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TETRACYCLINES AND YELLOW TEETH
743
converted into postgraduate institutes for practitioners, with small lecture theatres (or room with projector) and small library, as suggested by Sir George Pickering? Medical societies could meet in these centres. To the question of how this is to be paid for, I would answer that medical societies should recognise the need for maintaining the professional standards of their members and should support postgraduate programmes. Various organisations such as the Chest and Heart Association, the Diabetic Association, and the Multiple Sclerosis Society might find it an advantage to hold meetings at
such a centre. Moreover, most general practitioners would be prepared to pay a modest fee (with snack meal included) if the medical instruction is good. HARRY N. LEVITT Hon.
Registrar, Postgraduate Committee, College of General Practitioners.
London, S.W.3.
TETRACYCLINES AND YELLOW TEETH
borne in mind when neonatal oeriod.
discoloured yellow on
the
tetracycline
or
a
yellow-brown. drugs as
group of
number of them are Suspicion has fallen a cause.
They
were
given each of the affected children in the early neonatal period. Zegarelli et aLl reported tooth discoloration in children with fibrocystic disease of the pancreas. They believed it to be due to long-term tetracycline therapy. It is already well known that the tetracyclines are deposited in bone at the time of administration and that they show a bright-yellow fluorescence with ultraviolet light. to
Two of the children studied by one of us (P. A. D.) were examined briefly under an ultraviolet lamp and in both cases the teeth showed a yellow fluorescence. Recently it has been possible to examine with an ultraviolet microscope the lower central incisor tooth buds, and lower end of femur of an infant of approximately 30 weeks’ gestation who died at the age of 11 days, and who had been given a 5-day course of tetracycline. The last dose of the drug was given 48 hours before death. There was bright yellow fluorescence in both tissues and this
teeth, which appeared yellow even in The dentine was found to fluoresce much more ordinary light. than the enamel. Work at present in progress by one of us (K. L.) suggests that tetracycline is deposited on the organic matrix of bones and teeth as it prepares for calcification. In the immature tissue a greater proportion of matrix is available-hence the high tetracycline uptake observed in infants. In the animal experiments it was found that tetracycline was also deposited in the eye. Further investigations are in progress. There seems to be no evidence as yet that the presence of tetracycline in bone or teeth is harmful to the human. It is disquieting, however, that the drug should be retained for so long in certain tissues, and Bevelander et al.2 have shown that tetracycline given to chick embryos resulted in stunted malformed bones, and an arrest of the development of hsemopoietic elements. In adult patients with impaired renal function the drug persisted in the blood at higher levels and for longer periods than normal.3 was
very intense in the
It would be wrong to compare the newborn baby with either the chick embryo or a uraemic adult. Nevertheless, it is certain that the renal function of the newborn and particularly of the premature infant is immature, and the lessons learnt from chloramphenicol administration may have some relevance here. We feel these points should be 1.
2. 3.
Zegarelli, E. V., Denning, C. R., Kutscher, A. H., Tuoti, F., di Sant’ Agnese, P. A. Pediatrics, 1960, 26, 1050. Bevelander, G., Nakahara, H., Rolle, G. K. Nature, Lond. 1959, 184, 728. Kunin, C. M., Rees, S. B., Merrill, J. P., Finland, M. J. clin. Invest. 1959, 38, 1487.
PAMELA A. DAVIES. K. LITTLE.
Radcliffe Infirmary. Nuffield Orthopaedic Centre.
Radcliffe Infirmary, Oxford.
W. AHERNE.
THE OXYTOCIN DRIP
SIR,-Dr. Smyth’s observations (March 24) on the effect of oxytocin on the blood-pressure in normal and toxsemic pregnancy are useful, but they do not exclude the possibility that, in special circumstances, physiologi"
cal
"
levels of oxytocin infusion might cause pathological of renal vasoconstriction. We believe that as long as the causation of renal cortical necrosis in pregnancy remains obscure, all potential vasoconstrictors, including oxytocin, must be suspect. F. B. BYROM Department of Neuropathology, Maudsley Hospital, O. E. PRATT. London, S.E.5.
degrees
SIR,-During the past two years in the course of routine follow-up of premature and sick newborn babies, it has become apparent that the teeth of
prescribing the tetracyclines in the
CAROTICOVERTEBRAL STENOSIS sorry that ambiguity of expression should led Mr. Smith have (March 24) to think I had misquoted his work. The relevant sentence would perhaps have been better expressed: " Complete carotid occlusion usually causes a lowering of retinal artery pressure on the side of the occlusion (Liversedge and Smith 1961); in contrast to this, carotid stenosis usually does not." The diastolic ophthalmodynamometer reading is the more significant when used as a guide to perfusion pressure in the circle of Willis, because it must be more clearly related to mean pressure than is the systolic reading. It is interesting that Mr. Smith now reports a difference in
SIR,-Iam
retinal-artery
pressures
(systolic
and
diastolic)
in 5
patients
with carotid stenosis. On inspection of the two angiograms shown, it is clear that the arterial lumen in these cases was probably less than 5% of normal; this is a much severer degree of stenosis than is usually seen and Yates and Hutchinson reported stenosis approaching this severity in not more than 8 out of their series of 100 cases’! Mr. Smith’s criticisms of the calibration of the ophthalmodynamometer are based on an incomplete summary of the method. A detailed report of the calibration will soon be
published in St.
to
Archives of Ophthalmology. George’s Hospital Medical School, London, S.W.1.
Sirshould be grateful for Dr. Lowe (March 17).
an
ROBERT LOWE.
opportunity
to
reply
In my first letter I criticised him for drawing logically unwarrantable conclusions about cerebral blood-flow in atherosclerotic patients from experiments on young rabbits. In support of my contention that cerebral blood-flow is reduced in stenosed carotid arteries, I quoted the work of Nylin et a1.2 Dr. Lowe replied that he had been unable to find the information in the article cited, and quoted two excerpts from it stating that velocity of circulation is not measurably reduced by stenosis. In his article, Dr. Lowe treated arterial pressure and bloodflow as if they were the same thing. In his letter, he equates velocity with flow, which is equally inadmissible. The information about flow to which I directed his attention is in the quoted article. Flow is calculated from the area of the dilution curves obtained by samples from the jugular bulbs taken once every second after injection of 32P-labelled red blood-cells into the carotid arteries. Two patients with carotid stenosis had curves flatter than normal and of smaller area, indicating a reduction in flow. Yates, P. O., Hutchinson, E. C. Spec. Rep. Ser. Med. Res. Coun. Lond. 1961, no. 300. 2. Nylin, G., Silfverskiold, B. P., Lofstedt, S., Regnstrom, O., Hedlund, S. Brain, 1960, 83, 293. 1.
converted into postgraduate institutes for practitioners, with small lecture theatres (or room with projector) and small library, as suggested by Sir George Pickering? Medical societies could meet in these centres. To the question of how this is to be paid for, I would answer that medical societies should recognise the need for maintaining the professional standards of their members and should support postgraduate programmes. Various organisations such as the Chest and Heart Association, the Diabetic Association, and the Multiple Sclerosis Society might find it an advantage to hold meetings at
such a centre. Moreover, most general practitioners would be prepared to pay a modest fee (with snack meal included) if the medical instruction is good. HARRY N. LEVITT Hon.
Registrar, Postgraduate Committee, College of General Practitioners.
London, S.W.3.
TETRACYCLINES AND YELLOW TEETH
borne in mind when neonatal oeriod.
discoloured yellow on
the
tetracycline
or
a
yellow-brown. drugs as
group of
number of them are Suspicion has fallen a cause.
They
were
given each of the affected children in the early neonatal period. Zegarelli et aLl reported tooth discoloration in children with fibrocystic disease of the pancreas. They believed it to be due to long-term tetracycline therapy. It is already well known that the tetracyclines are deposited in bone at the time of administration and that they show a bright-yellow fluorescence with ultraviolet light. to
Two of the children studied by one of us (P. A. D.) were examined briefly under an ultraviolet lamp and in both cases the teeth showed a yellow fluorescence. Recently it has been possible to examine with an ultraviolet microscope the lower central incisor tooth buds, and lower end of femur of an infant of approximately 30 weeks’ gestation who died at the age of 11 days, and who had been given a 5-day course of tetracycline. The last dose of the drug was given 48 hours before death. There was bright yellow fluorescence in both tissues and this
teeth, which appeared yellow even in The dentine was found to fluoresce much more ordinary light. than the enamel. Work at present in progress by one of us (K. L.) suggests that tetracycline is deposited on the organic matrix of bones and teeth as it prepares for calcification. In the immature tissue a greater proportion of matrix is available-hence the high tetracycline uptake observed in infants. In the animal experiments it was found that tetracycline was also deposited in the eye. Further investigations are in progress. There seems to be no evidence as yet that the presence of tetracycline in bone or teeth is harmful to the human. It is disquieting, however, that the drug should be retained for so long in certain tissues, and Bevelander et al.2 have shown that tetracycline given to chick embryos resulted in stunted malformed bones, and an arrest of the development of hsemopoietic elements. In adult patients with impaired renal function the drug persisted in the blood at higher levels and for longer periods than normal.3 was
very intense in the
It would be wrong to compare the newborn baby with either the chick embryo or a uraemic adult. Nevertheless, it is certain that the renal function of the newborn and particularly of the premature infant is immature, and the lessons learnt from chloramphenicol administration may have some relevance here. We feel these points should be 1.
2. 3.
Zegarelli, E. V., Denning, C. R., Kutscher, A. H., Tuoti, F., di Sant’ Agnese, P. A. Pediatrics, 1960, 26, 1050. Bevelander, G., Nakahara, H., Rolle, G. K. Nature, Lond. 1959, 184, 728. Kunin, C. M., Rees, S. B., Merrill, J. P., Finland, M. J. clin. Invest. 1959, 38, 1487.
PAMELA A. DAVIES. K. LITTLE.
Radcliffe Infirmary. Nuffield Orthopaedic Centre.
Radcliffe Infirmary, Oxford.
W. AHERNE.
THE OXYTOCIN DRIP
SIR,-Dr. Smyth’s observations (March 24) on the effect of oxytocin on the blood-pressure in normal and toxsemic pregnancy are useful, but they do not exclude the possibility that, in special circumstances, physiologi"
cal
"
levels of oxytocin infusion might cause pathological of renal vasoconstriction. We believe that as long as the causation of renal cortical necrosis in pregnancy remains obscure, all potential vasoconstrictors, including oxytocin, must be suspect. F. B. BYROM Department of Neuropathology, Maudsley Hospital, O. E. PRATT. London, S.E.5.
degrees
SIR,-During the past two years in the course of routine follow-up of premature and sick newborn babies, it has become apparent that the teeth of
prescribing the tetracyclines in the
CAROTICOVERTEBRAL STENOSIS sorry that ambiguity of expression should led Mr. Smith have (March 24) to think I had misquoted his work. The relevant sentence would perhaps have been better expressed: " Complete carotid occlusion usually causes a lowering of retinal artery pressure on the side of the occlusion (Liversedge and Smith 1961); in contrast to this, carotid stenosis usually does not." The diastolic ophthalmodynamometer reading is the more significant when used as a guide to perfusion pressure in the circle of Willis, because it must be more clearly related to mean pressure than is the systolic reading. It is interesting that Mr. Smith now reports a difference in
SIR,-Iam
retinal-artery
pressures
(systolic
and
diastolic)
in 5
patients
with carotid stenosis. On inspection of the two angiograms shown, it is clear that the arterial lumen in these cases was probably less than 5% of normal; this is a much severer degree of stenosis than is usually seen and Yates and Hutchinson reported stenosis approaching this severity in not more than 8 out of their series of 100 cases’! Mr. Smith’s criticisms of the calibration of the ophthalmodynamometer are based on an incomplete summary of the method. A detailed report of the calibration will soon be
published in St.
to
Archives of Ophthalmology. George’s Hospital Medical School, London, S.W.1.
Sirshould be grateful for Dr. Lowe (March 17).
an
ROBERT LOWE.
opportunity
to
reply
In my first letter I criticised him for drawing logically unwarrantable conclusions about cerebral blood-flow in atherosclerotic patients from experiments on young rabbits. In support of my contention that cerebral blood-flow is reduced in stenosed carotid arteries, I quoted the work of Nylin et a1.2 Dr. Lowe replied that he had been unable to find the information in the article cited, and quoted two excerpts from it stating that velocity of circulation is not measurably reduced by stenosis. In his article, Dr. Lowe treated arterial pressure and bloodflow as if they were the same thing. In his letter, he equates velocity with flow, which is equally inadmissible. The information about flow to which I directed his attention is in the quoted article. Flow is calculated from the area of the dilution curves obtained by samples from the jugular bulbs taken once every second after injection of 32P-labelled red blood-cells into the carotid arteries. Two patients with carotid stenosis had curves flatter than normal and of smaller area, indicating a reduction in flow. Yates, P. O., Hutchinson, E. C. Spec. Rep. Ser. Med. Res. Coun. Lond. 1961, no. 300. 2. Nylin, G., Silfverskiold, B. P., Lofstedt, S., Regnstrom, O., Hedlund, S. Brain, 1960, 83, 293. 1.