GENERAL DISCUSSION 343 



Very slowly tliis gangrenous condition disappeared. Healing was obtained after several 

 months. At the time of the meeting, the man was present and showed his hand. It was 

 very difficult to distinguish between the normal fingers and the fingers which had had 

 such a severe dose. It seems that the therapeutic effects of Padutm could only be due to 

 some action on the blood vessels and that tliis hand has slowly received more blood, more 

 oxygen, and could recover. This is just to show that in clironic late stages, blood vessels 

 have certainly every importance. 



MOLE: I was just gomg to question the causal relation between the treatment and the 

 natural history because in radiation nephritis the condition comes to a kind of climax in 

 6 months to a year after exposure and if the patient doesn't die he improves spontan- 

 eously (Luxton, R. W. (1961). Lancet ii, 1220). It is probable that underlymg radiation 

 nephritis in man is a vascular lesion. It is m a sense self-hmiting. 



BACQ: A similar condition can be induced experimentally by cobalt salts, and you get the 

 same effects with Padutm on very carefuUy controlled cases. You camiot naturally make 

 controlled experiments like the one reported. It may be an extrapolation from other 

 casuses of atrophy in gangrene locahzed to the extremities. This unique observation, 

 although not entirely convincing, is nevertheless useful because, so far, no effective 

 treatment has been found for these late vascular effects. 



brinkman: I also have seen and read that in many cases the capacity of blood vessels, 

 especially the smaller ones, for regeneration is large, but you can read in books on 

 gerontology that that is not the case for the blood vessels in the bone-marrow, and I 

 should very much Like to know if anybody knows more about this, because tliis is a very 

 suggestive statement in books on gerontology. 



BACQ: Two Russian authors, L. Zhinkin and A. Zavarzin, have shown that cysteamine 

 is especially very highly concentrated in the waU of the blood vessels. 

 MAisiN: Is this lack of regeneration of the vessels of the bone-marrow so marked? In 

 irradiated rats, we know that directly after irradiation the capUlaries are dilated. Later 

 on I believe that the capillaries in the marrow must regenerate because otherwise how 

 can you explam the return to normal of erythropoiesis in the marrow? 

 brinkman: It depends of course on how much they have been damaged. 

 devtk: May I ask if there were any visible signs of loss of hair or keratinization of the 

 skin? If not, the dose might not have been too excessive. 



BACQ: Oh yes, it was a large dose and the man had a very marked oedema in the days 

 following accidental irradiation. The dose calculated was sometliing like 2,000 to 3,000 

 rem if my memory is correct. 



casarett: I would hive to say that there is plenty of evidence from observations of wound 

 heahng at all ages, that smaU vessels can maintam their regenerative capacity, but if 

 the tissue is not disturbed and no stimulus to regeneration is provided, then the geronto- 

 logical studies, including some of our own with microangio-radiography, show that there 

 is generally a net reduction in fine vasculature with age. We have done some work with 

 radiation of grafted and normal skin and studied the influence of the vascvdar changes on 

 the disappearance of radioisotopes injected into the skin and on occasion we have seen 

 that there is supra-vascularization in the regenerative phase in irradiated skin. However, 

 the disappearance curves for the isotopes are delayed just as in the case where there is 

 decreased vascularization. The reason for this is the great increase in the histohaematic 

 barrier, i.e. the connective tissue barrier between vessels and the dependent tissue. So 

 we tliink that the stimulus for the supra-vascularization resides in the histohaematic 

 barrier which is impeding the vascular functions, rather than something primarily 

 comiected with endothehal cells themselves. With regard to Dr. Mole's statement about 

 the nepliritic cases, patients who died or recovered in 6 months, I think that he is 



