557

***’I’his letter has been shown to Professor Griffiths, whose replyfollows.-ED. L.

SIR,- The multicentre trial to which Dr Green refers was adouble-blind comparison of acyclovir and placebo. The trial

therapy was given in addition to antiretroviral drugs prescribedopenly by each patient’s physician. Since most patients receivedthese drugs, it is essential to consider the combined effect of bothdrug treatments.1 .Green also raises the important issue of when information from

clinical trials should be made public. This has been done at severaldifferent stages for controlled trials of drugs in HIV-positivepatients. Each of these approaches has advantages and

disadvantages, and publicity has led to criticism from interestedparties. The discussion of results only after formal publication hasthe advantage of ensuring peer review but introduces a delay ofmany months. In the rapidly changing AIDS treatment scene, thisdelay 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 cofactoreffect can only be discerned if the data are examined to exclude thepossibility that the virus in question is acting opportunistically tocause disease in its own right.2 By analogy, the benefit of a treatmentcould only be attributed to inhibition of a cofactor effect if the drugdid not reduce opportunistic disease caused by the same virus. Thiswas the precise circumstance in which the acyclovir trial was

stopped, and I briefed a medical correspondent about the notion ofcofactor viruses. What I did not anticipate was that minor points inthe briefing, such as the potential ultimate benefits of combinationchemotherapy, would become major items of discussion, ratherthan the cofactor concept. The prominence given by journalists toan article depends on many factors other than its intrinsic merit. Iwas embarrassed by the publicity my briefing received and regretthe anxiety that some people with HIV infection and their doctorsmay have had. It is inevitable that more trials in patients with HIVinfection will be stopped, and an agreed protocol would be of benefitto 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 theAIDS Clinical Trials Group. Mortality in patients with the acquiredimmunodeficiency syndrome treated with either foscarnet or ganciclovir forcytomegalovirus retinitis. N Engl J Med 1992; 326: 213-20.

2. Webster A, Lee CA, Cook DG, et al. Cytomegalovirus infection and progressiontowards AIDS m haemophiliacs with human immunodeficiency virus infection.Lancet 1989; ii: 63-66.

Human rights in SudanSIR,-The fundamentalist, military government of Sudan is

notorious for its abuse of human rights. Its severe laws,discriminations, and punishments have been condemned by humanrights organisations world wide.Among its victims are a large number of doctors, who have been

detained without trial and tortured (often in secret houses). Onedoctor died in April, 1991, after torture in prison. Another wassentenced to death, but finally released in response to internationalprotest. Most, but by no means all, are no longer in prison. Mosthave 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 theUniversity of Khartoum, and a member of our College. We havebeen attempting to gain his release, with a view to his coming to theUK 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 ofDr Siraj, to the President of Sudan, Lieutenant-General al-Bashir,People’s Palace, PO Box 281, Khartoum, and to their localSudanese embassies.

Royal College of Psychiatrists,17 Belgrave Square,London SW1X 8PG, UK

A. C. P. SIMS

J. L. T. BIRLEYTHOMAS BEWLEY

Acute pressure area care

SIR,-Dr Bliss’ report (Jan 25, p 221) is a timely reminder thatpressure sores remain a serious problem. Nevertheless, there is stilla scarcity of information on the incidence of these sores shortly afteradmission to hospital.

Bliss’ figures for the frequency of sores in patients with fracture ofthe femoral neck seem alarmingly high ("over 60%"), andexpecially so when a similar survey in Nottingham’ showed a rate of42 3% in these patients. However, the definition of sores differed inthese two surveys, and from one of the reports indirectly referred toby Bliss (Versluysen M, unpublished) the surveys can be equatedby removing those patients who only have persistent discolourationof a pressure area (a potential sore) .2 When this is done Versluysen’sfigures fall to 43%, which is very close to that recorded byHawthorn and Nyquist’ who did not count potential 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 elderlypatients 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 minimalresidual Ph1 clone with IFN&agr; in CML

SIR,-Interferon-&agr; (IFNx) induces haematological remission inmost patients with chronic myelogenous leukaemia (CML).1-3 In afew patients, Ph1 chromosome disappearance has also been

accompanied by the loss of an aberrant restriction fragment of theBCR gene after IFN therapy. 3-5 So far suppression of the Ph cloneconfirmed by the polymerase chain reaction (PCR) to detect bcrlablhybrid transcripts has been reported in only one patient;6 thefollow-up sample was, however, PCR positive. We reportcontinuous suppression of bcrlabl hybrid transcripts and the timenecessary 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 revealedgranulocytic hyperplasia and the typical translocation

t(9;22)(q34;qll) in all metaphases (40/40 cells) carrying a bcr/ablrearrangement. We gave natural IFNot (’Sumiferon’, SumitomoPharmaceuticals, Japan) at a dose of 6 x 106 U daily subcutaneouslyfor CML. After 5 months of treatment the patient had achievedhaematological remission and complete suppression of the Ph1clone. Treatment was continued. In February, 1990, splenectomywas done and hydroxyurea (500 mg daily) was given in addition toIFNA thereafter. In all subsequent bone-marrow samples at

months 5,14,19,28,41 and 43 and in spleen (at month 23), neitherPh1 chromosome nor bcrlabl rearrangement were detected. With aPCR procedure7 the result was positive in bone-marrow at month19 and in spleen, but negative results were obtained at months 41and 43.

Although PCR-negative results may be attributable to down-regulation of gene expression, our observation suggests that

complete molecular elimination of the Ph’ clone takes more than 23months, after reaching the limits of the sensitivity of Southern blotanalysis. This might be important for the curative treatment ofCML with IFNfx.

Departments of Haematologyand Internal Medicine,

Research Institute for Nuclear Medicineand Biology,

Hiroshima University,Hiroshima 734, Japan

NOBUO OGUMACHIHARU SHIGETAKATSUHIKO TAKAUCHIKIMIO TANAKANANAO KAMADAHIRONORI KAWANOATSUKI KURAMOTO

1. Talpaz M, Kantarijian HM, McCredie KB, Keating MJ, Trujillo J, Gutterman JU.Clinical investigations of human alpha interferon in chronic myelogenousleukemia. Blood 1987; 69: 1280-88.

2. Koyama S, Moriyama Y, Shibata A, et al. Clinical investigation of natural interferonalpha (HLBI) in chronic myelogenous leukemia: a multi-institutional cooperativestudy in Japan. Jpn J Cancer Chemother 1988; 15: 2959-66.

3. Talpaz M, Kantarijian H, Kurzrock R, Trujillo JM, Gutterman JU. Interferon-alphaproduce sustained cytogenetic response in chronic myelogenous leukemia. AnnIntern Med 1991; 114: 532-38.