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Kingston; s.n; June 1959. 11,159 p. ills, tab.
Tese em Inglês | MedCarib | ID: med-13687


The terms "megaloblast" and "megaloblastic anaemia" are defined. The megaloblast is a pathological cell and it is only found, specifically, in anaemias which are attributable to a deficiency of certain essential haemopoietic factors present in liver. The morphology of normoblasts and of megaloblasts, i.e. a cell with some of the characteristics of both a megaloblast and a normoblast, is discussed. The charateristic changes in the granulocytic series of cells, which are seen in megaloblastic anaemias, are discussed. The development of knowledge with regard to the essential haemopoietic factors present in liver is described, and the possible roles, and interrelationships of folic acid, folinic acid and vitamin B12 are discussed. It is concluded that, although their precise functions are still uncertain, there is no doubt as to their importance in nucleic acid synthesis. The literature on megaloblastic anaemia of infancy is reviewed. The rather rare association between infantile malnutrition and megaloblastic anaemia are discussed, and the fact that anaemia of any severe degree is unusual in kwashiorkor is stressed. The few available bone-marrow studies in kwashiorkor are described. A megaloblastic bone marrow has not very commonly been seen in kwashiorkor except in Durban, South Africa. A condition which resembles kwashiorkor very closely has been reported from Sicily. These infants are often very anaemic and a megaloblastic bone marrow is commonly seen. The clinical, haematological and other laboratory findings on fifty cases of megaloblastic anaemia of infancy are presented. From the clinical point of view the most striking feature was that all the infants were very malnourished and grossly under-weight. On haematological examination the best valuable finding from a diagnostic point of view was found to be the haemoglobin level. If this is below 7.0 g percent the anaemia is almost certainly going to be megaloblastic. A full blood count with determination of mean corpuscular volume, and haemoglobin concentration is rarely helpful since the anaemia is usually normocytic and normochronic. A certain diagnosis can be made by bone marrow puncture. Of the 50 cases, 45 were tested with folic acid, and 5 received vitamin B12. Six of the folic acid treated cases died. In the 39 folic acid treated who recovered, the haematological and clinical response was excellent. The 5 cases treated with vitamin B12 also showed a good haemotological and clinical response, although the dosage used was large. The majority of cases received antibiotics, and some received several, but in no case was a haematological response observed. The morphology of the bone marrow in haemaloblastic anaemia of infancy is described and extensively illustrated. In addition to typical megaloblasts, erythroblasts of intermediate type were commonly observed. The characteristic white cell abnormalities are also described. Changes in the nuclear chromatin structure of the megakaryocytes were also noted, which resemble the changes seen in megaloblasts quite closely. The post-mortem findings in the six fetal cases are summarized. Extramedullary erythropoiesis was observed in the livers of three cases, and in two a severe chronic fatty change was presented. In one case an acute fatty change was seen. The results of liver biopsies carried out on twelve other infants are also reported. Extra-medullary erythropoiesis was found in seven out of the ten specimens which were sectioned histologically. This finding of extra-medullary erythropoiesis is regarded as being pathognomonic of the disease, although it is not invariably present. Five cases of sickle cell anaemia with associated megaloblastic anaemia are described. This association has only been reported once before in infancy. Three other instances are recorded in the literature in older children. The association is highly significant, since a total of five cases out of fifty exceeds the expected incidence by no less than 3 times. An unexpected and unexplained finding was that three of these cases were also demonstrably iron deficient. The pathogenesis of the disease is considered in detail. It is thought that dietary deficiency is the most important factor, but whether of folic acid or vitamin B12 is uncertain. A deficiency of folic acid seems more likely. The possible significance of ascorbic acid deficiency in the aetiology of the disease is discussed, and the literature on the experimental production of megaloblastic anaemia in monkeys by means of a diet low in folic acid and deficient in ascorbic acid is reviewed. Only one infant in the present series had frank scurvy, and in this case ascorbic acid was required in addition to folic acid to produce a satisfactory haematological and clinical response. The importance of infection in the causation of the disease is discussed. Infections of various types were extremely common especially upper respiratory infections and gastro-enteritis. The role of gastro-enteritis is illustrated by six case in which specific pathogens were isolated from the stools. The possible mechanisms, which may be of importance in the causation of the disease, are listed: (1) A dietary deficiency of haemopoietic substance is thought to be the most significant factor. (2) An intrinsic factor deficiency is suggested speculatively as possibly playing a part. (3) Impaired absorption of haemopoietic factors due to diarrhoea is undoubtedly important. (4) Excessive utilization of haemopoietic factors by an abnormal bacterial flora in the intestine may contribute to a deficiency. (5) Diminished synthesis of haemopoietic factors by an abnormal bacterial flora in the intestine may also play a part. In conclusion some possible lines of future investigation of the disease are discussed (Summary)

Humanos , Lactente , Pré-Escolar , Masculino , Feminino , Anemia Megaloblástica , Sinais e Sintomas , Anemia Megaloblástica/diagnóstico , Anemia Megaloblástica/tratamento farmacológico , Vitamina B 12/uso terapêutico , Eritropoese , Megacariócitos/análise , Fígado/patologia , Fígado Gorduroso , Células da Medula Óssea/análise , Células da Medula Óssea/citologia , Jamaica , Anemia Falciforme , Transtornos Nutricionais , Ácido Fólico/uso terapêutico , Deficiência de Ácido Fólico