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ANTENATAL DIAGNOSIS OF ADRENOCORTICAL HYPERPLASIA
1099 observations suggest that in-vivo synergy was present. The combination of carbenicillin with colistin was effective and safe, and one must support the proposal that carbenicillin should be used with a second drug (colistin, polymyxin B, or gentamicin) when used against Pseudomonas aeruginosa. The carbenicillin was provided by Dr. E. T. Knudsen and tests of synergy and serial M.LC. estimations were kindly performed by Dr. R. Sutherland. I thank Dr. R. A. Shanks, visiting physician, for his support. Department of Neurology, Hospital for Sick Children, Toronto 2.
p. 987), the usefulness of the estimation of pregnanetriol in amniotic fluid has not been refuted or confirmed since their study was published.4 They emphasise that the published data from the second study on the value of steroid estimations on amniotic fluid of mothers at risk concerns only the 17-oxosteroid content, and it is this that has given inconclusive results, according to the pre-congress publication.5 However, even if estimation of pregnanetriol in amniotic fluid has clinical value it will be much less troublesome if it is proved possible to achieve the same result by a simple analysis of pregnancy urine.
J. B. P. STEPHENSON.
SIR,-Ishould like to compliment Dr. Bell and Dr. Smith on their elegant experiment. However, I would respectfully disagree with their conclusion that carbenicillin should not be used alone for fear of promoting resistance. At this hospital we have tested over 2000 strains of Pseudomonas ceruginosa by the disc method (100 µg. carbenicillin per disc) and, as Dr. Bell and Dr. Smith found, they have all been sensitive.
In addition we have determined the minimum concentration inhibitory (M.l.c.) of 150 of these strains, and found that the mode was 250, and the median 187 µg. per ml.in either case blood-levels considerably in excess of these figures are easily obtained. This highlights the fact that, despite these apparently high M.iC.S, treatment with adequate dosage of carbenicillin will result in a cure. In my own clinical experience1 two organisms were " trained " in vivo to absolute resistance. I have no doubt that, if doses of 16-30 g. of carbenicillin per day plus concomitant probenecid had been administered, resistance would not have occurred. In passing one must also mention that findings such as these workers describe can be applied to all the penicillins-i.e., resistance can be trained. To carry the argument to its logical conclusion, the only effective anti-pseudomonas drug which could be given with carbenicillin, to " shield " it, would be gentamicin. Quite apart from potential toxicity, and the need for daily serum assay of the drug, gentamicin is the best available antibiotic for severe gram-negative sepsis. But because some people use it topically -e.g., on the skin or as a bowel disinfectant-the chance of gentamicin-resistant strains of organisms emerging is also high. Caabenicillin can be used alone if big enough doses are given, as my own results show.
D. M. CATHRO J. BERTRAND.
I.N.S.E.R.M., Unité de Recherches, Hôpital Debrousse, Lyon 5e, France. Department of Obstetrics and Gynaecology, University of Dundee, Scotland.
MARY G. COYLE.
EXPERIENCE AT A BURNS CENTRE
SIR,-In the article by Dr. Sachs and Mr. Watson (April 5, 718), if we exclude patients with burns of less than 15% body surface burned (B.S.B.) (or 30 burn units [s.u.s]), the mortality-rates in the various tables, in most cases, become doubled. Thus, in table 11, the total number of patients with burns in excess of 15% B.s.B. is 126, with an overall mortality of 27%. The total number of patients with burns exceeding 30 B.u.s is 133 (mortality 26%) in table III, and the total is 91 (mortality 13%) in table vi. In table iv, excluding burns of p.
less than 30 B.u.s, the mortality examined become, in the order
rates
for the four age-groups and
given, 10%, 20%, 36%
56%. The conclusions of Dr. Sachs and Mr. Watson are the same those reached by many workers during the past 15 years. One is left wondering how long it will be before the topical use of 0-5% silver-nitrate solution, and the management of burn shock, following the precepts laid down by Moyerare going to be adopted. There seems little to be gained from further " use of the categories " pyo-prone " and " non-pyoprone as is shown by the following figures from the graph in fig. 1: as
St. Vincent’s
Hospital, Fitzroy 3065, Victoria, Australia.
The appearance of Pseudomonas spp. B. C. STRATFORD.
ANTENATAL DIAGNOSIS OF ADRENOCORTICAL HYPERPLASIA
SIR,-Before reporting on this case (April 5, p. 732) we analysed the results ofoestriol excretion in 1440 pregnancies and the highest single result was 44 mg. per 24 hours at the 38th week of pregnancy for a singleton pregnancy and 48 mg. per 24 hours for a twin pregnancy. In a triplet pregnancy the excretion was 44 mg. per 24 hours at the 33rd week. We therefore assumed that 58 mg. per 24 hours at the 34th week of pregnancy was well above the range for normal pregnancy using the method of Brown and Coyle2 which is specific for the determination of oestriol. The method of Oakey3 measures total oestrogens excreted in the urine and hence is less specific than the method used by us. This may account for some of the very high results obtained by Dr. Oakey (April 26, p. 887) in two normal pregnancies. We apologise to Professor Jeffcoate and his colleagues for a misleading statement in our letter. As they point out (May 10, 1. 2.
Stratford, B. C. Med. J. Aust. 1968, ii, 890. Brown, J. B., Coyle, M. G. J. Obstet. Gynœc. Br. Commonw. 1963, 70,
3.
Oakey, R. E., Bradshaw, L. R. A., Eccles, S. S., Stitch, S. R., Heyes, R. F. Clin. chim. Acta, 1967, 15, 35.
on
the burn wound is
inevitable, regardless of the treatment used or the area affected.7 With the use of silver nitrate, the choice of antibiotic can be such as to give maximum benefit, least risk of producing resistant strains of bacteria, and least risk of overgrowth of resistant bacteria and Candida.
W. B. HOUSTON.
*** This letter was shown to Dr. Sachs and Mr. whose reply follows.—ED. L.
Watson,
SIR,-We agree with Dr. Houston that the mortality in burns with greater than 30 burn units of tissue destruction is high. Our figures show this, but it was also our endeavour by classifying burns in terms of depth and type to overcome the limitations of crude mortality-rates, and to indicate the class of case in which improved treatment might lead to at least a marginal reduction in mortality. We have not found shock a significant factor in mortality when adequate therapy is commenced soon enough after injury. We do not agree that, because the appearance of Pseudomonas aruginosa 4. 5. 6.
219.
7.
Jeffcoate, T. N. A., Fliegner, J. R. H., Russell, S. H., Davis, J. C., Wade, A. P. Lancet, 1965, ii, 553. Merkatz, I. R., New, M. I. Excerpta med. int. Congr. Ser. 1968, 157, 175. Moyer, C. A., Brentano, L., Gravens, D. L., Margraf, H. W., Monafo, W. W. Archs Surg. 1965, 90, 812. Brentano, L., Moyer, C. A., Gravens, D. L., Monafo, W. W. ibid. 1966, 93, 456.
p. 987), the usefulness of the estimation of pregnanetriol in amniotic fluid has not been refuted or confirmed since their study was published.4 They emphasise that the published data from the second study on the value of steroid estimations on amniotic fluid of mothers at risk concerns only the 17-oxosteroid content, and it is this that has given inconclusive results, according to the pre-congress publication.5 However, even if estimation of pregnanetriol in amniotic fluid has clinical value it will be much less troublesome if it is proved possible to achieve the same result by a simple analysis of pregnancy urine.
J. B. P. STEPHENSON.
SIR,-Ishould like to compliment Dr. Bell and Dr. Smith on their elegant experiment. However, I would respectfully disagree with their conclusion that carbenicillin should not be used alone for fear of promoting resistance. At this hospital we have tested over 2000 strains of Pseudomonas ceruginosa by the disc method (100 µg. carbenicillin per disc) and, as Dr. Bell and Dr. Smith found, they have all been sensitive.
In addition we have determined the minimum concentration inhibitory (M.l.c.) of 150 of these strains, and found that the mode was 250, and the median 187 µg. per ml.in either case blood-levels considerably in excess of these figures are easily obtained. This highlights the fact that, despite these apparently high M.iC.S, treatment with adequate dosage of carbenicillin will result in a cure. In my own clinical experience1 two organisms were " trained " in vivo to absolute resistance. I have no doubt that, if doses of 16-30 g. of carbenicillin per day plus concomitant probenecid had been administered, resistance would not have occurred. In passing one must also mention that findings such as these workers describe can be applied to all the penicillins-i.e., resistance can be trained. To carry the argument to its logical conclusion, the only effective anti-pseudomonas drug which could be given with carbenicillin, to " shield " it, would be gentamicin. Quite apart from potential toxicity, and the need for daily serum assay of the drug, gentamicin is the best available antibiotic for severe gram-negative sepsis. But because some people use it topically -e.g., on the skin or as a bowel disinfectant-the chance of gentamicin-resistant strains of organisms emerging is also high. Caabenicillin can be used alone if big enough doses are given, as my own results show.
D. M. CATHRO J. BERTRAND.
I.N.S.E.R.M., Unité de Recherches, Hôpital Debrousse, Lyon 5e, France. Department of Obstetrics and Gynaecology, University of Dundee, Scotland.
MARY G. COYLE.
EXPERIENCE AT A BURNS CENTRE
SIR,-In the article by Dr. Sachs and Mr. Watson (April 5, 718), if we exclude patients with burns of less than 15% body surface burned (B.S.B.) (or 30 burn units [s.u.s]), the mortality-rates in the various tables, in most cases, become doubled. Thus, in table 11, the total number of patients with burns in excess of 15% B.s.B. is 126, with an overall mortality of 27%. The total number of patients with burns exceeding 30 B.u.s is 133 (mortality 26%) in table III, and the total is 91 (mortality 13%) in table vi. In table iv, excluding burns of p.
less than 30 B.u.s, the mortality examined become, in the order
rates
for the four age-groups and
given, 10%, 20%, 36%
56%. The conclusions of Dr. Sachs and Mr. Watson are the same those reached by many workers during the past 15 years. One is left wondering how long it will be before the topical use of 0-5% silver-nitrate solution, and the management of burn shock, following the precepts laid down by Moyerare going to be adopted. There seems little to be gained from further " use of the categories " pyo-prone " and " non-pyoprone as is shown by the following figures from the graph in fig. 1: as
St. Vincent’s
Hospital, Fitzroy 3065, Victoria, Australia.
The appearance of Pseudomonas spp. B. C. STRATFORD.
ANTENATAL DIAGNOSIS OF ADRENOCORTICAL HYPERPLASIA
SIR,-Before reporting on this case (April 5, p. 732) we analysed the results ofoestriol excretion in 1440 pregnancies and the highest single result was 44 mg. per 24 hours at the 38th week of pregnancy for a singleton pregnancy and 48 mg. per 24 hours for a twin pregnancy. In a triplet pregnancy the excretion was 44 mg. per 24 hours at the 33rd week. We therefore assumed that 58 mg. per 24 hours at the 34th week of pregnancy was well above the range for normal pregnancy using the method of Brown and Coyle2 which is specific for the determination of oestriol. The method of Oakey3 measures total oestrogens excreted in the urine and hence is less specific than the method used by us. This may account for some of the very high results obtained by Dr. Oakey (April 26, p. 887) in two normal pregnancies. We apologise to Professor Jeffcoate and his colleagues for a misleading statement in our letter. As they point out (May 10, 1. 2.
Stratford, B. C. Med. J. Aust. 1968, ii, 890. Brown, J. B., Coyle, M. G. J. Obstet. Gynœc. Br. Commonw. 1963, 70,
3.
Oakey, R. E., Bradshaw, L. R. A., Eccles, S. S., Stitch, S. R., Heyes, R. F. Clin. chim. Acta, 1967, 15, 35.
on
the burn wound is
inevitable, regardless of the treatment used or the area affected.7 With the use of silver nitrate, the choice of antibiotic can be such as to give maximum benefit, least risk of producing resistant strains of bacteria, and least risk of overgrowth of resistant bacteria and Candida.
W. B. HOUSTON.
*** This letter was shown to Dr. Sachs and Mr. whose reply follows.—ED. L.
Watson,
SIR,-We agree with Dr. Houston that the mortality in burns with greater than 30 burn units of tissue destruction is high. Our figures show this, but it was also our endeavour by classifying burns in terms of depth and type to overcome the limitations of crude mortality-rates, and to indicate the class of case in which improved treatment might lead to at least a marginal reduction in mortality. We have not found shock a significant factor in mortality when adequate therapy is commenced soon enough after injury. We do not agree that, because the appearance of Pseudomonas aruginosa 4. 5. 6.
219.
7.
Jeffcoate, T. N. A., Fliegner, J. R. H., Russell, S. H., Davis, J. C., Wade, A. P. Lancet, 1965, ii, 553. Merkatz, I. R., New, M. I. Excerpta med. int. Congr. Ser. 1968, 157, 175. Moyer, C. A., Brentano, L., Gravens, D. L., Margraf, H. W., Monafo, W. W. Archs Surg. 1965, 90, 812. Brentano, L., Moyer, C. A., Gravens, D. L., Monafo, W. W. ibid. 1966, 93, 456.