HYPERCAROTENÆMIA IN GHANAIANS

531

reticulocyte-count was followed by no rise in the haemoglobin. And, in the anticonvulsant-induced ansemia, the response of the haemoglobin to folic acid was prompt. This appears to be the first reported case of megaloblastic anxmia due events casts

to

suspicion

nitrofurantoin. The sequence of on

the

drug-a hydantoin and

related chemically to other drugs which are known to lead to folic-acid deficiency and hence to megaloblastic anaemia. After this patient had received several courses of nitrofurantoin, megaloblastic anasmia occurred, as was proved at marrow-puncture. Yet free hydrochloric acid was demonstrated in the stomach by a test meal, smallintestinal function-as assessed by barium studies and analyses of fxcal fat-was normal, and the serumvitamin-B12 level was normal. On the other hand, the FIGLU test for folic-acid deficiency was positive, and treatment with folic acid cured the anasmia. Nitrofurantoin is a common drug and it is surprising that the onset of megaloblastic anxmia after its use has not been reported hitherto. But when Hawkins and Meynell (1954) described their first case of anticonvulsantinduced anaemia, the phenytoin anticonvulsants had been in use for many years; and a further investigation of

Preliminary

Communication

epileptics revealed more cases (Hawkins and Meynell 1958). I therefore plan to investigate patients attending genitourinary outpatient departments who might reasonably be expected to be taking nitrofurantoin. Further evidence of an association between the drug and megaloblastic anaemia may thus be obtained. Summary. A case of megaloblastic ansemia in a patient taking nitrofurantoin is described. This anasmia was similar to that caused by the hydantoin anticonvulsants. Nitrofurantoin is chemically related to phenytoin. The anaemia was due to folic-acid deficiency and was not attributable to small-intestinal disease or vitamin-B12 lack. I am grateful to Dr. Clifford Hawkins, of the Queen Elizabeth Hospital, Birmingham, for his help in preparing this paper. The FIGLU test was done in the biochemistry department of Queen Elizabeth Hospital. REFERENCES

Fuld, H., Moorhouse, E. H. (1956) Brit. med. J, i, 1021. Girdwood, R. H., Lenman, J. A. R. ibid. p. 146. Hawkins, C. F., Meynell, M. J. (1954) Lancet, ii, 737. (1958) Quart. J. Med. 27, 45. Rhind, E. G., Varadi, S. (1954) Lancet, ii, 921. Ryan, G. M. S., Forshaw, J. W. B. (1955) Brit. med. J. ii, 242. —

—

CONCENTRATION OF VITAMIN A AND CAROTENE IN THE SERUM

HYPERCAROTENÆMIA IN GHANAIANS CAROTENE-RICH foods, such as palm oil, mangoes, nkontomire (a green leafy vegetable), tomatoes, and pawpaw, are extensively consumed in some parts of West Africa. Palm oil, a common ingredient- of stews, may contain as much as 113,000 international units (i.u). of carotene per 100 g.,’ and a medium-sized mango (150 g.) over 8000 I.U. During the season many mangoes may be eaten each day. In these circumstances we suspected a hypercarotenaemia, and possibly also a hypervitaminosis A, in at least some of the inhabitants of Accra. Accordingly, we examined the concentrations of carotene and vitamin A in the serum and, wherever possible, also of the livers of men and women in Accra. METHODS

AND

RESULTS

Vitamin A and carotene in the serum were determined by the method recommended by the Interdepartmental Committee on Nutrition for National Defence,2 and vitamin A in the liver according to a modification of the method of Ames et awl. Calculations were made from a standard curve.

Carotene and vitamin A were determined in the sera of sixty-seven pregnant women (aged 15-44) and fifteen soldiers ;aged 22-45), as well as in forty-nine livers of patients coming to necropsy at the Korle Bu Hospital. The vitamin-A content of the serum in pregnant women ranged from very low values at the one extreme (6 fLg. per 100 ml.) to very high values (292 ug.) at the other (see table). However, in two-thirds of the women the vitamin-A levels were 70 ig. per 100 ml. or less, giving a mean value of 66 fLg. per 100 ml. The median value of 40 fLg. in the pregnant women corresponds closely with that of 43 ug. reported from the U.S.A., Great Britain, and Norway,l although the mean value of 66 ug. is considerably higher. In the fifteen soldiers the range in the vitamin-A content of the serum was not as wide as that observed in the larger group of pregnant women, and the overall average was less-56 u.g. 1 Moore,T. VitaminA. London, 1957. Manual for Nutrition Surveys. Interdepartmental Committee on Nutrition for National Defence. U.S. Government Printing Office, 1957. 3 Ames,S.R.,Risley,N. A.,Harris,P. L Analyt.Chem. 1954,26,1378

2

per 100 ml.

(see table). Nevertheless, this concentration is higher than the average reported by Moore1 from the Western countries. By contrast, the

concentrations in the serum were both in the pregnant women and in the soldiers, the average levels being 681 and 850 ug. In only two of the fifteen men and seven of the sixty-seven women were the carotene levels less than 400 ug. per 100 ml. Of especial interest was the observation that in the pregnant women very low levels of serum vitamin A, almost bordering on a vitamin-A deficiency (< 10 ug. per 100 ml.), were always associated with an excessive concentration of carotene (> 500 ug.). In the few cases where the concentration of carotene was less than 400 µg. the vitamin-A levels were variablei.e., either within " normal " limits or raised (> 100 µg.). No direct correlation could be established between the concentrations in the serum of carotene and vitamin A: we found abnormally high serum concentrations of carotene in association with both very high and very low concentrations of vitamin A. The vitamin-A content of the forty-nine livers varied considerably-from 32 ug. per g. to 3635 ug. Twenty-four of the livers showed vitamin-A levels above 300 ug. per g., while the average concentration for the whole group was 409 ug. The latter value is approximately four times as high as any reported in the livers of patients dying from various acute and chronic diseases in Britain’ and Holland,4and twice as high as the vitamin-A reserves in cases of accidental death reported from Scotland. Values approximating to those found in our series are reported from New Zealand where the highest value was carotene

exceptionally high

6867 l.u. per g. (2289 ug. per g.)6 The carotene concentrations in the livers of Ghanaians (range 10-603 ug. per g., median value 47 ug. per g., mean value 92 ug.) were low compared with those obtained for the serum, both in the pregnant women and in the soldiers. 4. 5. 6.

Wolff, L. K. Lancet, 1932, ii, 617. Dzialoszynski, L., Tomaszewski, W. Quoted by Moore (1957). Smith, B. M., Malthus, E.M. Brit. J.Nutr. 1962, 16, 213.

532 COMMENT

From these observations there seems little doubt that many of the Ghanaians in Accra show a distinct carotenasmia which could often be seen by naked-eye inspection of the serum. Abnormally high concentration of serum-carotene, exceeding 500 g. per 100 ml. was found in more than 80% of the sixty-seven pregnant women and fifteen healthy adult men. The sera of one-third of the pregnant women and of one-fifth of the men contained vitamin-A concentrations above 70 g. per 100 ml. Less easy to understand was the association of very low levels of vitamin A in the serum with a hypercarotensemia. Since half the livers contained more than 300 g. of vitamin A per gramme, and since vitamin A as such is not readily available in the diet, it would appear that much of the carotene consumed in the diet was converted into vitamin A and stored, at least in the liver. We suspect, though we have still to prove this by analysis of serum and liver in the same healthy subjects, that in some circumstances a hypercarotenaemia and low concentration of vitamin A in the serum may be associated with a high, liver content of vitamin A, suggesting, in the presence of excess carotene in the blood, some impairment in the mobilisation of vitamin A. The hypervitaminosis A may not be without consequence. This and other aspects of the consumption of excess carotene in Ghana are being investigated. We wish to express our appreciation to the Director of Medical Services, Ghana Army, and to Dr. F. Boi-Doku, specialist pathologist, Korle Bu Hospital, for their helpful cooperation. MAUD DAGADU M.S. State University, Iowa National Institute of Health JOSEPH GILLMAN. and Medical

Research,

M.B. W’srand,

P.O. Box M.32, Accra, Ghana

final stages the patient may roll into the fire or suffocate There is no sensory disturbance. All studies support the hypothesis that predisposition IS determined by a single gene, dominant in the female: this cannot be proved or refuted, though a genetic explanation of All a disease with such a high incidence is open to question. studies have failed to reveal an infective origin: the most likely infective cause seems to be a slow or latent virus infection or an infectious agent widely disseminated but genetically determined. Several workers have noted the remarkable parallel between kuru and scrapie-a fatal disease of sheep due to a filterable agent. Study of diets and food habits does not point to the presence of a deficiency or toxin. The course of the disease has been unaltered by changes of environment. Autosensitisation to undenatured brain antigens as a result of ritual cannibalism has been considered. Serological studies do not support this suggestion; but an abnormally high serum level of 3-globulin has been found. Psychotic or hysterical reactions as causes are ruled out by the neuropathological evidence of organic brain disease. Many of the possible factors might operate with

genetic dependence. Pregnancy seems to

retard the progress of the disease, which accelerates after a few months of lactation. Androgens fail to arrest the disease, and in high doses accelerate it. Corticosteroids do not alter the course. Whatever the aetiology, an outstanding feature is the age and sex distribution. The disease does not occur before the age of 41/2 years, and whereas in children the sex ratio is nearly equal, in adult life many more women than men are affected. It seems that in this disease neuroendocrine relationships should be further examined.

New Inventions

D.SC.

A CAPSULE FOR OBTAINING STERILE SAMPLES OF GASTROINTESTINAL FLUIDS

Medical Societies ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE Kuru

AT a meeting on Feb. 21, with Sir GEORGE McRoBERT, the president, in the chair, Dr. D. C. GAJDUSEK spoke on Kuru. This is an acute, rapidly progressive disease of the central system, restricted to members of the Fore cultural and linguistic group in one small region of the interior highlands of Australian New Guinea. It affects predominantly women and children, and rarely men. 1000 patients have been studied intensively since Dr. Gajdusek and V. Zigas described the disease in 1957. No-one from outside the kuru region has developed the disease after residence there or on close association with the victims. The disease is usually fatal within a year. Mortality varies in different local groups, but is greatest among those in South Fore (18.6 per 1000). Less than 10°of patients recover, and many of these suffer recrudescences and die. Studies suggest that the disease has been present for at least nervous

forty

years.

Kuru is primarily a disorder of motor coordination with ataxia. The clinical course is remarkably uniform, irrespective of age. The onset is insidious, but the patient first notices clumsiness. Excitement exaggerates the involuntary movements. There are three stages: (1) fine tremor, progressive ataxia, and emotional lability, predominantly euphoric; (2) inability to walk without support, choreiform movements, dysarthria, easily provoked inordinate laughter, strabismus; and finally (3) immobility, loss of balance, dysphagia. In the

THE growing need for a device for sampling gastrointestinal juice uncontaminated by organisms introduced during the passage of the instrument has prompted the design of a new culture capsule. Such a capsule must fulfil the following

conditions: 1. It should be small, so as to pass easily into the small intestine and to be tolerated by the patient. 2. It should be possible to sterilise it. 3. The inside of the capsule where fluid is to be sampled should be kept sterile throughout the passage of the capsule until the moment of sampling at any chosen area within the gastrointestinal tract. 4. After sampling, the capsule should again be closed to protect the sampled fluid from contamination during withdrawal of the instrument. -

The only other sampling device for culture purposes was that designed by Henning et al.l It is larger (44-5 12 mm,) and much more complicated. The instrument (fig. 1) consists of a smooth, oval-shaped, stainlesssteel capsule, 21 mm. long and 10 mm. at its widest diameter, carrying a bull-nosed cap (1) at its distal end, and a hollow connection (2) at its proximal end to which a graduated, radio-opaque length of plastic tubing can be attached. connected in turn to a source of low pressure, such as a syringe or vacuum pump. Fig. 2 shows the Internal structure of the cap sule. is

The hollow part

occupied by a longitudinal piston (3)Mh connection (4’ 0f smaller diameter to

Fig. 1-Capsule for obtaining sterile samoles of gastrointestinal fluid. 1.

Henning, N., Zeitler, G., Neugebauer, 100, 1858.

a

I

Munch med. Wschr 1959