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TERATOGENIC EFFECTS OF THALIDOMIDE
772 POSTMORTEM FINDINGS IN 16 MALNOURISHED INFANTS DYING WITHIN SEVEN DAYS OF ADMISSION
hypoglycaemia being such
the final
cause
of death
or
coma in
cases.
Changes observed in blood-levels must be due to changes in function of cells. The hypoglycaemia observed transaminase and by Dr. Wayburne, and the raised serum bilirubin discussed in my article,I together point to failure of hepatocellular function. Medical Research Council Tropical Metabolism Research Unit,
Mona, Jamaica.
A. E. M. MCLEAN.
TERATOGENIC EFFECTS OF THALIDOMIDE
SIR,-We injected thalidomide into the air-sac of fertilised eggs from a pure-bred White Leghorn hen in varying doses *Total body
water
is assumed
Hyponatrasmia is assumed
to
to represent 80% of be due to dilution alone.
s
body-weight.4
about 1 mEq. per litre in 24 hours. Some malnourished infants at the time of admission, however, appear to have lost the ability to reduce renal potassium loss, despite a depletion of body potassium, measured either by muscle biopsy (fig. 1) or by isotopic methods (fig. 2). Alterations in aldosterone secretion are unlikely to cause this excess renal loss. With the kind assistance of Dr. Gowenlock, the 24-hour urinary excretion of aldosterone was estimated in 6 oedematous infants and 5 non-oedematous, convalescent infants. The average values were respectively 0-2 {g. (range 0-0-7) and 1-16 p!.g. (range 0-4-3). If we can regard the
hyponatrasmia
as
predominantly
a
dilution effect, the depression of serum-sodium from the normal level (in Jamaican infants) of about 140 mEq. per litre will give an approximate indication of the excess water in which the body sodium is diluted. This excess water is invariably added to by oral or parenteral fluids, which contain a variable amount of sodium, and, since it is not unusual for hyponatrasmia to be interpreted as sodium deficiency, the lower the serum-sodium the greater the amount of saline solution given. Thus, more fluid is given to an already overhydrated infant; and if the fluid intake in 24 hours is added to the estimated excess water already present, the total excess fluid is directly related to pulmonary oedema, seen clinically and post mortem (see table). Theoretically the logical way to treat hyponatrsemic oedema is by removal of excess water. The use of this method has been reported from Rabat 6, where chronic infantile malnutrition is associated with the drinking of large amounts of water, tea, or sugary preparations without salt. The resulting hyponatrasmic cedema is treated by stopping all food and fluids until a spontaneous diuresis occurs, and the serum-sodium returns to normal level. McLean states that with modem treatment children with severe malnutrition survive, unless they have hepatic failure: since modern treatment usually includes parenteral fluids in the severe case, which must often lead to overhydration and pulmonary oedema, I think that he may be unduly optimistic. Central Middlesex Hospital, R. SMITH. London, N.W.10.
HEPATIC FAILURE IN MALNUTRITION SIR,-Dr. Wayburne’s observation (Feb. 23) of hypoglycaemia in 14% of children dying of kwashiorkor is very interesting. We have observed low blood-sugar values in a few of our cases, and agree that it is important to prevent
hypoglycxmia. Some of our children have become comatose while they were receiving 50% glucose into the inferior vena cava, or were taking oral glucose feeds. There is little likelihood of 6.
Paque, C. Maroc med. 1958, 37, 1063.
(0-2, 0-25,0-5, and 1 mg.) on the second, third, or fifth day after the onset of hatching. We subsequently found malformations which were not seen in our controls.
They affected the skull, chiefly the beak and the eyes, as well as the extremities and internal organs.
there
In addition,
delayed development compared with the conwas
trols. The earlier Above: control animals from untreated the eggs were ineggs. Below: animals from thalidomide. oculated, the more treated eggs. obvious were the abnormalities. The higher the doses, the greater the number of deaths among the embryos. Universitäts-Kinderklinik, Cologne.
BERTHOLD EHMANN.
TREATMENT OF COLLES’ FRACTURE
SIR,-Mr. Golden (March 9) has demonstrated from his results that under the age of 70 there is a close relation between the reduction and the functional recovery. I cannot however agree with his claim that his results show the advantages of an above-elbow plaster. In the first series treated with below-elbow casts he admits that these were all treated by doctors having only a brief acquaintance with fracture work and using various techniques. In the second series, treated with above-elbow casts, the treatment was given by those who had gained some experience in a particular method of reduction and immobilisation. For example, in the description of the application of the plaster, emphasis is placed on careful moulding of the forearm plaster before this is continued above the elbow. If Mr. Golden wished to demonstrate the superiority of an above-elbow cast then he should have made certain that the technique of application of the forearm cast was identical in both groups. My experience indicates that a forearm plaster, accurately moulded in the way I have described,2 is quite adequate to maintain reduction. In fact, one must be on the lookout to avoid over-correction in some cases. Mr. Golden suggests that a further X-ray be taken one wed after reduction. I would add that it may be necessary in many 1. McLean, A. E. M. 2. ibid. 1961, ii, 1410.
Lancet, 1962, ii, 1292.
hypoglycaemia being such
the final
cause
of death
or
coma in
cases.
Changes observed in blood-levels must be due to changes in function of cells. The hypoglycaemia observed transaminase and by Dr. Wayburne, and the raised serum bilirubin discussed in my article,I together point to failure of hepatocellular function. Medical Research Council Tropical Metabolism Research Unit,
Mona, Jamaica.
A. E. M. MCLEAN.
TERATOGENIC EFFECTS OF THALIDOMIDE
SIR,-We injected thalidomide into the air-sac of fertilised eggs from a pure-bred White Leghorn hen in varying doses *Total body
water
is assumed
Hyponatrasmia is assumed
to
to represent 80% of be due to dilution alone.
s
body-weight.4
about 1 mEq. per litre in 24 hours. Some malnourished infants at the time of admission, however, appear to have lost the ability to reduce renal potassium loss, despite a depletion of body potassium, measured either by muscle biopsy (fig. 1) or by isotopic methods (fig. 2). Alterations in aldosterone secretion are unlikely to cause this excess renal loss. With the kind assistance of Dr. Gowenlock, the 24-hour urinary excretion of aldosterone was estimated in 6 oedematous infants and 5 non-oedematous, convalescent infants. The average values were respectively 0-2 {g. (range 0-0-7) and 1-16 p!.g. (range 0-4-3). If we can regard the
hyponatrasmia
as
predominantly
a
dilution effect, the depression of serum-sodium from the normal level (in Jamaican infants) of about 140 mEq. per litre will give an approximate indication of the excess water in which the body sodium is diluted. This excess water is invariably added to by oral or parenteral fluids, which contain a variable amount of sodium, and, since it is not unusual for hyponatrasmia to be interpreted as sodium deficiency, the lower the serum-sodium the greater the amount of saline solution given. Thus, more fluid is given to an already overhydrated infant; and if the fluid intake in 24 hours is added to the estimated excess water already present, the total excess fluid is directly related to pulmonary oedema, seen clinically and post mortem (see table). Theoretically the logical way to treat hyponatrsemic oedema is by removal of excess water. The use of this method has been reported from Rabat 6, where chronic infantile malnutrition is associated with the drinking of large amounts of water, tea, or sugary preparations without salt. The resulting hyponatrasmic cedema is treated by stopping all food and fluids until a spontaneous diuresis occurs, and the serum-sodium returns to normal level. McLean states that with modem treatment children with severe malnutrition survive, unless they have hepatic failure: since modern treatment usually includes parenteral fluids in the severe case, which must often lead to overhydration and pulmonary oedema, I think that he may be unduly optimistic. Central Middlesex Hospital, R. SMITH. London, N.W.10.
HEPATIC FAILURE IN MALNUTRITION SIR,-Dr. Wayburne’s observation (Feb. 23) of hypoglycaemia in 14% of children dying of kwashiorkor is very interesting. We have observed low blood-sugar values in a few of our cases, and agree that it is important to prevent
hypoglycxmia. Some of our children have become comatose while they were receiving 50% glucose into the inferior vena cava, or were taking oral glucose feeds. There is little likelihood of 6.
Paque, C. Maroc med. 1958, 37, 1063.
(0-2, 0-25,0-5, and 1 mg.) on the second, third, or fifth day after the onset of hatching. We subsequently found malformations which were not seen in our controls.
They affected the skull, chiefly the beak and the eyes, as well as the extremities and internal organs.
there
In addition,
delayed development compared with the conwas
trols. The earlier Above: control animals from untreated the eggs were ineggs. Below: animals from thalidomide. oculated, the more treated eggs. obvious were the abnormalities. The higher the doses, the greater the number of deaths among the embryos. Universitäts-Kinderklinik, Cologne.
BERTHOLD EHMANN.
TREATMENT OF COLLES’ FRACTURE
SIR,-Mr. Golden (March 9) has demonstrated from his results that under the age of 70 there is a close relation between the reduction and the functional recovery. I cannot however agree with his claim that his results show the advantages of an above-elbow plaster. In the first series treated with below-elbow casts he admits that these were all treated by doctors having only a brief acquaintance with fracture work and using various techniques. In the second series, treated with above-elbow casts, the treatment was given by those who had gained some experience in a particular method of reduction and immobilisation. For example, in the description of the application of the plaster, emphasis is placed on careful moulding of the forearm plaster before this is continued above the elbow. If Mr. Golden wished to demonstrate the superiority of an above-elbow cast then he should have made certain that the technique of application of the forearm cast was identical in both groups. My experience indicates that a forearm plaster, accurately moulded in the way I have described,2 is quite adequate to maintain reduction. In fact, one must be on the lookout to avoid over-correction in some cases. Mr. Golden suggests that a further X-ray be taken one wed after reduction. I would add that it may be necessary in many 1. McLean, A. E. M. 2. ibid. 1961, ii, 1410.
Lancet, 1962, ii, 1292.