- Email: [email protected]
CIRCUMCISION
1263
clay-coloured, and bile drained freely, but in diminishing quantities, for the next 18-19 days. Cholangiography on the 23rd postoperativeday showed most of the dye around the tube, but a little had passed into the duodenum. The tube was then gradually clamped over a week, and then kept continuously closed for 3 days, with no ill effects except a little local discomfort. Further cholangiography showed that the dye passed into the bowel. The tube was removed on the 39th day. The patient has been quite well ever since as far as his The fractures required prolonged abdomen is concerned. rehabilitation, but he is now fit for light work.
The
outstanding features
of the
case were :
(1) The extreme collapse of the rendering anatomical identification
common
bile-duct,
in the bile-soaked
tissues difficult. (2) The involvement of the commencement of the cystic duct in -the tear, which excluded the use of this duct as an alternative bile channel by means of a
cholecystenterostomy. (3) The relatively smooth convalescence without as yet, 16 months later, symptoms of stricture formation, which would usually be expected within a year if this was going to be a troublesome development.
(4) The laceration on the under-surface of the liver, which suggests that the force may have been in such a line as to cause the liver to crush or tear the ducts against the vertebras—a mechanism suggested by Lewis.’ My thanks are due to Mr. R. L. Benison for permission to publish these notes and for his help with the operation. HENRY B. YOUNG.
Wolverhampton. "
CHEMOTHERAPEUTIC AGENT "ANTIBIOTIC
"
AND
"
SiR,-The purpose of my letter (Oct. 17) was to expose the implications, and possible consequences, which could arise from Dr. Erwin’s " suggested " basis for " a more " exact liberal definition of ’chemotherapeutic agent ’ an more recent use of " exact liberal (Oct. 24). His definition " clearly vindicates my point. No-one would regard aspirin as.an antibiotic simply because " a sufficient quantity destroys the life of man." All would, without exception, and unhesitatingly, regard it as a poison;and this quite apart from the fact that " antibiotics " act, as Professor Waksman (Aug. 22). has said, in dilute solution to destroy micro-organisms." " Terms," Sir, have connotations-they imply the attributes while denoting the subject. If " chemotherapeutic agent " and " antibiotic " are, as Dr. Erwin declares, " terms recently coined, and, therefore, still evolving," Dr. Erwin can scarce forbear to cheer the sanity and wisdom of Professor Waksman’s sober summary : "Proper definitions are available, without sacrificing historical perspective, scientific accuracy, or current usage, and this should not be left to the whim of individuals who decide to redefine important terms according to their own points of view." M. GLASS. Cape Town. CIRCUMCISION the literature on this subject, and in the SiR,-In excellent article by " Sir Daniel Whiddon " (Aug. 15), no mention is made of the fact that it is possible in normal persons, without any operation, to obtain the same endresult-namely, an exposed glans. The method is as
follows :
During the year or so before puberty the boy is told to retract his foreskin and clean the glans every time he takes a bath. Gradually as puberty approaches, and as the glans becomes hardened, the foreskin is kept retracted. This has the effect of allowing the glans to grow through the foreskin, leaving it behind. The end-result is a penis indistinguishable from, or superior to. the most skilfully circumcised one. Instruction in this procedure appears to be usually passed from father to son in certain families; few 1.
Lewis,
K. M.
Ann. Surg. 1938
108
237.
doctors seem to have heard of it. There is possibly some risk of balanitis, and the manceuvre should therefore be carried out preferably only under the intelligent supervision of the father. UNCIRCUMCISED. DEXTRAN SULPHATE
Sm,ņWe should like to answer Dr. Berenbaum’s comments (Nov. 28) on a statement in our paper reporting the
therapeutic
trial of dextran
sulphate.
One
patient
(case 8) died from coronary thrombosis while under treatment. The statement that staining with toluidine-blue of histological sections taken at necropsy failed to show storage of dextran sulphate is held to be a possible misinterpretation, since it is suggested that this method of demonstrating polysaccharides is unreliable unless the material is protein-bound or otherwise rendered insoluble. In the first place, while we would agree that toluidine-blue is an unreliable stain for neutral polysaccharides, since in fact it fails to stain these, in our hands it has been found capable of demonstrating, by the metachromatic reaction, concentrations as low as 1-2 ug. of highly sulphated polysaccharides (such as the material used in our clinical trial).
Secondly, during the preliminary biological screening of sulphate, we have had available material from given dextran sulphates of various molecular sizes. Comparisons have been made of tissues prepared by freezedrying techniques, by fixation, mounting, and staining in alcohol, and by the ordinary histological routine after treatment with fixatives containing mercuric salts or with formolsaline. It has been our experience that when material was demonstrable by either of the first two methods, it was also demonstrable by the use of the usual techniques in material dextran animals
fixed in watery fixatives.
Experimental evidence from animal studies suggests that while’ protein-binding is essential for the uptake of sulphated polysaccharides by the reticulo-endothelial cells, it is not essential for the demonstration of these compounds in the cell. For example, it has been shown that dextran sulphates of large molecular size form insoluble complexes with the plasma proteins and that these particulate precipitates are cleared from the blood-stream by the phagocytic activity of reticuloendothelial cells. Material staining metachromatically with toluidine-blue is demonstrable as granules within these cells where it persists for twenty-eight days or longer.’ Examination of these granules in freeze-dried material in the ultraviolet light microscope and measurement of the absorption at a wave-length of 2800A° gave no indication of the presence of protein in the phagocytosed material if the animal had been allowed to survive longer than four hours after the injection of the dextran sulphate. This suggested that the protein moiety of the phagocytosed material was split off and metabolised quickly by the active proteolytic enzymes known to be present in reticulo-endothelial cells, leaving the sulphated polysaccharide component to undergo slower katabolism.2 This is in keeping with the findings of Kaplan et al.3 and of Coons et allwho showed that even heterologous and foreign proteins disappear considerably more quickly from reticulo-endothelial cells than similarly phagocytosed polysaccharides. On the other hand, it has been shown that dextran sulphate of uniformly small molecular size (such as that used in the clinical trial) does not form insoluble complexes with the plasma proteins. In our opinion, it is for this reason that, even in much greater dosage than that used clinically, the injection of such material does not result in the appearance of granular metachromatic material in the reticulo-endothelial cells of experimental 1. Walton, K. W. Proc. R. Soc. Med. 1951, 44, 2. Walton, K. W. Brit. J. Pharmacol. (in the 3. Kaplan, M. H., Coons, A. H., Deane, H. W. 91, 15. 4. Coons, A. H., Leduc, E. H., Kaplan, M. H.
563.
press). J. exp. Med. 1950,
Ibid, 1951, 93, 173.
clay-coloured, and bile drained freely, but in diminishing quantities, for the next 18-19 days. Cholangiography on the 23rd postoperativeday showed most of the dye around the tube, but a little had passed into the duodenum. The tube was then gradually clamped over a week, and then kept continuously closed for 3 days, with no ill effects except a little local discomfort. Further cholangiography showed that the dye passed into the bowel. The tube was removed on the 39th day. The patient has been quite well ever since as far as his The fractures required prolonged abdomen is concerned. rehabilitation, but he is now fit for light work.
The
outstanding features
of the
case were :
(1) The extreme collapse of the rendering anatomical identification
common
bile-duct,
in the bile-soaked
tissues difficult. (2) The involvement of the commencement of the cystic duct in -the tear, which excluded the use of this duct as an alternative bile channel by means of a
cholecystenterostomy. (3) The relatively smooth convalescence without as yet, 16 months later, symptoms of stricture formation, which would usually be expected within a year if this was going to be a troublesome development.
(4) The laceration on the under-surface of the liver, which suggests that the force may have been in such a line as to cause the liver to crush or tear the ducts against the vertebras—a mechanism suggested by Lewis.’ My thanks are due to Mr. R. L. Benison for permission to publish these notes and for his help with the operation. HENRY B. YOUNG.
Wolverhampton. "
CHEMOTHERAPEUTIC AGENT "ANTIBIOTIC
"
AND
"
SiR,-The purpose of my letter (Oct. 17) was to expose the implications, and possible consequences, which could arise from Dr. Erwin’s " suggested " basis for " a more " exact liberal definition of ’chemotherapeutic agent ’ an more recent use of " exact liberal (Oct. 24). His definition " clearly vindicates my point. No-one would regard aspirin as.an antibiotic simply because " a sufficient quantity destroys the life of man." All would, without exception, and unhesitatingly, regard it as a poison;and this quite apart from the fact that " antibiotics " act, as Professor Waksman (Aug. 22). has said, in dilute solution to destroy micro-organisms." " Terms," Sir, have connotations-they imply the attributes while denoting the subject. If " chemotherapeutic agent " and " antibiotic " are, as Dr. Erwin declares, " terms recently coined, and, therefore, still evolving," Dr. Erwin can scarce forbear to cheer the sanity and wisdom of Professor Waksman’s sober summary : "Proper definitions are available, without sacrificing historical perspective, scientific accuracy, or current usage, and this should not be left to the whim of individuals who decide to redefine important terms according to their own points of view." M. GLASS. Cape Town. CIRCUMCISION the literature on this subject, and in the SiR,-In excellent article by " Sir Daniel Whiddon " (Aug. 15), no mention is made of the fact that it is possible in normal persons, without any operation, to obtain the same endresult-namely, an exposed glans. The method is as
follows :
During the year or so before puberty the boy is told to retract his foreskin and clean the glans every time he takes a bath. Gradually as puberty approaches, and as the glans becomes hardened, the foreskin is kept retracted. This has the effect of allowing the glans to grow through the foreskin, leaving it behind. The end-result is a penis indistinguishable from, or superior to. the most skilfully circumcised one. Instruction in this procedure appears to be usually passed from father to son in certain families; few 1.
Lewis,
K. M.
Ann. Surg. 1938
108
237.
doctors seem to have heard of it. There is possibly some risk of balanitis, and the manceuvre should therefore be carried out preferably only under the intelligent supervision of the father. UNCIRCUMCISED. DEXTRAN SULPHATE
Sm,ņWe should like to answer Dr. Berenbaum’s comments (Nov. 28) on a statement in our paper reporting the
therapeutic
trial of dextran
sulphate.
One
patient
(case 8) died from coronary thrombosis while under treatment. The statement that staining with toluidine-blue of histological sections taken at necropsy failed to show storage of dextran sulphate is held to be a possible misinterpretation, since it is suggested that this method of demonstrating polysaccharides is unreliable unless the material is protein-bound or otherwise rendered insoluble. In the first place, while we would agree that toluidine-blue is an unreliable stain for neutral polysaccharides, since in fact it fails to stain these, in our hands it has been found capable of demonstrating, by the metachromatic reaction, concentrations as low as 1-2 ug. of highly sulphated polysaccharides (such as the material used in our clinical trial).
Secondly, during the preliminary biological screening of sulphate, we have had available material from given dextran sulphates of various molecular sizes. Comparisons have been made of tissues prepared by freezedrying techniques, by fixation, mounting, and staining in alcohol, and by the ordinary histological routine after treatment with fixatives containing mercuric salts or with formolsaline. It has been our experience that when material was demonstrable by either of the first two methods, it was also demonstrable by the use of the usual techniques in material dextran animals
fixed in watery fixatives.
Experimental evidence from animal studies suggests that while’ protein-binding is essential for the uptake of sulphated polysaccharides by the reticulo-endothelial cells, it is not essential for the demonstration of these compounds in the cell. For example, it has been shown that dextran sulphates of large molecular size form insoluble complexes with the plasma proteins and that these particulate precipitates are cleared from the blood-stream by the phagocytic activity of reticuloendothelial cells. Material staining metachromatically with toluidine-blue is demonstrable as granules within these cells where it persists for twenty-eight days or longer.’ Examination of these granules in freeze-dried material in the ultraviolet light microscope and measurement of the absorption at a wave-length of 2800A° gave no indication of the presence of protein in the phagocytosed material if the animal had been allowed to survive longer than four hours after the injection of the dextran sulphate. This suggested that the protein moiety of the phagocytosed material was split off and metabolised quickly by the active proteolytic enzymes known to be present in reticulo-endothelial cells, leaving the sulphated polysaccharide component to undergo slower katabolism.2 This is in keeping with the findings of Kaplan et al.3 and of Coons et allwho showed that even heterologous and foreign proteins disappear considerably more quickly from reticulo-endothelial cells than similarly phagocytosed polysaccharides. On the other hand, it has been shown that dextran sulphate of uniformly small molecular size (such as that used in the clinical trial) does not form insoluble complexes with the plasma proteins. In our opinion, it is for this reason that, even in much greater dosage than that used clinically, the injection of such material does not result in the appearance of granular metachromatic material in the reticulo-endothelial cells of experimental 1. Walton, K. W. Proc. R. Soc. Med. 1951, 44, 2. Walton, K. W. Brit. J. Pharmacol. (in the 3. Kaplan, M. H., Coons, A. H., Deane, H. W. 91, 15. 4. Coons, A. H., Leduc, E. H., Kaplan, M. H.
563.
press). J. exp. Med. 1950,
Ibid, 1951, 93, 173.