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LARGER THAN LIFE
1024 reaction indicates a good natural response to injury and that it betokens a very favourable prognosis. The evidence from their patients and those of Grant and Reeve seems to justify such a conclusion in the case of young adults who have suffered minor injuries to the limbs. But in severely injured young children this reaction may be suddenly succeeded by a profound fall in blood-pressure ; and in such patients the hypertensive response should be viewed against the background of the severity of the injury and should give rise to a cautious attitude and repeated observation to ensure early recognition of the subsequent fall in blood-pressure. The hypotension which Howard et al. observed after administration of thiopentone emphasises the serious potential risk associated with the use of this agent in severely injured patients. Abolition of peripheral vasoconstriction in this way is especially evident in the hypertensive patient, but occurs also in patients whose apparently good circulatory condition is due partly to vasoconstriction and partly to the incomplete replacement of lost blood or plasma by transfusion ; the abolition of the vasoconstrictive element by induction of anaesthesia may be followed by deterioration in the patient’s condition. NEW TYPES OF PENICILLIN
WE have lately referred to the use of a new antibiotic, synnematin B, for the treatment of typhoid fever.1 Work on the microbiology and chemistry of this and related antibiotics has been proceeding for several years at the Sir William Dunn School of Pathology, Oxford, and in America in the laboratories of the Michigan Department of Health and the firms of Abbott and Parke, Davis. The story, which has been told by Sir Howard Florey,2 begins in 1945, when Prof. G. Brotzu, of Cagliari, isolated a species of cephalosporium from a sewage outflow in Sardinia.3 He grew the fungus on a liquid medium, from which he made a crude but active extract which he claimed inhibited the growth of a number of grampositive and gram-negative organisms, and was effective in the treatment of typhoid fever and brucellosis. A culture of the organism was sent to England in 1948 and studied in Oxford, and later by workers at the Antibiotics Research Station of the Medical Research Council. In the following year Gotteshall and others in the U.S.A. reported that certain members of the genus cephalosporium produced a water-soluble antibiotic, which they named synnematinand subjected to chemical and 5 In 1953 Olson, of Michigan, biological examination. and his co-workers s obtained a crude preparation of this antibiotic which they called synnematin B. The work begun at Oxford in 1948 bore fruit, and in 1951 the production of a family of antibiotics, cephalosporin P 1-5, from the Sardinian cephalosporium was announced 7 ; these were soluble in common organic solvents. In addition another antibiotic, soluble in water and with quite different properties, was described ; this was called cephalosporin N. A further antibiotic closely related to this, named cephalosporin C, was discovered this year by Newton and Abraham, of Oxford,in cultures of the cephalosporium. They purified cephalosporin N and found that it is related chemically to penicillin, with a side-chain derived from D-
and the American synnematin B, the two antibiotics have been compared side by side by teams at Oxford and in America, and it is now almost certain that synnematin B is identical with cephalosporin N,1O The evidence for their identity is as follows : the two substances show the same relative antibacterial spectrum and are inactivated by penicillinase ; they are indistinguishable with respect to antibacterial activity when run on paper chromatograms in a variety of solvent systems ; and after acid hydrolysis both show spots on paper chromatograms corresponding to penicillamine and D-rx-aminoadipic acid. Is cephalosporin N likely to be of any clinical value ? It differs strikingly from the common penicillins in its antibacterial activity as well as in its solubility, and there are indications that it may be useful in the treatment of typhoid and salmonella infections, and that it may produce fewer allergic reactions in patients sensitive to penicillin G. Cephalosporin C also appears to be related chemically to penicillin, but Newton and Abraham have found that it is not destroyed by penicillinase and that it inhibits the action of the enzyme. Against most organisms its action is weak compared with that of other antibiotics in use ; but this may be offset by its extremely low toxicity. Evidence that cephalosporin C may be of value in medicine was obtained by finding that mice infected with Streptococcus pyogettes could be completely protected by the repeated subcutaneous injection of 1 mg. of the drug. According to Sir Howard Florey it might be of value in the treatment of staphylococcal infections resistant to penicillin G and other antibiotics. It would probably have to be administered by continuous intravenous infusion, so its use would be restricted to the seriously ill. Because it is not readily absorbed from the gut it might be valuable in treating enteritis caused by staphylococci or other sensitive organisms. It might also have a place in the local treatment of infections. Cephalosporin P, though inferior to several other antibiotics, might be useful in the treatment of staphylococcal infections ; but it has not yet been tested in man. When Brotzu went fishing in the Mediterranean ten years ago he certainly caught a most versatile fungus. LARGER THAN LIFE
THE electron
microscope is past its teething troubles. remember that what is photographed is not the object in a state of nature but something analogous to an animal stuffed by a skilled taxidermist, we can accept the interpretations of those experienced in this method. It has told us much about the shape of virus particles and rather less about the structure of bacteria. Swain 11 and Czekalowski and Eaves 12 describe the minute structure of spirochaetes revealed by fixation and selective enzymic digestion. In general they confirm what had been surmised by others using older methods. The " backbone " of these organisms consists of one or more fibrils or axistyles, apparently held in tension and causing the spiral shape which is oftenlost at death. Round these is coiled, rather in the manner of twofold electric " flex," the cytoplasmic body in a cell membrane. There are no flagella, but it is possible that the elastic axistyle is responsible for locomotion. The chief interest of these observations lies in the comparison of the genera Borrelia, Leptospira, and Treponema, each of which appears to have a distinct structure. The naming and classification of bacteria are the subject of debate and despair among microbiologists. To the systematist function and habit, both labile characters, are a poor substitute for form ; but, within the larger groups, he has no others to guide him. These papers give hope of classification on a more solid basis. As
long
as we
10. Abraham, E. P., Newton, G. G. F., Schenck, J. R., Hargie, M. P., Olson, B. H., Fisher, M. W., Schuurmans, D. M., Fusari, S. A. Nature, Lond. 1955, 176, 551. 11. Swain, R. H. A. J. Path. Bact. 1955, 69, 117. 12. Czekalowski, J. W., Eaves, G. Ibid, p. 129.
WE have lately referred to the use of a new antibiotic, synnematin B, for the treatment of typhoid fever.1 Work on the microbiology and chemistry of this and related antibiotics has been proceeding for several years at the Sir William Dunn School of Pathology, Oxford, and in America in the laboratories of the Michigan Department of Health and the firms of Abbott and Parke, Davis. The story, which has been told by Sir Howard Florey,2 begins in 1945, when Prof. G. Brotzu, of Cagliari, isolated a species of cephalosporium from a sewage outflow in Sardinia.3 He grew the fungus on a liquid medium, from which he made a crude but active extract which he claimed inhibited the growth of a number of grampositive and gram-negative organisms, and was effective in the treatment of typhoid fever and brucellosis. A culture of the organism was sent to England in 1948 and studied in Oxford, and later by workers at the Antibiotics Research Station of the Medical Research Council. In the following year Gotteshall and others in the U.S.A. reported that certain members of the genus cephalosporium produced a water-soluble antibiotic, which they named synnematinand subjected to chemical and 5 In 1953 Olson, of Michigan, biological examination. and his co-workers s obtained a crude preparation of this antibiotic which they called synnematin B. The work begun at Oxford in 1948 bore fruit, and in 1951 the production of a family of antibiotics, cephalosporin P 1-5, from the Sardinian cephalosporium was announced 7 ; these were soluble in common organic solvents. In addition another antibiotic, soluble in water and with quite different properties, was described ; this was called cephalosporin N. A further antibiotic closely related to this, named cephalosporin C, was discovered this year by Newton and Abraham, of Oxford,in cultures of the cephalosporium. They purified cephalosporin N and found that it is related chemically to penicillin, with a side-chain derived from D-
and the American synnematin B, the two antibiotics have been compared side by side by teams at Oxford and in America, and it is now almost certain that synnematin B is identical with cephalosporin N,1O The evidence for their identity is as follows : the two substances show the same relative antibacterial spectrum and are inactivated by penicillinase ; they are indistinguishable with respect to antibacterial activity when run on paper chromatograms in a variety of solvent systems ; and after acid hydrolysis both show spots on paper chromatograms corresponding to penicillamine and D-rx-aminoadipic acid. Is cephalosporin N likely to be of any clinical value ? It differs strikingly from the common penicillins in its antibacterial activity as well as in its solubility, and there are indications that it may be useful in the treatment of typhoid and salmonella infections, and that it may produce fewer allergic reactions in patients sensitive to penicillin G. Cephalosporin C also appears to be related chemically to penicillin, but Newton and Abraham have found that it is not destroyed by penicillinase and that it inhibits the action of the enzyme. Against most organisms its action is weak compared with that of other antibiotics in use ; but this may be offset by its extremely low toxicity. Evidence that cephalosporin C may be of value in medicine was obtained by finding that mice infected with Streptococcus pyogettes could be completely protected by the repeated subcutaneous injection of 1 mg. of the drug. According to Sir Howard Florey it might be of value in the treatment of staphylococcal infections resistant to penicillin G and other antibiotics. It would probably have to be administered by continuous intravenous infusion, so its use would be restricted to the seriously ill. Because it is not readily absorbed from the gut it might be valuable in treating enteritis caused by staphylococci or other sensitive organisms. It might also have a place in the local treatment of infections. Cephalosporin P, though inferior to several other antibiotics, might be useful in the treatment of staphylococcal infections ; but it has not yet been tested in man. When Brotzu went fishing in the Mediterranean ten years ago he certainly caught a most versatile fungus. LARGER THAN LIFE
THE electron
microscope is past its teething troubles. remember that what is photographed is not the object in a state of nature but something analogous to an animal stuffed by a skilled taxidermist, we can accept the interpretations of those experienced in this method. It has told us much about the shape of virus particles and rather less about the structure of bacteria. Swain 11 and Czekalowski and Eaves 12 describe the minute structure of spirochaetes revealed by fixation and selective enzymic digestion. In general they confirm what had been surmised by others using older methods. The " backbone " of these organisms consists of one or more fibrils or axistyles, apparently held in tension and causing the spiral shape which is oftenlost at death. Round these is coiled, rather in the manner of twofold electric " flex," the cytoplasmic body in a cell membrane. There are no flagella, but it is possible that the elastic axistyle is responsible for locomotion. The chief interest of these observations lies in the comparison of the genera Borrelia, Leptospira, and Treponema, each of which appears to have a distinct structure. The naming and classification of bacteria are the subject of debate and despair among microbiologists. To the systematist function and habit, both labile characters, are a poor substitute for form ; but, within the larger groups, he has no others to guide him. These papers give hope of classification on a more solid basis. As
long
as we
10. Abraham, E. P., Newton, G. G. F., Schenck, J. R., Hargie, M. P., Olson, B. H., Fisher, M. W., Schuurmans, D. M., Fusari, S. A. Nature, Lond. 1955, 176, 551. 11. Swain, R. H. A. J. Path. Bact. 1955, 69, 117. 12. Czekalowski, J. W., Eaves, G. Ibid, p. 129.