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EXTERNAL CARDIAC RESUSCITATION
1328 PROPHYLACTIC ANTIBIOTICS AND RESPIRATORY INFECTION
SIR,-Dr. Orr (Nov. 17) urges the use of prophylactic antibiotics for the prevention of respiratory infection in patients with myxcedema coma without demonstrating any benefit from them. Dr. Thulbourne and Dr. Young (Nov. 3) have shown that prophylactic antibiotics do not reduce the incidence of postoperative chest infections in general surgical patients. In this neurosurgical unit the only demonstrable effect of prophylactic antibiotics in comatose or stuporose patients is to alter the sputum flora to predominantly intestinal organisms resistant to most or all of the standard antibiotics, so that if pneumonia develops subsequently the choice of antibiotics is often very limited, if sputum culture can be taken as a reliable guide to effective treatment. Regular turning of the patient two-hourly or hourly, energetic physiotherapy to maintain the airway clear of secretions, prevention of dehydration, and sputum culture is in our opinion the best means of trying to prevent pneumonia in comatose patients and of preparing for early, appropriate antibiotic therapy if pneumonia develops. Neurosurgical Research Laboratories, Atkinson Morley’s Hospital, London, S.W.20.
P. RICHARDS.
ANTIMICROBIAL EFFECT OF HYDROGEN PEROXIDE AND LACTIC ACID IN THE MOUTH SIR,-The fact that there is in human saliva an antimicrobial defence mechanism, notably against Corynebacterium diphtheria, was discovered by Dold 1 and confirmed by numerous other workers,2-lo and can hardly be denied.
he attributes to me-namely, that the acidity produced by the oral streptococci, or the hydrogen peroxide as such produced by them, is responsible for the antimicrobial action of human saliva. On the contrary, if anyone held such views, I would, in unison with Dr. Davis, regard them as wholly erroneous.
A. KRAUS. EXTERNAL CARDIAC RESUSCITATION
SIR,-Iwas interested to read Mr. Keen’s article of Dec. 8. I fail to understand, however, why no mention was made of the breathing (as in the letter on the same subject on p. 1229 of the same issue), assuming naturally that it ceased with the cardiac arrest. Did it return spontaneously with the recommencement of the heart action, or was some form of artificial respiration used ? Ashby-de-la-Zouch,
H M. M AMPBELL. A. H. A CAMPBELL. Leicestershire.... CALCIUM AND CANCER
SIR,-The ideas of Dr. Elkeles1 (described in your annotation of Nov. 24) run parallel to our own. We are investigating the effects of ionising radiations on the absorption of bivalent metal ions by filamentous algae.2 This work shows that calcium ions act in a radiation-protective capacity with regard to membrane damage and the eventual death of the algae. The protective action of calcium towards changes in membrane behaviour is thought to lie in its ability to retain certain permeability characteristics even when other constituents have been EFFECT OF FLUCTUATION OF CALCIUM-ION CONCENTRATION ON THE METABOLISM AND MUTATION-RATES OF THE CELL
9
The action of this defence mechanism has up till now never been fully explained. My own conception of its mode of action
is, I believe, best represented by the following equations from Engler:" I. CH;,.CHOH.COOH+H,0,=CH,.COH+CO+2H,0
adapted
acetaldehyde acetaldehyde reacts with the oxygen of the air to form acetylperoxide: II. 2 CHs.COH+2 0,=(CH;,CO)sO+H,02 In the presence of an oxidisable substance X (for instance, on the surface of a microorganism) this substance may be oxidised by the acetylperoxide formed in reaction II: III. CHa.COO +XO ’" " ’ 0-- CH.3COOH CH.3COOH CH..COO ’+X+H2 The
These equations (which, of course, do not only apply to free lactic acid, but equally to its neutral salts), especially equation III, taken in conjunction with the fact that alkylperoxides are not attacked by catalase,12 to my mind satisfactorily explain why human saliva has an antimicrobial effect against C. diphtheriae, in spite of the fact that this organism produces catalase. The same or similar explanations may hold good to explain the activity of saliva against other micro-
organisms. I believe that this explanation completely answers all Dr. Davis’s questions and arguments (Nov. 10), including the one concerning the activity of catalase. If Dr. Davis will read my letter again, he will find that nowhere did I express the views 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
Dold, H., Lachele, W., Du Dscheng Hsing, Z. Hyg. InfektKr. 1936, 118, 369. Holzl, H. ibid. 1941, 123, 500. Knorr, M. Arch. Hyg., Berl. 1941, 126, 59. Hegemann, F., Z. Hyg. InfektKr. 1942, 124, 202. Thompson, R., Shibuya, M. 1946, J. Bact. 51, 671. Bethge, J., Soehring, K., Tschesche, R. Z. Naturf. 1947, 2B, 12. Berger, H. Z. Hyg. InfektKr. 1952, 133, 371. Dold, H., Ochsenreither, F. ibid. 1940, 122, 51. Boennicke, R. ibid. 1955-56, 142, 339. Lammers, T. Dtsch. Zahn-, Mund- Kieferheilk. 1953, 18, 378. Engler, C. Ber. dtsch. chem. Ges. 1900, 33, 1103, 1109. Stern, K. G. Z. physiol. Chem. 1932, 209, 176.
*
f-- Direction of Ca2+ cycle. Points where X-rays are known to have an effect. They will also increase membrane permeability.
damaged (e.g., fatty acids decarboxylated+dehydrogenated). Cells exposed to changes in calcium-ion concentration in the extracellular fluid may transmit this situation to the intracellular fluid (viz. precipitation and adsorption of Ca2+) and so produce the result which was observed by Dr. Elkeles in case of stomach cancer.3 Bivalent metal ions are found in chromosomestheir removal leads to an increase in chromosomal aberrations,56 and their presence is essential to, or
enhances, many enzyme processes (e.g.,
A.T.P.
breakdown,’8
All these factors combine into a calcium-ion clotting, &c.). (ionic strength) cycle which may lead to harmful mutations9 (see table). Whether the observed changes in calcium concentration are 1. Elkeles, A. Nature, Lond. 1962, 193, 1089. 2. 2nd International Congress of Radiation
p. 195.
Research, 1962; abstracts,
3. Elkeles, A. Brit. J. Cancer, 1959, 13, 403. 4. Mazia, D. Proc. nat. Acad. Sci., Wash. 1954, 40, 521. 5. Wolff, S., Luippold, H. E. ibid. 1956, 42, 510. 6. Steffensen, D. ibid. 1955, 41, 155. 7. Ashwell, G., Hickman, J. J. biol. Chem. 1953, 201, 651. 8. Lowenstein, J. M. Nature, Lond. 1960, 187, 570. 9. Jayson, G. G. ibid. 1961, 190, 144.
SIR,-Dr. Orr (Nov. 17) urges the use of prophylactic antibiotics for the prevention of respiratory infection in patients with myxcedema coma without demonstrating any benefit from them. Dr. Thulbourne and Dr. Young (Nov. 3) have shown that prophylactic antibiotics do not reduce the incidence of postoperative chest infections in general surgical patients. In this neurosurgical unit the only demonstrable effect of prophylactic antibiotics in comatose or stuporose patients is to alter the sputum flora to predominantly intestinal organisms resistant to most or all of the standard antibiotics, so that if pneumonia develops subsequently the choice of antibiotics is often very limited, if sputum culture can be taken as a reliable guide to effective treatment. Regular turning of the patient two-hourly or hourly, energetic physiotherapy to maintain the airway clear of secretions, prevention of dehydration, and sputum culture is in our opinion the best means of trying to prevent pneumonia in comatose patients and of preparing for early, appropriate antibiotic therapy if pneumonia develops. Neurosurgical Research Laboratories, Atkinson Morley’s Hospital, London, S.W.20.
P. RICHARDS.
ANTIMICROBIAL EFFECT OF HYDROGEN PEROXIDE AND LACTIC ACID IN THE MOUTH SIR,-The fact that there is in human saliva an antimicrobial defence mechanism, notably against Corynebacterium diphtheria, was discovered by Dold 1 and confirmed by numerous other workers,2-lo and can hardly be denied.
he attributes to me-namely, that the acidity produced by the oral streptococci, or the hydrogen peroxide as such produced by them, is responsible for the antimicrobial action of human saliva. On the contrary, if anyone held such views, I would, in unison with Dr. Davis, regard them as wholly erroneous.
A. KRAUS. EXTERNAL CARDIAC RESUSCITATION
SIR,-Iwas interested to read Mr. Keen’s article of Dec. 8. I fail to understand, however, why no mention was made of the breathing (as in the letter on the same subject on p. 1229 of the same issue), assuming naturally that it ceased with the cardiac arrest. Did it return spontaneously with the recommencement of the heart action, or was some form of artificial respiration used ? Ashby-de-la-Zouch,
H M. M AMPBELL. A. H. A CAMPBELL. Leicestershire.... CALCIUM AND CANCER
SIR,-The ideas of Dr. Elkeles1 (described in your annotation of Nov. 24) run parallel to our own. We are investigating the effects of ionising radiations on the absorption of bivalent metal ions by filamentous algae.2 This work shows that calcium ions act in a radiation-protective capacity with regard to membrane damage and the eventual death of the algae. The protective action of calcium towards changes in membrane behaviour is thought to lie in its ability to retain certain permeability characteristics even when other constituents have been EFFECT OF FLUCTUATION OF CALCIUM-ION CONCENTRATION ON THE METABOLISM AND MUTATION-RATES OF THE CELL
9
The action of this defence mechanism has up till now never been fully explained. My own conception of its mode of action
is, I believe, best represented by the following equations from Engler:" I. CH;,.CHOH.COOH+H,0,=CH,.COH+CO+2H,0
adapted
acetaldehyde acetaldehyde reacts with the oxygen of the air to form acetylperoxide: II. 2 CHs.COH+2 0,=(CH;,CO)sO+H,02 In the presence of an oxidisable substance X (for instance, on the surface of a microorganism) this substance may be oxidised by the acetylperoxide formed in reaction II: III. CHa.COO +XO ’" " ’ 0-- CH.3COOH CH.3COOH CH..COO ’+X+H2 The
These equations (which, of course, do not only apply to free lactic acid, but equally to its neutral salts), especially equation III, taken in conjunction with the fact that alkylperoxides are not attacked by catalase,12 to my mind satisfactorily explain why human saliva has an antimicrobial effect against C. diphtheriae, in spite of the fact that this organism produces catalase. The same or similar explanations may hold good to explain the activity of saliva against other micro-
organisms. I believe that this explanation completely answers all Dr. Davis’s questions and arguments (Nov. 10), including the one concerning the activity of catalase. If Dr. Davis will read my letter again, he will find that nowhere did I express the views 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
Dold, H., Lachele, W., Du Dscheng Hsing, Z. Hyg. InfektKr. 1936, 118, 369. Holzl, H. ibid. 1941, 123, 500. Knorr, M. Arch. Hyg., Berl. 1941, 126, 59. Hegemann, F., Z. Hyg. InfektKr. 1942, 124, 202. Thompson, R., Shibuya, M. 1946, J. Bact. 51, 671. Bethge, J., Soehring, K., Tschesche, R. Z. Naturf. 1947, 2B, 12. Berger, H. Z. Hyg. InfektKr. 1952, 133, 371. Dold, H., Ochsenreither, F. ibid. 1940, 122, 51. Boennicke, R. ibid. 1955-56, 142, 339. Lammers, T. Dtsch. Zahn-, Mund- Kieferheilk. 1953, 18, 378. Engler, C. Ber. dtsch. chem. Ges. 1900, 33, 1103, 1109. Stern, K. G. Z. physiol. Chem. 1932, 209, 176.
*
f-- Direction of Ca2+ cycle. Points where X-rays are known to have an effect. They will also increase membrane permeability.
damaged (e.g., fatty acids decarboxylated+dehydrogenated). Cells exposed to changes in calcium-ion concentration in the extracellular fluid may transmit this situation to the intracellular fluid (viz. precipitation and adsorption of Ca2+) and so produce the result which was observed by Dr. Elkeles in case of stomach cancer.3 Bivalent metal ions are found in chromosomestheir removal leads to an increase in chromosomal aberrations,56 and their presence is essential to, or
enhances, many enzyme processes (e.g.,
A.T.P.
breakdown,’8
All these factors combine into a calcium-ion clotting, &c.). (ionic strength) cycle which may lead to harmful mutations9 (see table). Whether the observed changes in calcium concentration are 1. Elkeles, A. Nature, Lond. 1962, 193, 1089. 2. 2nd International Congress of Radiation
p. 195.
Research, 1962; abstracts,
3. Elkeles, A. Brit. J. Cancer, 1959, 13, 403. 4. Mazia, D. Proc. nat. Acad. Sci., Wash. 1954, 40, 521. 5. Wolff, S., Luippold, H. E. ibid. 1956, 42, 510. 6. Steffensen, D. ibid. 1955, 41, 155. 7. Ashwell, G., Hickman, J. J. biol. Chem. 1953, 201, 651. 8. Lowenstein, J. M. Nature, Lond. 1960, 187, 570. 9. Jayson, G. G. ibid. 1961, 190, 144.