1199

a slight rise in the blood-urea level, but no clinicaluraemia,. Routine observations of the urine volumeand specific gravity were the only measures whichwould readily reveal the renal lesion. In this countryMAHLER and STANBURY 12 have studied a patientin whom potassium depletion not only diminished theconcentrating power of the kidney but also led toexcessive loss of phosphate and sodium chloride inthe urine. CLARAE et al.13 demonstrated in healthyvolunteers that potassium deficiency prevents the

kidney from excreting a urine of maximum acidityafter the ingestion of ammonium chloride.Although there is some reason to believe that

vacuolation of the tubules may be produced by severalcauses,14 potassium depletion is certainly one of them ;and the evidence that it can lead to a reversible lesionof the renal tubules is very convincing and constitutesan important addition to our knowledge of themetabolism of this ion. The implications are far-reach-ing and shed light on the difficult differentiationbetween primary potassium-losing renal disease andConn’s syndrome, in which the body loses potassiumbecause an adrenocortical tumour is secreting excessiveamounts of aldosterone. In the fully developed syn-drome there is severe hypokalsemia, hypernatræmia, andalkalosis, with tetany and muscle weakness.15 CONN’Soriginal patient also gave a history of polyuria andnocturia for years, and hyposthenuria and slightproteinuria pointed to a defect of the renal tubules.These renal features of the syndrome may well havebeen due to the nephropathy of potassium depletion,and they disappeared when the electrolyte state

returned to normal after the removal of the adrenaltumour. The clinical distinction between such a

patient and one with primary potassium-losing renaldisease is thus not easy. The difficulty may be resolvedwhen a simpler and more accurate means of esti-

mating aldosterone becomes available. Presentmethods are not sufficiently critical for clinical use,and the problem is complicated by the fact thatsome renal diseases and other oedematous states arein any case accompanied by an increase in theexcretion of aldosterone.As MAHLER and STANBURY point out, the distinction

between primary renal and primary adrenal potassiumloss is a matter of great moment, for in Conn’s syn-drome removal of the adrenal tumour may bring aboutcomplete cure, while in primary potassium-losingrenal disease potassium supplements are the onlyuseful treatment (Dr. FLEAR and his colleagues discusssome aspects of oral potassium therapy in their articleon p. 1190) and complete renal failure is the expectedoutcome. COPE and MILNE 17 have discussed the pointson which the differentiation should be made and theysuggest that Conn’s syndrome is to be suspected whenthere is no history of a primary renal disease, whenvery large potassium supplements fail to lead to theimprovement expected, and when renal biopsyshows only the tubular lesions of potassium depletionwithout evidence of other renal disease. If there are

12. Mahler, R. F., Stanbury, S. W. Quart. J. Med. 1956, 25, 21.13. Clarke, E., Evans, B. M., Macintyre, I., Milne, M. D. Clin. Sci

1955, 14, 422.14. Kulka, J. P., Pearson, C. M., Robbing, S. L. Amer. J. Path

1950, 26, 349.15. Conn, J. W. J. Lab. clin. Med. 1955, 45, 3, 661.16. Luetscher, J. A. jun., Johnson, B. B. J. clin. Invest. 1954, 33

276.17. Cope, C. L., Milne, M. D. Brit. med. J. 1955, i, 969.

signs of an adrenal tumour, and if it is possible todemonstrate excessive amounts of aldosterone in theblood or urine, the diagnosis becomes easier ’. but ifdoubts cannot be resolved exploration of the adrenalsmay be justified.

1. Hutton, P. W., Lutalo, J. K., Williams, A. W., Tonkin, L.,Fox, W. Tubercle, Lond. 1956, 37, 151.

2. Fox, W., Hutton, P. W., Sutherland, I., Williams, A. W. Ibid,p. 435.

3. Gregg, N. M. Trans. ophthal. Soc. Aust. 1942, 3, 35.4. Adams, J. M., Heath, H. D., Imagawa, D. T., Jones, M. H.,

Shear, H. H. Amer. J. Dis. Child. 1956, 92, 109.

Annotations

AFRICAN TUBERCULOSIS

PULMONARY tuberculosis is said to be a more acute and

malignant illness in Africans than in Europeans. As theresponse to chemotherapy depends both on the action ofthe drugs on the bacilli and on the resistance of th host,it might be expected that Africans would respond lesswell than Europeans ; and this matter has recently beeninvestigated.The chemotherapy trials of the Medical Research

Council in this country have already provided muchprecise knowledge about chemotherapy in British

patients. In 1953 Professor Williams and his colleagues atMakerere College, Kampala, Uganda, in collaborationwith the tuberculosis research unit of the MedicalResearch Council, began similar trials in Uganda inAfrican patients.’ These trials closely followed the

pattern of the British ones, both in regimens of treatmentand in type of disease treated. The statistical design ofthe two series was similar, and so were the methods ofanalysis. It has, therefore, been possible validly to

compare some features of the disease and its response totreatment in African and British patients.2 63 patientsin Uganda with acute extensive bilateral pulmonarytuberculosis were compared with 136 British patients.Both groups were treated with isoniazid and either

streptomycin or p-aminosalicylic acid (P.A.S.) daily. TheAfricans were in rather worse clinical condition beforetreatment ; and they had more extensive disease andmore cavitation. But at the end of three months thechanges in the two series were similar. Radiographicchanges were assessed by a panel, the members of whichdid not know that the films were of patients of differentrace. Moderate or considerable improvement was

recorded for 52% of British patients and 57% of Africanpatients. Although the groups had slightly differenttreatment during the second three months, the resultsafter six months were still remarkably similar. Radio-

graphic results were also assessed by comparing thechanges in matched pairs of films in the two series ; andjudged in this way the Uganda patients seemed to haveresponded to treatment slightly better than those inBritain.

There was certainly no evidence throughout the

analysis that the early effects of antibacterial treatmentin Africans were inferior to those in Europeans. This

investigation is doubly interesting : it provides con-

vincing evidence that rational and competently supervisedchemotherapy can produce as good results in Uganda asin Great Britain ; and it shows the great value of

coöperation between research-workers in this countryand those in the less favourable environment of econo-

mically underdeveloped countries where tuberculosisremains a major problem.

VIRUS INFECTIONS IN THE EMBRYO

SrrNcE 1942, when Gregg 3 drew attention to congenitalcataracts in children born to women who had had rubellain early pregnancy, many examples of congenital defectsin such children have been described. Adams et awl. of

1200

Los Angeles have lately reviewed the subject of virusdiseases in pregnancy as they afFect the child. Abortionmay result from maternal infection with influenza orpoliomyelitis, but congenital anomalies attributed to adisease other than rubella are mentioned in only one ofthe reports to which Adams et al. refer, and in that one 5

poliomyelitis was thought to be responsible.Adams et al. infected mice with influenza virus intra-

nasally just before breeding. Death or abnormality ofthe embryos was not significantly more common than incontrols ; but technical points concerning the dose andtime of administration of virus need further investigation.On the other hand, Adams et al. found that chick embryos,infected with influenza at 48 hours of age, becamedeformed and died. Prior inoculation of .antiserum

protected the embryos, and antiserum inoculated up to5 hours after the virus gave partial protection. Theseresults with chick embryos may be compared with thoseof Henle et all who infected 8-day chick embryos withultraviolet-irradiated influenza virus and noted stuntingof growth of embryo and a,llantois during the succeeding7 days. Death in that period was unusual, and the experi-ments were not continued till hatching. Homologousantiserum gave protection when given at the same timeas the virus, but antiserum given even as soon as 1minute after the virus did not prevent interference withthe growth of the embryo.These experiments throw no light on what influenza

in the mother may do to a human embryo. The experi-ments with mice were inconclusive, and the chick

embryos, though undoubtedly damaged by the virus,were infected in a way which exposed their cells to directcontact with an inoculum of virus that was very largecompared with the dose that could cross a human

placenta. Furthermore, in Henle’s experiments the

embryos were damaged by virus whose infectivity hadbeen destroyed by ultraviolet light. Gregg has summedup the situation by saying that though congenital abnorm-ality has been attributed to maternal infection with

mumps, influenza, smallpox, chickenpox, poliomyelitis,and infective hepatitis there is no regular pattern ofanomalies as there is in the rubella syndrome.

5. Aycock, W. L., Ingalls, T. H. Amer. J. med. Sci. 1946, 212, 366.6. Henle, W., Henle, G., Kirber, M. W. Ibid, 1947, 214, 529.7. Gregg, N. M. Trans. Amer. Acad. Ophthal. Oto-laryng. 1956, 60,

199.8. Selected Papers of Sir Gordon Holmes. Compiled and edited

by Sir Francis Walshe, F.R.C.P., F.R.S. London : Macmillan.1956. Pp. 264. 20s.

9. Selected Works of John Hughlings Jackson. London. 2 vols.,1931 and 1932.

10. Selected Writings of Sir Charles Sherrington. London, 1939.

A PIONEER IN NEUROLOGY

THE guarantors of Brain have published 8 a selectionof the papers of Sir Gordon Holmes as a tribute to thisgreat neurologist on his 80th birthday. Though it hasnot been possible to produce as wide a selection as

was done for Hughlings Jackson 9 and Sherrington, 10 there is quite enough to show how much Holmes hascontributed to fundamental knowledge in neurology.His pioneer work on the cerebellum is represented byhis paper of 1908 on the connection of the inferior oliveswith the cerebellum in man, by the paper on a familialdegeneration of the cerebellum, by the greater part of hispaper with Dr. Grainger Stewart which, in 1904, establishedthe clinical signs of intracerebellar and extracerebellartumours, and by the Croonian lectures of 1922 basedlargely on his study of gunshot wounds of the cerebellum.The other writings which have been reprinted are con-cerned with the cortical representation of vision and withvisual orientation and attention, including the twoclassical papers of 1916 and 1918 in which Holmesestablished the point-to-point representation of the

retina, in the occipital cortex. Many neurologists willmiss the (toulstonian lectures of 1914 on the spinalinjuries of warfare, which contained much meticulousobservation, and the Horsley lecture of 1938 on thecerebral integration of ocular movements. The other

major omission is the paper with Sir Henry Head onsensory disturbances from cerebral lesions ; this has. infact, been reprinted 11 since it originally appeared, butin a volume which is not now easily obtainable.As Sir Francis Walshe points out in his preface, all this

fundamental work, and much more that is given in thebibliography, was carried out in the " spare time" ofa clinician busily occupied in hospital and privatepractice, and much of it, particularly on the cortical

representation of vision, while Holmes was on activeservice during the 1914-18 war.

This colledion will bring special pleasure to all the

house-physicians and clinical clerks who have workedat the National Hospital -with this celebrated teacher oflleurologv.

11. Head, H. Studies in Neurology. London, 1920.12. Ziff, M., Contreras, V., Schmid, F. R. Ann. rheum. Dis. 1956,

15, 227.13. Figge, F. H. J., Barnett, D. J. Amer. Pract. 1948, 3, 197.14. Hughes, J. G., Jordan, R. G., Hill, F. S. Sth. med. J. 1949,

42, 296.

JET INJECTION OF JOINTS

INTRA-ARTIcuLAR injections of hydrocortisone acetatenow have an accepted place in the treatment of rheuma.toid arthritis, especially in patients who have only a fewtroublesome joints. Ziff et al.12 have lately recordedresults with a "hypospray" jet injector which, theybelieve, can usefully replace the conventional syringe inthis type of treatment. This ingenious device 13 11 wasdesigned to introduce substances under pressure eithersubcutaneously or intramuscularly without using a

needle. The material to be injected is contained in smallmetal cartridges, hermetically sealed in a sterile alum-inium container, and it is forced through the skin as afine jet by a spring-activated plunger. To ensure

adequate penetration of periarticular structures, a

special injector, about 18% stronger than the standardinstrument, was developed. Only the nozzle of the

injector and the skin need be sterilised.In preliminary experiments a solution of a dye or a

suspension of hydrocortisone acetate was injected intojoints. The proportion of injected material which couldbe recovered by aspiration of the joint contents was ashigh as 60% for the dye, but much smaller for the hydro-cortisone-probably because much of it remained in thesynovial membrane or periarticular tissues. Jet injectionof a radio-opaque medium confirmed that the materialwas deposited in periarticular structures as well as

within the joint cavity. Ziff and his colleagues suggestthat the action of the hydrocortisone which actuallyenters the joint may be supplemented by the rest of thedose which is deposited around the joint. Clinically theresponse seems to have been much the same as that

produced by ordinary syringe-and-needle injection. Thesmaller joints responded best and the method seemedmost suitable for the digital joints, in which local treat-ment with hydrocortisone is often worth while and is

perhaps used less often than elsewhere. ;

Nearly all patients felt a sudden sharp or burningsensation at the moment of injection, and discomfort forseveral minutes afterwards, especially when small jointswere treated. ; but most preferred the hypospray toinjection with a needle. The only common reaction wasslight ecchymosis ; one patient bled from a small artery,and another had a small but persistent area of anaesthesiadistal to the site of injection. The method has thedisadvantage that it does not allow fluid to be withdrawnfor diagnostic or therapeutic purposes. Althoughattractively simple and quick, and apparently safe in