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rnent and persist, febrile convulsions which are followedby epilepsy which then remits, febrile convulsions whichare followed by persistent epilepsy, and a mixed groupof other convulsive disorders such as anaesthetic seizures.

Any convulsions among the brothers and sisters of theindex cases were classified in the same way, and so in each

group there was drawn a family pattern of convulsionsof the different types. In this way the group of indexcases with remittent febrile convulsions, remittent epilepsy,and convulsions followed by remittent epilepsy werefound to have much the same family pattern. The sibsshowed a high incidence (17-25%) of convulsions ofall types, most of these being remittent convulsions andabout a third epilepsy. The epilepsy was most oftenremittent epilepsy, or convulsions followed by remittentepilepsy. The sibs of the index cases with continuingepilepsy showed about the same amount of convulsionsof all kinds and of epilepsy (9%) but the epilepsy herein most instances was continuing and resistant to treat-ment, like that of the index case. In contrast to boththese was a family pattern found with convulsionsassociated with brain infection, encephalitis, or menin-gitis. Here the sibs had an incidence of convulsions ofall sorts of 6% and of epilepsy of-only 2% ; most of theepilepsy was of the continuing type. This patternmay well be that of any random sample of children.Thum 5 did in fact find an incidence of 6% of convulsionsin a group of over three thousand children in Boston,Massachusetts. Two other groups were of special interest.First, the group of children in whom the convulsionswent on continually until they died might perhaps beexpected to behave like the group with brain infections ;but the incidence of convulsions of all sorts in the sibswas nearly 30% and the incidence of epilepsy nearly17%, most of this epilepsy being of the continuous typeresistant to treatment. The other group of specialinterest were the children with temporal-lobe attacks,often assumed to be purely symptomatic. Here the familypattern was very much that of groups where the indexcases had remittent febrile convulsions or remittent

epilepsy, with 15% of convulsions of all sorts and 61/2%of epilepsy, most of which was remittent epilepsy.Genetic endowment would appear to play a part here too.This has of course no direct bearing on the value of

surgery for this disease.A possible interpretation of these findings in children

is that one genetic factor or group of factors predisposesto remittent febrile convulsions or remittent epilepsy,or sometimes temporal-lobe epilepsy; while another factoror group of factors predisposes to persistent epilepsyresistant to treatment but sometimes results only inremittent febrile convulsions. Febrile convulsions

continuing till death would then appear to be due to anintense form of the second group of factors.

5. Thum, D. A. Amer. J. Psychiat. 1942, 98, 574.6. Boland, E. W., Headley, N. E. Ann. rheum. Dis. 1954, 13, 291.7. Bunim, J. J., Pechet, M. M., Bollet, A. J. See Ibid, 1955, 14,

102.

NEW STEROIDS

COMPARATIVELY minor alterations in structure can

profoundly change the pharmacological characteristicsof a steroid hormone. Thus a halogenated derivative ofhydrocortisone, 9oc-fliiorohydrocortisoiie, exerts a muchgreater anti-inflammatory action, weight for weight, thanhydrocortisone, and in terms of mineralocorticoid activityit is proportionately even more potent. Because it

readily brings about sodium retention, this compound isunsuitable for use in the treatment of rheumatoidarthritis. There would be an obvious place for substancessuppressing inflammation without inducing sodium reten-tion ; and it has been claimed that two new syntheticsteroids-metacortandralone and metacortandracin--meet this need.Bunim et al. found from the administration of meta-

cortandralone to seven patients with rheumatoid arth-

ritis that it was three to four times more potent thancortisone, and two to three times more potent thanhydrocortisone. Effects on the clinical picture, the

erythrocyte-sedimentation rate, and C-reactive proteinwere similar to those of cortisone. With doses whicheffectively suppressed the signs of active arthritis, therewas no sodium retention or potassium loss. With rather

higher doses a negative nitrogen balance developed.The steroid did not raise the fasting level of blood-sugar,and in no case did glycosuria appear. The undesirableeffects, described as minor, included manifestations of

Cushing’s disease seen in some patients treated withcortisone-hirsutism, facial rounding, acne-and alsosleeplessness and transitory mental depression. Hyper-tension did not develop. The properties of metacortan-dracin were very similar. Bunim and his colleaguesemphasise that there is still no information about theeffects of long-continued administration of these newsteroids.

Metacortandralone and metacortandracin may proveuseful in cases where cortisone produces excessive sodiumretention. But probably many of the limitations ofcortisone are shared by these new derivatives-there is,for example, little reason to hope that in rheumatoidarthritis they will arrest damage to the joints any moreeffectively. In further trials the suppressive effect ofthese derivatives on the adrenal cortex will have to beassessed.

1. Balint, J. A., Slater, J. D. H. Gastroenterologia, Basel, 1954,6, 330.

2. Benedict, E. B. Gastroenterology, 1947, 8, 251.3. Flood, C. A., Hennig, G. C. Ibid, 1951, 19, 787.4. Allen, A. W., Welch, C. E. Ann. Surg. 1941, 114, 498.5. Ransom, H. K. Ibid, 1947, 126, 633.6. Avery Jones, F. In British Encyclopædia of Medical Practice.

London, 1952; vol. 11, p. 581.

DEFORMITY OF THE PYLORIC ANTRUM

THE most important cause of persistent deformity ofthe pyloric antrum is carcinoma ; but benign lesions ofthe stomach or duodenum or, occasionally, extrinsiccauses can give rise to very similar radiographic appear-ances. Balint and Slater point out that no singlediagnostic measure-clinical examination, radiography,gastroscopy, or even laparotomy-can be relied on todistinguish the benign from the malignant lesion. Gastro-

scopy and radiography are complementary methods ofexamination 2 ; some, such as Flood and Hennig,3emphasise the limitations of gastroscopy but others havefound it very reliable. Radiography is the simplestmethod of demonstrating antral deformities, but its valuedepends very largely on the individual radiologist. Evenin expert hands, it does not always reveal clearly whetheran ulcer is benign or malignant.

Allen and Welch 4 estimate that of all prepyloric ulcers75% are malignant ; but Ransom 5 found that in hisseries some 90% were benign. The gastric ulcer-par-ticularly at the antrum-that shows no signs of healingdespite clinical improvement should be regarded as

possibly malignant. On the other hand, apparent healingdoes not exclude malignancy. Gastric analysis may behelpful, in that the absence of free hydrochloric acid iscommoner in carcinoma than in benign lesions ; but

gastric carcinoma can exist in the presence of hyper-chlorhydria. s

In some cases of antral deformity no cause can bedemonstrated.l Flood and Hennig studied 42 cases of" benign antral disease," in 9 of which no evidence ofulcer was brought to light. Possibly the deformity issometimes due to true antral gastritis, and in one of thecases reported by Balint and Slater there was histologicalevidence of " chronic gastritis " ; but many radiologistshesitate to make such a diagnosis, particularly since it iscommonly not easy to confirm. Possibly, as Balint andSlater suggest, in other cases the deformity is the outcomeof recurrent peptic ulceration with persistent spasm orresidual scarring of the antrum ; and occasionally per-

1113

sistent spasm develops in the apparent absence of anylocal disease.7When the radiographic or gastroscopic appearances are

inconclusive, laparotomy is preferable to a policy ofwait-and-see. But laparotomy also has its limitations :an ulcer or early malignant infiltration is not alwaysdetectable, and a malignant ulcer may appear benignand an inflammatory mass around the duodenum

malignant 1 ; so sometimes the diagnosis can beestablished only by microscopic examination.

7. Jenkinson, E. L., Hammernick, F. J. Radiology, 1948, 51, 798.8. Drury, A. N. Physiol. Rev. 1936, 16, 292.9. Green, H. N., Stoner, H. B. Biological Actions of the Adenine

Compounds. London, 1949.10. Honey, R. M., Ritchie, W. T., Thomson, W. A. R. Quart. J. Med.

1930, 23, 485.11. Wayne, E. J., Goodwin, J. F., Stoner, H. B. Brit. Heart J. 1949,

11, 55.12. Drury, A. N., Szent-Gyorgyi, A. J. Physiol. 1929, 68, 213.

ADENOSINE AND THE HEART

Drury, in 1936,8 described detailed studies of theaction of adenosine derivatives on the heart in smallanimals. The main effect was on the conducting system,with sinus slowing and auriculoventricular block. Greenand Stoner 9 found that these compounds also caused atransient fall in blood-pressure. Honey et al.1o showedthat adenosine could produce heart-block in healthymen. The effect of magnesium adenosine triphosphateon the electrocardiogram (E.c.G.) was extensively studiedby Wayne, Goodwin, and Stoner 11 in patients who werereceiving intravenous injections of this substance as

treatment for rheumatoid arthritis. When the injectionwas made rapidly there was invariably subjective dis-turbance, consisting of hyperpnoea, cough, flushing, anda transient sensation of faintness. In all cases the blood-

pressure fell, the greatest reduction being by 100 mm. Hg.The changes in the E.C.G. were remarkably constant.Small doses (5-15 mg.) produced brief sinus bradycardiafollowed by sinus tachycardia. Larger doses (15-30 mg.)caused pronounced sinus slowing, and in addition

depressed the conducting tissues with consequent firstor second degree auriculoventricular block, Wenckebachperiods, and occasionally complete asystole for severalseconds. The action of adenosine was similar to that ofadenosine triphosphate but less distinct. The productionof auriculoventricular block by adenosine triphosphatewas prevented by atropine, indicating that this actionwas mediated through the vagus. Adrenaline produceda similar effect to atropine. The action of adenosinetriphosphate on the heart was not confined to the

conducting tissues ; alteration in the ST segment andventricular ectopic contractions suggested a direct effecton the myocardium. These myocardial effects were foundto be decreased by the magnesium ion, which potentiatedthe depressant action on the conducting system.Adenosine triphosphate also brings about dilatation of

the coronary arteries in animals,12 and various forms ofadenosine have been used from time to time in thetreatment of cardiac and peripheral vascular disease.Wayne, Goodwin, and Stoner 11 considered that use ofthis substance for such purposes might be unwise inview of the direct effects on the myocardium ; while

Honey et al.1o did not regard adenosine as useful forthe treatment of heart-disease. In a letter on p. 1125Dr. Somlo describes the treatment of supraventricularparoxysmal tachycardia by rapid intravenous injectionof adenosine triphosphate 20 mg. Both the subjectiveeffects and the E.c.G. changes were essentially similar tothose described previously, except that there was

invariably ventricular asystole, sometimes followed bymultifocal ventricular ectopic beats which in turn werefollowed by normal beats and then by normal sinusrhythm. There were no untoward side-effects.Adenosine triphosphate may prove a powerful thera-

peutic weapon against paroxysmal tachycardia. But itshould be remembered that supraventricular tachycardia

is often a benign condition which is a nuisance ratherthan a danger, and that attacks commonly terminatespontaneously. Most physicians, therefore, prefer firstto try simple measures, such as carotid pressure or" trick " manoeuvres to induce vagal stimulation, seda-tion, or oral administration of digitalis. But not all casesrespond to such treatment ; and long-continued paroxys-mal tachycardia may constitute a real danger to thepatient. In such circumstances adenosine triphosphatemight certainly be considered ; and this drug may bemore effective than others, such as methacholine chloride,quinidine, or procainamide, which are not uncommonlyused. Adenosine triphosphate might with advantage begiven as the magnesium salt, which has less direct actionon the myocardium.11- In view of its action on the myo-cardium, great caution is necessary in administering itto patients with organic heart-disease and much cardiacenlargement ; but need to terminate the ectopic rhythmmay justify the risks. Adenosine triphosphate shouldnot be given without E.C.G. control, and preferablyatropine should be at hand in case prolonged asystoleensues. It seems possible from Sorril6’s observationsthat adenosine triphosphate might induce ventriculartachycardia, but this has apparently not arisen on anyof over four hundred occasions, referred to by Dr. Somlo,when the drug was administered to terminate a supra-ventricular paroxysm of tachycardia.

Somlo considers that the response of supraventriculartachycardia to adenosine triphosphate is so specific asto constitute a diagnostic criterion. But of course, ashe would no doubt agree, the diagnosis should be estab-lished clinically and electroeardiographically before thedrug is administered.

A SNOW CENTENARY

EPIDEMIOLOGISTS have been accused of having a

Broad Street Pump fixation which blinds them to theneeds and opportunities of work on diseases of moreimmediate importance than cholera. Quite unabashed,the section of epidemiology and preventive medicineof the Royal Society of Medicine met on May 17 at theLondon School of Hygiene and Tropical Medicine tocelebrate the centenary of the publication of Dr. JohnSnow’s classic On the Jlode of Cornlnunication of Cholera.A group of students working for the diploma in publichealth had prepared an exhibition (which will be openfor a month) of Snow miscellania ranging from a hithertolittle-known portrait painted at the request of QueenVictoria to an account of the findings at necropsy afterhis tragically premature death from chronic renal diseaseat the age of forty-five. The exhibits outline the mainfacts of his life and the steps which led him to recordhis belief that cholera was spread through infection ofthe community’s drinking-water by the patients’ dejecta,first rather tentatively in 1849, and then with forcefulconviction in the more substantial edition of 1855. Thisbook, which as Wade Hampton Frost said in his intro-duction to the Commonwealth Fund reissue " shouldbe read once as a story of exploration and many times asa lesson in epidemiology," is indeed the exemplar of theepidemiological method at its best.

Prof. A. Bradford Hill, F.R.s., the section’s president,pointed out that Snow had to wait for confirmation ofhis thesis until the disastrous epidemics of the 1850s,when the removal of the intake of water supplied by theLambeth Company up the Thames to Ditton producedthe remarkable contrast in cholera mortality whichformed the basis of Snow’s " experiment on the grandestscale." In Southern London the pipes of both theLambeth Company and the Southwark and VauxhallCompany (which drew " the filthiest stuff ever drunk

by a civilised community " from the Thames in the heartof the city) went down every street supplying rich andpoor, clean and dirty, in a manner which had all the