1120

from enemata and the like. The doses employed weresimilar to those used by Carmichael and his col-leagues (namely, 1-2 c.cm. of 1/4000 prostigminmethyl sulphate) ; but they were repeated at intervalsof 2-4 hours until improvement resulted, and as

many as nine doses were employed on occasionwithout any unpleasant effect.

Prostigmin belongs to the group of drugs thatinhibit the action of the enzyme choline-esterasepresent in the blood and tissue fluids. These anti-cholinesterases impede the destruction of any acetyl-choline produced in, or introduced into, livingorganisms. The action of the parasympatheticsystem upon the intestinal movements is cholinergic-i.e., it is associated with the production of acetyl-choline at the nerve-endings in the intestinal wall-and anything that tends to preserve the acetylcholineso formed may augment the peristaltic activityproduced. In experimental work the augmentationof acetylcholine effects is usually obtained by con-tinuous perfusion of the tissue with a solution con-taining an anti-cholinesterase. It appears possiblethat the greater efficacy of prostigmin in repeateddoses, as employed by Harger and Wilkey, dependsupon the maintenance of a more uniform state of

acetylcholine preservation in the body than can beachieved with a single or widely spaced doses. If this

interpretation of the action of prostigmin is correct, itoffers a reasonable explanation of the different findingsof Carmichael and of Harger and Wilkey, and indicatesthe therapeutic importance of repetitive dosage.

ATELECTASIS AFTER ANÆSTHESIA

A RECENT discussion at the Royal Society ofMedicine showed substantial agreement among physi-cians, surgeons, and aneasthetists that collapse ofthe lung is generally the result of obstruction to abronchial tube. But several speakers then citedcases in which no such obstruction was present,especially when atelectasis followed rapidly on

external injury to the thorax. The nature of theanaesthetic was felt to bear only indirectly on theproduction of atelectasis, the salient predisposingfactors being the site of operation, its duration, andthe condition of the patient before operation.0. M. Jones and E. E. Burford have now describedmassive collapse following administration of Cyclo-propane in which atelectasis was in their opiniondue to absorption of gases in the alveoli. They point tothe great variation in the rate of this absorption inrelation to the gases present. Anaesthetic vapours,oxygen and carbon dioxide are all absorbed inminutes whereas the inert gases-nitrogen, helium,and hydrogen-require hours. Bearing this in mind,it is easy to see the possibility of massive collapsefollowing cyclopropane inhalation without anybronchial plug. As the inhalation continues thebronchial atmosphere may become devoid of inert

gas except for the small amount of nitrogen broughtfrom the tissues to the lungs by the blood in simplesolution and diffused into the alveoli. As the blood

normally contains about 1 per cent. nitrogen theamount so brought would have little effect in alveoliaccustomed to a nitrogen tension of 80 per cent.When the alveoli have lost the supporting propertiesof the inert gas conditions are present which favouratelectasis. The details of the four fatal instancesin which the paper is based certainly give supportto this theory. Jones and Burford recommend theroutine use of helium during the administration of

1 Lancet, March 12th, pp. 613 and 619.2 J. Amer. med. Ass. April 2nd, p. 1092.

cyclopropane and describe the most convenientmethod of carrying this out. But, as we have

already had occasion to point out,3 helium is more

readily obtainable for this purpose in Americathan here.

STUDIES ON TYPHOID FEVER ON THE

WITWATERSRAND

IN a monograph issued from the South AfricanInstitute for Medical Research, Dr. W. Lewin 4

records a series of observations on the diagnosis,prophylaxis, and serum treatment of typhoid fever.He confirms the findings of A. Felix, and of manysubsequent workers, in regard to the part played bythe Vi antigen in determining mouse-virulenceand immunising potency ; and he notes, again in

agreement with many other observers, that a vaccineprepared from a strain containing the Vi antigenwill induce an active immunity in mice, even

though the treatment employed in killing the bacillihas deprived them of the power of stimulatingthe production of Vi agglutinin in detectableamounts.

In a study of 229 strains of Bact. typhosum freshlyisolated from cases of enteric fever, he finds, as othershave done, that the great majority of such strainsare of the form which Kauffmann has named V-W.These strains contain the Vi antigen, but not in solarge an amount as to render the bacilli inagglutinableby an 0 antiserum in moderate dilution. Strainsof Kauffmann’s V type, in which the preponderanceof Vi antigen inhibits agglutination in an 0 antiserumare relatively rare (18 of 229 strains), and strainsof Kauffmann’s W type, in which the Vi antigen isabsent, or undetectable by direct agglutination, arerarer still (4 of 229 strains). No correlation could beobserved between the severity of the disease and thetype of infecting bacillus. The proportions of thedifferent types in a small series of strains isolatedfrom carriers were found to be very similar. It isnoted that repeated examinations of a single carrierat considerable intervals of time may yield strainsof all three types.The sections on diagnosis deal in the main with an

attempt to establish a " diagnostic titre " for H and0 agglutinins, using standardised bacterial suspensions.Taking the obvious point of departure, though itsobviousness has not always led to its adoption, theauthor first determined the frequency of agglutina-tion at various titres among 442 samples of serumobtained from normal persons in the district concernedwho gave no history of an attack of enteric fever,or of antityphoid inoculation. He found that 2-9 percent. of these normal sera gave H agglutination at atitre of 1 : 100, while 2-0 per cent. gave 0 agglutina-tion at 1 : 200. He adopted these titres for his

diagnostic tests because (a) at this level the odds wouldbe high against a false positive result, and (b) becausemost patients suffering from typhoid fever form

agglutinin to titres as high or higher than these,so that there should not be many false negativeresults. Two series of cases are described in whichthis method was put to the test. Both series wereobserved in hospital. In the first series only onespecimen of serum was examined from each patient.In 32 cases a provisional diagnosis of enteric feveron admission was confirmed by the isolation ofBact. typho8um from the blood or excreta. In 81 per

3 Lancet, April 30th, p. 1008.4 Typhoid Fever on the Witwatersrand: Bacteriological

Aspects, Serological Diagnosis, Specific Prophylaxis, andSpecific Treatment. Publ. S. Afr. Inst. med. Res. 1938, 8,413-550.