PATHOGENESIS OF RETROLENTAL FIBROPLASIA
1
381 of money is afforded the maximum publicity-whatever happened to the 2 million pounds designated for the obstetric services some four years ago ?-but the defects remain unpublicised. The more responsible members of the medical profession of course realise that the National Health Service as such cannot expand, or even maintain, its services with the limited financial resources now available. Is it not time the politicians realised this, too ? Windsor, Berks. JOHN H. HUGHES. PATHOGENESIS OF RETROLENTAL FIBROPLASIA R. M. FORRESTER. Pædiatric Department, Royal Albert Edward Infirmary, Wigan. N. R. C. ROBERTON. Hillingdon Hospital, Middlesex. SIR,-Your correspondents’ ideas (August 2, p. 265) about the role of light in the pathogenesis of retrolental fibroplasia (R.L.F.) are very interesting, but, at the moment, unconvincing. Several of their fundamental assumptions about R.L.F. are incorrect. 1. They assume that the retrolental mass is caused by damage to the " retrolental tissues ". In fact the disorder starts as a vascular disturbance of the retinal vessels, and the vitreous involvement is only secondary and terminal. In many cases the changes are confined to the retina. 2. The hyaloid artery is not present, even in the extremely premature eye. A hyaloid remnant may often be found, but it is totally non-functioning. This has been carefully recorded. 1 3. The negative role of light in the pathogenesis of R.L.F. was established in 1952 by Locke and Reese.2 4. The importance of oxygen in causing R.L.F. is clear, but its actual role often misunderstood. It is not the exposure to oxygen, but the removal of the oxygen- subsidised eye from high oxygen tensions which precipitates the disease. The early changes (retinopathy) can be made to regress, and the eyes saved from R.L.F., by returning the infant to a very high oxygen concentration.3 5. No new explanation for R.L.F. is needed. The natural history of the disease, and the results of treatment, make such a clear pattern that the introduction of a new element seems entirely unnecessary. R.L.F. still occurs in England and provides a steady trickle of blind children each year. Careful oxygen management of the premature baby is still the key to prevention. This must be accompanied by careful watch on the fundus oculi of each infant at risk. This can lead to successful treatment. Your correspondents suggest that ophthalmoscopic examina- tion should be avoided; but I must plead that they have not made out a case for the abandonment of this simple but vital precaution. SIR,-The letter by Dr. Riley and Dr. Slater provides an interesting theory of the aetiology of R.L.F. This can be easily tested by rearing susceptible newborn kittens in a high environmental oxygen tension, either in bright light or in darkness. The suggestion, however, that their theory is supported by the fact that babies born to mothers who have received supplementary oxygen therapy during pregnancy do not develop retrolental fibroplasia is not valid. Giving the pregnant mother 100% oxygen to breathe makes very little difference to the fetal carotid Pa02’ which is, in fact, much lower than the carotid Pa02 in healthy newborn premature 1. Jones, H. E. Br. J. Ophthal. 1963, 47, 39. 2. Locke, J. C., Reese, A. B. Archs Ophthal. N. Y. 1952, 48, 44. 3. Forrester, R. M. Devl. Med. Child Neurol. 1964, 6, 648. infants breathing air, and certainly well below the calculated danger level of oxygen tension to the retina of 160 mm. Hg. Until more definite evidence-even circumstantial-is obtained, I hope Dr. Riley and Dr. Slater do not expect us to stumble round in the dark while treating the sick premature, or abandon the use of the ophthalmoscope. FLUORIDES AND TEETH R. B. D. STOCKER. SIR,-Mrs. Dougall (Aug. 2, p. 265) implies that fluoridated salt would be as effective as fluoridated water. This is very doubtful. The official Swiss fluoridated salt has proved less effective but it is now widely believed to be much under-fluoridated. Hardwick gives this as the probable reason. An experiment to determine the optimum fluoride content for fluoridated salt, and its efficacy, has been begun in Bolivia and is briefly described by Restrepo. 2 Even with salt of optimum fluoride content it is doubtful whether deciduous teeth would derive much benefit because of the low average intake of salt at the ages when these teeth erupt. The question of dosage is discussed by Miihlemann.3 It is possible, and to be hoped, that salt will eventually prove to be as effective a vehicle as waterńor much more cost-effective-since many communities in which dental caries is endemic cannot even afford a public water-supply. On the other hand fluoridation of water is so cheap and effective, especially in our bigger towns, that it would be wrong to postpone it any longer in the hope of finding a cheaper alternative or one less liable to be the subject of "distasteful bickering." London S.W.10. A COMPOUND WHICH LOWERS BLOOD-UREA IN URÆMIC DIABETICS SIR,-We wish to report some interesting effects of y-guanidinobutyramide (HL523, Augmentin ’) in diabetic patients with raised blood-urea levels. This compound occurs naturally in a number of plant and animal species 4- including mammals 5-and causes hypoglycaemia when administered in doses of 0.6-1.0 g. per kg. in rats, rabbits, and monkeys.6 7 In chronic toxicity tests in animals, as required by the Dunlop Committee and the F.D.A., up to 3 g. per day, given in divided doses for up to 6 months, had no detectable adverse effects. 12 diabetic patients with pretreatment blood-ureas of 50 mg. or more per 100 ml., or blood-urea-nitrogen (B.U.N.) levels exceeding 25 mg. per 100 ml., have been studied at Guy’s Hospital and at the Pennsylvania Hospital. Their ages ranged from 44 to 87 years, and their fasting blood- sugars from 114 to 260 mg. per 100 ml. There were 6 men and 6 women: 4 were being treated with insulin (20-60 units daily), 2 with chorpropamide, 2 with phenformin, and 2 by dietary restriction. 2 were untreated, newly detected, diabetics. These patients received 0.6-1.2 g. y-guanidinobutyramide by mouth in 3 or 4 divided doses daily. There was no clinical evidence of a change in renal function and no detectable diuresis; but after 10-14 days the blood-urea or B.U.N. levels had fallen towards or within the normal ranges 1. Hardwick, J. L. Br. dent. J. 1965, 119, 529. 2. Restrepo, D. Int. dent. J. 1967, 17, 4. 3. Mühlemann, H. R. ibid. p. 10. 4. Thoai, N. V. in Comparative Biochemistry of Arginine and Deriva- tives; p. 5. London, 1965. 5. Mori, A. Personal communication. 6. Jones, H. E. Personal communication. 7. Berger, F. M. Personal communication.
Transcript of PATHOGENESIS OF RETROLENTAL FIBROPLASIA
381
of money is afforded the maximum publicity-whateverhappened to the 2 million pounds designated for the
obstetric services some four years ago ?-but the defectsremain unpublicised.The more responsible members of the medical profession
of course realise that the National Health Service as suchcannot expand, or even maintain, its services with thelimited financial resources now available. Is it not time the
politicians realised this, too ?Windsor,Berks. JOHN H. HUGHES.
PATHOGENESIS OF RETROLENTAL
FIBROPLASIA
R. M. FORRESTER.
Pædiatric Department,Royal Albert Edward Infirmary,
Wigan.
N. R. C. ROBERTON.Hillingdon Hospital,
Middlesex.
SIR,-Your correspondents’ ideas (August 2, p. 265)about the role of light in the pathogenesis of retrolentalfibroplasia (R.L.F.) are very interesting, but, at the moment,unconvincing. Several of their fundamental assumptionsabout R.L.F. are incorrect.
1. They assume that the retrolental mass is caused bydamage to the " retrolental tissues ". In fact the disorderstarts as a vascular disturbance of the retinal vessels, and thevitreous involvement is only secondary and terminal. In
many cases the changes are confined to the retina.2. The hyaloid artery is not present, even in the extremely
premature eye. A hyaloid remnant may often be found, butit is totally non-functioning. This has been carefullyrecorded. 1
3. The negative role of light in the pathogenesis of R.L.F.was established in 1952 by Locke and Reese.2
4. The importance of oxygen in causing R.L.F. is clear,but its actual role often misunderstood. It is not the
exposure to oxygen, but the removal of the oxygen-subsidised eye from high oxygen tensions which precipitatesthe disease. The early changes (retinopathy) can be made toregress, and the eyes saved from R.L.F., by returning theinfant to a very high oxygen concentration.3
5. No new explanation for R.L.F. is needed. The naturalhistory of the disease, and the results of treatment, makesuch a clear pattern that the introduction of a new elementseems entirely unnecessary.
R.L.F. still occurs in England and provides a steady trickleof blind children each year. Careful oxygen managementof the premature baby is still the key to prevention. Thismust be accompanied by careful watch on the fundus oculiof each infant at risk. This can lead to successful treatment.Your correspondents suggest that ophthalmoscopic examina-tion should be avoided; but I must plead that they have notmade out a case for the abandonment of this simple butvital precaution.
SIR,-The letter by Dr. Riley and Dr. Slater provides aninteresting theory of the aetiology of R.L.F. This can beeasily tested by rearing susceptible newborn kittens in ahigh environmental oxygen tension, either in bright light orin darkness.The suggestion, however, that their theory is supported
by the fact that babies born to mothers who have receivedsupplementary oxygen therapy during pregnancy do notdevelop retrolental fibroplasia is not valid. Giving thepregnant mother 100% oxygen to breathe makes very littledifference to the fetal carotid Pa02’ which is, in fact, muchlower than the carotid Pa02 in healthy newborn premature
1. Jones, H. E. Br. J. Ophthal. 1963, 47, 39.2. Locke, J. C., Reese, A. B. Archs Ophthal. N. Y. 1952, 48, 44.3. Forrester, R. M. Devl. Med. Child Neurol. 1964, 6, 648.
infants breathing air, and certainly well below the calculateddanger level of oxygen tension to the retina of 160 mm. Hg.
Until more definite evidence-even circumstantial-is
obtained, I hope Dr. Riley and Dr. Slater do not expect us tostumble round in the dark while treating the sick premature,or abandon the use of the ophthalmoscope.
FLUORIDES AND TEETH
R. B. D. STOCKER.
SIR,-Mrs. Dougall (Aug. 2, p. 265) implies thatfluoridated salt would be as effective as fluoridated water.This is very doubtful. The official Swiss fluoridated salthas proved less effective but it is now widely believed to bemuch under-fluoridated. Hardwick gives this as the
probable reason. An experiment to determine the optimumfluoride content for fluoridated salt, and its efficacy, hasbeen begun in Bolivia and is briefly described by Restrepo. 2Even with salt of optimum fluoride content it is doubtfulwhether deciduous teeth would derive much benefitbecause of the low average intake of salt at the ages whenthese teeth erupt. The question of dosage is discussed byMiihlemann.3
It is possible, and to be hoped, that salt will eventuallyprove to be as effective a vehicle as waterńor much morecost-effective-since many communities in which dentalcaries is endemic cannot even afford a public water-supply.On the other hand fluoridation of water is so cheap andeffective, especially in our bigger towns, that it would bewrong to postpone it any longer in the hope of finding acheaper alternative or one less liable to be the subject of"distasteful bickering."London S.W.10.
A COMPOUND WHICH LOWERS BLOOD-UREAIN URÆMIC DIABETICS
SIR,-We wish to report some interesting effects of
y-guanidinobutyramide (HL523, Augmentin ’) in diabeticpatients with raised blood-urea levels. This compoundoccurs naturally in a number of plant and animal species 4-including mammals 5-and causes hypoglycaemia whenadministered in doses of 0.6-1.0 g. per kg. in rats, rabbits,and monkeys.6 7 In chronic toxicity tests in animals, asrequired by the Dunlop Committee and the F.D.A., up to3 g. per day, given in divided doses for up to 6 months, hadno detectable adverse effects.
12 diabetic patients with pretreatment blood-ureas of50 mg. or more per 100 ml., or blood-urea-nitrogen (B.U.N.)levels exceeding 25 mg. per 100 ml., have been studied atGuy’s Hospital and at the Pennsylvania Hospital. Theirages ranged from 44 to 87 years, and their fasting blood-sugars from 114 to 260 mg. per 100 ml. There were 6 menand 6 women: 4 were being treated with insulin (20-60 unitsdaily), 2 with chorpropamide, 2 with phenformin, and 2 bydietary restriction. 2 were untreated, newly detected,diabetics.These patients received 0.6-1.2 g. y-guanidinobutyramide
by mouth in 3 or 4 divided doses daily. There was noclinical evidence of a change in renal function and nodetectable diuresis; but after 10-14 days the blood-urea orB.U.N. levels had fallen towards or within the normal ranges
1. Hardwick, J. L. Br. dent. J. 1965, 119, 529.2. Restrepo, D. Int. dent. J. 1967, 17, 4.3. Mühlemann, H. R. ibid. p. 10.4. Thoai, N. V. in Comparative Biochemistry of Arginine and Deriva-
tives; p. 5. London, 1965.5. Mori, A. Personal communication.6. Jones, H. E. Personal communication.7. Berger, F. M. Personal communication.
