Determination of Folic Acid Metabolites in Normal Subjects and in Patients with Nutritional Megaloblastic Anemia.

Abstract 1. In 9 patients with various types of megaloblastic anemia responding to treatment with vitamin B12, folic acid or liver extract, no significant deviations from the normal amounts of total or polymerized DNA were observed in the nuclei of red blood cells in marrow smears. 2. During the maturation of megaloblasts in the bone marrow there is a gradual loss of nuclear DNA. 3. This pattern is quantitatively and qualitatively similar for normal marrow and for that of pernicious anemia in relapse and after treatment.

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Differentiation between Vitamin B12—deficient and Folic Acid—deficient Megaloblastic Anemias with C14—Histidine

Blood ◽

10.1182/blood.v21.4.447.447 ◽

1963 ◽

Vol 21 (4) ◽

pp. 447-461 ◽

Cited By ~ 22

Author(s):

MATHEWS B. FISH ◽

MYRON POLLYCOVE ◽

THOMAS V. FEICHTMEIR

Keyword(s):

Folic Acid ◽

Vitamin B12 ◽

Specific Activity ◽

Megaloblastic Anemia ◽

Vitamin B12 Deficiency ◽

Normal Subjects ◽

Intermediary Metabolism ◽

Folic Acid Deficiency ◽

Acid Deficiency ◽

B12 Deficiency

Abstract Intermediary metabolism of the monocarbon pool and histidine in normal subjects and patients with megaloblastic anemia was studied by continuous measurement of pulmonary excretion of C14O2 and urinary excretion of C14 after injection of L-histidine-2(ring)-C14. Cumulative pulmonary and renal excretion of C14 for 1 month by two normal subjects approximates 45 per cent of the amount injected. Within 4 months after injection of the dose used in this study, the resultant average tissue radiation decreases below the average natural terrestrial and cosmic radiation level. Simultaneous determination of two parameters, (1) cumulative 1-hour pulmonary C14 excretion and (2) the time of occurrence of maximum C14O2specific activity (Tmax), may permit rapid and unequivocal differentiation between folic acid deficiency and vitamin B12 deficiency in the pathogenesis of megaloblastic anemia. Folio acid deficiency results in marked diminution of pulmonary C14 excretion (approximately 0.1 per cent of injection C14 in 1 hour) and marked prolongation of C14O2-specific activity Tmax (approximately 3 hours), while both parameters are normal (approximately 1 per cent and less than 1 hour, respectively) in patients with vitamin B12 deficiency and megaloblastic anemia. Measurement during periods of reticulocyte response to either folio acid or vitamin B12 demonstrate normal C14O2-specific activity Tmax but decreased pulmonary C14 excretion. These observations suggest that prolongation of C14O2-specific activity Tmax is a sensitive index of folic acid deficiency or block and that if Tmax is normal, pulmonary C14 excretion is a sensitive index of the relative partition of the active monocarbon pool between pathways for oxidation and pathways for nucleic acid synthesis. This type of breath analysis seems to provide a quantitative dynamic representation of metabolic function which may be particularly useful in differentiating between the alterations of intermediary metabolism that occur in patients with folic acid-deficient megaloblastic anemia and in patients with vitamin B12-deficient megaloblastic anemia.

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Cyanocobalamin, Ascorbic Acid and Pteroylglutamates in Normal and Megaloblastic Bone Marrow

Blood ◽

10.1182/blood.v15.3.376.376 ◽

1960 ◽

Vol 15 (3) ◽

pp. 376-387 ◽

Cited By ~ 8

Author(s):

E. V. COX ◽

D. M. MATTHEWS ◽

M. J. MEYNELL ◽

W. T. COOKE ◽

R. GADDIE

Keyword(s):

Bone Marrow ◽

Ascorbic Acid ◽

Folic Acid ◽

Pernicious Anemia ◽

Megaloblastic Anemia ◽

Normal Subjects ◽

Causative Factor ◽

Buffy Coat ◽

Plasma Ascorbic Acid ◽

Therapeutic Implications

Abstract The B12 activity as estimated by Lactobacillus leichmannii, the folic-acid-like activity by Streptococcus faecalis (F.A.A.) and the ascorbic acid concentration have been determined in the blood and buffy coat of bone marrow of normal subjects, 10 patients with pernicious anemia in relapse, a group of patients with non-Addisonian megaloblastic anemia and some patients with iron deficiency. A correlation between the serum B12 and the plasma ascorbic acid and their respective levels in bone marrow was observed. The marrow and serum B12 levels in prenicious anemia were abnormally low, but they did not differ from a group of 5 patients with hypochromic normoblastic anemia who had both low serum and marrow levels. The concentration of F.A.A. in the marrow of patients with pernicious anemia was reduced, but it was felt that this was more likely a manifestation of the megaloblastic anemia rather than a causative factor. One of six patients with megaloblastic anemia of pregnancy had no detectable deficiency, while the other five had reduced B12, folic acid and ascorbic acid concentrations. The possible therapeutic implications are discussed. There was a significant reduction in the bone marrow concentration of ascorbic acid in all patients with megaloblastic anemia.

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Megaloblastic Anemia of Pregnancy in Two Sisters

Blood ◽

10.1182/blood.v10.9.933.933 ◽

1955 ◽

Vol 10 (9) ◽

pp. 933-940 ◽

Cited By ~ 4

Author(s):

JAMES W. HOLLINGSWORTH ◽

FAE M. ADAMS

Keyword(s):

Folic Acid ◽

Megaloblastic Anemia ◽

Normal Subjects ◽

Sodium Chromate ◽

Before And After ◽

Radioactive Sodium

Abstract 1. Two sisters with megaloblastic anemia of pregnancy were reported. 2. Erythrocytes from the patients, both before and after therapy with folic acid, were tagged with radioactive sodium chromate and injected into normal subjects. The results of these studies were discussed.

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Determination of Factor XIII Activity and of Factor XIII Inhibitors Using an Ammonium-Sensitive Electrode

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665256 ◽

1983 ◽

Vol 50 (02) ◽

pp. 563-566 ◽

Cited By ~ 3

Author(s):

P Hellstern ◽

K Schilz ◽

G von Blohn ◽

E Wenzel

Keyword(s):

Factor Xiii ◽

Normal Subjects ◽

The Other ◽

Activity Measurement ◽

Factor Xiii Deficiency ◽

Assay Procedure ◽

Stabilization Factor ◽

Release Method ◽

Sensitive Electrode

SummaryAn assay for rapid factor XIII activity measurement has been developed based on the determination of the ammonium released during fibrin stabilization. Factor XIII was activated by thrombin and calcium. Ammonium was measured by an ammonium-sensitive electrode. It was demonstrated that the assay procedure yields accurate and precise results and that factor XIII-catalyzed fibrin stabilization can be measured kinetically. The amount of ammonium released during the first 90 min of fibrin stabilization was found to be 7.8 ± 0.5 moles per mole fibrinogen, which is in agreement with the findings of other authors. In 15 normal subjects and in 15 patients suffering from diseases with suspected factor XIII deficiency there was a satisfactory correlation between the results obtained by the “ammonium-release-method”, Bohn’s method, and the immunological assay (r1 = 0.65; r2= 0.70; p<0.01). In 3 of 5 patients with paraproteinemias the values of factor XIII activity determined by the ammonium-release method were markedly lower than those estimated by the other methods. It could be shown that inhibitor mechanisms were responsible for these discrepancies.

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GASCHROMATOGRAPHIC DETERMINATION OF STEROIDS IN THE URINE OF PATIENTS WITH CUSHING'S SYNDROME

Acta Endocrinologica ◽

10.1530/acta.0.0670303 ◽

1971 ◽

Vol 67 (2) ◽

pp. 303-315 ◽

Cited By ~ 14

Author(s):

A. J. Moolenaar ◽

A. P. van Seters

Keyword(s):

Liquid Chromatography ◽

Cushing’S Syndrome ◽

Normal Subjects ◽

Diagnostic Value ◽

Cushing's Syndrome ◽

Gas Liquid Chromatography ◽

Obese Subjects

ABSTRACT The 17-oxosteroids were estimated in the urine of 27 patients with Cushing's syndrome by gas-liquid chromatography (G. L. C.). The values of the various steroid fractions are compared with those of normal subjects, patients with thyrotoxicosis and obese subjects. The effect of the age of the patients on the diagnostic value of the invidual 17-oxosteroids and their ratios is discussed.

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SIMPLIFIED DEXAMETHASONE SUPPRESSION TEST

Acta Endocrinologica ◽

10.1530/acta.0.0610219 ◽

1969 ◽

Vol 61 (2) ◽

pp. 219-231 ◽

Cited By ~ 14

Author(s):

V. H. Asfeldt

Keyword(s):

Cushing’S Syndrome ◽

Normal Subjects ◽

Cushing's Syndrome ◽

Dexamethasone Suppression Test ◽

Clinical Value ◽

Suppression Test ◽

The One ◽

Steroid Excretion ◽

Dexamethasone Suppression

ABSTRACT This is an investigation of the practical clinical value of the one mg dexamethasone suppression test of Nugent et al. (1963). The results, evaluated from the decrease in fluorimetrically determined plasma corticosteroids in normal subjects, as well as in cases of exogenous obesity, hirsutism and in Cushing's syndrome, confirm the findings reported in previous studies. Plasma corticosteroid reduction after one mg of dexamethasone in cases of stable diabetes was not significantly different from that observed in control subjects, but in one third of the insulin-treated diabetics only a partial response was observed, indicating a slight hypercorticism in these patients. An insufficient decrease in plasma corticosteroids was observed in certain other conditions (anorexia nervosa, pituitary adenoma, patients receiving contraceptive or anticonvulsive treatment) with no hypercorticism. The physiological significance of these findings is discussed. It is concluded that the test, together with a determination of the basal urinary 17-ketogenic steroid excretion, is suitable as the first diagnostic test in patients in whom Cushing's syndrome is suspected. In cases of insufficient suppression of plasma corticosteroids, further studies, including the suppression test of Liddle (1960), must be carried out.

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DETERMINATION OF BLOOD CORTICOIDS USING THE IN VITRO RESIN UPTAKE OF 3H-PREDNISOLONE

Acta Endocrinologica ◽

10.1530/acta.0.0570023 ◽

1968 ◽

Vol 57 (1) ◽

pp. 23-32 ◽

Cited By ~ 2

Author(s):

Hironori Nakajima ◽

Mitsunori Murala ◽

Masumitsu Nakata ◽

Takeshi Naruse ◽

Seiji Kubo

Keyword(s):

Thyroid Function Test ◽

Normal Subjects ◽

Adrenal Function ◽

Function Test ◽

Before And After ◽

Adrenal Response ◽

Suppression Test

ABSTRACT The in vitro resin uptake of 3H-prednisolone was used for the determination of blood cortisol after addition of radioactive prednisolone followed by Amberlite CG 400 Type 1 to the test serum, and incubation of the mixture. The radioactivity of the supernatant was compared before and after the addition of the resin. The principle of this method is similar to that of the 131I-triiodothyronine resin uptake for the thyroid function test. The tests for the specificity, reproducibility and sensitivity gave satisfactory results. The mean basal value ± SD of the 3H-prednisolone resin uptake was 35.3 ± 9.2% in normal subjects, and 27.1 ± 4.8% in pregnant women. This method was valid in various adrenal function tests, i. e. the adrenal circadian rhythm, corticotrophin (ACTH) test, dexamethasone suppression test and the adrenal response to lysine-8-vasopressin. It proved to be a sensitive indicator of the adrenal function. These results suggest that this method should be useful for a routine adrenal function test.

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