocyte
expression was measured, on monocyte-derived macrophages, as the specific binding of the prototypical peripheral benzodiazepine ligand (tritiated Ro 5-4864), at a single concentration of 40 nmol/1, close to the dissociation constant. In vitro, IFN-y (100 U/ml, 72 h incubation) selectively restored altered PBZDR expression in monocyte-derived macrophages from the X-CGD patients whereas it remained inactive on PBZDR expression of monocytes from fourteen normal donors (figure). IFN-y did not influence PBZDR expression in monocytes from three patients with autosomal recessive CGD, who have normal cytochrome bS58 levels, whereas this was restored to a normal level in two patients with the type III variant of the autosomal recessive form who share with X-CGD the
cytochrome b558 deficiency (data not shown).
Am J Med 1987; 82: 907-14. Jokela J, Flynn T, Henry K. Thrombotic thrombocytopenic purpura in a human immunodeficiency virus (HIV)-seropositive homosexual man. Am J Hematol 1987; 25: 341-43. 9. Masud T, Kemp E. Corticosteroids in treatment of disseminated tuberculosis in patient with HIV infection. Br Med J 1988; 296: 464-65. 10. McFadden D, Edelson J, Hyland R, et al. Corticosteroids as adjunctive therapy in treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet 1987; i: 1477-79. 8.
International perspectives
on
HIV
SiR,—Iwelcome your mention of our latest publication, The Third Epidemic: Repercussions of the Fear of AIDS (Aug 4, p 304), but I regret that its contents have been misrepresented. The use of language in relation to HIV/AIDS to which you refer occupies less than 1 page of a 320-page volume. Furthermore, I can find no trace of "arguments presented against the central dogma of HIV ...
Effect of IFN-y treatment on PBZDR expression of monocytes from normal subjects and X-CGD patients.
