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THE IMAGINARY TEXTBOOK
630
cold history in the past; but they had fewer colds than those who did not complete the vaccination course. They also had relatively less absence from work because of colds and other respiratory-tract infections than did the remainder of the vaccinated subjects and much less than those who had received physiological saline solution. Ritchie’s second experiment compared the experience of volunteers randomly divided into four groups. As soon as they felt a cold was beginning, three of these groups were given oral antibitics to which their own mouth organisms were sensitive; the others received inactive tablets. Independent assessment of the respiratory infections suffered in the following winter showed that, while the incidence of insipient colds reported was similar, only 7% of those in the antibiotic-treated group went on to full development compared with 48% among the control series. Although it is always possible for the scientific purist to suggest inadequacies in experimental design or method, the care with which these small studies have been conducted combines with the consistency of the results obtained to suggest that the underlying thesis merits more extensive trial. Although such a trial might be carried out on a volunteer population drawn, like the present one, largely from relatively healthy workers in industry, the application of the methods involved would be particularly apposite in patients with chronic respiratory disease. The widespread use of antibiotics may carry the epidemiological risks involved in building up resistant strains. But in chronic bronchitics, where repeated serious infections hasten deterioration and death, there would be a useful place for this via media between continuous antibiotic medication and a policy of masterly inactivity.
worse
Students of tropical and general medicine and pathology should find much to interest them here, and excellent conditions for study; and the " twenty questions" section will provide a stimulating, if humiliating, test of what they have learnt. TWO NEW SULPHONAMIDES
THE introduction of sulphonamide compounds for the of bacterial infections by Domagk in 1935 marked the beginning of a new epoch in therapeutics. Their effectiveness encouraged the search for other agents suitable for the treatment of infections, and in due course penicillin and other antibiotics were discovered. These developments tended to overshadow the sulphonamides, though these are still widely used and there has been continuous progress in the introduction of new compounds. It was fitting that a recent conference in New York largely devoted to new sulphonamides should be opened by Domagk with a review of progress during the past twenty-five years.’ Two products-sulphachloropyridazine and sulphamethoxypyridazine-have attracted particular attention. Structurally they differ only slightly; the first is 3-sulphanilamido-6-chloro-pyridazine, and the second the corresponding 6-methoxy derivative. They both have high antibacterial activity, quantitatively and qualitatively similar to that of sulphadiazine and greater than that of sulphadimidine and sulphisoxazole.23 But there are some striking differences in their metabolism in the body, which greatly affect their administration and use in clinical
treatment
practice. Sulphamethoxypyridazine
is well absorbed after oral administration and diffuses freely into the body-fluids, particularly into the cerebrospinal fluid.4 These properties THE IMAGINARY TEXTBOOK are shared by many sulphonamides, but sulphamethoxyUNDER the title La Musée Imaginaire, André Malraux pyridazine is exceptional in the slow excretion of its free has written of those advances in pictorial reproduction form in the urine. As a result it provides higher and more that have made possible an abundance of art books of sustained levels in the plasma than any other therahigh standard, enabling us to enjoy in our homes fine peutically effective antibacterial sulphonamide.5-n The pictures from the world’s museums. The converse is a conjugated form is excreted much more rapidly through well-known feature of medical London, where the the kidneys, so that in the plasma most is present in the Wellcome Museum of Medical Science (183, Euston free state. Both forms are highly soluble in the urine.3s Road, London, N.W.1) is virtually a textbook on walls. In freshly drawn oxalated human blood, nearly all of the Here 10,000 visitors a year inspect the displays, which drug is in the plasma and little or none is found in the are very well produced and laid out. As when it was red cells.10 11 Therefore, levels in whole blood are, on founded in 1914, the museum is again devoted to diseases the average, only about 60% of the corresponding levels found in tropical countries; in each case there is a in the plasma. After a single oral dose of 0-5-4-0 g., peak written account of xtiology, diagnosis, prevention, and concentrations are reached in about three hours, and are treatment, prepared by experts or with their assistance, sustained for a further three or four hours.12 Thereafter with lavish illustrations-photographs, drawings, diathe concentration declines slowly and the time taken for a grams, photomicrographs, models, and specimens. There fall to half the peak value is about fifty-five bourse A is one living exhibit-a tank of Gambusia fish, which eat similar time is taken for the excretion in the urine mosquito larvx and provide a cheap tool in malaria of half the administered dose. In these circumstances control. the drug readily accumulates in the body. When a dose The emphasis of the exhibition changes with that of of 1-0 g. is given every forty-eight hours, a slight cumuthe branch of medicine it reflects. Prevention is becoming 1. Domagk, G. Ann. N.Y. Acad. Sci. 1957, 69, 380. more prominent in every section. The displays dealing 2. Neipp, L., Mayer, R. L. ibid. p. 448. 3. Litchfield, J. T. Int. Physiol. Congr., Brussels, 1956. with syphilis and plague are much smaller than they used 4. Boger, W. P., Strickland, C. S., Gyle, J. M. Antibiot. Med. 1956, 3, 378. 5. Roepke, R. R., Maren, T. H., Mayer, E. Ann. N.Y. Acad. Sci. 1957, to be, and syphilis is included among the other spiro69, 457. chaetal diseases. The section on tuberculosis is expanding 6. Foerster, D. K., Martin, W. J., McGuckin, W. F., Nichols, D. R. Proc. Mayo Clin. 1956, 31, 678. at the expense of that on leprosy, and the common cold 7. Frisk, A. R., Wassen, A. Antibiotic Annual, 1956-57 (edited by H. Welch and F. Marti-Ibanez); p. 424. London. and measles find a place. 48 panels are devoted to 8. Jackson, G. G., Grieble, H. G. Ann. N.Y. Acad. Sci. 1957, 69, 493. malaria and 33 to nutrition and malnutrition; no doubt 9. Jones, W. F., Finland, M. ibid. p. 473. 10. Nichols, R. L., Finland, M. J. Lab. clin. Med. 1957, 49, 410. these proportions will be reversed as the malaria11. Nichols, R. L., Jones, W. F., Jr., Finland, M. Proc. Soc. exp. Biol. N.Y. 1956, 92, 637. eradication campaign progresses, unless more energy is 12. Finland, M., Jones, W. F., Jr., Ziai, M., Cherrick, G. R. Amer. J. med. and world into Sci. 1957, 234, 505. population. correlating food-production put
cold history in the past; but they had fewer colds than those who did not complete the vaccination course. They also had relatively less absence from work because of colds and other respiratory-tract infections than did the remainder of the vaccinated subjects and much less than those who had received physiological saline solution. Ritchie’s second experiment compared the experience of volunteers randomly divided into four groups. As soon as they felt a cold was beginning, three of these groups were given oral antibitics to which their own mouth organisms were sensitive; the others received inactive tablets. Independent assessment of the respiratory infections suffered in the following winter showed that, while the incidence of insipient colds reported was similar, only 7% of those in the antibiotic-treated group went on to full development compared with 48% among the control series. Although it is always possible for the scientific purist to suggest inadequacies in experimental design or method, the care with which these small studies have been conducted combines with the consistency of the results obtained to suggest that the underlying thesis merits more extensive trial. Although such a trial might be carried out on a volunteer population drawn, like the present one, largely from relatively healthy workers in industry, the application of the methods involved would be particularly apposite in patients with chronic respiratory disease. The widespread use of antibiotics may carry the epidemiological risks involved in building up resistant strains. But in chronic bronchitics, where repeated serious infections hasten deterioration and death, there would be a useful place for this via media between continuous antibiotic medication and a policy of masterly inactivity.
worse
Students of tropical and general medicine and pathology should find much to interest them here, and excellent conditions for study; and the " twenty questions" section will provide a stimulating, if humiliating, test of what they have learnt. TWO NEW SULPHONAMIDES
THE introduction of sulphonamide compounds for the of bacterial infections by Domagk in 1935 marked the beginning of a new epoch in therapeutics. Their effectiveness encouraged the search for other agents suitable for the treatment of infections, and in due course penicillin and other antibiotics were discovered. These developments tended to overshadow the sulphonamides, though these are still widely used and there has been continuous progress in the introduction of new compounds. It was fitting that a recent conference in New York largely devoted to new sulphonamides should be opened by Domagk with a review of progress during the past twenty-five years.’ Two products-sulphachloropyridazine and sulphamethoxypyridazine-have attracted particular attention. Structurally they differ only slightly; the first is 3-sulphanilamido-6-chloro-pyridazine, and the second the corresponding 6-methoxy derivative. They both have high antibacterial activity, quantitatively and qualitatively similar to that of sulphadiazine and greater than that of sulphadimidine and sulphisoxazole.23 But there are some striking differences in their metabolism in the body, which greatly affect their administration and use in clinical
treatment
practice. Sulphamethoxypyridazine
is well absorbed after oral administration and diffuses freely into the body-fluids, particularly into the cerebrospinal fluid.4 These properties THE IMAGINARY TEXTBOOK are shared by many sulphonamides, but sulphamethoxyUNDER the title La Musée Imaginaire, André Malraux pyridazine is exceptional in the slow excretion of its free has written of those advances in pictorial reproduction form in the urine. As a result it provides higher and more that have made possible an abundance of art books of sustained levels in the plasma than any other therahigh standard, enabling us to enjoy in our homes fine peutically effective antibacterial sulphonamide.5-n The pictures from the world’s museums. The converse is a conjugated form is excreted much more rapidly through well-known feature of medical London, where the the kidneys, so that in the plasma most is present in the Wellcome Museum of Medical Science (183, Euston free state. Both forms are highly soluble in the urine.3s Road, London, N.W.1) is virtually a textbook on walls. In freshly drawn oxalated human blood, nearly all of the Here 10,000 visitors a year inspect the displays, which drug is in the plasma and little or none is found in the are very well produced and laid out. As when it was red cells.10 11 Therefore, levels in whole blood are, on founded in 1914, the museum is again devoted to diseases the average, only about 60% of the corresponding levels found in tropical countries; in each case there is a in the plasma. After a single oral dose of 0-5-4-0 g., peak written account of xtiology, diagnosis, prevention, and concentrations are reached in about three hours, and are treatment, prepared by experts or with their assistance, sustained for a further three or four hours.12 Thereafter with lavish illustrations-photographs, drawings, diathe concentration declines slowly and the time taken for a grams, photomicrographs, models, and specimens. There fall to half the peak value is about fifty-five bourse A is one living exhibit-a tank of Gambusia fish, which eat similar time is taken for the excretion in the urine mosquito larvx and provide a cheap tool in malaria of half the administered dose. In these circumstances control. the drug readily accumulates in the body. When a dose The emphasis of the exhibition changes with that of of 1-0 g. is given every forty-eight hours, a slight cumuthe branch of medicine it reflects. Prevention is becoming 1. Domagk, G. Ann. N.Y. Acad. Sci. 1957, 69, 380. more prominent in every section. The displays dealing 2. Neipp, L., Mayer, R. L. ibid. p. 448. 3. Litchfield, J. T. Int. Physiol. Congr., Brussels, 1956. with syphilis and plague are much smaller than they used 4. Boger, W. P., Strickland, C. S., Gyle, J. M. Antibiot. Med. 1956, 3, 378. 5. Roepke, R. R., Maren, T. H., Mayer, E. Ann. N.Y. Acad. Sci. 1957, to be, and syphilis is included among the other spiro69, 457. chaetal diseases. The section on tuberculosis is expanding 6. Foerster, D. K., Martin, W. J., McGuckin, W. F., Nichols, D. R. Proc. Mayo Clin. 1956, 31, 678. at the expense of that on leprosy, and the common cold 7. Frisk, A. R., Wassen, A. Antibiotic Annual, 1956-57 (edited by H. Welch and F. Marti-Ibanez); p. 424. London. and measles find a place. 48 panels are devoted to 8. Jackson, G. G., Grieble, H. G. Ann. N.Y. Acad. Sci. 1957, 69, 493. malaria and 33 to nutrition and malnutrition; no doubt 9. Jones, W. F., Finland, M. ibid. p. 473. 10. Nichols, R. L., Finland, M. J. Lab. clin. Med. 1957, 49, 410. these proportions will be reversed as the malaria11. Nichols, R. L., Jones, W. F., Jr., Finland, M. Proc. Soc. exp. Biol. N.Y. 1956, 92, 637. eradication campaign progresses, unless more energy is 12. Finland, M., Jones, W. F., Jr., Ziai, M., Cherrick, G. R. Amer. J. med. and world into Sci. 1957, 234, 505. population. correlating food-production put