1310

in a considerable deterioration of renal function. Despite eradi-cation of this infection, there was some permanent impairmentof renal function. Micturating cystography should be donewith caution in patients who have compromised renal func-tion-and should certainly be done under antibiotic cover.Nuffield Transplant Unit,Western General Hospital,Edinburgh EH4 2XU J. L. ANDERTON

DOWN SYNDROME AND RELIGIOUS GROUPS

SIR,-Dr Mulcahy (Oct. 21, p. 895) reported that the inci-dence of Down syndrome in Western Australia amongst Cath-olic women was more than double that in all other religiousgroups, and suggested that this high incidence, apparent in allmaternal age-groups, was connected with the practice of theovulatory method of birth control.By studying the prevalence of Down syndrome (3494

patients) amongst all registered patients in residential care inthe Netherlands’ we found similar differences between Catho-lics, Protestants, and other religious groups in each province(see figure). This is in accord with other findings in this

country.2 3 The world’s highest Down syndrome incidence andprevalence was found in Nijmegen and surrounding municipal-ties, an area which is mainly Catholic (>80%).

Prevalence of Down syndrome in residential care patients by re-ligion and by province of birth in the Netherlands.

In the late fifties and early sixties the ovulatory method ofbirth control was used in the Netherlands by about 35% ofCatholics, 18% of Protestants and 9% of others. But the largefamilies common among Catholics and, to a lesser extent

among Protestants,5 are also associated with shorter inter-

pregnancy intervals and longer reproductive periods, factorswhich, like the ovulatory method of birth control, may cause(before and after ovulation) overripeness of the ovum and age-ing of the spermatozoon and hence aneuploidy.6-9 This

hypothesis has a basis in experiments in animals. 10-12Huize "Maria Roepaan"

Centre for Mentally Retarded6595 NX Ottersum (L.), Netherlands

and Institute of Human Genetics,Free University,Amsterdam

P. H. JONGBLOETA. J. M. POESTKOKEA. J. H. HAMERSJ. H. J. VAN ERKELENS-ZWETS

1. Ministry of Health, 1977. Leidschendam, Netherlands.2. Stein, Z., Susser, M., Saenger, G. Am. J. Epidemiol. 1976, 103, 4473. Hustinx, Th. W. J., van den Berg-van Beukering, M. G., van Elteren, Ph.,

Rutten, F. J., Scheres, J. M. J. C. T. Maandschr. Kindergeneesk, 1977,45, 167, 175.

4. Moors, H. G. Child Spacing and Family Size in the Netherlands; p. 111.Leiden, 1974.

5. Blake, J. in Population Studies (edited by D. V. Glass); p. 27. London, 1967.6. Jongbloet, P. H. Maandschr. Kindergeneesk, 1968, 36, 352.7. Jongbloet, P. H. ibid. 1970, 38, 228.8. Jongbloet, P. H., van Erkelens-Zwets, J. H. J. Int. J. Gynœc. Obstet. 1976,

14, 111.9. Jongbloet, P. H., van Erkelens-Zwets, J. H. J. in Risks, Benefits and Contro-

versies in Fertility Control (edited by J. J. Sciarra); p. 520. Hagerstown,Maryland, 1978.

10. Simpson, J. L. ibid. p. 506.11. Shaver, E. L., Martin-Deleon, P. A. in Aging Gametes (edited by R. J. Blan-

dau); p. 151. Basle, 1975.12. Butcher, R. Int. J. Gynœc. Bost. 1976, 14, 105.

EXPERIMENTAL TREATMENTS IN END-STAGELEUKÆMIA

SIR,-I was disturbed by the paper by Dr Odom and his col-leagues (Sept. 9, p. 537) on an experimental treatment for end-stage leukaemia in two children. During their terminal illnessthe children were kept in an highly abnormal environment (theso-called "protected environment") and body fluids and tissueswere sampled. Patient 1 (presumably the 13-year-old) is saidto have gone home on the 62nd day with a normal blood pic-ture. What about the state of his psyche? During his last 8 dayshe had four bone-marrow biopsies, no doubt amongst othertests. This is a fate I would hope to be spared. The 7-year-oldseemed to fare no better.

Does this paper really reflect good patient management?Was the motive behind this research really to improve the lifeof children with acute lymphoblastic leukaemia, or was it to in-dulge in investigation of an interesting theoretical concept?Urpeth Riding,Kibblesworth,Gateshead 11,Tyne and Wear ALEX MILLS

Dr Mills’ letter has been shown to Dr August and his col-leagues, whose reply follows.-ED. L.

SIR,-Dr Mills raises important questions which concern allof us involved in bone-marrow transplantation. The motivebehind our transplants was primarily the cure of our patients.Our first responsibility was always to help our patients andtheir families bear the burdens of their disease. The psycho-logical effects of the protected environment, repeated fluidsampling, and so on in children transplanted at the Universityof Colorado Medical Center have been described in some detail

by Gardner et al. The boys we reported were the fourth andfifth patients included in that paper.

Specifically, at the time of his discharge, our first patientwas glad to be alive and delighted to be leaving hospital. Hegained strength and, shortly before his terminal illness, wasable to ride his trail bike up into the Colorado mountains nearhis home. The four marrow aspirates were done after he hadhad a cardiorespiratory arrest, while he was deeply comatose.These were done for the purposes of diagnosing infectionand/or leukaemic relapse.The 7-year-old child experienced a chronic graft-versus-host

reaction2 3 about which little was known at the time. After hissecond extramedullary relapse, his management was palliativeand he was cared for by his personal physician in the oncologydepartment of the Children’s Hospital of Denver.

In that the treatment of our patients was experimental andwas carried out in the setting of a classical research centre wefelt obliged to observe our patients’ clinical and haematologicalcourses as closely as possible. In this spirit we attempted towork with our patients in an atmosphere of maximum emo-tional support and maximum honesty, a critical element ofwhich was the informed consent obtained at the outset. Our

approach to this task is also described by Gardner et al.’ 1

Copies of the document used in our transplants will be madeavailable on request.

University of Pennsylvania/Children’s HospitalBone Marrow Transplant Unit,

Children’s Hospital,Philadelphia, Pennsylvania 19104, U.S.A. CHARLES S. AUGUST

Oncology Department,Children’s Hospital,Denver, Colorado LORRIE F. ODOM

Department of Pediatrics,University of Colorado Medical Center JOHN H. GITHENS

1. Gardner, G. G., August, C. S., Githens, J. Pediatrics, 1977, 60, suppl. p.625.

2. Shulman, H. M., Sale, G. E., Lerner, K. G., Barker, E. A, Weiden, P. L.,Sullivan, K., Gallucci, B., Thomas, E. D., Storb, R. Am. J. Path. 1978,91, 545.

3. Lawley, T. J., Peck, G. L., Moutsopoulos, H. M., Gratwohl, A. A., Diesser-oth, A. B. Ann. intern. Med. 1977, 87, 707.