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The use of copper and iron in the treatment of secondary anemia in children
THE USE OF COPPER AND IRON IN THE
TREATMENT
OF
SECONDARY ANEMIA IN CHILDREN JO~N F. CASON, M.D. DUaHA~, N. C. H E value of the administration of copper in conjunction with iron the t r e a t m e n t of secondary anemia has been demonstrated in animals, 1-8 in children, 9, lo, a~, la a n d in adults2 a B u t more, observations are needed on the ratio of copper to iron, and also on the comparison of the effects of cupric and ferric compounds, a n d cuprous and ferrous compounds, because of the reports that the latter are more efficacions.l~, as, 1G Six children suffering f r o m secondary anemia due to malnutrition or infections, whose hemoglobin varied f r o m 40 to 74 p e r cent (average 58.5 p e r cent) on admission were treated. Three times daily they were given f r o m 5 to 10 c.c. (according to their' ages) of a solution containing 0.5 gm. of cupric sulphate a~d 10 gin. of ferric a m m o n i u m citrate p e r 100 c.c. of 25 p e r cent ~romatic elixir solution (U.S.P.). Such a p r e p a r a t i o n can be p r e p a r e d at a cost of less t h a n t w e n t y cents per pint. I n this way, each patient received daily f r o m 10 to, 20 rag. og copper' and :from 250 to 500 rag. oY iron, which is: in. agreement with the dosage of iron f o u n d to be optimal by Minot and Castle. .7 Similar commereiM p r e p a r a t i o n s were considered, but, the m a j o r i t y of these contained less t h a n one-third of these amounts of copper and iron, and the costs were m a n y times higher. Different proportions of copper and iron were used at first in order to determine a palatable: ratio. I t was found that a p r o p o r t i o n (of available eo.pper to iron) higher t h a n 1 to 25 produced nausea and vomiting' in 20 per cent of the patients.
T in
Six children whose secondary anemia was similar to thug of the first group and' whose hemoglobin on admission averaged 63 p e r cent were given cuprous and ferrous g~utamate. ~~ This materiM was made up in capsules each of which eontMned 30 rag. of cuprous glutamate a n d 750 rag. of f e r r o u s glutamate. The dosage was three capsules daily, which provided the same amount of iron as 15 e.c. of the cupric and ferric eomponnd. The ratio of available copper to. iron was 1 to 34. The hemoglobin content of these children was determined at intervals for an average of f o u r weeks b y the Sahli method and recorded on a l~ead b e f o r e t h e S e c t i o n on P e d i a t r i c s of t h e M e d i c a l S o c i e t y of t h e S t a t e of N o r t h C a r o l i n a a t R a l e i g h , N. C., A p r i l 19, 1933. tVrom t h e D e p a r t m e n t of P e d i a t r i c s , D u k e U n i v e r s i t y School of M e d i c i n e , a n d D u k e I-tospital, D u r h a m , N. C. *The c u p r o u s a n d f e r r o u s g l u t a m a t e w a s k i n d l y f m ' n i s h e d to u s f o r t h i s p u r p o s e b y t h e Caleo C h e m i c a l C o m p a n y . 614
CASON:
USE
OF
COPPER
AND
IRON
IN
SECONDARY
ANEMIA
615
percentage basis, 16 gm. hemoglobin per 100 c.c. of blood being regarded as 100 per cent. While the children were in the hospital, examinations were made at least once a week, but those observed in the dispensary had their examinations at longer intervals. P r o b a b l y the curve of rising hemoglobin would have been s h a r p e r in its earlier stages, if determinations h a d been made ~tt more f r e q u e n t intervals. I n the children, whose anemia was due to m a h I u t r i t i o n the hemoglobin content increased rapidly; while in those who had infections, the rise usually did not occur until the infection had subsided. ~s, ~9, 2o As m a y b e
%
< %
14roe A z
G~'aph I.
seen in Gra{)h I, the children treated with tile cupric and ferric compound, and those given the cuprous and f e r r o u s compound showed tile same rate of increase in hemoglobin cmltent, n a m e l y 4.6 per cent per week. CONCLUSION
As f a r as can be judged f r o m this small series observed for a short period of time, a ratio of copper to iron of 1 to 25 is palatable and does not cause nausea; and a cupric and ferric compound is as efficacious in the t r e a t m e n t of secondary anemia in children as is a cuprous and ferrous compound.
616
TKE JOUgNAL 01~ PEDIATRICS REFEREN CES
1. Hart, E. B.; Stcenbock, i t . ; WaddetI, J . ; and Elvehjem, C. A.: J. Biol. Chem. 77: 797, 1928; and 83: 251~ 1929. 2. Waddell, J.; Steenbock, K.; and I-Iart, E. B.: Ibid 84: 115~ 1929. 3. Elvehjem~ C. A.; and Kart~ E. B.: Ibid 95: 363~ 1932. 4. McHargue, J. S.; Healey, D. J . ; and ]~Iill~ E. S.; Ibid 78: 637, 19'28. 5. Lewis, G. T.i WeiehsuIbaum, T. E.; and MeGhee, J. L.: ]?roe. Soc. Exper. Biol. and ivied. 27: 32,9, 1930. 6. Mitehe]l~ ~. 8., and Miller~ L.: J. :Biol. Chem. 92; 42]~ 1931. 7. ]Keil, I{. L.~ and !%lson, V. E. : lbid 93: 49, 1931. 8. Titus, 1~. W.; Cave, ~I. W.; and }[ughes, J. S.: Ibid 80: 565, 1928. 9. Josephs, It. W.: Bull. Johns ~Iopkins Kosp. 49: 246, 1931. 10. Lewis, M. S.: J. A. ~r A. 96: ]135, 193]. 11. Bloxsom, A. ]?.: South. M. J. 25: 401, 1932. 12. ]?arsons, L. G., and ttickmans, E. M.: Arch. Dis. Childhood 8: 85, 1933. 13. Mills~ E. S.: Canad. M. A. J. 22: 175, 1930. 1~. Correa, J. B.; Cruz, L.; and Monteiro de Barros Netto, J. ~.: (Abstract) J. A. ~r A. 100: 591, 1933. 15. Stal'kenstein, E.: Med. Klin. 25: 1720, 1929. 16. "~Vitts, L. J.: ]?roc. Roy. See. Meal. 2~: 550, 1931. 17. Minor, G. t{., and Castle, W. B.: Ann. Int. Med. 5: 159~ 1931. 18. Elvehjem, C. A.: J. A. M. A. 98: 1047, 1932. 19. Mackay, ~ . M. M.: Special Reioort Series, Medical Research Council. 9. 157. London, 193]. 20. Keefer, C. S.: Ann. Int. Med. 5: 740. 1931.
TREATMENT
OF
SECONDARY ANEMIA IN CHILDREN JO~N F. CASON, M.D. DUaHA~, N. C. H E value of the administration of copper in conjunction with iron the t r e a t m e n t of secondary anemia has been demonstrated in animals, 1-8 in children, 9, lo, a~, la a n d in adults2 a B u t more, observations are needed on the ratio of copper to iron, and also on the comparison of the effects of cupric and ferric compounds, a n d cuprous and ferrous compounds, because of the reports that the latter are more efficacions.l~, as, 1G Six children suffering f r o m secondary anemia due to malnutrition or infections, whose hemoglobin varied f r o m 40 to 74 p e r cent (average 58.5 p e r cent) on admission were treated. Three times daily they were given f r o m 5 to 10 c.c. (according to their' ages) of a solution containing 0.5 gm. of cupric sulphate a~d 10 gin. of ferric a m m o n i u m citrate p e r 100 c.c. of 25 p e r cent ~romatic elixir solution (U.S.P.). Such a p r e p a r a t i o n can be p r e p a r e d at a cost of less t h a n t w e n t y cents per pint. I n this way, each patient received daily f r o m 10 to, 20 rag. og copper' and :from 250 to 500 rag. oY iron, which is: in. agreement with the dosage of iron f o u n d to be optimal by Minot and Castle. .7 Similar commereiM p r e p a r a t i o n s were considered, but, the m a j o r i t y of these contained less t h a n one-third of these amounts of copper and iron, and the costs were m a n y times higher. Different proportions of copper and iron were used at first in order to determine a palatable: ratio. I t was found that a p r o p o r t i o n (of available eo.pper to iron) higher t h a n 1 to 25 produced nausea and vomiting' in 20 per cent of the patients.
T in
Six children whose secondary anemia was similar to thug of the first group and' whose hemoglobin on admission averaged 63 p e r cent were given cuprous and ferrous g~utamate. ~~ This materiM was made up in capsules each of which eontMned 30 rag. of cuprous glutamate a n d 750 rag. of f e r r o u s glutamate. The dosage was three capsules daily, which provided the same amount of iron as 15 e.c. of the cupric and ferric eomponnd. The ratio of available copper to. iron was 1 to 34. The hemoglobin content of these children was determined at intervals for an average of f o u r weeks b y the Sahli method and recorded on a l~ead b e f o r e t h e S e c t i o n on P e d i a t r i c s of t h e M e d i c a l S o c i e t y of t h e S t a t e of N o r t h C a r o l i n a a t R a l e i g h , N. C., A p r i l 19, 1933. tVrom t h e D e p a r t m e n t of P e d i a t r i c s , D u k e U n i v e r s i t y School of M e d i c i n e , a n d D u k e I-tospital, D u r h a m , N. C. *The c u p r o u s a n d f e r r o u s g l u t a m a t e w a s k i n d l y f m ' n i s h e d to u s f o r t h i s p u r p o s e b y t h e Caleo C h e m i c a l C o m p a n y . 614
CASON:
USE
OF
COPPER
AND
IRON
IN
SECONDARY
ANEMIA
615
percentage basis, 16 gm. hemoglobin per 100 c.c. of blood being regarded as 100 per cent. While the children were in the hospital, examinations were made at least once a week, but those observed in the dispensary had their examinations at longer intervals. P r o b a b l y the curve of rising hemoglobin would have been s h a r p e r in its earlier stages, if determinations h a d been made ~tt more f r e q u e n t intervals. I n the children, whose anemia was due to m a h I u t r i t i o n the hemoglobin content increased rapidly; while in those who had infections, the rise usually did not occur until the infection had subsided. ~s, ~9, 2o As m a y b e
%
< %
14roe A z
G~'aph I.
seen in Gra{)h I, the children treated with tile cupric and ferric compound, and those given the cuprous and f e r r o u s compound showed tile same rate of increase in hemoglobin cmltent, n a m e l y 4.6 per cent per week. CONCLUSION
As f a r as can be judged f r o m this small series observed for a short period of time, a ratio of copper to iron of 1 to 25 is palatable and does not cause nausea; and a cupric and ferric compound is as efficacious in the t r e a t m e n t of secondary anemia in children as is a cuprous and ferrous compound.
616
TKE JOUgNAL 01~ PEDIATRICS REFEREN CES
1. Hart, E. B.; Stcenbock, i t . ; WaddetI, J . ; and Elvehjem, C. A.: J. Biol. Chem. 77: 797, 1928; and 83: 251~ 1929. 2. Waddell, J.; Steenbock, K.; and I-Iart, E. B.: Ibid 84: 115~ 1929. 3. Elvehjem~ C. A.; and Kart~ E. B.: Ibid 95: 363~ 1932. 4. McHargue, J. S.; Healey, D. J . ; and ]~Iill~ E. S.; Ibid 78: 637, 19'28. 5. Lewis, G. T.i WeiehsuIbaum, T. E.; and MeGhee, J. L.: ]?roe. Soc. Exper. Biol. and ivied. 27: 32,9, 1930. 6. Mitehe]l~ ~. 8., and Miller~ L.: J. :Biol. Chem. 92; 42]~ 1931. 7. ]Keil, I{. L.~ and !%lson, V. E. : lbid 93: 49, 1931. 8. Titus, 1~. W.; Cave, ~I. W.; and }[ughes, J. S.: Ibid 80: 565, 1928. 9. Josephs, It. W.: Bull. Johns ~Iopkins Kosp. 49: 246, 1931. 10. Lewis, M. S.: J. A. ~r A. 96: ]135, 193]. 11. Bloxsom, A. ]?.: South. M. J. 25: 401, 1932. 12. ]?arsons, L. G., and ttickmans, E. M.: Arch. Dis. Childhood 8: 85, 1933. 13. Mills~ E. S.: Canad. M. A. J. 22: 175, 1930. 1~. Correa, J. B.; Cruz, L.; and Monteiro de Barros Netto, J. ~.: (Abstract) J. A. ~r A. 100: 591, 1933. 15. Stal'kenstein, E.: Med. Klin. 25: 1720, 1929. 16. "~Vitts, L. J.: ]?roc. Roy. See. Meal. 2~: 550, 1931. 17. Minor, G. t{., and Castle, W. B.: Ann. Int. Med. 5: 159~ 1931. 18. Elvehjem, C. A.: J. A. M. A. 98: 1047, 1932. 19. Mackay, ~ . M. M.: Special Reioort Series, Medical Research Council. 9. 157. London, 193]. 20. Keefer, C. S.: Ann. Int. Med. 5: 740. 1931.