Pernicious anemia, treatment

Treatment of subacute combined degeneration with masmve doses of citrovorum factor did not prevent neurological deterioration (Ungley, unpublished), and it appears very unlikely that this compound will protect the nervous system in pernicious anemia. Treatment with folic acid or citrovorum factor has no effect on the serum Bw levels of patients with pernicious anemia (Mollin and Ross, 1953b). 

Parallel to the activities in the treatment of pernicious anemia were observations in the 1930s that most farm animals had a requirement for an unknown factor beyond the vitamins then known. The lack of this factor became apparent, eg, when chicks or pigs fed a diet with only vegetable protein evidenced slow growth rate and high mortahty. It became apparent that the requited factor, termed animal protein factor, was present in animal sources such as meat and tissue extracts, milk whey, and cow manure. Subsequent to its isolation, it was rapidly shown that vitamin B 2 is the same as animal protein factor. 

Cyano- and hydroxocobalamin - both can be converted to the physiologically relevant coenzymes methyl- and 5 -deoxyadenosylcobalamin in the liver -are used for therapeutical applications. When pernicious anemia caused by chronic atrophic gastritis has been diagnosed, it is treated as follows During the first 7 days of treatment, 1000 pg of hydroxocobalamin/d are administered parenterally, usually intramuscularly. Then, the same dose is given once weekly for 4-6 weeks. The aim is to alleviate the deficiency symptoms and at the same time to replenish the stores. Afterwards, 1000 pg hydroxocobalamin should be given parenterally every 2 months lifelong to avoid relapse [1, 2]. 

The anemias discussed in this chapter include iron deficiency anemia, anemia in patients witii chronic renal disease pernicious anemia, and anemia resulting from a folic acid deficiency. Table 45-1 defines these anemias. Drugp used in treatment of anemia are summarized in die Summary Drug Table Drugp Used in die Treatment of Anemia. 

The chemistry, metabolism, and clinical importance of folic acid have been the subject of many excellent reviews (A7, Gil, H14, H20, Rl). Folic acid deficiency leads to a macrocytic anemia and leucopenia. These symptoms are due to inadequate synthesis of nucleic acid. The synthesis of purine bases and of thymine, required for nucleic acid synthesis, is impaired in folic acid deficiency. Detection of folic acid activity in biologic fluids and tissues is of the utmost importance it distinguishes between the various anemias, e.g., those due to vitamin Bi2 or folic acid deficiency. Because morphology of the abnormal red cell does not help in diagnosing vitamin deficiency, one must rely on assay methods for differential diagnosis. Treatment of pernicious anemia with folic acid has led to subacute combined degeneration of the spinal cord despite... 

Treatment of pernicious anemia and other megaloblastic anemias where vitamin B-12 is deficient (not effective). 

C. The only effective treatment of pernicious anemia is supplementation of vitamin B12.It is important to determine whether megaloblastic anemia is from a deficiency of folic acid or vitamin B12. Treatment of vitamin Bi2-deficient anemia with folic acid may result in neurological damage if vitamin Bi2 is not adequately supplemented. 

Lifetime treatment may be necessary with pernicious anemia... 

Cyanocobalamin A cofactor required for essential enzymatic reactions that form tetrahydrofolate, convert homocysteine to methionine, and metabolize l-methylmalonyl-CoA Adequate supplies are required for amino acid and fatty acid metabolism, and DNA synthesis Treatment of vitamin B12 deficiency, which manifests as megaloblastic anemia and is the basis of pernicious anemia Parenteral vitamin B12 is required for pernicious anemia and other malabsorption syndromes Toxicity No toxicity associated with excess vitamin B12... 

George R. Minot, William P. Murphy, and George H. Whipple Physiology/Medicine Treatment of pernicious anemia... 

In 1926, Minot and Murphy discovered that pernicious anemia could be controlled by eating one-half pound of raw or lightly cooked liver per day, a treatment which not all patients accepted... 

Cobalt must be supplied in the diet in its physiologically active form, vitamin B12. GI absorption of cobalt is about 25%, with wide individual variation excretion occurs mainly via the urine. The major part is excreted within days and the rest has a biological half-life of about two years. Originally, the therapy for pernicious anemia was to have patients eat large amounts of liver. The most reliable treatment now is monthly injections of cobalamin. 

Folic acid is administered orally and should not be used in the treatment of pernicious anemia (see Paul et al., 2004). 

In 1926 Minot and Murphy (4) announced that whole liver was effective in the treatment of pernicious anemia. The initial assay methods, which were clinical (5), coupled with what we now know are the exceptionally small amounts of Bi2 (even in a relatively rich source such as liver) required that two more decades pass before Folkers (6) and Smith (7) in 1948 simultaneously isolated crystalline vitamin Bi2 (1, R = CN). A further decade passed before it was realized that the so-called vitamin (cyanocobalamin) was an artifact of the isolation procedure and that the enzymatically active species is the vitamin Bi2 coenzyme (5 -deoxyadenosylcobalamin, 1, R = 5 -deoxyadenosyl). This initial observation arose during Barkers study on the conversion... 

Vitamin is involved in the manufacture of the red corpuscles of the blood. It can be used for the treatment of pernicious anemia, and it is perhaps the most potent substance known in its physiological activity 1 microgram per day (1 X lO g) of vitamin B g is effective in the control of the disease. The vitamin can be isolated from liver... 

In addition to these, another antibody to intrinsic factor may develop in a certain percentage of pernicious anemia patients, orally treated with hog intrinsic factor concentrate. As shown by Schwartz (S12, S13), this antibody is directed exclusively toward hog intrinsic factor concentrate and not human gastric juice or intrinsic factor derived from the human stomach. Apparently, it causes a topical antibody reaction at the mucosal level, hlocking the promoting action of hog intrinsic factor concentrate on intestinal absorption of vitamin B12 in these pernicious anemia patients. This produces refractoriness to oral treatment with vitamin B12 and hog intrinsic factor concentrate in many pernicious anemia patients (S15). 

The first natural product in which the presence of the metal cobalt (Co) was shown is Vitamin B12 (cobal-aminum). It was isolated from the liver simultaneously by K. Fokers (United States) and Lester Smith (England). The Vitamin B12 structure was established by Todd in 1955. The center of the molecule contains the metal Co(III) with a coordination number 6. It is connected with four mutually bound pyrol cycles. Vitamin Bi2 is used in the treatment of pernicious anemia. 

Epilepsy and osteoporosis are very common and frequently overlap. Nevertheless, the prevalence of low bone density appears to be disproportionately higher in patients with epilepsy, and patients with epilepsy have an excessive risk of fractures. A meta-analysis of 94 cohort studies and 72 case-control studies has shown that anticonvulsant treatment is highly associated with fractures (relative risk over 2) (117). Other risk factors were low body weight, weight loss, physical inactivity, consumption of corticosteroids, primary hjrperparathjroidism, type 1 diabetes melhtus, anorexia nervosa, gastrectomy, pernicious anemia, and age over 70 years. 

Pernicious anemia with a low vitamin B12 concentration and positive intrinsic factor antibodies has been reported in a 54-year-old woman who was receiving interferon alfa as a maintenance treatment for relapsing chronic hepatitis C (219). 

As techniques for structure determination by X-ray diffraction i evolved, molecules of even greater complexity could be studied. Two ilDolecules of special biological interest were penicillin, the important ntibiotic discovered by Alexander Fleming, and vitamin B12, used tin the treatment of pernicious anemia. Several possible structures had kbeen proposed for penicillin, but the / -lactam structure was considered wmlikely by Robert Robinson and John Cornforth from the point of view... 

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