CHOLINE DERIVATIVES

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discusses the subject clearly and concisely, andhis little book is particularly suitable for intelligentadult patients.

ENCEPHALITIS IN JAPAN

THERE was an epidemic of encephalitis in Japanin 1873 and another in 1911. The latter was lookedon as a cerebro-spinal meningitis, and it was notuntil the epidemic of 1924, in which over 6000 caseswere reported, that the true nature of the 1911outbreak was realised. In 1929 there was a smalleroutbreak, with nearly 2000 cases, and the diseasewas prevalent again in 1935 (5000 cases). Apparentlyit is more or less endemic in Japan, at any rate inthe summer months, especially in certain seaside

places. In 1933 a committee was appointed to

investigate it, and as head of this committee Inadais now reviewing its work in a French journal.!Real progress as regards the etiology of the diseasedates, he says, only from 1933, when Hayashisucceeded in transmitting it to Java monkeys.In the same year besides transmitting encephalitisto monkeys Webster and Fite in the United Statessucceeded in infecting mice. This opened up widepossibilities, which the committee fully used in the1935 epidemic. They find that up to the seventhday of disease inoculations of brain matter will

usually infect mice. It has also been possible toinfect them with blood, either directly inoculatedor transmitted through mosquitoes. Cerebro-spinalfluid was most infective for mice during the secondto fifth days of disease. It was noted that virulencesometimes increased after the third or fourth passagethrough the mouse. Monkeys, it now appears, are

less susceptible than mice, and their susceptibilityvaries with species and age. The incubation periodwhen human material is directly inoculated into the

monkey appears to be about 5-8 days. As regardsmode of infection, Inada considers two hypotheses-infection through the nasal mucosa and infection

by the bite of an infected mosquito. In weighingthese it must not be forgotten that the Japaneseepidemic and the St. Louis epidemic-with bothof which these observations deal-differed in several

ways from the great European epidemics of 1917-26.In particular, the difference in the season at whichthey occurred has a bearing on the mode of spread.The outbreaks in the European (lethargic) epidemicswere almost limited to the colder months ; theirrecurrent peaks were in the second half of the winter ;the Japanese and St. Louis outbreaks, on the otherhand, were in the summer. The idea that the diseaseis transmitted through the nose is based on the factthat typical changes have been found in the brainafter direct nasal infection of animals, and the findingof the virus in nasal washings ; the difficulty of

accepting it is the rarity of multiple cases of infectionin one household. All the Japanese workers agreethat in animals infection by the nose is more oftensuccessful than subcutaneous or intraperitonealinjection, and indeed is only second to direct cerebralinoculation. Twenty-four hours after nasal injectioninto the mouse the virus can be obtained from the

olfactory lobe and transmitted with it to anotheranimal. Infection by mosquito bites have beenunsuccessfully attempted in the United States, buthas been achieved in Japan with difficulty and afterrepeated passages. It seems evident that certainforms of mosquito can harbour the virus, but furtherobservations are necessary before one can decidebow far this fact affects mankind.

1 Inada, R. (1937) Pr. méd. 45, 99 and 386.

CHOLINE DERIVATIVES

NOT long ago 1 we referred to the modern tendencyto search among substances chemically relatedto powerful drugs and hormones in the hope of

discovering compounds in which a single activityof the parent substance is prominently exhibited,and by way of example we cited the action of carb-

aminoylcholine on the bladder in certain cases ofretention of urine. A valuable account of the effect ofthis drug on 26 normal persons has since been givenby Prof. Starr 2 of Philadelphia, and includes a

record of his own experience after taking a large dose.A similar investigation by Myerson, Loman, andDameshek 3 of Boston has been made for acetyl-beta-methylcholine (Mecholyl), and a comparison of theeffects of the two substances is interesting. Theyare both parasympathomimetic, acting on thecirculatory system, the alimentary tract, bladder,and skin. The effect of mecholyl is prompt, marked,and transient, and includes flushing of the faceand chest, perspiration, salivation, rhinorrhcea,lacrymation, fall of blood pressure, and an increasedpulse-rate which the authors are at a loss to explain.Carbaminoylcholine (Doryl) is slower but more

prolonged in its action which is otherwise similarin many respects to that of mecholyl. Prominentamong the symptoms to which it gives rise are,however, increased peristalsis and colic, and althoughflushing and sweating are conspicuous, the effects onpulse and blood pressure are slight. With both drugsatropine annuls unpleasant effects, though animal

experiments show that carbaminoylcholine has a

stronger " nicotine action " than mecholyl and theconsequent stimulation of autonomic ganglia mustpersist even after atropine. The action of mecholylon the alimentary tract is slight, but more work isnecessary before it can be assumed with confidencethat this is the drug of choice for circulatory effectsand carbaminoylcholine for visceral activity. The

length of time for which the substances act intro-duces a complicating factor. Thus Kramer 4 of

Philadelphia reports good results in peripheralvascular diseases using mecholyl, but finds difficultywith thrombo-angiitis obliterans. Starr, on the otherhand, records two cases of thrombo-angiitis obliteranswhich benefited greatly from carbaminoylcholine,the reason being, apparently, the more prolongedaction of this drug. The American investigatorsseem primarily interested in the relief of peripheralvascular lesions, and their results are on the wholeencouraging. They point out the danger of treatingpatients with a tendency to asthma with cholinederivatives, and although atropine is effective in

preventing disastrous effects, such patients are notlikely to benefit from the more desirable peripheralactions of the drugs.

Summer Time will commence in Great Britain,Ireland, the Channel Islands, and the Isle of Manon Sunday morning next, April 18th, at 2 A.M., whenthe hands of timepieces should be advanced one hour.It will end on Sunday, Oct. 3rd. Summer timebegan in France on Saturday, April 3rd, at 11 P.M.,and will end there at midnight on Saturday,Oct. 2nd.

1 Lancet, Jan. 30th, 1937, p. 276.2 Starr, I., Amer. J. med. Sci. March, 1937, p. 393,

3 Myerson, A., Loman, J., and Dameshek, W., Ibid,February, 1937, p. 198.

4 Kramer, D. W., Ibid, March, 1937, p. 405.