916

One of the important effects of corticotrophin or

cortisone in the nephrotic syndrome is a reduction of theabnormal glomerular permeability to the _plasma-proteins of smaller molecular weight," leading to a greatreduction of proteinuria. This is usually associated withan increase of glomerular filtration-rate. Heymannet also consider that diuresis is unlikely unless there is

significantly less protein lost in the urine, and they foundthat patients with the greatest reduction of serum-

protein levels often had a delayed diuresis compared withpatients less severely affected. The urine of nephroticpatients with severe oedema contains abnormally largeamounts of the sodium-retaining adrenal steroid, aldo-sterone,ll and in one such case 12 pure crystalline aldo-sterone was isolated. In a natural or hormone-induced

diuresis, urinary aldosterone is much reduced at thesame time as the output of urinary sodium increases.

ANTILEPROTIC ACTION OF DAPSONE ANDDERIVATIVES

DAPSONE is now regarded as the drug of choice in thetreatment of leprosy. The antibacterial activity of thissulphone was first examined because of its close chemicalrelationship to sulphanilamide.13 Both dapsone (4 : 4’-diaminodiphenylsulphone) and sulphanilamide have twoamino groups. In the sulphanilamide molecule only onesuch group is attached to the benzene ring, and its anti-bacterial activity is believed to depend on this ring beingfree :free

NH2B)S02.NH2 Sulphanilamide

NH20S020NH2 Dapsone

It has been assumed that the antileprotic activity of

dapsone likewise depends on free amino groups attachedto two benzene rings. Certain di-substituted derivativesof dapsone, such as solapsone and promanide, have beenprepared with a view to diminishing the toxicity (dapsonemay cause haemolytic anaemia and toxic hepatitis). Butit has been argued that these derivatives are inactiveper se, and owe their apparent activity to the liberationof dapsone in the body ; and Francis and Spinks 14showed that when solapsone and other soluble dapsonederivatives were administered orally they were convertedinto the parent dapsone in the stomach. But this explana-tion does not account fully for the antileprotic activityof these derivatives, because they are active when

injected, and very little is then converted to dapsone.Francis and Spinks noted that dapsone itself is notexcreted unchanged, but they did not identify the excre-tion products. Bushby and Woiwood 15 have now exam-ined these, and those of solapsone, by means of paperchromatography and paper electrophoresis. They findthat in man and the rabbit very little dapsone is excretedas such ; only about 5% is recoverable from the urine,the remainder being a conjugate in which one of theamino groups is blocked by glycuronic acid. This con-

jugate is also present in the blood. Bushby and Woiwoodhave also examined the excretion products of the di-sub-stituted dapsone, solapsone, both in man and in rabbits,and they find that when given parenterally it is not

changed to dapsone. Evidently the two free amino

groups are not essential for the activity of these sulphones.The picture is complicated by the fact that commercial

9. Lauson, H. D., Forman, C. W., McNamara, H., Mattar, G.,Barnett, H. L. J. clin. Invest. 1954, 33, 657.

10. Heymann, W., Gilkey, C., Salehar, M. Pediatrics, N.Y. 1955,15, 49.

11. Luetscher, J. A., Johnson, B. B. J. clin. Invest. 1954, 33, 276.12. Luetscher, J. A., Neher, R., Wettstein, A. Experientia, 1954,

10, 456.13. Buttle, G. A. H., Stephenson, D., Smith, S., Dewing, T., Foster,

G. E. Lancet, 1937, i, 1331.14. Francis, J., Spinks, A. Brit. J. Pharmacol. 1950, 5, 565.15. Bushby, S. R. M., Woiwood, A. J. Amer. Rev. Tuberc. 1955,

72, 123.

solapsone contains some 15% of semi-solapsone, in whichthere is only one free amino group, one only of the twoamino-groups in the parent dapsone being substituted.Bushby and Woiwood have shown that this mono-

substituted derivative of dapsone has antibacterialactivity, and that it is present in the urine of rabbitsinjected with pure solapsone free of semi-solapsone.Not all the substituted derivatives of dapsone are

converted in the stomach into the parent substance.Thus chromatography shows that 4-amino : 4’-carboxy-methyl-amino diphenyl sulphone is excreted unchangedafter oral or parenteral administration. According toBushby and Woiwood there can be little doubt thatdapsone exists in the body almost entirely as the con-jugate, with one amino group free, and they suggest thatthe activity of dapsone in man is due to this mono-substituted derivative, the presence of two free aminogroups being unnecessary for antileprotic activity. Cer-

tainly mono-substituted dapsone derivatives have anti-tuberculous activity in guineapigs,16 and, according toCochrane,17 the mono-substituted glycine derivative iseffective in the treatment of leprosy ; this compound isexcreted unchanged.15 The activity of solapsone admin-istered parenterally might therefore be due to thepresence of the semi-solapsone in the commercial productand to the formation of this in the body. If, as Bushbyand Woiwood say, the body detoxicates dapsone, and theproduct of detoxication is also active, it would seemrational to administer dapsone in a substituted detoxi.cated form. Mono-substituted derivatives with a higherantituberculous activity than dapsone itself are alreadyknown.

DR. ALBERT SCHWEITZER, O.M.Dr. Albert Schweitzer, musician, philosopher, and

medical missionary, came last week to London to receivefrom the Queen the honorary membership of the Order ofMerit. Their subsequent fireside chat on Bach’s music,of which he is the greatest living authority and exponent,will, he says, be among the most treasured memories ofa long life.He came also to thank the friends who help to support

his hospital at Lambarene. After the Harveian lectureon St. Luke’s day he took tea with the president andfellows of the Royal College of Physicians. Later heattended a general meeting at the Royal Society of

Medicine, and before signing his name as an honoraryfellow he thanked his hosts for their assiduity in forgingnew weapons which men like he, who had never written ascientific article in his life, were able to use in the serviceof humanity. The Royal Society of Tropical Medicineand Hygiene entertained him to dinner and welcomedhim as an honorary fellow. In his reply Dr. Schweitzersaid that he was feeling very much at home in the

tropical atmosphere which was now his native air. The

honorary doctorate of laws, conferred on him by theUniversity of Cambridge, gave him especial pleasure,for he maintains that he came to England through thegateway of Cambridge, where his old friend ProfessorBurkitt, whose grave he visited, had introduced his earlytheological works to the British public. Perhaps the high-light of his visit was one which illuminated but a luckyfew-those who listened to him playing Bach on the organof the Festival Hall late one evening, after the concert-goers had all unwittingly departed.

In December Dr. Schweitzer returns to his self-

appointed task in Equatorial Africa.

THE next session of the General Medical Council willopen on Tuesday, Nov. 22, at 2.30 P.M., when Sir DAVIDCAMPBELL, the president, will deliver an address. TheMedical Disciplinary Committee will meet on Wednesday,Nov. 23, at 2 P.M.

16. Smith, M. I., Jackson, E. L., Bauer, H. Ann. N.Y. Acad. Sci.1949, 52, 704.

17. Cochrane, R. F. Practitioner, 1951, 166, 373.