1166
maternal hypothyroidism, lack of elemental iodine in and the fetus.12 Proof of this, even in laboratory animals, will be difficult. The normal physiological response to iodine deficiency is a fall in serum thyroxine (T4) and a rise in serum thyrotropin; but serum triiodothyronine (T3) remains normal or is even raised.19-22 A further possibility therefore is that the fetus is harmed by an imbalance in maternal T3/T4, even though the mother is clinically euthyroid. Answers to these questions might well throw light on the aetiology and pathogenesis of other
not
through fetal and one possibility is a
forms of cerebral palsy. The severity and pattern of neurological damage is variable and we do not know which aspects of iodine deficiency are critical-the degree, the duration, or the timing. Might different areas of the brain be vulnerable at specific periods of development ? Is endemic cretinism a distinct entity within a population, or is there a range of mental retardation and motor incompetence with a quota of subclinical deficit which merges into normality? In the first article this week, Prof.CONNOLLY and his co-workers report a significantly better motor competence in those children whose mothers were not iodine deficient during pregnancy. Their findings suggest that the full syndrome of cretinism represents only the most obvious part of a large community disability. From a hitherto unknown endemic area in Zaire THILLY and others5 reported a goitre rate of 100% and a prevalence of cretinism of up to 7-6%. In Papua New Guinea the prevalence of cretinism among children in some villages approaches 15%.’ These figures serve to underline the enormous potential benefits of effective prevention.
Bacteriuria—When Does it Matter? SYMPTOMS, scars, and stones are the important consequences of bacteriuria. Urinary symptoms cause much morbidity and account for the consumption of huge quantities of antibacterial agents. The existence in Britain of a lay organisation, the U and I Club, for people with such symptoms testifies to the shortcomings of existing treatments. A more satisfactory approach may develop from two 19. Pharoah
POD, Lawton NF, Ellis SM, Williams ES, Ekins RP. The role of in the maintenance of euthyroidism in endemic goitre. Clin Endocrinol 1973; 2: 193-99. 20. Greer MA, Grimm Y, Struder H. Qualitative changes in the secretion of thyroid hormones induced by iodine deficiency. Endocrinology 1968; 83:
triiodothyronine (T3)
1193-98. 21.
Delange F, Camus M, Ermans AM. Circulating thyroid mic goitre. J Clin Endocrinol 1972; 34: 891-95.
hormones
in
ende-
22. Patel YC, Pharoah POD, Hornabrook RW, Hetzel BS. Serum triiodothyronine, thyroxine and thyroid-stimulating hormone in endemic goitre.
J Clin Endocrinol 1973, 37: 783-89.
pointers-the success of long-term low-dose antibacterial prophylaxis in the treatment and prevention of bacteriuria,1,2 and the suggestion of a
recent
possible bacterial explanation for "urethral syndrome".3It is now clear that no patient with urinary symptoms should be submitted to frequent courses of full-dose antibacterial therapy or to the regimen known as rotating antibiotics. Any patient with frequent symptomatic urinary infection should be referred for intravenous urography (IVP); after a course of an appropriate antibacterial, the patient should probably embark on a regimen of low-dose prophylaxis coupled with high fluid intake and regular and complete bladder emptying. In the adult with a normal IVP, a year without infection on this regimen probably means a low risk of subsequent infection. Adults with
radiological abnormalities and the very small minority with impaired renal function require longer supervision. The prognosis for adult patients with bacteriuria and renal scarring is not yet clear-in one study4 most such patients fared well, but we have yet to see whether control of bacteriuria can improve the outlook for the minority who deteriorate. About 20% of patients admitted to dialysis programmes have a primary diagnosis of bacterial pyelonephritis,’ and there is some general agreement about the natural history of this disease; renal scarring is associated with bacteriuria in the presence of vesicoureteric reflux; it usually begins in childhood when the kidneys are growing (often before the age of five); and it arises only rarely in the previously undamaged kidneys of an adult. There is also good evidence6,7-though not quite so widely accepted-that reflux in the absence of bacteriuria does not result in scarring. The other major risk to renal tissue which results from bacteriuria is the formation of friable mixed phosphate stones in the renal pelvis. Often the infection is due to a urea-splitting organism.8-10 If the infection is not controlled the stone may grow until it fills the renal pelvis and calyces, WR, Chamberlain DA, Fry IK, McSherry MA, Broughton C, O’Grady F. Long-term control of bacteriuria with trimethoprim-sulphonamide. Br Med J 1971; i: 377-79. 2. Smellie JM, Grüneberg RN, Leakey A, Atkin WS. Long-term low-dose co-trimoxazole in prophylaxis of childhood urinary tract infection: clinical aspects. Br Med J 1976; ii: 203-08. 3. Maskell R, Pead L, Allen J. The puzzle of "urethral syndrome": a possible 1. Cattell
answer? Lancet 1979; i: 1088-89. 4. Gower PE. A prospective study of patients with radiological pyelonephritis, papillary necrosis and obstructive atrophy. Quart J Med 1976, 45: 315-49. 5. Wing AJ, et al. Combined report on regular dialysis and transplantation in Europe, viii, 1977. Proc Europ Dialysis Transplant Assoc 1978, 15: 3-77. 6. Edwards D, Normand ICS, Prescod N, Smellie JM. Disappearance of vesicoureteric reflux during long-term prophylaxis of urinary tract infection in children. Br Med J 1977; ii, 285-88. 7. Ransley PG, Risdon RA. Reflux and renal scarring. Br J Radiol 1978, suppl 14. 8. Nemoy NJ, Stamey TA. Surgical, bacteriological and biochemical management of "infection stones". JAMA 1971; 215: 1470-76. 9. Wickham JEA. Matrix and the infective renal calculus. Br J Urol 1976; 47: 727-32. 10. Ghazali S, Barratt TM, Williams DI. Childhood urolithiasis in Britain. Arch Dis Childh 1973; 48: 291-95.
1167
destroying renal tissue by back pressure and sometimes causing pyonephrosis, septicaemia, and
teriuric
death.
greater in this group than in matched controls who were known not to have been bacteriuric in childhood. These observations emphasise the importance of detecting bacteriuria in children, but do not necessarily prove that screening is the best way to do this. Incidentally, one factor contributing to the considerable morbidity in their patients may have been that, throughout the study, episodes of bacteriuria were treated with short courses of antibiotics. KUNIN and co-workers comment on the "lack of evidence that current treatment effectively prevents recurrent infection", but the studies1S.19 they cite in support of this view were of short duration. SMELLiE and her colleagues2 have shown that prophylaxis may be needed for several years; we keenly await the data on adult follow-up of children who were kept free of bacteriuria in this
Despite many excellent long-term studies of bacteriuria, in both adults and children, there is still no certain way of detecting those patients in whom the disease is benign and in whom treatment need be directed only to relief of symptoms, and those in whom there is risk of renal damage. O’GRADyll lately concluded that "the effort of two decades ... has yet to produce a test that can be used in the clinic to identify, with a high degree of confidence, patients at special risk". A non-invasive test such as the search for antibody-coated bacteria in the urine has great attraction, but on p. 1172 this week K. A. MUNDT and B. F. POLK point out that this, too, has limitations. FASTH et al. 12 have reported significantly higher levels of IgG and IgA autoantibodies to Tamm-Horsfall protein in girls with "acute pyelonephritis" than in those with "acute cystitis"; girls with radiological scarring but no infection at the time of testing had significantly lower anti-TH levels than controls. Whilst these findings may further our understanding of the pathological processes in post-infection renal scarring, they do not offer a realistic means of selecting patients for radiological investigation and long-term follow-up. It seems that we must still rely on clinical acumen, urine culture, and radiography. Population screening for bacteriuria has been extensively investigated; with efficient communications between patient, obstetrician, and laboratory, screening for bacteriuria in early pregnancy can undoubtedly prevent morbidity and identify patients who need subsequent investigation.13 The justification for childhood screening is much less clear; the major screening programmes14-16 in the United Kingdom all led to the conclusion that widespread screening of schoolgirls, and radiological investigation of those with bacteriuria, would not be sufficiently effective in identifying those children at risk of serious disease to justify the use of resources necessary for the task. This judgment is questioned 17 by the pioneer of childhood screening, C. M. KUNIN, and his colleagues in Charlottesville, Virginia. They followed into adult life 60 bac11.
F. Urinary tract infection in women. J Roy Coll Physns Lond 1979; 13: 70-73. 12. Fasth A, Hanson LA, Jodal U, Peterson H. Autoantibodies to Tamm-Horsfall protein associated with urinary tract infections in girls. J Pediat 1979; 95: 54-60. 13 Williams JD, Reeves DS, Brumfltt W, Condie AP. The effects of bacteriuria in pregnancy on maternal health. In: Brumfitt W, Asscher AW, eds Urinary tract infection London: Oxford University Press, 1973; 103-07. 14. Savage DCL, Wilson MI, McHardy M, Dewar DAE, Fee WM. Covert bacteriuria of childhood. Arch Dis Childh 1973; 48: 8-20. 15. Newcastle Asymptomatic Bacteriuria Research Group. Asymptomatic bacteriuria in schoolchildren in Newcastle-upon-Tyne. Arch Dis Childh 1975; 50: 90-102. 16. Cardiff-Oxford Bacteriuna Study Group. Sequelæ of covert bacteriuria in schoolgirls: a four-year follow-up study. Lancet 1978;i: 889-93. 17. Gillenwater JY, Harrison RB, Kunin CM. Natural history of bacteriuria in schoolgirls. N Engl J Med 1979; 301: 396-99.
O’Grady
girls identified in 1959-62 by screening. Morbidity due to bacteriuria was significantly
way. An alternative
approach to childhood screening is emphasise the importance of identifying those children in whom bacteriuria gives rise to clinical illness-those with urinary symptoms, enuresis (especially girls2O), unexplained fevers, or failure to thrive. Given good laboratory facilities, general practitioners can identify such children in the sort of numbers revealed by screening programmes. 20 The team approach, so well exemplified in the screening programmes, should be applied to the subsequent investigation and management of these children. A team of paediatrician, microbiologist, surgeon, and radiologist will have all the necessary to
skills. There should be no unnecessary surgery for reflux of a degree likely to disappear spontaneously, and in those children who have reflux surgery bacteriological follow-up will be adequate; the unpleasant investigation of micturating cystography, which itself carries a high risk of inducing bacteriuria,21 will not be undertaken unnecessarily and repeatedly on children with normal IVPs in whom bacteriuria has been successfully controlled; and clinical management will include the teaching of good micturition habits as well as the rational treatment and prevention of infection, monitored by regular urine culture. A team approach of this kind is effective in the management not only of children, but also of adults,’ and POLAK22 and his colleagues have shown that it reduces morbidity in patients with infection stones.
JM. Duration of treatment for urinary tract infections in children. Br Med J 1975; iii: 65-66. 19. Smellie JM, Katz G, Grüneberg R. Controlled trial of prophylactic treatment in childhood urinary-tract infection. Lancet 1978; ii: 175-78. 20. Maskell R, Pead L. Urinary infection in children in general practice: a laboratory view. J Hyg Camb 1976; 77: 291-98. 21. Maskell R, Pead L, Vinnicombe J. Urinary infection after micturating cystography. Lancet 1978; ii: 1191-92. 22. Chinn RH, Maskell R, Mead JA, Polak A. Renal stones and urinary infection: a study of antibiotic treatment. Br Med J 1976; ii: 1411-13. 18. Stansfeld
maternal hypothyroidism, lack of elemental iodine in and the fetus.12 Proof of this, even in laboratory animals, will be difficult. The normal physiological response to iodine deficiency is a fall in serum thyroxine (T4) and a rise in serum thyrotropin; but serum triiodothyronine (T3) remains normal or is even raised.19-22 A further possibility therefore is that the fetus is harmed by an imbalance in maternal T3/T4, even though the mother is clinically euthyroid. Answers to these questions might well throw light on the aetiology and pathogenesis of other
not
through fetal and one possibility is a
forms of cerebral palsy. The severity and pattern of neurological damage is variable and we do not know which aspects of iodine deficiency are critical-the degree, the duration, or the timing. Might different areas of the brain be vulnerable at specific periods of development ? Is endemic cretinism a distinct entity within a population, or is there a range of mental retardation and motor incompetence with a quota of subclinical deficit which merges into normality? In the first article this week, Prof.CONNOLLY and his co-workers report a significantly better motor competence in those children whose mothers were not iodine deficient during pregnancy. Their findings suggest that the full syndrome of cretinism represents only the most obvious part of a large community disability. From a hitherto unknown endemic area in Zaire THILLY and others5 reported a goitre rate of 100% and a prevalence of cretinism of up to 7-6%. In Papua New Guinea the prevalence of cretinism among children in some villages approaches 15%.’ These figures serve to underline the enormous potential benefits of effective prevention.
Bacteriuria—When Does it Matter? SYMPTOMS, scars, and stones are the important consequences of bacteriuria. Urinary symptoms cause much morbidity and account for the consumption of huge quantities of antibacterial agents. The existence in Britain of a lay organisation, the U and I Club, for people with such symptoms testifies to the shortcomings of existing treatments. A more satisfactory approach may develop from two 19. Pharoah
POD, Lawton NF, Ellis SM, Williams ES, Ekins RP. The role of in the maintenance of euthyroidism in endemic goitre. Clin Endocrinol 1973; 2: 193-99. 20. Greer MA, Grimm Y, Struder H. Qualitative changes in the secretion of thyroid hormones induced by iodine deficiency. Endocrinology 1968; 83:
triiodothyronine (T3)
1193-98. 21.
Delange F, Camus M, Ermans AM. Circulating thyroid mic goitre. J Clin Endocrinol 1972; 34: 891-95.
hormones
in
ende-
22. Patel YC, Pharoah POD, Hornabrook RW, Hetzel BS. Serum triiodothyronine, thyroxine and thyroid-stimulating hormone in endemic goitre.
J Clin Endocrinol 1973, 37: 783-89.
pointers-the success of long-term low-dose antibacterial prophylaxis in the treatment and prevention of bacteriuria,1,2 and the suggestion of a
recent
possible bacterial explanation for "urethral syndrome".3It is now clear that no patient with urinary symptoms should be submitted to frequent courses of full-dose antibacterial therapy or to the regimen known as rotating antibiotics. Any patient with frequent symptomatic urinary infection should be referred for intravenous urography (IVP); after a course of an appropriate antibacterial, the patient should probably embark on a regimen of low-dose prophylaxis coupled with high fluid intake and regular and complete bladder emptying. In the adult with a normal IVP, a year without infection on this regimen probably means a low risk of subsequent infection. Adults with
radiological abnormalities and the very small minority with impaired renal function require longer supervision. The prognosis for adult patients with bacteriuria and renal scarring is not yet clear-in one study4 most such patients fared well, but we have yet to see whether control of bacteriuria can improve the outlook for the minority who deteriorate. About 20% of patients admitted to dialysis programmes have a primary diagnosis of bacterial pyelonephritis,’ and there is some general agreement about the natural history of this disease; renal scarring is associated with bacteriuria in the presence of vesicoureteric reflux; it usually begins in childhood when the kidneys are growing (often before the age of five); and it arises only rarely in the previously undamaged kidneys of an adult. There is also good evidence6,7-though not quite so widely accepted-that reflux in the absence of bacteriuria does not result in scarring. The other major risk to renal tissue which results from bacteriuria is the formation of friable mixed phosphate stones in the renal pelvis. Often the infection is due to a urea-splitting organism.8-10 If the infection is not controlled the stone may grow until it fills the renal pelvis and calyces, WR, Chamberlain DA, Fry IK, McSherry MA, Broughton C, O’Grady F. Long-term control of bacteriuria with trimethoprim-sulphonamide. Br Med J 1971; i: 377-79. 2. Smellie JM, Grüneberg RN, Leakey A, Atkin WS. Long-term low-dose co-trimoxazole in prophylaxis of childhood urinary tract infection: clinical aspects. Br Med J 1976; ii: 203-08. 3. Maskell R, Pead L, Allen J. The puzzle of "urethral syndrome": a possible 1. Cattell
answer? Lancet 1979; i: 1088-89. 4. Gower PE. A prospective study of patients with radiological pyelonephritis, papillary necrosis and obstructive atrophy. Quart J Med 1976, 45: 315-49. 5. Wing AJ, et al. Combined report on regular dialysis and transplantation in Europe, viii, 1977. Proc Europ Dialysis Transplant Assoc 1978, 15: 3-77. 6. Edwards D, Normand ICS, Prescod N, Smellie JM. Disappearance of vesicoureteric reflux during long-term prophylaxis of urinary tract infection in children. Br Med J 1977; ii, 285-88. 7. Ransley PG, Risdon RA. Reflux and renal scarring. Br J Radiol 1978, suppl 14. 8. Nemoy NJ, Stamey TA. Surgical, bacteriological and biochemical management of "infection stones". JAMA 1971; 215: 1470-76. 9. Wickham JEA. Matrix and the infective renal calculus. Br J Urol 1976; 47: 727-32. 10. Ghazali S, Barratt TM, Williams DI. Childhood urolithiasis in Britain. Arch Dis Childh 1973; 48: 291-95.
1167
destroying renal tissue by back pressure and sometimes causing pyonephrosis, septicaemia, and
teriuric
death.
greater in this group than in matched controls who were known not to have been bacteriuric in childhood. These observations emphasise the importance of detecting bacteriuria in children, but do not necessarily prove that screening is the best way to do this. Incidentally, one factor contributing to the considerable morbidity in their patients may have been that, throughout the study, episodes of bacteriuria were treated with short courses of antibiotics. KUNIN and co-workers comment on the "lack of evidence that current treatment effectively prevents recurrent infection", but the studies1S.19 they cite in support of this view were of short duration. SMELLiE and her colleagues2 have shown that prophylaxis may be needed for several years; we keenly await the data on adult follow-up of children who were kept free of bacteriuria in this
Despite many excellent long-term studies of bacteriuria, in both adults and children, there is still no certain way of detecting those patients in whom the disease is benign and in whom treatment need be directed only to relief of symptoms, and those in whom there is risk of renal damage. O’GRADyll lately concluded that "the effort of two decades ... has yet to produce a test that can be used in the clinic to identify, with a high degree of confidence, patients at special risk". A non-invasive test such as the search for antibody-coated bacteria in the urine has great attraction, but on p. 1172 this week K. A. MUNDT and B. F. POLK point out that this, too, has limitations. FASTH et al. 12 have reported significantly higher levels of IgG and IgA autoantibodies to Tamm-Horsfall protein in girls with "acute pyelonephritis" than in those with "acute cystitis"; girls with radiological scarring but no infection at the time of testing had significantly lower anti-TH levels than controls. Whilst these findings may further our understanding of the pathological processes in post-infection renal scarring, they do not offer a realistic means of selecting patients for radiological investigation and long-term follow-up. It seems that we must still rely on clinical acumen, urine culture, and radiography. Population screening for bacteriuria has been extensively investigated; with efficient communications between patient, obstetrician, and laboratory, screening for bacteriuria in early pregnancy can undoubtedly prevent morbidity and identify patients who need subsequent investigation.13 The justification for childhood screening is much less clear; the major screening programmes14-16 in the United Kingdom all led to the conclusion that widespread screening of schoolgirls, and radiological investigation of those with bacteriuria, would not be sufficiently effective in identifying those children at risk of serious disease to justify the use of resources necessary for the task. This judgment is questioned 17 by the pioneer of childhood screening, C. M. KUNIN, and his colleagues in Charlottesville, Virginia. They followed into adult life 60 bac11.
F. Urinary tract infection in women. J Roy Coll Physns Lond 1979; 13: 70-73. 12. Fasth A, Hanson LA, Jodal U, Peterson H. Autoantibodies to Tamm-Horsfall protein associated with urinary tract infections in girls. J Pediat 1979; 95: 54-60. 13 Williams JD, Reeves DS, Brumfltt W, Condie AP. The effects of bacteriuria in pregnancy on maternal health. In: Brumfitt W, Asscher AW, eds Urinary tract infection London: Oxford University Press, 1973; 103-07. 14. Savage DCL, Wilson MI, McHardy M, Dewar DAE, Fee WM. Covert bacteriuria of childhood. Arch Dis Childh 1973; 48: 8-20. 15. Newcastle Asymptomatic Bacteriuria Research Group. Asymptomatic bacteriuria in schoolchildren in Newcastle-upon-Tyne. Arch Dis Childh 1975; 50: 90-102. 16. Cardiff-Oxford Bacteriuna Study Group. Sequelæ of covert bacteriuria in schoolgirls: a four-year follow-up study. Lancet 1978;i: 889-93. 17. Gillenwater JY, Harrison RB, Kunin CM. Natural history of bacteriuria in schoolgirls. N Engl J Med 1979; 301: 396-99.
O’Grady
girls identified in 1959-62 by screening. Morbidity due to bacteriuria was significantly
way. An alternative
approach to childhood screening is emphasise the importance of identifying those children in whom bacteriuria gives rise to clinical illness-those with urinary symptoms, enuresis (especially girls2O), unexplained fevers, or failure to thrive. Given good laboratory facilities, general practitioners can identify such children in the sort of numbers revealed by screening programmes. 20 The team approach, so well exemplified in the screening programmes, should be applied to the subsequent investigation and management of these children. A team of paediatrician, microbiologist, surgeon, and radiologist will have all the necessary to
skills. There should be no unnecessary surgery for reflux of a degree likely to disappear spontaneously, and in those children who have reflux surgery bacteriological follow-up will be adequate; the unpleasant investigation of micturating cystography, which itself carries a high risk of inducing bacteriuria,21 will not be undertaken unnecessarily and repeatedly on children with normal IVPs in whom bacteriuria has been successfully controlled; and clinical management will include the teaching of good micturition habits as well as the rational treatment and prevention of infection, monitored by regular urine culture. A team approach of this kind is effective in the management not only of children, but also of adults,’ and POLAK22 and his colleagues have shown that it reduces morbidity in patients with infection stones.
JM. Duration of treatment for urinary tract infections in children. Br Med J 1975; iii: 65-66. 19. Smellie JM, Katz G, Grüneberg R. Controlled trial of prophylactic treatment in childhood urinary-tract infection. Lancet 1978; ii: 175-78. 20. Maskell R, Pead L. Urinary infection in children in general practice: a laboratory view. J Hyg Camb 1976; 77: 291-98. 21. Maskell R, Pead L, Vinnicombe J. Urinary infection after micturating cystography. Lancet 1978; ii: 1191-92. 22. Chinn RH, Maskell R, Mead JA, Polak A. Renal stones and urinary infection: a study of antibiotic treatment. Br Med J 1976; ii: 1411-13. 18. Stansfeld
