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Iron metabolism in hemochromatosis. II. Intravenous iron tolerance curves
American
Federation
EFFECT OF THE CITROVORUMFACTOR IN PERNICIOUSANEMIA. R. R. Ellison (by invitation), S.
Wolfe (by invitation), H. Lichtman, V. Ginsberg and J. Watson, Brooklyn, Jv. 2: The effect of the citrovorum factor (C. F.) administered parenteraliy to six patients with Addisonian pernicious anemia has been studied. The C. F. used was material containing 20 million units (3 mg.) per cc. Two patients given 5 million units daily had about half-optimal reticulocyte and red cell rises. Of two patients given 10 million units daily one had a maximal red cell and reticulocyte response and the other suboptimal. Clinical improvement was quite satisfactory. It is thought that 10 million units (1.5 mg.) may be approximately equivalent to 1 U.S.P. unit of liver extract but further study is indicated. Two patients were given aminopterin and PGA parenterally for ten days. In one patient there was no reticulocyte rise until C. F. was substituted for the PGA in a second ten-day period. In the other patient (on half the dose of aminopterin and the same amount of PGA) there was a moderate reticulocyte rise in the first ten-day period but a secondary reticulocyte peak occurred in the second ten-day period in which C. F. was substituted for PGA. It is thought therefore that C. F. is more effective than PGA in reversing the inhibitory effect of aminopterin. One patient who was given 10 million units of C. F. intrasternally showed no enhanced local maturing of megaloblasts at the site of instillation. IRON METABOLISMIN HEMOCHROMATOSIS. II. INTRAVENOUSIRON TOLERANCE CURVES. Stanley
Edward Gitlow, M.D. M.D., Brooklyn, _N. 1:
and Milton
R. Beyers,
A high serum iron with saturation of the ironbinding capacity has been suggested as being diagnostic in hemochromatosis. Intravenous iron tolerance curves were performed in normals, patients with various hematologic disorders, those with cirrhosis and diabetes without hemochromatosis and in four patients with hemochromatosis. The peak of the iron tolerance curve reflects the serum iron-binding capacity. Three of the four patients with hemochromatosis had high fasting serum iron with a high degree of saturation of the iron-binding capacity. One had a normal fasting level with saturation of the iron-binding capacity only slightly above normal. In two of the four, including the latter, the serum iron fell more rapidly from the peak OCTOBER,
1951
for Clinical Research
5**
values than normally and reached subfasting levels, a condition not found in normals. This reflects an increased avidity of the tissues for serum iron, suggesting a further defect in hemochromatosis besides that of the increased gastrointestinal absorption of iron. Determinations of fasting serum iron and serum iron-binding capacity are apparently not always sufficient for the diagnosis of this disease. Pernicious anemia in relapse and pal ycythemia vera may reveal similar abnormalities in the iron tolerance curve. STUDIES ON NITROGEN AND PHOSPHORUSMETABOLISM WITH RELATION TO THE HEMATOLOGIC RESPONSE IN PERNICIOUS ANEMIA PATIENTS AFTER CRYSTALLINE VITAMIN Blz. G. Watson James, III, M.D. and Lynn D. Abbott,
Jr., Ph.D.
(by invitation), Richmond, Vu.
In view of the response in hemoglobin synthesis caused by crystalline vitamin Bi2 in patients with pernicious anemia it was considered desirable to correlate hematologic observations with nitrogen and phosphorus balance studies before and during clinical remission in an attempt to elucidate further the metabolic effects of this substance. Four previously untreated patients with pernicious anemia were studied for several weeks on a constant diet. Positive nitrogen balance as great as 6 gm. per day was produced by vitamin Bi2 in each case. When negative nitrogen balance existed during the control period, it promptly became positive. Individual patients made from 18 to 37 gm. of hemoglobin per day for an average period of eleven days. Nitrogen required for hemoglobin formation alone equalled or exceeded the total nitrogen retained during the corresponding period. The following sequence of biochemical changes was observed: First, a prompt and striking decrease in urinary phosphorus which preceded any change in reticulocyte count; second, increased excretion of uric acid during the upswing of reticulocytes; and third, increased excretion of phosphorus during the period of greatest reticulocytosis. These clinical observations suggest that among the first metabolic effects of vitamin B12 is a profound influence on nucleoprotein synthesis. WEST NILE AND ILHEUS VIRUS INFECTIONSIN PATIENTS WITH NEOPLASTIC DISEASE. Chester
M. Southam, M.D> and Alice E. Moore, M.D., New 2’ork, N Y. West Nile virus and Ilheus virus have been shown by Koprowski and Norton to have an
Federation
EFFECT OF THE CITROVORUMFACTOR IN PERNICIOUSANEMIA. R. R. Ellison (by invitation), S.
Wolfe (by invitation), H. Lichtman, V. Ginsberg and J. Watson, Brooklyn, Jv. 2: The effect of the citrovorum factor (C. F.) administered parenteraliy to six patients with Addisonian pernicious anemia has been studied. The C. F. used was material containing 20 million units (3 mg.) per cc. Two patients given 5 million units daily had about half-optimal reticulocyte and red cell rises. Of two patients given 10 million units daily one had a maximal red cell and reticulocyte response and the other suboptimal. Clinical improvement was quite satisfactory. It is thought that 10 million units (1.5 mg.) may be approximately equivalent to 1 U.S.P. unit of liver extract but further study is indicated. Two patients were given aminopterin and PGA parenterally for ten days. In one patient there was no reticulocyte rise until C. F. was substituted for the PGA in a second ten-day period. In the other patient (on half the dose of aminopterin and the same amount of PGA) there was a moderate reticulocyte rise in the first ten-day period but a secondary reticulocyte peak occurred in the second ten-day period in which C. F. was substituted for PGA. It is thought therefore that C. F. is more effective than PGA in reversing the inhibitory effect of aminopterin. One patient who was given 10 million units of C. F. intrasternally showed no enhanced local maturing of megaloblasts at the site of instillation. IRON METABOLISMIN HEMOCHROMATOSIS. II. INTRAVENOUSIRON TOLERANCE CURVES. Stanley
Edward Gitlow, M.D. M.D., Brooklyn, _N. 1:
and Milton
R. Beyers,
A high serum iron with saturation of the ironbinding capacity has been suggested as being diagnostic in hemochromatosis. Intravenous iron tolerance curves were performed in normals, patients with various hematologic disorders, those with cirrhosis and diabetes without hemochromatosis and in four patients with hemochromatosis. The peak of the iron tolerance curve reflects the serum iron-binding capacity. Three of the four patients with hemochromatosis had high fasting serum iron with a high degree of saturation of the iron-binding capacity. One had a normal fasting level with saturation of the iron-binding capacity only slightly above normal. In two of the four, including the latter, the serum iron fell more rapidly from the peak OCTOBER,
1951
for Clinical Research
5**
values than normally and reached subfasting levels, a condition not found in normals. This reflects an increased avidity of the tissues for serum iron, suggesting a further defect in hemochromatosis besides that of the increased gastrointestinal absorption of iron. Determinations of fasting serum iron and serum iron-binding capacity are apparently not always sufficient for the diagnosis of this disease. Pernicious anemia in relapse and pal ycythemia vera may reveal similar abnormalities in the iron tolerance curve. STUDIES ON NITROGEN AND PHOSPHORUSMETABOLISM WITH RELATION TO THE HEMATOLOGIC RESPONSE IN PERNICIOUS ANEMIA PATIENTS AFTER CRYSTALLINE VITAMIN Blz. G. Watson James, III, M.D. and Lynn D. Abbott,
Jr., Ph.D.
(by invitation), Richmond, Vu.
In view of the response in hemoglobin synthesis caused by crystalline vitamin Bi2 in patients with pernicious anemia it was considered desirable to correlate hematologic observations with nitrogen and phosphorus balance studies before and during clinical remission in an attempt to elucidate further the metabolic effects of this substance. Four previously untreated patients with pernicious anemia were studied for several weeks on a constant diet. Positive nitrogen balance as great as 6 gm. per day was produced by vitamin Bi2 in each case. When negative nitrogen balance existed during the control period, it promptly became positive. Individual patients made from 18 to 37 gm. of hemoglobin per day for an average period of eleven days. Nitrogen required for hemoglobin formation alone equalled or exceeded the total nitrogen retained during the corresponding period. The following sequence of biochemical changes was observed: First, a prompt and striking decrease in urinary phosphorus which preceded any change in reticulocyte count; second, increased excretion of uric acid during the upswing of reticulocytes; and third, increased excretion of phosphorus during the period of greatest reticulocytosis. These clinical observations suggest that among the first metabolic effects of vitamin B12 is a profound influence on nucleoprotein synthesis. WEST NILE AND ILHEUS VIRUS INFECTIONSIN PATIENTS WITH NEOPLASTIC DISEASE. Chester
M. Southam, M.D> and Alice E. Moore, M.D., New 2’ork, N Y. West Nile virus and Ilheus virus have been shown by Koprowski and Norton to have an