I. Chanarin

Iron Deficiency and its Relation to Folic-acid Status in Pregnancy: Results of a Clinical Trial

impression that multiple metastases are more readily shown by scanning than by pneumography or angiography. Single metastases are often revealed by these latter methods, but second or third ones are not often shown. While it is possible to predict the pathology of a certain number of lesions by studying the topography, this is by no means always so. Planiol (1963) uses an entirely different technique by means of which she is able to make a specific diagnosis in a much higher percentage of cases. Her method depends upon the change in count rate at fixed points on the skull at intervals of 2, 24, and 48 hours after an intravenous injection of radioiodinated human serum albumin. She has shown that meningiomas take up the isotope early and metastases late, while the astrocytomas take it up at an intermediate point in time. Since Planiols method is based purely on count figures, there is no topographical representation of the tumours. Thus it is not possible by her technique to demonstrate, for example, an astrocytoma invading the corpus callosum. However, in her series she was able to diagnose correctly 92% (175 out of 190) meningiomas, 93% (292 out of 315) glioblastomas, 56% (48 out of 85) astrocytomas (corresponding to our grade I and grade II astrocytomas), and 90% (216 out of 240) metastases. The most reliable diagnosis of all in her series was related to abscess, where the accuracy was 100% (18 out of 18). In our single case the abscess was certainly very clearly defined (Case 46). It would seem that the best exploitation of the injected isotope would be derived from a combination of photoscanning with Planiols technique. It is our intention to pursue this in the near future.

Intestinal Absorption of Reduced Folate Compounds in Man

Summary. Oral administration of folate compounds was followed by a rise in L. casei active factors in blood. This was due to reduction and methylation of the folate compounds in the small gut and this was demonstrated by the use of dihydropteroylglutamic acid labelled with tritium.

MEGALOBLASTIC ANAEMIA IN A VEGETARIAN HINDU COMMUNITY

138 Indian patients with megaloblastic haemopoiesis were studied. All were lifelong vegetarians. The diagnosis was nutritional cobalamin deficiency in 95 and pernicious anaemia in 20; only 4 patients had folate deficiency. A third had intestinal malabsorption, 20 had features of osteomalacia, and 87 were iron deficient. Tuberculosis was diagnosed in 17. Cobalamin deficiency may have contributed to these complications via intestinal malabsorption and impaired bacterial killing of phagocytosed bacilli by cobalamin-deficient macrophages. The frequency of pernicious anaemia was the same in Indian subjects as in Caucasians.

THROMBOCYTOPENIC PURPURA IN CYTOMEGALOVIRUS MONONUCLEOSIS

Abstract A 33-year-old man presented with a generalised purpura and bleeding gums. Examination of his blood showed severe thrombocytopenia with many glandular-fever-like lymphocytes. The Paul-Bunnell test was negative. Cytomegalovirus was isolated from the urine and there was a high titre of cytomegalovirus antibodies in the serum. He made an uneventful recovery.

Normal dietary folate, iron, and protein intake, with particular reference to pregnancy.

A higher frequency of megaloblastic anaemia in pregnancy towards the end of winter and early spring was noted by Gatenby (1956), Thompson (1957), Forshaw (1957), and Coyle and Geoghegan (1962). Others have not observed this distribution in their cases (Giles and Shuttleworth, 1958 ; MacKenzie and Abbott, 1960; Lowestein et al., 1966b). In this study the frequency was three times as high in January to March as in the latter half of the year. As pointed out by others this is probably due to a decline in the availability of dietary folate and lack of fresh vegetables.

Absorption of Folic Acid and D-Xylose as Tests of Small-intestinal Function

It is of interest that the haemorrhagic episodes recorded occurred in several varieties of megaloblastic anaemia-Addisonian pernicious anaemia, megaloblastic anaemia of pregnancy, malabsorption due to steatorrhoea, and megaloblastic anaemia associated with primidone administration. This supports the conception that thrombocytopenia is part of the dyshaemopoietic state produced by lack of vitamin B12 or folic acid and is not an independent feature. Other factors may have contributed to the haemorrhagic tendency, but unfortunately they were not investigated in any detail in our patients. Hypoprothrombinaemia has been described in pernicious anaemia. In itself it is unlikely to be severe enough to account for haemorrhage (Warner and Owen, 1942), but it can form a contributory cause. Where intestinal malabsorption exists lack of vitamin K may likewise contribute to a bleeding tendency. These cases are reminders that post-partum blood loss, epistaxis, haematemesis, haematuria, and confluent purpura can have as their basis a megaloblastic anaemia. Thrombocytopenia is a significant factor in accounting for the bleeding and, like the anaemia, is corrected by vitamin B12 or folic acid. The condition is initially critical and usually calls for blood transfusion before haematinics can take effect.

Further Observations on the Relation between Iron and Folate Status in Pregnancy

This study was planned to determine whether iron deficiency in pregnancy predisposed to the development of folate deficiency and also the smallest daily iron supplement that maintained haemoglobin levels in pregnancy. Three groups of women were given oral ferrous fumarate supplying 30, 60, and 120 mg of iron; a fourth group was given 1 g of parenteral iron in early pregnancy followed by oral iron (60 mg); a fifth group received a placebo. Tablets were taken once daily. Oral iron 30 mg once daily maintained haemoglobin levels throughout pregnancy. Women whose marrows lacked demonstrable iron at the 37th week had a significantly higher incidence of megaloblastic haemopoiesis (28·7%) than those with demonstrable iron stores (15·3%); women taking oral iron did not have a lower frequency of megaloblastosis than those given a placebo. We concluded that iron does not have a direct effect on folate status in pregnancy, that the association of iron deficiency and megaloblastic anaemia in pregnancy is the result of poor nutrition, and that there is no cause-and-effect relation between them.

ASSAY OF GASTRIC INTRINSIC FACTOR IN THE DIAGNOSIS OF ADDISONIAN PERNICIOUS ANAEMIA.

ADDISONIAN pernicious anaemia is due to the failure of secretion of intrinsic factor by the gastric mucosa and the diagnosis is complete only when the absence of intrinsic factor from the gastric juice has been demonstrated. Ths is done indirectly by showing that isotopically labelled vitamin BIZ is absorbed normally only when it is given with an additional source of intrinsic factor. In recent years there has been considerable interest in methods for direct assay of the intrinsic factor content of gastric juice and these have been discussed in some detail in the comprehensive review on intrinsic factor by Glass (1963). The purpose of this paper is to record the results of an assay procedure for gastric intrinsic factor in a group of patients with megaloblastic anaemia and to draw attention to the value of the method as a .means of making a rapid and definitive diagnosis of Addisonian pernicious anaemia.

Cobalamin and folate: recent developments.

Introduction New concepts in this field continue to develop at the clinical level,within the laboratory and in the realm of basic research. The appreciation that the anaesthetic gas nitrous oxide (N20) specifically inactivates the cobalamin dependent enzyme, methionine synthetase, and produces megaloblastic anaemia in man, has made it possible to perform extensive animal studies on cobalamin-folate interrelations, and to test the methylfolate trap hypothesis in a meaningful way. This has led to the development of alternative ideas as to how cobalamin regulates folate metabolism, based on a large body of data obtained from study of animals in which cobalamin was inactivated. Cobalamin neuropathy, too, has been explored in greater depth than has been possible hitherto. On the diagnostic side, considerable claims have been made for the measurement of serum methylmalonic acid as an indicator of cobalamin deficiency.

Urinary excretion of histidine derivatives in megaloblastic anaemia and other conditions and a comparison with the folic acid clearance test

Urinary excretion of urocanic acid and formimino-glutamic acid in abnormal amounts following oral doses of histidine has been observed not only in most cases of megaloblastic anaemia, but in iron-deficiency anaemia, haemolytic anaemia, and neoplastic disease. The urinary excretion of these substances is increased in those disease states in which an abnormally rapid rate of removal from the plasma of intravenously injected folic acid has been demonstrated.