scholarly journals Some Aspects of the Metabolism of Antimegaloblastic Substances in Man

Blood ◽  
1953 ◽  
Vol 8 (5) ◽  
pp. 469-485 ◽  
Author(s):  
RONALD H. GIRDWOOD
Keyword(s):  
Folic Acid ◽  
Hydrochloric Acid ◽  
Serum Level ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Gastric Juice ◽  
Free Hydrochloric Acid ◽  
Related Substance ◽  
Pteroylglutamic Acid

Abstract 1. When the sera of pernicious anemia patients or controls were heated at 100 C. for 30 minutes, they developed the ability to support the growth of L. leichmannii by virtue of some substance other than vitamin B12. It seemed likely, however, that following the administration of the vitamin, such heating also liberated free B12 in the serum from a combined form. 2. The L. leichmannii assay did not appear to be satisfactory for showing possible difference in the levels of vitamin B12 in the urines or sera of pernicious anemia patients and controls. 3. Parenterally administered vitamin B12 did not cause any measurable rise in the serum level of folic acid or citrovorum factor in pernicious anemia patients or controls. 4. The synthetic folic acid conjugates pteroyldiglutamic acid and pteroyltriglutamic acid appeared in the sera and urines of pernicious anemia patients as pteroylglutamic acid or some related substance with folic acid activity for S. faecalis. 5. Orally administered citrovorum factor appeared to be largely converted by the gastric juice to folic acid if free hydrochloric acid was present. When administered parenterally, however, citrovorum factor was excreted in the urine largely unchanged.

scholarly journals PERNICIOUS ANEMIA IN CHILDHOOD REPORT OF CASE IN SIX YEAR OLD GIRL RESPONDING TO REFINED LIVER EXTRACT, FOLIC ACID AND VITAMIN B12 IN SUCCESSIVE RELAPSES

Blood ◽  
1949 ◽  
Vol 4 (12) ◽  
pp. 1361-1366 ◽  
Author(s):  
R. WENDELL DAVIS ◽  
RICHARD M. CHRISTIAN ◽  
DONALD M. ERVIN ◽  
LAWRENCE E. YOUNG
Keyword(s):  
Folic Acid ◽  
Hydrochloric Acid ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Gastric Juice ◽  
Liver Extract ◽  
Megaloblastic Anemia ◽  
Free Hydrochloric Acid ◽  
Neurologic Complications ◽  
Hematologic Response

Abstract A case of megaloblastic anemia without specific neurologic complications in a 6 year old girl is presented as an example of pernicious anemia in childhood despite the fact that a small amount of free hydrochloric acid was present in the gastric juice after injection of histamine. Prompt hematologic response was obtained following administration of refined liver extract, folic acid and vitamin B12 in successive relapses.

scholarly journals A Case of Juvenile Pernicious Anemia: Study of the Effects of Folic Acid and Vitamin B12

Blood ◽  
1961 ◽  
Vol 17 (5) ◽  
pp. 618-631 ◽  
Author(s):  
DAVID H. CLEMENT ◽  
CHARLES A. NICHOL ◽  
ARNOLD D. WELCH
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Gastric Juice ◽  
Intrinsic Factor ◽  
Later Life ◽  
Free Hydrochloric Acid ◽  
Specific Therapy ◽  
Sequence Of Events ◽  
Almost All

Abstract Observations on a 4-year-old boy with Addisonian pernicious anemia have been presented. Noteworthy clinical features included the onset of glossitis at the age of 4 months, followed by anemia severe enough to require hospitalization at the age of 1 year. Relapse occurred in the absence of specific therapy with vitamin B12 and was completely unaffected by the administration of folic acid. Studies with radioactive vitamin B12 demonstrated that almost all of the compound administered by mouth was unabsorbed and was recovered in the stools. When the vitamin was given simultaneously with a concentrate of intrinsic factor, however, approximately 70 per cent was absorbed. Furthermore, the child’s gastric juice, when mixed with radioactive vitamin B12 and fed to an adult with pernicious anemia in relapse, failed to enhance the latter’s absorption of the vitamin. The failure of our patient to absorb the vitamin alone, but his ability to do so when it was administered with intrinsic factor concentrate, was also confirmed by the "Schilling test," in which a proportion of the absorbed radioactive vitamin was "flushed" into the urine by parenteral injection of one milligram of conventional vitamin B12. Of special interest was the occurrence in the urine of an unidentified derivative of tetrahydrofolic acid, derived from orally administered pteroylglutamic acid. The presence of this compound in the urine was demonstrated chromatographically when the patient was critically ill with his disease prior to treatment with vitamin B12. Subsequent to therapy with vitamin B12, while the administration of folic acid was continued, the abnormal metabolite of folic acid could not be found in the urine. Similarly, the administration of folic acid did not lead to the appearance of this metabolite in the urine at a time when, after more than two years without specific therapy, a hematological relapse occurred that was much less severe than that previously observed. The implications of these observations, with respect to the metabolic interrelationships of folic acid and vitamin B12, are discussed. Of further interest were the findings of strongly acid gastric juice containing much mucus and free hydrochloric acid. A fairly normal gastric mucosa was demonstrated by biopsy. The meaning of these unusual findings is discussed and an hypothesis to account for them is offered. The probable sequence of events in these patients from childhood to the development of anemia, usually in later life, is set forth.

scholarly journals Pernicious Anemia without Gastric Atrophy and in the Presence of Free Hydrochloric Acid

Blood ◽  
1957 ◽  
Vol 12 (5) ◽  
pp. 461-468 ◽  
Author(s):  
J. N. HARRIS-JONES ◽  
H. T. SWAN ◽  
G. R. TUDHOPE
Keyword(s):  
Hydrochloric Acid ◽  
Gastric Mucosa ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Gastric Juice ◽  
Intrinsic Factor ◽  
Gastric Atrophy ◽  
Free Hydrochloric Acid ◽  
Normal Gastric Mucosa ◽  
Factor Activity

Abstract A case is described of Addisonian pernicious anemia in a girl aged 16 years, associated with a normal gastric mucosa and free hydrochloric acid in the stomach. Partial, but significant deficiency of intrinsic factor activity was demonstrated in her gastric juice by the use of Co56-labeled vitamin B12.

scholarly journals PERNICIOUS ANEMIA FROM ADDISON TO FOLIC ACID

Blood ◽  
1948 ◽  
Vol 3 (6) ◽  
pp. 702-702
Author(s):  
RUSSELL L. HADEN
Keyword(s):  
Folic Acid ◽  
Hydrochloric Acid ◽  
Pernicious Anemia ◽  
Free Hydrochloric Acid

Abstract The editorial footnote in "Pernicious Anemia from Addision to Folic Acid," by Dr. Russell L. Haden, in the January Blood (3:-24, 1948) should have read: "Wilkinson and Israëls, Waldenström and others report that free hydrochloric acid occurs in approximately 1 case of 100." The term "achlorhydria" was used in error.

scholarly journals THE INTESTINAL CONTENT IN PERNICIOUS ANEMIA OF FACTORS FOR THE GROWTH OF STREPTOCOCCUS FAECALIS AND LACTOBACILLUS LEICHMANNII

Blood ◽  
1950 ◽  
Vol 5 (11) ◽  
pp. 1009-1016 ◽  
Author(s):  
RONALD H. GIRDWOOD
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Gastric Juice ◽  
Large Intestine ◽  
Intestinal Content ◽  
Daily Output ◽  
Pteroylglutamic Acid ◽  
Consistent Increase ◽  
Small Intestinal ◽  
Lactobacillus Leichmannii

Abstract The gastric juice and small intestinal secretions of three cases of untreated pernicious anemia and two control patients obtained during a period of fasting contained only very small amounts of pteroylglutamic acid or of factors for the growth of L. leichmannii, which include vitamin B12; there was no evidence of a consistent increase or decrease of these factors along the intestine. Both pteroylglutamic acid and vitamin B12 appear to be synthesized in relatively large amounts in the large intestine; in a patient with pernicious anemia, the daily output in the stools may be about 5 micrograms of vitamin B12 and 0.5 mg. of pteroylglutamic acid. Similar quantities may be present in patients not suffering from this disorder.

JUVENILE PERNICIOUS ANEMIA

PEDIATRICS ◽  
1951 ◽  
Vol 8 (1) ◽  
pp. 88-106
Author(s):  
EDWARD H. REISNER ◽  
JAMES A. WOLFF ◽  
R. JAMES MCKAY ◽  
EUGENIA F. DOYLE
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Gastric Juice ◽  
Liver Extract ◽  
Macrocytic Anemia ◽  
Intrinsic Factor ◽  
The Other ◽  
Free Hydrochloric Acid ◽  
Laboratory Findings ◽  
Gastric Contents

Histories have been presented of two pairs of sibling children with recurrent macrocytic anemia with megaloblastic bone marrow responding specifically to liver extract and vitamin B12. The clinical features and laboratory findings were similar to those of adult pernicious anemia in every respect except for the inconstant presence of histamine refractory achlorhydria. All the patients responded to vitamin B12 given parenterally, but in three to whom it was given by mouth no response was obtained. Two of these subsequently responded to oral B12 when it was accompanied by normal gastric juice. The other two developed histamine refractory achlorhydria while in hematologic remission. This is interpreted as proof that the anemia was due to deficient intrinsic factor in the gastric juice. Three patients showed evidence of disease of the spinal cord, in two of whom the symptoms were severe. These symptoms were compatible with a diagnosis of dorsolateral sclerosis, and improved with antipernicious anemia therapy. In one of these patients, treated with folic acid, the neurologic lesions were aggravated severely. Pernicious anemia due to the absence of gastric juice intrinsic factor occurs in children. The presence of free hydrochloric acid in the gastric contents does not preclude the possibility of the disease.

New reaction for free hydrochloric acid

1906 ◽  
Vol 6 (1) ◽  
pp. 58-58
Author(s):  
F. Simon
Keyword(s):  
Nitric Acid ◽  
Hydrochloric Acid ◽  
Gastric Juice ◽  
Free Hydrochloric Acid ◽  
Blue Coloration

For the discovery of free hydrochloric acid in gastric juice, Dr. Simon proposes a new reaction based on the properties of guaiac gum to oxidize in the presence of various oxidants (for example, nitric acid) and give a characteristic blue coloration.

VARIABLE RESPONSE TO VITAMIN B12 OF MEGALOBLASTIC ANEMIA OF INFANCY

PEDIATRICS ◽  
1949 ◽  
Vol 4 (6) ◽  
pp. 723-729
Author(s):  
CALVIN W. WOODRUFF ◽  
HOWARD W. RIPY ◽  
J. CYRIL PETERSON ◽  
WILLIAM J. DARBY
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Megaloblastic Anemia ◽  
Variable Response ◽  
Pteroylglutamic Acid

Two cases of megaloblastic anemia in infancy have improved following treatment with vitamin B12. A third case failed to respond to this factor but subsequently responded to pteroylglutamic acid (folic acid). It is suggested that megaloblastic anemia may be a syndrome which embraces more than one entity.

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.

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