levoleucovorin and Anemia--Macrocytic

Topics: Anemia, Macrocytic; Animals; Anticonvulsants; Blood-Brain Barrier; Chemical Phenomena; Chemistry; Epilepsies, Partial; Epilepsy; Folic Acid; Humans; Leucovorin; Mice; Phenobarbital; Phenytoin; Primidone; Rabbits; Rats; Seizures

Thirty elderly patients suffering from macrocytic anaemia associated with chronic diseases were treated with folinic acid for 25 days at a dosage of 4-8 mg daily. For each patient routine laboratory tests have been carried out, the clinical parameters have been recorded at the beginning and at the end of the trial and after 8 days of treatment a possible reticulocyte crisis has been evaluated. The results showed a significant decrease of medium corpuscular volume (MCV), of mean corpuscular haemoglobin (MCH), of iron as well as an increase of folic acid in the serum. After 8 days of treatment a statistically significant reticulocyte crisis was observed.

Topics: Aged; Aged, 80 and over; Anemia, Macrocytic; Drug Evaluation; Female; Humans; Leucovorin; Male; Middle Aged

Topics: Acquired Immunodeficiency Syndrome; Anemia, Macrocytic; Anemia, Megaloblastic; Dapsone; Humans; Leucovorin; Pneumonia, Pneumocystis; Trimethoprim; Vitamin B 12 Deficiency

Megaloblastic anaemia is very rare in the first weeks of life and it is related to impaired metabolism of folic acid or vitamin B12. One of this disorders is the congenital transcobalamin II deficiency. The case of a three month old infant, with vomiting, diarrhoea and severe anaemia is presented. Both parents and the child had very low or undetectable levels of serum TC II, respectively. Using i.m. hydroxycobalamin at high doses, the clinical and laboratory responses have been satisfactory.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Infant; Leucovorin; Male; Transcobalamins; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Arthritis, Psoriatic; Female; Humans; Leucovorin; Methotrexate; Middle Aged

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Leucovorin; Nitrous Oxide; Time Factors

The role of vitamin B12 in the folate dependent biosynthesis of thymidine nucleotides is controversial. In an attempt to clarify this, three methods have been used to assess the relative efficacy of vitamin B12 (hydroxocobalamin) and various folate analogues in titrated concentrations at correcting 'de novo' thymidylate synthesis by megaloblastic human marrow cells: (1) The deoxyuridine (dU) suppression test which analyses the reduction in (3H)-thymidine labeling of DNA by unlabeled dU. Marrow cells were also labeled with (6-3H)-dU with assessment of (2) its incorporation into DNA and (3) the accumulation of (6-3H)-deoxyuridine monophosphate (3H-dUMP). The three methods gave similar results. In both, N6-formyl tetrahydrofolate (formyl-FH4) was the most effective agent at correcting thymidylate synthesis in megaloblastic anemia due to vitamin B12 or folate deficiency. Vitamin B12 corrected the lesion in vitamin B12 deficiency but not in folate deficiency. Tetrahydrofolate (FH4) and folic acid were effective in deficiency of vitamin B12 or folate, although in both deficiencies they were less effective than formyl-FH4. Methyl-FH4 was effective in folate deficiency but not in vitamin B12 deficiency. These results confirm the failure of methyl-FH4 utilisation in vitamin B12 deficiency. They suggest that if vitamin B12 is needed in the formylation of FH4, this is a minor role in provision of the correct coenzyme for thymidylate synthesis compared with its major role of provision of FH4 from methyl-FH4.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow; Deoxyuridine; DNA; Folic Acid; Folic Acid Deficiency; Humans; Leucovorin; Tetrahydrofolates; Thymine Nucleotides; Vitamin B 12; Vitamin B 12 Deficiency

The activities of 5-methyltetrahydrofolate (5-CH3THF) related enzymes and DNA polymerase alpha were determined in bone marrow cells obtained from patients with vitamin B12 deficient megaloblastic anemia and compared with those from healthy volunteers and patients with hemolytic anemia. 5-CH3THF homocysteine methyltransferase activity was significantly lower than that in the control subjects. 5,10-methylenetetrahydrofolate reductase activity was only slightly elevated to that in the control subjects. DNA polymerase alpha activity was significantly higher than that in the control. High deoxyuridine suppression test values in vitamin B12 deficient bone marrow cells were improved by tetrahydrofolate, but not by 5-CH3THF. These data indicate that, even though the reverse reaction catalyzed by 5,10-methylenetetrahydrofolate reductase may be operative in vitamin B12 deficiency, it is not sufficient to correct the disturbance in folate metabolism in vitamin B12 deficiency. Increased DNA polymerase alpha activity may be due to compensation for disarranged DNA synthesis.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; 5,10-Methylenetetrahydrofolate Reductase (FADH2); Adult; Aged; Alcohol Oxidoreductases; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow; Bone Marrow Cells; Deoxyuridine; DNA Polymerase II; DNA-Directed DNA Polymerase; Female; Folic Acid; Humans; Hydroxocobalamin; Leucovorin; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Tetrahydrofolates; Thymidine; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant; Injections, Intramuscular; Intestinal Absorption; Leucovorin; Malabsorption Syndromes; Probenecid

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Drug Combinations; Female; Humans; Leucovorin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Deoxyuridine suppression of labelled thymidine uptake tests were performed in the bone marrows of 58 patients with megaloblastic anaemia (haemoglobin less than 10.0 g/dl) and invariably gave values (range 10.3-58.8%) above the range in 16 control marrows (range 1.0-9.0%). Folinic acid corrected the test equally well in either folate or vitamin B12 deficiency, even at concentrations as low as 60 ng/ml. Folic acid also corrected the test equally well in either deficiency but was only effective at concentrations down to 5 microgram/ml. Vitamin B12 (100 microgram/ml) only corrected the test in vitamin B12 deficiency and 5-methyltetrahydrofolate only corrected the test in folate deficiency at the concentrations tested between 60 and 1.2 microgram/ml. Among 16 patients with subnormal serum levels of both vitamin B12 and folate, vitamin B12 partially corrected the test in eight, including all five with pernicious anaemia, but had no effect in the other eight. Despite the clear-cut results of the dU suppression test, measurement of the deoxythymidine triphosphate (dTTP) concentration in normal and megaloblastic phytohaemagglutinin stimulated lymphocyte cultures or short-term bone marrow cultures gave no clear-cut differences between normal and megaloblastic cells after addition of deoxyuridine nor did the addition of vitamin B12, folic acid or folinic acid either alone or with deoxyuridine produce consistent changes in the dTTP concentration in lymphocytes or bone marrow cells in megaloblastic anaemia. Alcohol caused a rise in deoxyadenosine triphosphate concentration in normal PHA-stimulated lymphocytes which was concentration dependent but caused no consistent change in any of the other three deoxynucleoside triphosphate (dNTP) concentrations. Diphenylhydantoin (10(-3)M, 10(-4)M) had no consistent effect on any of the four dNTP concentrations.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow; Cells, Cultured; Deoxyadenine Nucleotides; Deoxyuridine; DNA; Ethanol; Folic Acid; Humans; Leucovorin; Lymphocytes; Tetrahydrofolates; Thymidine; Thymine Nucleotides; Vitamin B 12

Topics: Adolescent; Anemia, Macrocytic; Anemia, Megaloblastic; Drug Therapy, Combination; Female; Folic Acid; Humans; Infant; Leucovorin; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Ascorbic Acid; Folic Acid; Formates; Humans; Leucovorin; Male; Middle Aged; Scurvy; Tetrahydrofolates

Topics: Administration, Oral; Anemia, Macrocytic; Child; Consanguinity; Female; Folic Acid; Folic Acid Deficiency; Humans; Injections, Intramuscular; Intestinal Absorption; Leucovorin; Metabolism, Inborn Errors; Recurrence; Stomatitis; Vitamin B 12; Yeast, Dried

Topics: Anemia, Macrocytic; Ataxia; Blindness; Central Nervous System; Child, Preschool; Deafness; Female; Fever; Folic Acid; Folic Acid Antagonists; Humans; Infant; Intellectual Disability; Leucovorin; Male; Pyrimethamine

Topics: Anemia, Macrocytic; Azathioprine; Humans; Kidney Transplantation; Leucovorin; Mercaptopurine; Transplantation, Homologous

Topics: Anemia, Macrocytic; Animals; Binding Sites; Biological Assay; Folic Acid; Folic Acid Deficiency; Humans; Lacticaseibacillus casei; Leucovorin; Methods; Milk; Protein Binding; Proteins; Radiometry; Spectrophotometry; Temperature; Tetrahydrofolates; Tritium

Serum disappearance curves in dogs after the intravenous injection of radioactive methotrexate, 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and folic acid followed first-order kinetics with half-disappearance times ranging from 1.3 to 9 hr respectively. Equilibration of spinal fluid tritium levels with those in serum was rapid (3.0 hr) for both of the reduced folates but was not observed at any time after folic acid and methotrexate. The only radioactive folate identified in the spinal fluid after intravenous injection of either 5-formyltetrahydrofolate or folic acid, as well as 5-methyltetrahydrofolate was 5-methyltetrahydrofolate. These findings indicated that 5-methyltetrahydrofolate was taken up preferentially into the spinal fluid and that the other folate congeners were converted to this compound before uptake. Diphenylhydantoin administration did not alter the uptake of 5-methyltetrahydrofolate into the spinal fluid but was associated with reduced renal excretion of this compound.

Topics: Anemia, Macrocytic; Animals; Biological Transport; Blood-Brain Barrier; Carbon Isotopes; Chromatography, Gel; Dogs; Female; Folic Acid; Kinetics; Leucovorin; Male; Phenytoin; Tritium

Topics: Administration, Oral; Adult; Anemia, Macrocytic; Blood Cell Count; Bone Marrow Cells; Diagnosis, Differential; Erythropoiesis; Female; Folic Acid; Humans; Injections, Intramuscular; Intestinal Absorption; Karyometry; Leucovorin; Malabsorption Syndromes; Metabolic Clearance Rate; Parity; Pregnancy; Pregnancy Complications; Xylose

Topics: Administration, Oral; Anemia, Macrocytic; Chromosome Aberrations; Cytogenetics; Diseases in Twins; Evaluation Studies as Topic; Female; Folic Acid; Humans; Infant; Injections; Leucovorin

Topics: Adult; Anemia, Macrocytic; Female; Folic Acid; Folic Acid Deficiency; Hemorrhagic Disorders; Humans; Leucovorin; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Hematologic; Thrombocytopenia

Topics: Anemia; Anemia, Macrocytic; Blood Platelets; Drug Therapy; Folic Acid; Hemoglobinometry; Humans; Leucovorin; Leukocyte Count; Metabolism; Myocarditis; Pigmentation Disorders; Purpura; Purpura, Thrombocytopenic; Pyrimethamine; Sulfonamides; Thrombocytopenia; Toxicology; Toxoplasmosis; Toxoplasmosis, Ocular

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Drug Therapy; Female; Folic Acid; Humans; Leucovorin; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic

Topics: Anemia; Anemia, Macrocytic; Blood; Bone Marrow Examination; Deficiency Diseases; Diarrhea; Diarrhea, Infantile; Folic Acid; Folic Acid Deficiency; Humans; Infant; Infant Nutrition Disorders; Infections; Israel; Leucovorin

Topics: Alcoholic Beverages; Alcoholism; Alkaline Phosphatase; Anemia; Anemia, Macrocytic; Aspartate Aminotransferases; Bilirubin; Blood Chemical Analysis; Blood Proteins; Bone Marrow Examination; Ethanol; Folic Acid; Folic Acid Deficiency; Hematopoiesis; Humans; Iron; Leucovorin; Liver Function Tests; Pharmacology; Reticulocytes; Toxicology

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Ascorbic Acid; Asian People; Blood Chemical Analysis; Bone Marrow Examination; Dietary Carbohydrates; Dietary Proteins; Folic Acid; Folic Acid Deficiency; Leucovorin; Lipids; Myanmar; Vitamin B 12

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Folic Acid; Humans; Leucovorin

Topics: Anemia; Anemia, Macrocytic; Folic Acid; Hematinics; Humans; Leucovorin; Vitamin B 12