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UNTREATED MYELOMENINGOCELE
1421 here since the true peak occurs very shortly after the end of the injection; at 20 min the concentration is falling rapidly because distribution of drug from the blood is still the dominant pharmacokinetic process. Equilibration with extravascular tissue occurs about 60 min after injection and, theoretically, it makes the best sense to monitor then since the concentration observed is a better reflection of that in the tissues, including the more inaccessible sites where infection may well be. Because of the rapidly falling concentrations at 20 min only small variations in timing, as is very likely on the wards, will cause large differences in the observed concentrations which could falsely be taken to warrant changes in therapy. Even a moderate shortening from 20 min might result in a very high level. A further practical point is that it is customary to monitor an approximate peak at 60 min after the intramuscular injection of an aminoglycoside. Constancy of advice in using the "one-hour level" for both modes of administration is less confusing for ward staff and removes a potential source of error. In their discussion on vancomycin the working party should have pointed out that the peak concentration should be measured at the end of the 60 min infusion (a true peak) and not some time after the infusion has been stopped. The report carries no warning about the use of benzylpenicillin at
the dosage recommended (12 megaunits daily) in the presence of reduced renal function, a finding not uncommon in endocarditis. This antibiotic has a potential for serious neurotoxicity if very high blood concentrations occur, and I have witnessed a patient with endocarditis having seizures in these circumstances. High dosage of benzylpenicillin requires empirical modification in renal failure or, better still, blood concentrations should be monitored. Department of Medical Southmead Hospital, Bristol BS10 5NB
Microbiology,
letters have been shown follows.-ED. L.
**These
D. S. REEVES to
Dr Simmons, whose
reply
SiR,—Dr Robinson rightly points out that for most penicillinsensitive streptococci the MIC and MBC of benzylpenicillin are much less than 1 mg/l. However, the working party’s use of the term "fully sensitive" should be interpreted in the context of its report. We recommended that penicillin and gentamicin should normally be used for the treatment of streptococcal endocarditis. The term "fully sensitive" was used to distinguish those organisms causing infections, for which the gentamicin should be given for only two weeks, from those "with reduced sensitivity to penicillin", for which gentamicin should be given for not less than four weeks. In this respect we regard an MBC of 1 mg/l as a suitable dividing line. She fears that some physicians, rendered overoptimistic by our terminology, may treat some patients, especially those with impaired renal function, with inadequate amounts of penicillin alone. "Low doses" of penicillin should never be used for the treatment of endocarditis in patients with normal renal function. If the dosage has to be reduced, provided the reduction is proportionate to the degree of renal failure, the blood levels should still be substantially above 1 mg/1. Dr Reeves says that we should not have used the term "peak" concentration when referring to the level in blood 20 min after an intravenous bolus injection. Although it is common parlance, he is correct. His comments about the relative merits of 20 min and 60 min gentamicin blood levels are ofinterest. When the working party looked at current advice in respect of the timing of the collection of blood after intravenous injections of gentamicin, we found that one data sheet (’Cidomycin’) indicated that peak levels were reached after 15 min and another (’Genticin’) gave no precise advice. The British National Formulary (1985, no 10: 201) recommends that plasma concentrations should be measured about 20 min after an intravenous injection, and since all of the members of the working party followed this recommendation, we included it in our report. However, if one hour levels come to be accepted as being more appropriate, the working party, when it reviews its recommendations, will certainly take note of the fact. Department of Clinical Bacteriology, Guy’s Hospital, London SE1 9RT
N. A. SIMMONS, Chairman, BSAC Endocarditis Working Party
UNTREATED MYELOMENINGOCELE
SIR,-The Newcastle group’s report (Nov 2, p 993) that
a
with extensive myelomeningocele survive if left untreated, but cared for at home, should be seen in context. The conclusion that, mobility apart, such children are ultimately "no more handicapped than the children offered immediate surgical treatment" need not be read as an invitation to return to a nonselective policy of treating babies with myelomeningocele. The 27 infants taken home represent just 11% of those not selected for immediate surgical treatment. How they differed from the 89% who were kept in hospital (and died) is not pursued, but perhaps a clue is that families usually requested discharge home "if the baby was still making satisfactory progress 2-4 weeks after delivery"; those not progressing well (most probably as a result of
proportion of babies
central
nervous system sepsis or rapidly increasing hydrocephalus) presumably kept in hospital. By inference, those babies taken home were largely self-selecting and likely to be inherently superior to the majority with large myelomeningoceles. They seem to have milder hydrocephalus since shunts had been inserted quite late and none had appreciable intellectual impairment. This runs counter to other experience, which is that many patients with lumbar and thoracolumbar myelomeningoceles have intelligence within the educationally subnormal range (or worse) and that, in general, the degree of intellectual impairment relates directly to the extent of the myelomeningocele and to the neurological deficit.l-3 Apart from their superior intelligence, the survivors appear to be just as handicapped as any others with extensive myelomeningocele. All were wheelchair bound, in contrast to only 50% of those selected for immediate surgery and, predictably, all had a neuropathic bladder, whereas around one quarter of the surgically treated cases escaped this affliction. Problems with the upper renal tracts are were
mentioned only en þassant although there is evidence that the risk of these increases with the extent of the myelomeningocele.4,5 Spinal deformities are not described, yet most of these children could be expected to be severely deformed by adolescence, in contrast to those with smaller lesions,3while pressure sores are another 3
probable complications A simple interpretation of this report is that there exists a small group of babies with lumbar and thoracolumbar myelomeningoceles who have mild hydrocephalus and, as a result, are more likely to survive and to have reasonably normal intelligence. In other respects their handicaps are predictably severe. This conclusion would be neither startling nor original and I remain puzzled (even after several readings) as to why the Dean of Durham and his colleagues (Nov 2, p 996) felt moved to agonise, yet agam, over the ethical issues involved. Department of Paediatric Urology, Hey Children’s Hospital, Liverpool L12 2AP. Alder
A. M. K. RICKWOOD
1. Hunt 2.
3
4. 5
GM, Holmes AE. Some factors relating to intelligence in treated children with spma bifida Devl Med Child Neurol 1975, suppl 35: 65-69 Lonton AP Location of the myelomeningocele and its relationship to subsequent physical and intellectual abilities in children with myelomeningocele with hydrocephalus. Z Kinderchir 1977, 22: 510-19. Rickwood AMK, Hodgson J, Lonton AP, Thomas DG. Medical and surgical complications in adolescents and young adults with spina bifida. Health Trends 1984; 16: 91-95. Hunt GM, Bishop MC, Whitaker RH, Doyle PT Sensory level and renal prognosis in myelomeningocele. Z Kinderchir 1981; 34: 384-89. Rickwood AMK, Thomas DG. The upper renal tracts in adolescents and young adults with myelomeningocele. Z Kinderchir 1984, 39: 104-06.
LATENT VITAMIN K DEFICIENCY IN HEALTHY INFANTS?
SIR,-Late onset haemorrhagic disease of the newborn (HDN) is life-threatening. Most cases have been observed in Asia: in Japan the incidence was 1 in 4500 in unselected babies and 81°70 of infants with HDN presented with intracranial haemorrhage.However, 20 cases over four years have been recorded in West Germany, suggesting an incidence of at least 1 per 100 000.2 Latent vitamin K deficiency without clinical evidence of bleeding may be more common. In a Japanese study PIVKA II, a marker of vitamin K 3 status, was not detected in 14% of healthy 1-month-old babies. Data for European infants have not been reported.
the dosage recommended (12 megaunits daily) in the presence of reduced renal function, a finding not uncommon in endocarditis. This antibiotic has a potential for serious neurotoxicity if very high blood concentrations occur, and I have witnessed a patient with endocarditis having seizures in these circumstances. High dosage of benzylpenicillin requires empirical modification in renal failure or, better still, blood concentrations should be monitored. Department of Medical Southmead Hospital, Bristol BS10 5NB
Microbiology,
letters have been shown follows.-ED. L.
**These
D. S. REEVES to
Dr Simmons, whose
reply
SiR,—Dr Robinson rightly points out that for most penicillinsensitive streptococci the MIC and MBC of benzylpenicillin are much less than 1 mg/l. However, the working party’s use of the term "fully sensitive" should be interpreted in the context of its report. We recommended that penicillin and gentamicin should normally be used for the treatment of streptococcal endocarditis. The term "fully sensitive" was used to distinguish those organisms causing infections, for which the gentamicin should be given for only two weeks, from those "with reduced sensitivity to penicillin", for which gentamicin should be given for not less than four weeks. In this respect we regard an MBC of 1 mg/l as a suitable dividing line. She fears that some physicians, rendered overoptimistic by our terminology, may treat some patients, especially those with impaired renal function, with inadequate amounts of penicillin alone. "Low doses" of penicillin should never be used for the treatment of endocarditis in patients with normal renal function. If the dosage has to be reduced, provided the reduction is proportionate to the degree of renal failure, the blood levels should still be substantially above 1 mg/1. Dr Reeves says that we should not have used the term "peak" concentration when referring to the level in blood 20 min after an intravenous bolus injection. Although it is common parlance, he is correct. His comments about the relative merits of 20 min and 60 min gentamicin blood levels are ofinterest. When the working party looked at current advice in respect of the timing of the collection of blood after intravenous injections of gentamicin, we found that one data sheet (’Cidomycin’) indicated that peak levels were reached after 15 min and another (’Genticin’) gave no precise advice. The British National Formulary (1985, no 10: 201) recommends that plasma concentrations should be measured about 20 min after an intravenous injection, and since all of the members of the working party followed this recommendation, we included it in our report. However, if one hour levels come to be accepted as being more appropriate, the working party, when it reviews its recommendations, will certainly take note of the fact. Department of Clinical Bacteriology, Guy’s Hospital, London SE1 9RT
N. A. SIMMONS, Chairman, BSAC Endocarditis Working Party
UNTREATED MYELOMENINGOCELE
SIR,-The Newcastle group’s report (Nov 2, p 993) that
a
with extensive myelomeningocele survive if left untreated, but cared for at home, should be seen in context. The conclusion that, mobility apart, such children are ultimately "no more handicapped than the children offered immediate surgical treatment" need not be read as an invitation to return to a nonselective policy of treating babies with myelomeningocele. The 27 infants taken home represent just 11% of those not selected for immediate surgical treatment. How they differed from the 89% who were kept in hospital (and died) is not pursued, but perhaps a clue is that families usually requested discharge home "if the baby was still making satisfactory progress 2-4 weeks after delivery"; those not progressing well (most probably as a result of
proportion of babies
central
nervous system sepsis or rapidly increasing hydrocephalus) presumably kept in hospital. By inference, those babies taken home were largely self-selecting and likely to be inherently superior to the majority with large myelomeningoceles. They seem to have milder hydrocephalus since shunts had been inserted quite late and none had appreciable intellectual impairment. This runs counter to other experience, which is that many patients with lumbar and thoracolumbar myelomeningoceles have intelligence within the educationally subnormal range (or worse) and that, in general, the degree of intellectual impairment relates directly to the extent of the myelomeningocele and to the neurological deficit.l-3 Apart from their superior intelligence, the survivors appear to be just as handicapped as any others with extensive myelomeningocele. All were wheelchair bound, in contrast to only 50% of those selected for immediate surgery and, predictably, all had a neuropathic bladder, whereas around one quarter of the surgically treated cases escaped this affliction. Problems with the upper renal tracts are were
mentioned only en þassant although there is evidence that the risk of these increases with the extent of the myelomeningocele.4,5 Spinal deformities are not described, yet most of these children could be expected to be severely deformed by adolescence, in contrast to those with smaller lesions,3while pressure sores are another 3
probable complications A simple interpretation of this report is that there exists a small group of babies with lumbar and thoracolumbar myelomeningoceles who have mild hydrocephalus and, as a result, are more likely to survive and to have reasonably normal intelligence. In other respects their handicaps are predictably severe. This conclusion would be neither startling nor original and I remain puzzled (even after several readings) as to why the Dean of Durham and his colleagues (Nov 2, p 996) felt moved to agonise, yet agam, over the ethical issues involved. Department of Paediatric Urology, Hey Children’s Hospital, Liverpool L12 2AP. Alder
A. M. K. RICKWOOD
1. Hunt 2.
3
4. 5
GM, Holmes AE. Some factors relating to intelligence in treated children with spma bifida Devl Med Child Neurol 1975, suppl 35: 65-69 Lonton AP Location of the myelomeningocele and its relationship to subsequent physical and intellectual abilities in children with myelomeningocele with hydrocephalus. Z Kinderchir 1977, 22: 510-19. Rickwood AMK, Hodgson J, Lonton AP, Thomas DG. Medical and surgical complications in adolescents and young adults with spina bifida. Health Trends 1984; 16: 91-95. Hunt GM, Bishop MC, Whitaker RH, Doyle PT Sensory level and renal prognosis in myelomeningocele. Z Kinderchir 1981; 34: 384-89. Rickwood AMK, Thomas DG. The upper renal tracts in adolescents and young adults with myelomeningocele. Z Kinderchir 1984, 39: 104-06.
LATENT VITAMIN K DEFICIENCY IN HEALTHY INFANTS?
SIR,-Late onset haemorrhagic disease of the newborn (HDN) is life-threatening. Most cases have been observed in Asia: in Japan the incidence was 1 in 4500 in unselected babies and 81°70 of infants with HDN presented with intracranial haemorrhage.However, 20 cases over four years have been recorded in West Germany, suggesting an incidence of at least 1 per 100 000.2 Latent vitamin K deficiency without clinical evidence of bleeding may be more common. In a Japanese study PIVKA II, a marker of vitamin K 3 status, was not detected in 14% of healthy 1-month-old babies. Data for European infants have not been reported.