operation on the king

1
576 ANNOTATIONS have a wide lethal or inhibitory activity against gram-positive and gram-negative bacteria in con- centrations of the order of 1 in 3000 to 1 in 60,000. They are neutral, stable in solution, non-corrosive to metals, non-irritating in wounds, and relatively non- toxic to tissues. They tend to froth and their activity is reduced in hard water ; but these dis- advantages can probably be overcome. Further disadvantages are their relatively poor action on spores, and their loss of activity at low temperatures or in the presence of soap, serum, and some detergents. On the other hand, it seems that they can safely be used over long periods, and they are likely to be employed increasingly for dairy purposes and for eating and drinking utensils. DA vis and RESUGGAN,2 among others, have reported favourably on these compounds for cleansing glasses in public- houses, where their low cost and freedom from effect on the "head" of beer are additional advantages. Since they are totally unlike phenol, the Rideal-Walker test is quite unsuitable for their evaluation. Fortunately there is no evidence that, as ordinarily used, they are subject to the kind of reversal seen, for example, when bacteria apparently killed by mercuric chloride are revived by the action of ammonium sulphide. Phenomena of this kind are commoner and more important than is generally recognised : thus the newer mercurials such as merthiolate and mercurochrome can be inactivated and organisms treated with them can be revived, by glutathione, which occurs in body tissues. These observations have further significance in relation to the testing of materials for sterility. Such tests, if they are to prove that a preparation is bactericidal and not merely bacteriostatic, should include the addition of any substance known to act as reviver. We may add that the development of the new dis- infectants should not be allowed to obscure the virtues of the old ones, such as the hypochlorites and lysol. A cheap disinfectant .with the wide and rapid action of lysol, but with slighter irritant and toxic properties, would be welcome. The study of disinfection requires a knowledge of both chemistry and microbiology ; but, as Professor BERRY remarked, the modern pharmacist should be competent to evaluate the claims of the different preparations and so provide valuable advice to workers in various branches of medicine. 2. Davis, J. G., Resuggan, J. C. L. Proc. Soc. appl. Bact. 1946, 1, 20. Annotations OPERATION ON THE KING ON June 1 it was announced that, after a week’s indis- position, the King had a small area of catarrhal inflamma- tion in the lung. A statement on Sept. 18 that structural changes had developed was followed last Sunday by a lung resection, performed successfully by Mr. C. Price Thomas with Dr. Robert Machray as anæsthetist. This operation was needed because there was bronchial obstruc- tion which was promoting infection and could not be relieved by other means. Besides the surgeon and anæs- thetist, the members of the medical profession who have been attending His Majesty are Dr. G. Mather Cordiner, Sir Daniel Davies, Sir Thomas Dunhill, Sir Horace Evans, Dr. Geoffrey Marshall, Sir John Weir, and Sir Robert Young. The concern, aroused by his illness shows the King, in sickness as in health, as a source of unity at home and friendship abroad. Millions of us feel his fortunes and misfortunes as our own, and share the hope for his speedy recovery. FUMAGILLIN IN AMŒBIASIS Two years .ago, anew antibiotic, originally called " H3 " and later Fumagillin,’ was isolated from cultures of a species of aspergillus by Hanson and Eble 1 in the U.S.A. Its activity against bacteria and fungi is small and it is inactive against viruses ; but the drug is extremely potent as an amoebicide. In vitro, McCowen et a1.2 found that it"inhibited a strain of Entamœba histolytica (NIH200), with a mixed bacterial flora, at dilutions as high as 1 in 130 million. In rats, cæcal infections with E. histolytica were cleared by giving a total of 11 mg. of fumagillin per kg. of body-weight in two days, and the antibiotic was also effective in young rabbits with amcebiasis. At the University of California, Hrenoff and Nakamura 3 have shown that fumagillin is strongly amcebicidal in the monkey. The infected animals received 50-125 mg. of the antibiotic per kg. body-weight daily ’for. five days and there were no recurrences in the 8-14 weeks of observation. No toxic manifestations 1. Hanson, F. R., Eble, E. jr. Bact. 1949, 58, 527. 2. McCowen, M. C., Calleiider, M. E., Lawlis, J. F. Science, 1951, , 113,’202." -’’’-’ 3. Hrenoff, A. K., Nakamura, M. Proc. Soc. exp. Biol., N.Y. 1951, 77, 162. were seen in these monkeys and their blood pictures remained normal, but tests with bromsulphthalein suggested that the highest dosage (125 mg. per kg.) might damage the liver, for in one monkey the dye was retained. The chemistry and toxicity of fumagillin have been investigated by Eble and Hanson,’1 who have obtained it in pure crystalline form. On the basis of its ultra- violet and infra-red spectra and the properties of some of its derivarives, they have tentatively concluded that fumagillin is a monobasic acid containing four conjugated double bonds and a dicarbonyl or x-hydroxy carbonyl group. Its acute toxicity is extremely low. In mice, when the drug is injected subcutaneously its L.D. 50 is about 800 mg. per kg. and doses -up to 2 g. per kg. are tolerated by mouth. The ideal amoebicide for clinical use should be active by mouth, should kill the amœbæ in the trophozoite or cystic stage in the lumen of the gut, and should reach the liver and other infected tissues in a concentration high enough to deal with trophozoites. Its toxicity must also be low. No known drug meets all these requirements. In view of its activity and apparent low toxicity in animals, there is clearly a case for a trial of fumagillin in human amcebiasis. THE WELFARE OF THE HANDICAPPED SiNcE 1920 the local authorities have had the duty of providing welfare services for the blind and partially sighted. The work has grown with the years, and they have found very useful the outline schemes for these welfare services provided by the Minister of Health. Not so much attention has been paid to the needs of people handicapped in other ways ; but the National Assistance Act, 1948, gives local authorities, for the first time, powers to provide a welfare service specially for those handicapped people whose needs have so far been left to the voluntary bodies. To help the authorities in their task the Minister has just published (circular 32/51) two new outline schemes-one for the deaf and hard of hearing, the other for the general handicapped classes, including cripples (spastics and arthritics among them) and epileptics. These schemes are based on the recom- mendations of his Advisory Committee for the Welfare 4. Eble, T. E., Hanson, F. R. Antibiotics and Chemotherapy, 1951, 1, 54.

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Page 1: OPERATION ON THE KING

576 ANNOTATIONS

have a wide lethal or inhibitory activity againstgram-positive and gram-negative bacteria in con-

centrations of the order of 1 in 3000 to 1 in 60,000.They are neutral, stable in solution, non-corrosive tometals, non-irritating in wounds, and relatively non-toxic to tissues. They tend to froth and theiractivity is reduced in hard water ; but these dis-advantages can probably be overcome. Furtherdisadvantages are their relatively poor action on

spores, and their loss of activity at low temperaturesor in the presence of soap, serum, and some

detergents. On the other hand, it seems that theycan safely be used over long periods, and they arelikely to be employed increasingly for dairy purposesand for eating and drinking utensils. DA vis and

RESUGGAN,2 among others, have reported favourablyon these compounds for cleansing glasses in public-houses, where their low cost and freedom fromeffect on the "head" of beer are additional

advantages. Since they are totally unlike phenol,the Rideal-Walker test is quite unsuitable for theirevaluation. Fortunately there is no evidence that,as ordinarily used, they are subject to the kind of

reversal seen, for example, when bacteria apparentlykilled by mercuric chloride are revived by the actionof ammonium sulphide. Phenomena of this kind arecommoner and more important than is generallyrecognised : thus the newer mercurials such as

merthiolate and mercurochrome can be inactivatedand organisms treated with them can be revived,by glutathione, which occurs in body tissues. Theseobservations have further significance in relation tothe testing of materials for sterility. Such tests, if

they are to prove that a preparation is bactericidaland not merely bacteriostatic, should include theaddition of any substance known to act as reviver.We may add that the development of the new dis-infectants should not be allowed to obscure thevirtues of the old ones, such as the hypochlorites andlysol. A cheap disinfectant .with the wide and rapidaction of lysol, but with slighter irritant and toxicproperties, would be welcome.The study of disinfection requires a knowledge of

both chemistry and microbiology ; but, as ProfessorBERRY remarked, the modern pharmacist should becompetent to evaluate the claims of the different

preparations and so provide valuable advice toworkers in various branches of medicine.

2. Davis, J. G., Resuggan, J. C. L. Proc. Soc. appl. Bact. 1946,1, 20.

Annotations

OPERATION ON THE KING

ON June 1 it was announced that, after a week’s indis-position, the King had a small area of catarrhal inflamma-tion in the lung. A statement on Sept. 18 that structuralchanges had developed was followed last Sunday by a

lung resection, performed successfully by Mr. C. Price

Thomas with Dr. Robert Machray as anæsthetist. This

operation was needed because there was bronchial obstruc-tion which was promoting infection and could not berelieved by other means. Besides the surgeon and anæs-thetist, the members of the medical profession who havebeen attending His Majesty are Dr. G. Mather Cordiner, SirDaniel Davies, Sir Thomas Dunhill, Sir Horace Evans, Dr.Geoffrey Marshall, Sir John Weir, and Sir Robert Young.The concern, aroused by his illness shows the King, insickness as in health, as a source of unity at home andfriendship abroad. Millions of us feel his fortunes andmisfortunes as our own, and share the hope for his speedyrecovery.

FUMAGILLIN IN AMŒBIASISTwo years .ago, anew antibiotic, originally called

" H3 " and later Fumagillin,’ was isolated from culturesof a species of aspergillus by Hanson and Eble 1 in theU.S.A. Its activity against bacteria and fungi is smalland it is inactive against viruses ; but the drug is extremelypotent as an amoebicide. In vitro, McCowen et a1.2found that it"inhibited a strain of Entamœba histolytica(NIH200), with a mixed bacterial flora, at dilutions as

high as 1 in 130 million. In rats, cæcal infections withE. histolytica were cleared by giving a total of 11 mg.of fumagillin per kg. of body-weight in two days, andthe antibiotic was also effective in young rabbits withamcebiasis. At the University of California, Hrenoffand Nakamura 3 have shown that fumagillin is stronglyamcebicidal in the monkey. The infected animalsreceived 50-125 mg. of the antibiotic per kg. body-weightdaily ’for. five days and there were no recurrences inthe 8-14 weeks of observation. No toxic manifestations

1. Hanson, F. R., Eble, E. jr. Bact. 1949, 58, 527.2. McCowen, M. C., Calleiider, M. E., Lawlis, J. F. Science, 1951,,

113,’202." ’

-’’’-’ -

3. Hrenoff, A. K., Nakamura, M. Proc. Soc. exp. Biol., N.Y. 1951,77, 162.

were seen in these monkeys and their blood picturesremained normal, but tests with bromsulphthaleinsuggested that the highest dosage (125 mg. per kg.) mightdamage the liver, for in one monkey the dye was retained.The chemistry and toxicity of fumagillin have beeninvestigated by Eble and Hanson,’1 who have obtainedit in pure crystalline form. On the basis of its ultra-violet and infra-red spectra and the properties of someof its derivarives, they have tentatively concluded thatfumagillin is a monobasic acid containing four conjugateddouble bonds and a dicarbonyl or x-hydroxy carbonylgroup. Its acute toxicity is extremely low. In mice,when the drug is injected subcutaneously its L.D. 50 isabout 800 mg. per kg. and doses -up to 2 g. per kg. aretolerated by mouth.The ideal amoebicide for clinical use should be active

by mouth, should kill the amœbæ in the trophozoite orcystic stage in the lumen of the gut, and should reachthe liver and other infected tissues in a concentrationhigh enough to deal with trophozoites. Its toxicitymust also be low. No known drug meets all these

requirements. In view of its activity and apparent lowtoxicity in animals, there is clearly a case for a trial offumagillin in human amcebiasis.

THE WELFARE OF THE HANDICAPPED

SiNcE 1920 the local authorities have had the duty ofproviding welfare services for the blind and partiallysighted. The work has grown with the years, and theyhave found very useful the outline schemes for thesewelfare services provided by the Minister of Health. Notso much attention has been paid to the needs of peoplehandicapped in other ways ; but the National AssistanceAct, 1948, gives local authorities, for the first time,powers to provide a welfare service specially for thosehandicapped people whose needs have so far been leftto the voluntary bodies. To help the authorities in theirtask the Minister has just published (circular 32/51) twonew outline schemes-one for the deaf and hard of

hearing, the other for the general handicapped classes,including cripples (spastics and arthritics among them)and epileptics. These schemes are based on the recom-mendations of his Advisory Committee for the Welfare4. Eble, T. E., Hanson, F. R. Antibiotics and Chemotherapy, 1951,

1, 54.