1200 children with established renal scarring and vesicoureteric reflux were particularly at risk, and of the 44 such children 12 (27%) showed extension of scarring; all of these had vesicoureteric reflux and all but 1 were infected for more than 30% of the time. While it was entirely appropriate to use a protocol of intermittent treatment in children with covert bacteriuria, it must also be recognised that effective antibacterial treatment is available for the prevention of reinfections of the urinary tract in children in whom this matters.
study
University College Hospital, London WC1
Southampton Southampton
General Hospital, SO9 4XY
J. M. SMELLIE I. C. S. NORMAND
SIR,-We would like to correct the description of our method of estimating the duration of exposure to bacteriuria given in our paper (April 29). The proportion of time that bacteriuria was present was estimated by dividing the sum of the intervals between each positive specimen and the preceding specimen by the total length of time of the follow-up period, as defined by the dates of the first and second X-ray examinations. This measure assumes that the remissions begin immediately after the last infected specimen. We hope that this description is clearer than our previous effort which now appears to be very confusing. At the same time, we would like to make three other minor corrections, which we thought we had put right when reading the proofs. In table 11 the numbers in parentheses refer to numbers of kidneys, not girls. In table in the % of time infected in column 3 was 50-74%, not 50-75%. Also in table in, the number of right kidneys with vesicoureteric reflux exposed to bacteriuria for 50-74% of the time was 5 not 9. Public Health Laboratory, Radcliffe Infirmary, Oxford OX2 6AH
R. MAYON-WHITE
Cardiff
A. W. ASSCHER
Royal Infirmary
FLUORESCEIN LEAKAGE: FIRST SIGN OF JUVENILE DIABETIC RETINOPATHY
SIR,-In a preliminary report on 30 diabetic children’ we described fluorescein leakages as the initial detectable lesions of diabetic retinopathy. These results were confirmed in a series of 87 diabetic children.2.3 Few angiofluorescein studies have been done in diabetic children, and Malone et a1.4 consider microaneurysms to be the first sign. Early permeability of retinal blood-vessels has been demonstrated in experimental diabetes, and these changes are probably secondary to opened endothelial junctions.5 In juvenile diabetics, the early breakdown of the blood/retina barrier to fluorescein has been measured by quantitative vitreous fluorophotometry.6 The findings confirm our work, showing that many juvenile diabetics have abnormal retinal vessels which cannot be detected except by sensitive techniques of angio-
fluorography or fluorophotometry. In our experience fluorescein angiography doubles the frequency of diagnosis of incipient retinopathy. Thus angiofluor-’ ography must be done annually after the onset of diabetes, and not only when microaneurysms are diagnosed by ophthalmo-
scopy. 10 ml of two more
are
are taken every second for 10 s, and taken 15 and 30 min after the fluorescein injec-
frequency of diabetic retinopathy, detected by fluorography, is correlated with the degree of diabetic control, retinopathy being found in 26% of those with good control, in 44% of those with unsatisfactory control, and in 67% of those I The
with poor control. 2,3
Clinique Universitaire de Pédiatrie, Hôpital Saint-Pierre, B-1000 Brussels, Belgium Clinique Universitaire d’Ophtalmologie, Hôpital Brugmann, Brussels
H. DORCHY
D. TOUSSAINT
ANTI-ALLERGIC DRUGS IN IDIOPATHIC NEPHROTIC SYNDROME OF CHILDHOOD
SIR,-Idiopathic nephrotic syndrome of childhood is more in atopic persons.’ Occasionally it occurs as a response to pollens,s and this has prompted the search for allergic factors in its aetiology, and for anti-allergic therapies--by avoidance or suppression of the response. common
We report a double-blind control trial of a new drug, the nitroindanedione derivative BRL 10833 (2-nitro-5,6-dimethylindane-l,3,-dione monohydrate) (Beechams Research Laboratories) on children with idiopathic nephrotic syndrome. BRL 10833 has anti-allergic activity in animal test systems. It probably acts by stabilising mast-cell membranes, inhibiting the release of the mediators of anaphylaxis in a similar way to disodium cromoglycateUnlike disodium cromoglycate, BRL 10833 is well absorbed from the gastrointestinal tract and retains its activity when given orally. The trial was approved by the local ethical committee and by the Committee on Safety of Medicines. Informed parental consent was obtained. Ten children (mean age 10 years) were included in the trial. All were receiving alternate-day prednisone therapy because of frequently relapsing nephrotic syndrome. The dose of prednisone was sufficient to maintain the urine free from protein (mean dose 20 mg/m2 every other day). All patients were in remission when the trial began. Five of the ten children were treated with BRL 10833 for 8 weeks, in a daily dose of 1-2 mg/kg body-weight in four divided doses; the remaining five patients received a placebo. The prednisone dose was reduced concurrently and stopped at the end of 4 weeks. Eight of the ten children relapsed within 12 weeks of stopping the prednisone. Of the five receiving BRL 10833 three relapsed while still receiving the drug and one 8 weeks after the therapy. Four of the five children receiving placebo similarly relapsed soon after stopping the prednisone. BRL 10833 therapy alone did not prevent relapse in children who had required more than 10 mg/m2 alternate-day prednisone to maintain a remission. This disappointing result has to be added to previously reported failures with disodium cromoglycate’ and doxantrazole in the treatment of idiopathic nephrotic syndrome of childhood. ’
Department of Pædiatrics and Child Medical Education Centre, Seacroft Hospital, Leeds LS14 6UH
Health,
S. R. MEADOW
J. T. BROCKLEBANK
Pharmaceuticals,
Brentford, Middlesex
GILLIAN WAINSCOTT
Toussaint, D., Dorchy, H. Bull. Soc. beige Ophtal. 1974, 168, 783. Dorchy, H., Toussaint, D., De Vroede, M., Ernould, C., Loeb, H. Nouv.
Presse méd. 1977, 6, 345. Dorchy, H., Toussaint, D., De Vroede, M., Ernould, C. Acta pædiat. belg. 1977, 30, 59. 4. Malone, J. I., Van Caldar, T. C., Edwards, W. C. Diabetes, 1977, 26, 673. 5. Wallow, I. H. L., Engerman, R. L. Invest. Ophthalmol. 1977, 16, 447. 6. Waltman, S. R., Oestrich, C., Krupin, T., Hanish, S., Ratzan, S., Santiago, J., Kilo, C. Diabetes, 1978, 27, 85.
3.
10% fluorescein solution is injected intra-
tion.’
Beechams 1. 2.
a
venously. Photographs
4. Meadow, S. R. Proceedings European Society of Pædiatric Nephrology 1975. (In the press.) 5. Reeves, W. G., Cameron, J. S., Johansson, S. G. D., Ogg, C. S., Peter, D. K., Weller, R. O. Clin. Allergy. 1975, 5, 121 6. Ross, J. W., Smith, H., Spicer, B. Int. Archs Allergy appl. Immun. 1976, 51, 226. 7. Bluett, N.
H., Chantler, C., Hughes, D. T Lancet, 1977, i, 809.
study
University College Hospital, London WC1
Southampton Southampton
General Hospital, SO9 4XY
J. M. SMELLIE I. C. S. NORMAND
SIR,-We would like to correct the description of our method of estimating the duration of exposure to bacteriuria given in our paper (April 29). The proportion of time that bacteriuria was present was estimated by dividing the sum of the intervals between each positive specimen and the preceding specimen by the total length of time of the follow-up period, as defined by the dates of the first and second X-ray examinations. This measure assumes that the remissions begin immediately after the last infected specimen. We hope that this description is clearer than our previous effort which now appears to be very confusing. At the same time, we would like to make three other minor corrections, which we thought we had put right when reading the proofs. In table 11 the numbers in parentheses refer to numbers of kidneys, not girls. In table in the % of time infected in column 3 was 50-74%, not 50-75%. Also in table in, the number of right kidneys with vesicoureteric reflux exposed to bacteriuria for 50-74% of the time was 5 not 9. Public Health Laboratory, Radcliffe Infirmary, Oxford OX2 6AH
R. MAYON-WHITE
Cardiff
A. W. ASSCHER
Royal Infirmary
FLUORESCEIN LEAKAGE: FIRST SIGN OF JUVENILE DIABETIC RETINOPATHY
SIR,-In a preliminary report on 30 diabetic children’ we described fluorescein leakages as the initial detectable lesions of diabetic retinopathy. These results were confirmed in a series of 87 diabetic children.2.3 Few angiofluorescein studies have been done in diabetic children, and Malone et a1.4 consider microaneurysms to be the first sign. Early permeability of retinal blood-vessels has been demonstrated in experimental diabetes, and these changes are probably secondary to opened endothelial junctions.5 In juvenile diabetics, the early breakdown of the blood/retina barrier to fluorescein has been measured by quantitative vitreous fluorophotometry.6 The findings confirm our work, showing that many juvenile diabetics have abnormal retinal vessels which cannot be detected except by sensitive techniques of angio-
fluorography or fluorophotometry. In our experience fluorescein angiography doubles the frequency of diagnosis of incipient retinopathy. Thus angiofluor-’ ography must be done annually after the onset of diabetes, and not only when microaneurysms are diagnosed by ophthalmo-
scopy. 10 ml of two more
are
are taken every second for 10 s, and taken 15 and 30 min after the fluorescein injec-
frequency of diabetic retinopathy, detected by fluorography, is correlated with the degree of diabetic control, retinopathy being found in 26% of those with good control, in 44% of those with unsatisfactory control, and in 67% of those I The
with poor control. 2,3
Clinique Universitaire de Pédiatrie, Hôpital Saint-Pierre, B-1000 Brussels, Belgium Clinique Universitaire d’Ophtalmologie, Hôpital Brugmann, Brussels
H. DORCHY
D. TOUSSAINT
ANTI-ALLERGIC DRUGS IN IDIOPATHIC NEPHROTIC SYNDROME OF CHILDHOOD
SIR,-Idiopathic nephrotic syndrome of childhood is more in atopic persons.’ Occasionally it occurs as a response to pollens,s and this has prompted the search for allergic factors in its aetiology, and for anti-allergic therapies--by avoidance or suppression of the response. common
We report a double-blind control trial of a new drug, the nitroindanedione derivative BRL 10833 (2-nitro-5,6-dimethylindane-l,3,-dione monohydrate) (Beechams Research Laboratories) on children with idiopathic nephrotic syndrome. BRL 10833 has anti-allergic activity in animal test systems. It probably acts by stabilising mast-cell membranes, inhibiting the release of the mediators of anaphylaxis in a similar way to disodium cromoglycateUnlike disodium cromoglycate, BRL 10833 is well absorbed from the gastrointestinal tract and retains its activity when given orally. The trial was approved by the local ethical committee and by the Committee on Safety of Medicines. Informed parental consent was obtained. Ten children (mean age 10 years) were included in the trial. All were receiving alternate-day prednisone therapy because of frequently relapsing nephrotic syndrome. The dose of prednisone was sufficient to maintain the urine free from protein (mean dose 20 mg/m2 every other day). All patients were in remission when the trial began. Five of the ten children were treated with BRL 10833 for 8 weeks, in a daily dose of 1-2 mg/kg body-weight in four divided doses; the remaining five patients received a placebo. The prednisone dose was reduced concurrently and stopped at the end of 4 weeks. Eight of the ten children relapsed within 12 weeks of stopping the prednisone. Of the five receiving BRL 10833 three relapsed while still receiving the drug and one 8 weeks after the therapy. Four of the five children receiving placebo similarly relapsed soon after stopping the prednisone. BRL 10833 therapy alone did not prevent relapse in children who had required more than 10 mg/m2 alternate-day prednisone to maintain a remission. This disappointing result has to be added to previously reported failures with disodium cromoglycate’ and doxantrazole in the treatment of idiopathic nephrotic syndrome of childhood. ’
Department of Pædiatrics and Child Medical Education Centre, Seacroft Hospital, Leeds LS14 6UH
Health,
S. R. MEADOW
J. T. BROCKLEBANK
Pharmaceuticals,
Brentford, Middlesex
GILLIAN WAINSCOTT
Toussaint, D., Dorchy, H. Bull. Soc. beige Ophtal. 1974, 168, 783. Dorchy, H., Toussaint, D., De Vroede, M., Ernould, C., Loeb, H. Nouv.
Presse méd. 1977, 6, 345. Dorchy, H., Toussaint, D., De Vroede, M., Ernould, C. Acta pædiat. belg. 1977, 30, 59. 4. Malone, J. I., Van Caldar, T. C., Edwards, W. C. Diabetes, 1977, 26, 673. 5. Wallow, I. H. L., Engerman, R. L. Invest. Ophthalmol. 1977, 16, 447. 6. Waltman, S. R., Oestrich, C., Krupin, T., Hanish, S., Ratzan, S., Santiago, J., Kilo, C. Diabetes, 1978, 27, 85.
3.
10% fluorescein solution is injected intra-
tion.’
Beechams 1. 2.
a
venously. Photographs
4. Meadow, S. R. Proceedings European Society of Pædiatric Nephrology 1975. (In the press.) 5. Reeves, W. G., Cameron, J. S., Johansson, S. G. D., Ogg, C. S., Peter, D. K., Weller, R. O. Clin. Allergy. 1975, 5, 121 6. Ross, J. W., Smith, H., Spicer, B. Int. Archs Allergy appl. Immun. 1976, 51, 226. 7. Bluett, N.
H., Chantler, C., Hughes, D. T Lancet, 1977, i, 809.
