264 within the patient’s choice. Society has, however, determined that "when to die" and "how to die" must remain firmly within the province of chance. So deeply entrenched is the prohibition of volition in these areas that one wonders what can be the deep-seated psychological reason for this attitude. As a relic of the age of faith in this present age of reason it has historical interest. In that it limits the freedom of rational beings it is high time it were challenged in favour of more civilised behaviour. Portland House,

Lindley,

S. L. HENDERSON SMITH

Huddersfield

DO ONLY A FEW CHROMOSOMES CARRY GENES OF PRIME IMPORTANCE FOR MALIGNANT

TRANSFORMATION?

SIR,-We have summarised data on 287 human neoplasms in which abnormal karyotypes have been established by chromosome banding. While the entire material has been presented elsewhere,’ we would like to set out some of the evidence underlying the conclusion that changes in the hereditary material must be intimately interrelated with the neoplastic transformation process. The 287 cases were grouped into ten tumour types. In perfect agreement with our compilation last year of 129 cases,2 the chromosome aberrations were clearly non-random and sometimes highly specific:

few chromosomes were inneoplastic groups, the series was characterised by clustering of aberrations to a few specific chromosome types nos. 7, 8, 9, 14, 17, 20, 21, and 22. Experimental work in our laboratory has shown that the aetiological factor is important in determining the chromosomal evolution in tumours.3-5 Furthermore, some of the experimental tumours were characterised by stepwise karyotypic evolution with predetermined sequences of chromosomal changes.6 This trend has also been found in some human malignancies,’ making it highly tempting to speculate that they, too, develop distinctive karyotypic patterns under the influence of different oncogenic agents. However, in man this cannot be tested experimentally. In our opinion, the clustering of aberrations indicates that only a few chromosomes carry genes of prime importance for malignant transformation, and that these genes are selectively engaged in the interaction with the inducing agent during carcinogenesis. The primary change(s) induced may or may not be discernible microscopically, but once the crucial gene(s) have been activated, the sequence of karyotypic changes will follow. The fact that they often take different routes-perhaps under the influence of different agents-shows that the development of malignancy is not bound to one specific chromosome constitution. Our hypothesis is compatible with results from other experimental approaches, such as the cell-culture work by Sachs et al. and the cell hypbridisation work of Wiener et

Apart from the fact that only

a

in both of which the role of chromosomes in malignancy has been emphasised. Data on the detailed chromosomal constitution of human tumours are rapidly accumulating, and we plan periodic reviews of the subject. We would welcome any further information-published or unpublished-about chromosome banding in human neoplasia. All such data will be included in the survey, copies of which will be sent to contributors. Department of Clinical Genetics, Lund University Hospital, S-221 85 Lund, Sweden FELIX MITELMAN

al.,9

Institute of Genetics, University of Lund

GORAN LEVAN

EFFECT OF A.C.T.H. ON CHOLESTEROL AND TRIGLYCERIDES IN HYPERLIPOPROTEINÆMIA TYPE V up, from the age of 5 to 11 months, infant with a severe encephalopathy with infantile spasms and hypsarrhythmia. The patient had hyperlipoproteinxmia type v’O (hypertriglyceridaemia, hyperchylomicroncemia, and hyperprebetalipoproteinxmia). We found increased values of chylomicroils in his father (51 mg/dl) and 8-year-old brother,

SIR,-We have followed

an

(43 mg/dl). The patient’s weight and the length were at the 75th centile, liver was enlarged, fundoscopy normal, hyperuricsemia (4-8 mg/dl), relatively high levels of insulin (22 nU/ml), abnormal glucose-tolerance test, and, while fasting, abnormal lactescence in the plasma. Because of his hypsarrhythmia the patient had been treated, at 5, 7, and 10 months, with three therapeutic cycles, of 20 days each, of intramuscular corticotrophin A.C.T.H., ’Synacthen Depot’). During each therapeutic cycle cholesterol, triglyceride, chylomicron and prebetalipoprotein values fell to normal. When A.c.T.H. therapy was interrupted these concentrations rapidly rose again to their pre-treatment levels. The values for the second

A.C.T.H.

cvcle

were

(in ms/dl:

volved in each of the above

Mitelman, F., Levan, G. Hereditas, 1976, 82, 167. Levan, G., Mitelman, F. ibid. 1975, 79, 156. Mitelman, F , Mark, J., Levan, G., Levan, A. Science, 1972, 176, 1340. Levan, G., Ahlström, U., Mitelman, F. Hereditas, 1974, 77, 263. Levan, G., Levan, A. ibid. 1975, 79, 161. Mitelman, F. Acta path. microbiol. scand. 1972, 80A, 313. 7 Mitelman, F., Levan, G, Nilsson, P. G., Brandt, L. Int J. Cancer (in the

1 2 3. 4. 5. 6.

press). 8. Yamamoto, T.,

Rabinowitz, Z., Sachs, L. Nature

new

Biol. 1973,

243, 247.

We report this case because hyperlipoproteinaemia type v is in childhood and exceptional at this agell-13 and because the effect of A.C.T.H. was so unexpected. We think that the decrease of plasma levels of lipids and lipoproteins is due exclusively to A.C.T.H. effect because the infant was not given any other drug and because the diet was not changed during the

rare

A.C.T.H.

and

non-A.C.T.H.

periods (95 calories/kg/day: 13

from proteins, 55% from carbohydrates, and 32% from fats). We cannot explain the A.C.T.H. effect, which seems to be paradoxical since A.C.T.H. normally acts as lipolytic drug and would therefore tend to increase plasma-lipids. Clinica Pediatrica Dell’ Università, I’oliclinico di Borgo Roma, 37100 Verona, Italy

GIORGIO ZAMBONI PIERLUIGI MARRADI

RAPID MEASUREMENT OF PLASMA-GLUCOSE use of the in the measurement of the laboratory ’AutoAnalyzer’ blood-glucose of patients attending the diabetic clinic a method was sought which would allow a single technician to provide this information rapidly and accurately on peripheral-blood samples obtained and processed within the clinic complex.

SIR,-Because of difficulties associated with the

central

9. Wiener, F., Klein, G., Harris, H. J. Cell Sci. 1971, 8, 681 10. Fredrickson, D S., Levy, R. I., Lees, R. S New Engl. J Med 1967, 276, 94 11

Kouvalainen, K., Nikkari, T., Maatela, J., Hiltunen, P, Parvinen, T. Pediat. Res 1970, 4, 208.

12. Desai, M. Indian Pediat 1974, 11, 677. 13. Desai, M., Bajaj, R. T., Babar, S T. ibid p. 695

265

Commentary from Westminster Expenditure Cut:

Income Raised

FROM A CORRESPONDENT

The method selected is based on the Calbiochem glucose no. 869204) and the Calbiochem LC 340 B

pack (catalogue

single-wavelength portable spectrophotometer (Calbiochem Ltd., Hereford). Approximately 1001 of peripheral blood was obtained by fiugerprick and transferred to a microcentrifuge tube containing 2 fll of anticoagulant solution (polyanetholesulphonic acid 50 flglml, Calbiochem). After centrifugation 10 1 of plasma were removed using a syringe pipette and transferred to a disposable 1 cm spectrophotometer cuvette containing 1.5 ml of glucose reagent. After mixing and incubation at room temperature for 3 min the optical density (O.D.) of the cuvette was read against a glucose reagent blank. A facderived from the extinction coefficient of reduced and used to calculate the plasma-glucose concentration (o.D.x437=mg glucose/dl; o.D.x24.3=mmol glucose/1). The instrument and reagents were checked at intervals using a control serum (’Caltrol- 350 Normal’). Glucose was measured by this method and on the central laboratory autoanalyser on 110 patients who attended the diabetic clinic over a two-day period, and the construction of a linear regression graph from ihe results (see figure) gave a correlation coefficient of r=0.96. Using this technique a single technician can measure plasma-glucoses at a rate of 25/h. tor was N.A.D.P.

We thank Dr T. M. Hayes, operation in this study.

Department

of

University Hospital of Wales, for his

co-

T. CLARK A. B. PARKES E. REYNOLDS

Medicine,

Welsh National School of Medicine, Cardiff CF4 4XN

UREA METABOLISM IN AN AZOTÆMIC WOMAN WITH NORMAL RENAL FUNCTION

SIR,-An error in the calculation of urea-synthesis rate in the paper by Richards and Brown’ resulted in underestimation of urea synthesis and therefore of urea metabolism (breakdown). This error obscured the fact that urea metabolism had in fact increased in proportion to the synthesis-rate, breakdown being the same proportion of the synthesis-rate as in healthy individuals. The correct figures are: urea synthesis 97 mmoL/h, urea metabolised 18.3 mmoi/h, metabolism 19% of synthesis, and urea metabolised in 24 h 3% of pool. St George’s Hospital and Medical London SW 1

1 Richards,

School,

P, Brown, C. L. Lancet, 1975, ii, 207.

PETER RICHARDS SUSAN ELL

THE cuts in the Health Service announced last week by the Chancellor were a mixture of the tried and untried-on the one hand, familiar recourse to cutting capital expenditure, and, on the other, new sources of major revenue from road-accident charges. Clearly Mr David Ennals, Secretary of State for Social Services, was less mauled in Cabinet than he might have been. But this will be little consolation to local health authorities who are being asked again to re-examine their spending programmes for 1977-78. When it became clear to Mr Ennals that he was going to have to find savings in the health and personal social services programme, his main objective was to protect the hard-pressed revenue allocations of the health authorities. This enabled him to say at the end of the operation that, despite reductions of ,E70 million in the programme in 1977-78, there would be no cuts in services provided for patients in the N.H.S. But, having ruled out cuts in revenue allocations Mr Ennals had to look elsewhere. A whole series of options was then examined, including a number of charges which would have been new to the N.H.S. But in the end these were all rejected as potentially unacceptable to the Labour Party both inside and outside Parliament. For the same reason prescription charges were left unchanged. These reservations did not apply to substantially increased dental and ophthalmic charges, and road-accident charges, despite Mr Ennals’ comment: "Most of these charges I find most unpleasant and I regret we are having to increase those that we are". Legislation to recoup mainly from insurance companies the full cost to the N.H.S. of treating road-accident cases will be introduced in the next Parliamentary. session. In a full year it is expected to bring in between ,E40 million and 45 million, but since the Bill is unlikely to get onto the Statute Book until half-way through next session, the income in 1977-78 is expected to be only about l20 million. The resulting levy is expected to work out at a rough average of 3 a year per motorist. Mr Ennals will now discuss with insurance companies the best way of collecting the charge. The legislation is unlikely to be opposed by the Tories, who, fortuitously have been considering similar increases among a whole series of higher charges they are planning. Both they and the Government have been attracted by the buoyancy of finance from this charge which could even protect the N.H.S. from future damag-

ing cuts. The increases in dental and ophthalmic charges, which will bring in an extra l20 million, have been described by Mr Ennals as "very steep"-a sentiment which is echoed by a number of Labour 4.p.s who may refuse to support the Government when the regulations come before the Commons. Although the charges were due to be raised in line with rising costs, the announced increases go much higher. The defence used by Mr Ennals is that those who have to pay for spectacles or