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ECONOMY IN THE BRAIN
1121 These results were presented at the vith International Conference on Sarcoidosis, held in Tokyo, in September, 1972. Third Department of Pathology, University of Helsinki, and Department of Dermatology, University Central Hospital, Helsinki, Finland. MAIJA HORSMANHEIMO.
ECONOMY IN THE BRAIN
SiR,-Professor Hunt and
Dr Stubbs (May 5, p. 997) be made by an unexpectedly few synapses operating in series in the brain. This conclusion is valid only if one considers the operation of the human brain as a linear progression through a single series of synapses when taking a particular decision. Taking their example of an 11-synapse series making a 1-bit decision, and assuming that each neuron will pass on an impulse to two others, and that the pathways thus formed in a branching manner will converge on a single " final common pathway ", 1534 synapses would be involved during the 11 msec. calculated by your corre-
concluded that decisions
can
spondents. Another consideration is the possibility of multiple How often is a stimulus restricted to one neuron for its transmission ? If several inputs are provided then several decision-taking pathways can be followed simultaneously within the brain. Thus many more than 1534 synapses could be used. Similarly, the number would be increased enormously if it were accepted that each neuron could pass on impulses to more than two others. In defining the maximum time available for neuronal decision-taking mechanisms to operate, Professor Hunt and Dr Stubbs have defined the minimum number of What synapses that could be involved in the process. happens in reality or in any model system designed to simulate it could well involve many more.
inputs.
Middlesex Hospital Medical School, Cleveland Street, London W1.
chlorpropamide with its long-acting effect was the chief associated drug. 90% of the patients were over the age of 60. 8 people died. These figures are probably a considerable underestimate of the true position, because, firstly, the figures were mainly derived from questionaries sent out to
physicians and, secondly, hypoglycaemic
Hadassah Municipal Hospital, Tel-Aviv, Israel.
RAFAEL
J. SCHEN.
SCREENING FOR CONGENITAL HYPOTHYROIDISM IN THE NEWBORN
SiR—The letter by Dr Taranger and others (March 3,
487) prompted thyroidism in the
p.
JOHN R. KIRWAN.
reac-
tions in elderly patients may be easily misdiagnosed as cerebrovascular accidents and so go unrecorded. Indeed, Berger believes there may be as many as 100 such cases a year in Switzerland. If the situation in other countries is comparable, there must have been many thousands of cases all over the world; if we accept the estimate that 6% of the patients die,2 the disturbing conclusion is that there may well have been hundreds of deaths. A number of observers have noted the susceptibility of the aged to the hypoglycaemic effects of the sulphonylureas.3-8 Surely, the time has come to question whether chlorpropamide and other long-acting sulphonylureas should be given to older patients. If a sulphonylurea has to be given in this age-group, tolbutamide seems to be the least dangerous. In the debate on the findings of the University Group Diabetes Program, little attention has been paid to the possibility that prolonged hypoglycasmia might affect the cardiovascular death-rate of diabetics taking sulphonylureas. The fact that, in 2 of our cases, hypoglycsemia was followed by severe cardiac complications hints at such a possibility.
us to record newborn.
our
experience with hypo-
Baby C, a male child, was born after a 40-weeks gestation. A sibling, a known cretin diagnosed at 3 months, was mentally retarded in spite of adequate thyroid therapy. At birth baby C CHLORPROPAMIDE: DANGEROUS HYPOGLYCÆMIA IN OLD AGE ? SiR,-Our experience does not conform with the widely held view that severe hypoglycaemic reactions to chlorpropamide are unusual. Over five years, 13 diabetic patients with severe hypoglycsemic reactions to chlorpropamide were admitted to the two general hospitals of the Tel-Aviv Municipal Medical Centre; no such reactions to other types of sulphonylurea drug were seen. The average age of the
was 70, 5 being over 80. All semi-comatose on admission and all needed prolonged intravenous infusions of glucose. The duration of the cerebral disturbance at home, together with the period of hypoglycaemia seen in hospital, was over twenty-four hours in 8 cases. In 3 cases there was evidence of renal insufficiency. A 63-year-old patient, on recovery from the hypoglycmmia, developed coronary insufficiency which culminated in a myocardial infarction two weeks after admission. 2 patients died: an 80-year-old woman never recovered full consciousness and died a week after admission; and an 83-year-old man developed pulmonary redema on the 2nd hospital day, atrial fibrillation appeared, and he died on the 13th day with signs of a cerebrovascular accident. I wish to draw attention to the report of Berger1 from Switzerland, describing 88 cases of severe hypoglycaemic reactions to the sulphonylurea drugs. As was to be expected,
were
1.
patients
comatose or
Berger, W. Schweiz. med. Wschr. 1971, 71, 1013.
have abdominal distension and at 48 hours of age meconium. The eyes were puffy, the features were coarse, and the child not very active. An enema resulted in the passage of the meconium plug. A subsequent barium enema A rectal biopsy showed normal was within normal limits. ganglion cells. X-ray examination of the knees showed the presence of both distal femoral epiphyses. A thyroid scan at 4 days of age A showed no uptake of technetium in the neck region. serum-thyroxine at 48 hours was 3-3 tJ.g. per 100 ml. The level of thyrotrophic hormone was greater than 21 ng. per ml. Thyroid antibodies were absent in the baby’s serum. The child was begun on L-thyroxine and has progressed well. was
noted
had not
to
passed
This case is the second child with congenital hypothyroidism in whom the distal femoral epiphyses were ossified. This casts doubt on the reliability of this radiological sign as a method of ruling out hypothyroidism. Hence it is of questionable value in screening of the newborn. The recent development of a sensitive radioimmunoassay for serum-thyroxine on small quantities of blood appears to hold greater promise as a technique to pick up neonatal hypothyroidism. Department of Paediatrics, Hospital for Sick Children, Toronto 2, Ontario.
R. M. EHRLICH J. B. J. MCKENDRY.
2. Presse méd. 1971, 78, 873. 3. Gardner, P., Goodner, C. J., Dowling, J. T. J. Am. med. Ass. 1963, 186, 991. 4. Bauer, H. G. Metabolism, 1965, 14, 220. 5. Siade, I. H., Iosefa, R. N. J. Am. geriat. Soc. 1967, 15, 948. 6. Frey, H. M. M., Rosenlund, B. Diabetes, 1970, 12, 930.
ECONOMY IN THE BRAIN
SiR,-Professor Hunt and
Dr Stubbs (May 5, p. 997) be made by an unexpectedly few synapses operating in series in the brain. This conclusion is valid only if one considers the operation of the human brain as a linear progression through a single series of synapses when taking a particular decision. Taking their example of an 11-synapse series making a 1-bit decision, and assuming that each neuron will pass on an impulse to two others, and that the pathways thus formed in a branching manner will converge on a single " final common pathway ", 1534 synapses would be involved during the 11 msec. calculated by your corre-
concluded that decisions
can
spondents. Another consideration is the possibility of multiple How often is a stimulus restricted to one neuron for its transmission ? If several inputs are provided then several decision-taking pathways can be followed simultaneously within the brain. Thus many more than 1534 synapses could be used. Similarly, the number would be increased enormously if it were accepted that each neuron could pass on impulses to more than two others. In defining the maximum time available for neuronal decision-taking mechanisms to operate, Professor Hunt and Dr Stubbs have defined the minimum number of What synapses that could be involved in the process. happens in reality or in any model system designed to simulate it could well involve many more.
inputs.
Middlesex Hospital Medical School, Cleveland Street, London W1.
chlorpropamide with its long-acting effect was the chief associated drug. 90% of the patients were over the age of 60. 8 people died. These figures are probably a considerable underestimate of the true position, because, firstly, the figures were mainly derived from questionaries sent out to
physicians and, secondly, hypoglycaemic
Hadassah Municipal Hospital, Tel-Aviv, Israel.
RAFAEL
J. SCHEN.
SCREENING FOR CONGENITAL HYPOTHYROIDISM IN THE NEWBORN
SiR—The letter by Dr Taranger and others (March 3,
487) prompted thyroidism in the
p.
JOHN R. KIRWAN.
reac-
tions in elderly patients may be easily misdiagnosed as cerebrovascular accidents and so go unrecorded. Indeed, Berger believes there may be as many as 100 such cases a year in Switzerland. If the situation in other countries is comparable, there must have been many thousands of cases all over the world; if we accept the estimate that 6% of the patients die,2 the disturbing conclusion is that there may well have been hundreds of deaths. A number of observers have noted the susceptibility of the aged to the hypoglycaemic effects of the sulphonylureas.3-8 Surely, the time has come to question whether chlorpropamide and other long-acting sulphonylureas should be given to older patients. If a sulphonylurea has to be given in this age-group, tolbutamide seems to be the least dangerous. In the debate on the findings of the University Group Diabetes Program, little attention has been paid to the possibility that prolonged hypoglycasmia might affect the cardiovascular death-rate of diabetics taking sulphonylureas. The fact that, in 2 of our cases, hypoglycsemia was followed by severe cardiac complications hints at such a possibility.
us to record newborn.
our
experience with hypo-
Baby C, a male child, was born after a 40-weeks gestation. A sibling, a known cretin diagnosed at 3 months, was mentally retarded in spite of adequate thyroid therapy. At birth baby C CHLORPROPAMIDE: DANGEROUS HYPOGLYCÆMIA IN OLD AGE ? SiR,-Our experience does not conform with the widely held view that severe hypoglycaemic reactions to chlorpropamide are unusual. Over five years, 13 diabetic patients with severe hypoglycsemic reactions to chlorpropamide were admitted to the two general hospitals of the Tel-Aviv Municipal Medical Centre; no such reactions to other types of sulphonylurea drug were seen. The average age of the
was 70, 5 being over 80. All semi-comatose on admission and all needed prolonged intravenous infusions of glucose. The duration of the cerebral disturbance at home, together with the period of hypoglycaemia seen in hospital, was over twenty-four hours in 8 cases. In 3 cases there was evidence of renal insufficiency. A 63-year-old patient, on recovery from the hypoglycmmia, developed coronary insufficiency which culminated in a myocardial infarction two weeks after admission. 2 patients died: an 80-year-old woman never recovered full consciousness and died a week after admission; and an 83-year-old man developed pulmonary redema on the 2nd hospital day, atrial fibrillation appeared, and he died on the 13th day with signs of a cerebrovascular accident. I wish to draw attention to the report of Berger1 from Switzerland, describing 88 cases of severe hypoglycaemic reactions to the sulphonylurea drugs. As was to be expected,
were
1.
patients
comatose or
Berger, W. Schweiz. med. Wschr. 1971, 71, 1013.
have abdominal distension and at 48 hours of age meconium. The eyes were puffy, the features were coarse, and the child not very active. An enema resulted in the passage of the meconium plug. A subsequent barium enema A rectal biopsy showed normal was within normal limits. ganglion cells. X-ray examination of the knees showed the presence of both distal femoral epiphyses. A thyroid scan at 4 days of age A showed no uptake of technetium in the neck region. serum-thyroxine at 48 hours was 3-3 tJ.g. per 100 ml. The level of thyrotrophic hormone was greater than 21 ng. per ml. Thyroid antibodies were absent in the baby’s serum. The child was begun on L-thyroxine and has progressed well. was
noted
had not
to
passed
This case is the second child with congenital hypothyroidism in whom the distal femoral epiphyses were ossified. This casts doubt on the reliability of this radiological sign as a method of ruling out hypothyroidism. Hence it is of questionable value in screening of the newborn. The recent development of a sensitive radioimmunoassay for serum-thyroxine on small quantities of blood appears to hold greater promise as a technique to pick up neonatal hypothyroidism. Department of Paediatrics, Hospital for Sick Children, Toronto 2, Ontario.
R. M. EHRLICH J. B. J. MCKENDRY.
2. Presse méd. 1971, 78, 873. 3. Gardner, P., Goodner, C. J., Dowling, J. T. J. Am. med. Ass. 1963, 186, 991. 4. Bauer, H. G. Metabolism, 1965, 14, 220. 5. Siade, I. H., Iosefa, R. N. J. Am. geriat. Soc. 1967, 15, 948. 6. Frey, H. M. M., Rosenlund, B. Diabetes, 1970, 12, 930.