1361 Six patients failed to achieve complete remission. Three achieved a good partial remission with blast-cell populations in the marrow between 5 and 10%. In the other three the response was poor, the blast-cell population in the marrow remaining above 20%. These patients were all elderly (aged 66, 67, and 75), but other elderly patients in our series have achieved full and long remissions and we therefore continue to treat such patients in the same way as the younger patients although the initial courses of therapy may be at half or twothirds doses. Remission has usually emerged after one or two D.A.T. courses and the severely cytopenic phase has therefore been short and we have not needed to isolate the patient or sterilise the gut. We do, however, emphasise the importance of general supportive care in the early detection and effective management of infective and hxmorrhagic episodes. Department of Hæmatological Medicine, University of Cambridge Clinical School, Cambridge CB2 2QL
J. K. H. REES F. G. J. HAYHOE
"COVERT BACTERIURIA" IN SCHOOLGIRLS
SIR,-Renal scarring resulting from urinary-tract infection
(u.T.i.) in childhood is one of the few preventable causes of renal failure, so I agree with Professor Arneil (May 20, p. 1093) that every effort should be made to diagnose u.T.i. in children. I agree also, however, with Professor Asscher and his colleagues (April 29, p. 889) that screening of schoolgirls is not the best way to do this. For one thing, asymptomatic bacteriuria is rare in boys,I,2 and therefore they have been excluded from screening programmes; symptomatic U.T.i., however, is not so rare, and renal scars develop in some of these boys.3,4 An alternative approach to the detection of bacteriuria in children is for general practitioners to be aware of U.T.I. as a possible diagnosis, not only in children with symptoms referable to the urinary tract but also in those with unexplained illness or who fail to thrive. Owing to the difficulties of specimen collection, general practitioners tend not to send urines from babies and young children for culture, and there is a need for cooperation between laboratories, paediatricians, and general practitioners to improve this. However, when we recorded the results of urine specimens sent to our laboratory by general practitioners from children between the ages of two and twelve years over the course of 12 months, we identified 231 girls and 56 boys with definite infection (108/1 pure growth), and a further 66 girls and 43 boys with probable infection (10V1 pure growth). These numbers equal, or exceed if the children with probable infection are included, the number of girls identified in Cardiff and Oxford by the screening programme, and these children had all presented as patients to their doctors. It may be that the correct approach is for general practitioners to be alert, to it, for laboratories to assist by arranging for specimen collection and transport, and for all children with a proven U.T.I. to be referred to a paediatrician and to have an intravenous pyelogram. The result of this investigation, and careful bacteriological follow-up would identify those in need of further investigation and long-term chemoprophylaxis,6 and the onus for supervision of the others would be on the parent and the general practitioner. Asscher states (June 10, p. 1266) that there is a sizeable spontaneous cure-rate. It would be interesting to know whether the children in whom this occurred had received antibacterial therapy from their general practitioners for other 1. Kumn, C. 2. Newcastle
M., Zacha, E., Paquin, A. J. New Engl. J. Med. 1962, 266, 1287.
Asymptomatic Bacteriuria Research Group 1975, 50, 90. 3. Cohen, M. Am. J Dis. Child. 1976, 130, 810. 4.
Archs Dis. Childh.
Hallett, R. J., Pead, L., Maskell, R. Lancet, 1976, ii, 1107. 5. Maskell, R M., Pead, L. J. Hyg., Camb. 1976, 77, 291 6. Smellie, J. M., Grüneberg, R. N., Leakey, A., Atkm, W. S. Br med. J. 1976, ii, 203.
of ampicillin, or even penicillin, for an upperinfection may well be effective in curing an respiratory-tract episode of bacteriuria. reasons.
A
course
Public Health Laboratory, St. Mary’s General Hospital, Portsmouth PO3 6AQ
ROSALIND MASKELL
TREATMENT OF ACUTE HEPATIC PORPHYRIA
SIR,-Your editorial (May 13, p. 1024) highlights
a
few of
the
problems of treating patients with an "inducible"’ porphyria. We agree that proper management, especially avoidance of an attack, can indeed reduce complications and fatalities in patients with porphyria. Proper management hinges to a great extent on an early diagnosis, using a reliable test,2 and a quick therapeutic intervention thereafter. We thus would like to correct your suggestion that hsematin "at present, should perhaps be reserved for those patients in whom clinical deterioration persists despite carbohydrate infusion." The porphyric attack should be terminated as quickly as possible if lasting neuronal damage is to be prevented. Once the neuropathy has reached a chronic phase, hxmatin is of little value.3 Thus hxmatin should not be thought of as the second, but rather the first drug of choice. Also, we do not consider infusion of haematin to be "less straightforward than administration of carbohydrates"; haematin is easy to prepare and, by curtailing an attack, cuts the costs of treatment. We have also dispensed hxmatin to other physicians for administration to their patients, even abroad, with gratifying results. Although we observed a transient renal insufficiency in one of our volunteers not then in an acute attack, this happened early in our experience when high doses were administered in a short time. At the dosage we now use no such side-effects have been observed. When we compared glucose and hoematinwe found hxmatin to be often decisive in its beneficial effect after glucose had led to insufficient improvement. Our policy now is to administer hsematin as early as possible in an attack, thereby not only correcting the biochemical abnormalities, but also, and more important, preventing chronic porphyric neuropathy. Our experience with hsematin has been most encouraging4 even with bulbar paralysis and quadriparesis. Medical Research Unit,
University of Minnesota, Northwestern Hospital, Mineapolis, Minnesota 55407, U.S.A.
C. A. PIERACH
C. J. WATSON
SIR,-Your editorial discusses the biochemical pathology and treatment of acute hepatic porphyrias and stresses the importance of preventing the acute attacks through diagnosis during the symptomless phase, avoidance of known precipitants, and erythrocyte enzymic tests. This, however, leaves unanswered the question whether a new (or existing) drug is likely to precipitate an attack. Results from this laboratory5 suggest that utilisation ofhsem by rat-liver tryptophan pyrrolase may provide a means of predicting drug exacerbation of hepatic porphyrias. The production of experimental porphyria in rats by administration of porphyrogens such as 3, 5-diethoxycarbonyl-l, 4-dihydrocollidine is associatedwith an early loss of some of 1.
Watson, C. J., Pierach, C. A., Bossenmaier, I., Cardinal, R. Proc. natn. Acad. Sci. U.S.A 1977, 74, 2118 2. Pierach, C. A., Cardinal, R., Bossenmaier, I., Watson, C. J. Clin. Chem. 1977, 23, 1666. 3. Bosch, E. P., Pierach, C. A., Bossenmaier, I., Cardinal, R., Thorson, M. Neurology, 1977, 27, 1053. 4. Watson, C. J., Pierach, C. A., Bossenmaier, I., Cardinal, R. Adv. intern. Med. 1978, 23, 265. 5. Badawy, A. A.-B. Biochem. J. 1978, 172, 487. 6. Badawy, A. A.-B., Evans, M. ibid. 1973, 136, 885.
J. K. H. REES F. G. J. HAYHOE
"COVERT BACTERIURIA" IN SCHOOLGIRLS
SIR,-Renal scarring resulting from urinary-tract infection
(u.T.i.) in childhood is one of the few preventable causes of renal failure, so I agree with Professor Arneil (May 20, p. 1093) that every effort should be made to diagnose u.T.i. in children. I agree also, however, with Professor Asscher and his colleagues (April 29, p. 889) that screening of schoolgirls is not the best way to do this. For one thing, asymptomatic bacteriuria is rare in boys,I,2 and therefore they have been excluded from screening programmes; symptomatic U.T.i., however, is not so rare, and renal scars develop in some of these boys.3,4 An alternative approach to the detection of bacteriuria in children is for general practitioners to be aware of U.T.I. as a possible diagnosis, not only in children with symptoms referable to the urinary tract but also in those with unexplained illness or who fail to thrive. Owing to the difficulties of specimen collection, general practitioners tend not to send urines from babies and young children for culture, and there is a need for cooperation between laboratories, paediatricians, and general practitioners to improve this. However, when we recorded the results of urine specimens sent to our laboratory by general practitioners from children between the ages of two and twelve years over the course of 12 months, we identified 231 girls and 56 boys with definite infection (108/1 pure growth), and a further 66 girls and 43 boys with probable infection (10V1 pure growth). These numbers equal, or exceed if the children with probable infection are included, the number of girls identified in Cardiff and Oxford by the screening programme, and these children had all presented as patients to their doctors. It may be that the correct approach is for general practitioners to be alert, to it, for laboratories to assist by arranging for specimen collection and transport, and for all children with a proven U.T.I. to be referred to a paediatrician and to have an intravenous pyelogram. The result of this investigation, and careful bacteriological follow-up would identify those in need of further investigation and long-term chemoprophylaxis,6 and the onus for supervision of the others would be on the parent and the general practitioner. Asscher states (June 10, p. 1266) that there is a sizeable spontaneous cure-rate. It would be interesting to know whether the children in whom this occurred had received antibacterial therapy from their general practitioners for other 1. Kumn, C. 2. Newcastle
M., Zacha, E., Paquin, A. J. New Engl. J. Med. 1962, 266, 1287.
Asymptomatic Bacteriuria Research Group 1975, 50, 90. 3. Cohen, M. Am. J Dis. Child. 1976, 130, 810. 4.
Archs Dis. Childh.
Hallett, R. J., Pead, L., Maskell, R. Lancet, 1976, ii, 1107. 5. Maskell, R M., Pead, L. J. Hyg., Camb. 1976, 77, 291 6. Smellie, J. M., Grüneberg, R. N., Leakey, A., Atkm, W. S. Br med. J. 1976, ii, 203.
of ampicillin, or even penicillin, for an upperinfection may well be effective in curing an respiratory-tract episode of bacteriuria. reasons.
A
course
Public Health Laboratory, St. Mary’s General Hospital, Portsmouth PO3 6AQ
ROSALIND MASKELL
TREATMENT OF ACUTE HEPATIC PORPHYRIA
SIR,-Your editorial (May 13, p. 1024) highlights
a
few of
the
problems of treating patients with an "inducible"’ porphyria. We agree that proper management, especially avoidance of an attack, can indeed reduce complications and fatalities in patients with porphyria. Proper management hinges to a great extent on an early diagnosis, using a reliable test,2 and a quick therapeutic intervention thereafter. We thus would like to correct your suggestion that hsematin "at present, should perhaps be reserved for those patients in whom clinical deterioration persists despite carbohydrate infusion." The porphyric attack should be terminated as quickly as possible if lasting neuronal damage is to be prevented. Once the neuropathy has reached a chronic phase, hxmatin is of little value.3 Thus hxmatin should not be thought of as the second, but rather the first drug of choice. Also, we do not consider infusion of haematin to be "less straightforward than administration of carbohydrates"; haematin is easy to prepare and, by curtailing an attack, cuts the costs of treatment. We have also dispensed hxmatin to other physicians for administration to their patients, even abroad, with gratifying results. Although we observed a transient renal insufficiency in one of our volunteers not then in an acute attack, this happened early in our experience when high doses were administered in a short time. At the dosage we now use no such side-effects have been observed. When we compared glucose and hoematinwe found hxmatin to be often decisive in its beneficial effect after glucose had led to insufficient improvement. Our policy now is to administer hsematin as early as possible in an attack, thereby not only correcting the biochemical abnormalities, but also, and more important, preventing chronic porphyric neuropathy. Our experience with hsematin has been most encouraging4 even with bulbar paralysis and quadriparesis. Medical Research Unit,
University of Minnesota, Northwestern Hospital, Mineapolis, Minnesota 55407, U.S.A.
C. A. PIERACH
C. J. WATSON
SIR,-Your editorial discusses the biochemical pathology and treatment of acute hepatic porphyrias and stresses the importance of preventing the acute attacks through diagnosis during the symptomless phase, avoidance of known precipitants, and erythrocyte enzymic tests. This, however, leaves unanswered the question whether a new (or existing) drug is likely to precipitate an attack. Results from this laboratory5 suggest that utilisation ofhsem by rat-liver tryptophan pyrrolase may provide a means of predicting drug exacerbation of hepatic porphyrias. The production of experimental porphyria in rats by administration of porphyrogens such as 3, 5-diethoxycarbonyl-l, 4-dihydrocollidine is associatedwith an early loss of some of 1.
Watson, C. J., Pierach, C. A., Bossenmaier, I., Cardinal, R. Proc. natn. Acad. Sci. U.S.A 1977, 74, 2118 2. Pierach, C. A., Cardinal, R., Bossenmaier, I., Watson, C. J. Clin. Chem. 1977, 23, 1666. 3. Bosch, E. P., Pierach, C. A., Bossenmaier, I., Cardinal, R., Thorson, M. Neurology, 1977, 27, 1053. 4. Watson, C. J., Pierach, C. A., Bossenmaier, I., Cardinal, R. Adv. intern. Med. 1978, 23, 265. 5. Badawy, A. A.-B. Biochem. J. 1978, 172, 487. 6. Badawy, A. A.-B., Evans, M. ibid. 1973, 136, 885.
