Clinical and experimental studies on folic acid deficiency due to anticonvulsants. I. Clinical and nutritional study on megalobastic anemia due to anticonvulsants

Two cases of megaloblastic anemia associated with anticonvulsant drugs were studied. Both cases were inpatients of psychiatric hospitals and had quite inadequate intakes of food. The former had lung tuber. culosis and the second had febril illness before the manifestation of anemia. Multiple examinations including bone marrow smears, serum iron levels, vitamin B12 levels, estimation of urinary formiminoglutamic acid after histidine loading and folic acid tolerance test revealed that this anemia was due to folic acid deficiency. Complete hematological responses were ob3erved with injection of folic acid. Retrospective nutritional study on the second case was carried out. The study revealed that folic acid content of the diet of this hospital was 152 fl.g of free folate and 522 fl.g of total folate. The folic acid mtake of the patient was about 80 /1.g of free folate and 280 l1.g of total folate daily during a month before the manifestation of megaloblatic anemia. Importance of additional factors for the development of megaloblastic anemia in patients receiving anticonvulsants was discussed and it was concluded that most important factor was nutritional deficiency of folic acid.</p

An investigation into folate deficiency in healthy underprivileged infants with special emphasis on the interpretation of the Figlu test after oral histidine

In South Africa, as: in other countries with a large underprivileged population group, the problem of malnutrition and its- associations and complications assumes considerable importance. Until the socioeconomic problems involved are solved, attention must be directed to early diagnosis, treatment and prophylaxis of malnutrition and its associations. At the Red Cross Children's Hospital, Cape Town, a considerable percentage of admissions are for marasmus and kwashiorkor. Anemia is a frequent association, (Walt, I.959) sometimes contributing to the mortality (Walt, Holman and Naidoo, 1957)

Safety and benefits of interventions to increase folate status in malaria-endemic areas.

For decades, folic acid has routinely been given to prevent or treat anaemia in children, pregnant women and people with sickle cell disease. However, there is no conclusive evidence that folate deficiency anaemia constitutes a public health problem in any of these groups. Industrial flour fortification is recommended and implemented in many countries to combat neural tube defects. Dietary folates or folic acid can antagonise the action of antifolate drugs that play a critical role in the prevention and treatment of malaria. Randomised trials have shown that folic acid supplementation increases the rate of treatment failures with sulfadoxine-pyrimethamine. The efficacy of antifolate drugs against Plasmodium is maximized in the absence of exogenous folic acid, suggesting that there is no safe minimum dose of ingested folic acid. We here review the safety and benefits of interventions to increase folate status in malaria-endemic countries. We conclude that formal cost-benefit analyses are required

Studies on the folate polyglutamyl components of human diets

Imperial Users onl

Observations on haemolytic disease

1. The thesis has considered the investigation of haemolytic disease and has discussed observations on seventy-six patients regarding the pathogenesis, natural history and management of excessive red cell destruction in the three conditions that are most commonly encountered in Great Britain, namely autoimmune haemolytic anaemia, symptomatic non-immune haemolytic anaemia and congenital spherocytosis. 2. The clinical features and the diagnostic value of routine examination of the peripheral blood, bone marrow and urine for signs of anaemia, reticulocytosis and acholuric jaundice, the classical indicators of haemolysis, are described in each group. Where applicable, study has been made of the role of serological investigation and of tests of red cell fragility. Since measurements of red cell survival using chromium - 51 as an erythrocyte label have formed a major interest, they have been considered in detail. The technique has been examined for reproducibility, studied in normal subject and various chronic and haematological diseases and compared simultaneously with the Ashby method. It was decided to use the TIC/. (the time in days when 50 per cent of the injected 51Cr has been cleared from the circulation) as the basis for comparison between data. The procedure for estimating the role of the spleen in a haemolytic process by measuring its uptake of radioactivity, due to sequestration of 51Cr labelled red cells, has been widely applied. The spleen sequestration index (the percentage increment in radioactivity over the surface of the spleen between the start of the test and T2Cr) and the spleen /liver ratio at TzCr have been used, but neither adequately describes the implication of the spleen; the former ignores any liver uptake of radioactivity and the latter does not take account of high blood flow through the spleen. Accordingly a new measurement, the Spleen Number, a multiple of the spleen sequestration index and the spleen/ liver ratio at TiCr has been proposed. 3. In the group of patients with autoimmune haemolytic anaemia, apart from two subjects with the cold haemagglutin syndrome, the nature of the red cell antibody has not clearly influenced the course of disease or its response to treatment. Blood transfusion has been used freely without incident; one patient required more than 40 litres in six weeks for survival. All patients received steroid therapy at some stage of their management; the dilemma that arises when response is poor or when the steroid preparation cannot be withdrawn to an acceptable maintenance level has been well illustrated; approximately one third of the patients had major complications from steroid therapy. Splenectomy was recommended in nine of the twenty-three patients; only one of these had a good result from operation while three others had a partial remission. From the data that are available a high Spleen Number (exceeding 300) appears to offer prospect of remission from splenectomy; it is also of interest that high Spleen Numbers were seen in those who had the best remissions from steroid therapy. The course of autoimmune haemolytic anaemia followed three paths; self limiting disease, chronic relapsing disease and fulminating, potentially fatal, disease. Three unique patients were considered in detail. The first died in infancy of a peculiar haemophagocytic reticulosis that had earlier killed two of his three siblings. The second was observed for several years; she was a good example of the chronic relapsing variety of illness and required sterol therapy only during exacerbations of anaemia; the haemolyti process was constantly active and during this time she had two normal pregnancies, in the second of which she was given large doses of prednisone in the first trimester without ill effects; she had two crises of anaemia, one while receiving folic acid supplements and one which was believed to be due to folic acid deficiency. The third patient developed a violent haemolytic process while being treated with prednisone for idiopathic thrombocytopenia, previously cured by splenectomy. Some influence on the condition was achieved by irradiation of the thymus; haemolysis was eventually arrested and the thrombocytopenia corrected by the combined use of the new antineoplastic agents, Actinomycin-C and BW 57 -322 (Imuran). 4. Studies on symptomatic non - immune haemolytic anaemia have been confined to patients with leukaemia, reticulosis and myeloid metaplasia. The usual signs of overt haemo- lysis, reticulocytosis and acholuric jaundice, were found in only one patient, despite markedly reduced red cell survival in many in the group. Neither splenomegaly nor its degree correlated with severity of red cell destruction or with the splenic uptake of 51Cr labelled red cells; all grades of splenic sequestration were found, the Spleen Numbers ranging from 26 to 1056. Irradiation of the spleen caused a valuable reduction in haemolysis in some patients, but this effect was not related to the Spleen Number; the role of this form of treatment has been discussed. Two patients in this group were subjected to autopsy shortly after red cell survival measurement with chromium -51 and it was possible to estimate the content of radioactivity in most body tissues. There was good agreement between the spleen /liver ratio at autopsy and that obtained earlier in vivo at T2Cr. The data from one of the patients suggest that the marrow may be a much more important site of erythroclasis than is generally realised. 5. Congenital spherocytosis was encountered over a wide range of age from the first months of life to sixty -two years. There were all grades of severity and many differen modes of presentation; there was a small incidence of menta defect, developmental anomaly, miscarriages and chronic dermatosis of the legs and this has been described. Only five patients (23 %) had gall stones. One simple point emerged that might be useful in the early steps towards diagnosis; the E.S.R. tends to be low in this condition and very high in autoimmune haemolytic anaemia, the only other haemolytic disorder which is commonly accompanied by sphero- cytosis. Splenectomy has been undertaken in all but four patient who have mild well compensated disease. Removal of the spleen appears to have arrested haemolysis in all but one patient who died in the post -operative period; red cell survival has returned to normal in the eight patients in whom this has been measured. Observations have been made which support the view that the role of the spleen in congenital spherocytosis is to "condition" the red cells and critically increase their spheroidicity and fragility rather than to destroy them; these show improvement in the osmotic fragility of red cells after splenectomy, some delay in the correction of red cell survival after operation and lower Spleen Numbers than have been encountered in some of the patients with acquired disease. Hypocholesterolaemia in untreated patients with congenital spherocytosis has been an incidental finding. The values for plasma cholesterol after the haemolytic process has been arrested by splenectomy are normal. 6. Megaloblastic erythropoiesis has been observed in seven patients, four with autoimmune haemolytic anaemia (one in early pregnancy and one with a previous history of gastroenterostomy) and three with congenital spherocytosis. While the available data suggest that conditioned deficiency of folic acid is most usually implicated and that the giving of folic acid supplements will correct leucopenia, reticulocytopenia and thrombocytopenia, if these be present, three of the patients (including the patient with previous gastro- enterostomy) had low levels of vitamin B12 in the serum

The Principles and Practice of Vitamin B12 Therapy with Reference to the Treatment of Patients with Pernicious Anaemia and Other Vitamin B12 Deficiency States

Abstract Not Provided