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ADDISON'S DISEASE WITH DIABETES MELLITUS
1083 radioactive materials within the lumen of the bowels for as long as 10-12 days,15 Dr. Latner and his colleagues must produce much more clinical evidence if . they wish to prove that the newly isolated fraction has factor activity. mucoprotein but little intrinsic factor activity, " may well definite intrinsic Department of Medicine, represent the fraction isolated by Glass et al." ; by inference New York Medical College, he contrasts this with his active material, which exhibits GEORGE B. JERZY GLASS. New York. high intrinsic factor activity and travels to the anode. This statement is disturbing in view of his knowledge of our earlier ADDISON’S DISEASE WITH DIABETES MELLITUS publication,4 which he quotes, where we have insisted that SIR,—The case reported by Dr. Baird and Dr. Munro our mucoprotein fraction showing intrinsic factor activity (May 8) is most interesting. In view of the suggested travels to the anode on electrophoresis and forms one of influence of adrenal overactivity in the pathogenesis the leading anodic peaks.4-6 This high negative mobility of of diabetic retinopathy, it would be interesting to know been to —8 has confirmed 8 X (-7 10-5) glandular mucoprotein by others.’ This obviously precludes that a substance having if this patient had diabetic retinopathy, and, if so, such a high negative charge could travel on paper electrowhether the condition of the fundi improved with the phoresis to the cathode at -pH 6-35 even by electro-osmosis, onset of Addison’s disease. Poulsen 16 recorded a case and makes Dr. Latner’s statement groundless. To prove his in which diabetic retinopathy regressed with the developpoint, Latner would have to compare the electrophoretic ment of Simmonds’ disease. mobility of his fraction and ours, using the same technique. National Maternity Hospital, Otherwise there is no evidence that his intrinsic factor M. I. DRURY.
that his intrinsic factor mucoprotein is different. Let us analyse these three points : (a) Dr. Latner implied earlier1 that the material present in his first cathodic electrophoretic peak, which contains much
differs from ours in electrophoretic mobility. (b) The second argument for specificity of the fraction is : " Its chemical analysis indicated that it could not possibly be identical with so-called ’soluble glandular mucoprotein.’ This has already been pointed out elsewhere." To us, the only two differences which appear valid are : Dr. Latner’s preparation contains about 1% less nitrogen than ours (11-2% according to Werner 8) ; and there is no hexuronic acid, as determined by Dische’s carbazol method, and as contrasted to the presence of this acid in our material, using Tracey’s technique. All the other data appear to be similar. As I pointed out in a discussion of Dr. Latner’s paper,9 the hexDsamine content is similar in both cases (8-8% in ours8 and 6%2 and 8% in Dr. Latner’s). Also the carbohydrate spectrum is similar and includes fucose and galactose, but no glucose. Finally, the Folin-Ciocalteu reaction for tyrosine and tryptophan is positive in both instances ; since we did not determine whether it is tyrosine or tryptophan in our substance which gives the positive Folin-Ciocalteu reaction, the absence of tyrosine in Dr. Latner’s preparation cannot be accepted as a differentiating point. Also the difference in hexuronic acid content cannot be accepted without a comparative study with the same technique. (c) The third argument is that this substance " has proved easily soluble at pH 2-0 which is an additional indication that it is not identical with solubleglandular mucoprotein.’ This is wrong. Our mucoprotein fraction is perfectly soluble at pH 2-0 after electrophoretic separation. It flocculates at pH 2-0 only after it has been previously denatured by acetone precipitation, which we use for its fractionation ; this denaturation decreases its solubility in the neighbourhood of the isoelectric zone.
Dublin.
mucoprotein
"
Since all these arguments can be faulted, I think that there is as yet no adequate evidence for differentiating Latner’s intrinsic factor mucoprotein from our mucoprotein fraction carrying intrinsic-factor activity. (6) The only characteristic feature of Castle’s intrinsic factor is its ability to promote the intestinal absorption of vitamin B12 in patients with pernicious anaemia. This can be assessed by any of the available isotope techniques.10-13 Because of the delicacy of all these methods, the evaluation of the results requires clear-cut data. Dr. Latner performed only two tests using Heinle’s method 10 ; he observed a fall of about 30 % in the faecal excretion of radioactive B12 after addition of his preparation. In Heinle’s original work, the fall was of the order of at least 60 %. Meyer 14 has recently shown that a fall of 30 % can occur without any obvious reason even in normal subjects, and we have observed retention of 5. Glass, G. B. J. Gastroenterology, 1953, 23, 219. 6. Pugh, B. L., Glass, G. B. J., Wolf, S. Proc. Soc. exp. Biol., N.Y. 1952, 79, 674. 7. Mack, M. H., Wolf, S., Stern, K. G. J. clin. Invest. 1953, 32, 862. 8. Werner, I. Acta Soc. med., Upsal. 1953, 58, 1. 9. Latner, A. L. Gordon Symposium on Metabolism and Vitamins. New London, New Hampshire, 1953. 10. Heinle, R. W., Welch, A. D., Scharf, V., Meacham, G. C., Prusoff, W. H. Trans. Ass. Amer. Phys. 1952, 65, 214. 11. Schilling, R. F. J. Lab. clin. Med. 1953, 42, 860. 12. Glass, G. B. J., Boyd, L. J., Gellin, G. A., Stephanson, L. Fed. Proc. 1954, 13, 54 ; Arch. Biochem. (in the press). 13. Glass, G. B. J. Clin. Res. Proc. 1954, 2, 32. 14. Meyer, L. M. Proc. Soc. exp. Biol., N.Y. 1953, 82, 490.
STRIPPING OPERATION FOR VARICOSE VEINS
SiR,-I would like to support Mr. Bolton Carter’s advocacy (April 10) of the stripping operation for varicose saphenous veins. It is indeed a good operation, especially when it supplements a complete diagnosis and a flush sapheno-femoral or sapheno-popliteal ligation. Stripping will not clear up inefficient communicating veins, such as those above and below the knee or above the ankle, in many cases will it relieve ulceration above the ankle. In my experience only about 40% of ulcerated ’legs are due to varicose veins : many of the rest follow phlebitis of the deep veins. With these qualifications, I agree that stripping does clear varicose veins and reduces much of the need for postoperative sclerosing injections. In this respect I have found it superior to the former method of internal abrasion and fractional injection of sclerosing fluid, which, though effective, did need a fair number of injections to remove varicose veins from the legs. Although stripping is a somewhat crude operation, it can be performed under a local anaesthetic and it is followed by comparatively little pain and few complications. None of my patients are given antibiotics unless there is active ulceration present ; the wounds of fat persons are usually " frosted " with sulphanilamide nor
powder. I note Mr. Bolton Carter’s use of ethamoline injections : I bracket this with sodium morrhuate as an undesirable and dangerous sclerosant, because it causes such intense pain afterwards that patients are often incapacitated for from 1 to 7 days, which gives ideal conditions for a clot to propagate deeply, not to mention the occasional syncope immediately after its introduction. Since October, 1946, when Mr. Riddoch introduced me to his phenol-glycerin solution, I have used it with consistent success and safety ; the present formula is phenol 3% and glycerin 30% in apyrogen water, and the dose is P/2-2 ml. It is supplied by most chemists. In dealing with bilateral varicosities, I agree that it is permissible to do both legs simultaneously with two surgeons, but otherwise it is safer to do one leg per session with an interval of 2 or 3 days. The incidence of deep calf thrombosis in my patients was quite appreciable when both legs were done at one operation with only one surgeon. I began using the stripping operation occasionally in 1951, and from Jan. 1, 1952, I have used it exclusively over 400 times. It is clearly an effective and safe method needing the minimum of aftercare, although patients are followed up for 5 years or more afterwards. HAROLD DODD. London, W.l. 15. Glass, G. B. J. 16. Poulsen, J. E.
Bull. N.Y. Med. Coll. 1953, 16, 1.
Diabetes, 1953, 2, 7.
that his intrinsic factor mucoprotein is different. Let us analyse these three points : (a) Dr. Latner implied earlier1 that the material present in his first cathodic electrophoretic peak, which contains much
differs from ours in electrophoretic mobility. (b) The second argument for specificity of the fraction is : " Its chemical analysis indicated that it could not possibly be identical with so-called ’soluble glandular mucoprotein.’ This has already been pointed out elsewhere." To us, the only two differences which appear valid are : Dr. Latner’s preparation contains about 1% less nitrogen than ours (11-2% according to Werner 8) ; and there is no hexuronic acid, as determined by Dische’s carbazol method, and as contrasted to the presence of this acid in our material, using Tracey’s technique. All the other data appear to be similar. As I pointed out in a discussion of Dr. Latner’s paper,9 the hexDsamine content is similar in both cases (8-8% in ours8 and 6%2 and 8% in Dr. Latner’s). Also the carbohydrate spectrum is similar and includes fucose and galactose, but no glucose. Finally, the Folin-Ciocalteu reaction for tyrosine and tryptophan is positive in both instances ; since we did not determine whether it is tyrosine or tryptophan in our substance which gives the positive Folin-Ciocalteu reaction, the absence of tyrosine in Dr. Latner’s preparation cannot be accepted as a differentiating point. Also the difference in hexuronic acid content cannot be accepted without a comparative study with the same technique. (c) The third argument is that this substance " has proved easily soluble at pH 2-0 which is an additional indication that it is not identical with solubleglandular mucoprotein.’ This is wrong. Our mucoprotein fraction is perfectly soluble at pH 2-0 after electrophoretic separation. It flocculates at pH 2-0 only after it has been previously denatured by acetone precipitation, which we use for its fractionation ; this denaturation decreases its solubility in the neighbourhood of the isoelectric zone.
Dublin.
mucoprotein
"
Since all these arguments can be faulted, I think that there is as yet no adequate evidence for differentiating Latner’s intrinsic factor mucoprotein from our mucoprotein fraction carrying intrinsic-factor activity. (6) The only characteristic feature of Castle’s intrinsic factor is its ability to promote the intestinal absorption of vitamin B12 in patients with pernicious anaemia. This can be assessed by any of the available isotope techniques.10-13 Because of the delicacy of all these methods, the evaluation of the results requires clear-cut data. Dr. Latner performed only two tests using Heinle’s method 10 ; he observed a fall of about 30 % in the faecal excretion of radioactive B12 after addition of his preparation. In Heinle’s original work, the fall was of the order of at least 60 %. Meyer 14 has recently shown that a fall of 30 % can occur without any obvious reason even in normal subjects, and we have observed retention of 5. Glass, G. B. J. Gastroenterology, 1953, 23, 219. 6. Pugh, B. L., Glass, G. B. J., Wolf, S. Proc. Soc. exp. Biol., N.Y. 1952, 79, 674. 7. Mack, M. H., Wolf, S., Stern, K. G. J. clin. Invest. 1953, 32, 862. 8. Werner, I. Acta Soc. med., Upsal. 1953, 58, 1. 9. Latner, A. L. Gordon Symposium on Metabolism and Vitamins. New London, New Hampshire, 1953. 10. Heinle, R. W., Welch, A. D., Scharf, V., Meacham, G. C., Prusoff, W. H. Trans. Ass. Amer. Phys. 1952, 65, 214. 11. Schilling, R. F. J. Lab. clin. Med. 1953, 42, 860. 12. Glass, G. B. J., Boyd, L. J., Gellin, G. A., Stephanson, L. Fed. Proc. 1954, 13, 54 ; Arch. Biochem. (in the press). 13. Glass, G. B. J. Clin. Res. Proc. 1954, 2, 32. 14. Meyer, L. M. Proc. Soc. exp. Biol., N.Y. 1953, 82, 490.
STRIPPING OPERATION FOR VARICOSE VEINS
SiR,-I would like to support Mr. Bolton Carter’s advocacy (April 10) of the stripping operation for varicose saphenous veins. It is indeed a good operation, especially when it supplements a complete diagnosis and a flush sapheno-femoral or sapheno-popliteal ligation. Stripping will not clear up inefficient communicating veins, such as those above and below the knee or above the ankle, in many cases will it relieve ulceration above the ankle. In my experience only about 40% of ulcerated ’legs are due to varicose veins : many of the rest follow phlebitis of the deep veins. With these qualifications, I agree that stripping does clear varicose veins and reduces much of the need for postoperative sclerosing injections. In this respect I have found it superior to the former method of internal abrasion and fractional injection of sclerosing fluid, which, though effective, did need a fair number of injections to remove varicose veins from the legs. Although stripping is a somewhat crude operation, it can be performed under a local anaesthetic and it is followed by comparatively little pain and few complications. None of my patients are given antibiotics unless there is active ulceration present ; the wounds of fat persons are usually " frosted " with sulphanilamide nor
powder. I note Mr. Bolton Carter’s use of ethamoline injections : I bracket this with sodium morrhuate as an undesirable and dangerous sclerosant, because it causes such intense pain afterwards that patients are often incapacitated for from 1 to 7 days, which gives ideal conditions for a clot to propagate deeply, not to mention the occasional syncope immediately after its introduction. Since October, 1946, when Mr. Riddoch introduced me to his phenol-glycerin solution, I have used it with consistent success and safety ; the present formula is phenol 3% and glycerin 30% in apyrogen water, and the dose is P/2-2 ml. It is supplied by most chemists. In dealing with bilateral varicosities, I agree that it is permissible to do both legs simultaneously with two surgeons, but otherwise it is safer to do one leg per session with an interval of 2 or 3 days. The incidence of deep calf thrombosis in my patients was quite appreciable when both legs were done at one operation with only one surgeon. I began using the stripping operation occasionally in 1951, and from Jan. 1, 1952, I have used it exclusively over 400 times. It is clearly an effective and safe method needing the minimum of aftercare, although patients are followed up for 5 years or more afterwards. HAROLD DODD. London, W.l. 15. Glass, G. B. J. 16. Poulsen, J. E.
Bull. N.Y. Med. Coll. 1953, 16, 1.
Diabetes, 1953, 2, 7.