Cystic fibrosis screening: research alternatives needed report has drawn attention to a hiccup in the of a cystic fibrosis (CF) screening test based upon detection of the specific mutation(s). Apparently, 25 % of those with a defective gene have multiple, different mutations, making it almost impossible to develop a gene-based test that would be more than 75 % reliable-a disappointing development. The drive towards a CF-carrier test may have been impeded by overzealous emphasis on the identification of the CF gene. Research into other means of carrier testing has been discouraged or even suppressed. The line of argument seems to have been that alternative approaches were no longer needed because the CF gene would soon be identified and a reliable screening test would follow. Research into alternatives has been stifled by loss of financial and academic support and is no longer readily available. The study of circulating CF factors, with a view to a carrier test, started some 20 years ago with the observation by Spock et aP of a ciliary dyskinesia factor in blood of CF homozygotes and heterozygotes. Such factors apparently develop as a result of the genetic dysfunction so they are present whatever the specific mutation that causes the abnormal gene. Work on the ciliary dyskinesia factor has been suppressed by lack of funds and by difficulty in publishing on the topic. Another circulating CF factor is the CF-lectin factor that I have been investigating for the past ten years,2with the object of developing a reliable, simple screening test for CF carriers and then identifying the factor so that its relation to the gene defect might be established. Publication has been difficult, primarily because of the attitude of peer reviewers mentioned. Even though the development of a test for CF-lectin factor is almost complete (the requirements for its performance have been clarified and it is more than 95% reliable), research has almost come to a standstill because of lack of funds and loss of technical staff. Medical science must return to the days when scientifically sound multiple approaches were encouraged not discouraged. This issue is not unique to CF. Advisers should not ignore data presented in support of a research project; they should make objective decisions on the basis of the facts and ignore fashionable trends.
Respiratory Disease Division, UCLA School of Medicine, Medical Center, Sepulveda, California 91343, USA 1.
people’s". Pathology Department, Western General Hospital, Edinburgh EH4 2XU, UK
fibrosis of the pancreas. Pediatr Res 1967; 1: 173-77. J, Schwartzman MN. Assay of a urinary CF-lectin factor diagnostic test for cystic fibrosis. Am J Med Sci 1990; 299: 103-06.
SIR,-Every health services manager should read your excellent editorial on the lamentable attempts to reorganise laboratory services in Glasgow (May 5, p 1066). Unfortunately, your penetrating comments may come too late to influence moves to "rationalise" laboratory services by the Lothian Health Board. The measures proposed could prove even more catastrophic than those in Glasgow, yet they have had no publicity. Lothian has three major acute hospitals (north Edinburgh, south Edinburgh, and West Lothian) all with their own laboratories on site. To avoid competitive tendering the health board has initiated a review of laboratory services. The proposals or options are well advanced for clinical chemistry and include the appointment of a laboratory manager and centralisation of the service on one site. Approval of these proposals (as seems likely) would suggest that the Lothian Health Board or its advisory committee has very little conception of the role of a modern laboratory service in hospital practice. As your editorial states, most people with first-hand experience of laboratories know that laboratory medicine is an integral component of clinical medicine. A centralised service would set back hospital medicine in Edinburgh 30 years. There is evidence that the other laboratory disciplines would quickly follow a similar reorganisation. A manager overseeing a centralised laboratory could hardly understand the role of that service.
J. N. WEBB
Charity and the NHS SiR,—Malcolm Dean (May 5, p 1085) cites the Worthing waiting list initiative as demonstrating a need for the reassessment of charities in the National Health Service. There are just two things that he should remember. Firstly, although "donation poaching had become endemic" the all-powerful media support given to national campaigns has resulted in enormous sums of money being siphoned from local charitable activities, and we see, as Dean explains, that many of the larger teaching and postgraduate hospitals have considerable trust funds which allow them to spend the income in pretty well any way that they decide is consistent with the charitable fund. Secondly, why shouldn’t the people of Worthing with serious sometimes debilitating conditions not contribute, if they wish, to a charitable fund where they can actually see in their daily life the results that their contributions have produced? Furthermore, until some sort of attempt has been made to prove the truth of his statement, "Affluent Worthing will always be able to raise four or five times as much as troubled Wigan", this does not in fact form a reliable argument. Creekside, Greenacres, Birdham, Chichester, West Sussex PO20 7HL, UK
Spock A, Heick H, Cress H, Logan WS. Abnormal serum factor in patients with cystic
The deplorable events in Edinburgh do not end here. The stimulus for reorganising the laboratories was, presumably, financial savings and cost-effectiveness. These have been ignored completely. The cost of the reorganisation remains uncalculated; given the problems the Lothian Health Board has with their finances the cost may prove incalculable. The planned centralisation would be clinically disastrous; the managerial implications could prove a nightmare for heads of department of National Health Service laboratories trying to run an efficient and cost-effective service; and the health board cannot demonstrate any economic benefits. It was Bismarck who said, in effect, that "fools learn by their own experience, wise men by other
M. W. N. NICHOLLS
Embryo research SiR,—This reply to your April 21 editorial is delayed. I did not want "screaming match" and also wondered how to convey
to be part of a
the calm fairness and moral fortitude expressed by Cardinal Hume in The Times of March 16. Laws code for society’s attitudes, actions, and conventions which are believed to be ethical. Ethics is concerned with the moral positions which ought to be adopted by a society, a group, or an individual. However, laws may not always embrace what is morally right. My study of medical ethics has highlighted the differences between utilitarianism, which judges actions to be correct according to their consequences, and deontology, which relies on moral rules which are absolute. We are essentially a utilitarian society, justifying research on human embryos of less than 14 days’ development either by devaluing them ("not people") or by being convinced that the benefits far outweigh the harm done to the developing embryo (its death); and we justify abortion by emphasising compassion on those who do not want to have a child. Your editorial rejects the suggestion that the Human Fertilisation and Embryology Bill, if enacted, will cause "incalculable harm" to society. Hume went deeper than that. He was arguing that abandoning respect for human life, fundamental human dignity, and basic and unconditional respect for each other (independent of our state of development, degree of handicap, or of how much we are "wanted") would harm our society. Moral absolutism is not popular today: we prefer the nebulous concept of actions being "acceptable" or "unacceptable" rather than "right" or "wrong". Abortion is "acceptable" because 54% of the British citizens interviewed in 1987 believed "a woman should not be forced to carry a child she does not want" and because an Act of Parliament
legalised it. Nevertheless abortion is destruction of human life. Killing has to be either right or wrong and our society needs a courageous voice to declare good as good and evil as evil, lest our growing children be unable to distinguish them. Embryo research is "acceptable" because we arbitrarily decide that embryos under 14 days old are not persons and thus not subject to the protection given to other research subjects. Your editorial argues for a society built on individual conscience but with no clear idea of right and wrong. has
Department of Medicine, Queen Elizabeth Hospital, Birmingham B15 2TH. UK
C. A. HAFFNER
Advertising for medical
Department of Surgery, Bristol Royal Infirmary,
Bristol BS2 8HW, UK
1. Fisher B, Redmond C, Poisson R, et al. Eight year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without radiation in the treatment of breast cancer. N Engl J Med 1989; 320: 822-28. 2. Wilson RG, Hart A, Dawes PJDK. Mastectomy or conservation: the patient’s choice. Br Med J 1988; 297: 1167-69. 3 Barr LC, Brunt AM, Goodman AG, et al. Uncontrolled local recurrence after treatment of breast cancer with breast conservation. Cancer 1989; 64: 1203-07.
Does hip dislocation matter in cerebral
palsy? SiR,—The final paragraph of your April 7 editorial may have left an unwarranted impression on many of your readers who see but a few children with cerebral palsy. You say "Results of prophylactic surgery are poor in severely involved quadriplegic children, especially if subluxation or dislocation occur early in life". You cite Kalen and Bleck,l Sharrard et a1,2 and Banks and Greento support
this view. Kalen and Bleck investigated the efficacy of soft-tissue-only
surgery and they concluded "Unfortunately, successful results
be expected in only about sixty percent of non-ambulators
flexion and adduction even when all overactive adductor and flexor forces have been eliminated or balanced. Even this is a considerable improvement on the dislocated, painful hip in a grossly deformed child that is the almost invariable result of purely conservative
with dismay the latest money-raising advertisements by the Imperial Cancer Research Fund (ICRF). A two-page colour advertisement, for example, in the May 5-11 issue of the Radio Times depicts in an emotive and grossly misleading fashion the difference between total mastectomy and "conservation" surgery. The advertisement shows the breast of a young woman, probably in her early 20s. In 1984, according to Cancer Research Campaign statistics, there were only 27 cases of breast cancer reported in England and Wales in women under the age of 25. The text implies, incorrectly, that good "conservation" surgery is minimal. Conservation surgery requires a wide removal of tumour-bearing tissue and axillary nodes should be sampled,l a point not made in the advertisement. Surgery is only a part of conservation therapy. These women will have to have postoperative radiotherapy which may mean five or six weeks of intensive outpatient treatment at a specialised unit which may be a long way from their homes and, indeed, from the unit where the surgery was done. This is one reason why many women prefer mastectomy.2 The criteria for selecting which of the currently available treatments is most suited to a woman with breast cancer have been clearly documented and many women have disease which would be inappropriately treated by conservation. The ICRF played only a part in this original research and it did not pioneer conservation therapy, as the advertisement implies. The consequences of the wrong therapeutic choice in terms of unacceptable rates of local recurrence (which then often requires mastectomy) or of uncontrolled local recurrence (which is virtually untreatable) make it the responsibility of surgeons involved in the care of these women to recommend treatment carefully on an individual basis.3 It is wholly inaccurate to depict mastectomy as outdated or old-fashioned. Even with careful selection conservation therapy gives results in terms of disease control and long-term survival no different from mastectomy. ICRF should not be using advertising tactics of this sort.
patients with scoliosis or pelvic obliquity and frequently additional bony surgery (.......) will be necessary to prevent dislocation of the hip Sharrard and colleagues’ fourth conclusion was "The need for operation is independent of age, severity of involvement or neurological maturity of the child". And earlier they had written "The most difficult were the severely affected, neurologically immature tetraplegic children, in whom the most that can be expected is a dysplastic or mildly subluxated hip that still falls into
Banks and Green’s results are not easy to analyse since the scoring not entirely clear (the preoperative hip state is not taken into account). But their work in no way supports your statement with respect to the prevention of dislocation. Surgery around the hip in cerebral palsy is not solely for functional gain but frequently for an improvement in the patient’s lifestyle, prevention of secondary deformity, and to ease the burden of care. You state,"Since the unstable hip does not necessarily cause functional complications to many such patients", but Cooperman et al4 estimate that half the dislocated hips will give rise to pain. To withhold early prophylactic surgery on current evidence is not a decision I would care to make on someone else’s behalf. is
London SE1 9RT, UK
V, Bleck EE. Prevention of spastic paralytic dislocation of the hip. Dev Med Child Neurol 1985; 27: 17-24. 2. Sharrard WJW, Allen JMH, Heaney SH. Surgical prophylaxis of subluxation and dislocation of the hip in cerebral palsy. J Bone Joint Surg 1975; 57B: 160-66. 3. Banks HH, Green WT. Adductor myotomy and obturator neurectomy for the correction of adduction contracture of the hip m cerebral palsy.J Bone Joint Surg 1960; 42A: 111-26. 4. Cooperman DR, Bartucci E, Dietrick E, Millar EA. Hip dislocation in spastic cerebral palsy: long-term consequences. J Ped Orthop 1987; 7: 268-76.
B12 deficiency and multiple sclerosis
S1R,- Vitamin B12 deficiency associated with pernicious anaemia in the differential diagnosis of neurological syndromes is regarded as compatible with multiple sclerosis (MS). Such consideration is especially salient when the neurological syndrome is characteristic of vitamin B12 deficiency. We report a patient who presented with asymmetrical neurological symptoms which reproducibly remitted in response to corticotropin (ACTH) and corticosteroids. A 46-year-old woman had painful paraesthesias associated with progressive right leg weakness. Myelography was normal. MS was diagnosed. During the following 15 years she was admitted about every 18 months for exacerbation of symptoms, and each time was treated with ACTH infusions which resulted in improvement. In June, 1987, magnetic resonance imaging of the brain showed bilateral high-signal-intensity abnormalities in the white matter. About 2 months later, a mean cell volume (MCV) of 100 fl was recorded. In 1988, at age 61 she was first seen by us, 5 months after exacerbation. At that time she denied cranial nerve, cerebellar, visual, or cognitive symptoms and noted that she was regarded as a "shark" at the poker table. She did not drink alcohol. She reported ocular myasthenia gravis in a brother and systemic lupus erythematosus in a sister. She had severe spastic monoparesis of the right leg associated with distal wasting. Vibration appreciation was bilaterally absent in the feet, with decreased pinprick appreciation to the mid-thigh on the right. Reflexes were symmetrically depressed with bilateral plantar extensor responses. The leucocyte count was 63 x 10/jil, haemoglobin 14 4 g/dl, mean corpuscular volume (MCV) 98-3 fl, and platelet count 163 000/1. The blood smear contained rare hypersegmented polymorphonuclear leucocytes. Serum vitamin B12 was less than 100 pg/ml and folic acid 8-2 ng/ml. Rheumatoid factor was raised (67 lU/ml) with an antinuclear factor