180 normal ranges.6,7There is, in the living animal, competition between aminoacids that share common transport systems but the effect is only severe when the blood concentration of the inhibitor is above normal.4,5,8 over
Our results in laboratory animals suggest that the entry tryptophan into the brain is likely to be increased in acute hepatic failure partly as a result of the direct action of insulin upon the system which transports it into the brain, and partly because there is a raised level of free tryptophan 9 in the blood in this condition. We therefore support the view of Curzon et a1. that the level of free tryptophan in the plasma is an important factor in determining the entry of this aminoacid into the brain. In acute hepatic failure not only are the concentrations of the branched-chain aminoacids in the blood reduced, but the concentrations of various other aminoacids-e.g. methionine and phenylalanine 10—are increased considerably. Because of these disturbances in the bloodaminoacid pattern, competition 4,5,8 between these and other aminoacids may play some part in cerebral dysfunction by altering the pattern of essential aminoacids which are being supplied to the brain from the blood. P. M. DANIEL Department of Neuropathology, E. R. LOVE Institute of Psychiatry, S. R. MOORHOUSE De Crespigny Park, O. E. PRATT. London SE5 8AF. of
TRANSPOSONS AND ANTIBIOTIC RESISTANCE editorial SIR,—In your (June 28, p. 1411), you comment at length on a review article of mine. 11 The overall impression is sufficiently at variance with what I actually wrote that I suggest that interested readers should refer to the original article. In this article I attempted to examine objectively the possible interpretation of sets of data (the reliability of the actual data was not questioned). I discussed the arguments for and against transfer. Surely such objective analysis is the essence of review articles ? Your editorial contains a very subjective view of antibiotic resistance. The following statements are either incorrect or should have had factual
backing: (1) The use of phage-typing and serotyping as epidemiological tools were not " cast aside ". After giving detailed examples of the instability of phage typing, I wrote " Thus phage typing has severe limitations in identifying specific strains of S. aureus over several years. This shortcoming of phage-typing possibly applies also to Salmonella typhimurium." Where is the evidence for the stability of phage type in this organism ? (2) " His [mine] explanations of observed facts seem less probable than those of the original observers." Since in most instances, a variety of explanations were offered, it is not surprising that some are more likely than others. I stated this clearly. The essential point I was trying to make was that transfer experiments in the laboratory may or may not apply in nature. More data from clinical sources are needed. Your editorial merely restates the traditional opinion; it does not strengthen it. (3) " Lacey suggests that the unnecessary use of antibiotics may, in some cases, actually be beneficial, because R+ bacteria may (by virtue of having to support the plasmid) be less virulent." 6. 7. 8. 9. 10. 11.
Baños, G., Daniel, P. M., Moorhouse, S. R., Pratt, O. E. Proc. R. Soc. B. 1973, 183, 59. Baños, G., Daniel, P. M., Moorhouse, S. R., Pratt, O. E. J. Physiol. 1975, 246, 539. Baños, G., Daniel, P. M., Pratt, O. E. ibid. 1974, 236, 29. Knell, A. J., Davidson, A. R., Williams, R., Kantamaneni, B. D., Curzon, G. Br. med. J. 1974, i, 549. Knell, A. J., Pratt, O. E., Curzon, G., Williams, R. 8th Symposium of Advanced Medicine; p. 156. London, 1972. Lacey, R. W. J. antimicrob. Chemother. 1975, 1, 25.
I did not mean or say anything like that. What I said was: " The overall impression is, therefore, that apart from the rare instance of the plasmids that determine specific ’virulence factors ’, R-factor and plasmid carriage is associated with loss I did not of virulence, although sometimes very slight." advocate the unnecessary use of antibiotics. (4) A worldwide increase in the frequency of chloramphenicol resistance in the typhoid bacillus is attributed by Prof. E. S. Anderson to the indiscriminate use of antibiotics and few would disagree with him. This was not disputed. In fact I said " R-factor carriage amongst dangerous pathogens, such as Salmonella typhi, is of grave significance." My point was that if R-factor transfer did occur at all frequently in nature, it is surprising that it took so long for any R-factor determining chloramphenicol resistance to appear in this organism.
Department of Bacteriology, North Cambridgeshire Hospital, Wisbech.
R. W. LACEY.
SPRUE AGAIN editorial1 you cite epidemiological observations conducted by our unit in Puerto Rico which document a concomitant peak seasonal incidence of both the onset of symptoms of overt tropical sprue and the occurrence of subclinical malabsorption among the general population of this island.Contrary to what is stated in the editorial, we noted a correlation between this seasonal incidence of intestinal disease, contamination of the small bowel by enterotoxigenic coliform bacterial and an increased dietary intake of long-chain unsaturated fatty acids (especially of linoleic acid) associated with qualitative changes in the dietary pattern of this population that occur during the Christmas season. We did not consider rainfall a significant factor. We should also like to point out that, as presented in the editorial, the hypothesised role of dietary lipids does not make sense. The editorial states: " When these fatty acids are displaced from the diet, bacteria may come in and induce and perpetuate the mucosal lesion." What we suggested is quite the opposite-namely, that the presence of increased quantities of long-chain unsaturated fatty acids in the diet may alter the intestinal bacterial ecosystem by virtue of the well-recognised effect of these lipids in suppressing the growth of gram-positive bacteria, which are the principal flora of the small bowel under normal circumstances, so that there is a decreased resistance to overgrowth by alien organisms such as enterotoxigenic coliform bacteria. Whether this indeed happens within the intestinal tract of man is untested, but we have been able to show that such is the case under laboratory conditions when the effect of linoleic acid on Lactobacillus-Klebsiella interrelationships is examined using a continuous culture system.4 Tropical Malabsorption Unit of the Universities of Rochester and FREDERICK A. KLIPSTEIN Puerto Rico, San Juan, Puerto Rico 00935. JOSÉ J. CORCINO.
SIR,-In
an
HUMAN PLACENTAL LACTOGEN AND DIABETIC PREGNANCY
SIR,—There could be an important aside to the study (July 12, p. 54) of human placental lactogen levels in diabetic pregnancy, which shows higher levels than in normal pregnant women. Since I have published evidence5 that lactogen is probably the cause of the physiological inhibition Lancet, 1975, i, 1019. Klipstein, F. A., Corcino, J. J. Am. J. trop. Med. Hyg. 1974, 23, 1189. Klipstein, F. A., Holdeman, L. V., Corcino, J. J., Moore, W. E. C. Ann. intern. Med. 1971, 75, 41. 4. Mickelson, M. J., Klipstein, F. A. Clin. Res. 1975, 23, 308A. 5. Wardle, E. N. Int. Res. Commun. Syst. 1973 (73-12) 15-14-21. 1. 2. 3
Our results in laboratory animals suggest that the entry tryptophan into the brain is likely to be increased in acute hepatic failure partly as a result of the direct action of insulin upon the system which transports it into the brain, and partly because there is a raised level of free tryptophan 9 in the blood in this condition. We therefore support the view of Curzon et a1. that the level of free tryptophan in the plasma is an important factor in determining the entry of this aminoacid into the brain. In acute hepatic failure not only are the concentrations of the branched-chain aminoacids in the blood reduced, but the concentrations of various other aminoacids-e.g. methionine and phenylalanine 10—are increased considerably. Because of these disturbances in the bloodaminoacid pattern, competition 4,5,8 between these and other aminoacids may play some part in cerebral dysfunction by altering the pattern of essential aminoacids which are being supplied to the brain from the blood. P. M. DANIEL Department of Neuropathology, E. R. LOVE Institute of Psychiatry, S. R. MOORHOUSE De Crespigny Park, O. E. PRATT. London SE5 8AF. of
TRANSPOSONS AND ANTIBIOTIC RESISTANCE editorial SIR,—In your (June 28, p. 1411), you comment at length on a review article of mine. 11 The overall impression is sufficiently at variance with what I actually wrote that I suggest that interested readers should refer to the original article. In this article I attempted to examine objectively the possible interpretation of sets of data (the reliability of the actual data was not questioned). I discussed the arguments for and against transfer. Surely such objective analysis is the essence of review articles ? Your editorial contains a very subjective view of antibiotic resistance. The following statements are either incorrect or should have had factual
backing: (1) The use of phage-typing and serotyping as epidemiological tools were not " cast aside ". After giving detailed examples of the instability of phage typing, I wrote " Thus phage typing has severe limitations in identifying specific strains of S. aureus over several years. This shortcoming of phage-typing possibly applies also to Salmonella typhimurium." Where is the evidence for the stability of phage type in this organism ? (2) " His [mine] explanations of observed facts seem less probable than those of the original observers." Since in most instances, a variety of explanations were offered, it is not surprising that some are more likely than others. I stated this clearly. The essential point I was trying to make was that transfer experiments in the laboratory may or may not apply in nature. More data from clinical sources are needed. Your editorial merely restates the traditional opinion; it does not strengthen it. (3) " Lacey suggests that the unnecessary use of antibiotics may, in some cases, actually be beneficial, because R+ bacteria may (by virtue of having to support the plasmid) be less virulent." 6. 7. 8. 9. 10. 11.
Baños, G., Daniel, P. M., Moorhouse, S. R., Pratt, O. E. Proc. R. Soc. B. 1973, 183, 59. Baños, G., Daniel, P. M., Moorhouse, S. R., Pratt, O. E. J. Physiol. 1975, 246, 539. Baños, G., Daniel, P. M., Pratt, O. E. ibid. 1974, 236, 29. Knell, A. J., Davidson, A. R., Williams, R., Kantamaneni, B. D., Curzon, G. Br. med. J. 1974, i, 549. Knell, A. J., Pratt, O. E., Curzon, G., Williams, R. 8th Symposium of Advanced Medicine; p. 156. London, 1972. Lacey, R. W. J. antimicrob. Chemother. 1975, 1, 25.
I did not mean or say anything like that. What I said was: " The overall impression is, therefore, that apart from the rare instance of the plasmids that determine specific ’virulence factors ’, R-factor and plasmid carriage is associated with loss I did not of virulence, although sometimes very slight." advocate the unnecessary use of antibiotics. (4) A worldwide increase in the frequency of chloramphenicol resistance in the typhoid bacillus is attributed by Prof. E. S. Anderson to the indiscriminate use of antibiotics and few would disagree with him. This was not disputed. In fact I said " R-factor carriage amongst dangerous pathogens, such as Salmonella typhi, is of grave significance." My point was that if R-factor transfer did occur at all frequently in nature, it is surprising that it took so long for any R-factor determining chloramphenicol resistance to appear in this organism.
Department of Bacteriology, North Cambridgeshire Hospital, Wisbech.
R. W. LACEY.
SPRUE AGAIN editorial1 you cite epidemiological observations conducted by our unit in Puerto Rico which document a concomitant peak seasonal incidence of both the onset of symptoms of overt tropical sprue and the occurrence of subclinical malabsorption among the general population of this island.Contrary to what is stated in the editorial, we noted a correlation between this seasonal incidence of intestinal disease, contamination of the small bowel by enterotoxigenic coliform bacterial and an increased dietary intake of long-chain unsaturated fatty acids (especially of linoleic acid) associated with qualitative changes in the dietary pattern of this population that occur during the Christmas season. We did not consider rainfall a significant factor. We should also like to point out that, as presented in the editorial, the hypothesised role of dietary lipids does not make sense. The editorial states: " When these fatty acids are displaced from the diet, bacteria may come in and induce and perpetuate the mucosal lesion." What we suggested is quite the opposite-namely, that the presence of increased quantities of long-chain unsaturated fatty acids in the diet may alter the intestinal bacterial ecosystem by virtue of the well-recognised effect of these lipids in suppressing the growth of gram-positive bacteria, which are the principal flora of the small bowel under normal circumstances, so that there is a decreased resistance to overgrowth by alien organisms such as enterotoxigenic coliform bacteria. Whether this indeed happens within the intestinal tract of man is untested, but we have been able to show that such is the case under laboratory conditions when the effect of linoleic acid on Lactobacillus-Klebsiella interrelationships is examined using a continuous culture system.4 Tropical Malabsorption Unit of the Universities of Rochester and FREDERICK A. KLIPSTEIN Puerto Rico, San Juan, Puerto Rico 00935. JOSÉ J. CORCINO.
SIR,-In
an
HUMAN PLACENTAL LACTOGEN AND DIABETIC PREGNANCY
SIR,—There could be an important aside to the study (July 12, p. 54) of human placental lactogen levels in diabetic pregnancy, which shows higher levels than in normal pregnant women. Since I have published evidence5 that lactogen is probably the cause of the physiological inhibition Lancet, 1975, i, 1019. Klipstein, F. A., Corcino, J. J. Am. J. trop. Med. Hyg. 1974, 23, 1189. Klipstein, F. A., Holdeman, L. V., Corcino, J. J., Moore, W. E. C. Ann. intern. Med. 1971, 75, 41. 4. Mickelson, M. J., Klipstein, F. A. Clin. Res. 1975, 23, 308A. 5. Wardle, E. N. Int. Res. Commun. Syst. 1973 (73-12) 15-14-21. 1. 2. 3
