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Ephedrine, being more stable, is effective when givenby the mouth. Chen and Schmidt showed that a doseof 60 mg. given in this manner to a man produceda rise in blood pressure amounting to 20-30 mm. Hgin 15-30 minutes, and that this rise persisted for threeor more hours. Another difference between theaction of the two drugs is also related to the higherstability in solution of ephedrine. Its action isless intense but more prolonged than that of adrenalin.For example, in a comparative study of the physio-logical actions of ephedrine, tyramine, and adrenalin,Chen and Schmidt found that ephedrine in a dose500 times as great as that of adrenalin produced asimilar rise in blood pressure when given intra-venously to anaesthetised dogs, but that the heightof the rise was more slowly attained and its durationabout seven times longer than the rise producedby adrenalin. The effect of tyramine on the bloodpressure of anaesthetised dogs was found to be inter-mediate, in intensity and duration of response,between that of adrenalin and that of ephedrine.Tyramine, however, in doses of 100 mg. by mouthproduced no rise in blood pressure in man, whilstan equimolecular dose of ephedrine raised the systolicand diastolic pressures by 15-20 mm. Hg underthese conditions. It seems probable that theincreased stability of ephedrine over tyramine, andof tyramine over adrenalin, is related to the numberof phenolic hydroxyl groups contained in the molecule,adrenalin possessing two, tyramine one, and ephedrinenone. These differences, however, are insufficient toaccount entirely for the differences in physiologicalresponse produced by the three substances. Werethis not so, the action of &bgr;-phenylethylamine on bloodpressure would be as prolonged as that of ephedrine,whereas in point of fact the action is of greaterintensity, but of much shorter duration. More-over, as shown by Chen, 3-phenylethylamine, likeadrenalin, is inactive when given in doses of 50-150 mg.by mouth to man, and pseudo-ephedrine, which differsfrom ephedrine merely in the reversal of the stereo-chemical configuration of the -HCOH group, showsan action similar in type to that of ephedrine on theblood pressure of man and of dogs, but much weakerin intensity. It is clear, then, that the constitutionof the side chain of the phenyl ring is an importantdetermining factor in the pharmacological action ofthese drugs.

A substance having the pharmacological propertiesof ephedrine should prove of great value clinicallyin those conditions in which a prolonged adrenalineffect is desired. Its action in man has recently beenthe object of a series of physiological and clinicalinvestigations. W. S. Middleton and K. K. Chenhave studied the objective and subjective effects ofits administration by mouth to man, the ophthalmo-logical effects of its local application, and the reactionsof asthmatics to the drug. They find that dosesvarying between 50 and 400 mg. produce an averagerise in systolic pressure of 28 mm. Hg, and that thisrise is usually accompanied by some quickening ofthe pulse. The rise in pressure is manifested about30 minutes after the oral administration of the drug,reaches its maximum in about one and a half hours, ’,and begins to fall about two hours later. The doserecommended by them is from 60-90 mg., and withthis amount such untoward symptoms as perspiration,tremor, palpitation, and faintness, sometimes observedwith the larger doses, were absent. They have alsobeen able to confirm the original observation ofK. Miura in 1887 on the mydriatic effect of the drug,in that dilatation of the pupil begins about15-30 minutes after instillation, reaches its maximumin 30-60 minutes, and lasts from 3-9 hours. Nosigns of conjunctival irritation were observed.Ephedrine has also been shown to be effective inthe treatment of spasmodic asthma. Its beneficialaction in this condition has been demonstrated byW. Berger and H. Ebster. and according to themit sometimes produces relief in cases of migraine.These investigators have recently made a clinical

study of the action of ephetonin, a synthetic substitute

for ephedrine. This substance also is active whengiven by mouth to man, and benefit is stated to havebeen observed in a large number of mild and moderatelysevere cases of asthma, in chronic bronchitis, and inhay fever, in which last condition the drug wasemployed in 5 per cent. solution as a nasal spray.It seems likely that in ephedrine we possess a valuabletherapeutic agent, but the extent and limitations ofits use can only be determined by more extensiveclinical investigation. ____

GERMAN DERMATOLOGICAL CONGRESS.

THE fifteenth annual congress of the DeutscheDermatologische Gesellschaft was held at Bonn fromSept. 5th to 7th, and was a notable gathering, bothfrom the scientific and the social point of view.Prof. Erich Hoffmann, of Bonn, whose name willalways be associated with that of Schaudinn in thediscovery of the spirochsete of syphilis, made anadmirable chairman, and was ably seconded by alarge staff. The meetings, at which no less than 115communications were offered for debate, were heldin the Beethoven concert hall, and the main featuresof the programme were papers and discussions onthe biological and physical characters and effects ofX rays and of the Bucky " borderland " rays whichhave been on trial in Germany for the past year.Dr. G. Bucky, who now lives in New York, himselftook part in the discussion. Among some 400 dermato-logists who attended the congress were Prof. P. G.Unna, who was described by the chairman as theNestor of dermatology, and Profs. Karl Herxheimer(Frankfurt), Josef Jadassohn (Breslau), J. R. Almkvist(Stockholm), Howard Fox (New York), and J. F.Schamberg (Philadelphia). The sessions began dailyat 9 A.M. and with a luncheon interval of two hours

continued till 6 P.M. On the last afternoon, at Prof.Hoffmann’s clinic, there was a demonstration of manyrare and interesting cases, these being afterwardsdiscussed in full conclave in the Beethoven hall.Official but quite informal entertainments were

provided every evening, not the least popular of thesebeing a river trip to Remagen by Rhine steamerwith fireworks and illumination of the Bonn frontage.Thanks largely to Frau Hoffmann and her lady

: helpers the meeting added fresh lustre to the reputa-tion for hospitality which the city of Bonn has so

: long possessed. ____

POISONING FROM SOLID FUEL.

DURING the war when methylated spirit was

difficult to obtain solidified fuel became popular asa substitute. It has certain advantages over a fluidfuel, such as portability, and many people still findit convenient especially for use when travelling.In the September issue of the Analyst Sir WilliamWillcox and Mr. C. Ainsworth Mitchell draw attentionto the danger of leaving such tablets within the reachof children. They describe a case where serious illnessfollowed the consumption by a boy of 16 of 5 g. ofa substance which was designed for use as fuel, andwhich on examination agreed in its characteristics andreactions with metacetaldehyde. The boy is said tohave swallowed a portion of a tablet in mistake fora sweet. No ill-effects occurred till seven hours afterwhen the patient became flushed, restless, anddelirious. A few hours later the temperature roseto 100 F. and convulsions occurred, followed byfive further attacks of convulsions. The urine hadsp. gr. 1-014, was very acid, and contained a traceof albumin. There was marked tenderness of thecalves of the legs during this period. The temperatureremained between 100° and 1010 F. for 36 hours andthen fell to 99 F., where it remained for 24 hours,afterwards becoming normal. The treatment con-

sisted in large doses of alkalis (in the form of sodiumcitrate, 60 gr. ; sodium bicarbonate, 30 gr. ; waterto 1 oz.) given every four hours by the mouth. Rectalinjections of 2 drachms of sodium bicarbonate to thepint of normal saline were given every six hours.Throughout the period during which the convulsions

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occurred chloral (10 gr.) and potassium bromide I(30 gr.) were given four hourly. The urine remainedvery acid for three days in spite of the large doses ofalkali that were administered. After the convulsionshad ceased potassium bromide, in doses of 15 gr.,was given three times a day for four days. The patientmade a good recovery, but the albuminuria persistedfor four days. After recovery there was some lossof memory for several days. Sir William Willcoxand his collaborator comment on the curious factthat metacetaldehyde should be so much more activethan its isomer, since relatively large doses ofparacetaldehyde (paraldehyde) can be taken withoutill-effects. It is possible, however, that the actionmay have been due to an impurity.

MUSCULAR EFFORT AND CARDIAC FAILURE.THE limitation ot muscular ettort ancl its rela-

tion to cardiac failure was discussed in the Julyissue of the Quarterly Journal of Medicine by A. E.Clark-Kennedy and Trevor Owen. Experimentswere performed on healthy young adults todetermine the respiratory exchange at increasingrates of work, which was of a very severe nature.The effect of breathing air containing 26 per cent.and 16 per cent. of oxygen, and also a mixture of airand 5 per cent. carbon dioxide, while performingsimilarly severe work was also determined. It isconcluded that the alterations in the respiratoryexchange during exercise, when air or other oxygen-nitrogen mixtures are breathed, are chiefly due tolactic acidosis, and when the pressure of carbondioxide in the inspired air is also increased, a

lactic and carbonic acidosis are concerned. Theauthors maintain that carbon dioxide eliminationas well as oxygen supply must be an importantfactor in determining the amount of work of whicha man in capable. An increase of oxygen in theinspired air makes the elimination of carbon dioxideeasier, by delaying the accumulation of lactates,the physico-chemical factor in the limitation ofvoluntary effort being a rise of hydrogen-ion concentra-tion in the blood and tissues. This is ultimatelydependent upon failure of the whole cardio-respiratorysystem, including the heart, lungs and blood, butthe output of the heart is sufficient to cope with thevenous return, and the circulation does not failbefore the ventilation. In heart failure due todisease, there is clinically venous congestion andcedema of the lungs and other tissues. This doesnot occur in extreme muscular exhaustion in health.It is therefore improbable that the mechanism isthe same in both cases-i.e., exhaustion of thereserve power of the heart. In compensated heartdisease congestive heart failure does not occur withviolent muscular effort, the exercise being com-

pulsorily abandoned before cardio-respiratory dis-integration occurs. This could be explained if theability to effect pulmonary ventilation is reducedin a degree corresponding with the reduction in theheart function, and it has been shown that the vitalcapacity is diminished in patients with heart disease.This may be due to a protective mechanism, and ifthis protective reaction fails, congestive heart failurewould occur. The article is illustrated by two platesshowing the apparatus used and full details are givenof the experiments on which this theory of heartfailure is based. In the concluding discussionClark-Kennedy and Owen compare the mechanismof limitation of effort in health with that which isfound in congestive heart failure, where not onlydoes circulation fail before ventilation, but thecardiac output no longer keeps pace with thevenous return ; for, as they point out, the term heartfailure is capable of more than one interpretation.To the physiologist it signifies that the heart is nolonger able to maintain an adequate blood-supplyto the active tissues ; oxygen-want, in other words,is their criterion, since all the manifestations ofcirculatory insufficiency consequent on violent exer-tion, in the normal healthy individual, can be

accounted for by oxygen-want. The clinician, onthe other hand, is accustomed to think in terms ofthe abnormal. He is concerned not with healthyyoung men, but with those less fortunate personswhose myocardium is already scarred by rheumaticor other infection. The clinician’s picture of advancedheart failure is something quite unknown in the realmsof physiology ; it is that of the patient with orthopnoea,oedema, and venous congestion of the internal organs.These symptoms are manifestations not of oxygen-want, but of the inability of the ventricles to keeppace with the venous inflow. It is with the first ofthese two conceptions that the writers’ experimentalobservations are concerned. Prof. A. V. Hill and hiscolleagues have shown that the duration of violentexercise is limited by the oxygen intake. When theoxygen requirements of the tissues are greater thanthe supply coming from the lungs the body contracts,as they express it, an " oxygen debt." The moreviolent the exertion the more rapidly does this debtmount up. But like other overdrafts it had itslimitations, and the attainment of these limitationsspelt the cessation of exercise. Thus the mile runnerhas to go more slowly than the sprinter or his oxygendebt will stop him before he reaches the tape. Havingworked out the limitations of oxygen intake andoxygen debt respectively, Hill was able to calculatethe speeds at which it is theoretically possible to rundifferent distances ; and he has shown that the timescalculated in this way were just a little better thanthe corresponding actual records established by theworld’s champion athletes. Clark-Kennedy and Owennow suggest that CO output as well as oxygen intakeshould be considered in this connexion ; and further,that the limitation of voluntary exertion in normalsubjects depends on a simultaneous failure of cardiacand pulmonary functions. The latter hypothesis isopposed to that which has hitherto been current-namely, that circulatory insufficiency supervenes whilepulmonary ventilation still remains adequate.

MECHANICS OF THE GALL-BLADDER.

THE exact mechanism by which the gall-bladderempties its contents is still unknown. The theorythat the flow of bile is regulated by any sphincter-like action at the mouth of the gall-bladder can nolonger be maintained, and in view of recent researchit is even difficult to find evidence of any activecontraction on the part of the muscle of the gall-bladderitself. The introduction of cholecystography by Dr.E. A. Graham has not only led to easier diagnosisin many cases of gall-bladder disease, but is enablingworkers in all parts of the world to investigate moreclosely the physiology of the biliary tract. The workof Dr. Graham himself and of his associates, G. H.Copher and S. Kodama, has suggested that ther6le of the gall-bladder is chiefly passive, itscontents being emptied mainly by the washing outof bile when fresh bile flows in, or by the elastic recoilof the distended gall-bladder at the moment whenrelaxation occurs of Oddi’s sphincter at the duodenaltermination of the common bile-duct. The chiefevidence for this view lies in an ingenious series ofexperiments in which a small rubber bag was sub-stituted for a gall-bladder in a dog and was shownto fill up with dye and subsequently empty itself injust the same manner as the gall-bladder itself haddone. Recent work by G. E. Burget i of theUniversity of Chicago goes to support the theory thatthe gall-bladder itself is incapable of contraction andthat its control of the bile flow is confined to theaction of a certain tonus which facilitates emptyingwhen the opening into the duodenum becomes patent.An opposite view is set out by A. Hamrick, of theMayo Foundation, Rochester. He has made numerousstudies with the aid of X rays of the movementsobserved in animals after the injections of iodisedoil into the gall-bladder. The opaque oil was

1 G. E. Burget: Amer. Jour. Physiol., 1927, lxxxi., 422.2 R. A. Hamrick: Amer. Jour. Med. Sci., 1927, clxxiv., 168.