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distinctly enlarged. An amended diagnosis of either c

double pregnancy in a bicornuate uterus with J

miscarriage from the left cornu (normal or rup- ]tured ectopic pregnancy) or fibroid of the uterus Iwith miscarriage was now made. The uterus and ibreasts continued to enlarge through April and

May, and the former was nearly up to the um- :bilicus.Early in June I again examined the patient and

found that the uterus had not continued to rise, Iand that the souffle was less distinct. Towards theend of June it was evident that the uterus hadsunk. There was no souffie and the breasts weresmaller.When again examined on August 3rd a solid

mass was felt per vaginam to the patient’s right,but matting made it impossible to differentiatethe parts. In view of the doubt as to the truecondition a laparotomy was decided upon, and thisI performed on August 8th, assisted by Dr. W. W.Moore and Dr. MacDonell. On examining the

pelvis through the median incision the uterus andleft ovary were found to be adherent to the leftside. The right broad ligament was obliteratedby a large fluctuating swelling in its substance,filling the pelvis; and the right ovary and extremityof the Fallopian tube were defined on the surfaceof this swelling. An incision parallel to the pelvicbrim let out a great quantity of dark brown fluid,together with what appeared to be a five-months’foetus with fair-sized placenta.

It was evident that a right tubal pregnancy hadruptured beneath the peritoneum at about thesixth week, and gestation had then progressed untilabout the sixth month, when it was stopped bywant of sufficient blood supply. Convalescence wasslow, but eventually the patient recovered perfectly.Hastings, New Zealand.

THE DIAGNOSTIC VALUE OF ABDER-HALDEN’S METHOD IN CARCINOMA.

BY R. ST. LEGER BROCKMAN, M.R.C.S. ENG.,L.R.C.P. LOND.,

HOUSE SURGEON AT ST. BARTHOLOMEW’S HOSPITAL.

Abderhalden, professor of physiology at Hallein Germany, in his work on ferments of the animalsystem has shown that the body has the power toprotect itself against substances which are foreignto it if introduced by subcutaneous or intravenousmethods. The injection of cane sugar and vegetableproteids will give the serum of a dog into whosesystem they are so introduced the power of break-ing down these substances into less complexiiiolecules-a faculty wanting in the serum of ananimal not so injected.

After Veit had shown that syncytial cells werepresent in various parts of the body during preg-nancy Abderhalden set to work to see if he couldshow that any attempt was made to defend thebody against such invasion, especially as thetoxaemias of pregnancy were being attributed to

syncytiotoxins. In 1912 he published articlesdescribing the means by which he and his pupilshad been able to demonstrate in the blood of a

, pi-egiiaiit woman the presence of a substance whichhas a proteolytic action on placental albumin. Healso showed that such a substance is absent fromthe blood of males and non-pregnant women, andfurther that this ferment is specific, acting on

placental tissue only. To do this he made use

of two methods-the dialysation method usedin the following cases, which will be describedlater, and the optical method. In this lattercase 1 c.c. of a 10 per cent. solution of .

placental peptone and 2 c.c. of serum from the

patient under question are placed in a small polari-meter tube, the initial degree of rotation of lightbeing at once read off. The tube is now placed inan incubator at 37°C., the tube being removed

occasionally and examined by means of a polari-scope. Incubation was allowed to proceed up to36 hours. Abderhalden found that the maximumchange of rotation with serum from a case of

pregnancy was as high as 0’2°, whilst that when anyother serum was used never exceeded 0’03°. Hisexperiments in the case of animals gave similar,results. The practical value of such methods in thediagnosis of pregnancy has been testified to byAbderhalden, Veit, Schwarz, and other observers.The object of the present paper is to show that a

specific ferment is formed against carcinomatoustissue, and to demonstrate the possibility of theexistence of such being made use of in the diag-nosis of carcinoma. In all the following cases thedialysation method of Abderhalden has beenused.

A piece of coagulated carcinoma tissue, the preparation ofwhich is described later, is placed in a dialysing tube, madefrom a fish’s swim-bladder. To this are added 1-5 c.c. ofserum obtained from the patient whose diagnosis is in

question. Outside the dialysing tube are 20 c.c. of steriledistilled water. Into a control tube are put 1. 5 c. c. of serumalone, from the patient, with 20 c.c. of distilled water out-side. The surface of serum and water in both cases iscovered with a thin layer of toluol to exclude as far as

possible all bacterial contamination. They are now incubatedat a temperature of 37° C. for 12 to 24 hours. At the endof that time 10 c. c. of the diffusiate in each case are addedto 0..2 c. c. of a 1 per cent. solution of a reagent knownas ninhydrin. (Ninhydrin, or triketohydrindene hydrate,with a formula gives a violet colour if

COheated with a solution containing minute traces of albumin,peptones, polypeptides, and amino-acids. It gives a reactionwith all substances in which the amido group is in a positionto carboxyl.) The solution is raised to the boiling point andmaintained at that temperature for one minute. If at theend of that time no change takes place in either case thetest is negative. If, however, in the case of the one con-taining carcinomatous tissue a violet colour results whilstthe other remains colourless, then a positive result has beenrecorded. In many cases a brownish tint remains afterboiling. This has no connexion with the unmistakable violetcolouration of a positive result.The coagulated cancer tissue was the same for all the

following cases. It was obtained from a woman with alarge spheroiclal-celled carcinoma of the breast. As soon asthe breast had been removed by a complete Halstead opera-tion the carcinoma was carefully separated from fat andbreast substance. It was then cut up into small pieceswhich were dropped bit by bit into a beaker of boiling dis-tilled water to which a few drops of glacial acetic acid hadpreviously been added. It was boiled thus for half an hour.The tissue was then washed carefully in distilled water for12 hours. It was kept ready for use in cold storage in dis-water tilled with a layer of toluol on top. Before any was usedit had been kept thus for three weeks. The water in whichit had been standing was then tested with ninhydrin with anegative result, thus showing that all the albumin had beenefficiently coagulated. It was then dialysed with water,saline, and healthy human serum severally. The diffusiatein all cases gave no reaction with ninhydrin. The presenceof dialysable products, sufficient to nullify the test, in thiscancer tissue was thus excluded. The dialysing tubes werethen tested as regards their permeability to peptones andtheir impermeability to coll)ids. Those which fulfilled theseconditions were then used for the tests-all others being

rejected. In referring to certain pitfalls and sources of

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error which await one in doing this test I will describe themethod employed in collecting the serum in these cases.

In the first place the fingers must be absolutely excludedfrom any direct part in the test. A drop -of ninhydrin onthe skin, especially if at all moist, will leave a deep violetstain. The contamination of the outer side of a tube with afinger, prior to dialysis, is sufficient to give a positivereaction on testing the diffusiate with ninhydrin. A pairof sterile forceps was used in these cases to lift tubes andtissue.A trace of saliva will equally well give a positive reaction.’

This means that the mouth ought not to be used for suctionwhilst using a pipette. I use a rubber bulb on the end of

my pipettes, though probably a plug of cotton-wool in theend of the pipette is sufficient to prevent contamination inthis way. Absolute asepsis must be observed. Air-borne

organisms such as B. subtilis and B. mesentericus do not,so far as my experiments go to show, nullify the test in48 hours, but S. pyogenes aureus and, to a lesser extent,S. epidermidis albus will, even in the presence of toluol,cause sufficient change in the serum with the subsequentpassage through the dialyser of the breakdown products in24 hours, thereby rendering the result of no value. Thiscan be understood when the liquefying action of these

organisms is remembered. The presence also of hæmo-

globin in the serum renders that sample utterly useless forworking the test.

In these cases the blood was taken with allthe precautions adopted in doing a blood culture.It was collected by means of a syringe, transferredto a sterile tube, and centrifuged at once. Theserum was then drawn off and used for the testwithout any delay. The serum ought to be clearand straw coloured. The opalescent serum obtainedfrom a patient shortly after a heavy meal is notreliable, since it contains dialysable substanceswhich give a positive result in the tube containingserum alone, so that the colour obtained in thatwith carcinoma tissue may also be due to the samecause.

In some cases at the beginning I put my bloodinto cold storage to allow the separation of serumto take place. The serum so treated gave negativeresults, whilst serum from the same patients ifused fresh gave a strongly positive result. Thisferment appears to be specific for cancer tissue.Serum giving a positive reaction with carcinomatissue gave a negative one if placental tissue oregg albumin was used. It is specific for cancertissue in general, but will work equally well in allvarieties of carcinoma, as will be seen from thefollowing list of cases. In the first place I did thetest on 25 cases which were undoubtedly carcinoma,and then on 20 odd cases in which carcinomacould be excluded beyond reasonable doubt, andin two cases beyond all doubt, as they subsequentlyfound their way to the post-mortem room. Thetest was positive in all 25 cases of carcinoma andnegative in the controls. In one case, whichsection has proved to be a carcinoma of the

larynx, a negative result was recorded, possiblybecause only 16 hours were given for incubation.

As can be seen from this list 14 were confirmedby section, the nature of the growth in these casesall being recorded. Of the other cases the tongueswere inoperable with secondary glands, the remain-ing breast was a cancer en cuirasse. The stomachcases were proved by clinical signs, test meals, andlaparotomy. The carcinomas of the cervix were

inoperable, a laparotomy being performed in onecase. The rectum, the gall-bladder with jaundice,and the larynx with secondary glands necessitatingtracheotomy were clinically undoubted cases ofcarcinoma. In all these the test was positive.To place against these are the controls which

gave negative results. So far I have not had a

patient without carcinoma who has given a positiveresult. The controls include healthy patients andthose with fractures, septic hands, tertiary syphiliticand tuberculous ulceration. There are some otherdoubtful cases which have not yet been proved byoperation, post mortem, or subsequent history.In addition there are a few cases which I thought

worthy of individual notice. For permission to

publish these I am indebted to the various membersof the clinical staff at St. Bartholomew’s Hospital.CASE l.-A man, aged 66, was admitted under Mr. H. J.

Waring complaining of stoppage of the bowels. He gave ahistory of increasing difficulty in getting his bowels open.The calibre of his motions had got decidedly smaller. Therewas no history of passage of blood or mucus. For five dayshe had passed neither fasces nor flatus. A colostomy wasperformed, an annular stricture of his pelvic colon beingfound. This was freely movable, and on subsequent resectionproved to be a columnar-celled carcinoma. Test posztive.CASE 2.-A woman, aged 52, was admitted under Dr.

Herbert Williamson, complaining of abdominal pain. Onexamination a tumour was felt rising out of the pelvis to thelevel of the umbilicus. Per vaginam the pelvis was occupiedby a fixed mass which could not be differentiated from the !

abdominal swelling. There was marked oedema of one lower

extremitv. The patient was thin and anaemic. The diagnosiswas made of ovarian cyst (? malignant). A laparotomy wasperformed and the swelling removed. A section showed itto be a papilliferous ovarian cyst in a degenerated condition,but with no evidence of malignancy. Subsequent to theoperation the oedema of the leg has completely disappeared.Test giegative.CASE 3.-A man, aged 32, admitted under Mr. C. Gordon

Watson with a swollen left testicle. He gave a history ofenlargement of the left testicle for two years, with a rapidincrease in size for two months previous to admission. A

hydrocele on tapping yielded clear serous fluid. The swell-

ing was painless and testicular sensation was lost. Wasser-mann was negative. The testis was removed and sectionshowed it to be a carcinoma. This patient has been seensince and now has a local recurrence. Test positive.CASE 4.-A woman, aged 34. was admitted under Mr.

W. McAdam Eccles complaining of a swelling of theumbilicus. Beyond slight induration around the navel

nothing could be felt. A piece removed for section showedthe structure of a simple adenoma with no evidence ofmalignancy. A laparotomy revealed a large mass in thestomach with a secondary swelling on the deep surface ofthe umbilicus, which section showed to be a columnar-celledcarcinoma. Test positive.

Conclusions.—There is here, I think, sufficientevidence to show that the blood of personssuffering from carcinoma contains a substanceabsent in the blood of all others, and that thissubstance has a proteolytic action on the carcinomatissue only. There are also several factors whichpoint to its being of the nature of a ferment. If theserum from a patient is left to get stale it becomesinactive, but the addition of a trace of fresh humanserum will activate it again. The reaction takes

place best at 37° C. At room temperature the reac-tion does not occur, whilst heating the serum to ,

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55° C. for five minutes inactivates it beyond recall.If, then, as is maintained, this substance is of a

protective nature it would be natural to expect tofind it present in larger quantities in patients whowere in good general health. The results of thesetests point strongly to such being the case. I havenoticed throughout the whole series that a patientwith a growth of the tongue or of the breast whois in good general condition will give an intensityof colouration in 12 hours which a patient in a lowstate of health would fail to give in 24.The case of carcinoma of the larynx which gave

a negative result only brings this test into line withothers. No pathological test known to us is in-fallible. It is obvious that for practical use such atest must give a reaction in the early stages of thedisease. Two of the tongue cases were earlylocalised ulcers, one intestinal growth was smalland easily removable, whilst one breast case was anearly scirrhus. All these gave a markedly positivereaction in 24 hours.The facts set forth here do, I think, point to the

test being of some practical advantage as an aid inthe diagnosis of carcinoma, especially in such sitesas the stomach and bowels, thereby allowing earlysurgical interference. These results have all beenobtained working in the pathological laboratory ofSt. Bartholomew’s Hospital, where the kind sug-gestions of Dr. Mervyn H. Gordon and Mr. MackenzieWallis have always been at hand.

(Since writing the above, corroborative resultshave been published by some German observers.Gambaroff has gone a step further and maintainsthe possibility of differentiating between sarcoma iand carcinoma by this method.) ’

Bibliography.-Abderhalden: Protective Ferments of the AnimalOrganism, J. Springer, Berlin, 1912; Serum Fermentation duringPregnancy and in Tumour Cases, Miinchener Medicinische Wochen-schrift, No. 8, 1913; Regarding the Question of Specificity of the Pro-tective Ferments, Miinchener Medicinische Wochenschrift, No. 9, 1913.Brandenburg: Albumin Completely Cleft by Fermentation and itsClinical Application. Gambaroff: Miinchener Medicinische Wochen-schrift, No. 30, p. 1644, 1913. Ruhemann : Triketohydrindenhydrate,Journal of the Chemical Society, No. 97, pp. 1436 and 2025,1910; No. 99,p. 792,1911. Fauser: The Protective Ferments, Deutsche MedicinischeWochenschrift, No. 52, 1912; Further Investigation with Abderhalden’sDialysation Method, Deutsche Medicinische Wochenschrift, No. 7,1913.

St. Bartholomew’s Hospital, E.C.

A NOTE ON FIVE CASES OF PORO-CEPHALIASIS IN MAN FROM

SOUTHERN NIGERIA.BY J. W. SCOTT MACFIE, M.A. CANTAB., M.B.,

CH.B. EDIN.;AND

J. E. L. JOHNSTON, M.B., B.S. LOND.,D.T.M. & H. CANTAB.

(From the Medical Research Institute, Lagos.)

Up to the time when Sambon published his

important paper on Porocephaliasis in Man 1 appa-rently but few cases had been recorded. In a

subsequent paper the same author added to hislist four other records. It has, however, beenpointed out by Lohlein3 that the infrequency of theoccurrence of this condition which might be de-duced from the small number of cases on recorddoes not really exist. He records how Seiffertfound porocephali in 7’8 per cent. of necropsiesperformed on coloured railway workers in the

1 Journal of Tropical Medicine and Hygiene, July 15th, 1910.2 Ibid., April 1st, 1913.

3 Beiheft zu Archiv für Schiffs- und Tropen-Hygiene, 1912,vol. xvi., No. 9.

Cameroons, and how he himself, in a series of 118post-mortem examinations on negroes, found 10infected with these larvae. Borden and Rodhainhave recorded cases from the Congo also, so that itwould appear that porocephaliasis is not very un-common in the natives of West Africa.The five cases briefly described below occurred

in Southern Nigeria. The first occurred at Ibàdan,a large native town situated about 120 miles northof Lagos, the second at Calabar, the third at Itu,and the fourth and fifth at Degama. We areindebted to Dr. J. D. Finlay for the interestingaccount of the first case, to Dr. J. Currie for thenotes on the second, and to Dr. A. H. Wilson for therecords of the remaining three.CASE l.-The patient was a native man, aged about 24,

who was brought to the Ibadan Hospital on July 31st,1913. He died immediately after his admission, andin consequence the history of his case is somewhatvague. He is said, however, to have been taken ill fivedays previously, and the symptoms observed were feverand vomiting. At the post-mortem examination, per-formed by Dr. Finlay, the body was found to be wellnourished, rigor mortis was present, and the conjunctivaswere noticed to be deeply stained. All the organs andtissues were intensely jaundiced. Lungs: The right lungwas normal ; the left lung was contracted, and the pleuralcavity was filled with venous blood and dark clot. Heart :The cardiac muscle was soft. No valvular lesion was present.Liver : The liver was greatly enlarged, bile-stained, andsomewhat soft. On its surface, just below the peritonealcovering, were several porocephalus larvas, and in the sub-stance of the organ a few more were found. There were alsosome lying free on the under surface of the liver. The

gall-bladder was filled with thick bile. On section theliver showed the condition known as "fatty nutmeg liver."Stomach : The stomach was contracted and thickened, andDr. Finlay compared its appearance to that of an ox.

Several round worms were present in the cavity. Duodenum :The duodenum was surrounded by a hard mass whichblocked the common bile-duct. On microscopical examina.tion this mass appeared to be of the nature of an adeno-carcinoma. Intestines : The small intestine appeared to benormal, but the ascending colon was adherent to the hardmass referred to above. Kidneys : The kidneys were

enlarged and stained a dark green colour. The larvæ onexamination proved to be those of porocephalus armillatus.Three individuals measured 18 mm., 16 mm., and 15 mm.in length, and comprised 21, 19, and 17 rings respectively.The rings in the middle of the body were 1 mm. apart, andstood out prominently. The breadth of all three was 3 mm.The cephalo-thorax appeared to be identical with that

figured by Sambon for this species.CASE 2.-The second case was that of an old Hausa woman

who was found dead by the police at Calabar in September,1913. Dr. Currie, who was called upon to make a necropsy,determined that death had been due to extensive and long-standing dysentery. In the course of his examination hefound a single larva of porocephalus armillatus encysted inthe edge of the liver. No more of the parasites were foundin other situations.

,

CASE 3.-The patient, whose "age was about 40, was a

native of Southern Nigeria, and an inmate of Itu prison.He was a big, well-developed man. who did not appear to beseriously ill. Only a very indefinite account of his illnesscould be obtained. He first complained of being sick onAugust 5th, 1910, stating that he was constipated andhad vague pains about the abdomen. At the same timehe noticed that his legs began to swell. He was firstseen by Dr. Wilson on August llth, and was found tohave oedema of his legs, scrotum, and abdominal walls. Theabdomen was distended, and contained free fluid. Therewas no enlargement of the liver and spleen, the urine wasnormal, and the heart and lungs appeared to be healthy.He was not very weak, and could get about fairly well. Thepatient was removed to Ikot Ekpene. On August 15th,when he was next seen, there was an increase of the dropsy ;dyspnoea was present, with a cough and frothy expectora-tion. On examination of the lungs moist crepitations were

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