Prevention of iatrogenic transmission of Creutzfeldt-Jakob disease

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patients will result in lack of the urea cycle or arginine, and lead to hyperammonaemia.

Prevention of iatrogenic transmission of Creutzfeldt-Jakob disease

short-bowel

intermediates, ornithine, citrulline

ETSUKO YAMADA YASUO WAKABAYASHI AKIKO SAITO KENGO YODA YOSHIFUMI TANAKA MASAO MIYAZAKI

Department of Anaesthesia, Kyoto 1st Red Cross Hospital, and Departments of Biochemistry and Anaesthesia, Kyoto Prefectural University of Medicine and Maizura National Hospital,

Kyoto 605, Japan

1. Motil KJ, Harmon WE, Grupe WE. Complications of essential amino add hyperalimentation in children with acute renal failure. J Parenter Enter Nutr 1980; 4: 32-35. 2. Grazer RE, Sutton JM, Friedstrom S, McBarron FD. Hyperammonemic encephalopathy due to essential amino acid hyperalimentation. Arch Intern Med 1984; 144: 2278-79. 3. Nakasaki H, Katayama T, Yokoyama S, et al. Complication of parenteral nutrition composed of essential amino acid and histidine in adults with renal failure. J Parenter Enter Nutr 1993; 17: 86-90. 4. Windmueller HG, Spaeth AE. Source and fate of circulating citrulline. Am J Physiol 1981; 241: 473-80. 5. Wakabayashi Y, Yamada E, Hasegawa T, Yamada R. Enzymological evidence for the indispensability of small intestine in the synthesis of arginine from glutamate I: pyrroline-5-carboxylate synthase. Arch Biochem Biophys 1991; 291: 1-8. 6. Wakabayashi Y, Yamada E. Arginine changes to be an essential amino add in the rat with massive resection of the intestine. Parenter Enter Nutr 1992; 16: 25. J

Dual-chamber pacing in patients with end-stage ischaemic cardiomyopathy SIR,-Long-lasting benefit has been achieved in patients with idiopathic dilated cardiomyopathy by permanent dual-chamber pacing with an atrioventricular delay of 100 ms.1 Although the mechanism is uncertain, we suggest that the efficacy of dualchamber pacing may be independent of the type of cardiomyopathy. The most common cause of dilated cardiomyopathy in Europe and North America is multiple infarctions due to coronary artery disease. We report successful with dual-chamber pacing of end-stage dilated cardiomyopathy due to coronary artery disease. treatment

EFFECT OF DUAL-CHAMBER PACING (EJECTION FRACTION I

I

I

-

%)

I

p 1098) is correct to state that evidence that properly processed instruments1 transmit Creutzfeidt-Jakob disease (CJD) or Gerstmann-StrausslerScheinker syndrome (GSS). However, the Advisory Group on the Management of Patients with Spongiform Encephalopathy (CJD) recommended in 19812 that neurosurgical and ophthalmic instruments should be disposed of if they have been used in patients with CJD. The relevant paragraph states: "Where the surgical procedure involves the brain (e.g. cortical biopsy), spinal cord or eye, the following additional precautions should be taken: (i) the least possible number of persons should take part in the operation; (ii) A one-way flow of instruments should be maintained; (iii) when it is necessary to use instruments not normally regarded as disposable these instuments should under no circumstances be re-used and should be destroyed. These precautions should also be observed when neurosurgical procedures are carried out on patients in whom the possibility of CJD enters into the differential diagnosis". In view of recent knowledge on the transmissibility of CJD under certain circumstances-for example, via human pituitary growth hormone (hGH)-it was felt advisable to extend this advice to those, like hGH recipients, who could be at risk of developing disease, because the factors influencing development of clinical disease and the infectivity of tissues such as brain during the incubation period are unknown. The aim of the recent advice is to prevent the possible iatrogenic spread of an incompletely understood fatal disease. The advice refers to specified patient groups only, and was issued after considerable consultation both within and outside the Department of Health. The advice in the letter dated December 7, 1992 referred to by Professor Ayliffe does not alter that issued in 19841 on decontamination of other instruments at 134-38°C for 18 min in patients known to have CJD, and this autoclaving cycle should be used for instruments not used on the brain, spinal cord, or eye wherever there is suspicion of CJD. The preliminary data on scrapie agent inactivation referred to by Dr Taylor and Dr Bell (see this page) need further validation and the Department is keeping the need for any revision of current recommendations on hospital autoclave practice under constant review.

SIR,-Professor Ayliffe (April 24,

there is

no

Department of Health, Skipton House, Elephant and Castle, London

Dual-chamber pacemakers were implanted in 3 patients

48; males 64, and 68) with chronic heart failure due

(female

to

coronary artery disease. The atrioventricular delay was set at 100 ms. The diagnosis of coronary artery disease was based on a history of myocardial infarction and typical angina pectoris, and was verified by coronary angiography. Surgical intervention was not possible. The patients had been on conventional drug treatment for years, yet still developed a progressive dilation of the heart. Before, and within 1 week after pacemaker implantation, clinical examination and radionuclide scintigraphy were done. Further examinations followed 6 and 12 months later (table). After pacemaker implantation, the patients were discharged from hospital within 2 weeks and were able to resume a relatively normal life. The frequency of anginal attacks and the use of glyceryl trinitrate were

reduced. These results show the potential of dual-chamber pacing support for patients with end-stage heart failure due to coronary artery disease and suggest that this approach might be of advantage in heart failure due to other causes. Departments of Internal Medicine, Sports and Cardiovascular Medicine, and First Department of Surgery,

University of Innsbruck, 6020 Innsbruck, Austria

MARGARETE HOCHLEITNER HELMUT HÖRTNAGL FRANZ GSCHNITZER

Hörtnagl H, Fridrich L, Gschnitzer F. Long-term efficacy of physiological dual-chamber pacing in the treatment of end-stage idiopathic dilated cardiomyopathy. Am J Cardiol 1992; 70: 1320-25. 2. Johnson RA, Palacios I. Dilated cardiomyopathies of the adult N Engl J Med 1982; 1. Hochleitner M,

307: 1051-56.

SE1 6LW, UK

A. L. WIGHT

Department of Health and Social Security. Management of patients with spongiform encephalopathy (Creutzfeldt-Jakob disease [CJD]). London DHSS, 1984: DA(84)16. 2. Advisory group on the management of patients with spongiform encephalopathy (Creutzfeldt-Jakob disease [CJD]). Report to the chief medical officers of the Department of Health and Social Security, the Scottish Home and Health Department, and the Welsh Office. London: HM Stationery Office, 1981: 1.

DA(81)22.

SIR,-Professor Ayliffe questions the validity of a recent Department of Health recommendation about patients who have, or are at risk of developing CJD or GSS. By including three further groups of patients now known to be at risk of developing these diseases, the recommendation updated previous guidance that surgical instruments not usually regarded as disposable should be destroyed if they have been used in neurosurgery or ophthalmic surgery in such patients.1 Ayliffe suggests that the expense incurred in instrument destruction is unacceptable and points out that thorough cleaning should reduce the amounts of infectivity instruments. However, these remaining on contaminated unconventional transmissible agents are resistant to conventional decontamination methods, survive for long periods in the general environmentand the process of cleaning might lead to crosscontamination. Quite properly, Ayliffe also refers to the recommended procedure for inactivation of CJD agent by porous-load autoclaving at 134-38°C for 18 min3 to achieve terminal sterilisation. This standard was based on data from experiments on scrapie agent4 which is accepted as an appropriate model. As Ayliffe indicates, there is no evidence that surgical instruments sterilised in this way

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have transmitted infection. However, more recent (incomplete and unpublished) data suggest that 134°C may not be completely effective against all strains of scrapie agent, at least under experimental conditions.s Until further work has been done, the Department of Health advice relating to disposal of selected instruments is sensible. AFRC and MRC Neuropathogenesis Unit, Institute for Animal Health, Edinburgh EH9 3JF, UK

Neuropathology Laboratory, University of Edinburgh, Western General Hospital, Edinburgh

This high false-negative rate for regular trisomy 21 suggests that FISH is not yet a real alternative to cytogenetics for aneuploidies. Cytogenetics is required, not only to detect the structural abnormalities, but also the missed aneuploidies. Departments of Medical Genetics and Obstetrics,

Hospital de Mar,

D. M. TAYLOR

Barcelona 08036,

Spain

A. SERES-SANTAMARIA V. CATALA E. CUATRECASAS R. VILLANUEVA

Gray JW. Cytogenetic analysis using quantitative, highsensitivity fluorescence hybridization. Proc Natl Acad Sci USA 1986; 83: 2934-38. 2. Verma R, Luke S. Variations in alphoid DNA sequence escape detection of aneuploidy at interphase by FISH technique. Genomics 1992; 14: 113-16. 1. Pinkel D, Straume T,

J. E. BELL

Security. Advisory group on the management of patients with spongiform encephalopathy (Creutzfeldt-Jakob disease [CJD]). London: HM Stationery Office, 1981: DA (81) 22. 2. Taylor DM. Inactivation of unconventional agents of the transmissible degenerative encephalopathies. In: Russell DR, Hugo WB, Ayliffe GAJ, eds. Principles and practice of disinfection preservation and sterilisation. Oxford: Blackwell Scientific Publications, 1992: 171-79. 3. Department of Health and Social Security. Management of patients with spongiform encephalopathy (Creutzfelds-Jakob disease (CJD]). London: HM Stationery Office, 1984: circular DA (84) 16. 1. Department of Health and Social

RH, Walker CA, Millson GC, et al. Disinfection studies with two strains of mouse-pasaged scrapie agent. J Neurol Sci 1983; 59: 355-69. 5. Taylor DM, Brown DA, Brown KL, et al. Inactivation of BSE and scrapie agents. Abstracts of a Meeting of the Association of Veterinary Teachers and Research Workers. Scarborough: 6-8 April 1993, p 26. 4. Kimberlin

Fluorescent in-situ hybridisation and Down’s syndrome SIR,-Fluorescent in-situ hybridisation (FISH) detects the most

frequently occurring aneuploidies, such as trisomies 21, 18, 13, or XXY, in just a few hours, which makes it a useful tool with fast results for prenatal and clinical diagnosis as no culture is needed. The technique makes it possible to see some areas of chromosomes by fluorescence, usually the centromeric and heterocromatic areas, so that the number of signals (chromosomes) for that probe can be counted. We have studied 156 samples simultaneously with cytogenetics and FISH over the past 6 months. Most were prenatal studies. Standard cytogenetic techniques were used. For FISH we used probes for chromosomes 13/21, 18, X, and Y systematically.l Among the samples studied, 5 had discordance between FISH and cytogenetics (table). Four of these had Down’s syndrome with regular trisomy 21 without structural abnormalities on cytogenetics, and the other was a chromosomally normal male. All showed 3 or 4 signals instead of 4 or 5. Over the same period we have detected 12 cases of Down’s syndrome by both methods. This represents a 25% false negative rate by FISH for Down’s syndrome. Discordance on probe 13/21 has also been described by others.2 Of the 5 cases we report, 4 were samples of amniotic fluid and 1 (case 5) a blood sample from a 6-year-old boy. In case 1, amniocentesis was done at 30 weeks gestation because the fetus had duodenal atresia on an ultrasound scan. In cases 2, 3, and 4, amniocentesis was done because of maternal age. The cytogenetic studies in cases 1 and 3 were done in fetal blood; case 2 was in amniotic fluid, placenta, and muscle after termination of pregnancy at 19 weeks; case 4 was in amniotic fluid; and case 5 in a blood sample. It is also notable that 4 of the 5 discordances had Down’s syndrome. Might there be a higher risk of trisomy among those who show heteromorphism in the centromeric area of chromosome 21? In case 2, the father carried such heteromorphism. We do not know yet who were the carriers in the other cases. CORRELATION BETWEEN CYTOGENETICS AND FISH

Aetiology of AIDS SIR,-Ipointed out (April 10, p 958) that epidemiological studies by Schechter! and Ascher2 and their colleagues on the role of drugs versus HIV in AIDS did not identify verified non-drug users with AIDS and failed to consider the toxicity of zidovudine, a drug prescribed exclusively to HIV-seropositive individuals. Replying (May 8, p 1222), both groups reassert that HIV is the cause of AIDS and that my drug/AIDS hypothesis is refuted. Dr Ascher and co-workers point out that "light" use of amyl nitrite inhalants (their table 2) includes "none". But they do not account for the use of cocaine, amphetamines, and zidovudine by these people, nor do they state that AIDS developed. Schechter and colleagues similarly refer to 19 HIV-positive men "who reported no recreational drug use" and had lost T-cells before zidovudine was introduced in 1987. But these men did not have AIDS by that time. Schechter and colleagues also remind me that a category of AIDS patients who inhaled nitrites "less than 20 times per month" included non-users. This study was published in 1992, but does not report on the use of zidovudine. It still concerns me that self-reported non-drug use was not verified. As one way to "refute my drug hypothesis" I exhorted Schechter or Ascher to show that HIV-free individuals who have used drugs for 10 years never get AIDS-defining illnesses. They now report (May 8, p 78 and 39 respectively), HIV-free drug users who did not develop AIDS. But a negative does not disprove my drug/AIDS hypothesis, just as the absence of AIDS in 1 million healthy, HIV-positive Americans does not disprove the HIV/AIDS hypothesis. Previously Schechter et al had reported 2291 and Ascher et al, 2302 drug users who were HIV-positive but did not develop AIDS. Again these negatives do not disprove either the drug or the HIV hypothesis. Other HIV researchers have joined the attack on my critique of the epidemiological evidence for HIV/AIDS; Professor Dalgleish asks (May 8, p 1223) readers to "treat Duesberg’s persistent abuses of selected facts with the contempt that they deserve", without documenting a single abused fact. Epidemiology cannot distinguish between a causal and a non-causal correlate of a disease and an observer’s bias can readily shift the decision between two correlates competing for causality from one to the other. The epidemiologists’ current bias is that HIV is toxic and mine is that drugs are. The decision can only be reached by functional tests. Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA

PETER DUESBERG

1. Schechter MT, Craib KJP, Gelmon KA, Montaner JSG, Le TN, O’Shaughnessy MV. HIV-1 and the aetiology of AIDS. Lancet 1993; 341: 658-59. 2. Ascher MS, Sheppard HW, Winkelstein W Jr, Vittinghoff E. Does drug use cause AIDS? Nature 1993; 362: 103-04.

CORRECTION Phenotypic differences in low Km aldehyde dehydrogenase in Japanese workers.-In this letter by Dr T. Takeshita and colleagues (March 27, p 837), proportions in parentheses in the final sentence of the penultimate paragraph should have read 35/105 and 89/135. In addition, the final author’s name is Jun-ichi Furuyama.