Talk:The Johns Hopkins Medical Journal 5 (1894)

Case 9. Pneumonia and Malaria. Siiouinc. fall by Ckisis.

101° until .30 hours before deiitli, wlieu it rose to 10-1°. Leucocytes ranged at 25,000 from admission until death. Autopsy. In addition to pneumonic consolidation above noted, P. had an acute fibrino-purulent meningitis due to the dip. pneumoniae.

15. G. W., aet. 35. Illness lasted 10 days. Right upper, middle and lower and left lower lobes involved. Temperature ranged from 101.5° to 104°, being 104.3° at death. Leucocytes 8,000 on admission, rose steadily until time of death 8 days later, when they were 30,000. Autopsy showed the pneumonic consolidation above noted. No meningitis nor endocarditis.

16. K. D., a;t. 47. Illness lasted 4 days. Right upper and middle lobes involved. Temperature ranged at 102.5° until death, with a pseudo-crisis to 99° 12 hours before death. Leucocytes 18,000 on admission, where they ranged until death. 15,000 just before death. No autopsy.

17. C. L., a?t. 3G. Illness lasted 21 days (,?V Lower lobes of both lungs involved. Temperature ranged steadily at 102° until 12 hours before death, when there was a pseudo-crisis to 99°, with a sharp rise to 103° just before death. Leucocytes 13,000 on admission, fell gradually to normal iu two davs. They began to rise 36 hours before death, reaching 32.000 just before the end. No autopsy.

18. J. C, a;t. 63. Illness Listed 11 days. Right middle and lower lobes involved. Temperature ranged at 103.5° until 2 days before death, when it rose to 106.2°, falling to 104° just before death. leucocytes S.OOO ou admission. Remained normal until day before death, when they rose to 30.000. falling to 14.000 before death. No autopsy.

19. F. tS.. :et. 50. History of alcoholism. Illness lasted 24 days (?). Right upper and middle lobes iavolve<L Temix^rature ranged at 104° during the four days preceding death.

no

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 43.

The afternoon of the fourth day the P., being left alone for a moment, climbed through the top of a window and fell to the ground outside, breaking vertebral column and both bones of right leg. Unsatisfactory coroner's inquest showed nothing beyond the fractures and the pneumonic consolidation above noted. Leucocytes 15,000 on admission; for the first 3 days fell gradually to 11,000, but after the accident above referred to, rose to 18,000. P. lived 4 hours after the accident occurred.

•ZO. H. L., tet. 41. Illness lasted 5 days. Right lower base involved. Temperature on admission 102.5°. For next three days it ranged at 104°, being 103.8° just before death. Leucocytes 10,000 on admission, after which time they ranged steadily below normal ; from 6,000 to 1,500. They were 4,000 just before death. Ko autopsy.

21. A. N., set. 47. Illness lasted 12 days. Lower lobes of both lungs involved. Temperature ranged from 103.5°-105°, until shortly before death, when it rose to 107°. Leucocytes 15,000 on admission ; 3 days later they rose to 28,000. Eanged at 22,000 until just before death, when they touched 30,000. So autopsy.

22. A. P., set. 22. Illness lasted 3 days. Left lower lobe

leucocytes were 39,500 and 43,000 6 and 8 hours after the chill, respectively.

Of the eight eases ending by crisis, in all but one there was a marked leucocytosis during the febrile period of the disease. In the remaining case the leucocytes, while ranging at normal during the greater period of the disease, touched 13,000 on one occasion. [Case 7.] Examination of the combined charts showed no daily correspondence of the two curves before crisis occurred. The leucocytes began to fall before the temperature in three cases, with it in two, and after it in three. The fall of leucocytes was only partial in six cases, however, and they did not reach normal until from two to eight days after the temperature. In cases 6 and 7 the leucocytes and temperature reached normal at the same time. In cases 7, 9, 11 and 12 the leucocytes reached their maximum daring the period of fall of temperature. In cases 5 and 8 there was a rise of leucocytes during that period, but the maximum had been previously attained. Most of these points are well shown in a combined chart of the eight cases, showing the average temperature and number of leucocytes, twelve, twenty-four and thirty-six hours before and after the crisis in temperature.

involved. Temperatui'e ranged steadily at 103° until death. Leucocytes 50,000 on admission ; fell steadily, being 20,000 when death occurred. Autopsy showed beside a double lobar

Taking up hrst the four cases ending by lysis, we see that in all there was a marked leucocytosis at some period of the disease. Examination of the combined leucocyte and temperature charts showed that before the temperature began to

fall there was no daily correspondence between the two curves. In all four cases the two curves began to fall together, the leucocytes not reaching normal until one, four and 'fourteen days after the temperature in cases 1, 2 and 3 respectively. In case 3 there was delayed resolution of the consolidation, it not having entirely cleared up on discharge.

In cases 1 and 3 the leucocytes reached their niaxiDuun during the period of fall of temperature. There was a iff&rp rise during that period in case 3, but the maximum had been reached before the temperature began to fall.

In case 1, where there was involvement of both lungs, the leucocytes reached 50,000. In the other three cases the lower portion of the right lung was involved and the range of the leucocyte curves was moderate, being above 30,000 in only one instance.

In cases 1,2 and 4 the fall in temperature preceded the fall of leucocytes.

Case 4 is interesting on account of its complication with rheumatism. The combined chart is given and it shows well the correspondence of the two curves. The occurrence of a moderate leucocytosis during the course of rheumatic fever has been mentioned by several observers. In cases 1 and 2 the

Blaclt = Uuciciitcs. Drnhcn = tfinpa-ature.

Chart showing Temperature and Leucocyte Curves op

Pneumonia. Crisis.

In case 9 the lower portions of both lobes were involved and the leucocytes touched the highest point reached in any of the cases, viz., 68,000. In case 11 however, where there was the same extent of involvement, the leucocytes only reached 29,000. In case 7 only the left upper lobe was involved and the leucocyte range was practically normal, only once being above 10,000. The prognosis in this case was thought to be grave at first on account of the absence of leucocytosis, the position of the consolidation, the alcoholic history and patient's age. The patient made an uninterrupted recovery however, and the infection was evidently a very mild one. In the other live cases only a portion of one lung was involved and the leucocyte curve ranged moderately high.

In only one of the eight cases was it possible to count the blood before and after the chill. This was case 9, in which the pneumonia came on while patient was being treated for malarial fever of the double tertian type. In the article on the leucocytes in malarial fever, previously referred to, the

November, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

lil

fact is brought out that in malarial fever the leucocytes range constantly below normal during the course of the disease. This is due in some way to the presence of the malarial organism in the blood. It is not settled as to whether it is a leukocytolysis (an actual destruction of leucocytes) or a leukopenia (a diminished production). Now in case 9 there was no leucocytosis either before or after the chill, until the exhibition of quinine caused the disappearance of the malarial organisms from the blood, when the leucocytes promptly rose. It is interesting to note how, as each new portion of the lung was involved, there was a corresponding rise in the number of the leucocytes. [See chart.]

Of the ten fatal cases only one (No. 20) showed a complete absence of leucocytosis during the entire course of the disease. In cases IG and 19 the leucocytes, while being always above normal, ranged relatively low, never being above 19,000. In case 14 the leucocytes behaved as one would expect them to in an uncomplicated case ending in recovery. In cases 1.5, 17 and 21 the leucocytes were practically normal on admission, biit gradually rose dui'ing the ensuing three or four days, touching just before death .30,000, 32,000 and 30,000 respectively. In cases 13 and 22 the leucocytes were high on admission, but fell steadily from that time on until death. In case 18 they were normal for the iirst two days, but rose sharply to 20,000 24 hours before death, falling slightly just before the end.

Thus we see that in fatal cases the behavior of the leiicocytes varies widely. In six cases there was absence of leucocytosis at some period of the disease, but the continuous absence is the exception, not the rule. In none of the cases was there any daily correspondence between the temperature and leucocyte curves. In the four cases in which the leucocytes rose at the end however, there was a corresponding rise in temperature. As regards the relation of the amount of leucocytosis to the extent of lung involvement, no definite conclusions can be drawn. In case 15, where the entire right lung and a portion of the left were involved, the maximum leucocytosis was only 30,000 just before death. None of the cases were seen until at least twenty-four hours after the chill, so that no data are furnished as to how early the leucocytosis appears.

Autopsies were obtainable in only three out of the ten cases. This does not include the coroner's inquest on case 19. The results of these autopsies bear out Tchistovitch's statements however. In case 14, where the leucocytes ranged above 20,000, an acute fibrino-purulent meningitis was found to be present. In case 15, where the leucocytes ranged from 17,000 to 30,000 for 5 days, extensive involvement of both lungs was found. In case 22, where the leucocytes ranged from 50,000 to 20,000, there was found at autopsy double lobar pneumonia, acute nephritis, fatty degeneration of the heart muscle, and haemorrhage into the pericardial sac, with the presence of the diplococcus pneumoniae in the latter situation. In case 19, where the leucocytes ranged at 18,000, the fracture of the spine was probably the immediate cause of death. In case 21 there was involvement of both lungs, with a leucocyte range above 20,000. All the remaining cases, with the exception of No. 13, showed a low range of leucocytes, and it is only fair

to consider it possible that in case 13 also, an autopsy might have revealed some complication or condition accounting for the relatively high leucocytosis.

There are a number of theories as to the cause of leucocytosis. Virchow held that it was due to proliferation within the lymph glands, that it only occurred in those cases of disease associated with glandular enlargement ; also that acute glandular enlargement was followed by leucocytosis. This is negatived by the absence of leucocytosis in many diseases accompanied by glandular enlargement (tuberculosis, acute Hodgkin's disease, etc.), and by the presence of marked leucocytosis in diseases associated with very slight glandular enlargement. [Pneumonia.] Every leucocytosis is probably associated with some glandular enlargement however. Such a leucocytosis as Virchow supposes would be a lymphocytosis, which is not the case.

Schulz's theory has been already mentioned. Its falsity would seem to be proved by the work of Goldscheider and Jacob (to be referred to later), who found that in cases showing a leucocytosis in the peripheral circulation, there was no corresponding diminution in the leucocytes in the central blood-vessels.

Romer (1. c.) thinks the increase due to direct multiplication (by amitosis) of the leucocytes, the exciting cause of such multiplication being the destruction-products of the alkaliproteins, as has been mentioned. He thinks chemotaxis to play a large part. No such changes as he infers are to be made out in the blood.

Von Limbeck (1. c.) holds leucocytosis to be due to the action (" Fernwirkung ") of the bacterial products themselves upon the leucocytes. He does not speculate as to the source from which the increase is drawn.

Bieganski's theory has been mentioned. Too little is known about the so-called blood-plates and eosinophiles to justify us in drawing conclusions from any variations in their number. Most authorities deny that the blood-plates are end-products of the polyuuclear leucocytes.

Lowit" holds that every leucocytosis is preceded by a diminution in the number of leucocytes. This is due, he thinks. to an actual destruction of the leucocytes, and he calls it leukolysis. This leukolysis is in turn followed by a pouring forth of young elements from the ha?matopoietic organs. This reparation far exceeds the destruction, in this way j^ii|ing about a leucocytosis. He demonstrates by injection experiments that the artificially-produced leucocytosis is preceded by a leukolysis. His ideas as to the source from which the increase is drawn would seem to l>e negatived by the absence of evidence of new formation. Were new formation to occur, the blood would show a large number of young elements. This it does not do.

The latest work on the subject is that of Goldscheider and Jacob". They make use of the t«?rms hypo- and hyj>erleucocytosis for leukolysis and leucocytosis respectively. Their conclusious are as follows : Ilypoleucocytosis is due to the leucocytes being driven into and detained within the capillaries of certain orgiius of the body. Actual destruction plays a minor role. Hyperleueocytosis is due to an increiised quantity of leucocvtes being carried to the blood by the lymph stream.

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[No. 43

There is no new formation of leucocytes, its absence being offset by the supposition that in the bone-marrow and spleen there are a large number of adult leucocytes held in reserve, as it were, which are carried off by the lymph stream into the general circulation when occasion arises. The occurrence of new formation is negatived by the absence of young forms in dried specimens.

All these phenomena are primarily due to the bacterial products or chemical substances in the blood. In most acute infectious diseases these substances are introduced into the circulation slowly and cause no diminution in number of the leucocytes, the latter rising immediately. This statement is borne out by experiment. This would mean that in pneumonia the leucocytosis would be found to be present at the time of the chill.

The authors are led to believe that the sources of the leucocytosis are the blood-making organs. But there is no evidence of new formation ; hence their theory of a reserve force of adult leucocytes within those organs. This theory seems rather to be constructed to meet the necessity of the case than to be founded on sufficient evidence.

Sherrington^ in a recent article reports observations of his own on inflammatory leucocytosis. He discusses most of the prevailing ideas, but formulates no new theory.

It is beyond the province of this article to enter into any further discussion of these theories. All we can sayis that the leucocytosis in pneumonia is probably due in some way to the products of the diplococcus pneumoniie. While the bacteria do not enter the blood as a rule, their products do, and in this way can influence the various organs of the body. There is probably no new formation of leucocytes, or at any rate it plays a minor role in the process, and some other source for the increase in number of the leucocytes must be sought for.

The behavior of the leucocytes depends upon the virulence of the bacterial products. In fatal cases where the virulence is great, a rise in the number of leucocytes is rendered impossible. It is doubtful whether there is any actual diminution of their number, there being no evidence that actual 'destruction of leucocytes takes place. The virulence may be so modified as to permit of a gradual increase in number of the leucocytes, yet still be potent to cause death. Cases may begin favorably and the leucocytes may range high at first ; the virulence of the bacterial products may then increase, causing a gradual reduction of the leucocytes, and death. The sharp rises sometimes observed just before death may be associated in some way with the pre-agonal leucocytoses. We must not forget that the disease may be present in so mild a form that the leucocytes are unaffected and remain normal throughout. This is shown in case 7 of our series. Most of the above points are shown in the following table:

1. V'ery mild infection : No effect on leucocytes. Normal range.

2. Moderate infection: Moderate leucocytosis.

3. Severe infection (as to e.\tent of lung involvement): Marked leucocytosis.

4. Severe infection (as to virulence of bacterial product): .Moderate leucocytosis.

.5. Very severe infection : No leucocytosis.

It has not been proved, as will be shown later, that the blood condition in the fatal cases differs in any way from the normal as regards the relative numerical proportions of the various forms of leucocytes.

If this be true, it is easy to see that the examination of the blood in pneumonia is not of absolute prognostic value. The blood only furnishes an indication of the virulence of the bacterial products; the extent of lung involvement, the general condition of the patient, and the temperature must also be taken into account in every case. For instance, should we be guided by the blood condition alone, our prognosis in cases coming under the heads of 1 and 5 in the above table would be either favorable or unfavorable according to the view we took. The error would of course be fatal.

The absence of leucocytosis in the fatal cases is evidently not the cause of death. Hence the failure of Von Jaksch's treatment by injecting such substances as would produce a leucocytosis in the healthy individual.

Regarding the question of the variations of the various forms of leucocytes, too much time was taken up by the actual counting to allow of much work in this direction. Twenty counts were made in the various cases showing a marked leucocytosis, with the following average result: Polynuclears, 91.2 per cent.; mononuclears, 9.6 jier cent.; eosinophiles, 0.2 per cent. Three counts were made in cases showing no leucocytosis, and the results were practically those which would have been obtained in counting the leucocytes in normal blood, thus agreeing with neither Rieder nor Bieganski.

Polynuclears.

(rt) 71.8 per cent.

(b) 73.5

(c) 76.1

Count (c) was in case 18. As has been mentioned, the leucocytes rose sharply just before death. A count was made two hours before death and the increase was found to be in tlie polynuclears solely. Polynuclears, 95.4 per cent. ; mononuclears, 4.3 per cent. ; eosinophiles, 0.3 per cent.

These counts would seem to make it doubtful that Bieganski's conclusions hold. The number of counts however, is too small to have any weight.

C0^fCLUSI0NS.

1. In cases of pneumonia pursuing a favorable course there is, as a rule, a marked increase in the number of the leucocytes during the febrile period of the disease. This leucocytosis is probably present at the time of the chill, and may be very marked within a few hours. There is no correspondence between the daily tonipcraturc and leucocyte curves during the febrile period.

2. In those cases in which the temperature curve falls by crisis, the leucocyte curve begins to fall within a few hours of the same time. The fall of the latter is only partial however, and rarely reaches normal as soon as the temperature curve, generally taking about 48 hours longer. In cases ending by lysis the two curves fall together, the temperature always reaching nornuil first. In cases of delayed resolution the leucocytes nuiy remain elevated for days.

Mononuclears.

Eosinophiles.

28.2 per cent.

26.1

0.4 per cent

23.4

0.5

November, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

113

3. In a majority of the cases the leucocyte curve rises during the period of fali of temperature, and may reach its maximum at that time. Such a rise is only transient, however, and is soon follpwed by a fresh fall.

4. In cases showing extensive involvement of both lungs, the leucocytes are apt to reach a higher point than in those cases whei'e the involvement is only moderate. The correspondence of lung involvement and amount of leucocytosis is a very rough one however.

5. The fatal cases may show either the presence or absence of leucocytosis. In those cases showing a leucocytosis, some other cause of death than the virulence of the bacterial poison must be sought for.

6. The prognosis in cases showing a complete and continuous absence of leucocytosis is unfavorable as a rule. A continuous absence of leucocytosis is the exception, most cases showing a leucocytosis at some period of the disease. The possibility of the absence of leucocytosis being due to extreme mildness of the disease must not be overlooked.

7. The leucocytosis in pneumonia is a so-called pure leucocytosis, i. e. an increase in the polynuclear elements solely. In cases showing no leucocytosis, the blood condition according to the observations here reported, is normal. Further investigations are necessary before the work of previous observers can be positively contradicted.

8. The presence or absence of leucocytosis only shows the

virulence of the bacterial poison, absolute prognosis.

Literature.

It is not a criterion of

Hamatopatliol., Leipzig, 1839.

Cellular Pathologie, 1871.

Untersuch. z. Phys. u. Path., 1889.

Prag. Zeitsch. f. Heilk., IV Bd., S. 198, 188.3.

Arch. Gen. d. Med., p. 257, 1884.

Deutsch. Arch. f. Klin. Med., Vol. 41, p. 323, 1837.

Arch. f. Klin. Med., Vol. 29, p. 481.

Festschr. f. Henoch., 1890.

Path. Anat. d. Blut. b. Croup. Lungcnentziindung. Inaug. Diss.,

Petersburgh, 1890. Berl. Klin. Woch., No. 36 & 51, 1891. Cb. f. Klin. Med., No. 5, 1892. Berl. Klin. Woch., p. 765, 1892. Beit, z Kennt. d. Leucocytose, Leipzig, 1892. Grundriss z. Klin. Path. d. Blutes, Jena, 1892. Ann. d. I'lnst. Pasteur, Vol. 5, pt. 7. Berl. Klin. Woch., No. 36 & 37, 1893. Arch. f. Klin. Med., 1893. 2 and 3. Arch. Ital. d. Clin. Med., No. 3, 1893. Bost. Med. and Surg. Jour., Vol. cxxx, No. 12. N. Y. Med. Jour., Dec. 16, 1S93.

Arch. d. Sc. Biol. Imp. Inst. St. Petersburgh, Vol. 2, No. 5, 1893. Deutsch. Arch. f. Klin. Med., Vol. 53, pts. 3 and 4, 1891. Studien z. Phys. und Path. d. Blut. u. d. Lymphe, Jena, 1892. Zeitsch. f. Klin. Med., Vol. 25, Pt. 5, 1894. Proc. Roy. Soc, Vol. 55, No. 332, pp. 161-206.

A. I'OSTSCRIPT TO THE REPORT OJSJ ^RRENDICITIS.*

By W. S. Halsted, M. D., Surgcon-in-Chief, etc.

Dr. Finney's remarks on the treatment of the wound in cases of appendicitis have been abbreviated so much as possibly to mislead those who are not familiar with our methods. When he speaks of "leaving the abdominal wound open" he means that the wound is drained with gauze, and not that no attempt is made to close it. The fact is that the wound is sewed up tight about the gauze, so tight that it is sometimes necessary to cut one stitch in order to remove the packing. Whenever pus is encountered either within the appendix or outside of it the wound is drained. Sometimes one or two narrow strips of gauze are sutlicient, sometimes very many broad strips are required. Ordinarily all of the gauze is brought out at one point and between stitches which, as I have said, embrace it snugly. The gauze is used not only for drainage, but quite as much to stimulate adhesions between the coils of intestine which surround it and thus effectually shut off the general peritoneal cavity from its infected portion. The gauze is gently packed about the stump of the appendix, and should reach into every recess of the pus cavity. AVhen tlie abscess is a large and ramifying one, or when there are several abscesses, we may bring the gauze packing out of the abdomen at more than one point in the wound.

These wounds are closed with mattress sutures ; but the sutures are not always buried as they are in all uninfected

• See Johns Hopkins Hospital Bulletin, June-July, ISOl.

abdomiinil wounds which are completely closed and in which the danger of stitch infection is not so great. The stitches, where they are not buried, are prevented from cutting into the skin by pieces of rubber tubing or of gauze. These wounds should be stitched with great care. All of the divided tissues (the peritoneum excepted) should be included in each stitch unless the stitches are buried. Inasmuch as the muscles retract unevenly the sewing is sometimes a difficult task. If the wound is sewed in this way, and if sufficient care is exercised to avoid the infection of the stitches as they are being introduced and tied, there is little if any danger that a hernia will ensue.*

Even the point at which the gauze traverses the abdominal wall is not a weak one. A connective tissue membniue, the wall of the obliterated sinus, extends from the stump of the appendix to this point in the wound and binds thciutestiues to

• At the meetingof the Johns Hopkins MedioAl Society, November

5, 1891, I presented a case of appendicitis to illustrate our tre.itment of the incision. Buried sutures of silver wire had been used to bring together the cut edges of the abdominal muscles, and an uninterrupted buried suture of silver wire closed the wound in the skin. The latter suture h.id already been withdrawn and a fine pink line indicated \vhere the skin incision had been made. A little below the centre of the wound was the orifice of a sinus from which a narrow strip of gaure had just been removed. The cicatrix was three weeks old.

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[No. 43.

each other, and to the underside of the lips of the open part of the wound. The thickness of this membrane depends principally upon the length of time that the gauze is allowed to remain undisturbed. I have found it so strong after ten days that I could with difficulty thrust my finger through it. This membrane atrophies in time. After two years I have found the walls of a sinus to the gall bladder attenuated to little more than a trace.

With our present resources it is not justifiable to attempt to disinfect an abscess cavity of the peritoneum, no matter how infiuitesimally small this abscess maybe. Bull and two others, whose names I am not at liberty to mention, are probably not the only ones who have furnished disastrous instances of such attempts.

In operations for appendicitis we have always the strangulated stump of the appendix and usually tissues more or less necrotic in its immediate vicinity as a complication. My experiments* demonstrated conclusively the result of inoculation of strangulated tissues in the peritoneal cavity.

The problem is a very different one when we have an abscess in the cancellous tissue of bone or in highly vascular soft parts to deal with. We may safely close such abscess cavities. If, for example, the so-called pyogenic wall of an abscess in muscle is excised and the parts are then thoroughly washed with an antiseptic solution, we may so far inhibit the pyogenic organisms that the tissues or, if there is a 'dead space, the prolific granulations, assisted possibly by the blood, may altogether destroy them. In the cancellous tissue of bone a cavity large enough to hold a hickory nut becomes completely filled with granulations in about three days. Blood clots occupying such cavities, if inoculated with virulent cultures of staphylococcus aureus, rarely break down. As a rule, the so-called organization of the clot takes place in from two to four days without suppuration. But an abscess in the peritoneal ca\ity is a very different affair because (1) the wall of the abscess consists in part of strangulated or more or less necrotic tissue which we cannot excise; (2) attempts. to disinfect such an abscess would probably be futile and might be worse than futile; (3) failure to disinfect might mean general peritonitis and the death of the patient, and not merely the retardation of healing.

There cannot be a definite incision for appendicitis. In general, if there is a large abscess, the incision should be made as near as possible to the crest of the ileum, so as to diminish the chances of entering the clean peritoneal cavity and to lessen the possibility of a hernia. The muscles are thick in this region, and when divided offer broad surfaces for coaptation by suture; and if the incision is too close to the ileum to admit

• The Johns Hopkins Hospital Reports. Report in Surgery, I.

of suture there is little danger of hernia resulting, as we know from a long experience with psoas abscesses, which we open by preference in this region. But the position of the abscess or, if there is no i^us or too little pus to be detected, the position of the appendix in the given case should determine the site of the incision. If there is an abscess the tissues over it should be most carefully studied as they are being incised for signs of infiltration with inflammatory products. A little oedema of the deeper muscles (transversalis or internal oblique) may guide us to a circumscribed spot of adhesion of caecum or omentum to parietal peritoneum and enable us to empty a large abscess without entering the uninfected part of the peritoneal cavity, or to thoroughly protect the intestines about the encapsulated pus cavity from the danger of infection before the pus is liberated. AYe place several yards of gauze between the healthy intestines and the abscess before opening the latter.

From a bacteriological point of view, we must often, if not always, inoculate the healthy peritoneum, but thus far we have not in a single instance had peritonitis supervene upon an operation for appendicitis, nor have we a single death to attribute to the operation. In the case of a large abscess, which we have evacuated without entering the uninfected peritoneal cavity, we still hesitate to search for and remove the appendix if its removal would necessitate our entering the clean peritoneal cavity.

When there is little or no pus to be discovered we make our incision directly over the appendix, which can usually be palpated. Here, too, we try to cut through thick muscles if possible. The instant that the peritoneum is opened, and before it is widely incised, v>'e introduce large towels of gauze, and with these press the intestines over the appendix out of the way and towards the left. AVhen the appendix is nicely exposed and a clear field for operation obtained, we introduce more gauze to serve as an inner lining to the outer ring of gauze. The adhesions which bind down the appendix are then slowly broken up by gentle finger pressure, and if pus is present it is caught as it leaks out by additional gauze sponges. If the iuner layer of gauze packing should by accident become soiled it is immediately replaced by fresh packing, the opening into the abscess being meanwhile stopped with a gauze sponge. And so, little by little, the abscess is emptied, and finally the appendix removed. After ligating the appendix and its mesentery we may excise the mucosa which is cut off by the ligature. We never sew up the end of the stump in the infected cases, as some surgeons have advised. This would be a foolish waste of time ; for the circulation of the part stitched has been cut off by the ligature applied to the appendix. The gauze for packing is rubbed full of a mixture of iodoform and bismuth and then sterilized.

THE JOHN'S HOPKINS HOSPITAL REPORTS.

Volume IV, No. 6 (Report in 8urgei*y II), !N"o\v Ready.

Contents: The Results of Opekatioxs for the CritE of Cancku of the Breast, performed at the Johns Hopkins

Hospital from June, 1889, to January, 1894.

By WM. S. HALSTED, M. D., Profensor of Surgery, Johns Hopkins Univerrily, and Surgtonin-Chitfto the Johnu Hopkins Hospital.

Price, $1.00.

Address Thk Johns Hopkins Pkkss, Balti.mure, Mu.

November, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

115

THERAPEUTIC USE OF EXTRACT OF BONE MARROW.

By John 8. ]}illixgs, Jr., Assistant Resident Physician. {Head before the Johns Hopkins Hospital Medical Society, .November 5, 1894.)

The use of bone marrow in cases of anaemia and in certain diseases of the blood-making organs was probably suggested by the success of the treatment of myxcedema with thyroid extract. The marrow is thought by most authorities to be the principal seat of formation of the red blood corpuscles. A diminution in number of the red corpuscles may be due to increased destruction or to diminished formation, and it was hoped that in either case the administration of the marrow as a medicine would stimulate the blood-making organs to increased activity, and thus make up the loss in red corpuscles.

The first case of anaemia treated in this manner was reported by Fraser.' A diagnosis of pernicious anaemia was made, based upon the histoi-y of the case, the number of red corpuscles and per cent, of haemoglobin, and the poikilocytosis of the red corpuscles. No mention was made as to the occurrence of nucleated red corpuscles, the presence of which in the blood in pernicious anremia being a point upon which Ehrlich lays considerable stress. The case was given bone marrow with arsenic for the first two months, then bone marrow alone for a month, and finally bone marrow and iron for three months. In the first two months the corpuscles rose from 1,006,000 per cmm. to 4,000,000, ranging at the latter point until discharge, four months later.

Bigger' reports a case of leucocytheemia in a boy, which was treated with the bone marrow. There was rapid diminution in the size of the spleen and marked improvement within a week. No mention is made of any examination of the blood, and it is possible that the case may have been one of splenic ana?mia or of the pseudoleukaemic infantile anfemia of Von Jaksch.

Danforth' reports a case of pernicious anajmia apparently cured by the use of bone marrow. Here also the report of the blood condition is incomjilete, as only the number of red corpuscles and per cent, of haemoglobin are stated. The latter rose from 35 per cent, to 80 percent. The bone marrow in this case, as in that of Fraser, was given in combination with arsenic.

In our own cases the marrow was given in the form of a glycerin extract which was prepared in the following manner. Twelve sheep's ribs, carefully scraped, were chopped into small fragments and rubbed up in a mortar with one pound of glycerin. This was allowed to macerate for three or four days, being kept in a refrigerator during that time. It was then strained through gauze, and the resultant liquid administered in teaspoonful doses three times a day. No complaint was made by the patients with regard to its taste.

Case 1.— Chlorosis. Girl, aged 20 ; admitted June 21, 1894, complaining of dyspnoea and weakness. Past history was negative. Present illness of four niontlis' duration. Physical examination

' Brit. Med. Jour., June 2, 1894. 'Lanoet, September 22, 1894. 'Chicago Clin. Review, IV, 1894.

showed nothing beyond marked anamia, and a loud functional murmur along the left sternal margin.

Blood count on admission, reds 2,898,000, whites oCOO ; haemoglobin 32 per cent. Stained specimens of the blood showed nothing beyond the pallor of the centre of the red corpuscles, so characteristic of chlorosis. No treatment was instituted for the first ten days, i. e. until July 1st, when the extract of bone marrow was begun. The blood count at that time was, reds 3,198,000, whites 5500 ; hfemoglobin 38 per cent. The extract was discontinued July 16, as patient insisted on leaving the hospital. The blood count on the morning of discharge was, reds 4,192,000, white 7000; hemoglobin 40 per cent. She was given Blaud's pills, and subsequently did well.

Case 2. — Chloro-anoemia in a boy. Past history was negative. For a month had complained of headache and gradually increasing weakness. Inspection showed a moderate grade of ansemia, physical examination being otherwise negative. On admission the blood count was, reds 3,290,000 per cmm.; haemoglobin 35 per cent. Stained specimens of the blood showed nothing beyond the pallor of the centre of the red corpuscles. Such a blood condition in a young female would certainly lead to a diagnosis of chlorosis, but the diagnosis of chlorosis in the male is always hazardous. The extract of marrow w'as ordered, and the condition of the blood gradually improved, the red corpuscles reaching a normal point (5,000,000 per cmm.) in about a month. The hfemoglobin rose more slowly, and on discharge (see chart 3) was only (38 per cent. As a rule, in chlorosis we must be satisfied if we can get the basmoglobin as high as 75 to 80 per cent.

Case 3. — Pernicious anaemia. Man, aged 51, admitted Jnne 15, 1894, complaining of vomiting and progressive weakness. He was very pale, and had first noticed the pallor ten weeks before. Had not lost very much in weight. Inspection showed a marked grade of ansemia, with the lemon-yellow discolorization of the skin so frequently seen in pernicious aniemia. Physical examination and examination of the stomach contents were negative. The case was at first suspected to be one of cancer of the stomach, but the absence of tumor, the readiness with which the gastric symptoms yielded to treatment, and finally the condition of the blood, all pointed to its being a case of the idiopathic ana;mia of Addison, th£ so-called primary pernicious anemia. Blood count on admission, reds 1,148,( 00, whites 4400 ; bsemoglobin 27 per cent. By July Ist the red corpuscles had sunk to 918,000, and the htemoglobin to 17 per cent. Stained specimens showed marked poikilocytosis and polychromatophilic staining of the red corpuscles. Several nucleated red corpuscles seen, the greater number being normoblasts. The remainder were typical megaloblasts, w^ith large pale nuclei and polychromatophilic protoplasm. Many micro- and megalocytes. A differential count of the leucocytes showed the per cent, of the small mononuclear forms or lymphocytes to be increased to 34 per cent., almost twice the normal. This technic.il description of the blood condition is given to show the grounds on which the diagnosis was based. The absence of any .npp.irent causative factor, and the fact that the per cent, of hjemoglobin was relatively higher than that of the red corpuscles, confirmed the diagnosis. The use of the extract of bone marrow was begun June 30th. At fiist the blood condition improved, the red corpuscles rising to 1,400.000. They fell again to 970,000, however, and the extract was discontinued July ISth, it having been given 19 days without causing improvement. Fowler's solution was ordered in increasing doses, and the patient gradually improved, being discharged October 12th in fairly good condition. Blood count on discharge, reds 3,(5C0,lC0, whiles 7C00 ;

red corpuscles. 'BroHtn=^\ia:mrnjlohin. = colo?le««(

No. 1. J. K. Pernicious An;emia. Case 3.

liKmoglobin C9 per cent. Stained specimens showed no poikilocytosis, no nucleated red corpuscles, and the per cent, of the various forms of leucocytes was normal. (See chart 1.)

Cau 4.— Pernicious antcmia. Man, aged 6.5, admitted August 15, 1894, complaining of weakness and shortness of breath. Illness began about one year before admission, and has been gradually progressive ever since. Has lost very little weight. Physical examination negative beyond a marked grade of ancemia Skin distinctly lemon-tinged. The urine was high-colored, but of low specific gravity, a condition which has been frequently observed in pernicious anromia, and whirh is supposed by Hunter to be due to the presence of pathological urobilin in the urine. The recent investi

gations of Hopkins (Guy's Hosp. Rep., 1893) would seem to make the existence of this substance improbable. He found only normal urobilin and hxmatoporphyrin in the urine in pernicious anremia. Blood count August 18, reds 2.048,000, whites 5000 ; hicmoglobin 45 per cent. Stained specimens showed a moderate grade of poikilocytosis, such as is seen in severe secondary anivmia. No nucleated red corpuscles. Percentages of leucocytes normal. The number of red corpuscles gradually sank, and between September 8th and October 6th ranged between 1,120,000 and 1,392,000; during this time patient was taking Fowler's solution.

Stained specimensof the blood taken September2d showed marked poikilocytosis, many micro- and megalocytes and many polychro

November, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN

Blac7c = red corpuscies. Brokctt= hminonlohiii. - ■ No. 2. J. R. Pernicious Anaemia.

- ^ co/or/c-w corpuscles. Cask 4.

matophilic red corpuscles. A relatively large number of nucleated red corpuscles were seen, 80 per cent, of which were typical megaloblasts, the remainder being normoblasts. A differential count of the leucocytes showed the lymphocytes to be distinctly increased (26.5 per cent.). On October (ith the blood count was, reds l,3-)8,000, whites, 30no ; haemoglobin 31 per cent. Up to this time the patient had had two courses of Fowler's solution, but the physiological limit of the dose had not been readied. On October 10th the extract of bone marrow was ordered, the blood count next morning being, reds 1,550,000, whites 3500; haemoglobin 35 per cent. The marrow was continued for two weeks, .luring which time the patient failed visibly, the red corpuscles sinking to 822,000 ; heemoglobin 18 per cent. On October 27 the extract was discontinue! and Fowler's solution in increasing doses was ordered.

Stained specimens of the blood, taken on Oct. 27th, showed an interesting state of things. While the poikilocytosis. or deformity in shape and size of the red corimscles, was markedly increased, the nucleated reil corpuscles had almost entirely disappeared, only one megaloblast being seen in four specimens. Such a disappearance of the nucleated red corpuscles from the circulation may be interpreted in two ways: either the blood condition has improved to such an extent that great activity on the part of the bloo<i-making organs is no longer necessary, or it has deteriorated so much that new formation is no longer ]>ossible. The latter condition obtained in a case of fatal purpura h.-emorrhagica rejwrted by the writer in the John.i Uopkim JfoajiiUit J5iill<!tin. May, 1894. Ehrlich has also reported two cases. In the present case this was also the condition that probably prevailed. Blood count Nov. 3d, reds

n

'

t

(

90.000

18,000

H,000

14.000

d on Nov. 3d showed about the same condition of things as on Sept. 2d. The differential count of the leucocytes is so typical that it will be given in full :

Large. Polynuclears. Lymphocytes, mononuclears. Transition. Eoslnopliiles. 52.1 per cent. 32.2 per cent. 2.4 per cent. 4.2 per cent. 6.1 per cent.

Nucleated red corpuscles again appeared in the blood in relatively large numbers, 59 being seen while making a differential count of 500 leucocytes.* This reappearance of the nucleated red corpuscles

may be taken as a relatively favorable sign, showing that the bloodmaking organs are once more active. If improvement occurs in this case under the use of arsenic it will be slow, as it requires some time to safely increase the dose to the physiological limit (20 to 25 min. t. i. d.). The general record of the case is given in chart 2.t

• This Is a very convenient mode of expressing tUc number of nucleated red c»v|iiisc1e8 pro.ipnt In n specimen of blood, but wo must always take Into vonsiilcraticin tlie numlicr of leucocytes per cmm. For example, suppose case

A shows 2000 leucocytes per cmm., and case H flUOO. Now while making B difTcrentinl count of 500 leucocytes in a stained specimen from A we see 12 nucleated reds, in a similar count in a specimen from case B we see only * nucleated reds. Yet the number of nucleated red corpuscles in the blood is about equal in the two cases, as in case B we cover only one-third of the ground that we do in case A.

tSincc the above went to press this imtlent has died. A final blood couut on Nov. 16, made SI hours before death, showed only 700,000 reds, 1000 whites: hiemoglobin 17 per cent. No autopsy.

November, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

119

It will be seen that the two cases of chlorosis were benefited by the use of extract of bone marrow, while the two cases of pernicious aufemia were unimj^roved. It is difficult to understand how this remedy could be of service in cases of pernicious anaemia. Its effects can hardly be considered as analogous to those produced by thyroid extract in myxoedema. In the latter case there is atrophy of the gland, giving rise to defective secretion, so that there is an indication for attempting to supply this defect by the administration of thyroid extract. But the marrow in pernicious anemia is, if anything, in a state of hypertrophy, and the condition is far more analogous to that of the hypertrophied and supposedly over-active thyroid glaud in exophthalmic goitre than to that of the atrophied gland in myxosdema. Besides, there is no proof whatever that the marrow acts as a gland in the ordinary sense of the word. The formation of red blood corpuscles by the bone marrow cannot be properly termed a secretion, it being rather a process of cell multiplication and development, and there is no proof that this process is influenced in any way by any chemical product of the marrow itself. As regards the cases reported by previous observers, two things may be noted.

First, there is room for doubt that they were true cases of pernicious anaemia. Second, the patients were given arsenic together with the bone marrow. ISTow it is well known that some cases of pernicious ansmia do remarkably well on arsenic, and several instances of apparent cure have been reported. Such an improvement is shown in Case 3 of our series.

It is different as regards the use of bone marrow in chlorosis. The marrow contains iron in considerable quantity, and we may reasonably suppose that the glycerin extract' contains sufficient iron in organic combination to be of service in chlorosis, a disease which yields so readily to iron in almost any form. Whether its value in such cases is greater than that of the various forms of iron used in medicine is doubtful. This is well shown in chart .3, where a blood chart of a case of chlorosis treated with Blaud's pills is given together with that of Case 2 of our series. The former does not suffer bv the comparison. The conclusion is that the extract of "bone marrow may be of value in cases of ordinary ana?niia and chlorosis, such as would be benefited by iron in other forms, but that there is no proof of its being of value in cases of primary pernicious ansemia.

PROCEEDINGS OF SOCIETIES,

THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of October 1, 1894. Dr. Kelly in the Chair.

Prof. J. J. Abel was elected Chairman for the coming year, and Dr. J. G. Clark was made Secretary.

Prof. W. D. Miller.of the University of Berlin, delivered an illustrated lecture in the amphitheater before an audience of Baltimore physicians and dentists, on "Some Points in Oral Pathology in Relation to Diseases of the Associated Parts and to general Diseases."

Meeting of October 15, 1894. Dr. Abel in the Chair. Case of Hereditary Chorea.— Dr. Osler.

Dr. Osier presented the case as illustrating a somewhat unusual feature in the family form of chorea, namely, the onset at a comparatively early age.

F. T., aged 28, a native of North Ware, N. H., was admitted Oct. 6, 1894, complaining of nervousness.

His father died at 59, after an illness of two weeks' duration. His mother died when 49 years old, of a disease similar to that with which he now suffers. She had nervous twitching for as long as he can remember. The trouble grew gradually worse, so tluit she could not move from her cliair and she finally became bedridden. He does not think that any other members of his mother's family were affected. He has liad four sisters and two brothers. One brother died at the age of 32, of inlluenza, afier he hail Iwen .afllicted for eight years with the .same sort of disease as the mother. The other brother and the sisters are well and strong and have no muscular twitchings.

Personal History. As a child he had the usual disorders, but he was very well and strong until the eighteenth year. He had a comfortable homo upon a farm, and though of a nervous temperament and troubled with weak eyes at times, he remained very well. He had an accident to the right elbow when he was fifteen years

of age. When seventeen he had occasional rheumatic pains in the joints, but which never kept him from work. He has never had gonorrhoea or syphilis.

The present trouble began when in his eighteenth year. It was first noticed as a very slight twitching of the arms and hands. The movements afterwards involved the other parts of the bodv— face, shoulders and legs. He thinks the latter were involved about eight months after the arms, and a little later the muscles of the face. The twitchings have persisted uninterruptedly to the present time. He has been able to work, however, until July of last year, but the involuntary movements now interfere with his doing manual labor. In 1888 he went to California for his health, having been troubled with a cough.

NOTES ON NTEW BOOKS.

BULLETIN

OF

THE JOHNS HOPKINS HOSPITAL.

Vol. V.-Nos. 44-45.

BALTIMORE, DECEMBER, 1894.

+++

Contents

A Contribution to our Knowledge of Organic Sulphur Compounds in tlie Field of Animal Chemistry. By Joun J. Abel, M.D., 123

A Case of Paranoia, with a Study of the Cerebral Convolutions. By Heney J. Berkley, M. D., 130

Angio-Sarcoma of the Ovary. By Thos. S. Cullen, M. B., - 134

Proceedings of Societies :

The Hospital Medical Society, 136

Exhibition of Specimens from a Case of Deciduoma Ma

lignum [Dr. J. Whitridge Williams] ; — The Best Method of Sharpening a Microtome Knife [Dr. Lotsy] ; — Ureterotomy [Dr. Kelly] ; — A New Method of exploring the Rectum and Sigmoid Flexure [Dr. Kelly] ;— Double Castration for Hypertrophy of the Prostate Gland [Dr. Finney].

Notes on New Books, 138

Books Received, 140

Index to Volume V, 141

A CONTRIBUTION TO OUR KNOWLEDGE OF ORGANIC SULPHUR COMPOUNDS IN THE FIELD OF ANIMAL CHEMISTRY.^

By John J. Abel, M. D., Professor of Pharmacology. {From the Pharmacological Laboratory of the Johns Hopkins University.)

It is well known to workers in the field of aniuiiil chemistry that when freshly voided dog's urine is shaken up with milk of lime, or is made thoroughly alkaline with sodium or potassium hydrate, a peculiar, penetrating, offensive odor is developed ; but beyond the merest passing references, nothing can be found in literature regarding the compound yielding this odor, and nothing seems to have been done toward determining its nature. Thus,' Biihrn and Lauge, discussing the applicability of Schlosing's method to the determination of ammonia in the dog's urine, remark that the addition to the urine of milk of lime gives rise to a peculiar, penetrating, garlicky odor, filling the whole bell-jar even after the lapse of 48-72 hours. V. Knieriem ' makes a similar reference, but no one has gone farther than to note the presence of this odor.

' The substance of a paper with the title : " On the occurrence of ethyl sulphide in the urine of the dog; on the behavior of ethyl sulphide dissolved in concentrated sulphuric acid toward oxidizing agents, and on certain reactions for llio detection of alkyl sulphides," appearing in the December number of the Zeilschr. f. physiol. Chemie.

'Archiv f. exp. Pathol, u. Pharmakol., Bd. 2, p. 368.

»Zeitschr. f. Biol., Bd. X, p. 2l>9.

There .ire many substances known to chemistry which may be said to have a penetrating, offensive, stupefying, and in some cases, garlicky odor. Among these are the mercaptmis, the organic sulphides, selenides and tellurides, the phosphines and the isocyanides, but in the present instance no help was derived from tlie smell in identifying the body, as no one whose judgment was asked in the matter could state positively that the odor was like lUiy other known to him.

I was obliged to direct my first efforts toward gaining some notion of the ultimate qualitative composition of the body. To this end I proceeded as follows: Air from an ordinary large glass gasometer was made to bubble through two liters of urine to which about 100 cc. of thick cream of lime had been added, and the whole thoroughly agitated for a few moments, and this air, laden with the odorous substance, was forced through an empty wash bottle, then through two Muencke's wash bottles made entirely of glass, each containing a 10 per cent, solution of hydrochloric acid, then through two similar wash bottles filled with a 40 per cent, solution of sodium hydrate, then through an empty Kettle, and then through a piece of combustion tubing 60 centimeters long, filled in its middle third with asbestos fiber which had preri

124

JOHNS HOPKINS HOSPITAL BULLETIN.

[Nos. 44-45

oiisly been heated piece by piece to a white heat iu the flame of a l^arthel's alcohol blast-lamp. Pure oxygeu taken from an Elkan's cylinder and well washed by being made to pass through both acid and alkali, was forced into the tube containing the purified asbestos at the point where the air laden with the odoriferous body entered it.

From the tube filled with the asbestos the current of air was next passed into a Geissler potash bulb half filled with a 2 per cent, solution of the purest hydrate of sodium. With the ap})aratus arranged as described, the combustion tube containing the asbestos was kept at a red heat in a short four-burner furnace for five hours, the air and oxygen passing at about the rate that is usual iu combustion analyses.

At the end of this time a portion of the sodium liydrate solution in the Geissler bulb was acidulated with hydrochloric acid and tested with a few drops of a solution of barium chloride, with the result that an immediate precipitation of barium sulphate occurred. It may here be noted that the air current after it had passed the heated tube turned a blue litmus strip red, whereas it had no action on litmus before being heated, thus demonstrating that the sulphur of our conij)Ound had l)ecn turned from a neutral into an acid combination. A blank experiment in which the urine was replaced hv distilled water was carried on for six hours, but in this case the sodium hydrate yielded no trace of sulphate. Our conclusion must therefore be that the volatile, odoriferous compound contains sulphur.

At this point two questions present themselves: First, can this sulphur compound be referred for its origin to the action of the hydrate of calcium upon one of the known so-called ' " neutral " sulphur compounds of the urine, such as cystin and allied compounds, or such as hyposulphurous, sulphocyanic or mercapturic acids ?

Second, does the air after passing through the system of wash bottles used in the combustion experiment, contain any other substances than this odoriferous compound 'i

The first question can be answered with considerable certainty by the method of exclusion. Cystin does not seem to be decomposed by treatment with milk of lime at room temperature. Baumann and Brenziger ^ have shown, however, that when ethyl cystein is heated with a free alkali, ethyl mercaptan is split off. M. v. Nencki' was the first to demonstrate that the nausesiting odor of the urine after asparagus has been eaten is due to methyl mercaptan, and also that methyl mercaptan is one of the products of the bacterial decomposition of proteids.' Karplus' has also found methyl mercaptan in the urine as the product of a special bacterium, and L. v. Nencki ° finds that it is always present among the gases of the large intestine. Because, then, of the proved occurrence of mercaptjms in animal fluids, one cannot neglect making the proper tests for them where an offensive, not strictly definable odor is

'Salkowski : Archiv f. path. Anat. u. Physiol., Bd. 58, p. 472. 'Zeitschr. f. physiolog. Chem., Bd. 16, p. 565. "Archiv f. exp. Pathol, u. Pharmakol., B.l. 28, pp. 200-209.

• M. v. Nencki and N. Sieber: Monatsli . f . Chemie, Bd. 10, pp. 52G-31 .

'Archiv f. pathol. Anat. u. Physiol., Bd. 131, pp. 210-222. •Sitzb. d. kaia. Akad. in Wien, Mathum. Classe III, Abth. 98, pp. 437-8.

met with. But in the case under consideration the making of such tests will be seen to be unnecessary, for the very process of setting free our odoriferous compound with alkalies would have bound the mercaptans and prevented them from leaving the bottle, and an impassible barrier would also have been found in the wash bottles filled with sodium hydrate.

As for the other neutral sulphur compounds of the urine, the acids above mentioned, it may be remarked that the calcium and alkali salts of at least one of them, sulphocyanic acid, is stable and therefore could not come in question. The alkali salts of hyposulphurous acid are readily soluble and stable; the calcium salt is equally soluble but unstable.

Now, to exclude hyposulphurous acid as a possible source of the sulphur found in our combustion experiment, we have only to state that this experiment yielded the same result when fixed alkali instead of milk of lime was used to free the odoriferous substance. But even with the employment of calcium hydrate it seems hardly possible for sulphur dioxide to escape from a fluid containing such an excess of lime.

As to the mercapturic acids being a possible source of our sulphur compound, we have only to note Baumann's ' discovery that when they are decomposed with alkalies mercaptans are split off, a fact that has been adopted into the methods of urinary analysis. But we have demonstrated that it would be impossible for a mercaptan to pass over into the combustion tube. A further proof that excludes both the mercaptans and also sulphureted hydrogen is seen in the fact that two strips of filter paper moistened with alkaline lead solution and placed, the one between the bottle of urine and the first wash bottle, and the other between the last wash bottle and the combustion tube, never showed the slightest change of color.

It is therefore fair to conclude that our sulphur compound is not a derivative of one of the known " neutral " sulphur compounds of the urine, but that it is split off by the milk of lime from a still unknown sulphur compound of the urine.

We now turn to the second question : Does the air after passing through the system of wash bottles used iu the combustion experiment contain any other substance besides this odoriferous compound ? If we bear in mind the contents of the series of wash bottles, it will be seen that no substance with acid or basic properties could have passed them ; in other words, that only a chemically indifferent substance could have been found with the sulphur compound at the end of the series of bottles. This disposes not only of the mercaptans, but of all the various compounds spoken of in the beginning as having an odor similar to the compound in question, with the sole exception of the organic sulphides."

The phosphines, too, are excluded, for, being basic substances,' they would be held back by the hydrochloric acid. Then, too, the phosphines are very readily oxidized, and in

' Baumann : Zeitschr. f. physiolog. Ch., Bd. 8, p. 194.

■The selenides and tellurides are obviously out of theciuestion as constant products of animal metabolism, but see a late interestinfi paper by F. Hofmeister in Arch. f. exp. Pathol, u. Pharmakol., Bd. 33, p. 198, on the ability of the organism to form the nauseating methyl telluride and selenide on the introduction of selenium and tellurium or the salts of their acids.

" With the exception of the primary phosphineB.

December, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

125

sniiill amoniits could not be made to bubble np through so many wash bottles without being destroyed by this long contact with the air. A long series of experiments was, in fact, undertaken to determine whether or not a volatile phosphorus compound was present along with the sulphur eoniponnd before it was washed, but all with negative results.

It therefore seemed fair to assume that our sulphur compound was the only substance carried by the air through the series of wash bottles, and all the subsequent experiments made to establish its identity furnish additional support for this assumption.

SOLUTION OF THE COMPOUND IN CONCENTRATED SULPHURIC ACID, AND PROPERTIES OF THIS SOLUTION.

A series of experiments was next undertaken to determine how this sulphur compound could be collected in suiBcient quantities for study and analysis. It was finally found that concentrated sulphuric acid completely absorbed the body and the resulting solution is without color and also without odor unless the air current is allowed to bubble through the sulphuric acid for several days, when a faint oniony smell is perceptible. In concentrated sulphuric acid we have then a means of storing considerable quantities of this sulphur compound.

Chapman suction pumps were used to draw air through large flasks containing urine and milk of lime, then through two wash bottles containing a 10 per cent, solution of hydrochloric acid, then through two wash bottles filled with a 40 per cent, solution of sodium hydrate, then through a U tube 12 inches high and 1 inch in diameter filled with pieces of potassium hydrate, then through two similar TJ tubes filled with granular calcium chloride, and from this last tube the air hiden with the sulphur compound passed through a Geissler bulb or through a small wash bottle containing concentrated sulphuric acid. The connections beiween the bottles were glass to glass held in place by the best black English tubin<r Iwo such circuits were usually kept at work bv the same suction pump, and the pump was operated day and night -Vfter about 72 hours, in which time 1.5-30 liters'of dog's urine had been exhausted of the sulphur compound, the (Jeissler bulb containing sulphuric acid was replaced bv another. On diluting with water some of this concentrated sulphuric acid hat has been charged with the body, or on neutralizing it with ree alkalies, or on the addition of almost any metallic salt at hand, an intense odor like that of one of the organic sulphides pervades the room. These properties of dissolvincr i„ considerable quantities in sulphuric acid and of formino- ^vith it a nearly or quite odorless solution, and of being^set free unchanged on dilution with water or on neutralization of the su phuric acid, are possessed, so far as I know, bv the sulphides' only among organic sulphur compounds. I have repeatedly dissolved 10 or 12 grams of ethyl sulphi.le in 100 cc. of concentrated sulphuric acid, having previously cooled both fluids and found that the resulting solution had no odor whatever but^i^idduigjo this solution half its weight of water, or,"

'In all probability, however, the analogous seleni.les and telh.rIdes behave in the same way toward concentrated sulplinric acid.

better still, of ice, the ethyl sulphide soon appeared floating on the top of the diluted sulphuric acid. Dimethyl sulphide and methyl ethyl sulphide were found to behave in the same way. Reference books on chemistry do not mention this property, and It was only after the completion of mv experiments that I learned that this method is employed in refining crude Ohio petroleum, and that Mabery and Smith ' had by it= help recovered alkyl sulphides from the "distillates of crude petroleum."

OXIDATION OF THE URINARY SULPHIDE.

The alkyl sulphides arereadily oxidized to the fluid sulphoxides, and then further to the very stable crystalline sulphones. Ihus, if ethyl sulphide, (CJUS, is oxidized with nitric acid specific gravity 1.2, ethyl sulphoxide, (aH;;,SO, is produced, a thick, unstable fluid, easily soluble in water. If. however, fuming nitric acid is used, then diethyl sulphone, (C.H,),SoJ results, which crystallizes in large rhombic plates vefy soluble in water, melting at 70° and distilling at 248° without decomposition. The sulphoxides have the property of being reducible with zinc and sulphuric acid to the original sulphide. The sulphones, however, are very stable substances, unaffected bv treatment with zinc and sulphuric acid. It was hoped that oxidation of the concentrated sulphuric acid solution of the sulphide from the dog's urine with potassium permanganate would yield a sulphone, the composition and properties of which would determine which particular sulphide we were dealing with. Accordingly, about 100 cc. of a concentrated sulphuric acid solution containing the sulphur compound rallected from about 25 liters of dog's urine was treated in the following manner: A beaker containing it was placed in pounded ice, and from time to time were added a few drops of a concentrated aqueous solution of potassium permano-anate also cooled to 0° C. When the permanganate ceased to be decolorized, a cold 4 per cent, solution of sulphuric acid wa* slowly added until the acid in the beaker was reduced in strength to about a 20 per cent, solution. The whole was then heated on the wat«r-bath. while potassium permanganate was again added.

I'nder the influence of the heat an additional quantity of the permanganate was reduced, and the heating on the waterbath was kept up as long as any permanganate was decolorized.

The slight excels of permanganate, when reduction no longer occurred, was removed bv the addition of a little sodium formate.

The solution was then made alkaline with potassium hydrate, evaporated till crusts of potassium sulphate formed; the potassium sulphate filtered off, ajrain concentrated, again filtered, and now evaporated to dryness. The drv residue was extracted with a little absolute alcohol, half of thealcohol evaporated on the w ater-bath and the rest allowed to evaporate

' Americ. Chem. Journ., Vol. 13, p. 243, and Vol. 16, p. 3S. R. H. Smith h»s also treated ethyl fulphide with an equal hulk of strong sulphuric acid diluted with much waterand neutralized with barium carbonate for the purpose of forming barium-ethvl-hvposa!pbite, but makes no mention of the separation of the sulphide on dilution with water. Journ. of tlie Chem. Soc, 22 (1S69), p. 302.

126

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[Nos. 44-45.

spontaneously. A small quantity of a deliquescent compound remained. To remove all trace of potassium carbonate, the residue was extracted a third time with absolute alcohol and the alcohol again evaporated. On the addition of dilute sulphuric acid to some of the deliquescent residue, the odor of acetic. acid became very apparent. The characteristic odor of acetic ether was at once brought out on gently heating with the addition of concentrated sulphuric acid and alcohol, and the addition of ferric chloride to a neutral solution gave the characteristic blood red color of a solution of ferric acetate. These properties, viz., the deliquescence of the potassium salt, the odor of the free acetic acid and of its acetic ether, and the color of its ferric salt, leave no doubt of the occurrence of acetic acid as an oxidation product of the sulphur compound under examination. I was unprepared for this outcome, as I had hoped to secure a sulphone. On the supposition that a little of the sulphone might yet be mixed with the acetate, I acidulated its aqueous solution with sulphuric acid, drove away the acetic acid as far as possible on the water-bath, and again extracted the dry residue with alcohol, but only a trace of potassium acetate and sulphate was taken up. I now repeated the oxidation experiment twice over, making slight . variations in the method, such as the employment of finely powdered potassium permanganate instead of an aqueous solution, and sodium instead of potassium hydrate, yi the neutralization. 1 used also a little less than the necessary amount of permanganate, so as to avoid the after-use of sodium formate, but the iinal outcome was the same as before: an acetate again appeared.

A blank oxidation experiment was next undertaken in order to determine whether the reagents used contained any thing oxidizable to acetic acid, but not a trace of acetate was found.

We may therefore safely conclude that our sulphur compound contains one or two ethyl groups. It is not easy to draw conclusions as to the presence of a methyl group in the sulphide, as such a group would have been oxidized to carbon dioxide and water. Carbon dioxide is, in fact, given off when the acid solution and permanganate are boiled, but this can be referred to the destructive oxidation of some of the sulphide, for it also takes place when synthetically prepared diethyl sulphide is treated in the same way.

OXIDATION OF SYNTHETICALLY PREPARED ETHYL SULPHIDE UNDER THE SAME CONDITIONS.

It was now in order to compare the behavior of synthetically prepared ethyl sulphide with our sulphide. Accordingly, a preliminary experiment was first made as follows: Five grams of ethyl sulphide, which distilled at 91.9°-92° C, were dissolved in .50 cc. of sulphuric acid, and oxidized by adding small quantities of powdered permanganate very gradually to the concentrated sulphuric acid kept in a freezing mixture, an hour and a half being consumed in adding 12 grams. When too much was added at one time, a Hash of light would appear, showing that some of the sulphide was being completely oxidized, and the odor of ethyl sulphide also became apparent. 25 cc. of cold concentrated sulphuric acid were now stirred into the mixture, and from time to time

small portions of a concentrated aqueous solution of permanganate were added together with about 20 cc. of water. A colorless solution of an oniony odor now resulted and this was slowly diluted with water up to a liter, permanganate still being added. The solution was then boiled for a short time and as the permanganate was still being reduced, more was added. AVhen no more permanganate was reduced about 200 cc. of the fluid was distilled off. This distillate, which was plainly acid, was caught in a little strong potassium hydrate and subsequently enough more hydrate was added to give a neutral reaction, and it was then evaporated on the water-bath. There was obtained a small quantity of a deliquescent salt consisting of potassium carbonate and potassium acetate, which gave the reactions that we have already mentioned as sufficient to identify acetic acid. In a similar experiment it was observed that when the distillation was undertaken before the oxidation was complete, that is, at a time when the permanganate was still being reduced, the distillate had a most disagreeable odor, reminding one both of onions and of acetic acid. Also when evaporated to dryness with an alkali, it gives all the reactions of a sulphite, viz., it reduces permanganate, it yields sulphureted hydrogen on reduction with zinc and sulphuric acid, it decolorizes an iodine starch solution, it gives a red color to a weak solution of sodium uitroprusside, and it gives off the peculiar stinging odor of sulphur dioxide on acidulation with sulphuric acid. In such a case, therefore, one must first oxidize the sulphurous acid with permanganate before undertaking the tests for acetic acid or the preparation of one of its salts. When boiling is resorted to in order to hasten the progress of the oxidation, it is found that much carbon dioxide is given off. It is evident that in the above experiments the greater part of the sulphide was oxidized to the end products, sulphuric anhydride, carbon dioxide and water.

As, to my knowledge, the alkyl sulphides have hitherto only been oxidized to sulphoxides and sulphones, and not as in the manner indicated above, to acetic and sulphuric acids, it seemed worth while to attempt the quantitative oxidation of ethyl sulphide to these latter products. Accordingly, 12 grams were dissolved in 100 cc. of concentrated sulphuric acid, the latter being cooled in a freezing mixture; 65 grams of finely powdered permanganate, somewhat less than the quantity theoretically necessary to oxidize the sulphide to acetic and sulphuric acid, were then dissolved in 200 cc. of cold sulphuric acid, and this solution was slowly added to the cold solution of the sulphide. The permanganate was at first entirely decolorized and none of the sulphide was liberated or destroyed, but toward the end of the operation, as more and more of the oily heptoxide of manganese from the bottom of the beaker came to be added, the black mixture began to foam up, flames now and then shot forth and much carbon dioxide was given off. A repetition of the exi)eriment led to no better results. In both cases, however, water was added to the black, agitated mass, and after diluting to about a liter, the odor of acetic acid became plainly perceptible. When diluted to several liters and distilled, a little of the distillate treated as before gave all the tests for acetic acid. A little silver acetate was also produced which crystallized out of water in

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long, shiuing needles, gave off fumes of acetic acid, deposited silver on gentle incineration, and also emitted the odor of ethyl acetate on treatment with concentrated sulphuric acid and alcohol.

On account of the fact, however, that by far the greater part of the sulphide had been destroyed, it was evident that it would be useless to attempt the estimation of the amount of acetic acid produced. It would seem, therefore, impracticable to oxidize ethyl sulphide in this way with the intention of securing a large output of acetic acid, but any one can convince himself by an off-hand experiment that acetic acid IS one of the products of the oxidation of diethyl sulphide under the above circumstances. This is another point of agreement between the sulphide from dog's urine and ethvl sulphide.

What light this oxidation throws on the natureof tJie union existing between ethyl sulphide and concentrated sulphuric acid, and also whether thio-acetic acid may not be an intermediate product in the oxidation with permanganate, 1 cannot here discuss.

DOUBLE COMPOUND WITH MERCURIC CHLORIDE.

As the new sulphur compound from the dog's urine has so many points m common with ethyl sulphide, its behavior towards mercuric chloride was next examined.

Some of the concentrated sulphuric acid solution of the sulphide from the dog's urine was placed in an ice mixture and diluted with a cold 4 per cent, solution of sulphuric acid until the resultant liquid was equal in strength to about a 30 per cent, sulphuric acid solution. The odor found to arise from such large amounts of the diluted fluid was vei-y strong, and not to be distinguished from the odor of ethyl sulphide dissolved in concentrated sulphuric acid and treated in the same way. Indeed, none of the workers in mv laboratory could tell in any given case whether I was using the compound obtained from dog's urine or that svntheticallv prepared. The diluted solution of the sulphide was now shaken out with ether and the separated ether was washed twice with distilled water; an alcoholic solution containing 1 gram of mercuric chloride was then added to the ether and the whole evaporated to about one-third on the water-bath, after wliich It was allowed to stand in vacuo over sulphuric acid. The residue, which smelled strongly of the sulphide, was well washed on a filter with water in order to dissolve away the excess of mercuric chloride. It was then dried on the filter over sulphuric acid, dissolved when dry in a little alcohol and allowed to crystallize. Some of the crystals, long, slender in-isms mixed with some amorphous material were collected and their melting-point taken without further purification I his was found to be in one case about U5° C, and in another batcii of crystals prepared in a verv similar manner, ir>0° C. The noteworthy fact in both determinations was that the crystals melted to a black fluid, and after the capillary tubes had cooled, long slender prisms could be seen to stand out from the congealed drop.

I am personally convinced that this sulphide from the urine of the dog forms a double compound with mercuric chloride aUhough it must he a.lniitted tiiat Iho evidence, so far as it*'

melting-point is concerned, does not furnish conclusive proof that this compound is (CJi^\S.KgC\.

In support of this opinion that a double compound is formed, we may urge the odor of the compound, its insolubility in water, its solubility 'in alcohol, its behavior in the melting tube and its crystalline character. After standing over sulphuric acid /« vacuo, no odor, or at least onlv a very faint odor, is perceptible; but exposed to the air fo"r only" a few moments, the odor of the sulphide becomes very marked. The mercuric chloride compound of ethyl sulphide behaves in the same manner.

It is exceedingly difficult to separate a small amount of this unstable double compound, say a few centigrams, from an excess of mercuric chloride ; the various operations, such as the long and repeated washings with water, the necessary drying, etc., all involve so much loss of substance that sharj) results cannot be obtained when there is onlv little material on hand.

MELTING-POIXT OF THE DOUBLE COMPOUND (C,H.).S.HgCI,

The plan that was followed above in the attempt to secure and purify the double compound of ethyl sulphide from the dog's urine was based on previous experiments made in the same way with synthetically prepared ethvl sulphide. Five grams (boiling-point 91.9° C.) were dissolved in 50 cc. of concentrated sulphuric acid, and by following out the method described above, except that less of the theoreticallv required amount of mercuric chloride was used, the double compound crystallizing out of absolute alcohol in long, transparent. highly refracting prisms was obtained. This"^ recrvstallized out of alcohol, washed with cold absolute alcohol aiid ether, and dried in vacuo over sulphuric acid and paraffine, began to melt at 118° C. and melted to a coloriess fluid at 119° C. Subsequent recrystallizations out of ether caused no change in the melting-point. When the double compound is prepar^ by mixing alcoholic solutions of the sulphides and of mercuric chloride the melting-point is also 119°.

AVheu some of the finely powdered crvstals that show a melting-point of 119° are allowed to sbmd'over sulphuric acid forjiwo weeks, the melting-point is found to have risen to 131° C. Some of the unbroken crystals, however, that had stood for the same length of time over sulphuric acid melted at 120° C. When the temperature reached 180°-1S5° C. a rapid evolution of gas bubbles took place, but the liquid remained transparent and did not blacken.

Now Loir' gives 90° C. as the melting-point of cC^H.^S.HgCl, crystallized out of ether. An observation made bv me in'^the course of the above experiments may perhaps explain how Loir came to put the melting-point at 90° C. I prepared some of the ethyl sulphide mercuric chloride, recrystjillized it out of absolute alcohol, washed it with absolute alcohol and ether, and exposed it for half an hour to an air current produced by a Bunsen suction pump. At the expiration of this time the melting-point was taken and it was found that the substance melted at 80° C, yielding a perfectly transparent, colorless

'.\nn. il. Chem. u. riiarm. S7, p. 370.

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liquid. After standing for twelve hours over sulphuric acid in vacuo the melting-point was found to have risen to 119° C. It may be remarked in passing that Blomstrand ' finds one of Loir's melting-points, that of the platinum compound 2(C,H,.),S.PtCl„ 70° too low, it "being in reality 178° instead of 108° as given by Loir.

HEHAVIOK OF THE SULPHIDE TOWARD SOI.UTIOXS OF BROMINE AND IODINE.

It must be remembered that we- are confined to solutions of the urinary sulphide in concentrated sulphuric acid for a study of its properties. The behavior of bromine and iodine toward these solutions is characteristic and in every respect like their behavior toward similar solutions of synthetically prepared ethyl sulphide. If a drop or two of a 2 per cent, solution of bromine in potassium bromide be added to a sulphuric acid solution of the urinary sulphide, or to an equally weiik solution of ethyl sulphide, it will be observed that bromine is absorbed. The same thing is observed when bromine vapor is allowed to fall into a sulphuric acid solution that has previously been diluted with a few drops of water. If the sulphuric acid be poured off from the undissolved drop of bromine after having been thoroughly agitated with it, and then be diluted with water, it will be found that the sulphide odor no longer returns. If a piece of pure washed zinc and a litt>e more concentrated sulphuric acid be added, the sulphide odor returns as the reduction proceeds. A solution of ethyl sulphide of about the same strength as that from the dog's urine behaves in the same way. But if a strong solution be made, the absorption of bromine is very evident, for now considerable bromine may be added before some of it remains undissolved. Such a concentrated solution of ethyl sulphide treated with bromine still smells somewhat of the sulphide after dilution with water, but if left to stand for a few days the odor disappears, and may then be caused to reappear on reduction with zinc and sulphuric acid. We are in all probability dealing here with the bromine addition compound (Ci;H5)jSBr„, which, as described by Rathke," forms with water a colorless solution. Out of its aqueous solutions, iodine in potassium iodide precipitates an iodine addition product, (CJl5)jSI„ as a dark oily iluid.

Far more striking is the behavior of iodine, the study of which has led to a reaction which may under certain circumstances serve to indicate the presence of an alkyl sulphide. On the addition of a few drops of a 6-10 per cent, solution of iodine in potassium iodide, or of a ^^ normal iodine solution, an immediate precipitation occurs. The sulphuric acid solution becomes a dark brown, turbid fluid in which a precipitate of infinite fineness is suspended. After standing over night a small quantity of a dark brown oil separates out in minute droplets and settles to the bottom. This is undoubtedly the addition product (C,H*5)aSI,."

If the acid be poured off and water be added to this oily substance, the odor of a sulphide becomes at once apparent. The addition of a few drops of potassium hydrate immediately

' ' ,Tour. f. pract. Chem. (n. f.), Vol. 24, p. 190. 'Ann. d. Chem. u. Pharmac, BH. 162, p. 214. ' Kalhke, loe. rit.

causes the oil droplets to dissolve, and bringsout the sulphide odor in full strength. Iodine solutions also cause the dark cloudy precipitations in sulphuric acid solutions of the sulphides even when these are very much diluted with water, so that this reaction must be regarded as a very sensitive one.

Furthermore, a drop or two of the sulphide shaken up with much distilled water, say 60 cc, also gives a cloudy precipitate on the addition of a ^V^ormal iodine solution, and this precipitation occurs even when the aqueous solution has been allowed to stand for weeks, when we niily be sure that the ethyl sulphide is really dissolved and not merely suspended. Out of these aqueous solutions of the sulphide to which iodine solutions have been added, the oily product referred to also settles on standing. This last reaction demonstrates very clearly that ethyl sulphide, contrary to the usual statements, is by no means insoluble in water. I daresay that its solubility in water is fully equal to that of ethyl mercaptan.

Methyl sulphide and methyl ethyl sulphide behave in almost the same way toward solutions of iodine. The oily compound that is precipitated from dilute solutions of methyl sulphide in sulphuric acid seems, however, to pass again into solution on standing.

If to a distillate of dog's urine that has been shaken with milk of lime or made strongly alkaline with a free alkali, a few drops of an ^"^-iodine solution be added, a cloudy precipitation, very like that seen under the same circumstances in aqueous solutions of ethyl sulphide, will be observed. In this instance, however, the reaction is of uncertain meaning, for Schiff ' has shown that the distillate of the dog's urine contains a primary amine, and Abbott ' has found that aqueous solutions of amines give cloudy precipitates on addition of /^-iodine solution.

BEHAVIOR OF ETHYL SULPHIDE TOWARDS NITROUS ACID.

While trying to establish the identity of the sulphide treated of in this paper, I observed that when a drop of an aqueous 5 per cent, solution of sodium nitrite was added to some of the sulphuric acid solution of the sulphide from the dog's urine, the latter at once took on a beautiful deep green color. A drop or two of Liebermann's' nitrose sulphuric acid solution gives the same color and is preferable as a reagent to an aqueous solution of a nitrite, as if used in e.xcess it does not so readily cause the disappearance of the green color. The color persists for some time, but disappears if the solution is left to stand over night, and when the nitrite is not added in excess the reaction will be found to be of great delicacy.

To get this reaction with the urinary sulphide in perfection it is best to conduct the well-dried air and sulphide as

' Zeitschr. f. physiol. Chemie, Bd. IV, p. 54.

• Private communication from Dr. A. C. Abbott, of the hygienic

laboratory of the University of Pennsylvania, on the detection of amines in sewer air with N/20-iodine solution, which induced me to study the behavior of aqueous solutions of ethyl sulphide toward iodine solutions.

•• Ber, d. deutsch. chem. Gesellsch., Bd. 20, p. 3231 b. In making up the solution of a nitrite in cone, sulph. acid I used sodium instead of potassium nitrite.

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described on p. 135, with at least 5 or 6 liters of urine in the circuit, through a few cc. of concentrated sulphuric acid in a test tube an entire day. Special attention must be given to the drying of the air laden with the sulphide, for it is only when a completely dry current is passed into the concentrated sulphuric acid for the length of time named that a solution is obtained which will give at once the deep green color referred to, although solutions that have not remained so long in the circuit will also give a tinge of green, in which case, however, only a mere trace of the nitrite, such as adheres to a glass rod dipped into a solution of it, should be added. Now a drop or two of pure ethyl sulphide dissolved in a few cc. of concentrated sulphuric acid gives identically the same reaction on the addition of a drop or two of a nitrite solution or of nitrose sulphuric acid.

WHAT CHEMICAL CHANGES OCCUR IN THIS KEACTION ?

As long as the color persists, the sulphide can be liberated by the addition of small pieces of ice or by dilution with water, but after standing over night exposed to the action of an excess of the nitrose sulphuric acid, the now colorless solution no longer throws out the sulphide on the addition of ice. The reason for this is that the sulphide has been slowly oxidized by the nitrous acid to a sulphoxide, while the latter is reduced to nitric or niti'ous oxide. That this oxidation has occurred is demonstrated by adding a few pieces of zinc and allowing the reduction to continue for some hours and then diluting with crushed ice, when the original sulphide will again make its appearance. No further demonstration is needed to prove that the sulphide has been oxidized to a sulphoxide in the above exjjeriment. Since methyl sulphide and methyl ethyl sulphide also behave in the same way toward nitrose suljjhuric acid, it is fair to conclude that the reaction holds for the series of sulphides of the general formula

(C„H,„^,).« It might be suspected that the color reaction just described is due to thiophene formed on dissolving the sulphide in concentrated sulphuric acid, in analogy with the pyrogenous synthesis of thiophene first demonstrated by Kekule.' That we are not dealing with thiophene is, however, shown by the absence of that characteristic play of colors (green, blue to purple) that is always observed when a little nitrose sulphuric acid is added to a freshly prepared, sulphuric acid solution of thiophene, and by the fact that a solution of thiophene in concentrated sulphuric acid soon fails to give Lieberniann's reaction, in consequence of the rapid conversion of the thiophene into thiophene sulphonic acid. Then, too, that the green color described does not owe its origin to thiophene is proved by the fact that solutions of ethyl sulphide in concentrated sulphuric acid do not give the indophenine reaction, a reaction quite as delicate as Liebernuiun's reaction for thiophene.

The mercaptans, too, do not appear to give this reaction. As is well known, these sulphur compounds, when dissolved in concentrated suli)huric acid, are changed to the corresponding disulphides. Sulphuric acid solutions of ethyl mercaptau, the only one of the mercaptans that 1 have thus far

'See V. Meyer : Ber. il. ileutsch. chem. Gesell., Bd. 18, p. lilTa.

prepared for comparison, become murky and take on a reddish yellow color on the addition of a few drops of Liebermann's solution. The sulphides of the series C„Hj„S also fail to give this reaction.' Ethylene sulphide and propylene sulphide, when dissolved in concentrated sulphuric acid in small amounts, yield slightly green solutions. On the addition of a few drops of nitrose sulphuric acid the green color instantly disappears, giving place in the propylene solution to a 3-ellowioh turbidity, while the ethylene solution remains colorless. Methylene sulphide gives a colorless solution with concentrated sulphuric acid, which undergoes no change on the addition of the nitrose sulphuric acid.

It may be mentioned in conclusion that the vapor of pure ethyl sulphide was subjected to a destructive oxidation by passing it mixed with moist oxygen over asbestos heated to redness, exactly as described in the combustion experiment with the urinary sulphide in the early part of this paper. Here, too, the air that escaped from the combustion tube was laden with acid vapors, and an examination of the weak sodium hydrate solution in the Geissler bulb showed that sulphuric acid was present. When the supply of oxygen was insufficient, the bulb also contained sulphurous acid.

HAS THE SULPHIDE AN INTESTINAL ORIGIN ?

'J'he fact that methyl mercaptan is found among the gases of the large intestine,' and that there exists between ethyl mercaptan and ethyl sulphide a close relationship, suggests for the latter a possible intestinal origin, and that after absorption it unites with a compound that prevents its oxidation to end products and allows of its excretion in the urine. But an experiment in intestinal antisepsis' with calomel performed on a large well-nourished dog, showed after six days of abstention from all food except water and the administration of a total of 8 grams of calomel during the last three days, no appreciable diminution of the amount of the sulphide yielded to concentrated sulphuric acid. While this result is not absolutely conclusive because of the lack of quantitative methods for estimating the sulphide, and also because we cannot be certain that the bacterial activity in the intestines was completely suppressed, yet the evidence, so far as it goes, is against the bacterial origin of the sulphide. More conclusive is the negative outcome of all attempts to tiud the sulphide in the fseces of the dog by the use of the methods successfully applied to the urine.

The negative outcome of both experiments at least points to the probability.- that ethyl sulphide is a product of retrogressive metabolism. The urine, too, appears to contain decidedly more of the compound when the dogs are put ou an exclusively meat diet than when fed on the mixetl diet of refuse from the hospital kitchens.

So far as I have been able to discover, crude petroleum is the only other natural source besides the dog's uriue, of the

' This point was not established in time for its appearance in the German version of this paper.

' L. v. Nencki : Sitzb. d. kais. .\kad. in Wieu, Malhem. Classe III. Abth. 9S. 43:--13S.

■' Baumann : Zeiteohr. f. physiol. Chem., Bd. 10, 1SS6, S. 129.

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saturated alkyl sulphides. Now that we have methods for their detectiou, it is not unlikely that they will be found to be as widely distributed as are the mercaptaus. I hope soon to be able to offer something definite as to the properties of the compound from which the sulphide is liberated in the dog's urine on treatment with alkalis, and also to be able to isolate the pure sulphide in sufficient amount for the determination of its boiling-point, etc. It is only after having accomplished the isolation of the compound with which the sulphide is united that wc can say anything definite as to amounts in which the sulphide is excreted. Since, however, easily demonstrable quantities of sulphuric anhydride can be obtained by o.xidizing its vapor, one is justified in the opinion that it is present in equal or greater quantity than are such compounds as sulphocyanic or thiosulphuric acid. And it seems fair to conclude that it will be found on quantitative estimation to answer to the still uuideutified sulphur compounds in the dog's urine.

KKSUJIK.

It will be seen that the difficulties encountered in the collection and study of the new compound were not few. The following points have, however, been clearly established :

1. When dog's urine is treated with alkalies, an odoriferous compound is liberated which contains sulphur and which is taken up with avidity by concentrated sulphuric acid and from which it is again liberated on dilution with water or on neutralization. The odor arising during the progress of the dilution or neutralization is not to be distinguished from that of ethyl sulphide, (0,115)38. Ethyl sulphide is likewise absorbed by concentrated sulphuric acid with great avidity.

2. Oxidation of the urinary compound in the form of its solution in concentrated sulphuric acid yields sulphuric aud acetic acids, thus demonstrating the presence in it of an ethyl group. Oxidation of ethyl sulphide under the same conditions yields the same products.

3. Mercuric chloride forms with the urinary sul2)hide a double compound which behaves, as far as could be determined, in regard to odor, solubility and crystallization, like the corresponding ethyl sulphide mercuric chloride, (CaHJjS.HgClj.

■1. Bromine and iodine behave toward its solutions in concentrated sulphuric acid in every way as toward similar solutions of ethyl sulphide.

."). A nitrite added to its solutions in couceutrated sulphuric acid gives the same intense green color as with solutions of ethyl sulphide.

6. The organic sulphide thus shown to exist in dog's urine is ethyl sulphide, (CjH5)jS. The mixed sulphide, methyl ethyl sulphide (CHj.CJIs)^, might be thought to have an equal claim with ethyl sulphide as a urinary constituent, since its solutions in concentrated sulphuric acid behave in the same way toward bromine, iodine and nitrous acid, and since the products of its oxidation by the method described are the same, but pure methyl ethyl sulphide that has been several times rectified is easily distinguishable from ethyl sulphide by its odor, which has an additional smell like that of rotten cabbages, not possessed by the latter.'

PURELY CHEMICAL RESULTS.

The points of more especial chemical interest are :

1. The oxidation of ethyl sulphide to acetic and sulj)huric

acids.

3. Its great solubility in concentrated sulphuric acid, and the

ease with which it can again be liberated from this solution

even when dissolved in minute quantities.

3. Its oxidation to a sulphoxide by nitrous acid ;ind its green color reaction with this reagent.

4. Its solubility in water and the ease with which its aqueous solutions can be detected with solutions of iodine in potassium iodide.

5. Also to be noted is the fact that the melting-point of ethyl sulphide mercuric chloride lies at 119° C, and not at 90° C. as stated by Loir and since his time in all- reference books on chemistry.

' See J. Finckh (Ber. d. deutsch. cliem. Gesellsch., 1894, No. 9, p. 1239), wlio finds that these organic sulphides lose their nauseating odor on being repeatedly heated to 290°-300° C. in a sealed tube with powdered copper.

A CASE OF PARANOIA, WITH A STUDY OF THE CEREBRAL CONVOLUTIONS.

By Henry J. Berkley, M. D., Clinical Lecturer in Psychiatry.

Since the pathology of the mental disease known as primary paranoia is entirely unknown, the macroscopic examiiuvtion of the brain in this case nuiy not be devoid of clinical interest. The reader's attention is i)articularly called in the right hemisphere to the region of the post-central furrow, the very broken arrangement of the gyri of the parietal region, the unusual development of the third f rontjil convolution, short, broad, and standing isolated from the other convolutions of the lobe except on its orbital aspect. The external aspect of the left hemisphere is much more in conformity to recognized types, but the inner surface has many points of dissimilarity with the opposite brain-half. Altogether the impression given by

both hemispheres is considerably at variance with the usual types of convolutional development, and the asymmetry between the hemispheres is very marked.

The early history of the patient, Sarah Janet N u, is to

a large extent shrouded in obscurity. Born in Scotland of respectable parents, she was given a fairly good education, and though moderately intelligent, she preferred wandering in the fields with the sheep and heather, to attending school.

She stated that she was always on good terms with her school companions, but at home was restless, all her affections centering in a sister, to the exclusion of the rest of the household. The parents, as well as the brothers and sisters, are

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represented as being healthy, mentally and physically. She also stated that she was married at an early age, and had two children by this husband and another by a lover.

About the age of thirty-five years she emigrated to this country and obtained employment as a housekeeper. She seems to have been fairly successful in giving satisfaction to her employers, though there were several changes during the five years previous to her admission to the City Asylum, and she was discharged from her last situation by reason of her quarrelsome disposition.

In 1890, when she was in her thirty-ninth year, the climacteric began, and by the commencement of July, 1891, all evidence of menstruation had ceased. There were during tlie menopause hemorrhages of some intensity from the uterus, for which she was treated at one of the city hospitals, where she resided several months and until she was obliged to leave. Finally she was sent to the City Almshouse (admitted August 6, 1889), where it was soon recognized that she was insane, being irritable, suspicious, and having marked delusions of persecution, the principal ones being that for a person of her position she was not treated with sufficient respect by the officers of the institution, and that her food was poisoned.

These delusions led to a number of outbreaks of violence against the inmates of the almshouse, and proceeded to the extent of an attack upon the superintendent, and on July 27, 1892, she was transferred to the City Insane Asylum.

At the time of her admission N. was extremely suspicious, and it took the physicians in attendance some time to gain her confidence, and then only by a complete acquiescence with her delusions, the slightest correction annihilating any one in her esteem, and afterwards it was impossible to make her hold any communication.

The jDatient was a tall, angular woman, without any marked signs of somatic degeneration. The skull was sub-brachycephalic, without irregularity in the cranial bones. Physical examination showed the viscera to be healthy with the exception of the lungs, these showing the signs of a beginning tuberculosis at the apices. The heart's action was steady, regular, and without abnormal murmur. There was no history of a traumatism, alcoholism, or of a previous attack of any of the infectious diseases, to supply an etiological factor for the development of the mental trouble.

After the few days necessary to overcome the suspicions she entertained in respect to the medical stafE of the liospit^il, she unburdened herself fully of her troubles and insistent ideas. Delusions of persecution were strongly marked, but by no means paramount. On account of her mission she was molested and persecuted by a multitude of enemies, and though she made a strong effort to preserve outward calmness, occasionally she burst into a torrent of invective upon the heads of her enemies, magnifying the smallest offense against herself into mountains of malice and wickedness.

The delusions of persecution were, however, of small interest in comparison with other fixed ideas, and by contrast sank into the. background. N. believed that she was a prophetess called of God, and was the " woman clothed with the sun, and the moon under her feet, and upon her head a crown of twelve stars," of the XII chap, of the book of the Revelation, and

that her present abode represented the allegorical wilderness where she was to be fed for a space of one thousand three hundred and threescore days, the time representing that of her earthly tribulations, at the end of which period there was to be the judgment day, and without dying she was to be translated to the presence of God. Not only was she to be translated undying, but in some way now unknown to her, and only to be revealed on that great and awful day, she was to take a chief part in the redemption of the human race and intercede between them and the Almighty. At the end of the day of judgment she was to ascend to her prepared abode in the heavenly Jerusalem amidst the rejoicings of the multitude and the "voice of mighty thunderings, saying Alleluia, for the Lord God omnipotent reigneth. Let us be glad and rejoice and give honor to him, for the marriage of the Lamb is come, and his wife has made herself ready" (Eev. xix).

The child spoken of in the first quoted chapter played a very secondary part in her delusion ; she considered the passage to refer to the last of her two male children and the subject played no further part in her history.

The mission on earth was to be a secret one, and while not hesitating to inform those in the immediate circle of her confidence of its purport, she chose not to herald it to the world, preferring to bide the proper time for the revelation.

N. had in her possession a small, well-thumbed Bible, which she carried with her even at meal-times, and coustiintly referred to; in truth, the principal part of her time was spent in delving over its pages, searching for references to herself. Each one when found she marked with a round lead-pencil mark of a definite size. Not only were the passages referring to her marked, but a large number of scattered verses of different import were equally distinguished by a mark, having special reference to some idea or thought.

A few typical passages referring to her may be selected, as (Judges xiii) " Behold thou shalt conceive and bear a son, and now drink no wine nor strong drink, neither eat any unclean thing," a mandate she faithfully endeavored to carry out : or. (I Kings iii) " 1 have given thee a wise and undersbiudiug heart, so that there was none like before thee, neither after thee shall any arise like unto thee," or, "For thy Maker is thine husband, the Lord of hosts is his name, and thv Redeemer the Holy one of Israel, the Lord of the whole earth shall he be called."

The other passages marked in the Hible were exceedinglj numerous. Commencing with a systematic indication in Judges, they increased greatly in .Fob and Psalms, gradually diminished in Isaiah and Jeremiah, and decreased to a small number in the latter books of the Old Testament, In the four Gospels they were comparatively infrequent, increase*! very slightly in the Acts and Epistles, except in Corinthians and Hebrews, where the marks were frequent, and then gradually diminished to Revelation, where only a few chapters were marked, these having especial reference to herself and the New Jerusalem. A rather pathetic notice of the loss of her personal liberty occurred in II Corinthians, where she had m.wked '• where the spirit of the Lord is, there is lil»erty."

The other very nnmerous marked verses may be arrayed under six headings: (1\ Every passage concerning women in

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travail and labor ; (2), all passages referring to the rebuilding of the Temple and descriptions of the New Jerusalem, which she appeared to confound ; (3), numerous references to her troubles: (4), ajjpeals for help; (5), occasional songs of rejoicing ; and lastly, denunciatory passages, which were everywhere indicated and were the most numerous of all, for example, " Behold the day of the Lord conieth, cruel both with wrath and tierce anger to lay the land desolate, and He shall destroy the sinners thereof out of it" (Isaiah xiii).

A considerable number of mouths passed, N. still retaining her delusions perfectly tixed and systematized, without the addition of hallucinations either visual or aural. She refuted all assertions combating any of these ideas by references to various passages in the Bible, and by the argument that all things in that book are from the mouth of God and therefore beyond the possibility of dispute.

Toward the end of the year 1893 the pulmonary tuberculosis began to make rapid advances, persistent diarrhceas set in, accompanied by much abdominal pain that narcotics only partially relieved. Neuralgic pains in the intercostal nerves also added greatly to her sufferings. Nevertheless she clung persistently to life and waited patiently for the day of her translation, not believing in the least that death would result from disease. Albuminuria now shortly developed, and finally death occurred on February 3, 1894.

A summary of the autopsy shows little of interest. All the principal organs with the exception of the lungs were normal. The brain was slightly reduced in volume; the membranes were normal, the gray matter not reduced in thickness to any appreciable extent. The general texture of the cerebral substance was firm.

The Desckiption of the CuREUituM akteii Hahdeninu. a) The Principal Fis^iireit.

The Sylvian fissures conform to the usual arrangement, neither ascending limb penetrating upward more than is ordinarily seen.

The Rolandic sulci of neither side show any unusual variations, though the right reaches a little closer to the interhemispheric fissure than its companion sulcus.

Inter-parietal sulci. — In the right hemisphere the post-central furrow commences in the depths of the Sylvian fissure, and extends to within 3 mm. of the margin of the interhemispheric fissure. It is unbroken by secondary gyri throughout its entire length. The inter-parietal furrow commences 33 mm. above the edge of the Sylvian fissure, and is entirely .separated from the post-central furrow by a tongue of cortical substance extending from the gyri of the superior parietal lobe to the inferior parietal lobe. After running oblicpiely upwards and backwards about 30 mm., the fissure is broken by a broad convolution connecting the upper parietal lobe with the region of the angular gyrus. x\gain commencing behind this gyrus, it immediately throws off a rectangular branch toward the median surface of the brain, the furrow being deeper and longer than is usual, and then following its usual course 30 mm. further, it breaks up into six deep but short radii, and ends, not pene

trating downward into the occipital region after the usual fashion.

The companion sulcus of the opposite hemisphere commences at the margin of the Sylvian fissure, runs obliquely upwards, then horizontally, and descending, penetrates deeply into the occipital lobe. The post-central gyrus of this side offers no anomalies in conformation.

The occipito-parietal sulci of both sides are deep; the left extends 3 mm. further into the lateral surface of the brain than the right, and at its innermost point there is a considerable depression, out of which extend five short branchlets, all having their origin in the fissure. The left fissure extends into the fissure of the hippocampal gyrus, the right runs into the calcariue fissure.

The calcarine fissures and tlie furrow of the corpus callosum follow the usual type.

The formation of the convolutions presents considerable variations from what may be considered the usual development.

b) (■omparison of Ike Conrohitions.

The gyri of the orbital surfaces of the frontal lobes, the convolutions of the island of Keil,the cerebellum and medulla oblongata, present neither asymmetry nor departure from the usual type.

The Frontal Lobes.— Eight Hemisphere.— The superior frontal is very narrow, only 14 mm. in average breadth ; and at its posterior end is almost completely separated from the paracentral lobe by a deep upward extension from the sulcus prtecentralis crossing through the lobe to the median aspect of the hemisphere. At its anterior end it is fused with the substance of the middle frontal gyrus. The surface is furrowed by a few transverse sulci of little depth. The superior frontal sulcus has nothing noteworthy.

Left Hemisphere.— The first frontal of this side is also narrow, averaging 13 mm. The posterior half of the convolution is split into two separate gyri by a horizontal extension forward of a branch of the pra-central sulcus. The upper limb of the convolution joins the convolutions of the prsecentral region, the lower turns obliquely downwards and joins the base of the middle frontal. At its anterior end it is fused with the intricate convolutions of the tip of the lobe. The first frontal sulcus is free from bridging.

Middle Frontal, Left Hemisphere. — This convolution is single, though in its posterior half it is 43 mm. broad, and is conjoined with the anterior central gyrus by a deep-seated pli-de-passage. The gyrus has a large number of short horizontal and transverse sulci of short extent.

Middle Frontal, Kight Hemisphere.— The convolution is much broken by short tertiary fissures, and averages 35 mm. in breadth. At its base a strong bridge is thrown across the pnecentral sulcus, uniting it with the gyrus cent. ant. About midway of its anterior border, a gyrus 6 mm. in breadth crosses the inferior frontal sulcus to the inferior frontal convolution, and divides the sulcus into two unequal portions, the anterior being the longer. The posterior limb of the sulcus turns downward, penetrates completely through the third frontal, and ends far within the fissure of Sylvius.

The Inferior Frontal, Left Side.— This convolution is

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diminutive in comparison with the extraordinarily thick though short fellow of the op2)osite hemisphere. It averages 11 mm. in breadth, and as already described, is united in its middle portion with the second frontal, and at its anterior extremity with the convolutions of the orbital aspect of the lobe, the inf. frontal sulcus extending far forwards, separating it completelv from the convolutions of the second frontal in this region.

The Inferior Frontal, liight ISide. — This convolution is of rounded oval form, averaging 32 mm. in width by 59 mm. in length. It is completely separated from all other convolutions of the lateral surface of the lobe ; in its posterior portion by the praicentral sulcus, and in all other regions by the inferior frontal sulcus, which winds completely around it and descends to the orbital surface of the lobe. This sulcus is confluent at its posterior end with the prajcentral furrow. The convolution is much more complicated than any other of the lobe, the tertiary gyri being numerous. The opercular regions present a uniform view in both lobes.

The sulci prsecentrales presentthe usual bridging extending from the frontal convolutions to the gyrus pri^centralis.

Right Prajcenti'al Gyrus. — This gyrus averages 11 mm. in breadth, and is sjjlit at its base by a deep tertiary fissure extending from the depths of the Sylvian fissure obliquely upward, finally debouching into the prajcentral furrow, thus separating off a portion of the convolution nearly Vi mm. in length. The superior third of the' gyrus is slightly broader than th,e middle portion, and is cut off from the pai-acentral convolution by a deejj transverse incision.

Left Paracentral Gyrus. — This convolution averages 10 nun. in breadth, and is completely broken in its middle third by an unusually deep transverse incision from the sulcus pra^centralis penetrating into the IJolandic fissure just above tlie mentioned bridge from the middle frontal. This deep incision is the only furrow on (he convolution, the remaining portions being smooth.

Right Postcentral Gyrus. — The convolution only averages 8 mm., otherwise there is nothing to note.

Left Postcentral Gyrus. — This fold is exceedingly uneven and rugged; in some portions it is (i mm. wide, in otiiers it is 15 mm.

Right Parietal Lobe. — Besides the unusual development of the gyri crossing the interparietal fissure, the upper lobe is much broken by small vertical sulci, some communicating with the interparietal sulci, others separate from it. In the upper lobe, the gyri supermarginales, while complicated, are not irregular. The angular gyrus is connected with the upper lobe by the above-mentioned inconstant gyrus, otherwise the usual api)earance of the region is retained.

Left Parietal Lobe. — The upper parietal lobe is divided into four gyri running vertically from tlie margin of the interparietal furrow. 'IMie inferior lobe luis no departure from the customary type.

The occipital convolutions on both sides conform to the ordinary arrangement. The intervening sulci are deep.

Right Temporal Region.— The superior convolutions are doubled in their posterior portions by tertiary sulci, and are correspondingly broad. The inferior convolution is narrow in its anterior half, but broadens out considerably where it is confluent with the third occipital gyrus. The fissures present nothing of importance. Tlie occipito-parietal and hippocampal gyri also have no departure from the usual form.

The left temjjoral region is in conformity with the usual type.

Median Aspect of the Right Hemisphere. — The inner aspect of the superior frontal averages 20 mm., in breadth, and is much broken by shallow transverse fissures. !Ncar the paracentral lobe a number of oblique fissures mingle with the transverse. The sulcus calloso-marginalis follows its customary course. The gyrus fornicatus is smooth, except where it merges into the pnecuneus, and averages 10 mm. in width.

The precuneus, cuneus, and the internal aspect of the occipital convolutions have no departure from the common types. The sulcus hippocampi is unbroken by bridges.

Median AsjDect of the Left Hemisphere. — The internal portion of the superior frontal averages 13 mm. in breadth, and is deeply incised by a tertiary furrow at the point where it joins the paracentral lobule.

Passing toward the corpus callosum we immediately come upon a secondary furrow, which, beginning under the knee of the corpus callosum, extends without break to the middle of the inner aspect of the paracentral lobule, ending within the lobule in a forked branch. Beneath- this fissure is a second convolution exactly paralleling the superior frontal, ha^^ng a breadth of 10 mm. It begins in a thin fold confluent with the superior frontal at a point 10 mm. in front of the optic commissure, and extends from tliis point unbroken by any deep incision into the anterior portion of the paracentral lobule, joining it just in front of the sulcus paracentralis by a tongue 3 mm. wide. Beneath this convolution lies the proper sulcus calloso-marginalis, which begins by an incision reaching nearly to the floor of the brain and immediately in front of the optic commissure, and after following the course of the corpus callosum, giving off on the way the sulcus paracentralis, it ends in the usiuil place behind the sulcus centralis. This configuration of the region gives a very broken lobus paracentralis, of less size than ordinary.

The gyrus fornicatns parallels the corpus callosum. is narrow and smooth, and joins with the i)i-a?cuneus after the usual manner.

There is nothing unusual to note in the configuration of the prtvcuueus, cuneus or lingual lobe, except that they are more broken into minor convolutions than in the corresponding regions of the opposite hemisphere.

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^:ngio-s^rcom^ ok the ov^^ry.

By Thos. S. Cullen. M. B.

(Reported at the Johns Hopkins Medical Society, Notember 5, 1894.)

L. R, £et. 48. Admitted to the .lohus Hopkins Hospital in the service of Dr. Kelly, July 3, 1894.

Upon entering, the patient complained of enlargement in the lower part of the abdomen, pain in the abdomen and also in the back.

Menstruation commenced at 14 years, has ahvays been regular. She has been married over twenty years, has had two children, the youngest of which is 12 years of age. There is also a history of numerous miscarriages.

Family history unimportant.

History of present illness. — In January the menses became profuse and painful and have continued to be so. During May she first experienced severe grinding pain in the left ovarian region. This has continued and at times radiates down the thighs. Simultaneous with the first appearance of the pain a mass was noticed in the abdomen just above the pubes ; this gradually increased in size.

On physical examination the lower zone of the abdomen is found distended. The superficial veins are congested, and palpation reveals a firm bilobate mass springing from the pelvis. This extends slightly higher on the left than on the right side.

The anterior lip of the cervix is flush with the vaginal wall ; the OS is very patulous, admitting the index finger, and on the left side of the cervical canal a soft mass can be felt. The uterus is enlarged and appears to be continuous with the mass on the left side.

July 7, 1894. Operation by Dr. Kelly. Patient in Trendelenburg position.

An incision 19 cm. long was made in the abdominal wall. On the left side the pelvis was found to be choked by a soft mass ; this was slightly movable, and extending over it was the rectum, which had been displaced toward the right side.

Both the rectum and sigmoid flexure were attached to the tumor by their posterior surfaces. The left ovarian vessels Avere secured and enucleation commenced. In loosening the left side the tumor conmienced to tear, and it was necessary to hurry the operation as much as possible on account of hemorrhage. The uterus was then amputated at the cervix and the cervical stump closed by five silk sutures. Nodules of the growth still remained in Douglas's cul-de-sac, on the left side where the tumor had been separated, and also between the cervical stump and the posterior wall of the bladder.

A large gauze drain was placed in the lower angle of the wound and the abdomen closed by silkworm-gut sutures which included all the abdominal coats. Duration of the operation 51 minutes.

On the following day the drain was removed and about 15 cc. of thick bloody fluid escaped. The discharge gradually assumed the character of pus, and was still present when the patient left the hospital. There was a slight rise of temperature for the first two weeks, 102.5° F. being the highest point reached T'atient discharged .September :i 1.S94.

Pathological report. — That portion of the uterus present is 10x12x9 cm. It is irregularly globular, bright red in color, and covered both anteriorly and posteriorly by a few delicate adhesions. The under cut surface is 5 cm. in diameter. The uterus is firm and non-yielding ; its walls average 2.5 cm. in thickness, and scattered throughout them are numerous homogeneous fatty-like masses, varying from .5 to 1.5 cm. in diameter. One of these presents dark red patches which are apparently small blood-vessels. The posterior part of the fundus is occupied by a submucous nodule 8x7x5 cm. This is somewhat lobulated and resembles raw beef in color. Springing from the lower margin of the nodule and continuous with it is a finger-like mass 6x4x1.5 cm. This projects into the cavity, and its lower teat-like extremity protrudes from thicervix. The uterine cavity is 7 cm. long and approximately 2.5 cm. in diameter. The mucosa on the anterior surface is whitish yellow in color and 1 mm. in thickness.

.Springing from the right side of the cavity is a polyp 1.5 cm. in diameter. The large submucous nodule which projects into the uteriue cavity is not covered by mucosa, but presents a slightly worm-eaten appearance.

The right tube and ovary are of small size and apparently normal.

On the left side of the uterus is a mutilated liiduey-shaped mass 16x10.5 cm., the convexity of which is directed away from the uterus, while the concave portion is adherent over an area 8x9 cm. During operation the tumor was partially divided into three lobulated masses. On separating these still further from one another, they are seen to be composed of fibres which run in parallel rows. These fibres are light red in color and resemble strands of muscle. In the centre of each fibre and running parallel with it is a delicate blood-vessel. Other portions of the tumor are pale, homogeneous and resemble brain tissue, but on further examination are found to be also composed of fibres. There is apparently no breaking down of the tissue. The left tube is 11 cm. long, 5 mm. in diameter. Its outer extremity is adherent to the tumor. The parovarian is intact. No trace of the ovary is to be made out.

Histological examination. — The left ovary is found intimately adherent to the tumor, there being no dividing lintbetween the two. A portion of the ovary is recognized by several large corpora fibrosa and a corpus luteum. The tumor mass is composed of spindle cells cut longitudinally and transversely, these tending to arrange themselves around bloodvessels, which are very numerous.

The vessels have an inner lining of endothelium, surrounding which in some places is a delicate muscular coat, the outer portions of which appear to have undergone hyaline degeneration. Immediately surrounding the muscular coat are 8 to 10 la)'ers of spindle-shaped cells running parallel to the vessel. Such is the condition present where the vascular fibres were seen.

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In other portions of the tumor the blood-vessels are not so abundant, and the spindle cells do not maintain any definite arrangement. Many of the spindle cells have large oval nuclei, others show nuclear figures, while some apparently contain 2 to 3 deeply staining nuclei.

Here and there the tumor shows coagulation necrosis, sometimes with, sometimes without nuclear fragmentation, while in other places polyuuclear leucocytes are present.

The Uterus. — The nodules scattei'ed throughout the uterine wall are composed of cells precisely similar to those of the tumor. There is, however, no tendency toward the arrangement around blood-vessels. The large nodule projecting into the uterine cavity is similar in nature and presents numerous necrotic areas. On its free surface very little degeneration can be made out.

Uterine mucosa. — The cervical glands are for the most part normal ; a few, however, ai'e dilated. The change from the cervical to the uterine mucosa is gradual, the latter being exceedingly thin. The surface epithelium is intact. The glands are scanty in number, cylindrical, and have an intact epithelial lining. Those glands in the depth of the mucosa run parallel to the surface. The stroma of uterine mucosa is of moderate density.

The left tube presents some hemorrhage in the muscular coat, and a few calcareous nodules are seen just beneath the peritoneum. Tiie right tube and ovary also contain a few calcareous nodules.

Z)f«^?iOA'js.— Angio-sarcoma of left ovary. Extension into uterus by continuity and also apparently by metastases, the growth in the uterus being a spindle-celled sarcoma. Atrophy of uterine mucosa, calcareous nodules in both tubes and also in right ovary.

Round and spindle-celled sarcomata of the ovary, although not common, occur with a moderate degree of frequency, and we have been able to gather more than 70 cases from the literature.

Angio-sarconia of this organ is, however, rare, and in most instances has been described under the title " Endothelioma."

Macroscopically the ovary may retain its normal contour, but be greatly enlarged ; sometimes it is lobulated and may be either firm or soft. On section it is often found to contain cyst-like cavities. Some of the tumors appear to be composed of fibres with blood-vessels traversing the centre of each fibre. In these cases a diagnosis can immediately be made.

These tumors have two chief sources of origin : 1st, those arising from the blood-vessels (Aniann (4 cases), Ackermann, Bckardt, Marchand) ; 3d, those springing from the lymphatics (Amann, Flaischlen, Leopold, Marchand, Pomorski, V. Rosthorn, v. Velits and Voigt). These two divisions are again subdivided according as the sarcoma arises from the outer sheath of the vessels or from their endothelial lining,

Otir ease was uniloubfedly perithelial in origin, growing from the outer coats of the blood-vessels. As it is sometimes very difficult, and in fact impossil)lo to say whether it arises from the outer or inner sheath of the vessels, we think the two

divisions are sufficient, viz., those arising from the bloodvessels and those springing from the lymphatics.

These tumors have occurred in children 7 years of age, and in women 64 years old. The average of 11 cases was 33 years.

The chief points in our case were the marked adherence of the tumor to the surrounding structures, the typical vascnlar fibres enabling us at once to diagnose it as angio-sarcoma, and the metastases in the uterus.

Dr. Welch. — I have jjut under the microscope a specimen of an angio-sarcoma which is parallel to that of Dr. Cullen's. It is a most typical example of angio-sarcoma. A large tumor had grown in the axillary region, developing from the axillary lymphatic glands. It was operated upon by Dr. Keyes in New York. The operation was of unusual difficulty on account of the severe and almost uncontrollable hemorrhage. After the operation the tumor rapidly returned and there were metastases widely distributed in many organs of the body.

Dr. Cullen described his tumor as looking like a mass of muscle fibres. In my case it looked more like a mass of nerve fibres running parallel to each other, each fibre presenting a small central lumen. The tumor consists of blood-vessels running parallel with each other, and the tumor cells form the covering to the blood-vessels. There is an endothelial wall, then a few strands of circular muscle, then a little hyaline material, and then the tiimor cells proper. The tissue between these strands is made up to a large extent of extravasation of blood, a few cells and a few strands of connective tissue.

Amann : Arcliiv f. Gyn., lS<t4, Bd. XLVI, S. 4S4.

Eckardt : Zeitschr. f. Geb. u. Gyn., 1SS9, XVI, S. 344.

Flaischlen : Zeitschr. f. Geb. u. Gyn., Bd. VII, S. 449.

Leopold : Arehiv f. Gyn., 1873-74, Bd. VI, S. 202.

Marchand : Beitrage zur Kenntniss der Ovarien-Tumoren, Halle, 1879, S. 50.

Pomorski: Endothelioma Ovarii. Zeitschr. f. Geb. n. Gyn., 1890, XVIII, S. 92.

v. Rosthorn: .Archivf. Gyn., 1891, XLI, S. 328.

V. Velits : Zeitschr. f. Geb. u. Gyn., 1890, XVIII, S. 106.

Voigt : Z'lr Kenntniss des Endothelioma Ovarii. Arcliiv f. Gyn., 1894, XLVII, S. 560.

Description of Pl.vte. f natural size.

The specimen is viewed from behind, the uterus being cut open. On the left side a large, somewhat lobulated and torn mass is se«n ; attached to the outer margins of this are a good many adhesions. The lower and inner portion of the tumor is composetl almost exclusively of fibres running parallel to one another. The mass is intimately adherent to theleft side of the uterus.

The uterus is at least three time.'* its normal siie, its walls being twice their usual thickness, while studding the uterine niascle are irregularly lobulated or round nodules. These are of a yellowish waxy appearance and stand out prominently. The uterine cavity is occupied by a large submucous nodule, attached to the lower surface of which is a ragged mivss that projects into the cervix. The lower portion of the uterine cavity and 'a small part of the cervical cjinal are visible.

To the right of the uterus portions of the right tul>e and ovary can be distinguished.

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PROCEEDINGS OF SOCIETIES.

THE JOILNS HOPKLXS HOSPITAL MEDICAL SOCIETY.

Meeting of November 5, 1894.

Dr. Kelly in the Chair.

NOTES ON XKW BOOKS.

BOOKS RECEIVED.