Tnz BIRITrom i AND 811 SEPT. 3,SEPT899.1 3, 188]AHSAADTSAETRAPHASIA TE'STAMENTAMY CAPACITY.AAIY 1 49DICALH RTSJO'UitlgAL 5 8 ANATOMICAL. SIXTY-SIXTH ANNUAL MEETING, I do not wish to go into the general subject of aphasia more OF THE than is absolutely necessary, and therefore I shall use scarcely any of those extremely technical terms which have grown into BRITISH MEDICAL ASSOCIATION, use of late years. I rather prefer to take it, as it were, from the physiologieal side, and to leave the anatomical questions Held at EDINBURGH July 26th, 27th, 28th, and 29th, 1898. as much as possible out of consideration. Still I cannot help saying just a word or two. Twenty, years ago aphasia was chiefly reaarded as loealised in, and associated with, what is PROCEEDINGS OF SECTIONS. called Broca's convolution-that is to say, the foot of the third or inferior frontal convolution, which, with a part of the foot of the parietal ascending convolution, constitutes what is SECTIONS OF STATE MEDICINE AND ealled Broca's lobe considered as a speech centre. But we are now obliged, partly from the physiological and experi- PSYCHOLOGY. mental evolution of the subject, and partly from the, actual, [JOINT MEETING.] clinical developments of it, to recognise that there are at least. Sir HENRY LITTLEJOHN, M.D. (President of the Section of four centres of localisation in the brain, lesions of which may State in the Chair. affect the power of speech and of writing language. There is Medicine) the Broca's convolution, and there is the auditory centre which lies somewhat further back, these playing upon one A DISCUSSION another, the auditory centre transmitting to Broca's convolu- ON APHASIA IN RELATION TO TESTAMENTARY tion the impressions of spoken words through the ear, and the mechanisms of speech, again, being set in motion from CAPACITY. Broca's speech centre in the brain; so that these two centres I.-Sir WILLIAM T. GAIRDNER, M.D., K.C.B., are concerned chiefly with the reception and the production of Professor of Medicine in the University of Glasgow; Physician in vocal speech. Then there are two centres which are connected Ordinary to Her Majesty the Queein in Scotland. with graphic language, with written or printed words- that is to say, the speech which goes by the sight. RETROSPECTIVE. The two centres just mentioned are concerned in the commu- As I understand that time is of great importance in the nications of speech by the ear and the voice, both ingoing Sections, I shall endeavour to make my remarks as brief as and outgoing, while the other two refer to the communica- possible. tions through the eye and the hand, both ingoing and out--- I do not think I can be very far wrong in saying that I going. I think that is almost all I shall think it necessary to trouble you with on the subject of localisation. There is was a very early contributor to the subject of aphasia. In a fifth centre, but I think Dr. Elder and most people admit fact, it had occupied my attention even before that famous that the localisation of this is not very easy. It is supposed chapter in Trousseau's Clinical Medicinze which was to most of to be the centre of ideation of the word as apart from the- us the means of directing our attention to it in a practical mechanism for the production of the word. That centre is sense. It is one of the most splendid chapters in any book of still not definitely localised, and therefore to a great extent medicine that I know, and it retains a great deal of its value we must keep it out of account. It will be sufficient for the- to the present day. I need not say that the literature of present purpose to take account of what I am in the habit of aphasia since that time has been enormous. Perhaps no calling the ingoing and outgoing mechanisms, and if we still subject in medicine has been so largely written about. I will further divide these into those that spring from the auditory mention only a very few of these contributions as being in centre (those that go by the ear to the speech centre) and the English language, and fairly accessible to you all, on the those that go by the eye to the speech centre, and the cor- many aspects of this wide subject which I shall be obliged to responding outgoing mechanisms of utterance and writing, omit. I think we have got enough of subdivision for our present My own earliest paper appeared in the Philosophical Tran- purpose. sactions of Glasgow, i866, not a very accessible place; and in THE MENTAL STATE OF APHAsICs. the Glasgow Medical Journal for i867 there was an account of Now when we come to consider further, we are confronted, a case, with some further general remarks. At the Liverpool in the first place with this ideal question, whieh also be- Congress of I883 I had an invitation from this Association to comes a practical question: Is aphasia consistent at all with open a discussion upon the subject in its more general rela- integrity of the mind? In other words, is a man who is an tions. A report of this appeared in the BRITISH MEDICAL aphasic necessarily prejudiced thereby as respects his mental JOURNAL for I884; but since that time the developments of capacity, that is to say, does he, in respect of his infirmity, the subject have been so great that if I had been asked to necessarily depart somewhat from the normal condition of speak upon it from the more general, and especially from the mind, so that you must regard insanity in a theoretical anatomical, point of view, I certainly should have declined sense as a part of his complaint ? That is a very difficult the task as being beyond my powers. In the admirable book question to begin with, and I cannot afford to deal with of Dr. Wyllie of this city on Disorders of Speech (I894), and in it at length. Most of you know the ingenious argument a smaller book, but scarcely less elaborate in the field which which Professor Max Muller has founded upon the Greek it covers, by Dr. Elder upon Aphasia and Cerebral Speech word " logos," and although I do not go to the extent of Max (I897) ; and, finally, in the most recent of all, the admirable Muller's eontention, yet I admit there is a great deal in it. book of Dr. Bastian on Aphasia and other Speech Defects, pub- " Logos," in Greek, signifies the word, but " logos," also means lished in I898, you will ind most of what is wanting in what the thought, the reason. Max Muiller says that one ex- I say now to you. pression does for the word and for the thought whiclh the word It is, however, only the last of these, Dr. Bastian's book, so represents. In point of fact, he says these are two different far as I remember, that makes the slightest reference to the aspects of the same thing, and they are practically insepar-- subject that we are engaged upon just now. Aphasia, treated able. If that is the case, then you might infer that, philo- from the physiological, from the anatomical, from the patho- sophically speaking, a man who is aphasic is to that extent logical point of view, has an enormous literature, but aphasia deprived of reason, but I do not think we can accept that as a treated from the special point of view of the testamentary practical conclusion. I should be willing to concede, how- capacity of aphasics has had comparatively few contribu- ever, that a human being who had never been otherwise than tions, and these mostly abroad. I will not name them, be- aphasic, who was congenitally deficient, let us say, in Broea's cause it would take me too far just now; but in a very inter- lobe, or in any of the mechanisms which go to make the- esting article by Dr. Byrom Bramwell in the BRITISH MEDICAL speech faculty, could never grow to the "logos," and so- JOURNAL for May 22nd, I897, you will find most of them fully become a reasoning animal: he could not rise much above the referred to. That is all that I can afford to say in the time at level of a dog, an elephant, or a horse. That I should be, my about the literature of this question. willing to concede. But when we come to the case of a mom disposal past [19661. 582 Km J D 1 SECTIONS OF STATE MEDICINE AND PSYCHOLOGY. [SEPT. 3, I898.

who is, by a sudden accident, lamed as regards the mechanism not sufficiency of mind to make it, or that she was weak and of this particular faculty, having had all his reasoning pro- was led into making it by other people." cesses well developed beforehand, I am unwilling to I think that is very much in accordance with the way in admit that he necessarily suffers any derogation at all of the which I put it in a letter to the BRITISH MEDICAL JOURNAL higher faculties, although I may be pressed into the admis- not long aao (June I2th, 1897), but in reference to an aphasic sion that theoretically he suffers, or is likely to suffer, sooner case: that a will which is a regular document, which is or later, in some degree. Of course, practically, he may suffer drawn out in reEsonable language and signed before two in almost any degree, because other faculties besides speech independent witnesses, maintains itself in the eye of the may be incidentally involved, as, for example, when an law-it proves itself, as it were; in other words, it throws aphasic is also comatose; but that is all I can admit. the onus probandi entirely on those who dispute its validity, The point here is how far does this either theo- and in the absence of clear proof to satisfy the jury either retical or practical laming of one faculty interfere with that the testator did not make the will or that he did not a man's capacity to make a will ? 1 do not think know what he was about, that he was not fully conscious of that is a questioni which can be answered in any general what he was doing when he made it, or, on the other hand, sense, but in order to get on the lines of our subject I must that he was misguided by interested parties, the will holds, direct your attention to what is the legal position in making and must hold. That is the position of the law at present in a will, how much intellect it requires, what, even in cases Scotland, and I believe also in England. that are not aphasic, are considered to be difficulties or How is that position altered by the case of aphasia? To doubts in the way of constituting a legal disposition of make a long story short, I would say that my view of it is property, and on the other hand, the extent to which the briefly this. I might say a great deal more about the details, legal instrument, commonly called a will, maintains itself but my view of the principle is briefly this, that the fact of against difficult positions by the force of its own character, as aphasia shifts the onus probandi. The fact of a hasia (unless it were. These are all very curious questions, and I should it be very limited in extent), interferes either with the hardly trust myself, not being a man of any legal information;, graphic and visual speech processes or with the auditory and to give any dicta upon them. It is, therefore, extremely vocal speech processes, and therefore throws the 0onU8 probandi lucky for me that we have had the subject presented within upon those who consider the will genuine, or wish to prove the last few days by the Lord President of the Court of the will genuine. It makes a difficulty in the way of a tes- Session, Lord Robertson, in words which can hardly be tator giving expression to his true desires and his true will, exceeded in precision as applying to this matter. The case he and those who support the will have to prove that the diffi- was dealing with had nothing to do with aphasia; but, never- culty was successfully overcome. This is not saying that the theless, it drew from his lordship a statement as to the legal will is technically bad because it was made by an aphasic position in respect to testamentary capacity; a statement person; that is not the position I am taking at all. I hold which I have never seen exceeded in precision for our present that an aphasic person- will push it to the full length of subject. There are, no doubt, Englishmen here present, and saying a man completely aphasic, but not otherwise insane or perhaps it may not be quite clear to some of them how far stupid-has, as regards his inner mind, probably the full the legal position is the same in England; but all I have to capacity of making a will of some kind. I do not say as good say upon that is that if the law and the state of the facts is or as elaborate a will as you or I could make, with the assist- not the same in England, you will have to show cause, as the ance of a lawyer, but he has quite sufficient to meet those law would say, how it is not, and why it is not. Because you legal conditions required for a simple and natural disposition may depend upon it that we Scotchmen will maintain that of this means. our way is the right way, and that the Scotch law, founded on I take for an illustration of this the case of M. Pasteur, who the civil law, and coming down to us in a long proces- had a left-sided paralysis, a lesion therefore on the right side sion of generations, is a much superior law to the of the brain, when I met him in London in i88I ; nevertheless, English judge-made law, which is a thing of shreds and he continued to manage that admirable laboratory of his, he patches. Taking the Scotch law, I take it for granted that I was the administrative head of a large scientific research de- am presenting the real first principles of the whole subject; partment, and of his mental capacity no mortal can entertain and the English law, so far as it is not in accordance with those a single doubt for a moment, even for much more complicated principles, has to get itself into accordance with them. Lord transactions than making a will. He was not an aphasic, of Robertson said this: "He must remind them (that is, the course; but he might have been so, had the lesion been on jury) that they had not got to try the question whether in the other side of his brain. Now M. Pasteur made the shortest the general sense the woman was sane or insane. The ques- and the simplest will that I ever heard of. It was this: " I tion was much more narrow and limited. It had reference to give all my goods to my wife." Is there the least reason to this particular will-had she enough mind to understand it, suppose that if, instead of being on the right side of his brain, and did she understand it ? because there were many people that lesion had been on the left side of his brain, even if in this world who had got what might be called a crack in Broca's lobe, or the auditory centre, had been destroyed, that them, and were really eccentric, and yet their wills were per- M. Pasteur would not have been able to form that will in his fectly good. They might think that it was too complicated own mind, would not have been able to make a valid will for the woman; and if so, then they would find against the leaving everything to his wife, provided he could have, some- will. On the other hand, they might think, although they how or other, by signs, or in some way, positively and clearly had heard a good deal of trash about the woman's eccen- impressed everyone that that was his will, and had got that tricities" -[observe the contemptuous way in which his lord- intention, somehow, put into a proper legal form? Illave no ship brushed aside all merely theoretical inferences tending to doubt whatever that his testamentary capacity under such an insanity]-" that still she had enough sense to make a will aphasic attack might have been unaffected except as regards if it was a will that she could understand. It was to be ithe outward mechanism of language. The difficulties, how- observed in favour of the will that it was not very compli- ever,4 in a practical sense, may be serious; for a flaw in the cated if they thought the woman really wanted it. They mechanism either of reception or of production-either in the then would have to consider whether there was satisfactory ingoingi or the outgoing mechanisms of language-may prove evidence that her mind was applied to it; but in the mean- Ito be something like a five-barred gate in a steeplechase: it is time, as regards the woman herself, no doubt she was a person an additional obstacle to be got over, and the multiplication of rather low intelligence. She had not been well-educated, and of these obstacles may incidentally preclude the possibility of there was in the family a strain of eccentricity." Then his lord- giving effect to an intention which, nevertheless, may be quite ship went into the details of the case, with which I will not clear if the testator could only get it out. trouble you, and theni comes tlis inportant statement: " They Now the question is, how far these difficulties go in a par- were left a good deal in the dark as to wlat slhare tlib woman tticular case. Dr. Bramwell, who I hoped would have been in had in the making of the will at all. His lordship's own im- tthis Section, has tackled this subject with his usual industry e pression was that she did not want her relations to get the aand completeness, and the only fault of it is that he has made money. But it was for the jury to say wlhether this will was iit so excessively complicated in his way of stating it, that I her will. They must not the will unless they really aam quite sure if I read the whole of it to you you would be thought that either she was unfit to make it that she had quite overwhelmed (as, indeed, I am myself) with the ex TM ftmm SEPT- 3; i APHASIA AND TESTAMENTARY CAPACITY. IMMILC" JOVAXAZ 583 898.1 = I treme subtleties of the argument. There are, perhaps, one saw in consultation a great many years ago a gentleman or two points where I should be disposed to differ from ilim, who became aphasic as the result of a hemiplegic attack. but I am not going to speak upon these just now, because I A friend of mine had married his daughter, but I did quite concur with him in his general statement of principle not see much of this patient latterly, as lie went away to that the question whether an aphasic person can make a will reside in England, wher e he died. Since this discussion and how far he can make a will, is a question of detail en- arose I took occasion to enquire whether he had made a will tirely; it is a question whliehl must be submitted to a jury on after he became aphasic. I found lie had not, and further- the basis of the individual facts of the individual case, and more, that lie would hiave liked to have done so, but the con- has got to be fought out in a court of law, not upon any ab- scientious people wlo were about him did not think lie was stract principle at all-I have stated the principle as far as I competent to do it, and thlus, although lie was, in a sense, all think it will go-but upon the individual details of the right as to his mind, lie was so deficient in the power of expres- individual case. In. fact, I apply to aphasia just the same sion as to have beeii regarded as not competent to give effect rule as Lord Robertson applied in the case I have quoted. It to what lie was known to have intended and desired to do. is not a general question of law, it is not a thing which can And thus (as his son-in-law wrote to me lately), tlhough almost be put into legal or into physiological categories at all. any change in the disposition of his propel ty after Iiis The question in that individual case was, Did the woman daughter's death, had lie made it, would have been more or know what she wanted ? Did she form a clear conception less in the interest of her family, and althouglh his own wishes of what she wanted, and did she succeed in giving effect to (in a general way) were known to them, yet the difficulties to that conception in the particular document that passed for be surmounted in the way of expression were such that her "will'"? Or was tlat document not really her will at all, (althouglh the son-in-law was a medical man) no attempt was but inspired or instigated unduly by others taking advantage ever made to put anything on paper, the original disposition of her infirmities ? These are exaetly the questions of detail (made before the aphasia) remaining unaltered to the last. that equally arise in dealing with the will of an aphasie. I regret very much that the exigencies of time and of space I happen to have some very interesting documents, which preclude me from making any more detailed references to I propose to hand round, only please observe that there must these and other cases, and also from discussing the general be no names mentioned at all. These are some attempts at subject more at large withl relation to the different kinds of utterance in writing in a case of aphasia recently under the aphasia and agraphia. care of Dr. Sinclair of Dundee; the case of a gentleman, well educated, and himself a very able lawyer and man of business, whom I saw in consultation, and who died aphasic. It was of [POSTSCRIPT BY SIR W. T. GAIRDNER.] great importance to get something done-it was not making a As this case is a really curious one, and is ceitain not to be will in this instance, but it was withdrawing from a set of ever more particularly recorded, it may be as well here to business transactions which he was eonnected with as factor insert the precise terms of the letter referred to by my friend or trustee, and it was of great importance to get this effectively whom I shall call Dr. X. The aphasic patient is referred to as done; but it was found to be impossible, and had he lived Mr. Y. longer there would have been an imperative need to apply to " In reply to your letter, Mr. Y. made no will after his the court about it; even seizure; the estate was dealt with in terms of a will made because as regards the simple assent before my marriage with his daughter, and of course before or dissent to a simple proposal it was found impossible to ob- died tain a clear or consistent "Yea " or "Nay." Yet this gentle- my wife's death; my wife before her father. For con- man seemed to be, in a general way, clear enough in his intel- venience of all parties interested he signed a document giving ligence except as regards language, and there was no apparent power of attorney to his two sons to give receipts for dividends, ground for questioning his sanity.i etc. I do not think lie knew what he was doing thein, but it Another case wlhich I want to refer to is the one I myself was a matter in which everyone was in agreement. Had he stated inaletter to thle BRITISH MEDICAL JOURNAL of June 12th, been able he would, I am sure from a conversation I had with I897, but as it is all in print, and as it contains a great deal of him after his daughter's death and about a year after his the substance of what I have said, I will not detain you with seizure, have alteredc his will somewhlat. We were very it. It is the only case in which I liave been persoinally con- friendly and he kept saying that if he had only thought that cerned where a dispute has arisen about an aphasic will; and his daughter's death would have occurred before his own he it would have been a very curious case indeed had it come would have arranged differently. But he was never in a con- into eourt. dition to give a clear asseint to any special point. He was to the end confusing and misnaming coins, dates, and occa- There is just one more case to whlich I must briefly refer. I sionally people." Z_ 1 The documents, wlhlich welre placed at the disposal of the iimectinlg in connection with the above very brief remiiarks, ale t f considerable initerest as showing in detail the gr-eat aimiounit of initerference botlh wvith the ELDER, M.D., ingoing processes tlhrough the auditory centie amid the outgoing through II.-WILLIAMl F.R.C.P.F., the graphic centre in regard to tlhe receptioni a,nd productioll of words Plysiciani to Leitli Hospital. and even letters. In multiplied attemiipts at writinig to dictation tllere is WHETHER a patient wlho suffets from aphasia is capable of only in one or two inistanees such an amount of resemblance to the word making a valid will proposed as would be legible to a thlirid party. In onie instance an Arabic (or exercisiiig his civil rights) is a ques- numeral (67) is fairly well written, but the rest of the address (Iiis owIn tion which it would be as absurd to answer with a " Yes" or a house) is a mere collection of scratches, witlh barely a trace of tlhe letters "No" as it would be to answer in a corresponding affirmative indicating the namie. His own and his sister's niame aire equally difficult, or negative fashion the question wlhether a patient if not impossible, to deciplher; on the other hand, he lhas oni one occasion .suffering written " sui-mmilel " a,nd "winter," not well indeed, but quite ilntelligibly. from cerebral tumour is capable of making a will or niot. Each He was able, apparently, to read his owIn name on an enivelope addressed ease must necessarily be judged on its own merits, and an to hiimself, and lie could usually, but not always oi consisteintly, carrly out answer given according to the symptoms whichl the patient a direction given himn by spoken words, as tlhus: " Hold up onie finger." " Put out your tongue." " Close your eyes." " Take off your eyeglasses." showed at the time that the will was made. At time same Dr. Sinclair writes in regard to the particular questions referred to above time, a few general principles can be laid down to guide us in as follows: On Marchl i6th, i898, Mr. Z. lhad an attack of right liemiiiplegia determining of the testamentary capacity of a patient suffer- with aphasia, and I send you some records of that condition. Oni June 5th he had an attack of cerebral hlemorrhage witlh convulsions and uncon- ing from aphasia. sciousness, and he died comatose on June 7tll. There is no doubt that At the oiitset of our inquiry we are met by the legal ques- Mr. Z.'s whole appearance anid deiimeanoulr wer-e those of a man wlio was tion: Whlat amount of intelligence or mental capacity in a- quite competent in idea to give inistructions as to the direction of his person is necessary in order testamentary affairs, and as his position of judicial factor for the trustees of an im- that the act which portant firm of business men was one of very great consequemie to his has been executed by that person may legally stand as his own estate as well as to the family and the creditors. his law agent will-or what amount of intelligence or mental capacity is it and all concerned were most anxious for hiis fiat. But the Inotes I senit necessary for a person to shiow in order to give directions to will show that at Ino timiie from his seizure on Ma,rch I6th last was lie able to give directionis on whichl reliance could be placed, eveni wlhen only a someone else to draw out his will? That is a general question simple assent oriegative was asked. In sioit I could never ascertain I must leave to others to answer, but I presume that a person, what his will ini the matter actually was. If ad hiis life beeii muich more in order to make a valid will, must in the first place be sane prolonged it would have beeni necessar-y to apply to the Court of Session lor his dischaige fromii the office. This, as you will readily understand, enough, and of sufficient strengtlh of mind, to know what he was a measure from whiclh his friends ratlher slhranik at the close of a lonig is doing, and to judge of what the effect and consequences of and honourable such as his. his intended disposition may be, and in the second place be 584 SECTIONS OF STATE MEDICINEMEICN AND .P&,YCHOLOGY.GYIET.3198LSEPT- 3, 1398, capable of carrying out in his actions what he psychologic- possible, of course, that a person both word-blind and word- ally intends; because, as is well known, to take a simple case deaf might have acquired the power of reading by the touch it is quite possible that a person may mentally desire to say and muscular sense, but such a case would be very ex- " No" and " Yes " by the outward expression of his mental ceptional.6 action. Not being able to understand any form of language, It must be laid down as a general principle that no one he would in all probability not be able to communicate his ,can make a will who does not possess the power of under- wishes by producing any form of language. In auditory standing and of producing language of some sort. I use the aphasia, if the motor articulatory centre acts at all, the word language ratlher than speech because it is not so apt to patient is paraphasic, that is, he can speak words, but these lead to confusion, although " speeclh" has come to be used words are not necessarily the correct ones, nor is he able to in almost as general a sense as "language." correct himself, because he cannot hear what he has said. In order to make a will it is necessary for an individual to Often such cases talk gibberish, especially if the auditory be able to communicate to others by means of some form of centre is not completely destroyed, or if the right auditory language what lie would like to be done after his death. It centre is particularly active. is necessary by law that the wislhes or desires of the person His other productive language centres are even less capable 1be put in writin-g. It would not, for instance, be held to be of communicating with his fellow-men than his motor articu- .a will if a person simply indicated by signs before he died latory centres. If he can write at all, it is only some very that lie wanted such and such a tlhingf done, nor would it be familiar words or letters, such as his signature or even the held to be a will if a person gave directions by word of mouth. first letter of his signature, and he may show "letter or The simplest and most primitive form of will is a holograph familiar word intoxication" in writing. It is to be noted will-that is, a will written and signed by the testator him- therefore, that a signature present on a document is no evi- -self. The law, however, recognises a will that has been dence that the person understood a word of what was in the written by someone else, provided it is signed by the person document, nor is it evidence that the person had command of makiiig it. In all these cases, however, it is necessary for language sufficient even to write. The signature in such a the signature to be attested by witnesses. The point I wish case is written automatically by the graphic centre, and is to make just now is that it is necessary for a person to be analogous to a reflex act. of at least some in order that lie may As a auditory aphasic is therefore incapable of possessed language complete a make a will, although the amount of language may not neces- making a will, so probably are all cases in whichthere is sarily be much. distinct impairment of the auditory word-centre. In cases in He must be capable of understanding language, so that he which the impairment is very slight, then the symptoms of and are often more distinct, the patient knows either what he reads or what is read to him. This paraphasia paragraphia written implies that he can hear and understand words, if he cannot oIn the one hand being able to understand spoken and read nor understand pantomimic language; but if he can and printed language better, but on the other hand producing read and understand what he reads, then it is not necessary language more freely, but often quite inaccurately. him to hear nor understand If he In such cases it would often be very difficult to say whether for pantomimic language. same can understand pantomimic language, the question might such a patient was capable of executing a will, and the arise whether it is necessary for him either to be able to hear difficulty would be met in cases of conduction aphasia, in or to read. It is possible also, of course, for a person's intel- which the auditory and visual word-centres escaped alto- ligence to be reached in other ways, as, for instance, by means gether, but the patient only showed the symptoms of para- and with These cases .of the muscular sense. On the other hand, given that a pliasia paragraphia word-intoxication. and _person understands what is in a document by any of these understand what is said to them, and can read writing methods, it is not necessary that lie be able to speak in order printed matter, but, in attempting to speak or write, they use -tlhat he may execute a testamentar y deed. He may indicate incorrect words and repeat themselves. They know, however, he wishes means of or or in that have or written incorrectly, but still it might whiat by writing, by pantomime, they spoken a -otlier ways. How, therefore, would the symptoms of the be difficult to say whether they were capable of making valid will. different forms of aphasia affect the testamentary capacity of must a patient suffering from each form ? There is one very rare form of auditory aphasia that have be on a different from the and that is the From the one form of aphasia of Broca, the varieties put footing others, cannot increased till at least one author recognises twenty-eight, but infrapictorial or subcortical variety, where the patient tlhese varieties are only. theoretical, and practically there are hear words, but can understand words written and printed, and can and write Such a case would be four clinical types, although I believe several varieties of speak correctly. suf- more or less importance of each of these types are seen occa- capable of executing a will provided lie had sionally. Of these types, two are sensory, and are an inter- ficient to read, but he would, of course, not understand what ference with some part of the reception and understanding of was read to him. language mechanism, and two are motor, and are an inter- ference witlh some part of the mechanism which has to do VISUAL APHASIA OR WORD-BLINDNESS. The are: audi- Here we would have to consider whether we had with the production of language. sensory (i) practically or -tory aphasia or word-deafness; (2) visual aphasia or word- to do with a case of pure word-blindness (infrapictorial blindness. The motor are: (i) motor aphasia or aphemia; subcortical visual aphasia, or of cortical word-blindness (pic- torial or cortical visual aphasia). In (or pure) (2) graphic aphasia or motor agrapllia. subcorticalable to read and There are many general symptoms affecting the mental or word-blindness, the patient would not be intellectual capacity of the patient which may be shown by understand either printed or written matter, but he would be the of any cerebral and have a direct able to hear and understand spoken language, and he would subject lesionl, very a there- bearing on the question of testamentary capacity. I put be able to speak and write correctly. Such patient, be of a will, provided the aside, however, those symptoms, and limit myself to the fore, might quite capable making the symptoms peculiar to each variety of aphasia. contents were read to him or he wrote them himself; but case would be different with a patient suffering from pictorial AUDITORY APHASIA. or cortical word-blindness. In that case lie would not be A person suffering from complete auditoryaphasia would be able to read nor understand written or printed language, nor not would he be able to write either voluntarily or to dictation. incapable of making a will. Complete auditory aphasia is only implies word-deafness but also word-blindness, because It is to be noted that here also, I believe, such a patient it is necessary for the auditory word centre to be capable of quite capable of writing his signature, or very familiar letters, the automatic action of the centre. But the fact acting in order that a person may understand what he reads, by graphic docu- so that the person with auditory aphasia would not be able to that he could not as a rule append his signature to any he understand what was in the read intelligently, nor would lie be able to understand what ment, even although might interest- was spoken or read to him. The understanding of panto- document from having it read to him, raises the very mnimic language might also be lost, but if it were present it ing question as to whether such a document would stand, he carried out the necessary in Scot- would certainly be very difficult to communicate to such an provided legal formality of individual the contents of a testamentary document. It is land of getting a notary to sign for him in the presence Thu Ba8ir SEPT. 3, I898.] APHASIA AND TESTAMENTARY CAPACITY. _MiDICAL JOURNAL 58°

witnesses. I believe that in a case of uncomplicated cortical cases is guided by the grapllic or cheiro-kiniesthetic centre on word-blindness the patient is quite capable of making a will, the left side, the impulses passing through the callosal fibres provided the contents are accurately read out to him before to the centres for the left lhand in the right cerebral cortex; he gives instructions to the notary to sicgi for him. The but whatever tlle explanation of such cases, a case might patient is practically in the position of a personl who is blind, arise where a patient paralysed on the left side from an in- with, of course, the additional general symptoms due to the ternal capsular or subeortical lesion might write his own will fact of his having a cerebral lesion. in mirror writing, witlh his left lhand, or might sign his will, writinof in this mirror faslhioii. MOTOR APhASIA OR APHEMIA. Sueh mirror writing, as I hiave pointed out elsewhere, is In this condition the testamentary capacity would vary often an exaet reproduction of his ordinary right-hand writ- according as the lesion was in Broca's centre alone (pictorial ing when looked at in a mirror. A person writingf a will in or cortical motor aphasia), or subcortically to Broca's centre this faslhion ouglht, I believe, to be considered quite eapable (infrapictorial or subcortical motor aphasia), wlat Bastian of executinig a testamentary deed if his otlher symptoms did calls aphemia. If infrapictorial or subc,rtical motor aphasic, not point to incapacity, but it is questionable whether it, the patient can read and understand written and printed would be lheld valid by law. language, can hear and understand spoken language, aind can write either voluntarily or to dictation, and therefore could CONCLUSIONS. write his own will; but it might be difficult for anyone to The conclusions I would draw from a consideration of the take directions from him for the making of his will, as lie wlhole subject are: would not be able to speak; but if an educated person, his i. That organic diseases of the brain may render a patient knowledge of language would be so perfect that hie would be incapable of making a will, and that some form of aphasia able to read will before he signed it. Hysterical mutism I may be produced also as one of the symptoms of the organic believe to be the functional form of this variety, and disease. hysterical mutes, therefore, are capable of making a valid 2. That some forms of aplhasia may render a patient in- will. capable of will making. In cortical or pictorial motor aphasia. we have a different 3. That auditory aplhasia, if at all well marked, incapacitates condition, however, and I am afraid there must still be some a patient from will making. difference of opinion ass to the testamentary capacity of 4. That some other forms of aplhasia, such as pictorial word- patients suffering from- the uncomplicated form of this dis- blindness, pictorial motor aplhasia, and graphic aphasia, may ease. TJntil within the past few years it has been believed render a patieint incapable of making a will, not necessarily that patients suffering from this form were almost always from being mentally incapable, but from the difficulty of agraphic. Bastian has, however, produced evidence which he carryingof out tlle legal formaiities. believes shows that patients with a lesion in Broca's centre, 5. That these difficulties in carrying out the legal formalities if limited to the third left frontal, do not suffer from agraphlia. necessarily vary according to the law of the particular The chief part of that evidence is a case published by Guido country. Banti, but I cannot say that that case nor the evidence that 6. Thlat simple uncomplicated cases of infrapictorial auditory, Bastian has produced is quite convincing, and the question infrapictorial visual, and ilnfrapictorial motor aphasia, are is therefore still in doubt. This, however, is not the place to capable of valid will making. enter into a discussion of this question. Sufficient is it to mention it, and to get over the difficulty by stating that ,clinically by far the majority of cases have agraphia as well III.-T. S. as motor aphasia, and therefore these cases would not be able CLOUSTOxN, M.D., F.R.C.P.Edin., to write a will, and if they signed such a deed, the simnature Pliysiciaui Superiiitecideiit, Royal Asyluii, Morniingside, Edinburgh. would be an automatic one, anid the will, to be legally exe- DR. CLOUSTON said there were two points which he in- cuted, would in Scotland 1-tquire to be signed for him by a sisted every man must attelnd to. The first was the test notary iti the presence of witnesses. But there is another quest o i, whetlher it was the will of the individual, or whether point about these cases still somewhat in doubt, that is, it had been suggested to him. The second was that in making whether a patient with pictorial motor aplhasia can read and the will of any aphasic patient it was the duty of every understand what lie is reading. I believe that some cani read medical man and lawyer to put the contrary case. A man had and understand what they reading, and some cannot-tIme left, say, £ioo to hiis wife and £ioo to his daughter--to A. and difference depending on the peculiar psychical constituitioin of B. They were bounid to ask him if it was for B. and C. or for the individual and the method of his education. Patients D. and E. that lie intended the money. No will of an aphasic with cortical motor aphasia can, however, understand what in spite of any judge or doctor, could be a legal and proper will they hear, so that if a deed was read over to them they would unless the doctor had put the contrary case, because an understand its contents, and they could give instruction by aphasic would asseint to anything if put to him in a certain pantomime to a notary to sign for them in the presence of way. It was essential that the mental condition of the would-be witnesses. Here a legal question might arise as to whether testator should be tested by a medical man. Dr. Clouston the instructions given by pantomime would be considered concluded by uraing that two practical points in the actual sufficient. making of the will must be attended to: (I) Test whether the GRAPHIC APHASIA. document is his own, and has not been suggested by others; No true case of cortical graphic aphasia has been authenti- (2) Put tlle contrary proposition, or a different proposition, cated, but in such a case the patient would be able to hear twice at least as to sums disposed of, and as to the persons to and understand spoken speech, to read and understand written whom the money or property is left. No will can be valid and printed language, and to speak correctly, so that his where these two points have not been most carefully gone knowledge of language would be complete except that he into. would not be able to write. He could, however, give- instruc- [It was found necessary owing to the pressure of business tion to a notary to sign for him in the presence of wit- to stop the discussion at this point.] nesses. Similarly with cases of paralysis of the right hand due to subcortical lesions or lesions of the cortical centres for the A DISCUSSION ON right hand, the patient could execute a testamentary deed by giving instructions as in the last case, or he might write with THE PLEA OF INSANITY IN CRIMINAL CASES. the left hand. In this connection a very interesting point I.-CHAS. A. MERCIER, M.B., M.R.C.P.Lond., might arise. I believe that in those cases of lesion subcorti- Lecturer on Neurolo y and Inoanity, Westminster Hospital Medical cal to the centres for the right hand the patient sometimes, Schlool, anid at the Medlial Sclhool for Women, especially if he has been an expert writer, may, when he London. attempts to write with the left hand, write in the peculiar way THE controversy between the medical and legal called mirror writing. I have elsewhere given my views as to thathas ragedforsolongroulil this subject is now rapidly the explanation of this. I -believe that the left hand in such extending. Judges, whiPe ad"eriig, as they consider- them- 1 586 _MurncLLT58. JoVRZ4ALJai,u. SECTIONS OF STATE MEDICINE AND PSYCHOLOGY. [SEPTr. 3, .1898. selves bound to do, to the terms of a well-known formula, not hope to obtain your immediate assent, although I trust contrive so to interpret that formula that upon the whole to secure it before I have finished. It is this: Very few substantial justice is done. Medical men, recognising that indeed of the insane are wholly irresponsible--by which I upon the whole substantial justice is done, cease to contend mean that there are very few indeed of the inaane whoi for an academically perfect formulation of the law, and re- ought never to be punished for wrong-doing. Or, to put it cognise that such a formula might be found. after all, to be with brutal plainness, it is in ma-ny cases right and just to inapplicable to outlying and exceptional cases without that punish an insane person for wrong-doing. I am afraid that, laxity of interpretation which renders the present law prac- I have made your flesh creep. There is doubtless a very tically effectual. No useful object can in my opinion be prevalent floating body of sentiment, which gets expressed served by a prolongation of this controversy, and I do not from time to time in expressions of horror and disgust at the propose to have any more to say with regard to it. notion of ever punishing a lunatic under any circumstances; for any act. The English Commissioners in Lunacy some WHAT MENTAL CONDITIONS SHOULD EXONERATE. years ago wrote in their report of a certain asylum that they The aspect of the plea of insanity which does demand dis- observed that a certain course of dealing with a patient had cussion at the hands of medical men appears to me to be this: been adopted, and they added: "We are of opinion that Are medical men agreed as to the mental conditions which this is punishment pure and simple "-or words to that effect. ought to exonerate a criminal from punishment, and if so, No further censure was uttered, evidently because it was felt what are these conditions? that no further censure was needed', or indeed that no stronger The first question must, I think, be answered in the nega- censure was possible; the implication, the omitted premiss, tive. I know of no statement of such conditions that has being manifestly that no lunatic ought under any circum- received the general assent of the . Several pro- stances to be punished. With a full appreciation.of the positions purporting to formulate these conditions have from obloquy and odium that I shall incur by the statement, I time to time been proposed, but no one of them has succeeded affirm that for very many of their misdeeds the majority of in obtaining universal or even general support. To every one of lunatics ought to incur some punishment; and, further, I them the opposition from within the medical profession has affirm that explicitly or implicitly this is the opinion of every been at least as strenuous as the opposition from without our practitioner who has had experience of the insane; and, ranks. While, therefore, we inhabit a dwelling so copiously furthermore, I affirm that punishment of the insane in provided with glazing, it would be well to refrain from the some form or other is in practice'in every institution for recreation of throwing stones. While no agreement upon lunatics. this point has yet been reached, it does seem eminently desir- able that such a general consensus of opinion should be PUNISHMENT BY WITHDRAWAL OF PRIVILEGES. attained, and in order to clear the way towards so desirable an Come, gentlemen, let us clear our minds of cant in this end, I should ask your assent to three general propositions. matter. Who is there among you who, if a patient on parole comes in drunk, will not refuse him his parole next time he applies for it? Who is there among you that, when a woman IMMUNITY FROM PUNISHMENT. has been fighting or smashing, will not forbid her to attend First, I ask you to agree that no insane person ought for the weekly dance? Who is there that will not stop the any act to be punished with the same severity as a sane tobacco of a man who is discovered pilfering or bullying? Is person ought to be punished for the same act. Or, in other it denied that these are punishments? It may be said that a. words, the punishment of an insane person ought never to woman who is so violently maniacal as to be fighting and be as severe as the punishment that a sane person would smashing is not fit to attend a dance, and is forbidden for rightly incur for the same act. To this proposition there will, that reason and not for punishment. And it may be said I think, be few dissentients in this room. Every institution that the man who comes in drunk is refused his parole, not. for the insane is conducted in accordance with this principle. as punishment, but as precaution lest he should come in When the lunatic steals, or assaults, or behaves indecently, drunk again. Bnt I expressly exclude the withdrawal of or wrongs his neighbour in any way, he is not put into a cell, punishment for any such reason. I speak of "punishment nor deprived of the society of his fellows, nor is he made to pure and simple," and I say that when a patient has been lie on a plank bed, nor is he placed on starvation diet. His smashing and tearing her clothes, not in an access of acute treatment is not assimilated to that of sane criminals, and mania, but in an outbreak of temper, she would be excluded the reason, the only reason, why it is not so assimilated, is from the dance, not because she was unfit to be present, but, that he is insane. Practically it is recognised every day, and as a punishment. If the man is refused the renewal of his all over the country-nay, all over the civilised world-that parole as a precaution, then the refusal must be permanent insanity carries with it, ipso facto, a certain immunity from But it is not permanent. We rely upon the temporary with- punishment; that the insane offender is not to be treated drawal of the privilege to act as a check in preventing its with the same severity as the sane offender. It would not be abuse in future, that is to say, we use it as a punishment. difficult to show that for this practice there are good sound It is sometimes denied upon another ground that these are scientific reasons; but I do not desire to labour the point, nor punishments; they are, it is said, not punishments, but do I desire to treat the subject from any but a strictly prac- withdrawal of privileges. Why, yes; and so to send a man tical point of view, and that the practice is as here stated must to prison is to withdraw from him the privilege of going about I think be admitted. at large. And to treat him to bread and skilly and the plank The second proposition to which I desire your assent is bed is not punishment, but merely withdrawal of the this: There is for every insane person a certain sphere of privileges of sufficient food and sleep. I say that to stop a. conduct for which he ought to be entirely immune from patient's tobacco or to forbid him the weekly dance is punishment; or otherwise put, every insane person may com- " punishment pure and simple " every bit as much as giving mit certain misdeeds for which he ought not to be punished. him a shower bath. If anyone here is in the habit of allow- We should all admit that it would be wrong to punish a suf- ing pocket money to his patients, he will corroborate me when ferer from delusions of persecution for assaulting his sup- I say that this practice gives him a very powerful control posed persecutor; or to punish a woman with puerperal over their conduct. The prospect of having his pocket money mania for trying to kill her infant; or to punish a general stopped will restrain a patient from practices of mischievous- paralytic for taking a watch that he thought belonged to him ; ness, destruction, and other evil habits. Experto crede. I or to punish a dement for upsetting the lamp and setting the have proved it again and again. And although it may be no bouse on fire. And similarly there are, for every insane per- punishment to deprive a man of his tobacco, as to which the son, misdeeds which, if they were done by a sane person opinion of habitual smokers will be all one way, yet it surely would be rightly punishable; but which, done by the insane cannot be denied that the infliction of a pecuniary fine is it would be clearly and manifestly wrong to punish at all. "punishment pure and simple." Of course, it will be said that I have advocated a return to THE: DEGREE OF RESPONSIBILITY OF THE INSANE. chains and manacles, to the lash and the bed of straw, and all So far, I trust, that I have carried the sense of the meeting the horrors of old Bedlam; and I shall be pointed at with the along with me, but my third proposition is one for which I do finger of scorn as the brutal castigator of the lunatic, when, THEBRITIS8 58 SEPT. 3, 1898.] THE PLEA OF INSANITY. _MEDICAL JOURNAL 587 in fact, all that I have done is to refuse 'to call a spade an 95 per cent., of these indictable offences, were committed by agricultural implement. persons in a state of intoxication. In regard to such authors Let me poinit out that this proposition-that for certain of crimes of violence, how does the law and how do experts offences luiiaties are rightly punishable-is in'volved and im- stand? The " judge-made" law of -I843, as some people term plied in the propositions to which you have already assented. it, would exculpate them from responsibility, for it exactly If it is asserted that no insane person ought to 'be punished meets their case. A person intoxicated cannot and does not with the same severity as a sane person, it is implied that the know the nature and quality of the act, or that it was a wrong insane person ought to be visited with some punishment. act, because intoxication is insanity of the most perfect type, When it is asserted that for every insane person there is a no matter how transient. But while " insane at the time " is sphere of conduet within which he ought to be immune from a proper defence in such cases, how many specialists will punishment, it is implied that without that sphere he ought enter the witness box and testify to that effect ? If they did, not to be immune from punishment. I do not believe any jury would convict of the capital charge. No; the judicial dictum of i843 is not, at all events in regard MITIGATED PUNISHMENTS. to them, at fault. It is not the law that is at fault, rather is The practical inmportance of these propositions with regard it the hesitancy of medical witnesses to take a proper stand, to the plea of insanity is this-that while there are some which is blameworthy, and likewise the fact that the accused ,eases in whieh we may rightly ask the court to refrain alto- as a rule, being poor, have not the means to secure legal aid gether from punishing the criminal, there are many more commensurate with the gravity and responsibility of the case. eases in which we cannot justly demand such complete im- Consequently sucCh cases, for the most part, fall into the munity, but in which we can fairly argue that the criminal is hands of inexperienced lawyers, and matters are made worse responsible to some extent but is not wholly responsible, and by the knowledge that the aid of the specialist cannot be got. that, therefore, while he ought to be punished, lie ought not No fund for such special cases is available in Scotland. Were to be punished with the same severity as an ordinary offender. it in existence, several of the verdicts of recent years would If this attitude be asumed by the medical witness, I feel sure have been different. In some of the worst cases there was that not only will he present his plea in a more just and practically not the semblance of a defence. equitable form, but he will stand a far better chance of hav- It is in this direetion a change is needed. In regard to ing it admitted. His contention will be more in harmony not such cases I would venture to point out some of the judicial only with the justice of the case, but with the sense of the fallacies that have arisen. One hears the occupant of the court and with the feelings of the community at large. Bench sometimes speaking of the "wilful" nature of the This, then, is the aim that, in my view, we should set our- drunken attack, the " voluntarily " induced state of mind of selves to attain. The total immunity of some insane offenders accused, and not least that the death sentenee is a " terror " for some acts, and the mitigation of punishment in more or to drunkards. In none of these views can I concur. Can a less degree for all crimes done by insane offenders. drunken man do a " wilful " act ? I should be inclined to think that tllis is highly problematical, and that it does not WHEN SHOULD THE INSANE CRIMINAL BE HELD IMMUNE? even afford that presumptive evidence required in a court of The acceptance of these principles, if they be accepted, will law. Much might be said against the theory of "voluntary" not help us much, however, to the solution of the practical drinking. Who can say with a degree of certainty in the problem' that confronts us in concrete cases, for in- a very advanced of a chronic drunkard's bout that the drinking large number of cases in which insanity is pleaded, the was voluntary? for that would imply the certainty of an prisoner has not been regarded as insane until the commis- absence of latent or patent physical and mental degeneration sion of the very crime for whieh he is now being tried. If our induced by the vicious or the diseased habit. The former in task were to establish the immunity, or partial immunity, of time merges into the latter. All is uncertainty. Then there a person who is admittedly insane, it would be an easy one. is the supposed deterrent effect whiCh the scaffold is said to What we are usually asked to do is- to show why this off'ender, produce in the minds of drunkards. There could be no who up to the time of the crime has been sufficiently sane to greater delusion, and drunkards were as numerous on the be allowed, rightly or wrongly, to be at large should, now that next " pay day " as ever they were, and deal out violence as lie has committed a crime, receive the benefit of the plea of freely and as maniacally as ever they did. The marvel is insanity. that, instead of having thirty indictments for murder every CONCLUSION. year, there are not I,ooo, and as a eonsequence eapital punish- The speaker then briefly summarised the circumstances ment multiplied a thousandfold. This is an aspect of the which, if proved, would establish the plea, namely: question which is overlooked. The violence of the drunkard i. Exonerating delusion. is not measured, so great is the mental disturbance of the 2. Such confusion of thought that the accused was incap- senses and faculties. It could not be otherwise real; col- able of rightly estimating the circumstances or the conse- sciousness either does not exist, or is of the dimmest. The quences of his act. intoxicated authors of crimes of violence are insane; the 3. Extreme inadequacy of motive. duration of the insanity from a medico-legal point of view is 4. Extreme imprudence in the aet. of no moment, and by the criterion of a possibility laid down 5. The non-concurrence in the act of the volitional self. in I843, the drunkard should not be responsible, and would not if the expert looked at the matter from the point of view now submitted. But if this view be not accepted, then the II.-JOHN F. SUTHERLAND, M.D., crime should be reduced from murder to culpable homicide, Deputy Commissioner in Lunacy for Scotland. as is the case in many countries. Some Scottish judges view I HAVE no fault to find with the criterion of responsibility laid it in this light. If " insane at the time" were proved, there dowii by the judges in in response to the request of the would still be the protection for society by detention in a safe House of Lords for a definiteI843 ruling. The criterion-a simple place of custody. one-amounted to this: Did accused at the time of committing the crimne know the nature and quality of the act, and did III.-GEO. F. BLANDFORD, M.A.Oxon., M.D., F.R.C.P.Lond., he kniow the act was a wrong one? This is a good enough Visiting Physician, Newlands and Otto House Lunlatic Asylun. detiliition for all purposes, and I have not known any injustice DR. BLANDFORD remarked with regard to the vexed question to insane persons result from it in Scotland. It may not be a of responsibility and knowledge of right and wrong, and the perfect law, but on the whole it has worked, thanks to the nature and quality of the act, that many lunatics knew right fairness of the Bench of this country, remarkably well. If from wrong, but they knew it as lunatics. A dog knew right you wish this judicial formula changed, as some seem to from wrong, a child knew right from wrong, but knew it as a think, we have the right to ask-(i) What do'you propose to child. A lunatic knew right from wrong, but the knowledge take its place ? and (2) to state wherein and to what extent it was that of an unsound not a sound mind. This was the has operated unfairly to accused persons. Cases in which the point to be proved. It might be right that he should be held plea is possible are few, because the number of crimes of vio- to be responsible to a certain extent-and it would be for the lence committed by insane persons is infinitesimal when the benefit of many lunatics that they should be held responsible whole is taken into, account. The bulk, perhaps no less than to a certain extent-but instead of hanging a man who com- 6 QTH BRITISH 588 MEDICAL JOURNALN SECTION OF PATHOLOGY. [SEPT. 3, 1898.

mitted a murder through drink, he would send him, not to question of modified responsibility at law, they would require Broadmoor to smoke his pipe for the rest of his life, but to to go to the lawyers and convince that clear-headed set of men penal servitude, where he could do some useful work. that the whole law of the land from the time of the Conqueror downward should be changed in principle. If punishment IV.--JOHN GLAISTER, M.D., was regarded as a deterrent from crime he could not concur Professor of Medical Jurisprudence and Public Health, St. Mungo's with Dr. Mercier's opinion that the partially insane would be College, Glasgow. in any way prevented from doing criminal acts by such graded PROFESSOR GLAISTER said that he generally accepted the pro- punishments. He believed it would be a good thing ifthey- positions laid down by Dr. Mercier, but he was not quite sure could devise a verdict by which insane persons should be that they would all be agreed as to the degree of acceptance. from public life without being sent to Broadmoor. Any amount of general discussion on the general question withdrawn. and of some value, but, after might prove largely interesting DR. MERCER's REPLY. a for a given all, when the responsibility of given person DR. MERCIER held to his that the withdrawal of pri- crime became a question of importance, perhaps of death, opinion then did significance. vileges was punishment. At aniy rate the infliction of a only the importance become of greatest fine was When one of Dr. Suther- In his view there was less possibility of injustice being done pecuniary punishment. the that the land's drunkards stood in the dock on Monday morning the .to insane than to the public. He was of opinion inflicted him a sentence five or growing sentimentalism of the public regarding the responsi- magistrate upon of shillings of certain for modifica- seven days, and the five shillings was the equivalent of the bility criminals, shown by petitions seven and the seven was the equivalent of the five tion of sentence and hoe of insanity, was a distinct days days post pleas shillings. Both were equally punishment. He was surprised danger. after the praises of the Scotch law to which he had listened, to find that in at any rate one respect the despised English V.-ALEX. ROBERTSON, M.D., F.F.P.S.Glasg., law was superior to thejus civile. Dr. Clouston hac said that. Professor of Medicine, St. Mungo's College, Glasgow. we should have to run counter to the whole course of the law DR. ALEX. ROBERTSON said that in the early part of his profes- as it had existed from the time of the Conqueror downwards. sional career he had published a paper entitled Modified But in England a verdict of guilty but strongly recommended Responsibility in Mitigation of Punishment, in which con- to mercy could be returned, and that recommendation was, clusions practically the same as those of Dr. Mercier in considered and effect was given to it by the judge. Having criminal cases, especially those of murder, were advocated. watched the course of criminal trials very closely for some It appeared to him that of late years judges and juries had years he was of opinion that judges and juries were more and made very full allowance for mental defect or disorder, more inclined to consider the mental condition of the prisoner when these were proved to exist in criminal cases, and to admit the plea of insanity, not in total exoneration, but, and that justice was done. He regarded the proposition in mitigation of punishment. maintained by Dr. Sutherland as dangerous to society. His proposition was that if in a condition of drunken- ness one should murder another, the mere fact of his SECTION OF PATHOLOGY. mind being disordered by alcohol-in other words, that lie was intoxicated-should reduce the charge againsthim from Professor W. S. GREENFIELD, M.D., President. murder toculpable homicide. Dr. Sutherland appeared to advocate achatnge in the law to that effect. If such change A DISCUSSION were made, would there not be a temptation to anyone who ON THE AGGLUTINATING OR SEDIMENTING had a feeling against another, probably known only tohim- self, to take two or three glasses of whisky, feign full intoxi- PROPERTIES OF SERUMS AND THEIR cation, and kill the man against whom he had this feeling? For he would comfort himself with the thought that in any RELATION TO IMMUNITY. case he would at any rate not be hanged. But, even though I.-HERBERT E. DURHAM, M.B., B.C., there was no question of feigning, it was very doubtful, in the Grocers' Research Scholar, Camiibridge. case of any drunkard who killed another when drunk, whether INTRODUCTORY. the charge should be modified. In all such cases the criminal SINCE the of serums was first brought It was agglutinating property had many times previously been violent under drink. forward as a means of differential diagnosis between different incumbent on all who were dangerous under drink kinds of allied bacteria, the validity of the principle has to refrain from its use; for, if they took it with that know- attracted a amount of notwith- for their veryconsiderable support, ledge, they were clearly culpable and responsible standing attempt to throw it into discredit as a test acts. All such cases might safely be left to thecommon Bordet's'The of the principle has sense of juries. method. importance agglutinating been raised into a high position by the observation that the blood serum of typhoid-fever patients may acquire this VI.-Professor Sir WILLIAM T. GAIRDNER, K.C.B. property ofclumpingcultures of the typhoid bacillus. This SIR WILLIAM GAIRDNER, speaking not as a specialist but as a observation was made first in the Hygienic Institute of teacher of the art of medicine in general, said what he had Vienna by Dr. Grftnbaum,. working at the suggestion of Pro- consistently taught had been in accordance-with Dr. Mercier's fessor Gruber. The subject was first brought forward by Pro- doctrine. What he had held and taught all along was that fessor Gruber at the Congress ftir innere Medicin in April, there never could be bare justice in regard to the insane until I896. But it would not be profitable to occupy time with there was a different form of verdict allowed from the pre- questions which are mere matters of history. With increas- sent. The jury could say that a prisoner was guilty or not ing knowledge of the varieties and species of bacteria, we guilty because of insanity. He desired that there should be are confronted with ever-increasing difficulties in finding a third verdict allowed-guilty, but insane. criteria whereby the different kinds may be distinguished. Whilst many and important differences may be demonstrated VII.-T. S. CLOUSTON, M.D., F.R.C.P.Edin., by the use of culture media of various composition, yet these Physician-Superintendent of the Royal Asylum, Morningside, Ediinburgh. not infrequently leave us in the lurch at the critical point. DR. CLOUSTON contested Dr. Mercier's position that the stop- We still have a resource to fall back upon in the action ex- pages of indulgences constituted punishment in any sense of hibited by the serum obtained from artificially-immunised the term. It was certainly not punishment in a legal animals. sense, and he considered it would be a dangerous thing SPECIFIC IMAIUNITY. to talk to the staff of the punishment of a patient. There are various ways of applying this principle of specific In all ages the proposal to adjust a punishment in immunity; these may be put under the following three proportion to the responsibility of a man who was headings: admittedlv defective in mind through disease of the brain i. Protective in respect of their power of affording protec- had been found exceeding difficult. With regard to the great ! Ann .fc Unc. Th-Wur, 896, '9. SEPT. 3, 1898.] AGGLITTINATION AND IMMUNITY. THE BRiTISH SEPT.I3, 1898.] AGGLUTINATIONAND IMMUNITY. LIEDICAL JOURNAL 589 tion to normal animals which are infected with the bac- completely, yet only a retardation of death, and not a perma- terium in question. nent protection may ensue. 2. Lysogenic, in respect of their power of determining Many authors have attacked the view of the existence the rapid degeneration of the bacterium in the peritoneal of any relationship or association between the agglutinative fluid of a normal animal (Pfeiffer's test), or in the presence of and the protective action. Unfortunately the number who perfectly fresh blood or serum from a normal animal (Bordet's have actually made comparative experiments seems few, whilst test). those who have argued from clinical ideas without the per- [Strictly speaking, according to my own belief this property formance of experiments appear to be many. It is well known should not be included here. The lysogenic power is pos- tlhat certainformsof protective serumshave absolutelyno agglu- sessed by all normal sera in the fresh state, and is demon- tinating action (for example, diphtheria antitoxic serum); strable when they are brought into contact with sufficiently agglutinating properties are, therefore, not essential in pro- weakened bacteria; the part played by the specific serum is tective sera. The problem before us is rather in the opposite merely that of weakening, whereby the bactericidal bodies are sense, viz., whether the agglutinating property is always asso- able to act; by means of other injurious agencies such as heat ciated with some degree of protecting power, in the case of similar effects can be produced.] such forms of serum as exhibit clumping power. Van de 3. Agglutinative, in respect of their power of causing clump- Velde has made some comparative observations by immunis- ing (agglutination) and sedimentation of the bacterium. ing two horses against two different races of streptococci, and a We have to consider how far these different modes of ex- third horse against both of these races. Streptococcus " As" perimentation are equivalent to one another as well as how was clumped by serum " A," but not by serum " P; " so also far the action of sera is truly specific; that is to say, have we streptococcus "P" was affected by serum" P," but not by evidence that races or kinds of bacilli which are recognisably serum II A " when tried in dilution of I to 50. Serum " A " had distinct by cultural methods are uniformly and equally with- protective action against " A," but not against " P; " similarly, out reaction when exposed to one or other form of serum test ? serum "P" protected against "P," 'but not against "A." As far as present knowledge goes,' this question cannot be Further, the serum "A" ± " P " had both protective and answered with an unqualified affirmative. agglutinative action on both of these races. Pfeiffer, in a paper in which he endeavours to discredit any THE ACTION OF NORMAL AND HETEROLOGOUS SERU-M. association between these two properties 2 gives the following Before entering upon the subject immediately before us, example, which is in the contrary sense to his desire. A per- I will allude to the qualities with which certain " normal" and son was given a " Haffkine " cholera injection: heterologous serums are endowed. In the days antecedent to the recognition of agglutination as one of the properties of Protective Power of Sedimenting Power certain specific serums, it was shown that some specimens of Serum. of Serum. normal serum had distinct protective properties; the protec- tion afforded by such serunms is in contrast with that given by specific serums, in that extremelyminute doses ofthelatterare Before inoculation ... o.6oo c.cm. :05 sufficient, whilst comparatively large doses of the former are x requisite. For the purpose of testing specific effects, it is Nine days after inoculationi... O.OIO c.cm. :0 I necessary to use samples of serum which are efficient in Eiglhteen days aftcr ,00.007 c.cm. 50 quantities of 20 to io cm. or less; probably doses of serum must not exceed about 50 mg. Control experiments must include those in which serum from the same kind of animal These observers found that in persons wlho had had similar is used (this is particularly necessary in the case of serum injections some months previously the agglutinating power derived from the horse, since even 50 mg. will sometimes had fallen to the level which is present in many normal serums, cause very distinct retardation of death apart from any special but that the protective power was still considerably elevated. or specific action). Some such serums will also determine a They argue that, on this account, there can be no relation lysogenic effect in a space of an hour or so. between these two phenomena. A study of their tabulated Turning now to agglutination, we find that many kinds of experiments shows that a complete lysogenic action only serum obtained from normal animals possess some degree of occurred in those cases (within about one hour) in which a clumping power; however this, like the protective action, dose of serum approaching the limit of clumping effectwas given. disappears when the proportions are sufficiently reduced. In Unfortunately they give no data concerning the condition of observing the protective action, we must employ minute the vibrios directly after the injection. Their other experi- doses, and in using the clumping power as a test we must ments, with old kept serums and alcohol precipitates, use sufficiently high dilutions-the higher the better. hardly show more than that low protective and lysogenic It is far from my purpose to follow those observers who powers were associated with low clumping power. One have tried to institute comparisons between the serums of form of experiment is designed to show that by growing normal and those of specifically immunised animals. Although cholera vibrios in cholera serum the agglutinating power is the effect may be similar, it does not follow that the cause is of entirely destroyed, whilst the protective power is only the same nature. These actions probably are more akin to tlle diminished. Pfeiffer had previously described an almost absorptive or combining action of brain matter upon certain identical experiment which was repeated several times by toxins (tetanus, botulismus) ; in the case of diphtheria toxin Professor Gruber and myself with serum and culture sent by Wassermann has shown that the serum of some persons Pfeiffer. Although we followed hiis instruction to the letter, who have never had the disease is capable of neutralising we were never able to obtain his results. Since then the ex- ten times the lethal dose of toxin. In the present state of periment has been modified, and some loss of protective our knowledge, it is a far cry still to the nature of natural power is admitted. In his last communication2 on the place insusceptibility and of specific immunity; and I have only of production of protective substances, he remains significantly mentioned the subject in order to avoid alluding to the possi- silent, and passes over the agglutinatinig power of the organ bility of fallacies being introduced from this source. extracts with the few words that it was ilnereased in certain cases. CONSIDERATION OF SERUMS OF IMMUNISED ANIMALS. We may now pass to the consideration of the three methods PFEIFFER'S TEST REACTION IN RELATION TO THE CLUMIPING of testing serums or bacteria by means of their actions upon one TEST. another. It is not uncommon to find that, although complete It has already been pointed out that Pfeiffer's test is not degeneration of the microbes in the free peritoneal fluid may necessarily associated with a complete protection. In reality have occurred within an hoar, yet the animal eventually the destruction or degeneration of the bacteria introduced succumbs to the infection. In the case of kinds of bacteria is only partial at the end of the time limnit ; for by killing which have but slight resisting power, such as vibrios, a com- the animal when all the bacilli in samples of the free peri- plete protection usually results when complete degeneration toneal fluid are turned into spherular bodies, it is found that has taken place; with more resistant organisms, however, 2 Pfeiffer anid Kolle, Cent. f. Bakt., xx, i896, p. 142. although the local process may be controlled more or less 2 (With Marx). Denit. med. Wl'och., i8'8, and Zei'. ,f Hyg., xxvii, I398, p. 272. TliE BRITISH 1 59590 MEDICALTu JOURNALJaiH SECTIOiN'ETO OFFPTOOYPATHOLOGY. [SEPT.SP.33, i898.88 abundant untransformed individuals are presenit upon the cholera), positive Pfeiffer's reaction and complete sediment- omentum, etc. I believe that the previous agglutination of ing effect, coiiibined with permanent protection, were invari- the bacteria forms an important adjuvant to tlle production of ably associated together. The concordance was too striking a this degenerative process in the free peritoneal fluid; for it fact to be overlooked. has been a very striking fact that these two factors have The following observations on other bacteria are similarly always been associated in the large series of experiments in harmony with tlle view that protective (and lysogenic) witlh vibrios wlhichl I carried out in Professor Gruiber's Insti- properties are associated witli agglutinins. tute. Some recent work of Ransom and Kitashima3 is of One more instance may be quoted in illustration of this interest in this connection; they obtained a race of cholera association. It may not be generally known that it is per- vibrios whichli was not affected by a certain clholera serum fectly possible to obtain a clumping serum by the administra- (this was effected by growing a number of successive genera- tion of a non-pathogenic organism. By treating an animal tions in the diluted serum-in fact, a process of artificial with cultures of the non-pathogenic Bacillus megatherium, I selection, the more susceptible individuals being gradually succeeded in obtaining a serum which had considerable weeded out). The virulence of the culture was not appreci- power of sedimenting this bacillus. When tested according ably affected tlhereby. This race of vibrios yielded a nega- to Pfeiffer's method this serum gave typical degeneration of tive reaction to Pfeiffer's test, although the original race was the bacillus, whilst the animal to which anotlher kind of both clumpe(d by anid afforded an almost complete positive serum was given with the bacilli afforded a typical Pfeiffer reaction with the same serum. control. Anotlher observer' has given some experiments in which he shows that a preliminary dose of opium prevents the complete PROPORTIONAL RELATIONSHIP BETWEEN PROTECTIVE, occurrence of Pfeiffer's reaction, althouglh efficient serum is LYsOGENIC, AND CLUMPING POWER. employed. This result lie explains by the assertion that the The question as to whether there is any evidence of the leucocytes are paralysed; but if I may be allowed to put a existence of a proportional relationship between the protective different interpretation on this complex experiment, I am in- and the clumping power of a serum entails the consideration clined to ascribe the result to the paralysis of the intestines of several matters. One fact is establishled withlout doubt, wlhereby the sweeping mechanism of the peritoneal cavity is namely, that the susceptibility of a race of bacilli to a given annulled, conse(luenitly all those vibrios wllich in a normal serum is a variable quantity. Early in our researches on animal would be gatlhered up and disposed upoil the omeIntum, vibrios, it appeared that the less virulent races were more etc., remain freely suspended in the fluid. susceptible to the agglutinins produced by the use of virulent varieties than were the virulent varieties themselves; more- Comparative Agqlutinating, Lysogenic, and Preventive Action of over, in harmony with this, the serum obtained by means of &rums Obtained from Sufferers in an Epidemic Associated with the the less virulent kinds, although very efficient upon these Presence of a Variety of B. enteritidis (Giirtner). kinds, had slight influence upon the more virulent sorts. Intraperitoneal Injection. This was subsequently confirmed by Pfeiffer and other observers. From more recent observation I fear that it is Limit Agglutinative Power Serum No. 19 = 0. No. 8 = 1: 500. not simply a matter of virulence, for a less virulent No. 13 > 1: 500. stock of B. enteritidis was found also to be less influenced by a given serum. It is better, therefore, to speak of greater and Examiiinatioin of less resistance and susceptibility to clumping serums. Guinea-pig. Dose. peritoneal fluid Result. Again, everyone who has watched the process of agglutina- after 2 liours. tion under the microscope must have been struck with the difference between individual bacilli, certain individuals being influenced loncr before others; some A, 260g. loop no serum. Very abundant IDead in less than indeed, may escape active bacilli. 20 lhours. altogether. Now, in measuring the agglutinating or sedi- B, 275 g. I loop + 20 mg. Abundant blacilli, IDead in less than menting potency of a serum by means of determining the seruin I9. mostly active. 20 hours. limit dilution at whichl a visibly recognisable effect is C, 220 g. I loop + 20 mg. Many spherules, IFound dead and serum 8. few bacilli, niot Ipartly eateniby engendered in a given time, we get some idea of the action many active. ccoimriades on tlle upon the susceptible individuals; but the resistant and less 6tlh day. susceptible ones are not heeded. This method of measure- D, 230 g. II lOOp + 20 ing. VerCy abundant IFound dead on 6tl serum splerules. A few day. ment could hardly be expected to yield any proportional I3. swollenl non-imeo- comparison between tlle protective and clumping power tile bacilli. of tlle serum. The following example may be cited in illustration. A sample of typhoid serum was found to have a sedimenting value of 1:20,000 when tested Lintit Agglutinative power Serumn No. 30 = 0, No. 25 = 1: 500, for the ultimate limit of dilution at whichl recogniisable effect No. 23 = 1 : 1,000. was produced; when tested with the same culture upon ain Intraperitoneal Injection. animal it was found that as much as 50 mg. only just pro- tected against about twice the minimal fatal dose; in a word, Examiiination Examiiination it was niot a powerful serum. How, then, can we reconcile ,Guinea-pig. Dose. of peritoneal of peritoneal Result. so high an apparent clumping power and so low a protective fluid after I hlr. fluidafter 3hrs. capability with any association between these two properties? The answer to this is: By testing the total effect of the serum upon a given quantity of bacilli. Even in a strength of 2 per A, 390 I loop no Many active Very miany Died in 23 hrs. cent. this serum could not cause complete precipitation of all seruml1. bacilli. active bacilli. the to this test the serum could not be B, 210 g. I loop + 20 ng.i Abundant Very maniy Died in 22 lirs. bacilli; according No. 30. active bacilli. active bacilli. called a potent one. In contrasting the protective and clump- C, 230 g. I loop + 20 mg. Mally splhe- Isolated Died in 47 hrs. ing efficiency of serums we must take heed of the effect pro- No. 25. rules. A few swollen bacilli. swollen non-Many splie- duced upon the more resistant as well as upon the more imiotile bacilli. rules. susceptible individuals. In working with vibrios it was D, 260 g. I loop + 20 mg. Occasional Many sphe-Died in 60 to 70 found that serums which were capable of causing the complete No. 23. swollen bacil- rules. No fr e lirs. sedimentation of about 2 mg. of the culture withi I c.cm. lus. Many bacilli. A few spherules. bacilli seCen of a I per cent. dilution were also capable of producing withliii pliago- positive results in Pfeiffer's test, with permanent survival cytes. of the animals, in a dose of about lo to 20 mg. Whilst the ultimate limit dilution at wlhieh agglutination can be Accordinig to my own observations upon sixteen kinds of discerned is totally out of proportion to the protective capacity, vibrios (six clolera and seven not cholera, three reacting like yet it may be in concordance with the relative protective of serum when tested Deut. med. Woch., 1898, p. 295. capacities of two or more sanwnles with 4 Cantacuzene, Ann. de f'lnst. Pusteur, I898, p. 273. the same culture; the experiments tabulated above may be SEPT. 3, I898.] AGGLUTINATION AND IMMUNITY. [ME(DICALTHZ BILT.TJot'tNAL 59 I cited as instances. Some authors liave argued that since a THE DIFFERENTIAL DESTRUCTION OF AGGLUTININS serum has hiigh clumping power on a weak race anid but IN VITRO AND IN VIVO. insignificant protective action agaii)st a virulentt stock, tlle It lhas been established that by growing the special existence of anly lin-k between these two phenonoena cannot microbe in a given homologous serum the power of clumping be entertained. It would perhaps be kindest to say nothing is diminislhed or entirely destroyed, according to the metlhod about such an argument. of experiment. On the otlher lhand, in the growtlh of insus- ceptible heterologous bacteria, moulds, etc., practically no RELATIONSHIP BETWEEN CI,U\IPING POWER AND CERTAIN diminution oCcurs. The same observation lhas been made INHIBITORY EFFECTS. with regard to the protective power of suclh serums-namely, When bacteria are grown in the presence of even small that thle like sort destroys, the uiilike leaves iiitact. Here, quantities of efficient agglutinating serum, they exhibit theni, we have another instanice of the parallelism between departures from their normal habit of growth ; for instance, these two properties, proteetive and agglutinative. It must the reducing power of a cholera vibrio may be ehecked, the be admitted that certain authors aver that agglutinins are not plhosplhoreseence of a luminous vibrio can be stopped, the destroyed by tlle presence of the homologous organism. This production of the pigment " pyoeyanin " by the B. pyocyaneus is due to the fact that unidiluted serums were infected, so that may be inhibited; morpisologically also we lhave the ten- the growth of the bacilli was interfered with too much. The dencyto grow in chains or threads by microbes, whieh natur- following experiment illustrates tlle effect of varying dilutions: ally do not present this feature. No one has as yet sue- Six porltionls of a sample of typlhoid seriuin werCe inoculatcd witli varying ceeded in out a so we are quanitities of typhoid, eniteritidfis, a,id coli cuiltuires; these were incubated separating pure agglutinin, that not fol 48 llouls t 37O C. andi(l tieii tested for thieir sediillelitiilg potency. able to say wlhether these inlhibitory actions are due to the Portioni A. inllected witlh trace of typlhoid brotlh culture. agglutinins tllemselves or to substances wllieh are associated B." 8, ~~~~~4 Pillit5ofts o with we in with C. ,, 49.,i them; are, fact, in the same position regard D. ,, like amount of brotli cultur c of GSrtner's to these inhibitory phenomena as we are in the case of the bacillus. protective agents. All that we can say is that a combination E. ,, like aoiiiont of brotlh culture of bacillus coli of clumping, inlhibitory, and protective substances is ex- comuIIniull; . tremely suggestiveof a close relationship in their nature. One Limit Sedi2menting Values after 48 hours Incubation at 370 C. author, Salimbeni5 regards the agglutination phenomenon as upon I'phoid Bacillus. a property whliehl is only acquired by the blood, etc., after it has been slhed; he states thlat it does not take place within A. B. C. 1). E. the living animal. This is entirely at varianee with my own experience, for numerous observations upon peritoneal iinjec- tions in immunised animals have always slhown that aggluti- I: I,OOO Slighlt 0 + nation occurs within the peritoneal cavity. If the examina- tion of the peritoneal fluid is made later than about five min- I: 2,000 Trace 0 0 Sliglht + utes after the time of the inoculation, all or most of the clumps I:5,ooo 0 0 0 0 have disappeared, for tlley have been swept away by the abdominal movements to the walls of the cavity. Salimbeni Witlh thte typlioid infectionl the loss is grieater tile Iiglher the dilution. also asserts that the presence of oxygen is a necessary factor for the It will be noticed that the presence of Giirtner's bacillus occurrence of clumping, inasmuclh as it fails to occur also caused some loss, whilst the colon bacillus was quite in vacuo. Here again my observations are in disagreement, indifferent at these dilutions. for on endeavouring to repeat his results I find that agglutina- tion takes in the in Another method of testing this differential loss of clumping place vacuum, the oxygen-free atmosphere power is to do it withlin a living animal. By giving a homo- produced by means of pyrooallol and caustic soda, and in an dose to ani animal some atmosphere of coal gas just as well as in the controls exposed logous which already possesses to the air. As hiis observations have been frequeintly quoted, agglutinating power in its blood the agglutinating value of it would be the blood cani be made to decrease. It is somewhat inviting of importance if others would give their experi- that as the are ence in this matter. to suppose agglutinins used up during the struggle against the new infection they take some share in the process, and are useful and not merely ornamental sub- BACTERICIDAL ACTION OF SEItUMtS WITH Cr,LUMNPING PROIPERTIES. stances. If the dose is from in Before the days of agglutination many authors examined recovered they reappear larger immunised serums for bactericidal action. For quantities than before, or, on the othcr lhand, the animal may instance, Sana- die of intoxication before they are completely destroyed. relli, working with cholera and other vibrios, found that con- Four guiniea-pigs werc prepar-ed by giviing tlhemii equal doses (I loop siderable destruction took place. More recent observations = 2 lllg.) Of living typlhoid bacilli subetatnucously ; thcy were tlheni kept (Bordet, Landsteiner) show that these serums are only really for about a fortniglst. Each One tlheni receive(1 a large dose of bacilli in its peritouieal cavity (6 loops of youing agar cuiltiire in eacli case). On the bactericidal when they are quite fresh; serums wliich have pr-evious days the blood was takeni in order to test its sedimenting been kept or which have been heated to 550 C. lose the power power. of absolute destruction although they may cause profound Guinea-pig A received typlhoid culture. effects tlle and of the the 13 ,, Gi5rtiner's bacillus. upon appearance growth organisms; C , var-iety of GAirtner's bacillus (tlhis variety has but bactericidal effect, however, is regained by the addition of sliglht mutuial reactioli with typlhoid). perfectly freslh normal blood or serum, which by itself is D ,, B. coli comnunis. unable to produce a like effect if the bacteria are sufficiently Sedimenting TValues for Typhoid Bacilluts (all were Tested with resistent (virulent). the samiie Sut.spension). Foerster6,in Isis experiments on the bactericidal power of the serum of typhoid-fever patients, only made use of the A. B. D. limit recognisable agglutinating effect in estimating the C. power of the sera he tested. As, moreover, he gives no data concerning the time which elapsed between the withdrawal o of the serlum and the performance of the experiment, it is Before injection 2...... > I 2,000 1 s,000 2,000 I 1,000 impossible to draw any conclusions from his results. Four lhours after- injectioin TIrace ait >1 50o I.o000 I 1,0 to observations the coccus of Malta 1:500 According my upon ( 1 s,ooo fever a high clumping potency of the blood was asso- ciated with the absence or scantiness of the coccus in the blood; on the other hand, when animals died witlh low clump- It will be observed that the result is merely a repetition of ing power (for example, I in 200 or less), the cocci were very the experimeint in vitro to which I have just alluded, for the numerous in the blood. It appeared, tlherefore, that the typhoid had most marked effect, the coli none wlhatever, the presence of the agglutinins was unfavourable to the existence other twowiths B. enteritidis being intermediate. Guinea-pig B, of the coccus in the blood and vice versd. whlich received Giartner's bacillus, deserves a few more words. A control normal animal whlich received only I loop (that is, A47nn.5 (le l'Inst. Pasteur, 1897, p. 277. one-sixth to died B GZeit.f. Hyg., xxiv, i896, p.523. tIle quantity given B) witllin 2I hours; T= BRITnH 1 592 MIMICALXUDICILLJOUR7AL]JOURFAL I SECTION OF PATHOLOGY. [SEPT.(SEPT- 3, 1898.x898. survived 6o hours. A sample of its peritoneal fluid withdrawn Kraus found that floccular coagula were produced by the immediately after tlle injection showed that most of the action of specific serum upon filtrates of cultures of the bacilli had already become clumped, and only a few were free homologous bacteria. He maintains, and his observa- and motile: after death there were very few bacilli in the tions are borne out by the confirmatory work of C. Nicolle, peritoneal fluid; there were, however, very many spherule that the reaction is quite specific. In the low dilutions in degeneration forms whieh on culture gave rise to a pure which these experiments were made (i in io, to i in 20) it growth of Gfirtner's bacillus. would not be likely that specific differences would be well When dealing with the passive protective action of typhoid marked when closely allied forms were put to the test, and serum on Gartner's bacillus, we find that it is capable of such, indeed, I find to be the case. Tlhus the serum of giving distinct retardation of death with doses of bacilli B. enteritidis with typhoid filtrate gives as good a coagulum which are rapidly fatal to control animals; just as the agglu- as with its own kind of filtrate. Whether this action is the tinating effect is less in degree than is the case with the real cause of agglutinative changes as these authors claim, is typhoid bacillus, so also the protective action is in lesser not as yet actually demonstrated, however probable it may degree. There is much variation, however, between the inter- appear. Hitherto my attempts to reduce the agglutinative actions of different samples of typlhoid serum and different power of serums by this action of filtered bacterial macera- varieties of B. enteritidis. tions have failed; there was no appreciable loss by the forma- Conmparison of Agglutinative, Lysogenic, and Preventive Serum tion of the coagulum, though I found that filtrates could cause agglutination. C. Nicolle claims to have isolated the Action of Typhoid Serum on B. Enteritidis (Gdartner). agglutinable substance from filtrates. But the field thus opened has not yet been sufficiently worked upon, and it - Dose. Peritoneal Sample Taken- must be left to further researches to show whether it is pos- sible to produce a serum which possesses solely the power of and which is devoid of and Guinea-pig A: I loop Grrtiler Imnmediately: Abundant active bacilli, clumping, inhibitory protective 390 grmis. + 50 mgr. no clumps. properties. vibrio seruni.* After x houtr: Abundant alctive bacilli, no CONCLUSION. A -glutinating clumps. Also a few spherules. The actions of normal and heterologous serums (clumping power = o. After 2o hours: Abundanit mnotile and non-mllotile bacilli. and protective) may be left on one side as hardly germane to hlours, T. 37.60. Deadin less tlhan 2I h1ourIS. Peritoneal our subject. We have evidence that when agglutinins are pre- 7 lhours, T. 35.50. fluid swariming witlh bacilli. sent, inhibitory and protective properties are also to be found. Hitherto an agglutinin free from these other substances has Guinea-pig B: loop GartnerlInmediate: Abundant smiiall clumips, act the 365 grms. + 50 mgi . Ty- also many active free bacilli. not been obtained. Agglutinins within living body plhoid serumn.* After I houtr: Many baicilli, nione motile, by causing clumping as well as in the test tube. Destruction Agglutinatinig many deformed bacilli, and maniy of occurs in an immunised animal after power: (a) Coiii- splierules. agglutinins actively plete precipita- Afler 2j' hours: No bacilli; :many infection with the homologous bacterium. tioni aboult 5 pcl swolleni spherules. There is no definite relationship between the limit dilution cenit., (b) in ul- at which clumping can be recognised and the limit dilution tiinate dilution a amount of I 200. at which complete effect is produced upon given . hours, T. 38.40. Sur-vived 7 days. Post-m2iortcmi1. only the bacteria. From the latter some clue as to the preventive 72 lhours, T. 37.i8. splicrules in peritonieal fluid: IlnIl- efficiency of a serum may be obtained. m )tile bacilli in pseudo-imielnibraiies Lastly, although the association of agglutinins with protec- on liver and spleen. tive substances may be shown to be fortuitous in future it will interest from the * Both thesesecrumis wre taken 3T years previously and kept scaled up in experience, yet always have attached sterile conditioni in glass tubes. The typlioid serum lhas niot apparelntly fact that the now well-established method of serum-diagnosis lost much of its agglutiiliatiing power since April, I895. in typhoid fever and other diseases owes its birth to this asso- ciation. The knowledge that protective qualities are acquired EFFECT OF HEAT AND TIME. bythe blood of typhoid fever patients led to the probabilitythat So far as present knowledge goes it appears that both the clumping property would also be developed. This resulted agglutinins and protective substances become destroyed at in Gruber's world-famous suggestion that this agglutinating about the same temperature ; thus both suffer but little at 600 in unless the heating is prolonged. Both are fairly well pre- property should be worked out typhoid and cholera patients. served after long keeping, although some loss does occur. In the animal economy after active immunisation with living II.-A. S. F. GRtNBAUM, M.D., bacilli both substances persist for considerable periods ; in Senior Demonstrator of Plhysiology, University College, Liverpool. some of the original experiments with Professor Gruber well- DR. GRtNBAUM said that he had worked chiefly with human marked agglutinating power was present in animals more than was He a serums, the agglutinative action of which often small. year after their infection. According to Pfeiffer the aggluti- thought that it was importanf to note that in low dilutions natinig power may be lost earlier than the protective property, the agglutinative power did not go hand in hand with the judging from a very few cases. protective power. He pointed out that even inanimate sub- FATAL ISSUE DURING THE PRESENCE OF HIGH AGGLUTINATING stances-for example, particles of French chalk-might be POWER OF THE BLOOD. agglutinated by various serums, and tlhat, therefore, the agglu- So far, no one, I believe, has proved the existence of tination was probably a physical process which prepared the agglutinins apart from any protective power of the serum. At bacilli for the action of other substances later on. Even non- first sight it may appear strange that an animal slhould die of motile organisms might show less of Brownian movement in a particular infection, although a few tiny droplets of its the presence of certain serums, probably from the swelling of a serum are capable of protecting numbers of other animals membrane round them. He suggested that a fourth property from a like infection. But this is an old and well-established might be attributed to the specific serums in addition to those fact, which, moreover, must have been confirmed by nearly mentioned by Dr. Durham--namely, a paralysing action on every worker in the field of immunity. What the meclhanism motile organisms. of the fatal issue may be (whether some toxic product or some initerference with some important organ) in such cases, I III.-E. J. MCWEENEY, M.D., must leave on one side. It is clear, however, that the fact Professor of Pathology and Bacteriology, Catlholic University, Dublin. that an animal may die with large quantities of agglutinins in PROFESSOR MCWEENEY said that in the course of his work on its blood is no argument against the association of these sub- the growth of the typhoid bacillus in bouillon containing a stances with protective bodies, unless it is also shown that certain proportion of the homologous serum, lie had arrived the latter are absent. And this has not yet been demon- at the following results: (i) The typhoid bacillus when strated. One of the best samples of serum which I obtained caused to grow in broth containing typhoid serum displayed at the commencement of my researclies was taken from a cei tain abnormalities; (2) these consisted in absence of moribund animal; it possessed high agglutinlating as well as nl ility and the formation of long, convoluted chains made high protective power. ul) of short individuals; (3) this mode of growth could, under POST-DIPHTHERIAL PARALYSIS. I Tz BRImTIs SEPT.--- -- 3,- I I898.]- I -.j LMBDICAL JOURNAL 593

a certain circumstances, be utilised for clinical purposes; (4) diphtheria could not be compared with the class of so-called the cases in whiell it might be advantageously used were those " antibacterial" serums of typhoid and cholera. Many ob- in which the clumping by the ordinary Gruber-Widal method servations showed that the serum prepared by means of was slow in coming on, or for any other reason left the ob- filtered diphtheria toxin did not afford so efficient a protection server in doubt. The method consisted in diluting the sus- against living bacilli as one prepared by immunising with pected serum witlh broth containing a small number of living culture. The effect of heat depended largely upon the typhoid bacilli and preparing hanging drops, which were degree of dilution of the serum before heating; serum diluted examined after varying periods of incubation. A moderately with normal saline soluition retained the clumping power active serum, diluted ioo times with sterile broth, and inocu- against higher temperatures for a longer time than undiluted lated with a few typlloid baacilli, yielded exquisitely con- serum. By adding to the diluting fluid " nutrose " or phos- voluted chains after about sixhlours at 370 C. By the aid of phates which prevented coagulation of the albumen still this methodhle lhad been able to clear up the nature of a greater resistance to heat was produced. ease of typiloid fever, the symptoms of wllich closely re- sembled those of meninigitis, and which had been admitted POST-DIPHTHERIAL PARALYSIS. under the eare of Dr. Murphy to the Mater Misericordiae Hos- pital, Dublin. The method was one that could hlardly be [ABSTRACT.] carried out by the ordinary clinical observer on account of the By G. SIMS WOODHEAD, M.D., F.R.C.P.Edin., F.R.S.E. absolute sterility required in all the manipulations. Professor Director, Researclh Laboratories of tlle Royal Colleges of Plhysicians McWeeney coneluded by giving a short lantern demonstra- aiid Surgeonis, Lolndoni. tion in illustration of Ilis results. STATISTICS. THE great attention aroused in diphtheria during recent years IV.-G. SINIS WOODHEAD, M.D., has caused us to study diphtherial paralysis more care- Director, Researelh Labolatories of the Royal Colleges of Plhysicians fully. How important this question is may be gathered aInd Suligeons, Lonidoin. from a study of the following figures. During the year I896 DR. WOODHEAD said that lhe could not llelp tliinking that there were examined at the laboratories 7,832 cases that had this was a subject whiiel miglit witli advantage be left to ex- been certified "diplhtheria." Of these cases 5,o68 had diph- perts. He would, however, speak as an outsider, or rather as theria bacilli in the throat and I,362 suffered from paralysis one who was interested in the question from a general point of a more or less marked kind. Of these cases, I,o96 had of view. There now appeared to be several actions in serums been treated with antitoxin, and there were 273 deaths which undoubtedly ran parallel for long distances, but which amongst them; 266 received no antitoxin (that is, they were appeared to diverge in various directions. He was very much most of them mild cases in all probability), and there were struck by Ellrlicil's experiments in wiiell he demonstrated 49 deaths. In I,764 of the cases examined in which no this in connection witli ricin and antiricin. He had already diphtheria bacilli were found, there were 177 cases of para- said in this Section that the toxins were by no means the lysis witll 59 deaths; 89 of these cases were treated with anti- simple substances that were at one time suggested, and they toxin-3I deaths. There were, moreover, 88 not treated with had just heard that the serums were equally complicated. antitoxin, 28 of these succumbing. He thought it extremely unfortunate that the agglutinative DATES OF ONSET OF PARALYSIS. serums of cholera, typhoid, etc., could not be raised to such account of a number of a of immunising activity as the immunising Mr. A. Miller,' M.B., B.C., gives an high degree cases of paralyses observed by him at the South-Eastern serums of diplitheria and tetanus in which, however, the agglu- I896 and 1897, in which power was comparatively low. He hoped that some Hospital during the years tinative the onset was primarily (i) in the muscles of the palate; time they might come across some organism which would muscles; in the muscles of enable them to produce a serum in whieh both powers were (2) in the oculo-motor (3) with other parts ; and (4) in cases of paralytic heart failure. highly developed. He was certainly inclined to agree of which I85 were primary para- Dr. Durham as against Widal that a Iligh agglutinating power He collects 494 cases, lyses of the palate, 197 strabismus, IO paralysis of other in either cholera or typhoid could scarcely be associated with 9I of which died and a low immunising power. The observations of Weigert and muscles, 102 cases of cardiac paralysis, I recovered. The bulk of the palatal paralyses occurred be- Ehrlich on the separable properties produced by the action none before the fourth. of micro-organisms and toxinls oni cells would indicate that tween the fifth and the fifteenth day, neutralisation of certain properties might be carried out in Of the oculo-motor paralyses the bulk occurred between the the bacteria themselves by substances separated from the fourth and seventeenth days, none before the fourth; of the tissue cells. He would like to ask Dr. Durham whether he primary paralyses of other parts, half of them occurred be- tween the tenth and fourteenth days, and none before the ear- had used higher temperatures tllan 550 C. or 6o0 C. for the of the palate occurred as purpose of determining whether there was any difference in lier day. A case of primary paralysis this respect between the agglutinin and the antitoxin-the late as the sixty-fifth day; of primary oculo-motor paralysis globulin precipitating temperatures, for example. He agreed the ninety-first day, and primary paralysis of other parts on the fifty-first day. The bulk of the cardiac paralyses oc- with Dr. Durham as to the necessity or non-necessity for the a few cases presence of oxygen. curred between the fifth and the tenth days; occurred even as early as tile second day, whilst this condi- tion occurred in a severe form (that is, ending fatally) in 2 V.-DONALD H. HUTCHINSON, M.D., on Edinburgh. cases on the fifty-fourth day and in i case whichl recovered DR. HUTCHINSON said that hle had inoculated hlimself witll the fifty-ninth day. had It is evident, then, that in the human subject these para- dead typhoid bacilli according to Wright's method, and lyses ocour at a comparatively early date, although in afterwards examined at sliort intervals of time his serum cases come on at very much later stages; and on living typhoid bacilli. He found in so numerous they as regards its effect one cannot help thinking that we have evidence of the doing that the first effect to appear was an interference with nerve cells or of a direct action of the serum appeared to primaly affection of the the motility of the organisms, that is, the poison on the muscular tissue in the fact that cardiac paralyses develop a paralysing action before it caused distinct agglu- occurred relatively at so much earlier a period than the other tination. forms of paralyses. Tile affection of the cells of the vaso- motor centres and perhaps also of the ganglia of the heart DR. DIJRHAM'S REPLY. being much more important in the regulation of the heart Dr. DURHAM tliought that too much importanee should not muscle, whicll is constantly in action, tllan in the case of the be ascribed to tIle paralysing effeet; absolute loss of motility otlher muscles, which in most cases are practically at rest, did not accompany complete agglutination, for fettered indi- and in whichl therefore tile demands on both the motor cells viduals could be seen exhibiting whirling movements. More- and the muscular tissue itself are comparatively slight. over, fresh serum and leucocytotic peritoneal fluid had muel paralysing influence apart from any specific action. Since Dr. MORBID HISTOLOGY. Woodliead and others had also been unable to obtain Salem- Without going into the tlieory of the causation of paralysis, beni's results they miglit be put aside. The antitoxic serums of I may refer to the segmental nerve degeneration described BtITIS 1 594 MEDICALCTHz JOUSRNALJ SECTION OF PATHOLOGY. [SE,PT. 3, 1898. by Meyer,2 Sidney Martin,3 Dejerine,1 and others. Compara- couple of degrees, and the respirations and even the heart tively recently, attention has been drawn to the fact that beats becom-e diminished in numiber. It is curious that certain slighlt and perhaps temporary changes may be observed altlhough there should be this marked muscular weakness, the during the first twenty-four hours in whicll toxinl may be act- animal is still very bright, continues to feed as long as there ing on the nerve cells. It is maintained that the cells so is food within reach, is on the alert for sounds, and affected either atrophy or recover at an early date, but that the gives the peculiar cooing noise so characteristic of a guinea- nerves for whicl these cells act as trophic centres undergo pig wlhen anyone sneezes or makes a slharp noise in its degenerative changes, perhaps of a Wallerian type, and that neiahbourhood. Even in those animals wlichl recover only then do we meet with the clharacteristic diphtheritic there is impairment of the muscular imovemenits for a con- paralysis. I have examined two cords from experimental siderable period. In point of time the majority of the animals treated with full doses of toxin, and in one case the cases appear on the 2ISt to the 23rd day after injection. chromolysis and vacuolation of the cells was fairly distinctly In connection with this point as regards time of appearance marked, in the other there was no perceptible deviation from of paralysis, Ehrlich9 has observed that in most of tlhe cases of the normal. It appears, as pointed out by Mouravieff,5 that paralysis in the guinea-pig whicll have followed injection of when there is no great demand on their functional activity nearly neutralised toxin the symptoms have manifested tliem- these changes appear to produce few or no symptoms; but, selves at the end of the second week, instead of at the end of owing to the trophic changes, the peripheral nerves over the third week as in Madsen's cases, and he suggests that this which they preside become markedly altered in structure, may be due to the fact that Madsen used the original method a kind of Wallerian degeneration going on, with the result of testing, that is, neutralising with a ioth of an antitoxin that they lose their conductivity, and paralysis is the re- unit, Ehrlichl's observations being made on animals in which sult. In this way, too, may be explained the peculiar want the neutralising amount of serum was one unit. The bearing of co-ordination that sometimes occurs, and the patchly dis- of this will be presently noted. The amount of swelling is tribution of the nerve lesions, a few fibres of a nerve under- certainly no indication as to the probability of the occurrence going degeneration corresponding to the large or small num- of post-diphtherial paralysis, as we have observed some cases bers of nerve cells in the cord that are affected. in which the amount of swelling is comparatively slight in Pernice and Scagliosi,6 in a series of post-mortem examina- which there has been paralysis, whilst in otlher eases where tions, five in number, found that in patients that died early there has been a large amount of swelling there has been no after infection tllere was marked inflammation of the meninges paralysis at all. Examples of this are given in the specimen of the brain and cord, any other changes being the result of cases which are merely a few selected for the purpose of illus- congestion in the first instanice, although there is also marked tration from a considerable number. They are most of them evidence of inflammation and degeneration of the peri- taken from records made in the second six months of I897 and vascular tissue and of the cells, not only of the anterior lhorn the first six months of i898. Madsen refers to an exceedingly of the spinal cord, but also of the brain cortex. They found, interesting fact, the bearing of whichl will be seen imme- however, in connection with these cells, that it was only the diately. Wlhen the French method of neutralising antitoxin protoplasmic processes which were affected. These changes is used, that is, where a single large lethal dose only is are observed very rapidly after the toxin gets into the neutralised by tlle antitoxin, paralysis is of very infrequent circulation; and it would appear tlhat, especially in acute occurrence, and when it does occur it usually disappears in cases, toxin acts directly from the blood vessels especially on the course of a few days. the protoplasmic processes of nerve cells, and that, as a result 13 Cases of Post-Diphtheria Paralysis (Guinea-pigs): Cases of the changes in these trophic centres, the medullary sheath, Selectedffrom a Series of Animals used for Testing the Strengt.4 and perhaps also tlhe axis cylinder itself, may afterwards be- Antitoxin. come degenerated, the process extending from the cell along of the trunk nerve. PARALYSIS IN ANIMALS. Local reaction. Escherich7 notes that post-diphtherial paralysis is a com- paratively rare phenomenon in the guinea-pig, and he attri- f: 2nd day. 4th day. butes this to the fact that in them in most cases the course of the disease runs only over a few days, though he points out that it has been shown that in certain animals which II 245 6 Sliglht local swclling Distinct indurated - 45 g. - s g survive a subcutaneous injection of toxins or bacilli, where sweIlllg S the process has been so severe that a necrotic area has been 2! 275 I4 'Large firm swelling Larage deposit !5 , formed, and which afterwards ulcerates, there is para- 3l 265 |5Narrow medium Brad 5 35 of hiard bandNi reodd lysis, especially the hinder limbs, and of the posterior 4 270 I8 Traces of firm swell- Nil |Nil !Not recorded portion of the body. Loeffler, in i8go, drew attention to ing this fact, but he also slhowed that this paralysis in some 5 285l I8 iTraces of swelling Sliglht stranid + 35 g. 6 280 19 Small firm swelliing Swellingnearlygone- 5 cases passed off, and that the animal afterwards was to a 71 265 20 Nil Nil Nil certain extent immune, and he looked upon this paralysis 8275 20 Nil ? Nil + 5, as one of the symptoms of a severe attack of the disease-an 91 295 20 Nairrow strand Firm narrow strand + 30 attack such as would confer a certain degree of immunity, and I0 270 22 Laige soft swelling Large firm swelling 30 70 g. II. 260 24 |Boad band of firm Narr-ow firm band 30 ,, Not recordecT. an immunity which would last for some little time. iIswellinig Madsen8 points outthat paralysis,when it occurs, as arule, fol- 122270 25 Large firmii swelling ILarge hard swelling -5 lows the infiltration which results from the injection of a dose I3 260 25 Veiry laioge fil Large hiard deposit 40 of toxin not fully neutralised. Although this swelling disap- pears, there very frequently occurs, some nineteen or twenty It will be seen at once with referenice to the table that the days after the injection, the first symptoms of paralysis, date of onset has little to do with the severity of the local which manifests itself in the form of a rolling of the hinder swelling. Indeed, if we were to take the local reaction as part of the body and of the hind limbs whenever the animal giving any indication at all it would appear that the less the attempts to make any active movements. This paralysis local reaction the more rapidly does the paralysis make its gradually becomes more distinct, and after a time may involve appearance, for in case No. I we find very slight local reaction the fore limbs. The animal at rest usually lies on its side, on the second day, although there is a distinct indurated but can raise itself when it makes a special effort. As a rule, swelling on the fourth day; whilst in ease No. I2, althoughl there is not complete loss of power and motion in these there is very firm swelling on the second day and a large hard muscles, but in many cases the loss is very marked. Madsen deposit remaining on the fourth day, the paralysis is not also notes that although recovery is possible, this condition well developed until the twenty-fiftlh day. It should be usually ends in death. The animal retains muscular power remembered, however, that the paralysis may in several longest in the head and neck, and in certain cases the only instances have occurred a little earlier than is here noted, means of progression that remains to it is by pulling itself especially wlhere Saturday, whliclh is always a somewhat hur- on by its front teeth. ried day, and Sunday, in which observations would not be In most of these cases the temperature falls sometimes a made, intervene; whilst in other cases the first symptoms of SEPT. 3, 1898.] POST-DIPHTHERIAL PALSY. [M BLmo 595 paralysis may have been overlooked. As regards weight, it Commiiittee of the Metropolitan Asylums Board, I898, p. 185. 2 Arch. f. Path. Anat., Bd. lxxxv. i88i, p. i8i. 3 BRiTISH MEDICAL JOURNAL, I892, will be noted that, speaking generally, the greatest loss vol. i, p. 64I. 4 Arch. de Physiologie, T. v, 1878, p. 107. 5 Arch. de Mled. Ex- occurs at the two extremes of the table, and it would appear per., T. ix, p. II05. 6 La Riforma M1edica, ef. Cent. f. Bact. it. Paralaskundie, that suCh loss of weight occurs: (a) When the general toxic Bd. xix, p. 887, I896. 7 Etiologie, etc., Diphtherie, I, I894, p. 131. 8 Experi- mentelle Undersogelser orrer Difterigiften, I896, pp. 115-X21. 9 Die Werthbe- action is very acute, as is Case i, or wlhere there is time for meisunig des Diplhtlieria Hcilserunms unld deren Tlheoretischle Grunidlagei considerable nutritional disturbance to come in, as in Cases 9, Klinisches Jahrbuch, Jela. I897. 10 Proc. Roy. Soc., vol. 59, I896. IO, II, and 12, in whiclh the onset of paralysis was delayed the most, and in only one was tllere amytlhing but a marke(d DIscUSSION. diminution in the weight on the fourth day. In most of the Dr. F. W. MOTT, F.R.S., congratulated Dr. Woodhead upon other cases the loss of weight was very marked, but in only one his valuable paper, and the important statistics based upon a or two instances lhas this weight been recorded. large number of observations which he had brought forward. Bearing in mind the fact that in the earlier experiments He referred to the large proportion of cases of diphtherial very few cases of paralysis among guinea-pigs were recorded, paralysis, and asked whether those inimical to the antitoxini although in later experiments such a eomparatively large treatment had any grounds for explaining it by the increased number are met with, some explanation becomes necessary, use of antitoxins. No doubt Dr. Woodhead would satisfactorily and this appears to be offered by the faet that paralysis dispose of this question, but he made the remark so that there amongst an equal number of guinea-pigs used for testing pur- should be no uncertainty in the minds of the public. Dr. Mott poses is greater when Ehrlieh's new method is used than when said that he had examined the nervous and muscular tissues the older method was employed. in five cases of diplhtherial paralysis. He had foun(d genierally fatty degeneration early and late of the muscles and some- LOCAL AND CONSTITUTIONAL ACTION OF THE TOXIN. times Wallerian degeneration of the nerves. He had observed In describing toxin hitlherto we have had its action divided extreme early fatty degeneration of the heart, and yet no into what may be called local and constitutional, the coInsti- degeneration of the vagus nerve. He was of opiinion that pro- tutional again being divided into those eausing rapid death bably the poison acted on the whole neuron, especially upon and those giving rise to rise of temperature and nutritional the terminal arborisations of the dendron and the end plates. changes or reactions. So far as the cases that I have noted The early cardiac failure, he thought, could be best explained here are concerned, it is evident that the paralysing substances by tlle effect of stress. The heart muscle and respiratory are not the same as those which produce the local tissue muscles could not rest, but even had to work harder. They reactions. would, therefore, more readily succumb to the action of tle- Martin pointed out that the albumoses separated from the poison. body-not highly poisonous substances-give rise to compara- Professor BAGINSKY (Berlin) said that his own observations tively slight local reactions, but when injected in small doses had led him to believe that cases of post-diphtherial paralysis. into the vein they cause marked rise of temperature, some were now less common, though some bad cases might still wasting, and slight paralysis. occur. He had been interested to lhear how early the intoxi- Cartwright Wood,10 who got rid of the enzymes froii thie cation by the diphtlheria poison millt begin in the body, and albumoses by heating at 650 for one hour, was able to differ- he thouglht that the observationis recorded by Dr. Woodhiead entiate the actions of the enzmes and the " albumoses " some- would throw light on the true nature and origin of the para- what more sharply. The rise of temperature following in-jec- lyses. His assistant, Dr. Katz, lhad examined the brain,. tion of the latter is accompanied by comparatively little thougl spinal cord and peripheral nerves, and found advanced more prolonged local reaction; but, on the other hand, these degenerative changes in all parts of the nervous system, botlh substances give rise to slight paralytic symptoms even when nerve cells and nerve fibres. Extreme degenieration of the injected in very large quantities. In animals in which paralysis muscle fibres of the heart and diaphragm was also found. hi occurs there is at first a sliglht rise of temperature: this is regard to post-diphtherial hemiplegia, he tlhoughlt that cere- almost invariably followed during the paralytic stage by a fall, bral embolism was the most usual cause. He lhad found thiis sometimes of a couple of degrees and in one or two instances condition present iil three such eases examined, and thouglht the temperature was as low as 980 a couple of days after the that a distinetion should be made between them and cases of onset of paralysis. I hope, however, to collect more accurate real diphtherial paralysis. In his opinion, early antitoxin information on this point. treatment was of the areatest value in diminishinlg the num- ber of cases of paralysis in diphtheria. FURTHER ENQUIRIES NECESSARY. Dr. E. W. GOODALL (London) said that since the introduc- The following statement may afford an indication as to the tion of the antitoxin treatment the incidence of paralysis lines on which it would be necessary to investigate further following diphtheria had certainly increased. The reason of~ the causes of this paralysis. This paralysis occurs more fre- this we believed to be that patients now recovered, or at any quently in animals used for testing the strength of antitoxin rate lived long enough to show symptoms of paralysis, wh-o serum, the greater the multiple of lethal units used in the without antitoxin would have died at an earlier period. But test dose-that is, there are more eases of paralysis when a thouglh the number of cases of paralysis, relatively as well as theoretically ten times lethal dose is than when one is used, absolutely, had increased, the number of fatal cases had dimin- and still more when the test dose is again multiplied by Io- ished. Moreover, if the serum treatment were commenced that is, when it equals Ioo. early enough, the number of cases of paralysis would be lower As Ehrlich has pointed out, there are certain substances instead of higher than before. This was well shown in t] e formed along with all toxins and also formed as the result of post-scarlatinal diphtheria cases in the Metropolitan Asylum a slight rearrangement of molecules of toxins, which, although Board's Hospitals during I896. These eases were all un(ler they combine with antitoxins, have to a great extent lost their skilled observation from the very commencement, and the power of killing guinea-pigs. Some of tllese substances, how- serum treatment was begun early. Among them the number ever, only combine with the antitoxin after the true toxins of paralysis cases was considerably less than among tlle have all entered into combination with the antitoxin, so that diphtheria cases admitted from outside during the same one can readily understand that these epitoxoids, as lie calls period, and there was only one case fatal from paralysis. them, may be present in large quantities uncombined after Dr. WOODIREAD, in reply to Dr. Mott, said that he was ncw the actively lethal toxins have been neutralised. It is evident thoroughly satisfied that antitoxin had no power of settinig up that the greater the multiple dose of toxin used the greater paralysis by itself. He had given it in large doses in guinea- would be the amount of epitoxoid in the test solution, and, pigs and rabbits, but had never seen a case in which by itself therefore, the greater will be the danger of a considerable it had produced any paralytic symptoms. He was very glad amount of this epitoxoid being left over after the neutralisa- to hear what Dr. Mott had said regarding the aetion of the tion of the actively lethal toxin. We should, therefore, expect toxin on the processes of the nerve cells; it bore out very that, if some such substance as this be the cause of the para- strongly the idea that the poison acted directly and rapidly lysis, the greater would be the proportion of paralyses as the on the nerve cells. As he had indicated in his paper, lie bc. test dose of the toxin becomes larger. lieved that the heart failed earliest and most frequently be- REFERENCES. cause it was the organ which really got least rest. Heihad 1Mdieal Supplement to the Report for the Ycar of the Statistical for the same in his on 7 1857 contended thing article Tetanus in 596 .5ICAL JOUNAL] SECTION OF PATHOLOGY. I[SJiPT. 3, ~IS9 II Allbutt's S&ysteni of Medicine. This condition of over-work and above-mentioned lateral bulging may be taken as evidence -of ill-nutrition was the great factor' even in those paralyses that this. In many cases the cells seem to have taken up the apeared 'late;. Tlhe poison did its work, but it was only stain very faintly. In i-hour and 2-hour sections there are a when muscle.and nlerve were called into functional activity few vacuolated cells. that the damage was unmasked and the tissues give way under (c) Condition and Relative Number of Wandering Cells.-The a strain wlich in lhealtlh they would readily stand. He quite number seems to vary directly with the length of the period agreed witlh Professor Baginsky and Dr. Goodall that cases of up to 24 hours. In i-hour and 2-hour sections the majority paralysis were noiw not so frequent as formerly, and that those show almost a uniform staining with hiematoxylin, the which did occur were less severe. He thought that the prac- nucleus not being clearly defined. In the earlier of these two tical outcome of the wlhole matter was that, if possible, the sections, however, there are cells showing apparently a noxmal antitoxin should be, used before degenerative changes had staining reaction with distinct nucleus. In both, where been set up, anid that enouglh alntitoxin should be given to nucleus is definable, it appears single. Seen for the first neutralise Inot onily the lethal action of the diphtheria toxin, time in 2-hour section, and being present in increasing num- but also its local alnd paralysis-producing action. cers in 3-hour-, 5s-hour, and ioj-hour sections, are round cells very faintly or not at all stained, and having a granular appear- ance. This appearance is not a question of faulty technique. A NOTE ON THE LOCAL ACTION OF These phantom cells are present in greatest numbers in 51- CRU'DE DIPHTHERIA TOXIN. hour sections. In 24-hour sections they have altogether disappeared. Appearing for the first time in 5--hour By J. J. DOuGLAs, M.D., F.R.C.P.E., section are polymorpho-nuclear cells with eosinophile Lonidon. granules-finely granular oxyphile cells. These are INTRODI)UCTORY. also present in io4-hour sections and in 24-hour sections. WHILE much work has been done on the cellular changes Fragmentation of nucleus is seen most markedly in 24-hour followiiig'the inj'ection of diphtheria toxin, attention has sections, though it is also seen, but to a less degree, in been'.chiefly directed to changes occurring in organs more or io'l-hour sections. In the former the nuclei appear shattered, less reinote from the'seat of inoculation. Thus, Baldassari1 recalling the appearance of pus cells. investigated clhanges in cells of liver and kidney, and (d) Cells apparently endothelial in character. These are Barbucci2 in cells of liver, spleen, and lymph glands. Welch oval cells with apparently one large nucleus and very little and Flexner,' howlever, while examining spleen, liver, and protoplasm. The chromatin network stains faintly with kidney, also investigated the histological changes at the seat hiematoxylin, but is distinct. They are present in all sections, of inoculation; tlhey, however, used living cultures of the perhaps in greatest numbers in the latest ones. bacilli. These observers demonstrated the affinity of the In most section-s there are signs of cloudy swelling of the toxin for the nucleus of cells, resulting in its fragmentation superficial muscular fibres. or in a modificationi of its staining reaction. They also found TOXIN HALF NEUTRALISED. evidence of proliferative changes. It was to study the local (2) Series treated with toxin and a half-neutralising dose of changes subsequent to the injection of the filtered culture antitoxin. Studied in a like manner it was found impossible that this researchl was undertaken. With the object of to be sure of the reality of cedema before 51 hours after injec- investigating the local antidotal effect of antitoxin doses of tion. From this period it increased up to 24 hours. Connec- this were injected in certain cases along with the crude tive tissue fixed cells appeared swollen in 20 minutes' toxin. section, and this swelling was present in all sections, and METHODS, ETC. was more marked in late specimens. The animals used were guinea-pigs. There were three The changes in the wanidering cells seemed to be very series of experiments made: (i) with toxin alone, (2) with similar to those in Series i. There were present uninuclear toxin and a lialf-neutralising dose (as regards its lethal cells with distinctly staining nucleus, cells staining uniformly activity) of antitoxin, and (3) with toxin and a fully- with haematoxylin, and having indistinct nucleus, gradations neutralising dose (as regards its lethal activity) of anti- between these and phantom cells, phantom cells, finely toxin. The full test dose of toxin was given in each granular oxyphile cells, and cells in which the nucleus was case. The injections were given subcutaneously in the fragmented. All of these appeared at nearly identical periods abdominal wall. The animals were killed at varying periods to those at which they appeared when antitoxin was not after injection: 20 minutes, i hour, 2 hours, 3 hours, 5l hours, used. Endothelioid cells were also present in most of the Io0 hours, 24 hours, and 3o hours. The skin of the abdomen specimens. was shaved and portions of tle abdominal wall removed, hard- TOXIN FULLY NEUTRALISED. ened in 2 per cent. formalin, inMtiller, embedded in paraffin, (3) Series treated with toxin and fully neutralising dose and cut in the ordinary way. Sections were stained with antitoxin. What has been said of Series 2 practically applies Ehrlich's hlematoxylin and eosin. It will be convenient in to this one. The changes appear almost identical, save for what follows to speak of i-hour, 2-hours, etc., sections, the earlier appearance of badly staining cells. meaning thereby sectionis of specimens taken from animals SUMMARY. killed Ihour, 2 hours, etc., after injection. Attention was elucidated this research seem directed to the subcutaneous tissue of the area into In conclusion the points by which the cellular are and injection had been made, and in it to (a) the presence or to be: (i) That changes degenerative, to fixed that there is no indication of proliferation of affected cells; absence of cedema, (b) the condition of connective and (2) that antitoxin, whatever may be its antagonistic effect tissue cells, to (c) the condition and relative number of' a to the wandering cells, and to (d) cells in the subcutaneous tissue generally, does not locally act as chemical antidote apparently eridothelial in character. toxin. Toxin Alone. TOXIN ALONE. (i) Series treated with toxin albne. It was not found possible to get a'30 hours' specimen, as the animals did not live so long. (a) Presence or Absence of UNdema.-The earliest section to show undoubted (edema was the 5, hours' one. It was more marked in the io4 hours' section, and still more in the 24 Uninuclear normal reaction + + + + + hours' one. In the earlier sections there was a condition cells,with staining which might possibly- be (edema, but wllich might also Cells uniformly stainiing '...... ,. + + + + + . depend uponi unabsorbed fluid of injection. (to) Condition of Fixed Conneotive Tissue Celk.-These in all Phantom cells ...... + + + + periods, fromi1 X to 24 hours, appear swollen. This swelling Finely granular oxyphile cells...... + + + seems to vary directly witlh the length of the period up to 24 ... hours. In some cases the cells show a lateral 'bulging. At Cells withl fragmented nucleus... + + no period are there! discernible signs' of fragmentation of the Cells of endothelial type ...... + + + + + nUcleus no of t'priferation of the cells, unless indeed the ,SEPT- 3, I:ggs. LOCAL ACTIOX OF DIPHTHERIA TOXIN. I ilw; 1. i.159-7--.

'Toxin alone: I hour after injection showing false cedema.' Toxin alonie: sot hours after injection showing marked cedema.

. Toxin alone: 2 hours after injection sliowinlg "false cedema." Toxin alone: 2.4 hours after injection showing marked cedema.

1;Qsp,lNon,#i: 4boi~rN ts ofqo true alone: -i hour4after injection shoyving 4woRen fixed CIIwilngp Joxin tissde O W'', conneotKe ST98MDICLJBUITIN _ 98 MZDICLL JOU.NALI SECTION OF- PATHOLOGY.------SEPT.- -- - - 3,- , 1898.- - .1 - -

Toxin alone: 3 hours after injection showing " plhantoml " cells, one-of Toxin alone: 3 hours after injection. Endothelioid cell marked x, which is marked x.

Tozin alone: 5A hours after injection showing "phantom" cells Toxin half neutralised: 24 hours after injection showing marked mar -ed x. cedema.

Toxin alone: 24 hours after injection. The cells have fragmented Toxin half neutralised: 24 hours after injection showing cells with nuclei, though this does not appear distinctly in photograph. fragmented nucleus. SEPT. 3, x898.1 SERUM REACTION (TYPHOID). 599 rod. The method has been tested on about 50 cultures from Toxin Hlalf Neutralised. diphtherial throats, and the characteristic appearances have been obtained in every case. The pseudo-diphtheria bacillus of Hoffmann does not give the granulation. A slightly longer 0 .4 treatment than that recommended by Neisser has seemed to yield better results-namely, five seconds in the blue and ten seconds in the brown. An attempt has been made to extend the method to swab- Uninuclear cells with normal staining-reaction + + + + + membrane from the throat. With swabbings the bings or about per Cells uniformly staining ...... + + + + + results were not very successful, an error of I4 cent. occurring in 30 cases. Phantom cells ...... + ? ? With fresh membrane, care being taken to avoid fallacy from the presence of fragments of leptothrix and diplococei Finely granular oxyphile cells ...... ? + + + + + which may simulate the diphtheria bacillus, Neisser's method Cells with fragmented nucleus...... + + often affords a rapid means of positive diagnosis. If a nega- tive result be obtained recourse must be had to culture Cells of endothelial type ...... + + + + + + methods. REFrERENCE. 7'oxin Wholly Neutralised. t Zcitschr. f. Hyg., xxiv, z897) P. 43. NORMAL SERUM IN RELATION TO THE DIAGNOSIS OF THE TYPHOID BACILLUS. .41 0 0 By S. R. CHRISTOPHERS, M.B.Vict., From the Pathological Laboratory, University College, Liverpool. sus- Ulninuclear cells witlh normal staining reaction + + + + IN the event of a positive reaction being given by any pected typhoid organism with typhoid serum, there are two -Cells uniformly staining ...... + + + + + possibilities which should be taken into account before the diagnosis is definitely decided. The first, which has been Phantom cells ...... - . ? + + amply demonstrated by Durham, is that of the mutual serum Finely granular oxyphile cells ...... + + + + + + interaction of the typhoid bacillus with that of Gdrtner's bacillus. The second, which has not received much attention, Cells with fragmented nucleus...... + + is that normal serum, apart from any specific reaction what- Cells of endothelial type ...... + + + ever, may with certain organisms give reactions equal in power and extent of dilution to so-called specific ones. The REFERENCES. fact that normal serum has some action on quite a number of 1 Cent. f. ACg. Path., ii,-vol.Wvii, I896. 2 Ibid. 3 Johns Hopkins Hospital organisms has always been recognised, but that this action in .Bulletin, 189I, No. 1I5. some conditions is immensely increased has received but DISCUSSION. scant notice. Dr. MuIR referred to the need for control experi- So long as the reaction is used as a clinical test for typhoid mnents with antitoxin as regards the time of appearance fever the importance of this increased normal serum action is of the finely granular oxyphil cells. The fact that they not very great. The cultures of typhoid used are of pretty appeared at an earlier date, when the antitoxin was injected uniform virulence, and human serum does not act on such as with the toxin, than when the toxin was injected alone, was a rule above i in IO dilution. But so soon as one has to deal suggestive in relation to the general question regarding the with organisms from various sources and of various degrees meaning of the local leucocytosis. It would be of value, if it of attenuation then this normal serum action becomes of very could be absolutely shown that, by reducing the quantity of great importance indeed. the toxic agent, the leucocyte emigration took place earlier, Trying serum reactions upon numbers of typhoid-like and and was more marked. Such changes should also be studied colon-like organisms isolated from shell fish, milk, and water, in relation to the blood or general leucocytosis. I was struck by the great dilution at which normal serum Dr. LAZARUS-BARLOW felt sure that if the specific gravity could strongly agglutinate many of the organisms. In many of the affected tissues were taken, evidence of output of fluid instances in dilution of I in 200 normal human serum caused by the blood vessels would be found far earlier than the 51 extremely marked agglutination, large clumps of motionless hours after injection at which Dr. Douglas had first recognised bacilli being formed, and the preparation exactly resembling it. He thought that research should be further conducted on a decided typhoid reaction. At first sight this pronounced the lines indicated by the author, as in that direction might action of normal serum upon certain organisms appeared to perhaps be found an answer to the question whether endo- be a specific one, for it equalled in degree and extent of thelial cells play a part in ordinary repair besides the new dilution even strong reactions given by the serum of typhoid formation of the blood vessels. patients upon the typhoid bacillus. But further investiga- tion showed that in no way eould this action be called spe- ON NEISSER'S DIAGNOSTIC STAIN FOR THE cific, and that it was in some way entirely due to a great sus- DIPHTHERIA BACILLUS. ceptibility of certainorganismstobeagglutinatedbyall serums. Those of the organisms most susceptible to human serumswere By RICHARD T. HEWLETT, M.D., M.R.C.P., also those liost susceptible to the serums of the horse, monkey Baeteriologist to the British Institute of Preventive Medicine. rabbit, and even of the frog. So uniform was the action of [ABSTRACT.] different serums upon these organisms, that I came to the con- A NEW differential staining method for the diphtheriabacillus clusion thatit was not a selective action due to the serums, but was recently published by Neisser.' The formula is as depended entirely on varying susceptibilities of the organ- follows: isms. In order to see how far this susceptibility was related I. One gramme of methylene blue (Grubleres) is dissolved in 20 c.cm. of to attenuation, a number of very susceptible organisms giving alcohol (96 per cent) and mixed with 950 c.cm. of distilled water and of the colon bacillus were contrasted as re- so c.cm. of glacial acetic acid. all the reactions II. Two granames of benzoin are dissolved in I,000 "c.cm. of 'boiling dis- gards pathogenicity with colon organisms which gave little or tilled water, and the solution is filtered. no reaction with normal serum. The result was most striking Cover-glass specimens prepared from fresh serum cultures are stained in every case the non-susceptible forms in small doses proved in No. I for I to 3 seconds, rinsed in water, counter-stained in No. II for forms in enormous 3 to 5 seconds, washed in water, dried, and mounted in Canada balsam. fatal to guinea-pigs, whilst the susceptible So treated, the diphtheria bacillus appears as a slender, doses failed to have any effect whatever. longish rod, stained brown, and generally containing granules The majority of these organisms resemble very closely the of a deep blue or inky tint. There are usually two granules, bacillus coli communis; others are extremely difficult to situated at the poles, occasionally a third at the middle of the distinguish from the typhoid bacillus. The following table A. .-l- 11511:56 ..;:.4 'I [SETYF. y, MINDICAL ;SMOTiON & A*ATHOLOGY. [SEPT. 3, A§8. higher dilutions, as i in 1,003. A comparison of the effectsl shows the reactions of so-me of the more typhoid-like of these higher dilutions, as I in i,ooo. A comparison of the effect& organisms and their behaviour with different sera. of these sera upon different races gave the following results:

iLaboratory' Typlhoid Colon Bacillus Culture. Stronig Reactioln at in ioo. Str-ong Reaction at I in 200. Typlhoid. Like. Like. Coli.

Liver t) 14 times I times Gelatine ...... - Non-lique- Non-lique- Noni-lique- fying fying tyinDg Vienla ...... '3 1 Gra'm's stain . ... Does not Does niot Does not stain Stain stain Guntlher '4 6 yy Glucose media at 20° ., No gas Gasformed Gasformed ~~~~~~~~~~~~~~~~~~~~~~~~~~f-forimed-o-rZ Giirtlner ...... IO 97 ., ,7°_ Nogas Gas formiiedGas formiied formed Indol forlnation in peptone _ No indol No indol Ildol The sera reacted more strongly oftener with a cultute salt solutionl obtained from the fatal case (Liver I) than they did with the Milk in 48 hours ... Not Not Coagulated other is in concord with the coagulated coagulated races (especially Gartner). This Growth on acid potato Very thin Tlhiin Thick results of the comparison withthe bacilli upon experimentally- Growth on carbolic gelatiine _ Grows Grows Grows produced sera. The remaining i i samples exhibited no agglu- Acid formiiationi in nlcutral 6 per cent. 2 per cent. I4 per cent. I9 per cenlt. tinative effect at i in ioo; some also failed to react at lower dilu- litmus wlhey i day doubted that suffered from Acid formatioln in neutral, pcr celnt. 7 per cent. 20 per cent. 20 per celnt. tions. Since it is hardly to be they litmus wlCey 5 days the same disease, these cases may be compared to those cases. Motility ...... Very activee Very aictivel Sluggislh of enteric fever in which either no reaction or but a slight and Flagella ...... - 6 to 8 long 6 6 to 8 wavy long wavy, fleeting one is developed towards the typhoid bacillus. Serum reactions: Further, 8 serum samples were tried in doses of 20mg. (see p serum iln i in in ,Typhoid (a) I 30 5o I 50 1In200 protective qualities against culture from the fatal ease- i 5go)for Typhoid serum (b) ...... I ill 200 Not I in ioCo Not inI00 iIoo of these had no effect and no - gave Strorngly actinlg n1 0 r a I I in I I in 6o Iin Ioo i in 200 'fwo agglutinative evidencee serum of any protective action and a negative Pfeiffer reaction. The Weak niormal serum...... Not I ill I in 20 2Ii20 Iin5o remaining 6 not only had agglutinative action, but also gaye Immuinised rabbit's serumii. I ill 500 Not I ill 50 Not I ill 50 Not I 'in 50 distinct evidence of proteetive action as wellas positive results. with Pfeiffer's test (lysogeniec). Thus the evidence in favour: Professor MCWEENEY said that he had repeatedly isolated of regarding the bacilli as the cause of the outbreak is made. from samples of drinking water coliform bacilli, which gave a more complete. typical clumping reaction with every specimen of human Guinea-pigs which were fed. upon living and killed cultures. serum, normal and pathological, with which he had tested of the bacilli acquired agglutinating properties in their. blood. them. He had carried the dilution of the serum as far as I Out of the 29 cases examined 5 gave minimal traces of reac- per cent., but not beyond that. The bacilli that gave this tion at i in ioo against the typhoid bacillus. At lower. dili- reaction were short, actively motile rods, growing rapidly at tions (especially by bringing undiluted serum in contact with the room temperature, and actively fermenting glucose and 9 and I9 drops of culture) some of these gave well-markeck lactose. He had not tested saccharose. Crystals of triple clumping with typhoid culture; so that in the absence 'of phosphate, or a diffuse cloudiness, regularly appeared in old differential tests they might have been returned as having gelatine cultures. He regarded them as excessively attenua- been obtained from typhoid fever patients. ted micro-organisms, perhaps derived originally from a The importance of making use of several different culturesw bacillus coli. for the purpose'of serodiagnosis in vitro (Gruber's reaction) a§x well as the necessity for comparative dilutions is well illus- ON AN EPIDEMIC OF GASTRO-ENTERITIS trated by 'these sera. Only one sample reacted sufficiently, ASSOCIATED WITH THE PRESENCE OF strongly against the race " Gartner" (that is, I in 500)for really: race bacilli A OF THE decisive information. If this and typhoid hadt VARIETY BACILLUS alone been put to the 'test much of the nature of the serums ENTERITIDIS (GAERTNER), and of the epidemic would have remained undiscovered. AND WITH POSITIVE SERO-DIAGNOSTIC EVIDENCE AND from experimental work, it is not improbable that1 (IN VIVO Judging be less IN VITRO). an epidemic caused by the race " Gartner" might easy- to distinguish from enteric fever-by the serum reactions than [ABSTRACT.] in the present instance, for these bacilli are rather more (From the Pathological Laboratozy of the University of susceptible mutually to their respective sera than are the Cambridge.) races with which the epidemic was associated. By HERBERT E. DURHAM, M.B., For controls 28 samples of serum were tested against all the Grocers' Research Scholar. raees above mentioned. None of them reacted at i in ioowith THE symptoms of the cases were similar to those whichl have two of the races obtained from the liver, nor with' the races. been described in outbreaks associated with the presence of Gunther and Vienna. Twelve of these sera were from persons the bacillus enteritidis of Gartner and varieties thereof. who had never had typhoid fever, the rest had either had or About I85 persons were affected. were suffering from that illness.' One of these normnal controls; From a piece of the liver of a fatal case various bacilli were was from a person who was associated with those who were isolated; a large majority of those were found tp agree in affected by the epidemic. ch,aracter with Gartner's bacillus. The preponiderance of The nature of the bacilli found in the fatal case together- these bacilli was suggestive of a causal connection with the with the serum reactions and the 'clinical symptoms in thq- epidemic. Eleven races of these bacilli from the liver were majority of the sufferers affords considerable presumptive. compared with the three other races of bacillus enteritidis in evidence that the epidemic was causally related to the bacilli." my possession-Gartner, GUnther, and Vienna-by means of Several of the outbreaks hitherto recorded have been asso-'; their reactions to the serum of animals immunised against ciated with the meat of diseaseKianimals (espeeially cows).' No- two of these varieties. It was found by this test that they such origin was traceable in the present instanee. resembled the races "Vienna" and " Gunther " more closely More information is required about the distribution, modes, than that of Gartner. of infection, etc., of the Gartner-like bacilli (of which Nocard's Blood serum was obtained from 29 individuals who had psittacosis and Thomassen's bacilli appear tobe va"rieties), not. sIuffered from the epidemic about four weeks previously. only in this country but also elsewhere,,,as in,;ndlia, where-' Differential diagnosis was triad against five varieties of the; choleraio disease is endemic. The observation of Grtunbaum bacillus enteritidis and also against the typhoid bacillus that cases of febrile jaundice miay give "typhoid reaction ,t' At, a dilution of in ibo it was found that i8 of these blood should be kept in mind. srponles- Pve g6od pobitive rea6tion with' one of the cultures 1 [A series of photographic lantern slides *was shown to illus- obtained, te liver toite were pvtefft enoughl to ract at- ,r,ate the morpholoy ofith-e bacilli- found in connection with' Tre' S*I'T. 3, 4801. EFFECTS IOTWAD 'TflBEROLE -BACILLI. SresA JheJoua2iiiUIw tr L

the epidemic-namely, the tendency to form threads on agar, most of my experi-ients on differenrt wtinal:, *bftrnm y of the the characteristic unstained poles in young gelatine cultures, results confirm those of Prudden and Hodenpyl. the abundant flagella, which are not distinguishable from I must also mention that Straus an( Ganialeia3 have to those of the typhoid bacillus in successful preparations. The some extent confirmed the results of the American authors by clumping action of the serum from one of the 'patients upon experimenting on guinea-pigs, rabbits, and dogs'. They say' the typhoid bacillus when brought into contact in low dilu- little about lesions in the liver. They did niot find giant cells tions, such as I to Ic, was also demonstrated.] in the nodules. That may be because in their experiments too few bacilli were arrested in one part, or because the centres of the nodules were not examined. Many of their THE PATHOLOGICAL EFFECTS OF DEAD animals wasted and died. When the clumps of bacilli were broken up and well distributed in the fluid the animals TUBERCLE BACILLI. wasted and died all the same, but no lesions were found. By STEWART STOCKMAN, Evidently several dead bacilli are necessary in one part to . Professor of Pathology, Dick Veterinary College, Edinburgh.' produce a lesion. If the number of bacilli was very small EXPERIMENTS WITH DEAD TUBERCLE BACILLI. tlle animals wasted, then recovered, and appeared, quite' SUCH experiments have been undertaken before. Koch healthy, but if a second small dose were administered they showed that dead tubercle bacilli produced an abscess in wasted and died. By using very small and ever-increasing guinea-pigs when injected subcutaneously. doses of the dead bacillus they immunised the animal against' Prudden and Hodenpyl2 experimented more fully on guinea- it. With the products of the bacillus in artificial culture pigs and rabbits. In their experiments they used dead they could produce no lesion. tuberele bacilli from cultures on glycerine, agar, and broth. TUBERCULOSIS OF THE UDDER. In some of their experiments they used bacilli that had been If one examines a number of tuberculous udders from the freed from their soluble products, but they found that the cow, one generally finds distinct caseous nodules, but that is results were the same whether they used bacilli from agar or not the only form that the tuberculous lesion may asume. At broth, and whether these had been washed free from their the Edinburgh abattoir during the last five years I have found soluble products or not. They concluded that the lesions a considerable number of very cirrhlotic udders without any produced were due to some substance-bacterio-protein-set appearance of a caseous nodule in their substance. On ex- free by disintegration of the microbes in thetissues, orextracted amining these microscopically I have found tuberclebacilli and in some other way. They incline more to the former view. tuberculous giant cells, although the former were not vely- By subcutaneous inoculation they produced an abscess in numerous. For that reason I think that the percentage Qf from two to six weeks. Tubercle bacilli stainable by the tuberculous udders has been slightly underestinmated. These ordinary methods were found in the pus. By intraperitoneal udders, however, will not very much increase the amount of and pleural inoculation with a milky emulsion of bacilli they tubercle-infected milk, because the affected quarters give produced nodules of various sizes on the serous membranes. little or no milk, and the cow is soon0 to be sent the abattoir. These were made up of a central creamy-looking part sur- The bacilli enter the udder by way of the bloodl vessels, and rounded by fibrous tissue. The central part consisted of epi- it is h-ighly probable that at an earlier date there were dis- thelioid cells and giant cells. Tubercle bacilli were abundant tinct caseous tubercles in these udders now eirrlhotic. Two in the central part; well-marked caseation was not found. possible explanations of the difference in these two lesions Intravenous inoculations were made into the auricular veins suggest themselves: of rabbits. The animals were killed and examined at i. The bacilli might have beein overcome by the tissues to intervals of from one to sixty days. A few died after such an extent that they could no longer produce distinct the third week. In animals killed after one day the caseation, but were still able to excite a proliferationi of the bacilli were found in the lungs, liver, and spleen, tissues anid cause the formation of giant cells. most abundantly in the first-mentioned organ. The older 2. The bacilli might have arrived in the gland in anl attenu- the tuberelethe fewerseemedtobethebacilli. Afterfive days ated condition, and were thus no longer able to produce the white nodules were found in the lung, some being micro- distinct caseous lesion. scopic, others quite visible tothe eye. Theywerepresent upto There is nothing wildly imaginative in these suggestions if the sixtieth day, the longest periodof observation. Thleirstruc- we think on what we know of the tubercle bacillus. It iswell ture consisted of epithelioid cells, giant cells, and leucocytes. known- that the bacillus first acts by excitinig a proliferation Bacilli were found between the cells and inside giant cells. of the tissues. The new cells, instead of completing their Later the nodule was denser and made up of epithelioid development, however, tend to become caseous. Still, we cells and loose connective tissue. After three weeks know that the cells do sometimes complete their development microscopic nodules, apparently having their origin inside the and form fibrous tissue. This is especially the case in the old capillaries, were found in the liver. After five or six weeks tubercles found in the ox and pig. They are often surrounded visible nodules were found in the latter organ. Prudden and by a rim of fibrous tissue, whichl is inivading, the caseous Hodenpyl conclude that the nodules originate in a prolifera- centre. Moreover, the tuberclilous lesions of the muscles- tion of time vascular endothelium under the stimulus of dead muscle is considered a bad i-ediuin for tlle growtlh of the and disintegrating tuberele bacilli. They say that "the dead tuibercle bacillus-which I have (lescribe(d in the pig were bacilli seem to aet as foreign bodies simply, curiously distinctly fibrous.' stimulating, it is true, but only foreign bodies after I may say, too, that I have once fonIIId ttibercle bacilli in all." I think too much is made here of the foreign body fibrous nodules under the mucous membranie of the fourth question. Everyforeign body does not produce this tissue stomachl of the ox, anid have several timies founid them in reaction, although the power to do so may not belong exclu- fibrous thickenings on the subearpal regions of the ox. These sively to the tubercle bacillus. The action of the dead are mainly the observations which lhave led mne to unidertake tubercle bacillus is in large part, at least, special to it, and it these experiments. is the foreign body of this order that we are most likely to Experiment I.-Irish terrier bitchl. I began to experimnent oni thiis animal meet with in the for tie purpose of trying to render lheiciimmine against tluberculosis by tissues. using the toxin and dead bacilli. I first injected her with tuberculin il At the conclusion of their paper these authors offer some doses ariving from i c.cm.tio o3 c.cem. Ther e w.as no tcipergtiitue reactiol. suggestions as to the influence of the products of the living 1 thicnl conitiniued with inijections of the products of the tuibercie bcilhis in germ on the degenerative changes in a true tubercle. They glycerine brothi, fromil which the miicrobes hiad beoen separate4Aby filtialtioAi through porcelain without previous hle.ating. Thi1e' (ctiltuires were, llowed suggest, too, the possibility of the more fibrous tubercles being to go for from 2 to 2' monthis a.nd longer. Beginniniig with-6.ce,exm.. I due to dead bacilli. welit to I0, 20, 40, 50, 95 c.cm. without disttirbinig thie- animal at all. Curiously enough it was that last idea and a wish to further With 95 c.em. the temperature rose o.80 F., but wa1s not above the physiological limits (102.6). I next gave her T90 cem. into 'tl'e ssels test an opinion which I had formed as to the origin of tuber- and under the skin. This toxin came from a gZl m1onitlhs' ciult'ure.. it pro. culous giant cells, that led me to undertake some experiments duced a rise in temperature of TO F. in 6l hlouis. TIThis slows tle feeble with dead baciili. I had conceived the idea and started ex- systemic effect of the tubercle toxin. TAinking th'at thle to.xin prepaled with knew of their paper. in the ordinaly way was too weak to, produce nimichi effect; for there perimenting dead bacilli before I followed no local lesion whatever-it thus difrels froil' thVe powerful diph- I have since read it very carefully, and wish here to acknow- theria toxin-I thought of trying th.e -effects of de'ad *Jnc;4er the ledge my indebtedness to the' authors. I have performed skin of the clhest region I inijected A thif eniulsion''b8rtlli.of Itub&dcle bacilli THE BRITISH 1 6o260 MFDIC4,LE1- JOURNAL]ORAL SECTION OF PATHOLOGY. LSEPT.SP.33, i898.88 killed by tlhree hours' steaming. The bacilli caine from a glycerine animal's hind leg. He killed her twenty days afterwards and was broth culture that had beei kept for for five months. An abscess formed good enough to let me have the lungs and portions of the iiver. The and burst tlhree days afterwards. A nionth later a second injection of lungs contained many sinall, flrm, greyish nodules, about the size of a bacilli in thick emulsion was given under the skin. The latter came pin's head. The liver showed no alteration to the naked eye, but the from a glycerine broth culture that had been in tlle incubator for four microscope revealed small cellular collections identical with those found months, and afterwards killed by three hours' steaming. On the third at the start of an ordinary tubercle caused by the living bacillus entering day a swelling about the size of a hen's egg formed at the seat of inocula- by way of the blood vessels. The temperature of this animal did not rise, tion. The skin over this abscess was asepticised, and some pus was but I think too few bacilli were used. aspigated into a sterilised syri nge by passing its needle into the cavity. Experiment II.-An aged pony was tested with tuberculin on February Cover-glass preparations made with the pus sinmply swarmed with tubercle I7th, I898. It did not give any reaction. The normal temnperature was bacilli; no other microbes were present. Glycerine agar tubes sown with 99.80 F. On February i8th two cultures of the B. tuberculosis in 55 c.cm. the pus remained sterile. The abscess then was caused by the tubercle of glycerine broth, which had been incubated for two months, were killed bacilli, which were beyond doubt dead. The abscess burst on the fifth by submitting them to the boiling temperature for one hour. The fluid day, and the wounds took a considerable time to heal up. The tempera- was pipetted off until the bacilli were left as a thick emulsion. As one ture rose to 1050 F. on the morning after the second injection. It fell to can understand, the microbes were very numerous. At 4.30 P.M., the 101.50 on the sixth day. On the afternoon of the sixt-h day 30 c cm. of a bacilli fronm the two cultures were injected into the left jugular vein of filtered tubercle culture were injected. The temperature next morning the pony with all antiseptic precautions. had risen to 104.50, and had fallen to 1020 the day after. Three weeks after the second injection of bacilli I injected subcutaneously about 4 c.cm. of CHART hI. the dregs left in the preparation of tuberculin. This material was very rich in bacilli, which had been killed at about xIO° C. Five days after- wards there was slight swelling and tenderness. but no distinct abscess F E B R U A R Y M A R C H I formed. The temperature rose iO on the day after, and fell to the normal T on the fourth da Dat One might draw the following conclusions from this experi- ment: (i) That the soluble products of the tubercle bacillus 105 produce little effect on the healthy organism, although they have a very decided action on animals whose bodies contain the tubercle bacillus, living or dead. (2) That the dead 104 bacilli are far more active than the soluble products, although this way be on account of their retaining a strong toxin in t'leir bodies. 1l03' This bitch ran about and enjoyed perfect health for ten months afterwards. I was anxious to see if she would still react to the dead bacilli. On the 22nd Marchl of this year the daily temperature ranged between 102' xoi.80 and 102.40 E>. She received into her jugular vein the greater part of the bacilli from a 2 months' culture of the tubercle bacillus in 50 c.cm. of glycerine broth, which has becen sterilised at IIOO C. 23rd March. Temperature 105.50. Animal rather dull. 101 24th March. Temperature Io4O. Aniimal briglhter. 25th March. Temperature 0o3.80. Animal brighter. 26th March. Temperature 1030. Animal apparently quite well. Up to the 3rd April the tenmperature fluctuated between 103.20 and lUV 103.40 F. From the 4th to tlhe 8tlh April the daily temperature at 12 o'clock was I0240.. On the gth April (i7 days after), at 9.15 a.m., when thetempera- -i ture was 1x0.60 F., 20 mm. of the dilute tuberculin were injected. My reasoni for starting at this hour was, of course, to get the observation over in one day. The above chart shows the temperature reaction after the inoculation, The ainnexed chart shows the temperature reaction. and also the result of the tuberculin test applied three weeks afterwards. The reaction was 0 F. It will be seen that the temperature after the injection of dead bacilli fell to the normal just about the time that it CHART I. should have been rising had the animal been inoculated with living bacilli. The animal was afterwards killed for the dissecting room, twenty-five days after the bacilli had been injected. Necropsp.-The lungs were simply studded with small white nodules. varying in size from a pin point to a pea. They to some extent resembled miliary tubercles, but they differed from them in being T T denser and less yellow. One or two small areas about the size of a bean were very solid and of an amber colour. The latter much resembled the larger nodules that one finds in the lungs of sheep affected with parasitic pseudo-tuberculosis. There was also slight broncho-pneumonia. The jugular vein at the seat of inoculation showed a nodule in its wall. This nodule was about the size of a Pea nut. It was comparatively firm, but showed one small softened centre. Cover-glass preparations made with the softened material and stained by carbol showed numerous bacilli. None of the other olganis showed lesionsfuchsin,visible to the naked eye. With several nodules from the lungs guinea-pigs were iiioculated into the peritoneal cavity. They did not become tubercl ous. The bacilli then were dead. Microscopic.-The lung nodules were made up chiefly of epithelioid cells 1U_ ibe -w n and loose connective tissue, containing a good many spindle cells. There C.7 were a few giant cells in some of the nodules. These giant cellst however were fewer in number and not quite so distinct as those found in naturai cases of tuberculosis. Numerous bacilli were present between the cells of the nodule, either as single rods or in clumps. At some places they assumed a somewhat circular arrangement, such as one often finds at the periphery of the giant cell in an ordinary tubercle. The bacilli were easily stainable by the ordinary methods used for the tubercle bacillus. There 1.20, go much was no distinct caseation, but there were some very small homogeneous The variation was thus but it did not patches which stained difusely. beyolnd the physiological limits. The results of tuber- The best method of showing the giant cell is to stain with picro- culin in the dog, however, have not been satisfactory, so carmine a section cut on the freezing microtome. It is difficult to find the test on 15 them in thin sections cut in paraffin, although distinct giant cells are well far at least. Cadiot records the result of enough seen in sections of ordinary tuberculous nodules cut in the latter tuberculous dogs. The rise in temperature amounted to way. Contrary to :what one finds in the ordinary tubercle. those caused from 0.50 to I.70 C. In 8 cases the temperature rose no by the dead bacilli are vascular. The lumen of the small artery, however, more than IO. In 3 cases there was no rise, but a diminution is oftenl nan-owed by a per-iarteritis. The nodule in the wall of the vein had a similar appearance to of temperature followed by death. those found in the lunig. The cellular centre however, was mliore ex- The animal was killed four months after intravenous injec- tensive, and tlhere was a tendency for it to drop out of uneinibedded tion of dead bacilli. The pleura showed .a large number of sectioiis. It seems to me that the giant cells are most numerous in the larger fibrous nodules which contained no bacilli. There were no nodules, and tllese conitain the greatest nuumber of bacilli. distiniet nodules in the lung. The liver showed numerous I attempted to repeat this experiment on another horse, but tuberculous nodules. the animal died of embolism, in great part, I think, due to air Experiment Ia.-Spaniiel bitchl. With a view to raising tIme tempera- turefoi acertainexper-iment of hiis own, Dr. Noel Paton injectedsomne bubbles in the fluid. dead tubercle bacilli into the external saplhenia vein of this I have now another animal under experiment, I will inject SEPT. 3, IS98- EFFECTS OF DEAD TUBERCLE BACILLI. - 3)' 1898.1~~~~~~~~~~~~~~~~~E IMEDICALTE BRSHJOURN'AL60603 him with tuberculin at several intervals in order to see if he small number of active ones, too few to be easil found in will cease to react. sections. One cannot say but what a few living bacilli may Experiment III.-This experiment was undertaken to see whether a very be as powerful as a large number of dead ones. Again, it large number of dead bacilli in one part would not produce distinct caseation or a more plentiful formation of giant cells. For the experi- might be that the tissues have overcome many of the bacilli ment I uised tubercle bacilli that had been incubated in glycerine broth in certain nodules, and prevented the changes from going for two months and then suibmitted to a tenperature of about 11O0 C. for further. 'Tle dead bacilli experimentally injected certainly half-an-hour. The dead cuilture lhad been kept for nine months and it nodules, and we may expect was sterile. On April 20th a dense emulsion of these bacilli was inijected do in time disappear from the (lirectly into the Inioig, througlh the clhest wall, using a very fine ileedle those killed in situ to do the same. In the centre of the so- From April 20th to May 2nd the temnperature ranged between ioo.80 and called giant-cell one may find a single stray nucleus; usually 101.30 F. Tlhe aniinal was well a,nd lively all the tine. This cat was killed only cliromatin substance, but even that may have by chloroform oni Ma,y 23rd, about one montlh from the time of inocula- one sees tion. A large nodule about the size of a pea nut was found in the lung. disappeared. Many of the nuclei at the margin are breakilng The nodule was niot caseous. The pleura was quite normal. The lung up. It is at the margin of the giant cell that they are mainly nlodule was fixed in corrosive sublimate for microscopic examination. found, and they may be to the number of twelve or more. If Microscopic.-The nodule was made up of epithelioid cells and spindle cells. There were very few giant cells, not onie distinct. The bacilli these nuelei be earefully looked at, one often sees that they aro were very nlumerous. There seemed to be less fibrous formation than in in reality surrounded by the cell bodies in different stages of the horse. The lung of thle cat is, I think, not so well suited as that of degeneration. This is best seen in the tubereles provoked by the lhorse for the study of giant cell formation. Pulmonary tuber-cle of the cat is often in the form of bronchlo-pneumonia without distinct the dead microbes, possibly because the caseation is neither niodules, but of this I do not wish at presenit to make too much, as I lhave so rapid nor so marked as in the case of active living bacilli. not had the opportunity of studying miany cases. In some of the former one can see contiguous cells Experiment IV.-The object of this experiment was to see whether the caseous bodies not yet fused. Their nuclei are (lead bacilli would act tlhrouglh the alimentary tract or not. So far as I with kinow this las never yet been tried. Tlhe importance of sucll experiments is still present, but show up less distinetly. Some of the great, because once we lhave boiled suspected milk or flesh we consider latter are in capillary vessels, and seem to arise from the thliat the daniger is past. For the experimeint I used a veiy young kitten, endotlielial cells. As easeation extends, other eells at the peri- as they are consi(lered easy to infect witlh tuberculosis by tile ingestionl of the cells first struck with miietlhod. On April 25th a kittein, six weeks old, received aboiit io c.cmi. of plhery are ineluded. The nuclei the emulsioni used in Experimeint III. Tlhis kitteni must hiave swallowed degeneration beeome disintegrated, while fresh ones are taken millions of dead bacilli. Sle lived in perfect healtlh unitil May 23rd, when up at the margin. By-and-by the degenerating pateh may slie was killed by clhloroform. All the organs appeared healthy. The and mesenteric glands and portions of the ileumiii were fixed in corrosive sub- inerease to suCh an extent that the cell-like form is lost, limate ior microscopic examiiination. They were founiid perfectly normal. it takes the appearance of a easeous area. Some of the cells Sections stained by carbol fuchsin slhowed not a single bacillus. included at the margin resemble certain of the white blood Experiment V.-A cat received by the moutlh laige doses of dead bacilli These may be phagocytes that have come out to ait intervals of several days. Whleni killed two milonths afterwards the corpuscles. ainiimal slhowed no signs of tuberculosis ill the miiesenteric glanids or surround the dead patch and have perislhed in an attempt to organs. No bacilli were found. digest the bacilli. These experiments seem to sliow so far that one may with SIGNIFICANCE OF THE GIANT CELL. impunity drink milk containing dead bacilli. That, of course, It is usually accepted that the tuberculous giant eell is the does not mean that cows with tuberculous udders should be result of a multiple division of the cell nucleus without a tolerated in byres. They also suggest the possibility that corresponding division of the cell protoplasm. By tuberculous some of the very chronic lesions in animals eontain only dead giant cells I mean the apparently multinueleated bodies with bacilli. To decide thlis, of course, one would have to inoculate a yellowish centre. I do not think that the multiple division products obtained from a large number of these lesions in theory applies to the giant cells found in animals. I cannot question. The production of a lesion in the abdominal organs see how degenerating cells, for such they seem to be, could be of guinea-pigs would not in all cases be enough to prove the capable of performing a function which is usually regarded as vitality of the bacillus, because one might possibly inject a a proof of vitality, namely, reproduction. sufficient number of dead ones to act. Artificial culture on Moreover, I have never observed mitosis in well formed glycerine agar, however, would decide the question. tuberculous giant cells. This, however, is not an insuperable REFERENCES. objection, as they might divide by another method. 1 Most of the work in this paper lhas beeni donc in the Laboratory of the I have seen several cells together apparently taken with Royal Colleger of Physicians of Ediniburgh, and(i I wislh liere to acknowledge my indebtedness to that illstitUtionl. 2 NVewV York illedical Journal, June degeneration in the act of nuclear division. The nuclei of 20tll, Il89. 3Arcih. (lC lied. Lxp. ct (I'Anat. Pat/h., 1891. 4 Veterinarian, these, however, were very indistinct, and their degenerate Maric-, I896. bodies had not yet completely fused. I do not think that the so-called tubereulous giant cell is really a cell, but that it DIscussioN. is simply the eommencement of caseation. I would explain Professor McFADYEAN said tllat Professor Stockman's experi- its formation somewlhat thus: Wlhen the tubercle bacillus ments were of considerable interest, though he did not think arrives in an organ it begins to multiply and stimulates the that the results obtained were very closely related to any- cells to proliferate; a nodule is the result. The bacilli will thing encountered in natural cases of tuberculosis. He be- be most numerous in the part where they are first arrested. lieved that the formation of lesions witlh dead tubercle bacilli Their products will there be more concentrated, and one may followed only when colossal quantities of the bacilli were reasonably expect to get the most marked initial changes at introduced. He could not agree that the formation of giant that place. Now, the local action of the living tubercle bacilli cells was similar to caseation, whiclh was an effect produced on the tissues is to produce caseation as well as to eause pro- only by living baeilli. liferation, and the former will begin where the microbes are Dr. WOODHEAD said he was interested in this paper because most numerous. The cells in the neighbourhood of the a series of experimeints whichl it had fallen to his lot to carry bacilli, then, will be the first to undergo caseation; their out had given a number of " bye results," if he might so say, bodies stain yellow with piero-carmine. The nuclei resist which had a bearing on the question. He found that dead longer, and they, along with broken up chromatin sub- baeilli injected locally set up a local lesion in which the stance, can be seen for a considerable time in the degenerated bacilli could be stained. From this lesion, however, no patch. secondary infection could be obtained. Injected into the It is known that the nucleins are not acted on by the veins, these dead bacilli madle their way principally to the gastric juice digestion, and can thus be separated from tissue lungs, where non-caseating, fibrous nodules were formed. cells. Possibly they are less easily acted upon by the toxins These nodules contained no infective material, and secondary than the cell bodies, and hence their persistence. In further lesions could not be obtained. The bacilli, when not quite support of this view of tlle giant cell I would point out that dead, still set up fibrous and non-caseating lesions. colonies of bacilli are frequently, thouglh not always, found Professor GREENFIELD said tllat the previous speakers had around the margins of the so-called giant cells, and in the practically acknowledged the existence of a possible flaw in tubercles produced by dead bacilli intravenously injected in their experiments. He asked if it were not possible that tile horse the giant cells seem to be most numerous where the some of the bacilli, supposed to be completely devitalised, bacilli have been arrested in clumps. The apparent absence might be still living. Froml his own reading, however, he of bacilli from the neighbourhood of certain giant cells might had been led to the conclusion that dead bacilli undoubtedly be explained by supposing that the damage was due to a very might produce elementary tuberele follicles with giant cells. 8 THE BRITISH 604 "MDCA jl-XL SECTION OF PATHOLOGY. [SEPT. 3, I898. TIe asked at wlhat period of time the lesionis described by the total number of leucocytes in the circulating blood in- Professor Stockman were found in the liver after intravenous crease, or is there simply an accumulation in the peripheral injection. HIe tllought it unnecessary to assume that the bacilli vessels from which blood is usually drawn? Recent producinig them must have beeni living, as it was quite pos- observations, of which those of Goldscheider and Jacob may sible for dead bacilli to pass through the pulmoonary capil- be mentioned (with which my own, so far as they go, agree), laries and lodge in the liver. slhow that the increase is a general one, and that in the peri- Professor MCAVEENEY inquired wlhetlher Professor Stockman pheral vessels there is the same proportionate excess over the had determiiied the virulence of his cultures before injectilng number in the blood of the heart as there is in the normal them. The saml-e effects could hardly be expected to result condition. There occurs therefore in leucocytosis an increase from the presence in the tissues of virulent as from that of of the total number of leucocytes in the circulating blood, or, attenuated organiisms, even thouah they had previously been in other words, an addition of leucocytes to the blood. devitalised. lle was of opinion that a determination of the Further, in the case of suppurative arid allied conditions, virulenee of the bacilli in the living state would be of great there occurs an enormous emigration of leucocytes from the value in the interpretation of results obtained by the injec- vessels, so that we see, for example, in clinical eases, several tion of devitalised cultures. ounces of pus discharged daily, and during this time, be it Dr. MOTT suggested that in the case of fibroid nodules pro- noted, the number in the blood is much above the normal. duced by organisms presumably devitalised, inoculation ex- In such conditions, where there is a continuous drain, and at periments should be made from them in fresh aiinilals. the same time an excess of leucocytes in the blood, the produc- tion must be much in excess of the normal. In the case of leucocytosis following injections of chemical substances there A DISCUSSION ON must first be an addition of cells to the blood, but after this addition has taken place it does not necessarily follow that it THE NATURE AND SIGNIFICANCE OF requires an increased multiplication to maintain it, though LEUCOCYTOSIS. such may occur. There are two points which also must be kept in view: (i) I.-ROBERT MUIR, M.D., F.R.C.P.Edin., The variety of leucocyte in excess in these conditions is almost Lecturcr on Pathological Bacteriology, Edinburgh Uiiiversity. exclusively the finely granular (oxyphile or neutrophile), ac- INTRODUCTORY. tively amoeboid leucocyte, with polymorphous nuCleus; (2) THE subject of the discussion which I have the honour of the enormous rapidity with which the leucocyte increase opening is at once one of the most important in modern occurs-namely, a doubling or more of the normal number in pathology, and has also a most important bearing on clinical a few hours. diagnosis and prognosis. It is, moreover, one which has very VARIETIES OF LEUCOCYTES.-THE ORIGIN OF THE FINELY wide connections, being on the one hand elosely involved GRANULAR LEUCOCYTES. with the tissue changes usually grouped together as iiiflamma- [The varieties of leucocytes, as met with in the blood of man tion and, on the other hand, intimately related to the defence and animals, were shortly described]. The distributioh of of the organism against noxoe of various kinds, especially these varieties is also of importance, but I wish specially to against microbes. The subject is, in fact, so wide, that on refer to the chief sites of multiplication of leucocytes, as this such an occasion as the present it can only be treated in one seems to me a point upon which sufficient stress has not been or two of its parts. The object or meaning of local increase, laid. In the first place, as everyone knows, leucocytes emigration of leucocytes, and their subsequent behaviour multiply by mitotic division in lymphoid tissue, lymphatic would imply in its discussion a consideration of the whole glands, Malpighian patches of spleen, solitary glands, etc. question of phagocytosis and of the bactericidal or other The cells there undergoing division are small spherical cells, antagonistic properties (direct or indirect) of the substances with relatively large nucleus and rather scanty hyaline pro- secreted by or contained within these cells. And further, the toplasm. These cells give rise to lymphocytes, which leave observations on the modification in the number of leucocytes by efferent paths, and a certain proportion reach the blood by within the blood as a whole, or the modification in the the thoracic duct. Secondly, leucocytes undergo division in number of different varieties, as observed clinically, are now the bone marrow. The great proportion of cells dividing so numerous that a consideration of them would occupy much there are of somewhat larger size than in the germ centres, longer time than I have at my disposal. Somne of these ob- and their protoplasm eontains fine granules whieh have a servations must be incidentally referred to, whiilst other definite (oxyphile, neutrophile, etc.) reaction. The coarsely speakers may refer to them in greater detail. I shall take as granular eosinophile cells also multiply in the same position, the main subject of my remarks the nature of leucocytosis as though they are fewer in number, and their multiplication is a process in general pathology. What is the fundamental less active, than is the case with the former variety. Now it change on which the leucocyte excess depends, and what is is to be noted that division among the finely granular cells in its standing in relation to the question of tissue reaction? the marrow in normal conditions is very active; in fact, so far as I have seen, as active as in the germ centres of DEFINITION OF TERMS. lymphoid tissue. How do the leucocytes derived from these The term leucocytosis may be applied to any condition in cells leave the marrow? One naturally concludes by the which there is an excess of leucocytes over the normal, blood stream, but in the blood stream there'are no cells with whether in the tissues or part of the vascular system, a local spherical or oval nucleus and with fine granules in the proto- leucocytosis, or throughout the circulating blood, a general plasm, which have the same reaction. Examination of the leucocytosis. We shall first speak of the latter. The general marrow shows, however, that the cells there present show great facts are well known-that in many acute inflammatory con- variation in the configuration of the nucleus, and, in fact, one ditions, occurring naturally or experimentally produced, such can trace all the intermediate stages from the simple rounded as pneumonia, erysipelas, etc., and especially in suppurative or oval nucleus through various degrees of lobulation to the conditions, the number of leucocytes in the circulating blood markedly multipartite nucleus of the finely granular, actively may be two- or three-fold the normal, or even more. Further, amoeboid leucocyte. And, if one examines sections, one can a similar condition may be produced by the introduction into see that leucocytes of this character are normally found in vary- the body of various chemical substances, of which the most ing number at the periphery of the blood channels, whilst the important classes may be said to be (a) bacterial products, larger cells from which these cells, in my opinion, spring, are, especially the so-called bacterial proteins; (b) extracts of as a rule, further removed from the blood stream. According various organs or tissues rich in cells, such as spleen, bone- to this view, then, the finely granular cells after division marrow, etc.; (c) a great variety of definite organic compounds undergo this peculiar change in the nucleus which specially -for example, peptone, curare, nucleic acid, etc. Leucocy- suits themfor amceboidmovements, and enterthe blood intheir tosis produced by such substances is sometimes spoken of as fully formed condition. I may add that I have failed to find toxic leucocytosis, but in its essence is closely related to that any amceboid movements in the larger cells in the marrow. occurring in inflammatoryconditions. One questionhas been The acquisition of this property would appear to be developed raised which must first be answered-namely, is the leucocy- parn passu with the change in the configuration of the tosis occurring in the conditions mentioned real ? that is, dces nucleus. THE --BRITIS 6 SEPT. 3, 1898.] DISCUSSION ON LLEUCOCYTOSIS. NtIrCDICAL JOURNAL 605

Another fundamental question in the inquiry is whether One cannot, I think, study the phenomena wliich follow, for any formation of the finely granular leucocytes with poly- example, ilitraperitoneal injection of various bacteria,without morphous nucleus takes place in the blood from the larger recognising that this process must be at work. Granted then hyaline forms witlh simple spherical nucleus. There is no a chemotactic substance, it may be -in such quantity as only doubt that in the latter, indentation and a certain amount to act locally-in othier words, we may have a small' local of lobulation of the nueleus may be seen, but does the inflammation or suppuration without leucocytosis, but. if tlle change go further It will be found that authors disagree local lesion be more extensive, then these substances which markedly on this point. At one time I considered that I produce chemotaxis are absorbed by the blood stream in such could find in humani blood transition forms between the " uni- quantities as to act on the leucocytes lying at the periphery of nucleated" and "multinueleated" leucocytes, as they were the blood-stream in the bone marrow, and the result will be a formerly called, but such transition forms appeared to be ex- general leucocytosis. This is in all probability the firs't factor ceedingly scanty and apparently quite insufficient in number in the production of the leucocytosis quickly following theli- in leucocytosis to account for the large number of multi- jection of chemical substances inito the circulation. But there nucleated forms. If we investigate the question in the blood is also tle increased multiplication of finely granulat leuco- of the rabbit in which the corresponding cells have the blasts (marrow cells), and this is probably due to a stimulat- granules much more pronounced, I think it will be impossible ing effect whlich these substances exert on the cells -it cet- to observe transition forms, in fact, the whole appearance tainly cannot be explained on any mechanical principle. We during the occurrence of a leucocytosis is as if a large have therefore the local leucocytosis and the general leuco- number of cells of exactly the same kind were rapidly added cytosis induced by tile same agency. This view very closely to the blood. On carefully considering, on the one hand, the corresponds with what Ehrlich and Lazarus have adopted in character of the cells in the blood, and, on the other hand, their latest publication.1 I may say, however, that. I have the eells in the marrow, there ean be little doubt---in my arrived at these conclusions quite independently, and that, so mind there is no doubt-that the polymorphonuclear leuco- far as I know, the changes referred to in tile bone-marrow cytes are formed ehiefly, if not entirely, from the latter, and have not been previously described. enter the blood stream in their fully formed condition. In interpreting the phenomena we may tilen say: (i) That the local leucocytosis is a most important means of defence; LEUCOCYTOSIS IN INFLAMMATORY CONDITIONS. (2) that the proliferative changes in the bone-marrow are the We must now pass on to the consideration of the evidence means by wlich the leucocytes concerned may be supplied in of increased multiplication of leucocytes in inflammatory large numbers at any given place of need; (3) that the leuco- conditions associated with leucocytosis. I may state, in a cytosis in the blood is an indication at least that this supply word, that neither in the tissues nor in the blood stream is is being maintained. We may also mention that the vqscul!ar there evidence of multiplication by mitosis amongst the arrangements in the marrow are such as, on the one hand, to polymorphonuclear leucocytes to account for the increase. permit a ready action upon its cells of chemotactic sub- The question regarding direct division is a difficult one, but stances circulating in the blood, and, on tile other land, to liere again facts are entirely wainting to show that such a allow a free and rapid passage of the cells into the blood. process plays an important part in the changes which occur. It is to be noted that chemical substances must be the If these conclusions are justified, an important question arises means by which a general leucocytosis is brought about, and -namely, Are any important changes found in the bone- tilerefore it is not surprising that, it can be produced where marrow when there is a constant drain on this variety of there is no local inflammatory lchange. Wliether in such a cell; in other words, when there is an inereased production case the leucocytosis really acts as a means of defencel by of this form of cell ? To answer this question I have made a combining with toxins in the blood, for example, in the considerable number of experiments, and shall briefly detail leucocytosis following injection of diphtheria toxin, must still the results. These experiments consisted in producing leuco- be considered an open question. Another question worthy of cytosis, or at least a removal of leucocytes from the blood, by study is whether, and if so to wliat extent, degenerating or subcutaneous or intraperitoneal injections of organisms, broken down tissues act as chemotactic agents in the produc- chiefly staphylococci. The experiments lasted for various tion of a general leucocytosis. periods of time up to four weeks and a half. The results are somewhat striking. I find that there occurs an important RELATIONS OF THE FINELY GRANULAR AND HYALINE change which is readily recognisable. This change consists LEUCOCYTES. in a general absorption of the fat of the marrow and a corre- I have said that in view of their chief sites of multiplication sponding hyperplasia of cells ; and, further, the important the great majority of leucocytes fall into two seiies, one in- point is, that the cells increased in number are the large cluding the lymphocytes and hyaline cells, the other includ- finely granular cells whieli may be called finely granular ing the finely granular leucocytes iand the finely granular leucoblasts, and whieh are the source of the finely granular leucoblasts of tile bone marrow, with possibly the eosiao- leucocytes. Tile number of mitotic figures present shows that phite series, (Tile consideration Qf the, relaion of basophiles these cells are undergoing rapid multiplication. The eoarsely has, necessarily been omitted; tiley certainly play a minor granular eosinophile cells are relatively, and it may be abso- part in the questions under consideration.) An important lutely, diminished. Erythroblasts or nucleated red corpuscles question, and one exceedin-gly diffiqult to answer, is whether are also much diminished. The giant cells may undergo de- or not hyaline cells acquire granules as they lie in the bone generative change and in great part disappear. (These cells marrow and become finely granular leucoblasts,. This is a do not contain granules, and are probably derived from the question which I am not prepared to answer, either in the larger hyaline cells.) The marrow in such a condition pre- affirmative or in the negative, but one must note, first, that sents a striking deviation from normal, and the change may during a prolonged leucocytosis mitosis in the finely grular be said to be of a corresponding nature to what occurs in the leugoblasts is sufficient to account for the leucocyte increase; erythroblasts after hlemorrhage (great increase intheirnumber and secondly, that although hyaline cells rare normally pre- an-d increase in the mitotic figures). If we call the latter the sent in the bone marrow, these do not become i.ncreased dur- " erythroblastic " type of marrow, then we may call that which ing leucocytosis. Whilst, then, the transformation is quite I have described the "leueoblastic" type of marrow. This possible, I have not found s.ufficient eyvidence from my ex- fact appears to me to throw light on the whole subject. If we periments that it plays an important part in. the pheno- consider the finely granular cells as a class say in a case of menon of leucocytosis. suppuration we find (a) locally an enormous number of finely Another point of importance may be referred to, namely, grallular leucocytes (pus corpuscles); (b) in tile blood a great that if we consider the two series of leucocytes as above increase in the number of the same cells; and (c) in the mar- described, and suppose an excessive proliferation of -one or row a great increase in the cells from which these leucocytes other, we have an explanation of the two forms of leuco- are derived. cythaemia. In the one form, as is well known, there is an Furthermore, it is very probable that the same cause would increase in.the blood and tissues of the lymphocytes, and it explain all tllese phenomena. It must now be accepted that may be of the larger hyaline cells. In the other form we h4ve bacterial products act as ehemotactic substances, and are the an increase of the. finely. granular leucobjasts (marrow cells). chief agents in the leucocyte emigration and accumulation. 1 Die Anumie, in Notlinagel's Specielle Pathologie und Tl&6rapie. THE BRITIsH 1 606 MEDICAL JOURNALJ SECTION OF PATHOLOGY. LSEPT. 3, I898. and an appearance of them in the blood, and at the same time EOSINOPHILE LEUCOCYTOSIS. a great increase in the number of finely granular polymorpho- Though leucocyte increase is usually due to increase in the nuclear leucocytes. finely granular leucocytes, attention has been within late LEUCOPENIA. years drawn to the conditions in whlicll eosinophile leucocytes. A few words must also be said with regard to diminution are proportionately in excess, thoughl the total number of' in the number of leucocytes- leucopenia-and we may coIn- leucocytes may be little increased-tlhe condition known as sider, first, the fall which may occur withi comparative " eosinophilia." Local accumulation of the eosinophile cells rapidity in inflammatory or infective conditions, or on the is common in a variety of conditions. I have observed it in introduction of certain chemical substances into the blood. various abnormal conditions of epithelium, for example, in Here, it is to be noted, the fall is chiefly, sometimes almost atrophie conditions of the gastric and other mucous mem- entirely, on the part of the finely granular polymorphonuclear branes, around cancerous growths, especially some varieties leucocytes. One may summarise thus the circumstances on of epithelioma; in some forms of malignant glandular affec- which this fall may depend: tion allied to the lymphadenloma; also in some subacute First, the rapid fall after the injection of various chemical iniflammatory conditions, for example, in organising serous bodies is due in great part, if not entirely, to the accumula- inflammations, and even in the wall of abscesses. In various tion of leucocytes in the capillaries of various organs, espe- affections of the skin, pemphigus, psoriasis, and several cially of the lungs. This has been proved by the experiments others, the number of leucocytes in the tissues may be very of Surgeon-Captain D. Bruce, of Goldscheider and Jacob, as great. And further, it has been observed that in bronchial well as my own. It can readily be demonstrated. Therefore asthma the leucocytes in the bronchial secretion are chiefly one may say that the rapid destruction of leucocytes supposed eosinophiles. The discussion of the behlaviour of these cells by Lowit to occur in these circumstances has at least not been would occupy muclh too long, but it is interesting to note that proved. a close analogy can be drawn between this form of leucocytosis Secondly, after injections-for example, of organisms into and the ordinary formn. There may be local accumulations of the the peritoneum-the fall may be due in part to accumulation eosinophile leucocytes without increase in the blood, but on of the leucocytes in the capillaries of the mesentery, peri- the other hand if the area affected, for example a skin lesion, toneum, etc., and in part to the emigrationi of leucocytes into be extensive, there may be an eosinopliile leucocytosis in the the peritoneal cavity, the latter occurring very rapidly. It is, blood. It is to be observed also that large eosinophile cells therefore, possible that a suddeni extension of the inflam- witlh simple nucleus are normally present in the marrow, and matory lesion may produce a fall in the number of leucocytes. that mitotic figures may sometimes be observed in them. So (Where, however, the inflammatory change is more gradually also in the medullary form of leucocytliemia these cells, botlh developed, as in most clinical cases, leucocytosis may not be the eosinophile marrow cells and the smaller eosinophile preceded by leucopenia.) leucocytes, may be implicated in the leucocyte increase. Im- Thirdly, in severe septic2mic and toxic conditions ani portant questions in connection with this subject are: DO enormous leucocyte degeneration and destruction can be finely granular leucoblasts ever become eosinophile leuco- traced in the spleen and to a less extent in the bone marrow, blasts, and do the finely granular leucocytes in tile blood or in and in certain circumstances there is great leucocyte accu- the tissues became eosinophile leucocytes ? Some facts sug- mulation associated with phagocytosis in these situations. gest that these two varieties of granular cells are closely related The removal of leucocytes from the blood stream by to one another, whilst others show that to a certain extent. their being entangled in coagula forming in the heart they behave as if they were independent. The great diminu- before death-for example, in pneumonia-may also be complete disappearance, in the blood in acute inflammatory mentioned. tion in the number of the eosinophiles, and it may be sometimes Fourthly, the fall may be due to interference withl the pro- leucocytosis is also worthy of note. This subject must be in- liferative changes in the bone-marrow, as a result of the vestigated along the same lines as the behaviour of the finely action of toxic substances. On this point further observation granular cells. The occurrenee of local accumulations of is necessary. lymphocytes and hyaline cells can only be mentioned as a Fifthly, whether substances exert a negative chemotaxis on subject also worthy of consideration. the leucocytes in the marrow or elsewhere and interfere with their passage into tile blood stream must still be left an open CONCLUSION. question. In conclusion, may I express the liope that this discussion It will be observed that in many of the circumstances may aid in determining the position wiliclh the term inflam- mentioned the conditions determining the leucopenia are of mation is to occupy in the science of pathology. It appears an unfavourable kind, whether they be excess of toxic sub- that much discussion might be avoided if a sharper distinetion) stances in the blood, excess of leucocyte emigration due to were drawn between the active and the passive phenomena rapid inflammatory spread, rapid leucocyte destruction, etc. concerned. By the former, I mean those which are of the No doubt in most cases a combination of circumstances is at nature of a defensive reaction, by the latter, those wllich are work-for example, in the fall of the leucocytes in pneumonia merely the evidence of the action of toxins or other nox,e on without a true crisis. But it is extremely important that in tissues, especially on living cells. The former ouglit to be re- all conditions where there is leucopenia the circumstances garded in the liglit of evolution as a provision for the protee- which bring it about should be accurately ascertained, not tion of the organism, the latter merely as evidence that living simply to establish scientific facts, but also to afford the basis structures are necessarily capable of damage. of possible therapeutical measures. Another interesting fact may be noted-namelv, that in II.-W. S. GIREENFIELD, M.D., F.R.C.P., various grave inflammatory or infective conditions when the Professor of Pathology in thc Uiliversity of Edinbuigl. leucocyte number falls, there appear in the blood stream some TwIE President, Professor Oreenfield, complimented Dr. MuiT of the finely granular leucoblasts of the marrow-the myelo- on the able manner in wilicl he had opened so important a cytes which are so numerous in the blood in medullary leuco- discussion. He did not wish to anticipate anything tllat cythiemia. Wlhetlher this is due to organic chancre in the might be said by others who wislhed to take part in the discus- marrow interfering with the normal relation of its cells, I at sion; but lie thought that the results obtained by Dr. Muir present cannot say. It, however, appears to be usually a bad threw on omen. were of the highlest value, and tilat they afresh light *Lastly, we may merely mention that the leucocyte number the whole question of leucocytosis. is diminished in several chronic conditions-for example, in pernicious anaemia, in some cases of clilorosis (as I pointed III.-D. J. HAMILTON, M.B., F.R.C.S.E., F.R.S.E., out several years ago), and in some cases of aniemia with Professor of Pathlological Ainatoimiy, University of Aberdeen. splenic enlargement. Here, again, the diminution is chiefly PROFESsOR HIAMILTON said tllat the subject was one of the oIn the part of the polymorphonuclear leucocytes; and greatest importance. There was this to be said about it, how- this association with defective blood formation or with ever, that, owing to the evidence on many points being as yet alterations in the function of the bone-marrow is worthy of scanty, and even contradictory, no one was entitled to offer an note. . opinion on any of tlle so-called facts of the process, and far TEuz BarTm 6o? SEPT. 3, 1898.] DISCUSSION ON LEUCOCYTOSIS. MEDICAL JOURXAL less upon the numerous theories bound up with the subject, V.-T. EDMONSTON CHARLES, M.D., LL.D., F.R.C.P., which might in the smallest degree savour of being dogmatic. Hon. Physician H.M. The Queen. Thus, in the first place, there were evidently leucocytoses and DR. CHARLES said that in examining the blood in some acute leucocytoses, probably differing widely in their causation and cases of Malta fever he had been struck by the absence of the significance, and it would be rash and foolish to conclude polymorphonuclear leucocytes, only lymphocytes with a because, let us say, an excess of leucocytes in the blood had single large nucleus were present. He thought at first that oocurred in one case as a protection against the effects of this appearance might be due to the particular stain employed morbid substances introduced into the system, that therefore (thionin), but he obtained the same results whatever stain leucocytosis in all cases was to be looked upon in a similar he used, for example, eosine and methylene blue. In other light. Even after what Dr. Muir had said of investigators fevers, for example, in typhoid fever, he had not found the being almost unanimous on the subject of leucocytosis being same absence of the polymorphonuclear cells, and he thought a general affection, that is to say, affecting the whole blood that this was a diagnostic point of great importance. It equally as a mass, yet he was certainly not convinced that often happened that a physician had considerable difficulty this was so universally concluded to be the case as Dr. Muir in distinguishing between typhoid and Malta fever, and he ihad made it out. Leucocytes under certain circumstances thought that a bedside examination of the blood would afford had a peculiar faculty of agglutinating within the capillaries, a rapid and reliable test. In further illustration of the value in some instances to such an extent as to form emboli; and of a clinical examination of the leucocytes, he instanced the it seemed very likely to the speaker that certain varieties of difficulty that was often felt in knowing when to grant a the phenomenon, such as that which so often precedes death, patient suffering from appendicitis permission to rise. In might be due to an arrestment of the leucocytes within the his experience this could be told with precision; for, if capillaries of the skin. The condition of leucopenia was leucocytosis was present, then the patient should not rise even known to be often caused by such an accumulation of leuco- though all other signs and symptoms had abated, and on the cytes within the capillaries of the lung and other organs, and other hand, if the leucocytosis had subsided, then the patient it did not seem illogical to suppose that a partial leucocytosis might safely rise, even though some tenderness still per- might occur in the vessels of the skin. Then, coming to the sisted. In conclusion, he quoted the case of a patient whom great question of chemotaxis being a frequent, if not the he had treated for a sore throat. The state of the throat im- most frequent, cause of leucocytosis, he was bound to say that, proved, but the temperature continued to rise. Examination so far as he had read and observed, the evidence confirmatory of the blood revealed a marked increase in the polymorpho- of this theory was of a flimsy and unstable nature; as he nucleur cells, and, in spite of the absence of any physical understood it, this chemotactic theory of the condition went signs, he was thus enabled to predict the onset of an acute on the supposition that something was introduced into the pneumonia or pleurisy, the latter hypothesis being verified on blood which had a positive attraction for the white cells con- the following day. tained in the bone marrow and other blood-forming organs. True as this may prove to be in the long run, it appeared to VI.-W. S. LAZARUS-BARLOW, M.D., him that a much more decided basis of proof was required Curator of the MuSeum, St. George's Hospital. before it could be accepted by an unbiassed observer. What DR. LAZARUS-BARLOW congratulated Dr. Muir on the im- was wanted in a matter of this kind was accumulated facts, pQrtant addition to the subjects of leucocytosis and phago- not theories, and it would be long before. the experimental cytosis that he had made by his observations on the bone evidence on the matter would have grown to such an extent marrow, and said that he considered that knowledge with as to settle the question one way or the other to the satisfac- regard to granular-cell leucocytosis was far more advanced tion of all concerned. Was there not a possibility, the speaker than with regard to non-granular cell leucocytosis. Probably asked, of those substances of a poisonous nature which called the granular-cell leucocytosis should be considered as forth a leucocytosis merely stimulating the lymph-corpuscle- being of the same nature as the increase of the granular forming glands to excessive secretion? leucocytes that took place in the tissues in inflammation, that is, as a reaction to an irritant of a purposive kind. The non-granular cell leucocytosis, however, was a matter of the IV.-G. SIMS WOODHEAD, M.D., F.R.C.P.E., greatest difficulty, principally because of the uncertainty as Director, Researchl Laboratories of the Royal Colleges of Physicians and to the nature of the cells concerned. In the case of lympho- Surgeons, London. cytosis, there was probably only a washing out of the DR. WOODHEAD said that he had listened with great interest lymphocytes from the lymph glands during digestion; but, to the paper, which he believed was of special value from the where the cells were of the large hyaline type, they might be fact that its subject matter had a bearing on every great ques- connective tissue cells, endothelial cells, or even possibly in tion in pathology. Its bearing on inflammation and im- some cases sarcoma cells. munity was of special interest to him, but all would appre- ciate its very great importance in connection with such a condition as leucocythemia. In regard to what Professor VII.-HERBERT E. DURHAM, M.B., Hamilton had said, he thought that we should not allow a Grocers' Research Scholar, Cambridge. separation into two camps merely, for after all chemiotaxis DR. DURHAM congratulated Dr. Muir on the success of his was conceived in Belgium, but was hinted at by a German, investigations on the bone marrow. He desired to emphasise and worked at by a Russian in Italy and in France. He quite the advisability of a routine examination of this tissue in agreed that chemiotaxis and phagocytosis should not be ac- infective diseases, since, in certain instances of bacterial cepted as proved. Theories of this kind should not perhaps infection, it was possible to demonstrate the presence of bacilli be dogmatically held, but he did believe in their use as work- there, although examination of other organs proved negative. ing hypotheses. Dr. Muir's work would, he believed, clear He also alluded to the period of resolution of a leucocytosis the ground for furtlher investigation. The locality of the when many cells rather of the lymphocyte type were present; small granular polynuclear cells having been fixed, and dis- he had been unable to find transition forms between the tinction being made between all those derived from the bone polymorphonuclear leucocyte and these lymphocytic forms. marrow and those from other sources, still further elimina- He referred also to the rapidity of the changes and the simi- tion became possible. He looked upon leucocytosis as evi- larity of the general type of the sequence of changes in the dence of a power of reaction in the tissues in which those leucocytes in the different cavities (vascular, synovial, peri- cells were formed, or on the part of the cells themselves. In toneal, etc.) of the body after experimental injection. The the local reaction of mild anthrax cases we had evidence of enormous number of leucocytes which appeared after injections powers of resistance of the tissues, and capacity to react in in immunised animals was compatible with the changes in the presence of the anthrax bacillus and its poison; so in "leucoblastic" bone marrow described by Dr. Muir. leucocytosis we had a manifestation of a power on the part of Wie cells (certain of which, as Dr. Muir had demonstrated, VIII.-T. H. MILROY, M.D., could be traced to their source in the bone marrow) to react Plhysiology Laboratory, University of Edinburgh. and multiply in the presence of proteid poisons and other DR. MILROY said that in the experimental leucocytosiscaused irritants. by the injection of nucleic acid there was an alteratign in the THE BRITISH 6o,6o8.', MEDIckk.,4PURNA.L] SECTIONSETO ''OFOFPTOOYPATHOLOGY. [SEPT.SP.33, i899.8g ratio letwqen t4e. amounts.of nitrogen,and P20-exereted ence is in all cases entirely withdrawn, and perhaps on this compared to thlat in healthi. This diffeence referred both to fact largely depends the somewlhat variable clharacter of the all &hsohlteO.'and relative i.ncrease in'theP ,0, compared to the changes in the blood which I have observed. nittobeh. .He also 'stated that in meduNlary 'leucocythaemia'- the 2'05 seemed to be both absolutely and relatively THE CORPUSCULAR ELEMTENTS. decrkasbd'compared to i'he, nitrogen, and said that this The ancemia which supervenes upon tlhyroidectomy was aipearo4t to 'stggegt' a check 'i tle breaking down of early pointed out; however, I canniot find that it is ever very leucocyt'eg.' intense, and it most certainly is not constant, in its occur- rence. The red corpuscles are reduced in number, the maxi- the DR. Mum'S 'REPLY.' pim reduction I have observed being 25 per cent., and and Dr. G`ItNBAUM faU in the lisemoglobin is roughly proportionate to that of the AFTER r,emarks by Dr. COPEMAN corpuscles, so that the aniemia is doubtless wholly due to a Dr. Muyi,, in reply, tlianked the m'embers wlho lhad ta.ken destructioni of the latter. part injthe discussion for the kind why 'in whiclh they had For examiiple, a dog witlh miiarked symptomis on the thlird day showed reeeivR,Q his remarks, and briefly referred to some 'of the red Corpuscles 5,700,000 thle normal beillg 7,600,ooo; hcnlobin 70, the which had been, raised. With regard to Professor nOrmal beinig Ioo. Anotlher dog, witlh intense symptoms, oil tlle tliird points, dayshowed red corpuscles 7,460,ooo, the inormiial being 7,130,000 (showinig a HaEilt,og!s observations, he said that h* admitted at oiee' slight inicrease) hTnmoglobini remaining unelhanged. the 6cwureicpe of merely. local.l'eucocytosis, but repeated thait I may mention that after a proniounced aniemia of this an increase of the.total,number of leucocytes had al.so to be type the liver gives an iron reaction with potassium ferro- dealt with. He considered that chemotaxis was the only cyanide. agpnt wirb.would explain many of' the 'phenomena present, Another well-known phenomenon is the leucocytosis which but1hat the stimulating effect on the cells of the marrow was invariably occurs. Numerous small, newly-formed leucocytes oft". jual, if not greater, importance. If lymphoid tissue was may often be found the day after the operation. The numbers concerned, it had still to be shown where the cells fpming flV¢tuate very considerably, as the following example shows: from it `becanie -tiansfo4med intfo 'the finel'y 'iranular poly- normal 8,ooo; first day 32,000; second day i7,000; third day morphonuclear cell~. The remaivks of, Dr. Edmondston 44,000. Clh,ales were of importance in showing that a fall of leucocyte CHEMICAL CHANGES. nuinber in one disease might not have- the same significance The fibrin of the blood is known to fluctuate to some extent as in another; in each case'thecircumstancese determining it in certain pathological conditiolns, usually in the direction of must be investigated. He agreed with Dr. Lazarus-Barlow increase, noticeably so after severe hIemorrhaages, and in some as to the difficulty in many cases of distinguishing hyaline infectious and inflammatory conditions. After thyroidectomy leucocyte'`from swollen 6ndotlielial cells and in determining the increase, in my experience, is invariable, and often con- the part which each played.- -In relation fo Dr. Durham's siderable; thius, for example, from a normal of 0.2 per cent. to remarks, he said that tlhe extent to.whicil organisms accumu- d.36 per cent., 0.3 per cent. to 1.14 per cent., 0.39 per cent. to lated in the spleen and' bone-iarrow. respectively.varied in o.56 per cent., but the increase is not always quite so large. different diseases'; so' far as his'6ob !+iVa:tions' went, they were The specific gravity, asimiglht be expected from the dimi- more numerous in tlle former, b'ut itwasfi'iteresting, to learn nution of the principal solid blood contents, becomes lowered. that thU converse'might'bh'the c?ise. He did nQt iptend to, The fall of course is largely dependent upon any considerable? draw! too' close an-analogy between the ma, row changes after anaemia, but it is very ievident that a change in the serum haimbrthrsge alld aft0r'leutcocytosis,'bit so far as the increase solids, such as we find in, the athyroidal condition, may have a of. t,he t classes of mother-celisi was concern,ed the analogy marked effect upon the specific gravity, so that, to my mind, of, i the method now in vogue of estimating hiemaglobin from the specific gravity is not always a quite reliable one. The proteids in the blood whiclh were estimated in every T1IJE BLOOD CHANGES AFTEIR EXPERIMENTAL case, underwent a varying diminution, as also did the total initrogen. Ti; ' I;It)ECTOMY.* Wlhen we come to consider the total solid contents' of the By ALhRED G. LEVY, MD. blood, we find they always undergo a reduction, and in most [Frion the Departmlnt of 'Patho1ogica Cl6eniistry of 'University College, instances their loss is more or less greater than that of the j ^ London.]' proteids, showing that one or more other substances besides MODE OF EX'PRRIMIENT. proteid material are destroyed under these circumstances. To NUM1IROVS observations, have hnow been niade on the strik'ing take a single example, the solids are reduced from 22.8 per and diverse phenomena incident upon tlie' removal of the cent. to 20.37 per cent, and the proteids from 20.37 per cent. to thyroid bodies of animals, yet the fact 'remains that we are ig.z per cent., that is, a loss of 2.43 g. solids against a loss of still very much in the dark&gdarfdihg the physiological func- 1.8 g. proteids. But it occasion-ally happens that the proteid tions of the thyroid- seeretion,' and of the pathological process loss is more or less larger than that of the solids-for example, which must occur when the secretion is absent from the i.2 g. loss of solids against 2.97 g. loss of proteids, indicating bo,dy. a considerable increase of some non-proteid material. So that The study of objective sy,mptom ,ean' only supply us with these facts, taken in combination, may be held to point to a hints as to the seat or the seats of the pathologicl. processes varying loss of some, and a varying gain of other, non-proteid whicl milst take place when an animal is in a state of matter. As regards these non-proteids, I have found that the cache',ia thyroidectomiqa. IBut these pathplogical,processes blood ash does not vary to any substantial extent, so that have ,been'but little directly inve'stigatec1.' The priucipal there remains the carbohydrate and fatty substances and the workqrs -in this line- have' been DuccheschX, who has made, extractives for further consideration, but I have not yet had some observations upon -the urine, ant infers thence a,destruc- an opportunity of pursuing the investigation in this direction. tion of proteid matte; "Vassale, histological investigations .of Of course when there is a considerable aniemia a large part the central nervous system,; and, contemporary with myself of the loss in proteids is directly due to this, but when the Posto ff has examined the blood, and last year published a anaemia is absent or inconsiderable a; large loss of proteids shQrt tote on his work. may still occur. To quote one example, in one of my dogs In lxprments of this lsind, 'it is, of coursef essential that loss of haemoglobin, o; loss of corpuscles, 5.8 per cent.; loss the piralhyrid.shqould be ,Qare~fqlly,emoved with the thyroid df solids, io per cent,; loss of proteids, I5 per cent.; so that gl9 c an 4lX, fortunately, in the dog is easy to accomplish; here it is the serum solids which principally suffer. but the small accessory thyroid bodies which are known some- times' to exist in the tissues around,the,aorta and large~ CONCLUSION. vessels, and which, according tQ Cvunningham, have an active Throughout the experiments I gave careful attention' to the function, render it difficult, to', b'e sure that the thyroid influ housing and feeding of the dogs after they had been thyroid- ectomised, for an animal in this condition is so peculiarly sus- * Towards the expeilses' of this research a graht was made by the Sci6nti#ic 4qnts Committee, of the 1British Medical AsSociatih.' Full deptible to external debilitating influences that otherwise it detal6 pvil be publisled in the Journ!aa of Paclology and BacterioLrYgYy.' *ould not be fair to ascribe its blood changes entirely to the 6o TL E BRITISH SEPT. 3, 1898.] PLEURAL IRRITATION AND PLEURISY. I MEDICAL JOtURNAL60 loss of the thyroid secretion, but when bled the majority of (2) a form in whiceh there is a general increase of thle connec- my dogs were in very good bodily condition, and one indeed tive tissue of the pleura without marked infiltration by cells increased in weight after the operation. and without "fibrinoid degeneration " of the connective I may remark the striking want of interdependence amongr tissue fibrils; (3) a form in which the whole thickness of the the various blood changes, and that none of these bear any inflamed pleura consists of hiighly vascular and very young relation to the severity or rapidity of onset of the general cicatricial tissue. He agreed with Neumann thatendlothelium symptoms of the cachexia. This apparently irresponsible might be found covering the "false membra,e,"andl that the, accentuation of certain structural blood changes, as also of connective tissue of the pleura itself might undergo the certain objective symptoms, may perhaps be partly referred changewwil was well termed"ifibrinoid degeneration." But toe the conditioning circumstances " such as temperature, lie did not agree that these changes were commonly-seen. In hygienic surroundings, food, and, as I have already men- the guinea-pig, in particular, the endotheliumdeglenierated is did not occur tioned, to the existence of accessory thyroid bodies ; but it to form a part of the false membranie, or if this only a full knowledge of the physiology of the thyroid gland it could be found lying beneath the false membra-e; in no which can satisfactorily ascribe to these things definite causal ease hiad it been found to cover it. In the greater number of relations. luman cases all trace of thle normal endothielium was lost, To Professor Vaughan Harley my thanks are due for many and reasons were given for not consideringthlis as dependent helpful suggestions in working out this research. upon post-norten change. So far as the exudation was con- cerned in experimental cases in guinea-pigs, it mi&oht briefly Dr. WELSH said that he had removed the parathyroids be said that as early as one hour after intrapleiiral injection alone in a few cases in cats, and, though he had never ex- of diphthieria toxin there was an enormous output of finely amined the blood during life, he had observed that the organs granular oxyphile (polynuclear, neutrophile) cells, fully and tissues after deathi were often anmemic, and showed evi- charged withl granules. Later the granules disappeared and dence of fatty degeneration. the nuclei of the cells broke up. Ultimately very few finely Dr. MOTT thought that the tendons and connective tissues granular oxyphile cells, but numbers of desquamated endo- blood chianges. large cells with granules, were should also be examined in relation to these thelial cells and unprovided of The theory that an excessive accumulation of mucin occurred present in the exudation; the origyin of the latter variety after removal of the thyroid was probably no longer held by cell is doubtful. anyone. He suggested that the reason why the relative loss [The paper was illustrated by an interesting series of lantern of the proteids and of e total solids varied so greatly might slidesand microscopic specimens.] be found in the thvariations in the nutrition of the dogs ob- in course experiments. DIsCUSSION. served the of the various not Dr. MuiR said that lie examined the blood in several cases Professor(+REREENFIELD said that Dr. Barlow's paper did of a in itself to as it embraced too wide a myxcedema in man, and had found slight leueocytosis readily lend discussion, funda- some cases, whilst it was absent in others. The degree of range of subjects, and included practically all the anemia also varied, butwvas usually slight. His general mental processesin general pathology. Hethoualgt that results were in the elemenets would be more studied ifthey were that the clhanges corpuscular these processes profitably such were not of a marked kind. considered separately. It was important in the stucdy of to bear in mind the different effects produced by changesdifferent irritants and at different periods of time. He re- ON PLEURAL IRRITATION AND PLEURISY. marked that for the last twenty years lie had been accustomed M.D., to some oftlle statements forwhich Dr. Barlow was now By W. S. LAZARUs-BARLOW, contending.teach Curator of the Museum, St. George's Hospital. Dr. WOODHEAD with Professor Greenfield that DR. LAZARUS-BARLOW considered the formation of "false quite agreed complicated the they had here to deal with a most difficult and membranes" and thickeniiigs of the pleura found when question. To begin witlh, it was impossible to ignorethe fact pleura itself or the subjacent lung was the seat of inflamma- that in different animals there were different types and struc- tion. The commonly accepted view was that the false mem- so that different processes must pro- tures of pleuroe, pathological branes, whiec were essentially associated with acute manifest different appearances, especially whenirritants of eesses, were formed by deposition of fibrin from a liquid in- different kinds are used. In the specimens exhibited evi- flammatory effusion. Certain authors, however (Grawitz, dence of this was very marked. Neumann's paperhad been Schleiffarth, Neumann, Borst), had dissented from this who had nothad muchex were accepted by many, especially those opinion, and maintained that the false membranes perience in the examination of specimens as introducing a chiefly formed by a modification of the subendothelialeon- new light on the question of pleurisy, but many of the points nective tissue of the serous membrane. This modification raisedlhad already been settled. It was useful to have such had been termed" fibrinoid degeneration" by Neumann. matters examined in fresh light. The one criticism he would Neumann, in particular, maintained that in the pleural make was that the pleurises differed widely in character and cavity the false membranes might frequently be found could not be generally grouped, and that the "young" eovered by endothelium, and not covering endothelium, fibrous tissue exhibited was really well-formed fibrous tissue as should be the case if theeommonly accepted view were of some standing. He recognised that fibrin could be found correct. Borst, working with the peritonealcavity of guinea- in the and that swollen connective tissue agreed with Neumann, but in addition found that in tlle lymph spaces, not pigs, of strands could be found in the pleura, but these were hya- earliest stages of an acute peritonitis, induced by injection line fibrinous substance. a solution of iodine in potassium iodide, there was often a Professor McFAXDYEAN said that liehad listened with special marked proliferation Qf endothelialeells. interest to Dr. Barlow's demonstration, because he had re- The had made serial sections of pleura parallel with pleurisies in author under cently examined a series of naturally occurring its surface (following herein Neumann's suggestion) thehorse. He thought that it was not reasonable to expect the following conditions: a common type of pleurisy whiclh naturally varied according A. Pleura of inormal. into the pleural to the cause, just as much as dermatitis or gastritis. Accordc guinea-pig: 2 after injection of diphtheria toxin ing tohis own observations,there was a remarkable constancy (I normal. between the nature of the changes and the irritant deter- 2 in hypostatic congestion. them. One could not expect identical changes in ex- 3 early pleurisy in diphtheria. mining a chemical B. Human 4 ,, pyminia. perimental pleurisies induced by the injection of Pleura. ,, i ,, lobar pneumonia. irritant as diphtheria toxin, and natural pleurisies which 6 but ti early pleurisy in glanders. such were often later,lt, ,, ,, generalised miliar-y were almost all due to bacteria. These bacteria 7 tuberculosis. present most abundantly in the deeper parts of the pleura, [Photographs of these were thrown upon the screen.] The and thus differences arose as compared with pleurisies due to author found that there were, at least, three distinct forms of surface irritation. pleurisy: (I) A form in which "fibrinoid degeneration" Dr. MuIR observed that in the results brought forward the occurs along with marked infiltration of the pleura by cells; nature of the irritant should be kept in view, as the agent was 610 NrF!X7TiRrRTTI I SECTION OF PATHOLOGY. [SEPT. 3, 1898. a cell poison, and maniiy of the miinor chancges nlight thus be Process.-Draw a minute drop of blood, touclh it with a produced, suclh as necrosis of the inuscle fibres in the guinea- microscope slide; mix with an equal quantity of io per cent. pig's pleura. The position of the endothelium might be solution of sodium carbonate, and then with a similar quan- affected by various circumstances. So far as his observations tity of a 20 per cent. solution of chloride of ammonium. After went, the endothelium in the human subject was not found mixing, put on a cover glass and let it stand for 30 minutes, above the exudation, but its cells degenerated and disap- preventing evaporation. The granules slowly increase in peared in the exudation; at an early stage swollen and endo- number the longer the slide stands; it is tlierefore neces- thelial cells miglht be seen at places still attached underneath sary to examine all specimens at about the same time after the exudation. He doubted the advisability of making dis- mixing. tinct varieties, as so much depended upon the stage of the To Examine.-Place under a microscope with an inclh process and the degree whichl the proliferation had reaclhed. objective glass and with a good liglht; choose a field about the Dr. WELSH thouglht that the chanaes in the connective ceintre of the cover glass, and count all the granules in the tissue of the pleura shiould be kept distinct from the changes field; then count all the red cells, and divide the former into in the exudation, as tlhe two processes were essentially dif- the latter. Counting is facilitated by somewlhat diluting the ferent. He deprecated the use of the term " fibrinoid " as ap- blood witlh the solutions, so as to diminish the number of cells plied to chances in tle fibrous tissue. In some cases in whiclh in a field, and by using a micrometer eye-piece. the irritant was very intenise, the fibrous tissue of the pleura The following are common relationis of granules and red did undoubtedly undergo necrotic changes, and become cells: swollen and lhyaline; but the resemblance to the fibrin In Ph)ysioloqical Conditions.-i-Io in morning; 1-20 in even proper was only superficial, and could not be affirmed witlhout ing; but more in chlildren than adults. confusing the true niature of the change. Pathological Conditions.-i-I to 1-5 in Briglht's disease and chronic gout; 1-30 to I-40 in fever. Any of the above quantities can be reproduced by the action THE PATHOLOGICAL EFFECTS OF BREATHING of drugs. Under all conditions tlle number of granules varies with the uric acid passing in the urine, and a diagram was OXYGEN AT A HIGH TENSION. shown to illustrate this point. A specimen of blood from By J. LORRAIN SAIITH, M.D., Briglht's disease was shown in contrast witlh a normal blood. Lecturcr on Pathology, Quieen's College, Belfast. REFERENCE. [ABSTRACT.] 1 Medical Times and Hospital Gazette, September, 1396. IT has been noticed by Bert and other observers that before oxygen lhas been raised to a tension whichl is fatal to MALFORM1ATION OF THE KIDNEY AND DIS- animals, various symptoms develop wlich indicate profound disturbance in the tissues. Bert lhas in particular defined the PLACEMENTS WITHOUT MOBILITY, effects on the nervous system, which he described as resembl- WITH ILLUSTRATIVE CASES AND SPECIMENS. ing those of tetanus poison. By DAVID NEWMIAN, M.D., F.F.P.S.G., The experiments nlow recorded deal with the effect of in- Sur-geon, Glasgow Royal Infirmary. creased oxygen tension on the lungs. The results show that [ABSTRACT.] oxygen at a tension of about 130 per cent. of an atmosphere ANONIALIES of the kidney have until recently been looked produces pneumonia in the lungs of mice in about 6o hours. upon simply as patlhological or anatomical curiosities; but If the tension be raised to i8o per cent. the time of survival is now that mnany of the diseases of the kidney come to be reduced to 24 hours. If 300 per cent. be reached the period of placed under the surgeon for treatment by operation, all survival may be as shlort as 5 hours. departures from the normal, wlhether in respect of number, In the case of small birds similar pneumonic effects are pro- form, size, or situation, must be considered of moment to duced; but, wlhen a tenson of 270 per cent. is reached the those who lhave frequently to operate upon the renal organs. tetanic symptoms described by Bert develop in about io If we simply study the cases recorded it will be found that minutes. This effect can be abolished at this tension by they group tlhemselves together and may be naturally exposing the animal, as a preliminary measure, to a lower under the following heads: tension, sufficient to start the process of inflammation in the classified lung. It reappears, however, when the tension is raised to A. DISPLACEMENTS WITHOUT MOBILITY. I. Congenital displaceimienit witlhout defoirmiiity. 450 per cent. of an atmosphere. Further, it is found that IT. Congenital displaceimienit witlh deformiiiity. tetanic symptoms do not arise in mice till the atmosphere to I1. Acquire-d displacemnents. which they are exposed contains oxygen at this tension of 450 B. MALFORMATIONS OF THE KIDNEY. per cent. The fact that birds with damaged lungs and normal I. Variations in inumiiber. mice have similar power of actively absorbing oxygen indi- Y. Supernumierar-y kidney. cates that 2. Single kidney. the onset of the tetanic symptoms at a given oxygen (a) Congenital absence of one kidtncy. tension depends on the integrity of the active power of absorb- (b) Atroplhy of one kidney. ing oxygen on the part of the lung. Absencie of both kidnieys. That the effect depends on the tension, and not on the Il. Variations in form aiid size. I. General var'iation ill formiii, lobulatioll, etc. quantity, of oxygen in the blood may be further proved by 2. Itypertroplhy of onie kidney. exposing an animal to an atmosphere containing carbonic 3. Fusioni of two kidneys. oxide and oxygen at a high tension. The tetanic symptoms (a Horseshoe kidiney. then develop at the same tension as before, though a large (b) Sigmoid kidney. percentage of the ha-moglobin is saturated by carbonic oxide. (e) Disc-shaped kidney. The experiments slhow that oxygen tension at a moderate C. VARIATIONS IN PELVIS, URETERS, AND BLOOD VESSELS. height produces pneumonia, and at a considerably higher ten- A.-DISPLACEMENTS WITHOUT MOBILITY. sion produces the tetanic effect described by Bert. I. Congenital displacement without deformity of the organ is by no means uncommon. CASE I.-Fixed displacement of the right kidney above Poupart's liga- A DEMONSTRATION OF THE GRANULES PRE- ment simulatirg a perityphlitic abscess; operation.' The patient was CIPITATED IN THE BY admitted complaining of paini in the righit iliac region. There was a BLOOD CHLORIDE sliglht fulness of the abdomen in the right iliac and lowerlumbar regions, OF AMMONIUM. and a rounded swellinig was felt passing upwards and backwards. Tile swelling was cut down upon, when it was found to liave a rounded out- By ALEXENDER HAIG, M.A., M.D.Oxon., F.R.C.P., line, witlh a distinct hilum towards the inner and upper aspect, and being semi-clastic but firm imnediately suggested a displaced kidney. Physiciani to the Metropolitan II ospital, etc. CASE iI.-Left kidney displaced downwards and forwards in a patient THE method is that proposed by Mr. Barker-Smithl1 as modi- uiponl*whom lumbar colotoniy was performed. On mnaking an incisioln fied and adapted to quantitative purposes by the author. from the lower border and tip of the last rib on the left side to a point lilalf an inch behind the centre of the crest of the ilium, the upper The granules are pale, more or less spherical bodies of one- border of the left kidncy preseilted itself at the lowermost limit of the sixth to one-third the size of a red corpuscle. incision. SEPT. 3, 1898.] SECTION OF STATE MEDICINE. [MC JURNL 6IJ CASE III.-Right kidney displaced downwards and rotated on its antero- (a) Horseshoe is the most common of posterior axis, slhortened ureter entering upper aspect of bladder. At kidney form fusion. the post-mortem examination the right kidney was found to be displaced The two organs are joined together at their lower ends, some- and firmly fixed; the pelvis of thle kidney looked upwards, iniwards, and times by a simple band of tissue. forwar-ds, wlhile the conivex aspect of the organ rested upon the brim of CASE I4.-Horseshoe kidney united by an istlhmus of fibrous tissue the pelvis. at the level of the bifurcation of the aorta; renal form well retaiiied.7 w In the three cases above described, where tlle kidneys CASE I5.-Horseshoe kidney witlh lobulatioii and complete fusion of both kidneys; malfornmatioin of pelves and alnomalous distiibution of occupied abnormal positions, the fixed misplacements were blood vessels. Both kidnieys retaini to some extenit tlieir renial form, and not associated with any deformity of the organs. are united at tlleir lower enids by a distinct lobule, wlhiell is miiarked off by two deep grooves. - II. CONGENITAL DISPLACEMENT WITH DEFORNIITY. CASE I6.-Horseshoe kidney, witlh complete incorpoiation of th7etwo CASE 4.-Right kidney at the brimn of the pelvis, anomalous distribution organs; lobulatioin of botlh segments, the ureters deformiled, aid anoma- of blood vessels, and deformiiity of the kidney.2 The riglht kidney was lous distribution of the blood vessels.8 The two kidnieys aie completely found lying oni the brim of the pelvis. At the upper limiiit an artery united at their lower ends, anid the whole renal inass, although lobulated, enters the kidniey directly fromi the aorta. Froni the kidniey. close to the is, rouglhly speaking, unliformii in diameter, anld in this respect conltrasts uttermost limit of the pelvis, a large vein passes directly to the venia with the previous speciimienis. cava. (b) Sigmoid Kidney.-Sigmoid kidney is an end-to-end fusion CASE 5.-Malposition of botlh kidneys, onie to the right of the pro- of the two organs. In this both montoly of the sacrum, the otlher in the iliac fossa; riglht kidney sinall anomaly kidneys occupy and witlh nio hilum.3 In this case the kidney was founid to be situated one side of the body only, but while the condition is uni- about lhalf ani inclh to the right of the promonitory of the sacrumi. anid the lateral it cannot be properly included under the term " single left kidney was discovered in the left iliac fossa 2 inchIes to the left of the kidney." sacro-iliac synchondrosis. CASE 6.-Right kidney flat, oval in form, supplied witlh two arteries; (c) Disc-shaped Kidney.-Disc-shaped kidney is applied to one ureter from its anlterior aspect.4 In this case the riglht kidilcy was those instances wliere incorporation of the two organs is very situated at the brim of the pelvis, lhalf in the cavity and lhalf out. complete, as, for example, in a case published by Drs. Suther- land and Edington in the Glasgow Medical Journal, February, III. ACQUIRED DISPLACEMENT OF THE KIDNEY. 1898. CASE 7.-Acquired displaceinent of the right kidney by a perinepliric NOTES AND REFERENCES. abscess. The kidmiey was discovered with its convexity lookinlg upwvards 1 and lying close to the diaplhragm, wlhile the pelvis was turned down- This case is published in detail in the Scottish Ifedical and Sutrgical Journal, vol. i, No. I, p. 53. 2 Glasgow Royal Infirmiary Museum, Series 7, wards. No. 2. 3 Newman, Surgicaf Diseases of the Kidney, p. -. 4 Royal Infirmary B. MALFORMATIONS OF THE KTDNEY. Museum, Series 7, No. I. 5 Ibid., No. 9. 6 Ibid., No. I3. 7Ibid., No. 3. i. Variations in Number. Ibid., No. 4. i. Supernumerary Kidney.-SuDernumerary kidney is ex- tremely rare. We have only seen one instance of this anomaly; lying close to the upper margin of the left kidney there was a small pear-shaped body, supplied by a branch of SECTION OF STATE MEDICINE. the renal artery, and having a distinct ureter which passed Sir HENRY D. LITTLEJOHN, M.D., President. into the left ureter half an ineh below the pelvis of the left kidney. 2. Single Kidney.-A careful distinction must be drawn DIPHTHERIA IN LONDON, 1896-98. between " single kidney " due to conaenital defect of develop- By F. A. DIXEY, M.A., M.D., ment of the opposite organ, and those instances in whicli a Fellow of Wadlhaimi College, Oxford. kidney lhas become wasted and functionally useless as a AT two previous meetings of the British Medical Association1 consequence of disease, while its neighbour has undergone I compensatory hypertrophy. have attempted to deal witi the statistical materials fur- CASE 8.-Completc absenlce of the left kidney, ureter, and vessels, com- nished by the weekly returns of the Registrar-General, in so far pensatory hypertroplhy of 1iglyt kidiiey. The right kidney was normal in as they are concerned with the prevalence of fatal diplhtheria its position, but thc whole organl was greatly enilarged, weighing 12m in the metropolis. My last communication to the Association ounces, and measuring 5 illClIes in length and 4 inclhes in breadth. No was made two and since trace wais founid of the left kidlicy or of its vessels and ureter, and no years ago; that time so much of opeining inito the bladder could be discovered correspondinlg to the Cle- interest has lhappened in regard to the present recrudescence traniec of the ureter. of London diphtheria, that I venture to think hardly any CASE g.-Coingeiiital absence of the left kidney, vessels, and ureter. The apology to be needful for once more preparatioi slhows wvitlh tme r-iglht kidniey, the bladder, and the riglht introducing the subject. uLreter. A miiost carefutl scarcli at the time of the post-mnortem examination The points to which I have given special attention are (i) the failed to finid any trace iii the J)ody of the left kidney or ureter. general course of fatal diphtheria in London; (2) its seasonal The following cases show how one kidney may atrophy or relations; ( ) the important question of the influence of become functionally inactive, either as a consequence of want school-attendance on the spread of diphtlheria ; (4) the rela- of growth, or from disease in early life. tion of diphtheria to so-called " croup; " (5) the effect of the CASE O.-Extieilec atroply of the left kidney, witlh double pelvis but treatment by antitoxic serum. In examining the mieans single iureter.5 I lhave no details of tlle post-nortem examination in this which recent statistics our case. The kidney tissue is almost completely destroyed, and the whole put into hands for attacking these organ is about the size of a walnlut. The pelvis is branched, and there is and similar questions, and for confirming or modifying con- 110 hlilum; tllc upper limilb of the pelvis springs from the inner amid upper clusions previously reached, it may be well for me to state aspect of the atroplhied olgaii, while th -lower limb arises from tlle lower that I have no views to border of the kidiiey. preconceived uphold, my only object CASE rx.-Atroplhied kidniey, the renal tissue being almost entirely being to extract from the available evidence suchl information replaced by fat.6 Tlh riglt kidney was IO ouncesi theleft kidney weighed as it seems fairly capable of affording. Nor do I wislh, on the half aii ounice; very little renal tissue could be tound in tlle imass, aIid present occasion, to propose what reiimainied was completely embedded in firm fat. remedies, my only business just CASE I2.-Atrophy of the right kidniey witlh compenisatory lypertroplhy Inow being to draw attention to facts. of the left kidiiey; disease of the suprarenal capsules. The riglht One word I may be allowed to add on tile special usefulness Onlly weiglhed I ounlce, the left 7 2ouuces. of the weekly return-s. This seems to me to consist largely in these two points: (i) That by their means we are enabled to II. VARIATIONS IN FORM AND SIZE. the seasonal relations of fatal i. General Var-iation in Formn, Lobulation, etc.-Slight changes study diseases and the imme- from the normal are no means un- diate as well as remote effects of varying meteorological con- in shape typical kidney by ditions; and (2) that we are able to bring our results more common, and in more marked instances the organ may be exactly up-to-date tlhan if we had to wait elongated so as to become sausage-shaped, or it may be for the publication increased in thickness and globular in form, resembling the of annual reports, wlhichl nlecessarily occupy muclh time in their shape of the kidney in the foetus. In a few cases the kidney preparation. has beenl found to assume the discoid shape. i. THE one of one GENEIRAL COURSE OF DIPHTHERIA IN LONDON, I896-98 2. Iypertrophy of Kidney.-Hypertrophy kidney is With respect to the general prevalence of the disease since not often met with independent of some condition which has the middle of there is little to produced a functional weakness of its fellow. 1896 record. London is still CASE I3.-Silmple lhypertrophy of the left kidniey only-; righlt kidney suffering from the outbreak of diphtheria which may be said niormiial in size and appearance. The right kidney was liorinal in weight, to have begun early in 1892, and whichl reached alarming pro- 62 ounIces, wlhile tllc left weighed iml ouilces. portions in the autumni of 1893. The number of notifications 3. Fusion of twvo Kidneys.-The amount of fusion that takes and of fatal cases in I896 botlh shlowed an increase over the place between two kidneys varies greatly. corresponding LIigures for I895; but in 1897 both underwent 9 THz BRITISH 1 ,6. z2 .MEDICAL JOURNALJ SECTION OF STATE MEDICINE. [SEPT. 3, I898. I some diminution, though the notification figures were still and III. I have before stated my conviction that Mr. Shirley well above the average of the last four years, including the Murphy's views are fully justified by the available evidence, fatal year I893. During the present year the tendency on the and I would here draw attention to the fact that in both of whole has been a downward one. the years I896-97 now under review the drop in the number The following table (Table I.) gives the London mortality of fatal cases corresponding with the period of summer holi- week by week since the beginning of I896, according to the days is again perfectly apparent even in the curve for " All Registrar-General's ret-urns. The corrected ten-yearly means Ages." As some of my readers may be aware, I am inclined for the corresponding weeks are also added for comparison. to think that the Christmas holidays can also be shown to With regard to tlle last-named figures, it should be remem- have their influence on the curve of fatal cases, though this, ,bered that they are to be used with caution-not from any as might be expected, is of a less pronounced character. No suspicion as to their substantial accuracy, but because the doubt in any given year the operation of this school-attendance average results for a period of years in the case of a disease factor tends to be obscured by other circumstances; but when which varies in its incidence so much as diphtheria are some- several years are taken together, the other influences are what artificial ifconsidered asan index of its normal prevalence.2 found to counteract each other, and the holiday fall with its Nevertheless, if studied with due regard to the actual cir- succeeding rise comes more clearly into view. An examina- cumstances, these weekly ten-year averages are not without tion of the successive ten-year averaaes will slhow that as the 'their interest and value, even in the case of a disease like general prevalence of the disease is increased or maintained, -'diphtheria. the "holiday drop " exhibited by the ten years' mean becomes TABLE 1.-London, 1896-98: Weekly Deaths from Diphtheria, more and more distinct. The lowest point reached by these with Corrected Means special and temporary depressions in the course of the regular for Ten Years of the Corresponding curve is most often to be found (as shown by the ten years' Weeks. mean) in the third and thirty-fifth weeks of the year respec- I~~~~~~~~~~~~ tively. Thus in the eight years from I89I to i898, the bottom I896. I897- I898. 1896. '897- of the first or January depression was reached four times in the third week, twice in the fourth; while on two more 2. te_,c~ C e-zo occasions it was deferred until the sixthi. In the seven years Weeks. Weeks. I6 "I U,; from I89I to I897 the second or August depression reached its CI1) -~ lowest point four times in the thirty-fifth week, twice in the 0 u thirty-sixtl, and once in the thirty-fourth. Looking at the facts as a whiole, I do not see any way of escaping the in- ference tllat there is a factor at work, distinct from ordinary seasonal conditions, which is sufficiently powerful to induce a Jan. 'I 66 35.8 71 40.4 50 46.9 July 28 47 33-4 36 36-7 ,~2 132.22 52 34.8 44 38-4 ,, 29 55 31.2 42 35.8 fairly regular disturbance of the course of fatal diphtheria at 3... 59 25.6 63 32.6 33 37-9 4 ,30 50 36.6 41 40.2 two definite times of the year, these times corresponding I ,,4 51 31.9 53 35.8 36 39.0 ,Aug. 31 43 38.0 42 41. 5 Feb. 5 61 36.1 42 44.1 ., 32 witlh the usual lholiday periods of schools. If this conclusion 6... 46 40.9 54 36-7 38 40-7 63 33-9 37 38-5 45 40.6 33 59 35-2 29 39.6 should appear to be well grounded, those responsible for 7..7 45 32.6 40 35.3 33 37.9 59 32.2 28 36.o action in the matter will doubtless not be content with a mere 8... 34-7 Sept..34 48 31.9 62 35 .6 46 39.8 32 31 35 3.3-7 Mar. 48 31.2 abstract acquiescence in its probable truth. 9.. 43 34.2 38 36.7 36 49 30.3 25 34-4 46 28.2 53 31.5 33 35.7 0 37 48 37-3 35 40.8 38 45 33.1 37 36-3 36 38.8 ! 49 40.9 45 44-4 4. DIPHTHERIA AND " CROUP." 52 29.3 43 32.8 53 36.o f 39 6i 47-5 49 51-7 It is now, I think, admitted on all hands that in former 5I 26.2 41 3o. 6 Oct. 40 44.8 -A '3 45 33.5 69 53 49.0 - cases Apl. 14 45 29.1 23 32.2 29 , 41 52 42.9 45 46-3 years many of fatal diphtheria have appeared in the I5 45 3I.0 30 33.8 34 - 7 42 66 48.0 55 52.I Registrar-General's returns under the heading of "croup." 42 27.5 40 30.2 3' _ s 43 57 44.8 48.2 30.2 65 '7 41 40 32.3 39 _ Nov. 44 64 43.6 59 48.2 TABLE II.-London, 1896-98: Weekly Deaths fron "Croup," May i8 36 29.4 26 27 - 32.2 9 45 53 48.I 46 51.0 with Corrected Means for Ten Years of the Correspondinq 29 4I 3'.'I 42 33.4 20 46 6o 44.0 37 47-5 20 Weeks. 43 32-3 33 35.8 3' , 47 59 46.6 21 63 56 29.9 36 '33.6 27 - Dec. 48 48 43-5 52 47.1I JUn1C 22 40 30.3 33 33.0 49 6o 49.6 58 54.4 896. 81898. I896. | 897- ,2 23 52 27-4 39 3I.6 ?I 50 52 47.3 63 50.9 I8q197- I 24 49 32-9 29 36.3 5I 58 40. I 56 44-3 25 40 33.0 24 35.7 52 38 41.6 53 44-5 J 26 37 3I.8 32 34.6 53 4I.6 49 Weeks. l~ 1 jWeeks. July 27 ... 43 33.1 43 36. I I lC) 0 0 (t C; The same facts are shown- in graphic form by the diagrams I 0 (exhibited), in one set of which is represented the actual ; l l- number of deaths returned week by week, while in another the conspicuous inequalities of the curve are removed by the Jaii. I 3 I0.8 I II 8.9 July 28 | 5.6 use of Mr. Bloxam's method. 6 II.7 I I0.8 9.8 - 3 29 5-(5-35.3 4.0 7 1O.1I I 9.7 5 9.' 30 - 4-3 31 6. 2. SEASONAL RELATIONS OF DIPHTHERIA. 4.. 5 9.5 I 9.2 I 7.6 Aug. Feb. 5 8-3 I 7.I 2 1 9 32 - 5.' 4-7 There is nothing exceptional about the seasonal prevalence 6... 5 IO.1 2 8-3 2 7-7 I 4-7 - 4.2

of diphtheria in either of the years now chiefly in question. 7.. 2 11.0 3 9.9 I 8.5 34 I 5-5 4-9 I1.9 Sept. 6 4.2 The usual autumnal rise was better marked in I897 than in 8... I 3 10.3 I 9.0 35 4-3 Mar. 9 10.9 7 the preceding year, and the curve maintained its elevation for 4 9.9 3 9.3 36 4 5-1 4-9 9!10 I 7.6 - 6.o 2 5-7 37 3 6.2 2 5.6 a longer period. The gradual rise that took place throughout ... 5.2 ,1 II 2 11|.0 3 8.8 - 7.6 38 - 5-9 I the spring and summer of I895 was an unusual feature that 3 8.4 2 2 7.5 39 4 7.6 2 6.6 21 loct. 40 53- lhas not been repeated. '9 3 9-3 3 8.3 l-l 7-5 April 4 ... 4 8.8 - 8.1I ~141 4 7.2 6.6 I5 ...| 6 8.7 2 7.6 - 42 7 11.3 xo.6 3. DIPHTHERIA AND SCHOOL ATTENDANCE. I6 ...l I21 6.o 2 6.o - 43 5 8-7 2 7.6 6-7 -- NOV. 3 9-31 I 8.3 Connected with the subject of personal prevalence comes a ,,17 ...| 3 7-3 44 9.8 I 9.2 question of great practical importance: that of the influence May I8 ...1 4 6.4 3 6.o - 45 5 1 I 9 ...| 21 4-7 2 4.2 - 46 2 8-7 I 7-9 on the spread of diphtheria of infection contracted at school. It 20 ... 4 7-7 3 7.2 - 47 I 8-5 3 7-4 2 Dec. 48 I 7.2 is hardly necessary to point out this is a matter on which 5-5 I 5-4 - 2 6 9.6 there still exists much difference of opinion. For recent June 22 ...1 4-3 1- 4.1 -| I 49 3 9.1 ... 5.2 - - 50 2 9.6 I 8.4 the point I would refer to Dr. Newsholme's 2s23 4-3 dlscussions of 24 5.8 2 4-9 5'1 5 9.2 I 9.1 work just mentioned, and especially to Mr. Shirley Murphy's 25 ... 4-3 3 3.6 - 52 2 9.9 2 8.4 I 9.9 Annual Report for 1896 of the Medical Officer of Blealth of the 26 ,... 2: 4-7 - 3.5 - 53 JU1y 27 ... 5-5 12E 5-4 Administrative County of London, p. 36, with Appendices 1, II, SEPT.3, 1898.] DIPHTHERIA IN LONDON. THzD BoUTaL 613 Nor is there much doubt that, although cases of true diph- taking, was quite borne out by the result, the proportion of theria are tending more and more to be referred to their deaths to notifications for I896 being, as will be seen by refer- proper category, the register of "c roup" still contains cases ence to Mr. Shirley Murphy's report, lately published, only that have escaped transference. The preceding table (Table II) I9.3 per cent. in I896, as against 20.4 per cent. in I895 and -which contains data for "ccroup" corresponding to those of 23.6 per cent. in 1894. Since the date of the materials dealt Table I for diphtheria-demonstrates for the period since I895 with in that report the figures for I897 have become available, now under discussion that the gradual shrinkage of the and it is satisfactory to find that the diminution in case- " croup" returns which began many years ago is still con- mortality still continues, the percentage of cases to notifica- tinuing, while the comparison given below of the annual tions for last year having sunk to the comparatively low number of deaths recorded under the two headings since figure of 17.7. The following table (Table V), the data for I893 shows that even the present reduced mortality from which are derived partly from Mr. Shirley Murphy's report, "c roup" sufficiently reflects that from diphtheria to suggest partly from the Registrar-General's weekly returns, and the inclusion of a common element in both. partly from the monthly list of notifications published in the TABLE III.-London, i893-97: Annual Total of Deaths columns of the Lancet, shows that this diminution in case- from mortality has progressed in spite of fluctuations in the'number Diphtheria and " Croup." of both cases and deaths. Deaths. TABLE V.-London, I893-I897: Annual Deathsfrom] Diphtheria, and Percentage Year. with Notffications Case-mortality. Diplhthelria. "Croup." Case-mortality per Year. Deatlhs. Notifications. cCelt. 1893 ...... 3,264 217 I894 ...... 2,674 i66 I893 ... ,3264 13,694 3 1894 2,674 I,190 23.9 I895 ...... 2,316 144

I895 ... 2,3i6 I896 ...... 2,684 147 I1,229 2C.6 i896 2,684 13,608 19.7 1897 ...... 2,26I 72

I897 ... 2,26I I2,807 17.7 In I896 I published a table showing that the decline in the N.B.-Tlhe figures in this table, being in some instances derived from mortality from " croup " had oa the whole affected the winter rettulrns wliicli have niot uiidergone their final revision, slhow some slight period rathler than the spriing, wlich is what might be ex- differeces from those given in the text above. Tlhere is, lhowever, no pected if Dr. Wlhitelegge's opinion is correct tllat the old material discrepanicy. wilnter and spring maxima of " croup " were due to different It may be added that the experience of I898, so far as it has causes-the former more especially owing its existence to gone, makes it probable that a still further reduction in the inclusion of cases of true diphtheria. I am now able to relative fatality may be looked for. If anyone doubts that present the table in a more complete form by the addition of this improvement in the case-mortality of diphtheria is due the years I896-97, and it will, I thlink, be seen that the new to the introduction of the serum treatment, I think he may evidence points in the same direction as the old. Putting fairly be called upon to say what other factor can have been together the seveni years fromii 1891 to 1897, and comparing at work since I894 capable of producing the present result. them witlh the teni years from i88i to I890, we find that the The fact of the dimiinution in case-mortality cannot be dis- average number of Mlarch deatlhs from "croup" has fallen1 puted, and of this the more or less general adoption of the from 70 to 24, while that of D)ecember deaths lhas declined antitoxin treatment would seem to supply the most feasible from 80 to 21; that is to say, tlhe Mareh fatality has fallen 65 interpretation. per cent., but the December fatality as muclh as 74 per cen-t. The conclusions arrived at in the present paper may be This is all in favour of Dr. Whitelegge's contentionl. brieflv summarised as follows: i. The amount of diphtheria present fn London is stiji high, TABLE IV.-London: Average Number of Deathsfrom " Croup' but is now diminishing after a temporary exacerbation in in. March and December for the Periods I88I-90 and I891-97, I 896. together wvith the Actual Number qf Deaths during the same 2. The experience of the last two years has disclosed Months in each ofthe latter Seven Years. nothing exceptional with regard to the seasonal relaticns of diphtheria. I88i-90* i8gi 1892 1893 i894 1895 I896 I 317 I8gI-;7t 3. The interruption to the usual course of diphtheria mortality coincident with the two chief school holidayperiods is again apparent in both I896 and 1897. The new evidence, Mareli ... 70.5 57 37 17 17 i6 I2 I 5 24-4 like the old, tends to show that school infection is an important, though not the sole factor, in the spread of December ... 8o.5 36 27 29 17 x6 ii6 5 21I.3l diplhtheria. Excess in 4. A considerable, but yearly diminishing, number of March - 21 }I - 0 0 - 7 3. 1 cases of true diphtheria are still returned as " croup." 5. A marked diminution in the case-mortality of Excess in 1.I diphtheria December - 12 0 0 4 - set in at the end of 1894, and has continued up to the present IO.O _ time. This diminution is coincident with the of the treatment by antitoxin serum. * Mean of Io years. t Mean of 7 years. N.B.-The months here are not calendar months, but periods of 5 weeks corresponding to March and December respectively. In remarking on Dr. Dixey's paper Dr. F. J. ALLAN (Strand) pointed out that he had drawn attention in his annual report 5. EFFECT OF THE ANTITOXIN TREATMENT. for I896 to the point that the Christmas and Easter holidays It is a fact admitting of no dispute, that whatever the afforded better evidence of school influence than did the cause, the case-mortality of diphtheria in the metropolis has longer holidays in the summer, when so many children were undergone a steady diminution since I894, the year of the away at the seaside or in the country. Moreover, the summer introduction of the serum treatment. In a paper to which I holidays in the London schools did not all begin simultane- have already referred, read at the Carlisle meeting of the ously, whereas those at Easter and Christmas did so. British Medical Association in I896, I anticipated that by the REFERENCES. end of that year the case-mortality for the twelve months 1 See BRITISH MEDICAL JOURNAL, August 31st, I895, and August 22nd, would for the first time on record have sunk below 20 per i896. 2 This objectioni has been well stated with reference to yearly averages by Dr. Newsholime in his valuable work lately published on cent. This expectation, based on the course events were then Epidemic Diphtheria (London, I898). THE BRITISH 1 STATE MEDICINE. SP.3 88 614 MEDICALor~~~~~~~SCTOJOURNAL] SECTION OF [SEPT. 3, i898. parison in giving percentages to count the number of infecting THE ETIOLOGY OF " RETURN CASES " OF cases rather than the number of return cases. SCARLET FEVER. PROPORTION OF RETURN CASES. By C. KILLICK MILLARD, iI.D., D.Sc.(Public Healthi), Of the 4,8IO patients from whom my figures were drawn, in Medical Superintenident, City Ihospital, Biri-iiigihamii. 158 cases the return home was followed at varying intervals of OF all the diseases usually treated in isolationi lhospitals, in from a few days up to six weeks by a fresh outbreak of scarlet none is it so difficult to pronlounce with certainity as to the fever, resulting in the admission to hospital of 171 so-called: condition of a patient witlh regard to hiis freedomil from in- return cases. This is a percentage of 3.4 infecting cases, or3.y fection, or the reverse, as in the ease of scarlet fever; and it return cases. is not surprising, therefore, that with this disease the dis- Considering the special pains that lhave been taken by us; charge of patients from hospital is less rarely associated with to reduce the number of our infecting cases to a minimum the conveyance of infection to others, and the resulting so- these figures may not look so small as might have been called " return case" than with any other disease. expected when compared with the published results of some The importance of this subject from an administrative writers. Tlle explanation of this, however, lies very largely point of view was more forcibly impressed uponl me thlan in the arbitrary limitation which is set by some to the length would otherwise have been the ease in consequence of an of the "interval." Some writers have actually fixed this as action brought against the Corporation of Birmingham some low as seven days, refusing to count as return cases those three years ago by the parents of a chiild wlho was dischiarged coming to hospital after a longer interval than this. They from the Birmingham City Hospital slhortly before my ap- take seven days as being the maximum incubation period of pointment as Medical Superintendent. This case-Ke'egan scarlet fever, and assume that a patient returning home still v. the Corporation of Birmingham-was, I believe, unlique, infectious will at once infect otl-her members of the family or and attracted a good deal of attention. Certainily the verdict not at all, and that, therefore, cases occurring at a later periodS came as a great surprise. TThe jury before wlhom the ease was must be accounted for as accidental coincidences. Had I tried found that the infection of scarlet fever lhad beeni carried adopted such a short interval as this, my percentage would' home by a child discharged from the City Hospital, witlh the have been less tllan 2 per cent., or little more than. half what. result that another child had contracted the disease anld died, it really is. A more usual period to adopt is three weeks, but and they awarded the plaintiff damages to the extelnt of £50, even for this there is no scientific reason. The principle I although adding a rider to their verdict acquittinir the lios- have acted upon is to count all cases, and to do this I find it. pital officials from any negligence. I cannot myself believe is necessary to extend the duration of the interval to six that such a verdict would have been upheld. Did it really weeks. I have found that practically no cases occurlaterthanr represent the law on the subjeet, the position of tllose re- this. sponsible for the management of isolation hospitals would be Aniother cause which I venture to think accounts for the^ a most unenviable one. It is certainly, however, most de- apparent smallness of some figures that have been published, sirable in their interests that the precedent created by the is that unless searching and systematic inquiry is made in above case should be overruled as soon as possible. the case of every patient admitted to hospital, it is quite Amongst those writers-and they are not very numerous- certain that maDy return cases will escape being recorded. who have approached this subject during the past few years, As an example of this I would mention a report issued some few, if any, have attempted to classify or analyse system- time ago by the Metropolitan Asylums Board upon this; atically cases in suclh a way as to give statistics whichl would subject of return cases. The conclusion there arrived at form some reliable basis for comparison an-d deduction. This apparently was that they almost doubted the yery existence appeared to me to be desirable, and I lhave therefore been of return cases, at least in their hospitals. I understand, how- endeavouring for the past two and a half years to collect the ever, that they are making further inquiries, and in due time, material for my present paper. I presume, will issue another report. I shall be curious to The tables are based on an analysis of 4,8IO eases of scarlet see whether this confirms their previous conclusions. fever discharged from the Birmingham City Hospital during In the following table (Table I) I have classified my I58 the above period. The exact condition of these patients at infecting cases according to the length of the interval: the time of their discharge, and other details, were recorded in a register specially kept for that purpose. TABLE I.-Showinq Length of " Interval." DEFINITION OF TERMIS. Weeks...... I 2 3 4 5 6 Before going further it will, perhaps, be advisable for me to define exactly the meaning of the special terms I propose to Cases ...... 62 44 28 14 9I use in connection with my subject. Percentage ...... 39.2 27.8 I7.7 8.8 5-7 I count as a " return case" any patient coming to the hos- pital with scarlet fever from a house to whicll a patient dis- charged from hospital has recently retirned.1 Tlle latter, It will be observed that the cases are most numerous, as we called some writers the " should expect, during the first week, and decrease uniformly by original case," I slhall speak of as during the succeeding weeks until they have practically dis- the "infecting case." Theperiodelapsingbetween thereturn in the 6th week. This table shows home of the "infecting case " and the onset of the first symp- appeared conclusively I toms in the "return case " is the " interval." think the necessity of taking an interval to cover all the cases. The time from Those in the and weeks are the onset of illness in the infecting case to the time it finally occurring 4th 5th undoubtedly as- leaves is the " of isolation." Wlhere, as some- much connected with the return home of the infecting cases. hospital period as those occurring earlier. times happens, patients are not admitted until some little The return should not time after the onset of their illness, as in the case of patients explanation why eases always oceur admitted it becomes to directly upon the discharge of the infecting case with merely- desquamating, important distinguish an interval to the this from merely "time in hospital," as spoken of by some corresponding incubation period is not, writers. The time from the onset of the illness in the infect- difficult. ing case to the onset of illiness in the return case, deducting I. DOMESTIC ISOLATION. four days for incubation period, is tlle " duration of infection." In many eases the parents make an attempt, more or less: It not infrequently happens that an infecting case is conscientiously, in compliance with the instructions received followed by more than one return case. If, lhowever, there is from the hospital, to keep the returned child apart from any- an interval of several days between the occurrence of the other members of the family who might be likely to take it. latter, it is probable that only the first one is a true return After a few days or a week, or perhaps after the full fortnight. case, the later ones being infected from the first. To prevent enjoined, this precaution is relaxed, and if inquiry is directed: this element of confusion it is better for purposes of com- to this point it will often be found that this accounts for many of the 1 The only exception to this is wlher e it can be conclusivcly shown that longer intervals. Sometimes, indeed, the returned: the patient returining lhome could not have been tlle source o! infection. patient is sent away for a time after leaving hospital to be-. This occasionally happens. followed by a return case immediately upon his return home_. THE BRITISH 6 15 SEPT. 3, 1898.1 " RETURN CASES " OF SIARLATINA. NIEDIC AL JOURNAL A 2. RECRUDESCENCE OF INFECTIVITY. ones whlichl lhave to be sent out at last in desperation. At the There is no doubt that many cases wlhich appear free from same time, wlhilst taking I2 or I3 -weeks as a fairly safe infection at the time they leave lhospital really are so tlhen, as maximum period of isolation, I believe that infection may be far as their power of inifecting otliers goes, but suffer from a caliried il rare cases after as long as I4 or even i6 weeks. sort of recrudescence at varying periods after their returni In Table III I lhave classed the infecting cases into two and thereby again become infectious. This is frequently groups only, those under 9 weeks' isolation aind those over. manifested by the recurrenice, or even primary developmenit TABLE III.-&Showing p)ropo)rtion of Injecting CGases anid all Cases of a nasal or ear discharge. i6(olrtted under 9 wreeks andit oter 9 weeks respeclively. 3. SLIGHT DEGREE OF INFECTIVITY. Some cases are probably so slightly infectious that they Under Over require to be brought into the closest possible contact, and Period of isolation ...... Nveeks.w 9 week-s. " that repeatedly, before the infection takes," so to speak. PerceltagC of iInfectilg CIISCaS ...... 69.0 31.0

4. VAItYING SITSCEPTIBIL1TY OF INDIVIDUALS. Perecitagc of allczses ...... 5c.0 41.0 It is a well-known fact that patients admitted to a scarlet fever ward on an erroneous diagnosis may develop the disease This brings out the fact tllat the proportion of infecting at any period during thleir stay in hospital. Thiey by nio cases after less tlhan 9 weeks is unduly large, whilst, con- means always develop it during the first week. Probably this versely, the proportion after over 9 weeks is unduly great. reason is the strongest of all. Taking, this fact togetlher witlh Table II, I conclude tlhat, independently of a patient's apparent fitness for dischlarge, " PERIOD OF ISOLATION" OF TIHE INFECTING CASES. risk of Isis infection begins to fall after 9 weeks. This is a very important point, because the occurreince of a the carrying return case is ofteni, righltly or wi-ongly, lheld to be aIi indi- AGE DISTRIBUTION OF " INFECTING CASES." cation of premature discharge, and undoubtedly the period of In Table IV the infectinc cases are grouped into age isolationi must exercise ani importanit iI)flueince on their occur- periods, and the figures are also given as percentages, with rence. The exact relationslhip betweeil tlhe durationi of the the corresponding percentages of " all cases " for comparison. period of isolation and the number of return cases is not, however, so clear. The average period of isolation of "all TAIBLE IV.-Shmobinq Ale Distribution of Ifecting Calses. cases " discharged during the time over wlhicll my inquiry extends was 8.5 weeks, and, curiously eniougol, the averaae Age Period in Years ... 0-5 5 0 IC-I5 I upards. period of isolation of my infectiing cases was 8.3, or very Inifecting Cases ...... 27 54 20 8 2 nearly exactly tire same. Taking the figures as they stand, it would look as if the period of isolation lhad very little in- Percentagc of Cases ... 24-3 45.6 I8.° 7.0 I.8 fluence. In order, lhowever, to see if this was really so, I all Cases 23.7 I I9.6 3. 2 have prepared Table II, in wlhichl I have grouped the in- Pcrecitage of 4 .4 6.9 fecting cases according to their periods of isolation, slhowinig I lhad tlhoucrlgt it possible that ani undue proportion of in- the percentage of the wlhole in eaclh division, and giving also fectinig cases would lhave occurred at some particular age- for comparison-lwich, of course, is the important thing-the period-for example, amongst chlildreln unider 5. Tlle age percentage of "all cases" wlich were discharged after the distribution, however, being almost exactly proportionate to same periods. that of " all cases," we can only conclude tllat age lhas no TABLE II.-Showving " Period of Isolation" of " Iiifectiny Cases inifluence on the tenidency to carry infection. as coepartred with "All Cases." SEX. Of my infecting cases 88 were females, and only 69 were Unider Over males. Tllis excess of females may possibly be accidental, Period of isola- 6 6-7 7-8 8-9 9-o0 I0-II II-I2 12.13 13 tioii ill weeks but it is quite conceivable that a difference in the doimestic sexes for it. No. of iifectiing 31 30 39 27 7 5 5 4 lhabits and relationslhips of the two may account cases ine acli I Tlhus a girl would probably be more kissed onl her return per-iod lhome by other members of her family. Perentage of 3.2 20.5 i9.6 25.5 117.5 4.5 3.2 3.2 2.6 ditto. I lhave also found that infection is more frequently con- Percenitage of 5.5 i6.o 211.0 i6.2 I1.2 8.7 5.8 4.7 I0.4 veyed by one sex to the same sex than to tlhe opposite sex. all cases Tlhus 87 of tlle infecting cases were of tlhe same sex as the return cases they gave rise to, and only 64 of the opposite sex. Averalge pei-iod of isolatioil of iilfectiiig calses, 8.3 Nvceks. Tis, again, is nIo doubt due to domestic relationshlips, some ,, all cases, 8.D wveeks. I 1 9 1 ? attempt at grouping the sexes in their sleepingc arraligements I anticipated that an unduly large proportion of the in- being made eveni in the most households. fecting cases would be found to be patients wlho had been dis- primitive charged after the minimum period of isolation, and that tlhe SEASONS. average would lhave been equalised by a few cases that lhad Boobbyer, of Nottingham, in a paper on the subject which been detained exceptionally long. As a matter of fact, hiow- he contributed to Pueblic Health in June, I896, stated his ever, the table shows that io suclh generalisation can be opinion that return cases of scarlet fever were more prevalent, accepted, for whilst the propoltion of infecting cases is about thlat is that tlle percentage was greater during the autumn the same as that of " all cases " in the first thlree columns, it months of the year, and lie attributed thlis to the accommo- becomes distinctly greater in the 8 and 9 weeks' columns, anid dation in fever lhospitals beinig generally strained at that then very much smaller in the remaining columns, until in season, so that there would be a tendency to reduce the the last one, namely, over I3 weeks, the percentage is only 2.6 period of isolation. MNy experience as yet has been of too as against 10.4 of " all cases." short duration to enable me to speak as to this. In November The explanation I would give is this: The patients dis- and December, I896, we did certainly lhave a very marked charged after the shorter periods of isolation, that is, under increase of return cases, but it was not repeated the following 8 weeks, are principally the simple uncomplicated cases year. Nor was it due to aniy reduction in the period of whereas the complicated eases-more especially those com- isolation, the mean duration of the latter being equal to the plicated with otorrllhea or rhinorrhea-that is, the cases most average for other months. calculated to carry infection, are always detained longer. With this discrimination we see that the period of isolation TYPE OF RETURN CASES. becomes a very important factor, and that after 12 weeks the It lhas been found by several writers that the type of the risk of infection becomes exceedingly small. The safety disease in return cases is somewhat more severe on an induced by such prolonged isolation is probably greater than average, and therefore thley are more fatal than when con- appears merely from the table, because the cases leaving tracted in an ordinary maniner. My experieniee corroborates hospital after 12 weeks include those chronic and ineural 1. this, for out of tlle I7I return cases 13 were fatal, or a case- lirz BvinsH I 6i6 SEPT 3, 6otaityMIWWALof JOURWALJ SECTION OF STATE MEDICINE. SEPT. 1s998 r OFnt 3,r cet.fo"al mortality Of 7.6 per cent. as against 4.8 per cent. for "1all and dressing have been properly performed by the nurses. It cases" during the same periods. As time is an important leaves a record of the patient's exact condition at the actual factor in reducing the vitality of infection, it might have been time of leaving the hospital, and it gives an opportunity for expected that it would reduce virulence also. It must be the medical officer to interview the friends, who are in a remembered, however, that the patients which carry in- waiting-room in the same block, and to give them any in- fection out of hospital are, so to speak, selected cases; for it structions or advice. Lastly, it is a check on the primary is just because the infection in the infecting case is active examination, and ensures that it will be carefully and and resistant that the infection is carried out. minutely made. On examining convalescent scarlet fever patients at the end TYPE OF INFECTING CASES. of six or seven weeks various lesions or traces of the disease It is not possible to consider the severity of infecting cases may be discovered-for example, desquamation, usually on by the simple but accurate method of comparing their case- the hands or feet, inflamed throats, enlarged glands in the mortality with that of " all cases," for the obvious reason that neck, sores, cracks, excoriations, etc., albuminuria, otorrhoea, it is necessarily only those patients who recover who can and rhinitis. Patients manifesting any of these conditions become infecting cases. I do not, however, think that the are usually detained for a longer period of isolation, and in cases which carry infection are much more severe than tlhe average, the majority of cases it is possible to get them perfectly clear and certainly some cases are of the very mildest. I do, before sendinig them out. This is not, however, always however, think that complications, more especially feasible. Somnetimes the lesions referred to are exceedingly certain complications, are more common. unyielding and persistent; often the parents decline, not unnaturally, to have their children indefinitely detained, CONDITION OF INFECTING CASES ON DISCHARGE AND occasionally it is desirable for the patient's own sake that he SUBSEQUENT HEALTH. should be sent out. In practice, then, a certain number of I will first briefly mention the routine method adopted at cases are senthome afterv arying intervals with one or other the Birmingham City Hospital before patients are allowed to of these colnditionis prcscnt. It has been one of my chief return home. All cases are detained fora minimum period of objects in tllis inquiry to endeavour to ascertain in what six weeks, counting from the onset of their illness, not from degree, if at 1II, these different lesions are likely to be asso- the day they come to hospital. A special register is kept in ciated with tlm carrying out of infection, and Ihave prepared each pavilion, in which is entered the name and number of a table (No. 5) with this in view. It would obviously have the patient,the datehe was taken ill, the period of isolation, been of little use merely tohave tabulated the number of the the number of children at home (if any) wh1olhave nothad different lesions noted at the time of discharge amongst the the disease, and any special remarks. If the casehas been "infecting cases " only. It was essential for such figures to previously examined, the condition then noted is also in- be of real value that we should also kniow in what pr-oportion in the cluded. The patient is minutely examined best lighlt the same lesions existed amongst " all cases " disclharged. available, and the bed chart consulted to ascertainthe type This, fortunately, I have been able to obtaiin from our and course of the attack, complications, etc. The patient's registers. exact condition at the time of examination is then recorded, In preparing this table it was necessary to guard against whether it is decided to" pass" him to go home or not. In certain possible errors. Inthe first place it not infrequently a sent or the former case printed notice is to the parents happens that when a patient is an only child, or is returning friends asking them to bring the necessary clothing two days to ahouse where there are no susceptible individuals,he later. At the appointed time the patients going home are is allowed out with lesions still present sooner than would taken to the "bathing-out"pavilion, which is of the approved otherwise be the case. Obviously it is highly improbable, if type, and consists of a double suite of rooms for males and not impossible, that sucll patients will give rise to return females, each containing waiting-room, undressing room, bath cases, and therefore they must be excluded. Secondly, I a common" " room, dressing-room, and opening into finishing have alreadyshlown that the risk of a patientconveying infec- room. A special staff of nurses is told off on discharging tion afterthirteen weeks' isolation is very small indeed, no days for the duty of"bathing-out" the patients, and the matter what his condition may be, andtherefore all cases following special rules have to be observed:- discharged beyond that period must, in fairness, also be BATHING-OUT RULES. excluded. r. The batlhing-out to be commenced iimimediately upon receipt oftlhe patient's clothes, and to be performed as quickly as possible compatible on :kith thoroughness and care. TABLE V.-Showcinq Condition Discharqe of"Infecting If insufficient clothing is brought, or if the nurse considers it unfit Cases " as comparedwvith All 6ases. for wear, she must at once inform the Matron. 3. The patient's own clotlhes to be kept carefully separated fromtlhe infeted ones worn in hospital. cn 4. Each patient to have a clean batlhslheet. 222 0o The bathing-ouit nurse to wear clean apron and sleeves. C ondition . C : > " = =i 6."Izal to be added to the water until it becomes distinctly milky. on Dischlarge. 5 cae 7. Carbolic soa to be used and the patienit washed all over with it. The heador eahicliid to be rubbed witli carbolic oil after the bath. .. The hair of each adult must, aftertlle usual waslhing be dipped in mooo formalin,; in the case of women this should beaone andtile lhairdried before the batli is given. 1I No. 5 4 2 36 92 o. The nose andears to besyringged out, if thislhas not already been 5 5 done in the ward, withl in 2.000formalin. Infecting, Per. xi. No patient to belhanded over to friends until the lair is quite &ry centager. 7.0 3.T 2.1 3. 3.21 o.6 2.2 22.9 55.2 3i. Every patient to be seen bythle miiedical officer on duty after bathing. 205 59 13. The nurse to at once repor-t anythling about a patient whichselimaay All No. 1I37 55 26 13 2I5239 I8I5 discover andwhlich is not noted in the Disclharge Register. Cases.t Per- 14. Every patient hlaveto hlota drinik anid somethlinig to eat before being handed over to the friends. centage. P 5.4 2.3 2.2 2.0 0.5 2. 6 72.6 By order of the Medical Supeirintendent. * The final disinfecting bath having been given, the patients Applies almost exclusively to late desquainiation on the feet only. t Based onl records Of 2.500 cases dischiarged, and not oa the total 4,820 re again examined before being handed over to the friends. " This second examination I prefer should not be done by cases amonagstwhlichl theinfectiing cases occurred. myself, but by one of my colleagues, the condition already Some explanation is also necessary as to the meaning noted by me being checked in the register. I strongly attached to the headings of thle different columns. "Desqua- believe in this dual examination. In the first place, it mation " refers almost exclusively to desquamation on the feet tot very infrequently happens that in the interval since only. As already pointed out, desquamation on the body hee patient was first examined some fresh development generally, and on the hands, is nearJy always completed within oeeurs which may render it desirable to detain the case for a the minimum period of isolation, and in any case is seldom huger period. In ensures that the process of bathing, drying, pslQ1onged -much beyond it.a Fauces Abnormal" includes [THU Bamax 61 SEPT. 3, i898.] "RETURN CASES" OF SCARLATINA. IME JOURNAL6ua

tonsils as well as mucous membrane. specially liable to be disseminated by currents of air, we slhould enlarged congested " " of fever to one,have "Sores and excoriations " includes and all expected the striking distaince scarlet have been a long cracks, abrasions, and a scarlet fever lhospital to be a great centre of infectiol to its neigh- raw surfaces other than tlose in or about the nostrils. "Aden- bourlhood. As a iatter of fact, however, the reverse is the case, thoug& itis" means hypertropliied cervical glands. "Skin eruptions" scales of epitlheliuin must float away witlh every breeze to be deposited in includes all forms of eruption liable to occur during convales- the surrouniding lhouses. cence. "Albuminuria" chronic On the other hand we can seareely say that it has yet been includes chiefly nephritis. that the old and classic view is not even " Otorrhcea " means purulent discharge from the middle ear. proved correct, though " " Klein has failed to find his special organism in the desqua- Rhinitis I have used to include all cases, however slight, mating cuticle. Moreover the process is essentially a specifie where there was any reason to suspect the nasal cavity, and it be held that its existence ig whether there was actual discharge from the nostrils or not. one, may reasonably very an indication that the disease is still present. For myself I It frequently happens that after a rhinorrhcea has ceased, or consider that the question has not yet been settled, and even wlhere there has been no visible purulent discharge, an to unhealthy condition may still be detected at the nostrils. prefer withhold my judgment. There may be redness or actual excoriation, or crusts may be OTORRHIIEA. found just inside them. Sometimes no discharge may be This complication differs in one respect from rhinitis in seen until the nose is syringed, when thick, dried-up, puru- that it is more definite both in its onset and termination, lent discharge may be found in the return lotion. Frequently at least as regards its external manifestations. Consequently there is a thin, water-y mucus oozing from one nostril, scarcely it is much more easy to decide whether or not it is present in distinguishable from normal nasal secretion. any given case. This is the reason why it has played but a small part in the causation of our return cases. Being firmly RHINITIS. convinced of its highly infectious nature, I make a routine I have for some time believed in the special infecting practice of detaining all cases for at least thirteen weeks' isola- power of any discharge from the nose following scarlet this I believe the risk of its but I was for a tion. Beyond period carrying fever, scarcely prepared suc11 very striking infection is very slight. The longest duration of infection confirmation of this as is given in the table I am now con- amongst from the onset of the illness in sidering. It will be seen on contrasting the percentage of my cases, countinig the infecting case to the onset of the return case, with a lesions in infecting cases with those of " all cases" that in deduction of four days for incubation period, was just thirteen almost all the columns, oxcept that for rhinitis and otorrliea, weeks. The next two were twelve and the remainder the percentages are fairly uniform, and in the columns for weeks, a shorter period. As a precaution, h-owever, I usually supply "desquamation," "adenitis," and "abnormal throat," we at the parents of all ehildren returning home with otorrhcea,. least have evidence that the conditions there included have the not cured is very small played little or no part in the present series of return cases, as thouglh proportion in hospital indeed, witlh a syringe and other materials for continuing their percentage occurrence amongst the infecting cases is treatment at home. even smaller than that amongst " all cases." On the other antiseptic hand the very excessive proportion in wlhiclh "rhiinitis " SUBSEQUENT HEALTH. occurs-nearly 4 to i-proves undoubtedly that this lesion far I have already referred to the possibility of patients under- more than any other tends to carry infection. I would going a recrudescence of infectivity. I think all will agree emphasise however the fact already mentioned, that the with me that this does undoubtedly occur. The following term as I have used it includes the very sliglhtest cases where case is a good example: there be more on an external obser- may nothiing apparent W. D. (Reg. No. 83). aged 8, was discharged from hospital early in the vation than a slight redness or a little moist oozing. present year after eighit weeks' isolation. lie had had a simple attack witlhout complications, and was apparently in good healthl. He returned DESQUAAMATION. home and mixed witlh the otlher memibers of the family witlhout bad I feel satisfied that confined to the feet, effects. Tlhree weeks later, howvever, hlis niose began to diselarge, and a desquamation later hiis to the disease. and occurring long after the process of desquamation on the week sister, aged io, began sickenlwitlh body generally has been completed, is no source of danger. This case is by no means exceptional. I have made special The epidermis on the feet has very special anatomical charac- inquiries in my last 6o infecting eases, with the result that I teristics. This probably accounts for the fact that desqua- find that out of 33 of them who went home apparently quite mation in this region not only may not begin until the well, two subsequently developed otorrhcea, and no fewer tha,n has been and than io suffered from a discharge from the nose (sufficiently process entirely completed elsewhere, the marked to attract the mother's attention), in all cases, of cuticle take much longer in separating, but it is more liable return than elsewhere on the body to recur a second or even a third course, prior to the occurrence of the case. time. Whether the desquamating cuticle of a scarlet fever CONCLUSION. patient is specifically infectious-that is, more than would be In conclusion, I would say that I think that attempts to accounted for by its close contiguity to an infectious body, or as is often as due to in other explain away return cases, done, being words, whether it contains the germs of the disease other causes than an infectious condition of the patient in itself or only carries them as any fomites might do, is a much to be debated returning home are deprecated. Other causei question. At first sight the distinction I have indi- may perliaps operate very occasionally, but there can cated may not appear of much practical importance, but, be no doubt that in the majority of cases the infection is reallk nevertheless, it is so, because if the shed epithelium only carried by the patient leaving hospital. Nor do I think that obtains its infection as fomites, it can no longer be regarded the infection- is carried superficially as might be done by as a criterion of infectivity as it used to be and probably still any person coming from an infectious atmosphere. Th6 is by a majority of the profession. We all admit, of course, "bathing-out " precautions sufficiently provide against this' that a patient desquamating about the body or hands is and the infection, if carried in this way, would almost certainl'y almost certainly infectious, because we know that the stage of be conveyed at once, that is, in the first day or two, or not at all. infectiousness usually lasts longer than the process of general We a sort of control in the case and therefore it is a rule to liave, moreover, experimenit desquamation, good practical of our nurses and wardmaids who, since they live in an in'- regard a desquamating patient as still infectious. At the fective atmosplhere under nearly similar conditions, might be same time there are certain considerations which rather also to out infection in the same way, I against tlle scientific correctness of the old and expected carry wllich point, think, practically we know they do not do. accepted view: We have no to assume that the virus of scarlet' f16*t x. right Tue infection certainly persists in very many cases for weeks and we can no even montlhs after all trace of desquaniation lias disappeared. There is has really left the system merely because longek obviously tlhen some source of infectioni independeilt of desquamation. find any visible manifestation of it. In other infectious 2. Although there is abundant evidence to prove that desquamating diseases-for example, syphilis, we know that the virus ina patients are infectious, there is not, as far as I am aware, any positive for months and evidence to show that the desquamation is itself the special source of persist, and be potent to spread infection evele infection. years. In a disease in many ways analogous to some cases of There is evidence, gradually accumulating from fever that scarlet nasal infectivity la3 hospitals, fever, namely, diphtheria, niat' pert te desquamation, more especially secondary desquamation, is not a as was shown Mr. J. C. of source of infection. My own figures point to this. sisi, conclusively by Heaven, 44.From the physical character of dry epithelial scales rendering thoemi Bristol (in a valuable paper read before the Society of Med-ical THz BRiTisH I 6i8 MEDICAL JOURNILJJOURNAL] SECTION OF OBSTETRICS A-.,NDAND DISEASES OF WOMF-N.WOMEN. [SEPT. 3, 1898.I8gS.

Officers of llealth in March i896), for as long as six montlhs. The following metlhod of operation is tlle one wlichl I find In this (disease, however, bacteriology comes to our aid, and it most satisfactory. After the preliminary cleansing and dis- is in the direction of the latter science that we must look in infection of the vagina and vulva, the cervix is fixed by a the future for assistance in scarlet fever also. I think it very suitable instrument (teinaculum, or some of its modifications). probable Wte slhall fiiid that it is really in the nasal cavity As the anterior lip of the cervix is so frequently involved in that the organism of scarlet fever most readily finds a lodg- the disease, the tenaculum is best applied to tlleposterior ment in those cases where the infection is unduly prolonged. lip. Where the growtlh resembles the so-called cauliflower In the meantime it is to the condition of this cavity that we excreseence, it may be absolutely necessary to remove a must pay most attention in examining patients witlh a view portion of the disease in order to obtain a hold witlh the to pronouncing them free from infectioni. tenaculum. Certaini resolutions adopted at tlle conclusion of tle business I always make the posterior incision first (tlhe posterior of the Section will be found on page 363 of the BRITISH cervical lip being previously drawn forwards), because if the MEDICAL JOURNAL of August 6tlh. anterior incision is made first the liaemorrliaae tends to ob- scure the view. It is also a good plan to prolong the incision into the lateral fornices. After sligllt separation of the bladder anteriorly, and especially laterally, in order to lift the ureters forwards, tlle posterior vaginal wall is separated. The THE SECTION OF OBSTETRICS AND ligatures slhould then be applied to tlle uterine arteries, in DISEASES OF WOMEN. order to arrest the lhiamorrhage from tlle growth. Before any great traction efforts are made on the uterus, the pouclh of Professor A. R. SIM,PsoN, MI.D., President. Douglas slhould be opened in order to investigate the presence or absence of cysts, fibroids, or tubal swellinas wlieh may CLA3MP AND LIGATURE IN VAGINAL [IYSTER- complicate the operation. I lhave found this precaution very advantageous wlhen operating on eomplicated cases. In one ECTOMY FOR MALIGNANT DISEASE where a large cervical sarcoma was complicated witlh fibroid OF THE UTERUS. outgrowtlhs into the blood ligaments, I found on examination witlh the finger in Douglas's pouclltlhat, on the left side of tlle By F. J. MCCANN, M.D., C.A., uterus the fibroid outarowth was smaller, and accordingly the Phlysiciani to Outpaticiits, Saimaritan IIospital, London. left broad ligament was ligatured and completely divided, MY purpose in tllis slhort paper is to elicit opinion as to tlle thus permitting tlle uterus and right broad ligamiient to be relative merits of the clamp and ligature, or a combination of pulled downwards. In this case traction on the uterus did botlh in vaginal hysterectomy for malignant disease of the not pull that organ downiwards, on account of the size of the uterus. In my first cases I used the ligature alone, fol- fibroid outgrowtlhs. If cysts are found they should be lowinr tie method wlhiclh I first saw adopted by Professor punctured. Leopold of Dresden. The bladder slhould now be completely separated, and the A larger experience of malignant cases convinced me that utero-vesical pouclh of peritoneum opened by grasping the recurrence was best prevented by a free excision of the broad peritoneum witlh forceps and snippiing with scissors. Tlle ligaments, and for this purpose clamps are undoubtedly more opening may tllen be enlarged. The body of the uterus .s,rviceable. Ligatures cannot be applied close to the pelvic slhould now be grasped by a strong tenaculum as near the -walls, as there is great difficulty in tying the knot deep in the fundus as possible and pulled outwards. A long clamp can pelvic cavity. The ligature is most suitable as a then be applied from above downwards to eacll broad liga- means of temporarily arresting the htemorrhage from the ment, including as muclh of the ligament as possible. If the growth-where tlle cervix is involved--by securing the ovaries are to be removed, the clamp slhould be applied ex- uterine arteries in the bases of tIme broad licaments. ternal to eaclh ovary. The uterus is cut away, and the vagina The objection to the use of clamps for this purpose is that cleansed. Gauze is packed into the vagina between and they occupy more space, and thereby hinder the further around the forceps in long strips. steps of the operation. The gauze slhould be chlanged when the clamps are removed In operations for malignant disease of the body of the at tlle end of forty-eight lhours. There is so much oozing of uterus, tllis preliminary ligature of the uterine arteries is blood and serum after vaginal hysterectomy tllat it is too great most important. The great desideratum is to prevent the a strain on tlle antiseptic properties of the gauze to leave it patient losing blood; for most of the unfortunate sufferers are in situ longer tlaln forty-eight hours. Moreover, the patient already affected with anaimia. Doyen and others advocate is rendered more comfortable when the gauze is clhanged. as is traction on the uterus as a means of arresting hlamorrliage. I never employ douchling after vaginal lhysterectomy, it In many cases where the disease is well marked the uterus daiigerous slhould the peritoneum not be completely sihut off. cannot be pulled down, and, moreover, ineffectual attempts Swabbing out the vagilna daily with pledgets of wool steeped at traction are frequently the cause of considerable lhmmor- in corrosive sublimate is much more efficient. It has been thage. Wlhen the base of the broad ligament is secured on stated that operation by means of the clamp is more rapid eacti side it may be divided between the ligature and the thain by the use of the ligature. Much, however, depends uterus thus permitting the latter to be pulled downwards. on the skill of the operator and the nature of the case. A sufficient separation of the bladder anteriorly and the In cases of early cancer of the cervix, where tlle uterus is vaginal wall posteriorly for that purpose can be effected with- small and freely movable, the operation can be easily done by out the necessity of drawing down the uterus. Much blood the ligature alone in lhalf an hour. It is doubtful if there is -is frequently lost where the growth is scraped away by the any great difference in rapidity wheln the two methods are -fingers or curette. It is much better to secure the uterine employed by a skilled operator. arteries before this is done. The great advantage of the clamp is that a larger amount of I am firmly convinced that the less the malignant growth the broad ligament on each side can be removed. This cannot is scraped or cut tlhe better for the patient. Such a pro- be done equally well by the ligature alone, and unless the broad cedure may favour dissemination. For this reason I am ligaments are freely excised in cases of cancer of the cervix, opposed to tlle method of splitting the anterior wall of the I fail to see the advantage of total extirpation over supra- uterus, and still more to mo-cellement. If the uterus be vaginal amputation. It is further stated that convalescence small, splitting the anterior wall is unnecessary; if large, is delayedaftertle use of the clamp, and that there is more pain. it can be easily removed by separation of one broad ligament From my own experience I have not found the convalescence previously ligatured from below upwards. The uterus can delayed, nor lhave I found the large amount of slouglling after then be pulled downwards and outwards, and the remaining the operation whiell some authors deseribe. Much depends broad ligament clamped from above. The cut end of the on the degree of care in the use of antiseptics before, during, other broad ligament can now be pulled outwards and a clamp and after tlle operation. I believe that gauze plugs left too put on outside the ligatures, wlich are then cut away. long in the vagina may account for the increased sloughing. Cases wlhere thme uterus is much enlarged should be treated As to the amount of pain after the operation, this varies by abdominal total extirpation. considerably. Wlhere violent traction has been employed, 19E SEPT. 3, I898.] SECTION OF OPHTHALMOLOGY. [Tw Btsr- I = I more pain will be experienced, and here let me add that the shock of the operation is thereby much increased. SECTION OF OPHTHALMOLOGY. Patients who suffer from cancer of the uterus do not, as a rule, stand prolonged traction on that organ. Perhaps there D. ARGYLL ROBERTSON, M.D., LL.D., President. may be more pain after the use of the clamp, but from my own cases I have not observed any appreciable difference. THE USE OF HOLOCAINE IN OPHTHALMIC There is no one method of operating applicable to all cases PRACTICE. of malignant disease of the uterus treated by vaginal liysterec- tomy. I believe, however, that a judicious combination of By JAMES HINSHELWOOD, M.A., M.D., F.F.P.S.G., clamp and ligature will ultimately become the usual method Surgeon to the Glasgow Eye Infirmiary. adopted. I hope, however, to have the advantage of hearing [ABSTRACT.] the opinion of those wlho have had a large experience of the OF late several new drugs have been introduced into oph- operation uinder consideration, in order that we may be able thalmic practice as substitutes for cocaine. Of these the most to settle on the method most advantageous to our patients. recently discovered, holocaine, has been the subject of con- siderable attention since its discovery by Tauber in the beginning of 1897. The first communication regardinig it will A TABLE OF CASES OF INDUCTION OF be found in the Centralblatt fiii praktische Augenheilkunde, PREMATURE LABOUR. January, I897, where Professor Hirschberg, of Berlin, gives a By JOHN MOIR, M.D., F.R.C.P. short note regarding his experiences with a new drug as a substitute for cocaine. This new drug had been given to him DR. MOIR submitted the accompanying table, showing the for trial by Dr. E. Tauber, Priciat-docent of Chemistry in the result of hiis practice in the induction of premature labour in Technical High School of Berlin. Professor Hirschberg cases of malformed pelvis. He desired to point out the a few of i cent. solution of advantages of the initiated remarks in his note that drops per practice, by Professor Hamilton, this drug rendered the eye insensitive in a few seconds, so of gradual dilatation of the os and cervix over the modern could be removed from cornea without practice of forcible dilatation of these parts and accomplish- that foreign bodies the the whole of in a pain. ing process delivery single day or less. He This communication was rapidly followed by others, chiefly believed that the latter mode of practice was attended with who their risk to the mother and of ulterior by German and French ophthalmic surgeons, gave great danger damage-such experiences of the use of the new drug. All those who have as prolapsus and its consequent evils-and little chance of recorded their experience with holocaine, while differing in having a living child, which was the chief end and object of of are that the of the The table women matters detail, agreed chlorohydrate holo- operation. showed that 29 who went to caine can be substituted with advantage for the chlorohydrate- the full time were pregnant 49 times, and that not one of these as a local in children was or could have been born of cocaine aniesthetic ophthalmic practice by 49 alive. Premature reason of certain decided advantages which it possesses over labour was induced as above indicated in these 29 women, cocaine. I have tllought it might prove interesting to the and the result was the birth of 66 living and healthy children; members of this Section who have not yet tried this new 17 only were stillborn or lived only a very short time. But ansesthetic to hear the experience of one who has used it in a for the induction of premature labour not one of these 66 considerable number of cases. children would have been born alive, whereas, to Dr. Moir's is a derivative of from many of them became and healthy and Holocaine para-phenetidin, which knowledge, strong also are derived phenacetin and lactophenin. It is a strong were themselves parents of families. For the details of the base, insoluble in cold Waterbutreadily soluble in alcohol and practice Dr. Moir referred to his paper on this subject pub- of which lished in the Transactions of the Edinburgh Obstetrical ether. The chloroliydrate holocaine, Tauber pro- posed as a local aniaesthetic for the eye, takes the formn of Society, 1897-98. white needles, slightly soluble in cold water, but more readily Table of Thirty-one Cases ofMalformed Pelvis in which Premature soluble in warm. Its aqueous solution is neutral, and under- Labour was Induced. goes no change on prolonged boiling. Before using it for operative purposes or in the diseased eye, TABLE I. TABLE II. I made a large number of observations on the effect of the instillation of a few drops of a i per cent. solution of holo-- Labour at Full Time, oi 9 Molnths. Labour Induced after 7 Months. caine into the normal eye. The following is a brief summary of the facts observed: i. There is complete ancsthesia of cornea and conjunctiva Childreni. Children. produced in from I5 to 30 seconds after instillation. Cases. Living. Dead. Cases. Living. Dead. 2. The anTesthesia produced lasts about IO minutes. 2 Very severe. 6 ... 2 Very easy (8th month) 4 0 3. There is immediately after instillation a slight feeling of burning, which rapidly passes off. 4. There is produced shortly after instillation a slight Remaining Twenity-nine Cases. of the bulbar and which Times. Times. hypersemia palpebral conjunctiva, q One-embryotomy o 9 7 One ... 7 o rapidly passes away. I Two 0 2 6 Two ... 8 4 5. There is no alteration in the size of the pupil. 2 Three ,, o 6 s Thlree ... 24* I 6. There is no disturbance of accommodation. I Four ,, o 4 4 Four ... 13 3 There is no alteration in the tension of the 3 Five ,, 0 u 3 Five ... 7 8 7. eye. II One-forceps O I Eight ... 7 8. The corneal epithelium is not changed in the slightest, 2 One-version 0 2 - - but retains its normal appearance. - 31 66 17 In short, to put it concisely, holocaine seems to have no 31 0 49 *Twinsin one case. other effect upon'the eye than rendering it anesthetic. Herein lies its advantage over cocaine, which causes a conjunctival Maternal Mortality. anaemia by constriction of the vessels, dilates the pupil, and Accouchemnents ...... 139 often causes a desiccation of the corneal Another Deatlhs ...... 2 epithelium. Both deaths were from septic poisoning, one in her fifth, the other in her great advantage of holocaine as evidenced by these observa- third premature confinement. tions is the great rapidity of its action, producing complete ansesthesia in from 15 to 30 seconds. AN exhibition of improved clothing for women and of women's My experiences of holocaine in ophthalmic practice may hygiene will be opened in Berlin during the next two weeks. be divided into two groups. It is organised by the Berlin branch of the Society for the Improvement of Women's Clothing. It contains a special I.-IN INFLAMED EYES. section for sick nurses and monthly nurses, which will contain It was used in conjuntivitis,phlyetenularaffections, corneitis, in addition to clothes specimens of various objects of use in etc., to soothe the patient, to relieve pain and blepharo3pasm, the.sick room. and so admit of a more exact examination -of the eye. 10 Twz BiLiTm I . 6ATo MZDICAL JOUILNA.Lj SECTION OF OPHTH[LMOLOGY. [SEPT. 3, i898. I have found holocaine particularly useful in lhospital prac- further effect on the eye whatever. It seems to act simply tice, where its rapidity of action leads to a very considerable by paralysis of the sensory nerve endings, and lhas no other saving of time. For examining inflamed eyes with photo- action on the eye, leaving the pupil accommodation and ten- phobia and blepharospasm, a few drops of the I per cent. sion quite unaffected. The rapid action of the drug is also a holocaine solution will enable one within a very few seeonds decided advantage, and in dispensary practice where one is to get a good view of the cornea. I have used it also very dealing with a large number of patients, leads to a consider- frequently for little manipulations such as the application of able saving of time. According to Heinz a i per cent. nitrate of silver or sulphate of eopper to diseased lids, when solution of holocaine is powerfully antiseptic, as proved by you are able to make your applications with but little dis- experiments on the growth of bacteria, and therefore boiling comfort to the patient within a few seconds of the instillation the solution to sterilise it is not necessary. This is a further of the drops. It has been claimed for holocaine by some advantage that the solution is itself a powerful antiseptic. observers that where the conjunctiva is inflamed and the vessels enlarged, its anmesthetic effect is more profound than DISCUSSION. that of cocaine. My experience does not harmonise with such Mr. EDGAR BROWNE (Liverpool) said he had used holocaine observations. I made a number of observations, putting I for some time, and found it very satisfactory. It must be had per cent. holocaine in one eye and a 2 per cent. solution of from a first-class chemist, as it was very difficult to make up cocaine in the other. I found that the anmesthetic effect of the and did not keep long. The cornea never became flaccid cocaine in these inflamed eyes was quite as great as that of under its use, as it did after cocaine. He had used it in all the holocaine, but that the cocaine was much slower in its superficial operations, less in the deeper ones. He had not action. I tested this also in several cases of hypopyon ulcer, noticed that it penetrated more rapidly than cocaine, into a where the anterior clhamber had to be tapped several times chalazion, for instance. It was not so good for the patients' in succession in the same patient by using lholocaine and own use as cocaine in painful ulceration of the cornea. It cocaine alternately. This I considered an exeellent test for acted in I per cent. solution in about 15 seconds. In reply to seeing if holocaine in eases of inflamed eyes had a superior Mr. NETTLESHIP, Mr. Edgar Browne said that he had not aniesthetic effect to the coeaine. All the patients however not used it in the form of an ointment. agreed in saying that there was no appreciable difference in Dr. ARGYLL ROBERTSON said he had tried a 2 per cent. the amount of pain, wlhether the operation was performed solution which had been made up by Messrs. Duncan and with holocaine or cocaine. So far as my observations have Flockhart; it was a clear solution. He had found it infinitely gone in such cases, holocaine does not produce a more pro- inferior to cocaine as a local aniesthetic. found an.ethesia, but only acts mueh more rapidly. Dr. HINSHELWOOD, in hiis reply, laid great stress on the difficulty in getting even a i per cent. clear solution. It must be made up with fresh distilled water. He believed all cases II.-IN OPERATIONS. of failure to be due to badly-prepared solutions. He had a I have used holocaine in 154 cases of operative interference solution made up freslh every week, and found it would not on the uninflamed eye. Cases keep longer than a fortnight. Removal of foreign bodies ...... I08 chalazion ...... I2 tumour of conjunctiva ...... I CASE OF POLYPOID GROWTH FROM A Tenotomies ...... 4 Muscular advancement ...... MEIBOMIAN CYST. Pterygium ...... 2 Iridectomies ...... 9 By J. FALLOWS, L.R.C.S.Edin., Extractions ...... s8 Extramural House-Surgeon, Royal Ear Hospital, Solio Square. Needliing operations ...... 9 THE patient, a girl aged Ig, presented a swollen appearance of '54 the upper right eyelid. Wlhen tlle lid was everted a flat poly- In the removal of foreign bodies from the cornea, hiolocaine poid growth possessing a very narrow base spriniging ap- is an excellent anoesthetic, enabling one to remove the foreign parently from the site of a Meibomian cyst, wlhich lhad been body within I5 or 20 seconds after the instillation of tlle drops. opened surgically, was seen. This cyst was one of a series of Only three or four drops of the solution are necessary for eom- five from which the patient had suffered withini the space of plete aneesthesia. In all the conjunctival operations the three montlhs. The series of cysts themselves had apparently holocaine proved an efficient aniesthetic. The anmesthesia, slowly developed after a general severe attack of eczema for sufficient after 20 or 30 seconds to begin the operation, seemed which she was treated by Dr. Alfred Eddowes two years ago. to last longer than that of cocaine, so tllat the instillation was She was cured in five weeks and had no relapse or further repeated only at rare intervals, and very little of the solution trouble so far as the skin was concerned. It was suggested was used. In none of these operations was any holocaine by Dr. Eddowes that the infection of the follicles and forma- injected under the conjunctiva, but after cutting tllrough it, tion of the Meibomian cysts might be due to the extension of a few drops were let fall directly on the conjunctival opening. the same infective process that had given rise to the acute In the operations in wlhich the globe was opened, the holo- attack of seborrhlieic eezema. From hiis own recent observa- caine acted well. In the iridectomies it has the very great tions Mr. Fallows was disposed to think that there was a close advantage of not altering the size of the pupil, and this will connection between these cysts and eczema. be of very special value in operating on cases of glaucoma. In the extractions and needling operations the only special advantages of the holocaine was that it enabled us to operate ON THE SURGICAL TREATMENT OF CATARACT. sooner than would have been possible with cocaine. No toxic By ERNEST F. NEVE M.D., F.R.C.S.Edin., or any disagreeable effects whatever have been observed in any of these cases. Heinz has found by experiment on MR. NEVE related the results of 730 operations for cataract. animals that holoeaine is a poison producing convulsions and Of this number 677 were successful, 39 failed, and in I4 cases analogous to stryehnine. He found its toxic action more the patients left the hospital before the result was known. In intense than that of cocaine or eucaine on hypodermic injec- the last 200 cases the percentage of failure had been reduced tion of the drug. I have, therefore, refrained from using it from 6 per cent. to 3< per cent. Success in cataract operations hypodermically until we possess more definite knowledge as was to be attributed to selection of cases and to antisepsis, to the doses whiclh can be employed with safety. No toxic but it was not right by the selection of only good cases to con- effects have been noticed by any observers from the use of the demn many to hopeless blindness. The success of the opera- per cent. solution. The reason of this is doubtless because tion was affected by previous disease; old iritis was very such a very small quantity of the drug is required to produce prejudicial. in such cases the proportion of successes did not a complete ancesthesia of cornea and conjunctiva, and herein exceed 50 per cent. In glaucoma, also, the results lies one of its advantages. were poor. With regard to the method of operating he Holocaine is therefore a most valuable agent for the pro- reeommended that the incision should not be too peripheral, duction of aniesthesia of the eye. Its peculiar value lies in and found that both iridectomy and capsulotomy were advan- the fact that apart from the aniesthesia, it seems to have no tageous. With regard to inflammatory sequelse, he had met SEPT. 3, 1898.]JA NEW METHOD OF MAKING CASTS. [ THz BJz .62I with panophthalmitis in 5 cases, septic infiltration of the the whole mass-cast and mould-in warm. water until the cornea in 3 cases, irido-cyclitis in i, and glaucoma in 5. In wax becomes soft and plastic. In fact, in very delicate sub- 6o cases iritis occurred, ending ir. recovery in 41 cases, in jects the whole of the wax may be melted away, though this occlusion in 13 cases, and in partial occlusion in 6 cases. is rarely necessary. In this way the laborious proess of chiselling away the waste mould, with the attendant a iety for the safety from injury of the contained cast, is entirely A CASE OF CAVERNOUS ANGIOMA OF ORBIT. got rid of, and the mould comes away with almost as much By C. H. -USHER, M.B., ease as one would lift a layer of gauze from the surface of the Ophthalmic Surgeon, Royal Infirmary, Aberdeen, etc. body, and with quite as little damage to the underlying G1. C., aged 40, a farmer, came to the Aberdeen Royal surface. Infirmary on October 12th, I897. One disadvantage of this process is that the apparatus is History.- For about eighteen months he had noticed his left somewhat expensive and cumbersome, the principal expense eye gradually "Igetting bigger" (some time later he stated being in connection with the " electric motor" and air pump. that someone had noticed this for five or six years). It had The place of this may be taken for ordinary work by a pump never been painful, only slight irritation and watering caused worked by hand or foot power, and connected to an air cylinder by the wind. The sight of his left eye had been getting properly fitted with valves. It is necessary, however, to gradually worse; a year ago he could read large print with it. furnish oneself with a pressure of some io or 12 lbs. to the 'The eye had never been injured. For many years he had square inch, and this in considerable volume. been subject to headaches, usually frontal and on the left Briefly it may be stated that the process consists in spray- side the pain was often very severe, keeping him awake at ing melted paraffin over the whole surface, cooling it by night. spraying ice-cold water at the same time, strengthening the State on Admisston.-Left eye, V=p.l., very great proptosis. mould with plaster-of-paris and removing it in as many The eyeball projects straight forwards, its movements are fairly sections as the nature of the subject calls for. free, they are limited mostly in an upward direction. The THE APPARATUS. proptosis is not appreciably diminished on pressing the globe backwards, there is no tenderness, no pulsation, and no bruit. No growth can be felt in the orbit; cornea clear; pupils equal; left pupil acts sluggishly to- light. Tension normal. Fundus imperfectly seen owing to vitreous opacities; optic disc is pale. Right eye appears normal, but V is only Ay, no hypermetropia, vision not improved by lenses. Reads i J. at 9 ins. Field full. Description of Growth.-The growth was situated within the muscular cone and was removed subsequent to enucleation of the globe. It had a dark blue smooth surface, studded with small nodules, and had considerable elasticity. .tEAA" A DEMONSTRATION OF A NEW AND ORIGINAL METHOD OF MAKING CASTS.- Given beJore the Surgical Section of the British MedicalAssocia- tion at Edinburgh, JTuly, 1898, By GEO. A. PETERS, M.B., F.R.C.S.ENG., Associate Professor of Surgery and Clinical Surgery,'University of Toronto, Toronto, Canada. IT has long been desirable to have a better method of casting living objects, anatomical subjects, and pathological speci- mens than that which has hitherto been in vogue. Up to quite a recent period plaster of paris has been the material' almost universally employed, and certainly many useful casts have been made by its use. Recently Cathcart and others have used gelatine, papier mache, wax, etc., and for certain subjects these substances fulfil many desirable conditions. Some six or seven years ago I began to work with paraffin wax in a molten state, and after considerable experimenting and many failures I have elaborated the apparatus which I am about to describe, and with which I gave several demon- strations at the recent meeting of the British Medical Asso- ciation at Edinburgh, and subsequently in Dr. Sims Wood- head's laboratory at Examination Hall, London. Paraffin wax possesses many qualities desirable in a material for making moulds. It is a clean, inert, homogeneous, workable substance, capable of taking a finer impression than almost any other material, and contracting but little in passing from a hot liquid state to a firm solid mass. It "iworks " easily, and can be used over and over again with but little deterioration in quality. Hard wax, with a melting is the which I have found moat Fig' x.-A. The jacketed paraffin. container, with "jacketed tube point of about 1250 F., quality leading to C, the paraffin ejector. B. Tank containing ice-cold useful. Moreover, it possesses another quality which I find water, with single tube leading to D, the cold water ejector.E The is appreciated to its full extent by those only who have had 44pressure blower," or air pump,I which forces air into the air in the older method of casting from cylinder F which is provided with four exit pipes guarded by stop- experience plaster-of- coceks. (The pressure may be regulated with great nicety by open- paris moulds, namely, the mould can be separated from the ing or closing a greater or lesser nmuber of tl*s.) G cfwelitrl cast with the greatest possible facility simply by immersing motor.