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FRACTURES DUE TO CORTICOTROPHIN AND CORTISONE
907
.
penicillin. This assumes that the component in question accounts for a major part of the penicillin bound by the cell. 4. In the few examples where the resistant organism had a lower combining affinity with penicillin, the vulnerable component may have lost some of its power to react with penicillin. In view of what happens with naturally resistant bacteria,l this fourth possibility was expected to be the ruleinstead of which it proved to be the exception. 5. If a quantitative rather than a qualitative difference between sensitive and resistant strains is to be sought, extension of the fourth possibility might reconcile the conflicting evidence for strains with induced resistance as distinct from strains with natural resistance. The latter require no argument because the facts about them fit the assumption of a quantitative difference in reactivity with penicillin between sensitive and resistant strains. To sustain this line of reasoning for the strains with induced resistance it is necessary to assume that the
binding
of
penicillin by
bacteria involves
a
number of
components and may only partly reflect the affinity of the vital component or components inactivated by penicillin. The fraction of penicillin bound to vital components might be so small a part of the total that a significant change in it might be masked by the unchanged binding affinity of the other non-vital penicillin-reactive components of the bacterial cell.
Those who consider that this kind of reasoning represents perhaps an over-determined attempt to rescue a good hypothesis from a difficult set of facts will none the less agree with Eagle that it is worth re-examining the proposition that trypanosomes resistant to 6arsenicals 4&a cute; and mycobacteria resistant to isoniazid owe their increased resistance to decreased permeability. To conclude the present phase of the debate, Eagle briefly . analyses recent work on drug-resistant Escherichia coli 7 and concludes that the only explanation of resistance which was reasonably consistent with all the results was that an enzyme-protein of the resistant bacteria had a decreased affinity for the inhibitor as compared with the normal substrate. Obviously, we may expect this debate to continue-as it should, for we know too little about the nature of bacterial resistance to antibiotics to feel certain that we are using these valuable drugs in the best way.
Most histologists deny that such experimental lesions identical with those in rheumatic fever. The recognition of the potential toxicity of streptococcal proteinase adds a little to our knowledge of the aggressive group-A streptococcus but does not at present aid in the prevention or treatment of rheumatic fever. are
FRACTURES
DUE TO CORTICOTROPHIN CORTISONE
AND
DECALCIFICATION of the skeleton is a recognised of treatment with corticotrophin or cortisone, and there have been some reports 1-5 of pathological fractures. Curtiss and his colleagues 6 have recently described four cases of multiple pathological fractures of the spine in male patients under treatment with these hormones. Although these patients also had chronic rheumatoid arthritis and disuse atrophy, Curtiss et al. consider that long-continued cortisone or corticotrophin was an important cause of the osteoporosis that led to pathological fracture. The lesions might be prevented
complication
by encouraging physical activity, by giving testosterone, by limiting the intake of the hormones, and by being very careful when treating patients predisposed to osteoporosis-namely, elderly patients, postmenopausal women, and patients with severe arthritis.
DECOMPRESSION SICKNESS DECOMPRESSION sickness, or caisson disease, is known to workers in compressed air under many names, according to the presenting symptoms. Muscular and joint pains are called " the bends " ; vertigo, which if severe may give rise to symptoms resembling Meniere’s syndrome, is called " the staggers " ; air-hunger, which simulates bronchial asthma, is called " the chokes " ; and the cutaneous manifestations—pruritus and erythema-are referred to as the itch." In mild cases the only symptom is slight muscular and joint pain, which passes off spontaneously or after recompression. In very severe cases there may be paralysis, aphasia, and ataxia, due to air emboli in the vessels of the brain and spinal cord ; avascular necrosis of bone may occur 7-9 and result in osteo-arthritis and the formation of loose bodies ANOTHER STREPTOCOCCAL TOXIN in joints. INFECTION with group-A streptococci is well known to Diving for sponge and pearls is an ancient occupation, initiate rheumatic fever in the susceptible ; but how the and Spanish writers of the 16th century describe bleeding organism brings about this effect is unknown. At least from the mouth, nose, and ears among divers in the Gulf seven of the components and products of streptococci of Mexico. Paul Bert in 1878 proved once and for all (hsemolysin, leucocidin, erythrogenic toxin, streptokinase, that decompression sickness " was due to the extra air, hyaluronic acid, hyaluronidase, and type-specific M which had been dissolved in the body while under protein) probably have pathogenic properties 8 ; and now pressure, being given off as bubbles within the body when a further product-the enzyme, proteinase-is suspect. the pressure was suddenly reduced." Further work by Elliott 9 showed that proteinase is produced by most of J. S. Haldane and A. E. Boycott led to prevention by the group-A types and is active against some proteins, gradual decompression, the diver rising to the surface in including the M protein of the streptococcus itself. stages. The treatment of decompression sickness by Proteinase, like some other enzymes of the streptococcus, recompression, followed by gradual decompression, also is antigenic in man and animals-though Todd 10 found no became established at this time ; and now all places difference in antibody titres between patients with where work in compressed air is carried out have a special rheumatic fever and patients with other streptococcal medical lock for this purpose. disease. Paton and Walder 10 have lately reported on comThe toxic effects of streptococcal proteinase have been illness in men working on the construction pressed-air demonstrated by Kellner and Robertson," who found of the Tyne tunnel between June, 1948, and July, 1950. that in rabbits, guinea pigs, and mice a single small. The whole at risk were investigated. Only intravenous dose rapidly produced focal necrosis of severe casespopulation of decompression sickness, causing loss of cardiac and sometimes of skeletal muscle. Several working capacity, are reported to the Chief Inspector workers have reported myocardial necrosis after experi1. Demartini, F., Grokoest, A. W., Ragan, C. J. Amer. med. Ass. mental injection of streptococcal filtrates, and possibly 1952, 149, 750. is one case of these lesions. proteinase 2. Teicher, R., Nelson, T. C. J. invest. Derm. 1952, 19, 205. 4.
5. 6. 7. 8. 9. 10. 11.
Eagle, H., Doak, G. O. Pharmacol. Rev. 1951, 3, 107. Eagle, H., Magnuson, H. J. J. Pharmacol. 1944, 82, 137. Barclay, W. R. Transactions of the 12th Conference on the Chemotherapy of Tuberculosis, 1953, p. 249. Davis, B. D., Mass. W. K. Proc. nat. Acad. Sci. 1952, 38, 775. Wilson, G. S., Miles, A. A. Topley and Wilson’s Principles of Bacteriology and Immunity. London, 1946 ; vol. 1, p. 592. Elliott, S. D. J. exp. Med. 1945, 81, 573. Todd, E. W. Ibid. 1947, 85, 591. Kellner, A., Robertson, T. Ibid, 1954, 99, 495 ; see also Lancet, Oct. 2, 1954, p. 702.
"
3. Soffer, L. J., Bader, R. J. Amer. med. Ass. 1952, 149, 1002. 4. de Sèze, S., Hubault, A., Renier, J.-C. Pr. méd. 1953, 61, 819. 5. New Engl. J. med. 1953, 248, 945. 6. Curtiss, P. H. jun., Clark, W. S., Herndon, C. H. J. Amer. med. Ass. 1954, 156, 467. 7. Kahlstrom, S. C., Burton, C. C., Phemister, D. B. Surg. Gynec. Obstet. 1939, 68, 129. 8. James, C. C. M. Lancet, 1945, ii, 6. 9. Ronald. J. Ibid, 1953, ii, 855. 10. Compressed Air Illness. By W. D.M. PATON and D. N. WALDER. Spec. Rep. Ser. med. Res. Coun., Lond. no. 281. H.M. Stationery Office, 1954. Pp. 44. 5s.
.
penicillin. This assumes that the component in question accounts for a major part of the penicillin bound by the cell. 4. In the few examples where the resistant organism had a lower combining affinity with penicillin, the vulnerable component may have lost some of its power to react with penicillin. In view of what happens with naturally resistant bacteria,l this fourth possibility was expected to be the ruleinstead of which it proved to be the exception. 5. If a quantitative rather than a qualitative difference between sensitive and resistant strains is to be sought, extension of the fourth possibility might reconcile the conflicting evidence for strains with induced resistance as distinct from strains with natural resistance. The latter require no argument because the facts about them fit the assumption of a quantitative difference in reactivity with penicillin between sensitive and resistant strains. To sustain this line of reasoning for the strains with induced resistance it is necessary to assume that the
binding
of
penicillin by
bacteria involves
a
number of
components and may only partly reflect the affinity of the vital component or components inactivated by penicillin. The fraction of penicillin bound to vital components might be so small a part of the total that a significant change in it might be masked by the unchanged binding affinity of the other non-vital penicillin-reactive components of the bacterial cell.
Those who consider that this kind of reasoning represents perhaps an over-determined attempt to rescue a good hypothesis from a difficult set of facts will none the less agree with Eagle that it is worth re-examining the proposition that trypanosomes resistant to 6arsenicals 4&a cute; and mycobacteria resistant to isoniazid owe their increased resistance to decreased permeability. To conclude the present phase of the debate, Eagle briefly . analyses recent work on drug-resistant Escherichia coli 7 and concludes that the only explanation of resistance which was reasonably consistent with all the results was that an enzyme-protein of the resistant bacteria had a decreased affinity for the inhibitor as compared with the normal substrate. Obviously, we may expect this debate to continue-as it should, for we know too little about the nature of bacterial resistance to antibiotics to feel certain that we are using these valuable drugs in the best way.
Most histologists deny that such experimental lesions identical with those in rheumatic fever. The recognition of the potential toxicity of streptococcal proteinase adds a little to our knowledge of the aggressive group-A streptococcus but does not at present aid in the prevention or treatment of rheumatic fever. are
FRACTURES
DUE TO CORTICOTROPHIN CORTISONE
AND
DECALCIFICATION of the skeleton is a recognised of treatment with corticotrophin or cortisone, and there have been some reports 1-5 of pathological fractures. Curtiss and his colleagues 6 have recently described four cases of multiple pathological fractures of the spine in male patients under treatment with these hormones. Although these patients also had chronic rheumatoid arthritis and disuse atrophy, Curtiss et al. consider that long-continued cortisone or corticotrophin was an important cause of the osteoporosis that led to pathological fracture. The lesions might be prevented
complication
by encouraging physical activity, by giving testosterone, by limiting the intake of the hormones, and by being very careful when treating patients predisposed to osteoporosis-namely, elderly patients, postmenopausal women, and patients with severe arthritis.
DECOMPRESSION SICKNESS DECOMPRESSION sickness, or caisson disease, is known to workers in compressed air under many names, according to the presenting symptoms. Muscular and joint pains are called " the bends " ; vertigo, which if severe may give rise to symptoms resembling Meniere’s syndrome, is called " the staggers " ; air-hunger, which simulates bronchial asthma, is called " the chokes " ; and the cutaneous manifestations—pruritus and erythema-are referred to as the itch." In mild cases the only symptom is slight muscular and joint pain, which passes off spontaneously or after recompression. In very severe cases there may be paralysis, aphasia, and ataxia, due to air emboli in the vessels of the brain and spinal cord ; avascular necrosis of bone may occur 7-9 and result in osteo-arthritis and the formation of loose bodies ANOTHER STREPTOCOCCAL TOXIN in joints. INFECTION with group-A streptococci is well known to Diving for sponge and pearls is an ancient occupation, initiate rheumatic fever in the susceptible ; but how the and Spanish writers of the 16th century describe bleeding organism brings about this effect is unknown. At least from the mouth, nose, and ears among divers in the Gulf seven of the components and products of streptococci of Mexico. Paul Bert in 1878 proved once and for all (hsemolysin, leucocidin, erythrogenic toxin, streptokinase, that decompression sickness " was due to the extra air, hyaluronic acid, hyaluronidase, and type-specific M which had been dissolved in the body while under protein) probably have pathogenic properties 8 ; and now pressure, being given off as bubbles within the body when a further product-the enzyme, proteinase-is suspect. the pressure was suddenly reduced." Further work by Elliott 9 showed that proteinase is produced by most of J. S. Haldane and A. E. Boycott led to prevention by the group-A types and is active against some proteins, gradual decompression, the diver rising to the surface in including the M protein of the streptococcus itself. stages. The treatment of decompression sickness by Proteinase, like some other enzymes of the streptococcus, recompression, followed by gradual decompression, also is antigenic in man and animals-though Todd 10 found no became established at this time ; and now all places difference in antibody titres between patients with where work in compressed air is carried out have a special rheumatic fever and patients with other streptococcal medical lock for this purpose. disease. Paton and Walder 10 have lately reported on comThe toxic effects of streptococcal proteinase have been illness in men working on the construction pressed-air demonstrated by Kellner and Robertson," who found of the Tyne tunnel between June, 1948, and July, 1950. that in rabbits, guinea pigs, and mice a single small. The whole at risk were investigated. Only intravenous dose rapidly produced focal necrosis of severe casespopulation of decompression sickness, causing loss of cardiac and sometimes of skeletal muscle. Several working capacity, are reported to the Chief Inspector workers have reported myocardial necrosis after experi1. Demartini, F., Grokoest, A. W., Ragan, C. J. Amer. med. Ass. mental injection of streptococcal filtrates, and possibly 1952, 149, 750. is one case of these lesions. proteinase 2. Teicher, R., Nelson, T. C. J. invest. Derm. 1952, 19, 205. 4.
5. 6. 7. 8. 9. 10. 11.
Eagle, H., Doak, G. O. Pharmacol. Rev. 1951, 3, 107. Eagle, H., Magnuson, H. J. J. Pharmacol. 1944, 82, 137. Barclay, W. R. Transactions of the 12th Conference on the Chemotherapy of Tuberculosis, 1953, p. 249. Davis, B. D., Mass. W. K. Proc. nat. Acad. Sci. 1952, 38, 775. Wilson, G. S., Miles, A. A. Topley and Wilson’s Principles of Bacteriology and Immunity. London, 1946 ; vol. 1, p. 592. Elliott, S. D. J. exp. Med. 1945, 81, 573. Todd, E. W. Ibid. 1947, 85, 591. Kellner, A., Robertson, T. Ibid, 1954, 99, 495 ; see also Lancet, Oct. 2, 1954, p. 702.
"
3. Soffer, L. J., Bader, R. J. Amer. med. Ass. 1952, 149, 1002. 4. de Sèze, S., Hubault, A., Renier, J.-C. Pr. méd. 1953, 61, 819. 5. New Engl. J. med. 1953, 248, 945. 6. Curtiss, P. H. jun., Clark, W. S., Herndon, C. H. J. Amer. med. Ass. 1954, 156, 467. 7. Kahlstrom, S. C., Burton, C. C., Phemister, D. B. Surg. Gynec. Obstet. 1939, 68, 129. 8. James, C. C. M. Lancet, 1945, ii, 6. 9. Ronald. J. Ibid, 1953, ii, 855. 10. Compressed Air Illness. By W. D.M. PATON and D. N. WALDER. Spec. Rep. Ser. med. Res. Coun., Lond. no. 281. H.M. Stationery Office, 1954. Pp. 44. 5s.