557
***’I’his letter has been shown to Professor Griffiths, whose reply follows.-ED. L. multicentre trial to which Dr Green refers was a double-blind comparison of acyclovir and placebo. The trial therapy was given in addition to antiretroviral drugs prescribed openly by each patient’s physician. Since most patients received these drugs, it is essential to consider the combined effect of both
SIR,- The
drug treatments.1 . Green also raises the important issue of when information from clinical trials should be made public. This has been done at several different stages for controlled trials of drugs in HIV-positive patients. Each of these approaches has advantages and disadvantages, and publicity has led to criticism from interested parties. The discussion of results only after formal publication has the advantage of ensuring peer review but introduces a delay of many months. In the rapidly changing AIDS treatment scene, this delay has led to accusations of excessive secrecy. A possible explanation for the acyclovir trial result is an effect of the drug on a viral cofactor that drives HIV replication. A cofactor effect can only be discerned if the data are examined to exclude the
possibility that the virus in question is acting opportunistically to cause disease in its own right.2 By analogy, the benefit of a treatment could only be attributed to inhibition of a cofactor effect if the drug did not reduce opportunistic disease caused by the same virus. This was the precise circumstance in which the acyclovir trial was stopped, and I briefed a medical correspondent about the notion of cofactor viruses. What I did not anticipate was that minor points in the briefing, such as the potential ultimate benefits of combination chemotherapy, would become major items of discussion, rather than the cofactor concept. The prominence given by journalists to an article depends on many factors other than its intrinsic merit. I was embarrassed by the publicity my briefing received and regret the anxiety that some people with HIV infection and their doctors may have had. It is inevitable that more trials in patients with HIV infection will be stopped, and an agreed protocol would be of benefit to all. Department of Virology, Royal Free Hospital School of Medicine, London NW3 2PF, UK
P. D. GRIFFITHS
1. Studies of ocular complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med 1992; 326: 213-20. 2. Webster A, Lee CA, Cook DG, et al. Cytomegalovirus infection and progression towards AIDS m haemophiliacs with human immunodeficiency virus infection. Lancet 1989; ii: 63-66.
Human
rights in Sudan
SIR,-The fundamentalist, military government of Sudan is notorious for its abuse of human rights. Its severe laws, discriminations, and punishments have been condemned by human rights organisations world wide. Among its victims are a large number of doctors, who have been detained without trial and tortured (often in secret houses). One doctor died in April, 1991, after torture in prison. Another was sentenced to death, but finally released in response to international protest. Most, but by no means all, are no longer in prison. Most have not been allowed to return to work and many have fled the country. One of those still in prison is Dr Ahmed Osman Siraj, president of the Sudanese Society of Psychiatrists, a senior lecturer in the University of Khartoum, and a member of our College. We have been attempting to gain his release, with a view to his coming to the UK for a period of personal and educational recuperation. So far, we have had no success. The regime has shown itself to be sensitive to world opinion. May we therefore call on Lancet readers world wide to write, on behalf of Dr Siraj, to the President of Sudan, Lieutenant-General al-Bashir, People’s Palace, PO Box 281, Khartoum, and to their local Sudanese embassies. Royal College of Psychiatrists, 17 Belgrave Square, London SW1X 8PG, UK
A. C. P. SIMS J. L. T. BIRLEY THOMAS BEWLEY
Acute pressure
area care
p 221) is a timely reminder that remain a serious problem. Nevertheless, there is still a scarcity of information on the incidence of these sores shortly after admission to hospital. Bliss’ figures for the frequency of sores in patients with fracture of the femoral neck seem alarmingly high ("over 60%"), and expecially so when a similar survey in Nottingham’ showed a rate of 42 3% in these patients. However, the definition of sores differed in these two surveys, and from one of the reports indirectly referred to by Bliss (Versluysen M, unpublished) the surveys can be equated by removing those patients who only have persistent discolouration of a pressure area (a potential sore) .2 When this is done Versluysen’s figures fall to 43%, which is very close to that recorded by Hawthorn and Nyquist’ who did not count potential sores.
SIR,-Dr Bliss’ report (Jan 25,
pressure
sores
Royal National Orthopaedic Hospital, Stanmore, Middlesex HA7 4LP, UK
PETER T. LOWTHIAN
1. Hawthorn
PJ, Nyquist R. The incidence of pressure sores amongst a group of elderly patients with fractured neck of femur. Care Sci Pract 1988; 6: 3-7. 2. Lowthian PT. The classification and grading of pressure sores. Care Sci Pract 1987; 5: 5-9.
Molecular elimination of the minimal residual Ph1 clone with IFN&agr; in CML SIR,-Interferon-&agr; (IFNx) induces haematological remission in patients with chronic myelogenous leukaemia (CML).1-3 In a
most
patients, Ph1 chromosome disappearance has also been accompanied by the loss of an aberrant restriction fragment of the BCR gene after IFN therapy. 3-5 So far suppression of the Ph clone confirmed by the polymerase chain reaction (PCR) to detect bcrlabl hybrid transcripts has been reported in only one patient;6 the follow-up sample was, however, PCR positive. We report continuous suppression of bcrlabl hybrid transcripts and the time necessary to eliminate the minimal residual Ph1 from serial analysis. A 55-year-old man presented in September, 1987, with leucocytosis of 10-2 x 109/1. Bone-marrow examination revealed granulocytic hyperplasia and the typical translocation t(9;22)(q34;qll) in all metaphases (40/40 cells) carrying a bcr/abl rearrangement. We gave natural IFNot (’Sumiferon’, Sumitomo Pharmaceuticals, Japan) at a dose of 6x 106 U daily subcutaneously for CML. After 5 months of treatment the patient had achieved haematological remission and complete suppression of the Ph1 clone. Treatment was continued. In February, 1990, splenectomy was done and hydroxyurea (500 mg daily) was given in addition to IFNA thereafter. In all subsequent bone-marrow samples at months 5,14,19,28,41 and 43 and in spleen (at month 23), neither few
Ph1 chromosome nor bcrlabl rearrangement were detected. With a PCR procedure7 the result was positive in bone-marrow at month 19 and in spleen, but negative results were obtained at months 41 and 43. Although PCR-negative results may be attributable to downregulation of gene expression, our observation suggests that complete molecular elimination of the Ph’ clone takes more than 23 months, after reaching the limits of the sensitivity of Southern blot analysis. This might be important for the curative treatment of CML with IFNfx.
Departments of Haematology and Internal Medicine, Research Institute for Nuclear Medicine and Biology, Hiroshima University, Hiroshima 734, Japan
NOBUO OGUMA CHIHARU SHIGETA KATSUHIKO TAKAUCHI KIMIO TANAKA NANAO KAMADA HIRONORI KAWANO ATSUKI KURAMOTO
Talpaz M, Kantarijian HM, McCredie KB, Keating MJ, Trujillo J, Gutterman JU. Clinical investigations of human alpha interferon in chronic myelogenous leukemia. Blood 1987; 69: 1280-88. 2. Koyama S, Moriyama Y, Shibata A, et al. Clinical investigation of natural interferon alpha (HLBI) in chronic myelogenous leukemia: a multi-institutional cooperative study in Japan. Jpn J Cancer Chemother 1988; 15: 2959-66. 3. Talpaz M, Kantarijian H, Kurzrock R, Trujillo JM, Gutterman JU. Interferon-alpha produce sustained cytogenetic response in chronic myelogenous leukemia. Ann 1.
Intern Med 1991; 114: 532-38.
***’I’his letter has been shown to Professor Griffiths, whose reply follows.-ED. L. multicentre trial to which Dr Green refers was a double-blind comparison of acyclovir and placebo. The trial therapy was given in addition to antiretroviral drugs prescribed openly by each patient’s physician. Since most patients received these drugs, it is essential to consider the combined effect of both
SIR,- The
drug treatments.1 . Green also raises the important issue of when information from clinical trials should be made public. This has been done at several different stages for controlled trials of drugs in HIV-positive patients. Each of these approaches has advantages and disadvantages, and publicity has led to criticism from interested parties. The discussion of results only after formal publication has the advantage of ensuring peer review but introduces a delay of many months. In the rapidly changing AIDS treatment scene, this delay has led to accusations of excessive secrecy. A possible explanation for the acyclovir trial result is an effect of the drug on a viral cofactor that drives HIV replication. A cofactor effect can only be discerned if the data are examined to exclude the
possibility that the virus in question is acting opportunistically to cause disease in its own right.2 By analogy, the benefit of a treatment could only be attributed to inhibition of a cofactor effect if the drug did not reduce opportunistic disease caused by the same virus. This was the precise circumstance in which the acyclovir trial was stopped, and I briefed a medical correspondent about the notion of cofactor viruses. What I did not anticipate was that minor points in the briefing, such as the potential ultimate benefits of combination chemotherapy, would become major items of discussion, rather than the cofactor concept. The prominence given by journalists to an article depends on many factors other than its intrinsic merit. I was embarrassed by the publicity my briefing received and regret the anxiety that some people with HIV infection and their doctors may have had. It is inevitable that more trials in patients with HIV infection will be stopped, and an agreed protocol would be of benefit to all. Department of Virology, Royal Free Hospital School of Medicine, London NW3 2PF, UK
P. D. GRIFFITHS
1. Studies of ocular complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med 1992; 326: 213-20. 2. Webster A, Lee CA, Cook DG, et al. Cytomegalovirus infection and progression towards AIDS m haemophiliacs with human immunodeficiency virus infection. Lancet 1989; ii: 63-66.
Human
rights in Sudan
SIR,-The fundamentalist, military government of Sudan is notorious for its abuse of human rights. Its severe laws, discriminations, and punishments have been condemned by human rights organisations world wide. Among its victims are a large number of doctors, who have been detained without trial and tortured (often in secret houses). One doctor died in April, 1991, after torture in prison. Another was sentenced to death, but finally released in response to international protest. Most, but by no means all, are no longer in prison. Most have not been allowed to return to work and many have fled the country. One of those still in prison is Dr Ahmed Osman Siraj, president of the Sudanese Society of Psychiatrists, a senior lecturer in the University of Khartoum, and a member of our College. We have been attempting to gain his release, with a view to his coming to the UK for a period of personal and educational recuperation. So far, we have had no success. The regime has shown itself to be sensitive to world opinion. May we therefore call on Lancet readers world wide to write, on behalf of Dr Siraj, to the President of Sudan, Lieutenant-General al-Bashir, People’s Palace, PO Box 281, Khartoum, and to their local Sudanese embassies. Royal College of Psychiatrists, 17 Belgrave Square, London SW1X 8PG, UK
A. C. P. SIMS J. L. T. BIRLEY THOMAS BEWLEY
Acute pressure
area care
p 221) is a timely reminder that remain a serious problem. Nevertheless, there is still a scarcity of information on the incidence of these sores shortly after admission to hospital. Bliss’ figures for the frequency of sores in patients with fracture of the femoral neck seem alarmingly high ("over 60%"), and expecially so when a similar survey in Nottingham’ showed a rate of 42 3% in these patients. However, the definition of sores differed in these two surveys, and from one of the reports indirectly referred to by Bliss (Versluysen M, unpublished) the surveys can be equated by removing those patients who only have persistent discolouration of a pressure area (a potential sore) .2 When this is done Versluysen’s figures fall to 43%, which is very close to that recorded by Hawthorn and Nyquist’ who did not count potential sores.
SIR,-Dr Bliss’ report (Jan 25,
pressure
sores
Royal National Orthopaedic Hospital, Stanmore, Middlesex HA7 4LP, UK
PETER T. LOWTHIAN
1. Hawthorn
PJ, Nyquist R. The incidence of pressure sores amongst a group of elderly patients with fractured neck of femur. Care Sci Pract 1988; 6: 3-7. 2. Lowthian PT. The classification and grading of pressure sores. Care Sci Pract 1987; 5: 5-9.
Molecular elimination of the minimal residual Ph1 clone with IFN&agr; in CML SIR,-Interferon-&agr; (IFNx) induces haematological remission in patients with chronic myelogenous leukaemia (CML).1-3 In a
most
patients, Ph1 chromosome disappearance has also been accompanied by the loss of an aberrant restriction fragment of the BCR gene after IFN therapy. 3-5 So far suppression of the Ph clone confirmed by the polymerase chain reaction (PCR) to detect bcrlabl hybrid transcripts has been reported in only one patient;6 the follow-up sample was, however, PCR positive. We report continuous suppression of bcrlabl hybrid transcripts and the time necessary to eliminate the minimal residual Ph1 from serial analysis. A 55-year-old man presented in September, 1987, with leucocytosis of 10-2 x 109/1. Bone-marrow examination revealed granulocytic hyperplasia and the typical translocation t(9;22)(q34;qll) in all metaphases (40/40 cells) carrying a bcr/abl rearrangement. We gave natural IFNot (’Sumiferon’, Sumitomo Pharmaceuticals, Japan) at a dose of 6x 106 U daily subcutaneously for CML. After 5 months of treatment the patient had achieved haematological remission and complete suppression of the Ph1 clone. Treatment was continued. In February, 1990, splenectomy was done and hydroxyurea (500 mg daily) was given in addition to IFNA thereafter. In all subsequent bone-marrow samples at months 5,14,19,28,41 and 43 and in spleen (at month 23), neither few
Ph1 chromosome nor bcrlabl rearrangement were detected. With a PCR procedure7 the result was positive in bone-marrow at month 19 and in spleen, but negative results were obtained at months 41 and 43. Although PCR-negative results may be attributable to downregulation of gene expression, our observation suggests that complete molecular elimination of the Ph’ clone takes more than 23 months, after reaching the limits of the sensitivity of Southern blot analysis. This might be important for the curative treatment of CML with IFNfx.
Departments of Haematology and Internal Medicine, Research Institute for Nuclear Medicine and Biology, Hiroshima University, Hiroshima 734, Japan
NOBUO OGUMA CHIHARU SHIGETA KATSUHIKO TAKAUCHI KIMIO TANAKA NANAO KAMADA HIRONORI KAWANO ATSUKI KURAMOTO
Talpaz M, Kantarijian HM, McCredie KB, Keating MJ, Trujillo J, Gutterman JU. Clinical investigations of human alpha interferon in chronic myelogenous leukemia. Blood 1987; 69: 1280-88. 2. Koyama S, Moriyama Y, Shibata A, et al. Clinical investigation of natural interferon alpha (HLBI) in chronic myelogenous leukemia: a multi-institutional cooperative study in Japan. Jpn J Cancer Chemother 1988; 15: 2959-66. 3. Talpaz M, Kantarijian H, Kurzrock R, Trujillo JM, Gutterman JU. Interferon-alpha produce sustained cytogenetic response in chronic myelogenous leukemia. Ann 1.
Intern Med 1991; 114: 532-38.
