1210 bedtime and his morning stiffness lasts for half an hour. He says this is the longest remission he has experienced. It is difficult to draw any conclusions from just one case but, on the other hand, I do not think it should be ignored. A few R.A. patients with anaemia show improvement in their symptoms after blood-transfusion (the cause for this selectivity is not known). Whatever the cause, the improvement in symptoms after blood-transfusion in the case of R.A. I have described, and other R.A. patients with anxmia, could certainly be due to dilution of the substances causing R.A. at

Partial exchange transfusion should be investigated as an alternative therapy to prednisolone and immunosuppressive agents in R.A. Leicester General Hospital, Gwedolen Road, Leicester LE5 4PW.



SIR,-Dr Russell and her colleagues (Oct. 25,

797) proposed a model of polyamines as biochemical markers of growth and death of tumour cells. They suggested that in cancer patients the increased serum and urine levels of spermadine reflected release of intracellular polyamine as a result of tumourcell loss. Putrescine levels in serum and urine were thought to represent the proliferative compartment of the tumour. We should like to present some findings which cannot be readily explained by their hypothesis. In human urine, and probably in serum as well, polyamines are present predominantly as conjugates which produce the free polyamines after hydrolysis.’ Acetylated polyamines are the only conjugates which have been identified in human urine. We have examined some of the polyamine conjugates in p.


(see table). The highest ratio was observed in the urine of a patient with hepatoma (10-3) and the lowest in the urine of a normal subject (1.1). The considerably higher levels of N’-acetylspermidine in the urine of the hepatoma patient is noteworthy. These findings indicate that the differences in urine polyamines between normal subjects and cancer patients are not only in the levels of polyamines but also in the nature of the polyamine conjugates. One of us (M.M.A.) has proposed that intracellular conjugation is the major route of elimination of the polyamines from cells and that the tumour cell has a higher spermidine N’-acylase activity than the normal cell. This proposal is now being tested experimentally. Although our data are preliminary, it seems that there are qualitative and quantitative differences between intracellular polyamines and polyamines in the urine and also between the urinary conjugated polyamines of cancer patients and normal subjects. These differences are not readily explained by the hypothesis advanced by Dr Russell and her colleagues. Department of Medicinal Chemistry,

College of Pharmacy, and


Department Medicine, Medical School, University of Minnesota, Minneapolis, MN. 55455, U.S.A.


SIR,-Dr Leighton and his colleagues (Nov. 22, p. 1012) are in their conclusion "that the value of savings in health alone will probably far outweigh any costs of a screening programme" for neural-tube defects, provided: (1) The incidence of spina bifida is at least 2-5/1000 total births in

correct care

area in which screening is provided. (2) The screening test is as sensitive for mass screening between the


16th and 20th weeks of pregnancy as it dozen women in the 16th to 26th weeks




be amongst


(i.e., 90% sensitive for open

spina bifida). (3) That to achieve 90% sensitivity the specificity of the

test is no

less than the 95% cited. (4) That no more than 5% of women fail to be screened. (5) That almost all those with a positive result agree to amniocentesis and possible termination, even though their chance of bearing a liveborn child with myelocele is 3-4%, while that of "iatrogenic abortion" might be 1%. (6) That costs of publicity, genetic counselling, ultrasonography, and radioimmunoassay are included in the screening programme. (7) That if future streams of costs and benefits are discounted, as they should be,’ a low rate (not more than 10%) is employed. *Ratio

of NI-acetylspermidine to N8-acetylspermidine.

Many of these conditions

are unlikely to be met. However, feel that to measure the economic savings to society of screening for neural-tube defects it is necessary to consider total benefits including those which fall outside the health sector--e.g., special education. We have found the non-health benefits to be about as great as those within the health sector.2 One further point should be considered. If the test specificity were set as low as 95%, the volume of amniocenteses generated would be several times that currently undertaken in most centres for all indications taken together. This might act to delay the development of other programmes such as antenatal diagnosis of Down syndrome. The choice of a higher specificity would probably allow the simultaneous development of several programmes, but at the cost of missing many more cases of spina bifida. we

the urine of 3

cancer patients who had not received chemotherapy and 3 normal subjects and confirmed the presence of acetylputrescine, acetylcadaverine, Nl-acetylspermidine, and N8-acetylspermidine in appreciable amounts. In all the samples examined, the amounts of free putrescine and spermidine were less than one-twentieth of the respective acetyl conjugates. On the other hand, within cells the polyamines are present predominantly in the free form. If the elevated serum and urine levels of spermidine in cancer patients were produced by tumour-cell loss, a much higher ratio of free/acetylated spermidine would be expected. The low levels of free spermidine in serum and urine may be attributed to the presence of spermidine acylases in serum and/or in liver or to higher urinary clearance of the acetylated spermidines. However, there is no experimental evidence to justify such speculations.

We have determined the ratio of N’-acetylspermidine to N8-acetylspermidine in the urine of both normal subjects and cancer patients using methods developed in our laboratories.2 The 3 cancer patients had considerably higher ratios ofN’-acetylspermidine/N8-acetylspermidine than the 3 normal subjects 1.

Russell, D. H., Levy, C. C., Schimpff, S. C., Hawk, I. A. Cancer Res. 1971, 31, 1555. 2. Abdel-Monem, M. M., Ohno, K. Unpublished.

Health Services

Operational Research Unit, 73 Rottenrow, Glasgow G4 0NG


Greater Glasgow Health Board and University Departments of Community Medicine and Medical Genetics.


1. Walsh, H.

G., Williams,

A. Current Issues

Stationery Office, 1969. 2. Hagard, S., Carter, F., Milne,


R. G. Br. prev.

Cost Benefit Analysis. H.M. soc.

Med. (in the press).

Letter: Acetylspermidines in human urine.

1210 bedtime and his morning stiffness lasts for half an hour. He says this is the longest remission he has experienced. It is difficult to draw any c...
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