Neurologic Sequelae in Macrocytic Anemia of Gastrointestinal Origin Following Folic Acid Therapy

1948 ◽  
Vol 18 (10) ◽  
pp. 811-814 ◽  
Author(s):  
Leo M. Meyer
Keyword(s):  
Folic Acid ◽  
Macrocytic Anemia ◽  
Acid Therapy ◽  
Neurologic Sequelae

scholarly journals FOLIC ACID IN THE TREATMENT OF PERNICIOUS ANEMIA

Blood ◽  
1947 ◽  
Vol 2 (1) ◽  
pp. 50-62 ◽  
Author(s):  
LEO M. MEYER
Keyword(s):  
Folic Acid ◽  
Pernicious Anemia ◽  
Liver Extract ◽  
Macrocytic Anemia ◽  
Signs And Symptoms ◽  
Well Being ◽  
Blood Picture ◽  
Acid Therapy ◽  
Small Doses ◽  
Symptoms And Signs

Abstract 1. Folic acid in daily doses of 15 to 50 mg., orally, or 20 mg. intramuscularly, usually produced a submaximal reticulocytosis in patients with pernicious anemia. 2. In 3 patients the hemoglobin and red cells rose to a level of about 12.0 Gm. and 4.3 million respectively without further rise after 3 months of therapy. 3. Folic acid in the above doses failed to prevent the development or progression of neurological symptoms indicative of subacute combined sclerosis. 4. In 5 patients folic acid in doses of 5 or 10 mg. orally daily combined with ½ unit of liver extract injected intramuscularly daily produced a reticulocytosis greater than that anticipated from adequate liver extract therapy alone. 5. With combined liver extract and folic acid therapy there was evidence of improvement in the symptoms and signs of subacute combined sclerosis in 3 patients. 6. Folic acid, combined with ½ unit of liver extract, was found to produce a complete hematological remission. 7. Folic acid, alone or in combination with small doses of liver extract, produced an improvement in appetite and general well-being in patients with pernicious anemia. 8. The possible enhancing effect of liver extract when combined with folic acid cannot be due to the folic acid content of the former since 1 unit of liver extract contains only 0.38 micrograms of folic acid.31 9. Folic acid administered to a patient with macrocytic anemia due to faulty postoperative intestinal digestion and absorption, produced a complete remission in the blood picture and a marked improvement in signs and symptoms.

scholarly journals The Effects of Combined Folic Acid and Liver Extract Therapy

Blood ◽  
1951 ◽  
Vol 6 (12) ◽  
pp. 1213-1233 ◽  
Author(s):  
ROBERT B. CHODOS ◽  
JOSEPH F. ROSS
Keyword(s):  
Nervous System ◽  
Folic Acid ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Liver Extract ◽  
Macrocytic Anemia ◽  
Subacute Combined Degeneration ◽  
Acid Therapy ◽  
System Disease ◽  
Gastro Intestinal Tract

Abstract 1. Folic acid, when administered alone, did not prevent the development or progression of subacute combined degeneration in 12 of 22 patients receiving this agent for from twelve to twenty-five months. 2. One patient with total gastrectomy and a macrocytic anemia developed subacute combined degeneration after five months of folic acid therapy. 3. Neurologic disease did not develop in 6 pernicious anemia patients treated with folic acid and liver extract for three and one-half to thirty-nine months. 4. In 10 pernicious anemia patients with good nutrition, neurologic relapses did not progress when liver extract or vitamin B12 therapy was instituted, even though folic acid therapy was continued. In 2 patients with abnormal nutrition and complicating organic abnormalities, nervous system disease progressed after institution of liver extract therapy. 5. Our observations are best explained by the theory that the hematologic and neurologic manifestations of pernicious anemia and other macrocytic anemias associated with gastro-intestinal tract pathology and inadequate nutrition are due to a deficiency of more than one substance. The administration of folic acid may improve the hematologic status but induce a deficiency of another substance or substances, e.g., vitamin B12, which are essential for the maintenance of a normal blood picture and the integrity of the central nervous system. This deficiency will eventually result in the development of a suboptimal blood picture or subacute combined degeneration of the spinal cord, or both. 6. The hematologic status of patients with pernicious anemia is not maintained in a more satisfactory state by supplementation of liver extract or vitamin B12 therapy with folic acid. 7. Folic acid therapy did not produce neurologic disease in patients with iron deficiency anemia who had free gastric hydrochloric acid in their gastric secretions and presumably sufficient intrinsic factor. It did not influence response to ferrous sulfate therapy. 8. Patients with sprue, nutritional macrocytic anemia and other macrocytic anemias associated with gastro-intestinal tract pathology who are treated with folic acid should also be given supplemental liver extract or vitamin B12 to insure against the development of nervous system disease.

Variations in the Lipid Profile of Patients with Chronic Renal Failure, Treated with Folic Acid

2003 ◽  
Vol 73 (3) ◽  
pp. 215-220 ◽  
Author(s):  
de Gómez Dumm ◽  
Giammona ◽  
Touceda
Keyword(s):  
Renal Failure ◽  
Folic Acid ◽  
Chronic Renal Failure ◽  
Density Lipoprotein ◽  
Plasma Homocysteine ◽  
Lipid Profiles ◽  
Erythrocyte Membranes ◽  
Favorable Effect ◽  
High Dose ◽  
Acid Therapy

Dyslipidemia and increases in plasma homocysteine usually occur at end-stage renal disease; both are recognized as risk factors for atherosclerosis. Folate administration reduces homocysteine concentration. In this study we determined the effect of a high dose of folic acid (40 mg intravenous injection three times a week) on plasma and red blood cell lipid profiles in twelve chronic renal failure patients on regular hemodialysis. Fasting blood samples were taken at the beginning of the study (baseline) and after 21, 42, and 64 days of treatment. Folic acid supplementation decreased plasma homocysteine. Plasma triglyceride levels decreased whereas polyunsaturated fatty acid values increased after 21 days; then they returned to baseline levels at the end of treatment. Total cholesterol and low-density lipoprotein (LDL) cholesterol were higher than those of the baseline during all the study, whereas high-density lipoprotein (HDL) cholesterol was reduced. In erythrocyte membranes, folic acid therapy enhanced cholesterol/phospholipid ratios and the fluorescence anisotropy of diphenyl-hexatriene. We conclude that large doses of folic acid produce a favorable effect, reducing plasma homocysteine levels and protecting patients from atherosclerosis. However, as this therapy induces significant alterations in both plasma and erythrocyte membrane lipid profiles, plasma lipid values should be controlled throughout the treatment of patients with renal failure.

Effect of Anticonvulsants on the Uptake of 5-Methyltetrahydrofolic Acid by the Choroid Plexus in Rabbits

1977 ◽  
Vol 53 (1) ◽  
pp. 75-80
Author(s):  
H. Taguchi ◽  
Z. Abdul-Cader ◽  
J. Perry ◽  
E. H. Reynolds ◽  
I. Chanarin
Keyword(s):  
Folic Acid ◽  
Low Temperature ◽  
Choroid Plexus ◽  
Incubation Medium ◽  
Pernicious Anaemia ◽  
Inhibitory Effect ◽  
Anaerobic Conditions ◽  
Acid Therapy ◽  
Pteroylglutamic Acid

1. The isolated choroid plexus of the rabbit takes up 5-methyltetrahydrofolate from the incubation medium. 2. Other folate analogues (pteroylglutamic acid, methotrexate, 5-formyltetrahydrofolate = folinic acid) inhibited the uptake of 5-methyltetrahydrofolate. 3. The uptake of 5-methyltetrahydrofolate was inhibited by low temperature, anaerobic conditions and dinitrophenol. 4. The anticonvulsant drugs, diphenylhydantoin and phenobarbital, had no effect on 5-methyltetrahydrofolate uptake. 5. The inhibitory effect of pteroylglutamic acid on the uptake of 5-methyltetrahydrofolate by the choroid plexus may explain the effect of long-term folic acid therapy in aggravating vitamin B12 neuropathy in pernicious anaemia.

Folic acid therapy in liver-resistant pernicious anemia

2009 ◽  
Vol 130 (S206) ◽  
pp. 315-320
Author(s):  
Tage Espersen ◽  
Jørgen Jørgensen
Keyword(s):  
Folic Acid ◽  
Pernicious Anemia ◽  
Acid Therapy

scholarly journals Efficacy of Folic Acid Therapy in Primary Prevention of Stroke Among Adults With Hypertension in China

JAMA ◽  
2015 ◽  
Vol 313 (13) ◽  
pp. 1325 ◽  
Author(s):  
Yong Huo ◽  
Jianping Li ◽  
Xianhui Qin ◽  
Yining Huang ◽  
Xiaobin Wang ◽  
...  
Keyword(s):  
Folic Acid ◽  
Primary Prevention ◽  
Acid Therapy

scholarly journals Combined vitamin B6 plus folic acid therapy in young patients with arteriosclerosis and hyperhomocysteinemia

1994 ◽  
Vol 20 (6) ◽  
pp. 933-940 ◽  
Author(s):  
Michiel van den Berg ◽  
Diana G. Franken ◽  
Godfried H.J. Boers ◽  
Henk J. Blom ◽  
Cornelis Jakobs ◽  
...  
Keyword(s):  
Folic Acid ◽  
Vitamin B6 ◽  
Young Patients ◽  
Acid Therapy

scholarly journals Experimental Production of Nutritional Macrocytic Anemia in Swine

Blood ◽  
1952 ◽  
Vol 7 (10) ◽  
pp. 992-1004 ◽  
Author(s):  
G. E. CARTWRIGHT ◽  
BETTY TATTING ◽  
DORIS KURTH ◽  
M. M. WINTROBE
Keyword(s):  
Bone Marrow ◽  
Folic Acid ◽  
Vitamin B12 ◽  
Soybean Protein ◽  
Macrocytic Anemia ◽  
Experimental Production ◽  
Vitamin Supplement ◽  
Normal Limits ◽  
Erythroid Hyperplasia ◽  
Pteroylglutamic Acid

Abstract A total of 20 swine were fed a diet adequate in all known respects except that soybean protein was substituted for casein, succinylsulfathiazole and a folic acid antagonist were added, and vitamin B12 and pteroylglutamic acid were withheld from the vitamin supplement. The animals developed macrocytic anemia, leukopenia and neutropenia, accompanied by erythroid hyperplasia of the bone marrow. Tue erythroblasts consisted mainly of immature macronormoblasts but a few atypical megaloblasts were also observed. The anemia responded rapidly and completely to the administration of both vitamin B12 and pteroylglutamic acid. The administration of pteroylglutamic acid alone resulted in an immediate return of the blood and bone marrow to within normal limits but after several months there was a partial hematologic relapse in spite of continued therapy with this vitamin. The administration of vitamin B12 alone resulted in only partial remission of the anemia and the bone marrow remained macronormoblastic although the megaloblasts tended to disappear. Growth of the animals was stimulated by the administration of either vitamin but the administration of both vitamins simultanseously resulted in the greatest rate of growth. No manifestations of neurologic disturbances or of inscreased pigment excretion were observed in the deficient swine.

scholarly journals THE DEVELOPMENT AND PROGRESSION OF SUBACUTE COMBINED DEGENERATION OF THE SPINAL CORD IN PATIENTS WITH PERNICIOUS ANEMIA TREATED WITH SYNTHETIC PTEROYLGLUTAMIC (FOLIC) ACID

Blood ◽  
1948 ◽  
Vol 3 (1) ◽  
pp. 68-90 ◽  
Author(s):  
J. F. Ross ◽  
H. BELDING ◽  
B. L. PAEGEL
Keyword(s):  
Spinal Cord ◽  
Folic Acid ◽  
Pernicious Anemia ◽  
Liver Extract ◽  
Blood Levels ◽  
Rapid Progression ◽  
Neurologic Disease ◽  
Subacute Combined Degeneration ◽  
Acid Therapy ◽  
Oral Doses

Abstract 1. Twenty-one patients with pernicious anemia were maintained on synthetic folic acid (pteroylglutamic acid) therapy alone for periods ranging from eight to seventeen months. Satisfactory blood levels were maintained in all cases receiving daily oral doses of 1.25 to 15.0 mg. Severe hematologic relapse occurred within six months in a case treated with monthly injections of 30 mg. 2. Synthetic folic acid in oral doses of 15 mg. daily induced satisfactory hematopoietic responses in 3 patients with pernicious anemia in severe relapse, but only slight hematopoietic response in a fourth patient with mild pernicious anemia but severe subacute combined degeneration of the spinal cord. 3. Ten patients showed a significant improvement in blood values for a few months after substitution of folic acid for liver extract. With one exception these subsided after six or more months to pre-folic acid levels comparable with those previously maintained with liver extract alone. 4. These observations suggest that a combination of orally administered folic acid and parenterally injected liver extract may maintain a better hematologic status than either substance alone. 5. A previously untreated patient with severe subacute combined degeneration of the spinal cord failed to show improvement in neural disease during twentyeight days of folic acid therapy. 6. Eleven patients developed, or showed progression of, subacute combined degeneration of the spinal cord during folic acid treatment. Neurologic disease developed in most of these patients when the peripheral blood was normal. 7. One patient showed an extremely explosive onset and rapid progression of neural disease. The progression of the disease was rapid in 3 other cases. 8. The institution of liver extract therapy in adddition to folic acid in 5 patients who developed subacute combined degeneration during folic acid maintenance therapy failed to prevent progression of the disease in 4 cases, and only partially arrested the disease in the fifth, in which improvement occurred more rapidly when folic acid was discontinued. 9. Subacute combined degeneration occurred with greater frequency in patients on large daily doses of folic acid than it did in patients with small or intermittent doses. 10. The possibility is discussed that folic acid in large daily doses may actually precipitate or aggravate neurologic disease. 11. It is suggested that folic acid may interfere with the metabolism of 1(+) glutamic acid in the central nervous system and possibly disturb the formation or function of acetylcholine.

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