Talk:The Johns Hopkins Medical Journal 6 (1895)
22 cases of laryngeal diphtheria (croup) reco^'ered without operation 21 cases of croup recovered without opcratiou.
Deducting 8 cases in a hopeless condition on admission, there was only one death among the noo-traeheotomized cases, a death rate of only 2 7 per cent.
Of the intubated cases 7 died in les-q than 21 hours after admission. Deducting these, the fatality from Intubation was only 18.1 per cent.
Deducting 15 deaths in less than 24 hours after admission, the total fatality is reduced to 9.7 per cent. These cases are those treated iu the Iinpital Trousseau in Paris from the middle of Sept. to Dec. 25, 1894.
12 laryngeal diphtherias recovered without operation. During period in which the supply of serum failed the general fatality rose to 53.2 per cent, and that of operated cases to 68.9 per cent.
In 14 cases presenting symptoms of moderate laryngeal stenosis upon admission, these symptoms disappeared after injection of antitoxin without operation.
During period when supply of serum failed the ^neral fatality rose to 65.6 per cent. Heim treated altogether 48 cases in two groups, but of his 2d group of 21 cases 13 were still under treatment at date of report and these are not included in mv table.
313 cases of diphtheria treated In the same hospital (Greifswald) from Oct., 1893, to Sept., 1694, gave a fatality of only 14.5 per cent.
In 13 previous series of tracheotomies in each group the
average of deaths numbered SV. The 7 unoperated cases were mild.
During a period of exhaustion of the supply of serum
the general fatality rose to 50 per cent. These data are
from abstracts in the British Med. Jour., Feb. 2. 1895.
and the Deutsche Mod. Wocbenschrift, 1894, No. 5:;.
The general serum fatality is variously given as 187
per cent.. 20.3 per cent, and 22 per cent.
Only one adult in this scries.
Collection of cases treated in private practice by several physicians in Minden.
After intubation (U cases) no death,
after intubation and tracheotomy 1 death,
after tracheotomy 1 death.
10 cases of croup rt'covercd without operation.
The fatality of 42 unoperated cases not treated with
antitoxin was 33.4 per eent., that of 20 tracheotomizcd
cases not so treated was 85 per cent.
3 of the 4 deaths were from croup.
Of Kossel's 44 cases of laryngeal dii^litheria treated with
antitoxin, 31 (47.7 per cent.) recovered without operation ; of
von Widerhofer's 130 stenotic cases treated with serum 22
(16.9 per cent.) recovered without operation ; of von Ranke's
63 cases, 21 (33.3 per cent.); of Vierordt's 24 cases, 9 (37.5
per cent.); of Ganghofner's 56 cases, 12 (21.4 per cent.); of
Bokai's 63 cases, 14 (22.2 per cent.); of d'Espine's 21 cases,
10 (47.6 per cent.). Von Ranke says that before the use of
serum at most 5 per cent, of his cases of laryngeal stenosis
escaped operation, whereas now 33 per cent, escape. Of Ganghofner's stenotic cases formerly 12 per cent, escaped operation, whereas now 21 per cent, escape. The experience of
Heubner and many others is similar.
In this respect, as in so many others, the results in the Paris hospitals have been most favorable. Of Moizard and Perregaux's 145 cases of croup, 90 (63.1 per cent.) recovered without intubation or tracheotomy. Roux, Martin and Chaillou say, " Of 169 children, admitted to the service for diphtheric angina, 56 presented laryngeal symptoms ; 31 had hoarse voice, and in 25 the voice was so far extinguished and the dyspnoea (tirage) so marked that one might believe that the latter patients should be operated on. Under the influence of the serum (and in these cases one should not fear to make an injection every twelve hours), the dyspnoea diminished, then occurred only paroxysmally, the child coughed up false membranes, and at the end of two or three days the respiration became normal, to the great astonishment of the interns and personnel of the pavilion who, with their large experience of children affected with croup, indeed thought that operation could not be avoided. To-day in the presence of a child with dyspnoea it is not necessary to press for operation. One can inject the serum and wait as long as possible. Since the introduction of the serum the number of tracheotomies in the pavilion has diminished."
Out of his large experience Baginsky exjjresses himself in these vigorous words : " Here again the observation of the individual cases of laryngeal stenosis, and more especially of those which do not come to the point of operation, speak to me more forcibly than the statistical figures. The surprising regression of the laryngo-stenotic respiratory phenomena, the freedom of breathing, the disappearance of the hoarse voice and the croupy cough, the euphoria of the children, the change in their general condition so that two days after the injection they are sitting up in bed, playing and contented and observant of their surroundings ; all of these things produce in him who has had before his eyes for years the hopeless picture of continually progressing laryngeal stenosis, in very truth ineffaceable impressions."
Experience based upon such a large number of oases and careful clinical observation must be regarded as representing the norm. That there may be deviations from tliis norm, even in a fair number of eases, seems to be illustrated by the experience of Leichtenstern and Wendelstadt, who in 123 cases of diphtheria, with 37 tracheotomies, were not able to note any material reduction in the proportion of cases requiring tracheotomy as compared with former series of cases. Their observations were uncontrolled by bacteriological diagnoses.
Another point to be considered in this connection is of capital importance as an indication of the value of serum treatment. Cases which are free from symptoms of laryngeal involvement at the time of injection of the serum do not develop such symptoms later, or do so only very exceptionally, unless evidences of such involvement appear within twentyfour hours after the injection.
Regarding neither this nor any other point is there entire unanimity of opinion in the various reports, nor is such to be expected from observers of limited numbers of cases with unequal distribution in the various groups of mild cases, of early cases, of anginas, of croup, of pure diphtheria, of septic diphtheria, etc., to say nothing of the absence in some reports of any bacteriological control of the diagnosis and of treatment by insufficient doses or inferior quality of serum. I am only surprised that the conflicting statements are not more numerous. But there are not many points concerning which there are so few diffei'ences of statement as concerning the efficacy of antitoxin in preventing descent of the diphtheritic process to the larynx and the trachea. Over and again one can read in the reports such statements as that in all of the patients who entered without laryngeal diphtheria, the larynx remained free, or that unless the symptoms of stenosis appeared within the first twenty-four hours after injection of the serum, they were not observed at all or onlr most exceptionally. Among the many vouchers for these statements may be cited Kossel, Roux, Baginsky, von AViderhofer, Heubner, von Ranke, Vierordt, Ganghofner, Escherich, Bokai, Van Nes, Kurth.
It is this power of antitoxin to check the spreiid of the diphtheritic process from the tonsils and pharynx into the larynx, and from the larynx into the bronchi, which has impressed many observers in favor of the new treatment more forcibly than any other feature of their experience with its action. Thus Vierordt observed that of 24 children with diphtheria who were admitted with unaffected larvns and treated with antitoxin, only one developed temporarily a hoarse cough on the third day. In all of the others the larynx remained free. Of 23 patients who were admitted with unaffected larynx not long before the introduction of the serum treatment, nine afterward developed croup. This is doubtless a somewhat unusual experience as regards the large proportion of cases of croup developing under previous methods of treatment.
It follows from what has been said that the ratio of oj>erative cases in antitoxin statistics will in general be smaller than in statistics of Ciises of the same character treated by other methods. On the one hand there will be fewer larvugeal stenoses developing after commencement of the treatment, and on the other hand a larger numlHT of recoveries from laryngeal diphtlieria without the necessity of o|KTation,
The following figures serve to illustrate this jwint. In the service from which the cases report<Hl by Roux were derived. tracheotomy was performed before the serum jwriod in 50 per cent, of the cases of diphtheria, after the introduction of serum in 40 per cent. The later Paris reports give a much greater reduction in the ratio of tracheotomies. In Bjiginsky's service 43.9 per cent, of the cases were o}->erate<l on Wfore the use
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JOHNS HOPKINS HOSPITAL BULLETIN.
[Nos. 52-53.
of serum, and 18.1 per cent, after its introduction ; in von Ranke's service the corresponding figures are 57 per cent, before and 43.5 per cent, after; in Bokai's 65.6 per cent, before and 40.8 per cent, after. As already mentioned, Leichtenstern's figures, 32 per cent, before and 30 per cent, after serum, are exceptional.
It is furthermore to be considered that in view of the power of antitoxin to abate beginning and moderate symptoms of stenosis, operation will be delayed rather than hastened, and, when performed, the indications for it will generally be undent. For manifest reasons, most of the operations will fall within a period not remote from the time of injection of the serum. Of the 121 tracheotomies in the report of lloux, Martin and Chaillou, 102 were performed either before the first injection of antitoxin or within 12 hours afterward; 14 between the 12th and the 36th hour after inception of the serum treatment, and only 5 later than 36 hours after the injection of the serum. Of the 23 tracheotomies with 12 deaths reported by Kossel, the operation was performed within the first twelve hours in all of the fatal cases, and of the 11 successful cases it was performed in 9 on the day of admission to the hospital, in 1 on the second day and in 1 on the following day. Kossel refers the increase in the stenotic symptoms after injection of the serum in the two last cases to the separation of the false membranes, a point to which others have also called attention as an effect of antitoxin and which is to be borne in mind in cases of croup treated by antitoxin.
Turning now to the results of tracheotomy and intubation in cases treated with antitoxin, we find in Table II that in 11 reports there were 648 tracheotomies with 258 deaths, a fatality of 39.8 per cent., and 342 intubations with 99 deaths, a fatality of 28.9 per cent., and 26 intubations followed by tracheotomy with 14 deaths, a fatality of 53.8 per cent. These are not unheard of fatalities from these operations, but they are so low as to indicate decidedly remedial action of antitoxin.
The percentage of fatality from tracheotomy in diphtheria given by Monti from a total of 12,730 cases up to 1887 is 73.3. The percentage given by \^ Ilirsch in 1054 tracheotomies in diphtheria, in von Bergmann's clinic in Berlin during the last ten years and seven months (up to July 31, 1894), is 68.7, the fatality during the first four years of this period being 70.5 per cent, and during the last four years 03.8 per cent. The fatality during the first year of life was 98.8 per cent. and sank for each year to the ninth, when it was 41.7, and after the tenth year it rose again.
More proper, however, than comparison with these latter percentages is comparison with the percentages of fatality in the same hospital or place from which the respective groups of cases are reported. It will be observed that with one exception in the table the percentage of deaths following operation in cases treated by antitoxin is lower, and generally very much lower, than the previous or simultaneous fatality. Kraske's exceptional series is of so few cases (only 5 with and 12 without serum) as to be without any significance. The lowest fatality thus far reported in a series is 3 deaths in 31 truchcolouiii'.s with serum treatment, or a fatality of only 9.67
per cent. This is reported by Schroeder from the hospital in Altona.
If for each group of cases we estimate the number of deaths which would have occurred in the tracheotomized cases treated with serum on the assumption that the previous or simultaneous fatality in cases not treated with serum had obtained, we obtain the following result : The actual percentage of deaths in 510 tracheotomized cases treated with serum was 42.5. The percentage of fatality in these cases estimated on the basis of previous or simultaneous fatality in the same hospitals would be 64.5. There was therefore an apparent reduction in-fatality by the serum treatment of 34.1 per cent. This difference between actual and estimated fatality is greater than is observed in any ordinary experience of variations in fatality during a series of years in the same hospital from tracheotomy in diphtheria.
I confess to some surprise that the analysis of the tracheotomized cases treated by serum should have yielded results so strikingly favorable to antitoxin treatment. When one considers that the benefits of serum treatment are most strikingly apparent when the treatment is begun early in the disease and become more and more doubtful after the third day, it would not have been a convincing argument against the treatment if these benefits were not conspicuously manifest in cases of diphtheria requiring tracheotomy, for, as has been explained, the great majority of these tracheotomized cases are already the subject of advanced laryngeal stenosis when the antitoxin is first injected. There are, however, not a few cases which begin apparently as laryngeal diphtheria {croup d'emblee), or ill which the involvement of the larynx occurs within twentyfour or forty-eight hours after the onset of the attack. That careful observation would reveal in many of these apparently primary or early laryngeal diphtherias a latent or slightly manifested diphtheric angina I believe to be true.
It is interesting to note that in several reports the benefit of serum treatment has been much more evident in the operated cases than in those not operated on, although this is not the rule. Indeed Leichtenstern and Wendelstadt find in their series of 123 cases that the difference in favor of the serum in tlifir non-operated cases was so small as to be without significance, whereas there was a difference in favor of the serum of 20.8 per cent, in their tracheotomized cases with and without serum treatment. They attribute, therefore, the entire benefit of the serum in their experience to its action in tracheotomized cases. Their experience, however, is exceptional, although in a measure approached by that of Ganghofuer and of Van Nes. On the other hand, in Vierordt's experience the entire benefit of antitoxin seemed to be in the non-operated cases. As has been repeatedly explained, such diversities of experience with limited numbers of cases is to be expected, and the norm can be established only by observations of large numbers of cases in different places and at different times. This norm is that both operated and not o]>erated cases are benefited by antitoxin, and that the difference in each class between serum fatality and fatality from other methods of treatment is a large one.
The fatality of intubated cases in 'J'able II, treated with antitoxin, is 28.9 per cent., which is 10.9 per cent, less than the
July-August, 1895.]
JOHNS HOPKINS HOSPITAL BULLETIN.
113
fatality of traclieotomized cases. Before the introduction of the serum treatment a collective investigation was set ou foot by the German Gesellschaft fiir Kiuderheilkuude to determine tJie average fatality following intubation. In 1893 von Kanke reported to the Society that 1445 cases of diphtheria with laryngeal stenosis treated by intubation gave a fatality of 63.5 per cent. This i-esnlt was interpreted in favor of intubation as opposed to tracheotomy. There is a difference of .33.6 per cent, between this percentage and that obtained from our 342 intubated cases treated with antitoxin. This difference is so great that, after making all possible allowance for differences in the series of cases entering into the two groups of statistics, it seems impossible to explain it otherwise than as a powerful additional support of the arguments already presented in support of the claims of antitoxin. Here certainly the objection that the cases treated by antitoxin were light ones cannot be made.
Table II enables us to compare the fatality of 250 intubated cases treated with antitoxin with the fatality estimated ou the assumption that the previous or simultaneous fatality from intubation in the same hospital had obtained in the several groups. By this calculation we find the actual fatality to be 31.6 per cent., and the estimated fatality 62.4 per cent. In other woi'ds, thei'e was an apparent reduction in the fatality of intubated cases of 49.5 per cent, as the result of the serum treatment.
However distrustful one may be of statistical evidence in therapeutics — and previous experience justifies much distrust — I fail to see on what credible assumption this striking reduction of fatality can be explained otherwise than as demonstrative of the specific curative power of antitoxin in diphtheria.
Lamentable for the victims but adapted to convince the skeptical were the experiences of Baginsky and Ganghofner during the periods of failure in the supply of serum. During the euforced two months' interruption of the serum treatment (August and iSeptember) in Baginsky's service there were 116 cases of laryngo-steuosis with a fatality of 62.2 per cent., as opposed to a fatality of 37.8 per cent, in the serum periods which preceded and followed the pause. The percentage of operations rose to 55.2 as opposed to 18.1 per cent, during the periods of serum treatment, and this without any change in the general character of the cases admitted. During the serum periods there were more intubations than tracheotomies, whereas during the pause there were 45 tracheotomies and 19 intubations, 13 of the latter requiring secondary tracheotomy. In (ianghofner's service the fatality of the operated cases rose from 13.6 per cent, to 68.9 per cent, during the interruption in the supply of serum.
'i'here remain two points to be touched upon before dismissing the laryngeal stenoses. These are the substitution of intubation for tracheotomy in a larger and larger proportion of the laryngeal diphtherias reipiiring operative interference and treated by the serum, and the shortening of the period during which the tube or the tracheal canula is required to be kept in the air passage.
An agent which would arrest the progressive descent of the diphtheritic process from the larynx into the bronchi and
hasten the disappearance of the obstructive exudate is just what was needed to make intubation the ideal operation for the relief of the great majority of cases of croup requiring operative interference. Such an agent we now possess in antitoxin for a large group of cases, and we arc not surprised, therefore, to find that the employment of intubation, as a substitute for tracheotomy, has been greatly extended by the introduction of serum therapy.
Several writers give figures showing that serum therapy materially hastens the time when extubation or removal of the tracheal canula is permissible, but I have not attempted to collect these figures.
Of the 3127 not operated cases, including as already stated many cases of croup, 350 died, giving a fatality of 11.2 per cent. In V. Hirsch's statistics of diphtheria from von Bergmann's clinic for ten years the average fatality of not operated cases (1004j was 26 per cent, varying only from 25.9 per cent. during the first four years of the period to 27.3 per cent, during the last four years. There is, however, no general standard of fatality for cases of diphtheria not operated on. The variations are within very wide limits, as might be expected. Only a comparatively small number of the reports give separately the previous or simultaneous fatality of non-operated cases not treated with serum. I find in the reports the following data ou this point. In Roux, Martin and Chaillou's report the previous fatality of non-operated cases averaged 83.9 per cent., the minimum being 32.1 per cent., and the maximum 47.3 per cent., as opposed to 12.8 per cent, under the serum treatment; in Baginsky's report the corresponding figures are 31.6 per cent, versus 10.9 per cent.; in Bokai's 34.5 per cent. versus 14 per cent.; iu Ganghofner's 15.8 per cent, (the lowest in a series of years) versus 12 per cent.; in ^'au Nes 33 per cent., the average of ten years, with a minimum of 16 per cent, and a maximum of 41 per cent, versus 13.3 per cent; in Leichtenstern and Wendelstadt's 15 per cent, versus 10.4 per cent.
Age is a factor of such prime importance iu the prognosis of diphtheria that I have prepared the following UMe (Table 111), in which the cases treated with serum collected from twenty-five reports are classified according to age. Unfortunately there is very little uniformity of system iu the different reports in giving the results according to the ages of the patients, many of the reports simply stating the number of adults or the maximum age of the children or the uumber of cases under a certain age or the uumber between arbitrarily selected limits of age, etc., so that many of the reports were not used for the following bible. In each space iu the table the upper number is the total uumber of the cases iK'lougiug to the heading, aud the lower uumber is the uuuil)er of deaths among these cases.
The most frequently quoted percentages of fatality in diphtheria according to the ;ige are those of Herz, aud are as follows :
Under 1 year SO per cent.
1-3 years 45 "
3-5 " 40 "
5-10 " IT "
Over 10 years 17
As the cases in the preceding table were not classified according to the ages bj a uniform plan in the different reports they
cannot all be summarized in a single table, but the chief results can be presented as follows:
14 Reports.
Total.
0-3 yrs.
3-4 yrs.
4-6 yrs.
C-8yrs.
8-10 yrs.
10-12 yrs.
13-15 yrs.
' ' ndetermined.
Cases
Deaths
Percentages
1234
215 17.4
187
60
33.1
337
70
31.4
297 176
48 19
16.3 10.8
114
8
i
0.63
32
5
1.6
21
4.1
(H)
(0)
(0)
In the following table the cases under 4 years are from 20 reports containing 1630 cases (fatality 17.0^) and those over 4 are from 17 reports containing 1451 cases (fatality 17.4^).
Cases
Deaths
Porcentag:es
0-2 years.
Over 15 years.
The following table gives the results for each year up to
5 and over 5 years.
18 Reports.
Total.
Under 1 year.
1-2 years.
3-3 years.
3-4 years.
4-5 years.
Over 5 years.
Undetermined.
Cases
Deaths
Percentages
983
179
18.3
34
10
47.1
112
37
33
118
36
30.6
116
17
14.7
140
31
23.1
452
42
9.3
1 (10)
(0)
(0)
The table furthermore shows under one year 35 eases with 16 deaths or ib.1% ; under 2 years 291 cases with 97 deatlis, or 33.3^ ; under 3 years 304 cases with 93 deaths or 30.6^, and under 4 years 692 cases with 122 deaths or 17.6^ {each of these four groups of cases being from a total number of cases in the first group of lOSO cases, in the second group of 1914 cases, in the third group of 1140 cases and in the fourth group of 1S65 ea»e», the average fatality for the whole number of cases being 17.3^.)
The percentages of fatality in V. Hirsch's statistics of 2658 cases from the surgical clinic in Berlin for 10 years and 7 months (ending July 31, 1894), according to age are:
Under 1 year 88.3 per cent.
1-2 years .". 82.5 "
3-4 " 63.9 "
4-5 " 56.0 "
5-6 " 46.9 "
6-7 " ; 43.7 "
7-8 " 36.1 "
8-9 " 28.1 "
9-10 " : 31.1 "
10-11 " 31.3 «
11-12" 20.9 "
12-13 " 18.5 "
13-14 " 16.7 "
14-15 " 15.
15-16 " 13.5 "
Adults (72 cases) 11.1 '■
Baginsky gives the following percentages from his service in the Kaiser- und Kaiserin-Friedrich Childreir s Hospital in Berlin as the mean of the four years 1890 to 1893 inclusive:
Under 3 years 60.2 percent.
2-4 years 51.3 "
4-6 " 38.
6-8 " 28.9 "
S-10 " 24.5 «
10-12 " 38.8 "
12-14 " 18.5 "
Baginsky's results in Table III may be compared with this last list of percentages, otherwise I do not consider that these
statistics of Herz, Ilirsch and Baginsky furnish any certain standard of comparison for the percentages of fatality derived from Table III. I have cited them, however, in the absence of any such standard to show in a general way that these latter percentages indicate a low fatality according to age. The contrast between a fatality percentage of 33.3 for ca^es of diphtheria under two years of age treated with serum, and that of 60 to over 80 for cases of the same age not so treated is a striking one, even if a large allowance be made for differences in the characters of the cases in the two groups.
We come now to the consideration of the influence upon the fatality of the length of the interval between the onset of diphtheria and the first injection of antitoxin. In experiments upon animals this factor is decisive in determining the resultIt is the factor which Behring from the first has put in the foreground. His claim is that no death will occur from diphtheria if antitoxin is injected in suflicient dose at the beginning of the disease, and that the fatality will fall under 5 per cent, if the treatment in proper manner is begun before the third day of the disease.
Of course the only significance of this great emphasis upon the importance of early treatment is as an expression of the fact that cure is rendered more ditticult the larger the number of the diphtlieria bacilli, the greater the amount and intensity of their toxins, the greater the damage already inflicted by the bacilli and their toxins, and the more serious the complications and secondary infections. There is. however, no absolute parity between the length of time the disease h:»s lasted before beginning treatment and the increase of these d.ingers. One ease may become desperate within forty-eight hours after the onset, and another may present no grave symptoms after a week's duration. The virulence, tli.> nmnli.r and the
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JOHNS HOPKINS HOSPITAL BULLETIN.
[Nos. 52-53.
microbic associations of the infecting bacilli, and especially the local and general susceptibilities of the patient, are factors no less important than the single factor of time in inlhiencing the issue.
The individual peculiarities of each case must be considered. If all is judged according to one simple uniform standard — antitoxin cures the case or it does not cure the case — and it must be confessed this is all which seems to be in the minds of many, then the practitioner will not come to any clear conception of the wonderful powers of the healing serum. The sins of some observers in this matter seem incredible. They lump together indiscriminately all of their cases, including those complicated with measles, scarlet fever, tuberculosis and other diseases, the mixed infections, the anginas, the croups, the advanced and the early cases, the true and the false diphtherias, the infants and the adults, and throw tlien\ into the scale to be weighed for or against antitoxin. An unsuccessful case is put down to the discredit of antitoxin without reference to its peculiarities. On the basis of experience in treating a dozen cases, the writer boldly attacks results established by the careful observation of hundreds of cases. It is true we need these brute figures for comparison with former fatality statistics of diphtheria, and they have served to demonstrate the curative efficacy of antitoxin, but reports of personal experience with the serum treatment should at least contain the data for an intelligent analysis' of the cases treated. Such an analysis is requisite in order to reveal the full scope and capabilities of the new treatment. We have ali-eady seen that the study of the cases with reference to laryngeal involvement has brought to light evidence in favor of the serum treatment more convincing than that derived from the gross statistics of all cases treated, and evidence of a kind which meets many of the objections which have been urged against the interpretation of the gross statistics as demonstrative of the efficacy of antitoxin. We shall now see that the analysis of the cases according to the day of the disease on which the serum treatment is begun almost, if not completely, substantiates Behring's original claims, astounding as they seemed to be.
There is, of course, in many cases considerable uncertainty as to the exact duration of the disease at the time when the patient is first seen by the physician. The statements of parents or of those in charge of the children are often the only evidence on this point which can be obtained. Satisfactory information will be particularly difficult to obtain in the class of patients in the diphtheria wards of hospitals, these patients being chiefly the children of laborers. We are also to consider that a diphtheric affection of the throat may exist without such manifest disturbance as to attract even intelligent observation, or it may be mistaken for a simple sore throat. A tabulation of cases of diphtheria according to the day of beginning treatment will be, therefore, only of relative value, but we cau fairly assume that the duration of the disease will very rarely, if ever, be shorter, but often longer, than that stated.
In the excellent reports on antitoxin treatment from the Paris hospitals, the cases are not analyzed according to the day of beginning treatment, as Koux, whose scheme of classili
cation has been followed by most other French writers, stated
in his original article that it was practically impossible to
obtain trustworthy statements on this point from parents of
the children. Most of the reports, therefore, which enter into
Table IV are from German and English sources.
The statements as to the day of the disease are entirely from information obtained from parents and others, and are not estimates on the part of the physician, although in several instances the reporter says that the condition of the patient plainly indicated a longer duration of the disease than that assigned by the parents and put down in the report. It will be observed that not all of the reports in the table fit into any one system of classification, and therefore not all can be summarized in a single table. In each space the higher number is the total number of cases belonging to the heading, and the lower is the corresponding number of deaths.
As is well known, the fatality from diphtheria by any approved method of treatment is smaller the earlier in the disease the treatment is begun. This is clearly shown in the following table from the statistics of Y. Ilirsch of the cases treated in the surgical clinic in Berlin for ten years preceding August, 1894, and of course before the employment of antitoxin. The results are according to the day of the disease on which treatment was begun.
First Day.
Secoiid Day.
Third Day.
Fourth Day.
Cases, . . .
Deaths, . . .
Percentages, .
241
44
18.3
405
92
22.7
333
124
38.1
416
223
53.6
Fifth Day.
Sixth Day.
Seventh
Day.
Eighth Day.
Cases, . . .
Deaths, . . .
Percentages, .
203
136
67
525
219
67.4
- 506
367
72.5
239
191
81.6
The preceding table is not intended to serve as a standard of comparison for my tables giving the results of cases treated by antitoxin, as the classes of cases in the two groups are not comparable.
Philip* has reported from Baginsky's service the results of treatment, before the use of antitoxin, begun in the earliest stages of diphtheria, the patients being brothers and sisters of children with diphtheria who were examined for Loffier bacilli, 80 that opportunity was given for recognition of the disease at its onset. The fatality was 10.5 per cent, lower in these cases recognized and treated early than in the others. The fatality of the cases treated by Baginsky with serum during the first three days of the disease was 32.2 per cent, lower than the preceding average fatality of cases not treated with serum. Plainly some more potent healing factor than merely that of early treatment was present. The only difference in the methods of treatment of the two groups of cases was the use of antitoxin in the one and its absence in the other.
•Philip: Arch. t. Kinderheilk., Bd. XVI.
July-August, 1895.]
JOHNS HOPKINS HOSPITAL BULLETIN.
117
TABLE IV.
FATALITY ACCORDING TO THE DAY OF DISEASE UPON WHICH ANTITOXIN IS INJECTED.
(la each space the higher number is the total number of cases treated on the corresponding day, and the lower number is that of the deaths.)
REPORTER.
Total number
of Cases
Treated.
1st
Day.
2nd 3rd
Day. Day.
4th
Day.
5th
Day.
6th
Day.
After
6th
Day.
Undetermined.
REMARKS.
Koseel
117
13 (11.1 per ct.)
14
30 1
29
9 1
11
2
6
3
12
5
6
1
Fatality for first three days was 1 4 per cent.
KOrte
121
40 (33-1 per ct.)
Of 37 severe and moderately severe cases injected
during the first three days 8 died (21.6 per cent). The
results following injection begun after the third day
were less favorable.
Baginsky
625
83 (15.-6 per ct.)
111
3
134
14
92
13
62
12
39
14
13
4
29
12
55
11
All of the three fatal cases of the tirst day were far
advanced on admission, therefore the statements of
the parents as to the date of beginning of the disease
were probably erroneous (liaginsky). Fatality for
fii^st three days was 8.9 per cent. •
V. Mering
74
4 (5 per ct.)
Treatment begun on 1st or 2nd day in nearly all cases.
V. Noorden
81
19 (23 per ct.)
Treatment begun on the 3rd or later day in nearly all
cases.
Schroeder
63
8 (12.7 per ct.)
1st & 2nd Day.
23
1
3rd & 4th Day.
27 3
After 4th Day.
13
4
Vierordt
65
8 (14.6 per ct.)
3
14
2
17
2
9
7 1114 3 1 1 1
Kumpf
26
2 (8 per ct.)
18
1
3
1
After 3rd Day.
5
i cases were still under treatment at date of the report.
Ganghofner
110
14 (12.7 per ct.)
3
30
2
35
3
18
i
9
3
2
13
2
Heim
27
6 (22 per ct.)
9
2
1
7
1
3
1
1
5 3
BOrger
30
2 (6.6 per ct.)
3
13
9
3 1
1
1
1
Hager
25
1 (4 per ct.)
14
1
5
4
1
1
Private practice. The single fatal case died of complications after cessation of the diphtheria.
Kuntzen
25
3 (12 per ct.)
3
6
7
1
2
2
1 1
1
Schmidt
14
3 (21.4 per ct.)
The three fatal cases were not treated until after the
disease had lasted for 8 to 14 days. Private practice.
Seitz
35
2 (5.7 per ct.)
10
12
9
After 4th Day.
The two deaths were in infants lH years and 13 months old with advanced laryngeal diphtheria on day of admission, presumably therefore treated after 2nd or 3rd day, although this is not stated.
Hall
11
3(27.3 per ct.)
2
4
4 2
1
1
Epidemic in Trieste
Hospital cases
105
27 (25.7 per ct.)
6
30 6
29
9
20
5
11
4
7
3
2
1
Epidemic in Trieste
Cases in private prartice
72
5 (6.9 per ct.)
14
27 2
18
1
8
2
2
1
11 2
Witthauer
36
5 (14 per ct.)
4
8 2
4
1
6
3
Blumenfeld
50
2 (4 per ct.)
1st & 2nd Day.
40
3rd & 4th Day
8
1
2
1
3
Of the 2 fatal cases, in one the treatment began on the
4th and in the other on the 5th day. Private practice.
Uapmund
100
7 (7 per ct.)
39 1 34
15 1 5
3
1
The deaths are given for the 1st and 2nd, the 3rd and
«h and the 5th, 6th and after 6th day respectively.
2
3
2
Scbaewen
15
6
3
1
Ot the 5 undetermined cases the statement is that they had been ill several days before the injection.
Kisel
114
9 (7.9 per ct.)
78
4
21
4
4
4 5 1
- 89 of these cases were treat«d at their homes, and S in
1 1 hospital. They were mostly children.
V. Muralt
58
2 (3.4 per ct.)
11
18
17
After 3rd Day | 1
12 1 1
Uodd and Whitehouse
11
4(36.4 per ct.)
1
2
5 2
1
1
1
Winkfleld
22
4(18.2 per ct.)
8
2
7
1
4
1
1
m the 2 fatal cases in which it i? -; .n •■ ■ was made on the 2nd day, in one tbire >• sion advanced larynuial and nasal cV: glandular swellings, and in the othi i branes in the throat, nasal discharge . swellings.
Howard
40
3(7.5 per ot.)
24
2
1 "
Private practice.
Van Nes
62
12 (23 per ct.)
a
1
13
1
10
1
'■
7
No details given of fatal >
day of the disease, but it
tlo'n of the day was vti;.
patients ichildren of lal>. i . ,
Kurth
97
10 (10.3 per ot.)
12
36 2
16
1
19
3
5
1
a
1
Ot thc2fat.ll cases in which it >
began on the ind day. one was
and died 18 hours afterward: tlv
after disappearance ot the loc-.-ii .iiptitinria wnn
albuminuria and broncho-pncunionia.
The following table is the sumvMrt/ of the 19 reports of the preceding table in ichieh the nwnber of <A« eatts vHh th^ rettUl* corrttpondimg to rA« disease on loJiich antitoxin treatment toas begun is gicenfor each day up to and after the 6th day.
19 Reports.
Total. Isi Day.
2nd Day.
8rd Day.
4th Day. 6th Day.
168 116 32 84 19 29.3
6th Day. "^'rtatTf" | Cndctermlned.
Cases
Deaths
Percentages
1489 x'^
212 1 5
14.2 2.2
45ii
. m
S.l
311
42
13.5
44 101 («»
IS » OS)
34.1 3S.: (1T.8I
118
JOHNS HOPKINS HOSPITAL BULLETIN.
[Nos. 42-53.
Including teith the preceding 19 reports those of Schroeder, Bliimenfeld and liapmund, we hare the following table tohich gives the results of antitorin treatment begun on the \tt and '2nd, on the Zrd and ith, and after the ith day.
22 Reports.
Total.
1st and 2n(l Day.
3rd and 4th Day.
After 4th Day.
Undetermined.
Cases
Deaths
Percentages
1702
229
13.5
814
45
5.5
534
81
15.2
286
91
31.8
(681
(12)
(17.6)
It may alio be computtd from the table that of 1729 cases of diphtheria teith a fatality of 14. 9;^, 1115 cases treated with antitoxin during the first three days of the disease yielded a fatality of 8.5^, whereas 54G cases in which antilonn was first injected after ilie third day of the disease yielded a fatality of 27.8%. 0/232 cases in which treatment was begun on the first day 5 (2.15^) died; of 492 cases in which treatment was begun on the second day, 38 (7.7;i) died; o/331 eases in which treatment was begun on the third day, 43 (13^) died.
Kohts, an opponeut of the serum, treatment, at the recent Congress for Internal Medicine in Munich, claims for his method of local treatment no deaths among cases treated on the first day of the disease. For later days his results are much higher than those in the serum statistics. The percentages of deaths according to the day of beginning his treatment, as given by Kohts, without a statement of the number of cases treated, are as follows: 1st day, 0; 2nd day, 20 per cent.; 3rd day, 47 per cent.; 4th day, 55 per cent.
Table IV shows that out of 233 cases in which it is alleged that antitoxin was injected on the first day of the disease, 5 died. As a matter of fact, however, the assumed duration of the disease in each of these fatal cases is doubtful, as it rests solely on the statements of parents or those who cared for the children, and is aj)parently contradicted in at least the three cases concerning which any details are given by the condition of the patient on admission. Baginsky's three cases (\os. 311, 479 and 511 of his tables) when admitted were far advanced in the disease, with extensive membranous exudates, cyanosis and very bad general condition. Hager's case may more readily be accepted, as it occurred in private practice, but here the patient died after disappearance of the diphtheria from complications, whether or not referable to the diphtheria is not stated.
Of the fifth fatal case reported by Van Nes no details are given in such form that the case can be identified from^his description, but he himself places little reliance upon the alleged duration of the disease in the class of patients admitted to the hospital, these being the children of laborers.
I am not aware of the report of any fatal case of diphtheria properly treated Vjy antitoxin within the first 24 hours after the beginning of the disease, in which the duration was positively determined, still as I have not read every article which has been published on the subject it is possible that such a case may have been reported. There are, however, many such cases of prompt recovery reportecl as that quoted from Hall in Table IV.
It is noteworthy that the percentage of deaths in SN cases in which treatment was begun before the third day of the disease is only 5.5. If the doubtful deaths attributed to the first day be excluded, the percentage actually falls a trifle short of 5. If we furthermore make allowance for the fact that the assigned duration of the disease can scarcely be shorter, but may readily be longer than the actual duration, then our tabulation of 1702 cases of diphtheria according to the day of beginning treatment verifies Behring's original pre
diction. I do not, however, consider that it is justifiable from
so small a number of cases and from material of the kind
composing our table to draw any definite conclusions as to the
exact percentages of deaths according to the date of beginning
treatment.
According to the table the percentage of deaths in cases in which the serum treatment is begun on the 3rd and 4th days of the disease is nearly three times greater than that in cases treated on the 1st and 2nd day, and the percentage after the 3rd day is 3} times greater than that of cases treated~within the first three days.
We are of course not to infer from these results that antitoxin may not be beneficial when administered after the 3rd or 4th day of the disease. There are cases which are still mild after this duration, but which subsequently become serious, and even in desperate cases antitoxin holds out some hope of cure.
It is apparent that the largest proportion of cures by antitoxin are to be expected from private practice among those who call the physician in at an early stage of the disease. While a similar statement may be made concerning any other suitable method of treatment, it is not, I believe, true in the same measure as for the serum treatment.
The main purpose of this article has been the study of the evidence thus far published concerning the curative power of antitoxin in diphtheria. I do not propose to consider the practical points relating to the employment of antitoxin, nor to consider in detail the specific effects of injection of the healing serum. There has been much diversity of opinion as to these effects, and I shall present briefly the principal points which seem to me to be established.
Most writers approve of the continuance of such measures of local and general treatment as have hitherto been found to be useful, but recommend the avoidance of all irritating and caustic local applications.
The injection of the serum may be followed in a few hours by local pain, swelling and redness, but there is no danger of abscess formation if the serum is uncontaminated and proper antiseptic precautions are taken. In over 3000 injections Martin observed the formation of an abscess only three times.
In twenty-four to forty-eight hours after the injection the general condition of the patient is remarkably improved in the great majority of those patients who are in a condition to be benefited at all by antitoxin. This general improvement is accompanied by a fall of temperature, which may be a critical fall, especially if the disease is not far advanced;
July-August, 1895.]
JOHNS HOPKINS HOSPITAL BULLETIN.
119
ofteu it is a fall by lysis. hJoiiie hold that there may be a temporary rise of temperature as an immediate effect of the injection. Accompanying the fall of temperature is improvement of the pulse as to frecjueucy and tension, but the heart's action may for some time, even into the period of convalescence, remain weak.
In the favorable cases the local diphtheritic process is arrested, ixsually within the first twenty-four hours after the injection. Membrane may appear upon spots previously inflamed and invaded by the bacilli, but otherwise there is no extension of the membrane in the majority of the cases which are benefited. The area covered by membrane becomes sharply demarcated and the swelling of adjacent mucous membrane disappears. The membrane may disappear by rapid separation or by gradual softening. Sometimes it persists for several days after disappearance of all other local disturbance. Large membranous casts are coughed up from the larynx, trachea and bronchi under the serum treatment more frequently than under former methods. The rapid separation of the membrane in the lower air passages may cause sudden increase of stenotic symptoms. Nasal discharge is lessened. The swelling of the glands in the neck and the surrounding CEdema disappear, so far as these are not referable to secondary infections.
The most uncertainty prevails as to the influence of antitoxin in preventing the three most important complications or sequelte of diphtheria, nephritis, heart failure and paralysis. The weight of evidence is that genuine nephritis is far less common in cases treated by antitoxin sufficiently early than under other methods of treatment, but it is questionable whether albuminuria is less common, although it is considered to be by Kossel, Roux and others. If there is an albuminuria in any way directly referable to the injection of the serum, and this is by no means established, it is simple albuminuria with perhaps a few narrow hyaline casts but without evidence of any serious damage to the kidney. Peptonuria, it is claimed by Hecker, is an effect of the serum, but it is without clinical significance. Albuminuria is such an extremely common symptom of diphtheria that it must be very difficult to determine that it can be referred to the serum in any case.
Many writers emphasize especially the favorable influence of antitoxin upon the heart, but there are some who have observed that with decided improvement in all other symptoms the force of the heart may still remain weak and occasion anxiety. Baginsky's experience is that the minor disturbances of the cardiac action are not less frequent in cases treated with serum, they appear to be even more fre([uent as a larger number of cases survive, but that actual death from heart failure is far less common in the serum cases than in others.
I'ost-diphtheric paralyses may occur in cases treated with serum as early as the second or third day of the disease. Whether they occur in cases treated within the first twentyfour hours is not certain. According to some, paralysis is even more common in the serum cases than under former methods of treatment. This is doubtful, but if true, it may be attributed to the survival of a larger proportion of cases.
It is apparent from what has been said that antitoxin is most strikingly beneficial in progressive fibrinous diphtheria and especially in the prevention and cure of laryngeal diphtheria. In septic diphtheria the serum treatment is of little avail.
Antitoxic serum may produce unpleasant effects, but these do not involve danger to the patient. They are in all probability referable to the serum as such and not to the healing, so-called antitoxic, substance contained in the serum. The most common undesired effect is some form of exanthem, usually erythema and urticaria, sometimes an eruption like measles or scarlatinal rash. The same exanthems have been observed by Bertin after the injection of ordinary serum of the horse, and by Richardiere after injection of Marmorek's anti-streptococcus serum.
The serum from some horses is more likely to cause these exanthems than that from others, and there may beindividnal idiosyncrasies favoring their occurrence. Some writers report the occurrence of an exanthem in not more than five per cent, of their cases, others have observed them in over fifty per cent, of the cases treated with serum. They may be localized in the neighborhood of the seat of injection or extend from that over the greater part of the body, or make their first appearance at a distance from the point of injection. Often without noticeable fever they may be accompanied by considerable elevation of temperature and by pain and swelling in the joints. A rarer but more severe form of serum exanthem resembles erythema multiforme, and when this is accompanied, as it may be, by high fever, and severe pain in the bones and joints with swelling of the joints, the condition of the patient may really seem serious, but these patients recover. Some have attributed a petechial eruption to injection of the serum, but this may occur in diphtheria without serum treatment.
These occasional untoward effects of the healing serum are annoying, but, being unattended with danger to life and without serious consequences, they do not contraindicate the use of the serum.
There have been a few cases reported in which the writers, without any satisfactory evidence whatever, have referred the death of the patient to the use of the serum. The essential harmlessness of the serum has been demonstrated by over a hundred thousand injections,* and if future investigations should show that through some idiosyncrasy on the part of the patient death ever is attributable to the injection of the serum, this would probably count for about as much as the rare deaths from the use of ether or chloroform.
I shall leave untouched the question of the immuuiiing properties of antitoxin.
The principal conclusion which I would draw from this paper is that our study of the results of the treatment of over 7000 cases of diphtheria by antitoxin demonstrates beyond all reason:!-' .'"'i" that anti-diphtheric serum is a sj>ecific ciira
- Tlus v\ I'll 1.1 ^^.■^■m to be at least a moilerate estimate, as writing
November 20, 1S94, Beliring says that there had been t>p to that (late certainly over 40,000 injections (Das neue Diphtheriemittel, von Dr. Behrinp, Berlin, 1S94, p. 25).
120
JOHNS HOPKINS HOSPITAL BULLETIN.
[Nos. 52-53.
tive agent for diphtheria, surpassing in its eflBcacy all other known methods of treatment for this disease. It is the duty of the physician to use it.
The later reports show in general a decided improvement in the results of the treatment over the earlier ones, and there is every reason to believe that the results of the second year's employment of the new treatment will make a much more favorable showing than those of the first year. We shall come to a clearer understanding of the mode of action of the healing serum. Improvements in the methods of preparation and preservation of the serum, and possibly the separation of the healing substance, at least from other ingredients which produce the undesired effects, may be expected.
The discovery of the healing serum is entirely the result of laboratory work. It is an outcome of the studies of immunity. In no sense was the discovery an accidental one. Every step leading to it can be traced, and every step was taken with a definite purpose and to solve a definite problem.
These studies and the resulting discoveries mark an epoch in the history of medicine. It should be forcibly brought home to those whose philozoic sentiments outweigh sentiments of true philanthropy, that these discoveries which have led to the saving of untold thousands of human lives have been gained by the sacrifice of the lives of thousands of animals, and by no possibility could have been made without experimentation upon animals.
A MORE RADICAL METHOD OF PERFORMING HYSTERECTOMY FOR CANCER
OF THE UTERUS.
By J. G. Clark, M. D., Resident Gynecologist.
The onset of carcinoma of the uterus is so insidious, and its early stage gives rise to so few disagreeable subjective symptoms, that finally, when the patient is forced by repeated hemorrhages, which usually first alarm her, to consult a ghysician, the disease has passed beyond the possibility of a radical operation for its cure.
The route of upward extension is almost invariably by the broad ligaments; and on account of the close attachment of the lower portion of the ligament to the cervix, the progress is rapid through the intraligamentary lymphatics, and if not checked in the early stage is soon beyond the limits of any operation.
The downward growth on the vaginal walls and the metastasis from this point is often so very extensive that it also cannot be removed by the usual methods.
A casual review of the literature of the operative treatment of carcinoma is sufficient to convince one of the inadequacy of any method of treatment; but as the operative method is the only one which offers any chance of cure or benefit at present, it should be emploj'ed in all cases where the disease has not passed beyond the palliative effect of hysterectomy.
If the broad ligaments are densely infiltrated and the cervix deeply excavated, any form of radical operation is out of the question, as there is no possibility of even alleviating the symptoms.
If on the other hand the cervix is extensively ulcerated and the broad ligaments only slightly involved, the prognosis is favorable at least for the euthanasic effect of hysterectomy, and in a certain proportion of cases the disease can be removed completely even by the ordinary methods of hysterectomy.
During the last six months the clinical courses of three inoperable cases admitted to the gynecological wards of the .Johns Hopkins Ilosjjital have been closely followed, and in reviewing the histories of these cases in conjunction with the autopsy notes, we are more than ever convinced that any measure which offers the slightest prospect of mitigating the
agonizing pain and relieving the symptoms caused by pressure of the growth upon the rectum and ureters should urgently be advised.
Death in cases which are not operated upon is usually caused by obstruction of the ureters (uremia), i)eritonitis, or toxaemia from septic absorption.
The involvement of the ureters is usually late, but many weeks before this complication arises the sacral plexus may be pressed upon in one or both sides of the pelvis by the cai'cinomatous masses wedged into the inferior strait, and the patient suffer the most agonizing sacral and sciatic pain.
One of the three cases just referred to was of this type. The patient was admitted to the hospital six months before her death, and throughout the remaining days of her life was not free from pain a single hour, even under the influence of large doses of morphine.
The autopsy revealed a dense board-like infiltration of the broad ligaments which extended out to the jielvic wall, involving the sacral plexus at its points of egress from the sacrum. In this case had the uterus and broad ligaments been totally extirpated, e.veu six months before the patient was admitted, the i)rogress of the disease would jirobably not have been arrested, but she would have been sjiared the frightful agony of the last six months of her life by the relief of the pressure on the nerves. The left ureter in this case was completely blocked, and in addition to the pressure pains which she suffered there was present a partial uraimic toxaemia for three months before death which caused constant -nausea and considerable vomiting.
The second patient, a nuilado woman, was admitted three mouths before death with a deep crater-like excavation of the cervix and dense induration of the broad ligaments. She suffered intense pain, which was only j>artial]y controlled by morphine, and at last died of peritonitis from perforation of the lateral wall of the uterus into the peritoneal cavity. Iler abdomen became intensely tynipauitic, and for five days before death her temjierature ran as high as 105° to 107° F.
July-August, 1895.]
JOHNS HOPKINS HOSPITAL BULLETIN.
121
In the third case death resulted from urtemiu, both ureters being blocked, and in addition there was a ])yelone])hrosis and ureteritis on one side. For 73 hours before death there was total suppression of urine. In these cases we have exemplified the three usual terminations of carcinoma which are not subjected to operation: (1) asthcmia and uraemia from toxic absorption ; (3) peritonitis from perforation of the uterus, and (3) ura3mia, and pyelouephrosis from septic infection. These three cases also give us a vivid composite picture of the frightful suffering which these unfortunate women experienced.
The offensive discharge from the necrotic tissue is another excessively disagreeable symptom which invariably appears as soon as the ulcerative process is well under way, and can only be stopped by a complete removal of the carcinomatous tissue. This is of itself a justifiable indication for operation, as the discharge is always checked for some time, and frequently does not reapj>ear even though the disease continues to extend.
It is Dr. Kelly's rule to advise hysterectomy in all cases which have not passed beyond the limit of the palliative effect of the operation, even though there is no jiossibility of a cure, simply for the relief of the inevitable sym])toms which must arise if the uterus is not removed.
For the radical cure of cancer of the uterus the same surgical rule obtains as in cancer of other regions, viz. total extirpation of the primary focus and as extensive areas of adjacent tissue as possible to insure the complete eradication of the disease.
It cannot be gainsaid that it is better to have a local recurrence and ultimate death from metastasis following the removal of the uterus, with a decided amelioration of the usual distressing symptoms, than to have these symptoms increasing in their severity until death without operation.
The faults common to all methods of removing the uterus are (1) the broad ligaments are cut too close to the uterus, and (2) too small portions of the vagina are removed. (Fig. III.)
In at least 95 per cent, of cases where there is upward extension of the disease it is through the lymjjhatics of the broad ligaments. The local recurrence which we so often see on the margins of the vaginal incision also demonstrates very clearly the fact that usually too little of the vagina is removed.
In carcinoma of the fundus the extension is invariably through the broad ligaments, and any operation which removes a considerable portion of these structures offers the greatest hope of a permanent cure.
The usual methods of performing hysterectomy have been extremely unsatisfactory to every gynecologist, for the reason that only a small jiortion of the broad ligaments is removed and the remainder usually conceals nests of e])ithelial cells which fall outside the limit of the knife. The same may be said of the vagina. The results of the pathological examination of the uteri removed by hysterectomy in the Johns Hopkins Hospital not only definitely sustain this clinical observation, but also point strongly to the necessity of a more radical method than yet projiosed.
Of the last 30 cases, the specimens have been submitted to a most careful pathological examination, which has shown
that in 15 cases the carcinomatous process had passed beyond the limit of operation ; in one case the result was doubtful, and in only four cases could it be definitely said that all of the disease had been comj)letely removed.*
No stronger argument than this can be advanced for a more radical operation.
In at least five instances where the extension had occurred along either one or both broad ligaments, the carcinoma could not have passed more than a few millimeters beyond the limit of operation, as the epithelial cells were very sparse and were only barely perceptible in the margins of the incision.
In other cases there was no involvement of the broad ligament, but too little of the vaginal wall had been excised.
In comjjaring Fig. Ill of a uterus removed by vaginal hysterectomy and Fig. IV of the specimen from Case II which was removed by the method which I shall describe, it will be seen that none of the broad ligament or the vaginal wall is removed with the former, while with the latter there is a large portion of the broad ligaments and a considerable cuff of vagina.
The great danger of cutting or ligating the ureters in the past (Fig. 11) has prevented a wide excision of the broad ligaments, but now that Dr. Kelly has entirely removed this danger by introducing bougies into the ureters in all operations where they may be involved, we can turn our attention with greater conlidence to the more extensive extirpation of the tissues adjacent to the uterus.
The value of this procedure has been freiiueutly demonstrated in Dr. Kelly's clinic, and if generally adopted will no doubt save many lives which are lost from cutting or tying the ureters.
After laying a plan before Dr. Kelly for the more complete extirpation of the uterus, the broad ligaments and a portion of the vagina, and receiving his cordial endorsement and encouragement, I was granted the opportunity in April, 1S95, to put into effect the principles embodied in the proposed operation. There are three essential steps in this operation which differ from those now employed: 1st, the introduction of the bougies; 3d, the ligation of the upper portions of the broad ligaments, including the round ligaments and ovarian arteries, cutting them close to the jielvic walls, opening the two layers and dissecting the uterine artery out to its origin and ligating before excising any tissue, and 3d, the excision of a much larger jiortion of the vagina than usual.
•In a forthcoming article by Dr. IJussell upon the clinical course of cases subsequent to hysterectomy for carcinoma in the Johns Hopkins Hospital, it will appear that there is a greater percentage of permanent cures than the pathological examination of these 20 cases would seem to indicate. From the openinf: of the hospital in 1SS9 to August ISiM, 4S hysterectomies were performed ; of this number 41 were vaginal, 4 abdominal and 3 combined vaginal and abdominal. The results of these operations are as follows : 5 died from the primary effect of the oi>eration, 17 died subsequently from extension of the disease, t> have not been heard from, and 20 <ir are living and 3 dead, there are 4S per cent of these cases still living, certainly a very gratifying result, as it has now been nearly a year since the last of this series of cases was operated upon.
122
JOHNS HOPKINS HOSPITAL BULLETIN.
[Nos. 53-53.
By carefully ligating the artery in this way, and introducing the bougies, we eliminate the dangers of iieniorrhage and of injury to the ureters, and are enabled to extirpate the uterus, its broad ligaments, and the upper portion of the' vagina en masse.
The value of excising the carcinomatous tissue in one }iiece is dwelt upon with much stress by Dr. Ilalsted in the description of his operation for cancer of the breast, by means of which he has reduced the ratio of local recurrence from 50 to 20 per cent.* The same rule must hold good here.
He says " the suspected tissue should be removed in one l>iece: (1) lest the wound become infected by the division of tissue invaded by the disease or of lymphatic vessels containing cancer cells, and (2) because shreds or pieces of cancerous tissue might readily be overlooked in a ])iecemeal extirpation."
The j)rincipal reason for the careful dissection and exposure of the uterine artery is that one can tie it well out in its course and then, by making traction on the uterus towards the opposite side from which we are cutting, the broad ligament can be cut away close to its pelvic attachment. Figs. I and IV.
If one attempts to ligate the artery in the tissues any distance from the uterus without first dissecting it out, there is great danger of including carcinomatous tissue within the ligature and thus defeating the object of the operation.
Another reason for first ligating the artery as far ou't as possible is that there is no possibility of removing any more tissue after the broad ligament is once divided, as that portion attached to the pelvic wall at once retracts, carrying with it the artery and any carcinomatous tissue which may lie beyond the ligatures. This is the essential principle in the o])eration which is now proposed, and if followed will unquestionably give better results than where the broad ligament is ligated with one or two ligatures en masse and cut away close to the uterus.
While the introduction of the bougies is highly essential to this operation, it can be performed, but with much less facility, by following the course inirsued on one side in Case I.
The bougie was not introduced in the right ureter for reasons stated further on, and when the enucleation was begun it was found necessary to dissect out the ureter in its course and draw it to one side with a loose traction ligature, after which the operation was completed with as much ease as on the side where the bougie was introduced.
This necessarily requires more time, and consequently it shoiild be the invariable rule to lay bougies in both ureters, as the operation must be done with the most painstaking care if it is to be of any more value than the methods now pursued.
The details of the operation will be given in the description of the cases, and in the remarks following dase I defective points in the Icrhniqtie are noted which are corrected in Case II.
Case I. — Mrs. .L I'., mulatto, aged -18 year.s, adinilird A|iril 24, 180.5.
•The Johns Hopkins Ho.s|iital Reports, Vol. IV, No. (1.
Complainl — Hemorrhage from uterus and offensive vaginal discharge.
Marital Ilistorii — Married 25 years ; 12 children ; no miscarriages. All labors normal except the last in November, 1894; child still-born. Menses began when she was 14 years of age ; flow always regular and painless, lasting one and a half days. Since the birth of her la.-^t child she has had almost constant hemorrhage.
Leworr/(/B« for many years ; up to six months ago the disclnirge was odorless, but at that time became very ])rofuse and offensive.
Fam ill/ Histo rij — Negati ve.
Personal History — Patient has always been a very healthy woman.
Present Ailtnent — In August, 181)4, when patient was about six months ])regnant, the leucorrhffial discharge above noted became very offensive and irritating, and she began to grow weak and lose flesh. November 16th, 1895, she gave birth to a still-born child, and about one month later had a copious hemorrhage from the vagina, which has continued more or less up to the time of her admission to the hospital. She has at no time suffered the slightest pain, and barring the weakness and general debility, which is more apparent to her friends than herself, feels very well. Urination normal, bowels costive, no pain during defecation. Patient is auEEmic and has lost considerable flesh. Appetite poor, sleeps moderately well.
Examination — Abdominal walls lax and flabby, numerous liuea albicantes. Vaginal outlet much relaxed; beginning on the vaginal wall 2* cm. from the cervix there is a fungatiug mass which almost fills the vagina and completely involves the cervix. The broad ligaments are slightly involved close to the uterus. The fundus uteri is slightly enlarged and freely movable. Api)eiidages normal.
Diagnosis — Cancer of upper portion of vagina and cervix.
Operation, April 2G, 1895 — Urethra anaesthetized with cocaine, and ureteral bougie inserted into the left ureter through a No. 8 vesical speculum. The patient being very nervous, and as the right broad ligament seemed quite free, it was deemed best to proceed at once with the general anaesthetic, only a slight attempt having been made to lay a bougie in this side, which was not successful. An incision 15 cm. in length in the median line exposed the pelvic organs, which were found as described in the examination. The bougie in the left ureter could be felt as a solid cord running up along the side of the cervix and then curving gently outward in company with the iliac vessels and up over the brim of the pelvis. At the base of the broad ligament it lay at least IJ to 2 em. outside of the indurated area, and could easily be disjjlaced 1 cm. further out towards the pelvic wall, thus throwing it entirely out of the carcinomatous process.
'i'he operation was begun by tying the upper portion of the Itft broad ligament, including the ovarian artery, as closely Ik the pelvic wall as possible, clanqiing the uterine side and cutting between.
I laving divided the round and the upj)er portion of the broad lii^aiuents, and se]»arated the two layers of the latter, the vesical peritoneum was sni]i])ed with (he scissors, following the crease where it is reflected onto the uterus, around the anterior
July-August, 1895.]
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face of the uterus to the opposite broad ligament. By spreading the layers of the broad ligament apart, with a stalk sponge tlie uterine artery was exposed in the intraligameutary cellular tissue, it appearing somewhat tortuous, aud near the uterus imbedded in carcinomatous tissue. A careful dissection was now begun, au assistant in the meantime making strong traction with a small vulsellum forceps caught in the fundus, thus enlarging the normal space between (he uterus and pelvic wall and making the artery taut.
The artery was bared for 2i cm. from the uterus, the dissection being carried well down towards the internal iliac artery, which could be seen pulsating close to the point of ligation. A small blunt-pointed curved aneurism needle proved of great service in carrying the ligature. As the vessel ■walls seemed somewhat atheromatous, a second ligatui-e was placed for double security. This step in the operation was rather difficult on account of the close proximity to the large vessels, which were in danger of injury. During this dissection the ureter was constantly under touch, thus eliminating all possibility of injuring it.
The ureter was next dissected out of its bed and ])ushed toward the pelvic wall ; aud the broad ligament and the intraligamentary tissue ligated on the pelvic side close to the internal iliac vessels, with imbricated ligatures, each including 1 cm. of tissue.
Having reached the vaginal vault, the dissection was carried down along the lateral aud anterior vaginal walls with the fingers, by means of which the walls were pushed away from their attachments. There had not been the slightest loss of blood up to this point.
The upper portion of the opposite broad ligament was now ligated on the pelvic side aud clamped on the uterine side and cut. The two layers were then separated with a stalk sponge, the uterine artery dissected out aud doubly ligated. At this point careful palpation showed the broad ligament to be more extensively involved than the preliminary examination had indicated, and in order to remove as much as possible it became necessary to know the exact position of the ureter lest it inadvertently be ligated or cut.
With the other ureter as a comparative landmark, this ureter was easily located in the broad ligament and dissected out. A loose traction ligature was then thrown around it, and while the dissection was being carried down back of (he vaginal Avails, was drawn out of the way by an assistant. The broad ligament was ligated close to the pelvic wall as on the op])osite side and cut. At this point it became evident that the carcinomatous process had not only penetraled (he pos(erior vaginal wall, but had involved I lie anterior reetal wall to a considerable extent.
On account of the close relation of the recial and vaginal walls which were bound (ogedier by (he inllamnuitory process, an assistant was direc(ed to insert his index-finger into (be rectum while a\i attempt was made to separate the two walls. This could not be acconii)lished satisfactorily. The rectouterine rellection of jieritoneuni had been previously snipped aiul pushed oif in the same manner as the vesico-uterine rellection. ]5y making strong u]iward traction on the uterus, the vagina was also drawn mnvard and made t|uito tense. By
light percussion, a procedure suggested by Dr. Kelly to be emi^loyed in all cases of hysterectomy for accurately distinguishing the cervico-vaginal juncture, the point for amputation can be located accurately. An opening was made in the anterior vaginal wall with the sharp-pointed scissors, aud from this ])oint the vagina wa^ encircled by an incision made with Dr. Kelly's special hysterectomy spud, which proved of great value here in cutting so deep in the pelvis. Unfortunately a small area of carcinomatous tissue on the rectum could not be removed. With this exception the enucleation seemed to be very thorough. Considerable bleeding from the vaginal walls, which required several ligatures to control it, followed the amputation of the vagina. Before completing the operation another attempt was made to clear the rectal wall of the carcinomatous tissue by a careful dissection, but proved impossible. One or two large strips of iodoformized gauze were packed down into the space occupied by the cervix aud upper portion of the vagina, after w^hich the pelvic cavity was closed by whipping together the recto-uterine and vesicouterine reflections of peritoneum by a continuous suture, beginning at the stump of oue ovarian artery and running aci'oss to the opposite stump, thus effectually closing off the peritoneal cavity, which was then irrigated with 1 litre of normal salt solution (Fig. Y). The abdominal wound was closed with buried silver wire and subcutaneous catgut.
The vaginal gauze was removed in five days. Patient discharged in 24 days. Examination at (his time as follows: Vaginal vault smooth and vaulted, small line of cleavage felt where the vaginal walls haA'e united. No sign of local recurrence of the disease.
The pathological examination had by this time been made l)y Dr. Gullen, who confirmed the clinical observation that all of the carcinoma had not been removed, consequently the j)atient was requesled to return in one month for examination. June 20 — Patient examined to-day, and on the anterior rectal wall there is a minute area which is unquestionably carcinonuiious. The patient is perfectly comfortable, has gained five pounds, the hemorrhages have not appe;ired and she believes she is jierfectly well. The pelvis appears to be free, and by rectum there is no trace of induration on either side.
Jieinarks. — AVliile the dissection of the ureter in which no bougie was introduced was satisfac(orily aoconii)lisheil, it was much slower (liau on the opposite side, and in contrast much more diflicult. The bleeding from the vaginal walls following the excision of the uterus should be obviated by first jierforating with sharp scissors the vagina ;uitoriorly well below the carcinomatous area and then ligatiug the vaginal wall in snuvU segments and cutting, thus controlling all hemorrhage as the operation proceeds (vid. Case II).
With the exce]>(ion of the one point on the rectum which could not be removed, the operation was very Siitisfaclory. As far as (he ((uestion of complete cure is concerned, unfortunately for the patient this is quite as serious as though a much larger area was left.
Case 11. — Jlrs. E. Y., In-rman housewife, agetl 57 years. admitted dune 4th, IS'.'o.
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[Nos. 52-53.
Gomphint — Excessive loss of blood from uterus.
Maritul Hhlorij — Married twice, one child and one miscarriage during first marriage, labors easy and not followed by any untoward symptoms. JIarried 23 years to second husband, during which time she has borne three children and had ten miscarriages. Nothing out of the normal course of events occurred in any of the labors, and no pain or discomfort followed the miscarriages. She was attended in all of her confinements by a German midwife. Menopause occurred in her 47th year, up to that time menses ill ways regular and normal since they first appeared in her I'.Uli year.
Fain ily History — Xegati ve.
Persomil Histori/ — Patient has always been very strong and healthy since childhood.
Present Ailment — One year ago she began to have a slight leucorrha?al discharge, which continued for six months, when it became blood-tinged ; since then it has grown more profuse and hemorrhagic until the present, when it is almost pure blood.
About Eiister, 1895, she had a severe hemorrhage, losing about one pint of blood.
General Condition — Slight an;eniia, no cachexia, very slight pain in lower part of pelvis, no loss of flesh. Appetite good, bowels regular, no urinary complaint. Heart and lungs normal.
Examination — Vaginal outlet relaxed, faint scar tissue in posterior vaginal wall. Projecting into vagina from cervix there is a fungating mass 2.5x5 cm., which is very fi-ialile and bleeds freely during the examination.
The cancerous process seems to be circumscribed and extends only slightly onto the vaginal walls. Fundus uteri small, senile, freely movable, not involved by the carcinoma. Broad ligaments very slightly involved. Ovaries not detected, probably senile.
Diagnosis — Cancer of cervix.
Operation, JuneCi, 1895 — Urethra anaesthetized with cocaine and patient ))laced in knee-breast posture. After an inffectual search for the ureteral orifices it was considered best to place the patient in the elevated dorsal posture, when t,liey were quickly located and bougies inserted into both.
Especial care was observed in this case as in the preceding to disinfect thoroughly the vagina. The broad ligaments were tied oflf and the dissection of the artery niade in the same way as in the preceding operation.
After freeing the vaginal walls for 2* cm. below the cervix, the vagina was i)erf orated anteriorly, but instead of at once completing the am])utation, a small segment of the vaginal wall was ligated and cut and then another, and so on around the entire circumference, so that by the time the uterus with the upper portion of the vagina had been removed all bleeditig was checked.
The oi)eratioii was coni)ileted by j)acking gauze into the ui)])er part of the vagiiui and closing tlie j)eriloneum over this, nuiking the seat of ojieration entirely extra-jieritoneal. This o]ieralioM rei|uired two hours for its coni])]elioii, the dissection
of the xiterine arteries requiring more time than any other step. It was practically bloodless and there was no variation in the patient's pulse from the beginning to the end.
The subsequent notes on the case are as follows :
June 1th — Patient recovered from ether by the time she reached the ward; at that time her pulse was 92, full and strong. She has passed a comfortable night. Temperature 99 J° r. ; pulse 100 this morning.
JuJie dth — Bowels moved thoroughly from the effects of fractional doses of calomel and an enema. Feels well ; no tenderness or distension in abdomen.
Jrine MUh —Cxiiuze pack removed from vagina; no odor; slightly blood-stained.
June ISth — Temperature normal ; abdominal wound inspected; subcutaneous catgut absorbed, union perfect, line of incision represented by only a faint hair-line.
July 5/A— Patient discharged, feeling perfectly well. Highest temperature on fourth day 100° F. ; pulse 112. The vaginal vault is entirely closed in, is perfectly smooth and dome-like. The line of union between its walls is represented by a small, almost imperceptible cicatrix. No induration in the lateral pelvic walls. Prognosis as to radical cure good.
August MUh — Patient returns to-day by appointment ; again examined and same condition found as just noted.
In conclusion, the steps of this operation may be summarized as follows :
1. Insert bougies under the local effects of cocaine, thus saving time and conserving the patient's vital powers for the operation.
2. Make abdominal incision of suflicient length to insure free manual movements.
3. Ligate upper portion of broad ligament with ovarian artery; divide vesico-uteriue peritoneum around to opposite side; push bladder off, and spread layers of ligament apart, exposing uterine artery.
4. Dissert uterine artery out for 3j cm. from uterus beyond its vaginal branch and tic.
5. Dissect ureter free in the base of the broad ligament.
(5. Ligate remainder of broad ligament close to iliac vessels and cut it away from its pelvic attachment.
7. Carry dissection well down below carcinomatous area, even though cervix alone seems to be involved.
8. Proceed on the oj)posite side in the same manner as on the first side.
9. Perforate vagina with sharp-j)ointed scissors, making strong traction on uterus with small vulsellum forceps so as to pull the vagina up and make its walls tense, then ligate in small segments (1 cm.), and cut each segment as it is tied.
10. Insert iodoformized gauze from .above into raw space left by the hysterectomy; draw vesical and rectal j)erituneum over this with a continuous fine silk suture.
11. Irrigate i)elvic cavity and close abdomen without drainage.
July 15, 18!)5.
FIG. I.
In this plate the pc-ritoncum of one side of the pelvis is dissected oflf. showing the intimate anatomical relation of the bladder.
uterus, uterine artery and ureter. Bougies are inserted into the ureters making them stand out as rigid tubes. The close relations
of uterine artery and ureter and the ureter and cervical portion of uterus are well demonstrated, showing the imp<.ssibilitv of a wide
e.xcision of the broad ligaments without the introduction of the bougies into the ureters.
NOTES ON NKW BOOKS.
PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.
THE JOHNS HOPKINS HOSPITAL REPORTS.
BULLETIN
OF
THE JOHNS HOPKINS HOSPITAL.
Vol. Vl.-Nos. 54-55.
BALTIMORE, SEPTEMBER-OCTOBER, 1895.
+++
Contents
A Case of Anthrax Septicsemia in a Human Being associated
with Acute. Anthrax Endocarditis and Peritonitis. By
George Blumer, M.D., 127
A Study of Subcutaneous Fibroid Nodules. By T. B. FutCHER, M. B., 133
Cases of Amoebic Dysentery. By Cunningham Wilson, M. D., 142
Proceedings of Societies :
The Hospital Medical Society,
143
Hyperpyrexia in Typhoid Fever [Dr. Oslek] ; — Abscess of the Liver, perforating the Lung [Dr Osleb]; — Pyarthrosis [Dr. Finney]; — Specimen of Stomacli removed after Francke's Operation for Gastrostomy [Dr. Finney] ; — Schede's Operation for Varicose Veins of the Leg [Dr. Finney].
Notes on New Books,
146
Books Received, .--- 146
A CASE OF ANTHRAX SEPTICEMIA IN A HUMAN BEING ASSOCIATED WITH ACUTE ANTHRAX ENDOCARDITIS AND PERITONITIS.
By George Blumer, M. D., Assistant in Pathology, and Hugh II. Young, M. D. (From the Pathological Laboratory of the Johns Hopkins University and Hospital.)
k
The following case of the (Edematous form of aiitlirax seems worthy of being recorded, on account of the rarity of this form of the disease iu this country, and also because of certain other interesting features of the case, namely, acute peritonitis and endocarditis due to the bacillus anthracis. The case has already been briefly referred to by Dr. Flexuer in the Johns Hopkins Hospital Bulletin for May-June, 1895.
C. B., aged 59, a native of Germany, and a laborer in a hair factory, came to the Johns Hopkins Hospital Dispensary on Saturday, May 11, 1895, complaining of the swelling of the lids of the riglit eye. His history was as follows :
Family History. Ilis father and one brother died of some lung trouble, the exact nature of which he does not know: one brother died of cancer of the liver. The family history is otherwise negative.
Past History. He had the usual exanthems as a child. Denies venereal history, and gives no history of secondary lues. Drinks one glass of beer daily. Does not use tobacco. Had typhoid as a young man, but since that time has always been strong and healthy. He has worked in a luiir factory for thirteen years.
Present History. Two days ago, while working with South American hair, he scratched his right eye with his hand, as it was itching. The next morning he noticed that the eyelids were slightly swollen, and itchy, and by this morning they were so swollen that he came to the dispensary.
At the time of the visit the swelling was confined to the lids of the right eye, and was fairly sharply localized: it was (Edematous in character, and quite boggy, the overlying skin appearing almost of a natural color. Two small incisions were made, one into each lid. and a small quantity of rather thin, whitish fluid, resembling diluted milk, was evacuated. Cultures upon agar-agar were made at this time, and two days later the tube inoculated showed a pure growth of an organism which resembled the bacillus .anthracis. aud which upon inoculation killed a mouse iu "24 hours. Further to5tfi proved it to be the anthrax bacillus.
The patient Avas admitted to the hospital on May 13, four days from the onset of the disease. The physician who attended him at his home, from Saturday until his admission on Monday, stated that his temperature had been subnormal during the entire period. On admission the patient com
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[Nos. 54-55.
plained of nothing but slight pain beneath the right side of the jaw ; otherwise he felt perfectly comfortable. He had no headache or malaise. His mind was perfectly clear. The following note was made at this time:
Patient is in bed on his back. Temperature F. 102°. Pulse 133 per minute, regular, volume fair, tension not increased. Kespirations 16 per minute, easy. Tongue has a slight white coat. The mucous membranes are of a fair color, not cyanosed.
Both eyes are closed by oedema. On the left side the swelling is not nearly so marked as on the right, the lids being distended by a modei-ately lirm, watery cedema.
The lids of the right eye are much swollen, hard, and tense, and the overlying skin is occupied by several vesicles, varying in size from a pea to a bean, and filled with clear, yellowish serum.
The eyes themselves appear uniuvolved.
Over the whole of the right side of the face and neck, and extending ujo onto the scalp, is a marked cedema of varying consistency; immediately around the right eye it is very hard, and covered by tense shiny skin; over the forehead, neck and remainder of the face, as well as over the implicated scalp, it is much less firm and can be easily pitted by pressure.
The oedema extends across to the left side of the forehead, and occupies the neck as low down as the clavicle. On the inside of the mouth, the right cheek is mai'ked with the imprints of the teeth, and has a yellow -gray sloughy appearance.
The thorax is rather barrel-shaped, but expands well and equally.
The lungs are hyper-resonant throughout on percussion; on auscultation the breath-sounds are clear, but expiration is 1 prolonged.
The point of maximum cardiac impulse is neither visible nor palpable. The heart-sounds are best heard in the fifth intercostal space 3 cm. within the mammillary line. The souuds are rather distant, but apparently clear. Tile area of relative cardiac dullness is almost obliterated by lung tympany.
The border of the liver is indistinctly felt just below the costal margin.
The spleen cannot be palpated.
The abdomen is natural in a])pearance, but is universally tender to the touch.
The shins are clean. There is no oedema.
The glands on the right side of the neck are moderately enlarged, and tender. Their consistency cannot well be made out, on account of the overlying oedema.
The glands elsewhere are not enlarged.
May 14, 10 a. m. The patient is much worse this morning. He has had several involuntary passages of urine and fu'ces during the night. The mind is quite clear, and he an.swers questions rationally. He complains a good deal of cramp-like pains in the abdomen. The pains are situated in the umbilical region, and are sharp and constant, with occasional acute exacerbations, during which he has a desire to defecate. The abdomen is extremely sensitive to pressure this morning. The spleen cannot be palpated. The pulse at
the wrist is almost imperceptible and practically uncountable.
The heart-sounds are extremely distant and feeble.
The temperature has been subnormal since 4 a. m. this morning and is now F. 97°.
The right eye is somewhat more swollen than it was yesterday, and the oedema now occupies the whole of the scalp, and has spread down the right side of the chest to the level of the pectoral fold; it also occupies all the tissues overlying the upper part of the sternum.
The patient gradually sank, and died quietly at 4 p. m. on the 14th.
Before death the adema had spread further over the left cheek, and had also extended somewhat further down the chest. The patient became very cyanotic before death. There was no respiratory distress at-any time. His mind was perfectly clear to within fifteen minutes of his death.
On the morning of the 24th he had three loose watery stools, of a grayish color, and apparently containing no blood.
The urine was passed involuntarily and could not be examined.
Autops)', May 15th, 18 hours after death, the body in the meanwhile having been preserved on ice. Body 174 cm. long, moderately well nourished, strongly built. Rigor mortis in both extremities. The right eyelids are redematous, closing the eye ; they are congested and glazed, and the epidermis is peeling off. The whole right side of the face, below the eye, is oedematous, and the oedema extends over the head and neck. The left eye and left side of the face are less swollen. The oedema is well marked anteriorly over the neck and clavicles, and can be followed well down on the chest. On incising the skin, above the clavicles, much clear serum-like fluid escapes. The oedema extends beyond the median line to the left, and is immediately evident after incision, extending to the sternum. Subcutaueous fat is moderate in amount.
Peritoneum. The peritoneal cavity contains turbid fluid; at least 2000 cc. of such fluid is present in the cavity. The serosa is- injected, its reflection lost, the vessels very hyperaemic. Smaller and larger ecchymoses are seen beneath the serous membrane. In the smaller omentum, in the region of the pancreas, a large ecchymosis is seen.
In several situations along the small intestine the serosa is very hyperaemic, or even hemorrhagic, over areas as large as a silver (juarter, and at these places the walls of the intestine are bulged outwards. The tissues about the kidneys and pancreas are translucent in appearance and very (edematous.
Mediastinum. On removing the sternum the mediastinal tissues are swollen, cedematous, and contain gas bubbles. The cedema of the mediastinal tissues can be traced downwards from the neck, passing in with the cellular tissue below the clavicle. Large gas bubbles or spaces occupy this tissue.
Lungi^. Both lungs lie free in the pleural cavities. They are both em])hyseniatous, particularly in the upper lobes, and along the anterior borders, which almost meet in the middle line of the body, anteriorly.
The heart is nearly covered by lung.
On incision the two lungs present similar ajipearances. They mx> cedematous and very hyperasmic, the cedema and
September-October, 1895.]
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129
hyperajinia being particularly noticeable in tlie lower lobes. There is no actual consolidation.
Pericardium and heart. On incising the pericardium there is an escape of gas. No excess of fluid in the pericardial cavity. Both layers smooth and pale.
The heart is not enlarged; its cavities appear normal. The valves show no chronic change; the auriculo- ventricular orifices not perceptibly abnormal. Along the free edge of the mitral valve, and less along the aortic segment, are several small elevations, appearing to be quite recent vegetations, covered by small red clots. The aorta is quite smooth. The heart's flesh fi'iable and pale.
Liver. The capsule is free from adhesions. Surface smooth. On section, dark in color, quite cloudy ; consistency perhaps diminished.
Spleen. Free from adhesions ; well up under the costal margin ; moderately large ; only moderately soft ; red in color ; pulp abundant.
Kidneys. Both alike. Capsule strips off easily. The organs are swollen, the surface almost uniformly congested, the congestion being still evident on section. Stria? are coarse. Glomeruli visible and red. Ureters noi-mal.
Adrenals and pancreas appear normal.
Stomach. In the pyloric region there is in the mucous membrane a lai'ge, deeply congested area, measuring 8x6 cm. in extent. It is not clear that there is a false membrane over it, but some grayish-yellow material adheres to the surface.
Intestines. The duodenum is congested uniformly. Beginning in the jejunum, which is less congested, there occur at intervals small, elevated, deeply congested, or hemorrhagic foci. These are quite circumscribed, although the mucous membrane about them is congested. They average 2 mm. in width and project I mm. above the surface of the intestine ; they do not seem to correspond with the lymphatic follicles. The serosa over them is often the deeply congested, bulgedout portion already described ; this is, however, not exclusively the case. These foci are quite numerous in the jejunum, at least 15 being present in this part of the gut alone. At times, two or three were close together, though, as a rule, they were more separated. In the ileum they were also seen, in this situation perhaps a little more separated, but in all as many were present as in the jejunum. In connection with one of these areas in the ileum, what appeared to be a false membrane occurred. If a membrane, it was thin, and easily scraped away. Several of the nodules showed superficial ulceration. There was uo relation detected to the lymphatic apparatus, and the nodes were less numerous near the ileo-cajcal valve. The large intestine shows no such localized foci, only a diffuse congestion.
Mesiyit eric glands were swollen, congested, hemorrhagic, and softened.
Brain and cord not examined.
Bladder contained a small amount of turbid urine: the mucous membrane appears uornuil.
BaCTERIOLOGICA L E KAMI X ATION.
Cultures were made, at the time of the first visit to the dispensary, from the incision made into the upper lid. Cover
slips and cultures were made during life, from the serous
fluid from one of the vesicles over the right eye, and also
from the blood.
The cover-slips from both the vesicle and the blood showed large bacilli, occurring usually in chains, and morphologically resembling the bacillus anthracis.
The cultures taken on the first visit, and also those from the vesicles and _ blood, all showed large numbers of graywhite colonies.
Transplantations were made from these colonies, upon agaragar, gelatine, bouillon, potato, and litmus milk, the resulting growths resembling in every particular the growth of bacillus anthracis ; and cover-slips showing large bacilli similar to those obtained from the vesicle and blood.
A mouse inoculated subcutaneously with an oese of the original culture died 34 hours later with local oedema and swollen spleen, and the organism was found in abundance in its heart's blood and other organs. At the time of the autopsy coverslips were made from the peritoneal fluid, hearfs blood, cedematous fluid in the neck, spleen, kidneys and lungs. Typical anthrax bacilli were present in all these preparations, in the peritoneal fluid associated with pus cells.
Cultures from the heart's blood, spleen, peritoneum, liver, kidney and lung, all showed a pure culture of the bacillus anthracis.
Cover-slips and cultures from the urine were negative. At the time of the autoi)sy three mice were inoculated subcutiineously :
1. With one oese of blood from the heart.
2. With 2 oeses of urine (the surface of the bladder having first been sterilized).
3. With a small piece of tissue scraped from one of the intestinal nodules.
All three animals died within a short time of one another, about 24 hours later. Autopsies showed local cedema and swelling of the spleen, and cover-slips from the site of inoculation, and from the spleen, showed typical anthrax bacilli.
Histological Examixatiox.
Sections were made from the heart valve (including one of the fresh vegetations), from the lung, liver, kidney, spleen. stomach and intestine.
Heart valve. The valve itself appears to be normal, with the exception of an adherent triangular mass attached to one surface of it. This mass represents one of the small fresh vegetations. It is attached by its base, its apex lying free, the principal points of attachment being at the two angles. At its point of attachment the vegetation consists almost entirely of fibrin ; the body of the mass contains, beside fibrin, granular material, red blood corpuscles, many polynnelear leucocytes, and a few cells of an epithelioid type. The jwlynuclears and epithelioid cells are not equally distributed throughout the mass, but in certain places form closely packed aggregations of cells.
The valve itself appears to be free from anthrax bacilli, these being limited to the vegetation. Here they are extremely numerous, much more so than in the blood, and are distributed throughout the mass, being jH?rhaps a little more
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numerous in the cellular masses described above than elsewhere. The bacilli occur at times singly, but are generally in groups or long chains.
Lung. The lungs show a moderate degree of chronic interstitial pneumonia, with compensatory emphysema, and some congestion.
The anthrax bacilli are more numerous here than in any other organ ; they occur in the blood-vessels of the alveolar walls in large numbers. Xone are to be seen in the alveoli themselves.
Liver. The liver shows some thickening of the capsule and a well marked interlobular cirrhosis. In places there is a marked increase in bile pigment in the cells. A few localized areas of extensive fatty degeneration, with fragmentation of nuclei are seen scattered through the organ.
The bacilli are not very numerous in the liver ; when seen, they are in small groups between the cells, evidently in the blood-vessels.
Kidney. The surface of the kidney is covered by a slight exudate very similar to that obtained from the peritoneum. It consists mainly of red blood cells, but a few poly- and mononuclear elements are also present.
The organ shows here and there thinning and adhesion of the capsule with localized conuective tissue formation. A few fibroid glomeruli are seen. The kidney cells are well pi^served, as a rule, but in places, especially in the convoluted tubules, are swollen and granular.
The anthrax bacilli are present in moderate numbers; a few are seen in the exudate on the surface, and they are scattered throughout the organ, being most numerous in the glomerular vessels.
Spleen. The chief change in the spleen seems to lie in the accumulation of blood within its tissues ; the amount of blood is very large, and is evidently largely responsible for the swelling of the organ. The number of polynuclear leucocytes in the organ is very evidently increased.
The bacilli are found throughout the organ, most abundantly in the Malpighiau corpuscles; they appear to lie in the blood spaces.
Stomach. The changes here are rather sharply localized in the area situated in the pylorus, the gross appearance of which has been described. There is some slight necrosis of the outer layers of the mucosa all through the section, and a much more marked necrosis in the region of the local lesion.
The lesion consists in a sharply localized infiltration of the mucosa with anthrax bacilli. The bacilli forming this mass evidently originally came by means of the blood current, as deep in the mucosa two blood-vessels are seen, both of which show distinct breaks of continuity, with hemorrhage into the surrounding tissue. The mass of bacteria stretches continuously from these vessels, through the mucosa, to the mucous surface of the stomach, and consists of myriads of closely interwoven bacilli. The mass is not of even width from the surface to the depths, but spreads out widely in two places, one immediately beneath the mucous surface, and the other midway between the surface and the muscularis mucosa, thus forming two spreading masses connected witli each other and
with the ruptured vessels by comparatively thin pedicles of bacteria.
The mucous membrane surrounding this mass is very necrotic, though there is but little reaction, only a few polynuclears being seen about the focus.
Intestines. In the diseased areas, described macroscopically, the intestinal wall is much thickened.
The surface epithelium in these areas is almost entirely destroyed, and in many instances the villi have also disappeared, their bases remaining on the level of the openings of the follicles of Lieberkiihn. The denuded surface thus left is ragged, but is practically free from exudate of any description. The villi which remain show two distinct processes. A certain number of them show a markedly more cellular conuective tissue than normal, the increase in cells being of the lymphoid variety, and perhaps being only apparent, as the tissue is much compressed from the dilatation of the central vessels.
Certain others of the villi show a necrotic appearance, their cellular elements being greatly reduced in number, the nuclei of the cells which remain staining poorly, and the mass of the affected villus having a hyaline appearance and staining sharply with the eosin. This necrotic process on the surface of the intestine is not confined to the mucosa immediately over the diseased foci, but is found on the surface of the intestine elsewhere.
The muscularis mucosa is seen as an indistinct line, the indistinctness being due to its infiltration by cells, most of them polynuclear leucocytes, which spread apart its fibres, and render its distinction from the submucosa difficult.
In jilaces it is pushed up towards the mucous surface, by the much dilated blood-vessels of the submucosa; in places it is pushed down towards the submucosa by the dilated vessels in the mucous coat.
in the submucous coat the most marked changes are seen, these changes being responsible for most of the increase in thickness of the intestinal wall.
The blood-vessels are intensely dilated and full of blood, in which it is easy to see that an excess of polynuclear leucocytes exists. In places there has been actual rupture of the vessel-wall, with extravasation of blood into the surrounding tissues.
Surrounding the blood-vessels, and filling up the entire area between the muscularis mucosoe and the internal muscular coat, is a dense cellular mass, thickest at the centre of the diseased area, and gradually shading off at the periphery into approximately normal tissue. The return to normal is more rapid towards the jieritoneal tium towards the mucous surface.
The mass consists almost exclusively of leucocytes with polyform nuclei, as a rule, densely packed, but, in places, separated by masses of granular or fibrillar fibrin.
Towards the mucous surface of the intestine the cellular infiltration practically stops at the muscularis mucosa, this structure containing only a moderate number of leucocytes, and but a very few being found in the mucosa.
Passing towards the serous surface of the intestine, we find that the polynuclears have passed between the fibres of the
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circular muscular coat, in places spreading these fibres widely apart by their accumulation, and have penetrated into and through the longitudinal coat, appearing in large numbers on the serous surface of the intestine.
The longitudinal coat contains, in places, large numbers of the pus cells.
Here and there, throughout the cellular mass in the submucous coat, are small areas of necrosis with nuclear fragmentation.
The cell infiltration in the submucous coat is, as a rule, diffuse, but in places it appears as small circumscribed nodules. These nodules, under the low power, strongly resemble the normal lymphoid follicles of the intestine, the resemblance being made more striking by their situation in the submucous coat, and pushing up to, though not into the mucous coat. Under the high power, however, they are found to be made up of polynuclear leucocytes.
The nodules then are small, round or oval areas of cells situated about in the normal position of the lymphoid follicles, but having no relation whatever to these follicles, as their structure proves, and being in fact focal inflammatory lesions.
The collections of ganglion cells, both in the submucous coat, and between this coat and the internal muscular layer, are widely separated by the wandering in of polynuclear leucocytes between the cells.
The lymphatic vessels just beneath the muscularis mucosa are in places widely dilated, and crowded with bacilli.
In places on the peritoneal surface is an exudate composed of many red blood cells, a good many polynuclear leucocytes, a few mononuclear leucocytes, and fibrin.
The anthrax bacilli are found in all portions of the intestinal wall, though in greatest number in the submucosa.
The necrotic areas on the surface of the mucosa show very large numbers of bacteria ; in the majority of instances, however, these do not appear to be anthrax bacilli, but a much shorter bacillus, though an occasional long bacillus resembling anthrax is seen.
In places, however, on the necrotic surface, masses of practically nothing else but anthrax bacilli arc seen.
In the deeper parts of the mucosa, both the anthrax and shorter bacilli are seen, the anthrax bacilli being more numerous near the surface.
In the submucosa the bacilli are numerous; they are scattered throughout the inflammatory areas in small groups, and are found in large numbers in certain regions, viz. :
1. In or immediately beneath the muscularis mucosa in the form of a baud of bacilli, closely woven, of about the normal thickness of the muscularis mucosa. Those immediately beneath the muscularis mucosa are evidently at times in the dilated lymphatics described above.
2. Along the borders of the blood-vessels of the submucosa, liaving a similar band-like formation, and being most numerous along the border of the vessel nearest to the mucosa.
3. At the junction of the longitudinal and circular muscular coats, in the form of a loose network.
The bacilli are found scattered through the cinular muscular coat in fair numbers, often in quite large masses between
the muscle fibres, and in these instances in the same areas where the polynuclears are abundant. The longitudinal muscular coat and the peritoneal exudate show a few bacilli,
usually singly or in twos and threes.
Remarks. Clinically the case presents no very striking features. The cedematous form of anthrax is certainly rare in this countrv, but numerous cases have been reported elsewhere. That the infection took the a?dematous form was probably due to its location, most cases of this variety occurring about the eyelids, presumably on account of the thinness of the skin and the loose character of the cellular tissue in this region.
Debrou' reported a very similar case in 186.5, though in his case the intestinal lesions were not so far advanced as in ours, and there was no endocarditis present.
The occurrence of clinical symptoms, pointing to peritonitis and intestinal lesions, is worthy of note, as in a number of cases with extensive intestinal involvement no local svmptoms at all were present.
Mahomed' and Haase' report such cases, whilst Verneuil* and Houel, on the other hand, report cases similar to ours, with well marked abdominal symptoms.
The presence of abdominal symptoms may be of value in pointing out beginning intestinal involvement, as in a recent and interesting case reported by Schiitte,* in which there were independent infections of the skin and intestinal tract at quite long intervals.
Schiitte's case also illustrates the differences between primary and metastatic anthrax.
The patient was a butcher's apprentice, who assisted in killing a cow affected with anthrax.
Five days later there appeared on the upper lid of the right eye a carbuncle, the patient not complaining of abdominal symptoms until fourteen days afterwards.
At this time he had pain in the abdomen, constipation having preceded the pain for several days.
Death occurred on the 16th day after infection. Already at this time the malignant pustule had begun to disappear. but there was an extensive cedema over the face and neck, as well as of the mucous membrane at the entrance to the epiglottis. Moreover there was a typical anthrax -mycosis int«stinalis," with hemorrhagic lymphadenitis of the mesenteric and retro-peritoneal lymph glands.
Although the spleen was not ineonsiderablv eularsred. anthrax bacilli could not be found, either in it or in the osdematous skin of the neck, neither could thev be found in the neighborhood of the pustule, which was opened four hours post mortem : but streptococci and staphylococci were cultivated from the bloody fluid.
From the mesenteric lymph glands, iu addition to colon bacilli, and streptococci, anthrax bacilli showiu? jrreat virulence for mice were cultivated. These latter were found in large numbers iu the pathological lesions iu the stomach and intestines, where they occurred especially thickly, and at the inner margin of the necrotic tissues, becoming progressively fewer as the deeper layers were reached. They were never found iu the blood-vessels, though in these
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there were mauy streptococci, these being especially uumerous in the spleen.
In this case we have to deal with a primary carbuncle of the skin, and also a primary intestinal infection. From the latter situation the lymph glands became infected through the lymphatics. Upon these lirst infections there was added later a general streptococcus infection through the blood current. How did the intestinal infection occur?
It could uot have occurred at the same time as the skin infection, inasmuch as fourteen days elapsed between the two. It could then only have occurred either in consequence of the scratching of the itching pustule by the patient himself (in which pustule, during life, anthrax bacilli had been demonstrated), the bacilli having thus been carried to the mouth ; or the original blood had become dried on his hands or some other part, and the spores had been carried by himself into the intestinal canal.
Our case evidently differed entirely from this, the intestinal affection being secondary to the local one, and taking place through the blood current; the clinical symptoms show that the intestinal lesions occurred within a day or two of the original lesion, and the pathological findings leave no doubt as to the part played by the blood-vessels.
The case is interesting from a pathological point of view on account of the endocarditis, the peritonitis, and the intestinal lesions.
Endocarditis due to the bacillus anthracis ajipears to be rare; we have only been able to find two cases reported, both of them by Eppinger.'
Our case differs from both of Eppinger's, in that we found a perfectly fresh endocarditis on a previously normal valve, whilst in both of his cases, though there was a fresh endocarditis, there was also evidence of old valvular disease, the latter of course probably not due to the anthrax bacillus. The fresh vegetations in Eppinger's cases, and ours, were, judging from his description, of similar formation, though apparently the anthrax bacilli were present in much smaller ijumbers in his cases.
In one of his cases the evidence goes to show that the endocardial infection was not conveyed, at any race not entirely, by the heart's blood, but took place by means of infective emboli, occluding the newly formed vessels in the chronically diseased valve. As Eppinger points out, this process could not occur in a normal valve, which is free from blood-vessels.
and was only possible on account of the pathological vascularization brought about by the old endocarditis.
Actual peritonitis due to the anthrax bacillus would also seem to be rare.
In the cases of Mahomed," Houel, and Waldeyer," the peritoneal cavity contained large quantities of fluid of a serous character, but in none of these cases was fibrin present, though in Waldeyer's case the visceral peritoneum was injected and slightly cloudy. In none of the cases were the microscopical characters of the fluid ascertained.
In Krumbolz's' case fluid was also present, and though its microscopical characters are not mentioned, the anthrax bacillus was found in it, both in cover-slip and culture. It is quite possible that cultures and cover-slips would have shown the bacillus in all these cases, for in our case the fluid did not at all resemble pus, nor the ordinary serous peritoneal exudate, whilst the description of the fluid in the cases above mentioned would lead us to believe that it was probably similar in character. The intestinal lesions found in our case correspond very accurately, as far as the gross appearances are concerned, with those described by v. Recklinghausen,'" v. Wahl," Baumgarten" and others. We have been unable to find any minute microscopical description of these lesions, though in general characteristics the lesions seem to have corresponded fairly well with ours.
Literature.
1. Debrou : .\rchives Gen^rales de M^decine, October, 1865.
2. Mahomed : Transactions of the Pathological Society, London,
18S2-3.
3. Haase : Thesis, Wurzburg, 1894.
4. Verneuil : Gazette Hebdomadaire de Medecine et de Chirurgie,
May 29, 1857.
5. Houel : Gazette des Ilopitaux, Paris, 1850. 3 S. Vol. II, 485.
6. Schiitte : Dissertation, Gottingen, 1895 ; Abstract in Bericlit
iiber die aus dem Pathologischen Institut der Universitiit GiJttingen in Etatsjahr 1891-5 veroSentlichen wifisenschaftliclien Aibeiten.
7. Eppinger : Die Hadernkrankheit, Jena, 1894.
8. Waldeyer: Virchow's Archiv, Bd. 52, 1871.
9. Krunibolz: Beitriige zur Path. Anatoiuie iind zur allgemeinen
Pathologic, 1894, XVI, 240.
10. Von Recklinghausen : Virchow's Archiv, Bd. 30, 1804.
11. Von Wahl : Virchow's Archiv, Bd. 21, 1861.
12. Baumgarten : Lehrbuch der Pathologischen Mykologie, Vol.
II, 1890.
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A STUDY OF SUBCUTANEOUS FIBROID NODULES.
By T. B. Futcher, M. B.
During the last two years several patients have been admitted to the Johns Hopkins Hospital, in Professor Osier's service, in whom this interesting complication has been observed. Considering the comparative infrequency of the condition and the meagreness of the literature on the subject in the medical journals of this country, it seemed appropriate that these cases, together with a number derived from other sources, should be reported. Before doing so, however, a short review of the literature will be given.
Although our knowledge of subcutaneous fibroid nodules is for the most part recent, yet they had been observed at least as early as the latter part of the last century, when Sauvages * described them, though he did not note their association with rheumatism, the merit of which is ascribed by Jaccoud to Froriep. Froriep's observation was made in 1843, but there has been some doubt expressed as to whether or not what he described was the true subcutaneous fibroid nodule of rheumatism. Hillier^'f described them in 1868, whilst in 1871 Jaccoud" gave a very accurate and concise account of the nodules in his TraiU de Pathologie interne. Meynet," of Lyons, reported a case in 1875, one year after Barlow and Warner" observed the first case of their series. It is to the last mentioned writers that we are indebted for a good deal of our information concerning the subcutaneous nodules. They reported a series of 37 cases before the International Medical Congress held iu London in 1881, and were the first to systematically study the nodules and draw definite conclusions from their observations. Since the report of their series, quite a number of cases have appeared in the literature, most of them, however, in British and French journals. In looking up the literature of the subject one would be led to suppose that subcutaneous fibroid nodules are a rare occurrence in this country, judging from the comparative infrequency with which cases have been reported iu the medical journals. Dr. Osler^" is of the opinion that rheumatism occurs much less frequently in Philadelphia and Baltimore than in London, and that subcutaneous fibroid nodules as a complication of rheumatism are a "great rarity" in these two cities. The first case reported in this country, so far as can be ascertained, was from Dr. Osier's clinic at the University Hospital, Philadelphia, by J. K. Mitchell'* in December, 1888.
Cheadle'" attributes the fact that the nodules are so often overlooked and so seldom described, to three reasons: (1) because they are rarely seen in adults, and that it is from adults that we take our ideas of rheumatism as a disease ; (2) that they are not known of or looked for by the physician ; (3) that they often escape notice by their smallness.
The nodules usually vary in size from a hcmpscod to a walnut. They are situated generally in the subcutaneous tissue, and as a rule are quite freely movable. Not infrequently
• Davaine is the authority for this statement (Ref. 21). f See literature at the eiul of the article.
they may be attached by their deep surface to the deep fascia, the sheaths of tendons and muscles, and occasionally to the periosteum. Sir Dyce Duckworth-* is of the opinion that there are several different varieties of the nodules, and our observations would lead us to conclude that there are at least two distinct forms: (1) those which are comparatively small, extremely firm, distinctly rounded, and easily movable beneath the skin ; (2) those which often grow larger, are softer in consistency, somewhat flattened and lobulated, and to which the skin occasionally is slightly adherent. The first class comprises the larger number of cases, and to it belongs the typical subcutaneous fibroid nodule. Those belonging to the second type appear to be of a fibro-lipomatous character, and seem to be less frequently associated with endocardial complications than do those of the first type. In certain cases both forms will be found associated in the same patient, as in cases V and VI of the jjresent article.
Angel Money "^^ claims that the subcutaneous tissue is not alone the only situation where rheumatic fibroid nodules are to be found. He holds that the heart muscle may be the seat of nodular masses similar in appearance and structure to those found in the subcutaneous tissue. He speaks of " nodular pericarditis" and "pericardial nodules," and considers the two conditions to be distinct. In an autopsy on a woman aged 20, the whole pericardial sac was found obliterated by fairly recent adhesions, and nothing nodular about the pericarditis could be detected. Three definitely sub-pericardial nodules were found, however, each about the size of a hempseed. Angel Money holds that they are the "true homologues of subcutaneous nodules and ought to be called subpericardial nodules."
The subcutaneous nodules may be found either in the neighborhood of joints, or, as is quite commonly the case, over the fleshy bellies of the muscles. The fingers, dorsal surfaces of the hands and feet, the vicinity of the olecranon and condyles of the humerus, the margins of the jiatella and neighborhood of the malleoli are the most common situations. Other less common situations are the superior curved line of the occipital bone, the temporal ridge and forehead, the vertebral and scapular sj)ines, crest of the ilium and the fibrous structures of the intercostals. The skin over the nodules is usually freely movable and natural in color, although in certain instances it has been found somewhat thickened and reddened, and adherent to them as iu Middletou's" case. When such a condition exists, it is supposed that friction has set up a cert^iin amount of inflammation in the skin, resulting iu its becoming adherent to the nodules. Karely is there any pain complained of, but in some cases the nodules have been the seat of pain in damp weather, and their presence has also been associated with slight itching, as in the last mentioned case. At times slight pain is complained of during the growth and disappearance of the nodules, as iu Case VI.
It would appear that instead of the nodules occurring as
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distiuct localized swellings, there may be a diffuse thickeniug of the subcutaneous tissue as in liershman's case/* which was reported as "A Case of Progressive Enlargement of the Hands." As a proof that such a condition may possibly exist, this same patient had typical subcutaneous nodules about both elbows and over one patella, sections of one of these showing the general characteristics of the nodules, and there was in addition a distinct history of repeated attacks of rheumatism.
The nodules occur most frequently in children and young adults. Dr. Osier" has found them oftener in adults. In Barlow and Warner's series of 37 cases, 17 of whom were boys and 10 were girls, all the patients were under 19 years of age. Without being able to state positively, it would appear from the cases which have been reported, that females are affected oftener than males. The duration of the nodules varies very much. The shortest duration from the eruption to the disappearance of a single nodule in Barlow and Warner's cases was 3 days, and the longest 5 mouths. Sir Dyce Duckworth" reported two cases, in which in one instance the nodules lasted 18 months, and in the other 30 mouths. There may be only a single crop of the nodules, or, as is more commonly the case, a succession of crops, some nodules diminishing while others are increasing in size. They very rarely appear about joints that are acutely inflamed. Usually they make their appearance after the acute symptoms have subsided and the temperature has become normal. The onset of the nodules is not accompanied by a fresh rise in temperature.
Tn examining a patient for the presence of subcutaneous fibroid nodules, it is always necessary to make a very close examination of the body. If the nodules are quite small the patient himself will in all likelihood be ignorant of their presence, owing to the fact that in the majority of cases their growth is not associated with pain. An inspection of the body is therefore not sufficient ; the neighborhood of the joints and the skin over the bellies of the muscles should be carefully palpated, as the nodules may be so small that their presence nuiy be revealed only by this means.
Fereol and Davaiue" have reported a number of cases of rheumatism, in which the skin and subcutaneous tissue presented small thickenings, which were due, not to a definite formation of fibrous tissue, but apparently to a localized cedema. These nodules rarely lasted longer than three days, and in many instances disappeared within 24 to 36 hours after their appearance. On account of their rapid onset and disappearance, and their association with rheumatism, they have been called by Fereol " uodosites cutanOes c'j)henii'res chez les arthritiques." Some writers consider them to be quite distinct from the ordinary subcutaneous fibroid nodule, whilst others consider them allied, differing only in degree of development.
A number of very interesting cases have been reported in which subcutaneous fibroid nodules have been found associated with severe attacks of migraine. A case reported by J. Ilobbs", of Bordeaux, is particularly interesting in this connection. The patient, a fenuile, had for twelve years suffered from severe attacks of migraine, which were almost invariably associated with the onset of the menstrual periods, and on
repeated occasions accompanied by the appearance of a subcutaneous nodule over the left frontal region. Upon the cessation of the menstrual flow the migraine and nodule disappeared. During one of the attacks the patient had quite an extensive crop of nodules over the forehead and scalp and about the right elbow. There was a distinct family history of rheumatism, and the patient's hands showed marked changes from chronic rheumatism. Davaine"' reported three cases in which the onset of migraine was in each instance associated with the appearance of subcutaneous nodules over the frontal region. This condition is interesting as it seems to afford proof to the theory that migraine is sometimes rheumatic in origin, and the presence of the nodules would give a clue to the true cause of the migraine in cases where there was no apparent joint involvement.
Several instances have been recorded where subcutaneous nodules have been found in cases of osteo-arthritis. Newton Pitt"' has reported several such cases, and states that the nodules have the same histological structure as those of rheumatism, although differing from them clinically in the following points : (1) they occur in adults ; (3) they are much more chronic and last for years ; (3) they are at times extremely painful and tender, the pain returning from time to time; (4) they are usually unassociated with any cardiac lesion ; (5) they may vary in size from a small shot up to one inch in diameter, but they are generally larger than those of rheumatism. Payne"^ and Mahomed" have both observed the nodules in osteo-arthritis, the latter stating that they are not identical with those of rheumatism.
As regards the gross appearance of the nodules, Cheadle"^' says that " when they are exposed by dissection, they appear as oval, semi-transparent, fibrous bodies, like boiled sago grains." The accounts of microscopical examinations vary considerably, but agree in a general way in that the nodules appear to be made up essentially of fibrous tissue in various stages of development. The examination made by Barlow and Wanier showed the nodules to be made up of a fibrous network, with caudate, spindle-shaped and nucleated cells and a large number of blood-vessels. They suggested that the appearance presented many of the characteristics of organizing granulation tissue. In a number of instances where microscopical examinations were made, the blood-vessels have been found markedly increased in number, and special stress has been laid on the changes in the blood-vessels themselves. In Middleton's case already mentioned, the nodules were made up largely of connective tissue in various stages of development. Hlood-vessels were almost entirely absent from the centre of the nodules, but at their periphery the arteries were abnormally numerous, and in many instances their coats were thickened by an infiltration of cells, the tunica intima being frecjuently particularly affected. The middle coat was also considerably thickened and dissected by a collection of cells. Groups of these cells frequently extended to a considerable distance from the vessels, and in many instances they mapped out the course of the minute vessels in the papillae of the skin. Middleton thought, on account of the marked changes in the blood-vessels, that the nodules might possibly be vascular in origin, as if produced by some irritant carried
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in the blood. Cavafy" found a marked proliferation of the endothelial cells in many of the blood-vessels in addition to the changes in the vessel-wall noted above. The vascular changes are not always a feature, however. In .7. K. Mitchell's'^' case the histological examination made by Dr. Osier showed "a dense fibrous stroma, with cells chiefly ovoid, the ends prolonged into fibrils. There was no such arrangement of round-celled elements, as in granulation tissue, which Barlow found in his specimens. The extreme toughness of the nodules indicates that they have undergone conversion into fibrous tissue. In teased specimens there were places in which the fibres were closely set together, as in embryonic connective tissue, but in the larger part very few cells could be seen among the wavy bundles of fibres."
The microscopical examination of the nodules from Case I of the present article (the full account of which will be given with the report of the case) showed several interesting features which, so far as can be ascertained, have not been previously noted. Briefly stated, these consisted of a definite hyaline degenerative change in the fibrous tissue in many places, whilst in other situations areas of calcareous degeneration were to be made out. The sections also showed the presence of giant cells and minute hemorrhages.
One of the most interesting features in regard to the nodules is that they disappear without leaving any apparent indication of their previous existence or situation. This seems remarkable, as definitely formed fibrous tissue, when once present, is not supposed to undergo absorption and disappearance. The same nodules may at various times undergo a diminution and increase in size. On account of the marked vascularity of the nodules this would be readily explained by a vaso-motor influence causing contraction or dilatation of the vessels.
Barlow and Warner stated that the nodules were in their nature probably homologous with the inflammatory exudations which form the vegetations on the cardiac valves. F. D. Drewitt"- has suggested that they might be related in their origin as well as in their nature. In the case of the cardiac vegetations, they generally occur on the free margins of the cardiac valves, where they are constantly subjected to the friction of the blood current, and when the valves become inflamed, to friction on each other as well. Likewise, the nodules are most commonly found over the most prominent part of the joints, where they are most liable to be subjected to injury and friction. Dr. Drewitt brought forward further proof of his theory that friction may be a factor in the production of the nodules, or at least in determining the position where the nodules occur. He stated that if the nodules make their appearance in a patient with rheumatism, who is kept constantly in bed on his back, they will occur in greatest numbers over the occiput and the spinous processes of the vertebra;, situations in which, under ordinary circumstances, they rarely occur.
Subcutaneous fibroid nodules are considered by such authorities as Barlow and Warner and Cheadle as a positive indication of the existence of a rheunuitic taint in the individual in whom they may be found. It would appear that rheumatic cases with endocardial complications seem to be most liable
to this interesting complication. This is borne out by the fact that in the majority of the eases which have been reported endocarditis has been present. A synopsis of Barlow and Warner's series of cases shows how grave the cases are in which the nodules occur. Of the 27 cases there was a distinct history of arthritis in 19, whilst 6 others had definite joint pains. In every case there was evidence of endocarditis, either mild or severe; pericarditis was present in 8 cases; in 10 there were definite choreiform movements, and 8 out of the 27 cases proved fatal. Cheadle holds that the presence of the nodules in a case of rheumatism is of very grave import, especially when they occur associated with definite signs of endocarditis, as he has found in his experience that the heart complication is "persistent, uncontrollable and marches almost infallibly to a fatal end "' and is practically equivalent to signing the patient's death-warrant. He also maintains that the gravity of the case is in direct proportion to the number and size of the nodules. Other observers have noted the progressive character of the heart lesion in cases of rheumatism associated with subcutaneous nodules.
Edge'" is of the opinion that cases in which the nodules occur without any associated endocarditis appear to be more common in adults than in children.
In some instances it has been noted that the heart murmur has diminished in intensity with the disappearance of the nodules. Whether or not this is of any practical importance is doubtful, as the intensity of the murmur bears no definite relationship to the gravity of the heart lesion.
C. H. Brown'- reported a case which was particularly interesting, in that it was the first case reported in this country in which thei'e was an association of rheumatism, chorea, endocarditis and subcutaneous fibroid nodules. Case II showed a similar combination, and as far as can be ascertained these are the only two such cases that have been reported in this country. Brown is of the opinion that cases of rheumatism which are associated with chorea are specially liable to the occurrence of subcutaneous fibroid nodules.
Fibroid nodules are rarely an accompaniment of acute rheumatism. They occur most commonly after the acute symptoms have subsided and their presence indicates that the rheumatism is very likely to run a chronic course, so that one should be guarded in his statements to the patient or his friends as to whether or not recovery will be rapid and complete.
Just as the nodules have been shown to be of some value from a prognostic standpoint, so in certiiin cases they may aid us in establishing a relationship between rheumatism and certain morbid conditions found in a patient. For instance, they were of great importance in arriving at the cause of the neuritis in Case VII. Xot infrequently the nodules occur in patients without there being any evidence or history of paiu or swelling of the joints. If we are to believe the statement of Barlow. Warner and Cheadle that the presence of the nodules is an absolute indication of a rheumatic taint, then their occurrence in cases of chorea and endocarditis without any joint involvement would prove the connecting link l)etween these diseases and rheumatism.
There are several conditions which might be mistaken for the subcutaneous nodules of rheumatism:
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1. Traumatic painful subcutaneous nodules. In this case there would likely be a history of traumatism; the nodules would be limited to possibly one or two in number and would be painful.
2. In the case of the ephemeral nodosites of Feruol, the true skin itself is involved; the nodules are not so hard and librous and disappear very suddenly.
3. Erythema nodosum might possibly be mistaken for the rheumatic nodules. In this condition the skin between the knee and ankle is usually the part involved. The thickening is in the true skin. The nodes are larger in diameter than the tibroid nodules usually are, the skin over the affected area is usually reddened and undergoes a series of changes in color. The affected areas in erythema nodosum are painful and tender to the touch.
i. Subcutaneous syphilitic gummata might at first present a somewhat striking resemblance, but in this condition the skin would soon become adherent to the mass, and the whole would present the characters of an inflammatory tumor. A possible history of lues and other evidences of syphilis would put one on his guard.
.5. In cases where tophi are deep-seated about the joints, as they not infrequently are, there might be some difficulty in diagnosis. Where such are present, there would most likely be others present in the ears, showing the deposition of iirate of soda. The history of the case would also give a clue to the true condition.
(i. Urticarial wheals show a slight resemblance, but would be distinguished by the skin itself being involved, and the areas presenting a whitish centre surrounded by a reddish halo. Pruritus would be marked, and there would in all probability be a history of gastric disturbance.
7. Heberden's nodosites might be mistaken for the nodules. The former are limited to the sides of the distal phalanges, are hard aud firmly united to the phalangeal bones of which they form a part.
8. A number of cases of subcutaneous nodules associated with syphilis have been reported. These do not appeal" to be gummatous in character, and present a striking resemblance to fibroid nodules of rheumatism. Careful inquiry should be made for a syphilitic history in all cases where nodules are present without any apparent joint complication. Cases of fibroid nodules in syphilis have been reported by Lailler,*' Dr. Stephen Mackenzie," Sir Dyce Duckworth,^^ and Dr. Kingston Fowler.'^'
9. The fibroid nodules of osteo-arthritis are very similar to those of rheumatism, but Dr. Newton Pitt claims to be able to distinguish them by the points already given.
10. Certain benign growths, as lipomata and fibromata, might be mistaken for fibroid nodules. The lipomata are larger, softer and more lobulated than the nodules, and are situated most commonly over the back and shoulder-blades. More difficulty would be found with the fibromata, as the fibroid nodules are really of a fibromatous nature.
The nodules seem to have a life history of their own and appear to be uninfluenced by any special treatment. One should treat the disease of which they are only a symptom.
Case I. — No history of rheumatism ; enormous hypertrophy and dilatation of the heart ; adherent pericardium; chronic proliferative peritonitis with ascites; subcutaneous fibroid nodules ; no endocarditis.
Louisa R., aged (on a<lmission) 13, an occupant of Ward G, with the exception of a few months at a time, from May 14, 1891, to December 8, 1894.
Father and mother are living and well ; no rheumatism in the family.
The patient has had measles, scarlet fever, and whooping-cough ; she has never had rheumatism or chorea. The mother is positive that there never has been any swelling or tenderness of the joints. Some time before admission to the hospital she had for a time pains in the muscles of the right arm.
Her illness began in the summer of 1891 with swelling of the feet and shortness of breath.
In the three years and a half during which she was under observation she had all the signs of enormous dilatation and hypertrophy of the heart ; there was a loud, rough apex systolic murmur, and we regarded the case as one of extreme mitral insufficiency from disease of the valve, with secondary great enlargement of the right heart. She had a pulsating liver, which gradually shrank. The recurring ascites was attributed to proliferative peritonitis and perihepatitis, and it was thought probable that she had adherent pericardium.
She never at any time bad swelling of the joints ; for the past eighteen months she had extreme and persistent cyanosis of the arms and legs.
About two years before her death we noticed for the first time the presence of subcutaneous fibroid nodules. They were most numerous about the elbows and along the margin of the ulnae. A few were also noticed about the wrists and over the ankles. The majority of them were small and shottj', though one or two about the elbows were larger and broader. They never were at any time painful ; a majority of them were very persistent, but one or two of these about the elbow disappeared.
This case is of a good deal of interest, as the presence of the subcutaneous fibroid nodules, even in the absence of a rheumatic history, rather tended to corroborate our view that she had disease of the mitral valve segments.
The autopsy showed colossal enlargement of the heart, which occupied nearlj' the whole of the front of the chest. The pericardium was adherent, particularly over the right chambers. The cardiac orifices were enormously dilated, but the valves themselves, beyond a trivial thickening, were not involved.
On microscopical examination the nodules are seen to be made up essentially of fibrous tissue in various stages of development. The older portions consist of a rather dense fibrous connective tissue in which the fibres are arranged in bundles running parallel to each other. Other portions are composed largely of cellular elements, which under a high power are seen to consist of small round cells, fibroblasts and polynuclear leucocytes. In these situations blood-vessels are quite numerous, so that to a certain e.xtent there is a resemblance to granulation tissue, as Barlow and Warner noted in their specimens. Several giant cells were present in the younger portions of the nodules, twenty-six nuclei being counted in one of these. The transition from the young portions to the well developed fibrous tissue is quite gradual.
Some of the sections show a very interesting feature in the occurrence of a definite hyaline degeneration of the fibrous tissue in certain situations. Where this degenerative change is most marked, the fibrous tissue appears to be arranged in bundles with a concentric distribution of the fibres, so that when the bundles are cut transversely they appear to be made up of a series of concentric rings. Til is hyaline degeneration also occurs, though to a less marked degree, in situations where there is not this special arrangement of the fibres. A further interesting feature is the occurrence of a distinct calcified change in these areas of hyaline degeneration at certain points. Portions of the fibrous tissue which have
undergone hyaline change show quite marked cellular infiltration, which, however, is almost entirely absent in the areas of calcification. The calcareous deposit appears to take place between the layers of fibres which have undergone hyaline change.
The vascularity of the nodules is quite a striking feature. The blood-vessels are most numerous at the periphery of the nodules, the central portions being comparatively free, excepting in the areas of cellular infiltration where minute blood-vessels are present. Some of the larger vessels show an infiltration of small round cells into their walls, these, in certain instances, extending some distance into the surrounding tissue. Many of the bloodvessels contained an excess of polynuclear leucocytes, which in some cases almost fill the vessel ; other vessels are occluded with plugs of fibrin. In one or two instances there is a distinct proliferation of the endothelial cells, the lumen of the vessel being almost filled with the proliferated and desquamated cells.
Minute hemorrhages into the connective tissue are seen in several situations.
The nodules are for the most part quite circumscribed, although cellular infiltration into the surrounding connective tissue does occur to a greater or less extent.
Case II. — Rheumatism, chorea, endocarditis and subcutaneous fibroid nodules.
F. F., male, set. 16, was admitted to the Johns Hopkins Hospital in Dr. Osier's service, June 29, 1894, complaining of pains in the wrist joints and nervousness.
The family history was unimportant; no history of rheumatism in any member of the family.
The patient had measles, chicken-pox, mumps and diphtheria when a child. There was no history of his having had scarlet fever. From childhood up to the onset of the illness for which the patient was admitted to the hospital he ha<l always had good health. Used tobacco and stimulants moderately ; denied having had gonorrhoea or syphilis.
The patient's illness began 10 weeks previous to admission to the hospital with sudden swelling of the right ankle-joint, which was also very tender to the touch. Skin over the joint was reddened. During the first week of the illness almost all the large joints became affected, the ankles, wrists, left tempero-maxillary joint, knees and hips being involved in the order named. All these joints were swollen and painful, so that during the second week he was unable to move in bed. Improved gradually during the third week, andat the end of the fourth week patient was able to get up. Since then patient had several relapses, having had to go to bed for one week.
Five days previous to admission, patient began to have involuntary movements of the arms, legs and tongue, which, however, were not so severe as to prevent his getting about. Two days previous to admission, however, the movements of the arms became very violent and uncontrollable, and those of his tongue interfered very much with his talking. Deglutition was not interfered with. There were sliglit spasmodic movements of the facial muscles, but the patient could not say how long they bad been present.
No symptoms specially referable to the heart were complained of.
An examination of the patient on admission, showed but slight evidences of rheumatism, all tlie joints being moved quite freely without causing much pain. Complained of slight pain in the metacarpo-phalangeal and phalangeal joints of both iiands, which were slightly tender on palpation.
The backs of both hands showed numerous subcutaneous fibroid nodules, particularly in the neighborhood of the metacarpo-phalangeal joints, about each one of which there were from four to five nodules. The nodules were present also about the phalangeal juints, but in smaller numbers. The wrists were free, but there wore several nodules about the elbow-joints, chiefiy over the olecranon processes and condyles. No nodules were to be found on any other part of the body. The nodules varied in size from a pin's head to a split pea, the skin being freely movable over them and not red
dened. Those over the metacarpo-phalangeal joints were best seen
by tightly closing the hands.
The patient exhibited slight, but definite choreiform movements in the arms and hands, with occasional twitchings of the leg and facial muscles.
The lungs were clear throughout on percussion and auscultation.
Thepointof maximum cardiac impulse was bestseen in the fourth space in mammillary line. No thrill was to be made out. Relative cardiac dulness began at the third rib ; extended transversely from the left sternal margin to a point 2 cm. outside the nipple line. At the point of maximum cardiac impulse there was a rough systolic murmur to be heard, this being also well heard along the left border of the sternum.
The examination of the urine showed it to be practically normal, although at a subsequent examination a faint trace of albumen and a few granular casts were found.
The general condition of the patient while in the hospital improved markedly. The examination of the patient on August 15th, the day on which the patient left the hospital, showed thattbe choreic movements had practically ceased and the joints had entirely cleared up. An occasional nodule could still be made out on the backs of the hands and there was one still to be seen over the right elbow.
The examination of the heart showed that it had undergone a definite change. The point of maximum impulse was now in the fourth space 2 cm. outside the mammillary line. Relative dulness began at the second rib. The first sound at the apex was sharp and snapping, and was followed by a slight systolic whiff, traceable into the axilla. There was now a short presystolic murmur audible at the apex. A slight, soft systolic murmur was to be heard over the base of the heart and a systolic puff over the vessels of the neck.
The thyroid gland was distinctly enlarged, the right side being a trifle the largar. Eyes were not particularly prominent. The usual range of the pulse was between 108 and 128.
The highest temperature at any time during his stay in the hospital was 101°, and it had been normal for 3 days previous to his discharge.
The treatment was rest withol. gaultheriae and liquor arsenicalis in increasing doses. Patient was taking 20 minims of Fowler's solution 3 times a day previous to his leaving the hospital.
The above case is interesting in that it shows the very unusual association of rheumatism, chorea, endocarditis and subcutaneous fibroid nodules in the same patient. It was also interesting on account of its showing that the cardiac changes were progressive, the heart increasing definitely in size and tlie murmurs changing in character. An effort has been made to try and find ont the patient's present condition, but we were umible to get any information with regard to him. So far as can be ascertained, the only other similar case reported in this country was that of C. II. Brown. Mackay reported a similar c;ise in the Lancet, the patient making an excellent recovery.
Case III. — Rheumatism, aneurysmal dilatation of tht aorta, and subcutaneous fibroid nodules.
P. H. D , colored, male, ret. -19. was admitted to the Johns Hopkins Hospital, in Dr. Osier's service, November 22, 189-1. complaining of pain in the left side and shortness of breath.
The family history was unimportant ; no hereditary disease in the family.
There was no history obtainable of the patient baring had any of the diseases of childhood. Had small-pox when 29, and facial erysipelas when he was 30 years of age. There was no history whatever of rheumatism previous to three years before admission, when patient began to complain of severe pain in the fore part of
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the left foot, which was excessively tender and considerably swollen. Confined to bed two weeks. No other joint involvement. Had gonorrluea when 39 ; no history of the initial lesion or any secondary symptoms of syphilis obtainable.
Eight years ago, five years i)revious to the " rheumatic " attack, patient noticed in front of his right knee a small lump which felt like a shot under the skin. Four or five months later a similar lump appeared over the front of the left knee, and subsequently one appeared over the right and left elbows in the order named. The nodules made their appearance without any apparent cause. They felt to the patient like "bird-shot" beneath the skin, were always freely movable, and at no time painful. Their size had gradually increased until one year previous to admission, since when they had remained stationary. Patient never knew them to diminish in size and increase again. He had never seen similar lumps on any other part of the body.
The symptoms of which the patient complained, on admission to the hospital, began three weeks previously, with pain of a constant aching character in the lower part of the left side of the chest. Occasionally the pain was sharp and shot up towards the left shoulder, but never down the arm. It was worse on exertion and deep breathing. Patient had had dyspncea for four or live days, and occasional attacks of palpitation and vertigo. No histor of oedema of the feet. Appetite good ; bowels regular.
An examination of the patient, on admission, showed him to be a well formed, well developed man. There was marked pulsation of the carotids and suhclavians, and that of the radials was visible. Radial pulse was 76 to minute, regular in force and rhythm, good volume, and somewhat collapsing in character, though not typically so.
On the left elbow there were two large, subcutaneous, movable, lobulated nodules, the larger, 3x4 cm., being situated just behind the internal condyle, the smaller, 2.5x2.5 cm., just below the tip of the olecranon. On the right elbow, just below the tip of the olecranon, there was a still larger nodule, measuring 4x5 cm., and just by the side of this a smaller one, not larger than a split pea. On both knees, just below the patella, were similar nodules, the one on the left side being 3x3 cm., that on the right being a trifle larger and consisting of an agglomeration of smaller ones. These nodules were all moderately firm. They had never been painful and were not tender on palpation.
Lungs were clear throughout on f)ercus8ion and auscultation.
The examination of the heart showed rather interesting changes. The point of maximum cardiac impulse was in the fifth space, 1 cm. outside the mammillary and 11 cm. from the midslernal line. Kclative dulness began at the fourth rib, extended transversely from the left sternal margin obliquely outwards to the point of maximum impulse. At the point of maximum impulse the first sound was dull, preceded by a very faint rumble, and followed by a slight systolic murmur, which was lost 4 cm. outside the point of maximum impulse. Second sound quite sharp. Immediately inside and above the point of maximum impul.se the first sound was preceded by a distinct presystolic rolling sound, which was heard over a very small area. Passing inwards and upwards from this point the sounds were represented by a double murmur, a systolic and a diastolic, the latter being best heard along the left border of the sternum and in the aortic area. In the second right interspace the sounds were quite loud, the first being represented by a harsh systolic murmur, the second by a well marked, somewhat accentuated second sound, followed by a slight murmur.
The further physical examination of the patient revealed nothing of importance, with the excejition of a symmetrical enlargement of the parotid glands.
On December 23 it was noted that the radial pulse had become distinctly collapsing in character.
On January 24, 18!)5, there was notice<l for the first time a pronounced throbbing over the second costal cartilage and interspace on the right side close to the sternum. This was both visible and
palpable. Percussion note was slightly dull over this area. The double murmur was still audible as on admission. Tracheal tugging was just to be made out.
An examination of the patient on February 8, 1S95, revealed a striking difference in the volume of the two radial pulses, the right being much smaller than the left. There was no inequality of the pupils. The pulsation above noted had extended upwards, and on this date there was a distinct lifting of the inner end of the right clavicle and the sterno-clavicular articulation with each heart beat. This pulsation was most marked in the recumbent posture, almost disappearing when the patient sat upright. It seemed to be less marked over the second right cartilage and interspace where it was first noted. No thrill was to be made out over the pulsation, but a distinct thrill was to be felt over the vessels of the neck. .
About two weeks later, February 26, the patient became very hoarse and cough was very distressing. Large quantities of ropy, tenacious sputum were expectorated. Microscopical examination of the sputum on this and subsequent occasions failed to show the presence of tubercle bacilli. For the first time it was noted that there was an inequality of the pupils, the right being larger than the left. Patient had been passing a diminished amount of urine, which contained a distinct trace of albumen and numerous hyaline and finely granular casts. The lifting of the right clavicle did not seem so marked as on previous examinations. The double murmur was to be heard as before.
From this date on the patient's general condition seemed to be gradually getting worse. He suffered intensely from severe attacks of dyspncea and palpitation of the heart. A laryngoscopic examination by Dr. Warfield on March 8th showed a complete paralysis of the left aryteno-epiglottidean fold, although the cords did not seem to be affected. The attacks of dyspncea and palpitation gradually became more severe, and face became swollen, particularly on the right side.
The subcutaneous nodules were much the same as on admission, being possibly a trifle smaller. There had been no appearance of any fresh nodules on any part of the body. Patient did not have any evidences of arthritis while in the hospital.
On March 14 the patient became unconscious and died at 9.30 p. m.
Postmortem . Only the most important parts of the post-mortem examination will be given. The heart and aorta showed very interesting changes. The heart was both bypertrophied and dilated ; both ventricles were involved, particularly the left. Left ventiicle averaged 19 mm. in thickness and was 9 cm. in length. Average thickness of right ventricle was 4 mm., the length being 9 cm. Mitral orifice measured 10 cm. in circumference, and the mitral valve appeared quite normal. Tricuspid orifice measured 12.5 cm. in circumference ; valves were normal. Pulmonary valves were normal. Both auricular apjiendages contained recent thrombi. The aortic valves were thickened and retracted at their margins. The aorta measured 8 cm. in circumference just above the valve. There was a diffuse dilatation of the ascending and transverse portions of the arch of the aorta. The circumference of the aorta, at the origin of the innominate, was 10 cm. At the beginning of the thoracic aorta there was a farther dilatation which extended for a distance of 17 cm. It extended backwards and to the left, was spindle-shaped and involved all the coats. The central part of the dilatation was covered « ith light, adherent, laminated fibrin. This dilatation measured 12 cm. in circumference at the beginning, 13 cm. at the widest part, and 8 5 cm. at its inferior extremity. It was adherent to the fourth and fifth dorsal vertebra", the bodies of which were eroded by pressure. The aorta was the seat of extensive nodular endarteritis. There were adhesions between the pericardial sac and the aorta.
Both lungs were partially bound down by old adhesions.
Kidneys showed marked chronic diffuse nephritis.
The left pneumogastric and recurrent laryngeal nerve were pressed on by a calcified pigmented gland.
Unfortunately no specimens of the nodules were obtained at the
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autopsy, so that a report of the microscopical examination of tliese cannot be given.
The above case is interesting on account of the long duration of the nodules — 8 years, and from the fact that they appeared 5 years before the patient had had an attack of rheumatism. The heart and aortic changes were interesting, as the aneurysmal dilatation practically took jjlace while the patient was under observation in the hospital wards.
Case IV. — Rheumatism and subcutaneous fiOroid nodules without endocarditis.
J. B. T., male, let. 28, a hospital employee, was admitted to the Johns Hopkins Hospital, Dr. Osier's service, June 24, 1895, complaining of pains throughout the body, vomiting, diarrhoea and sore throat.
Father was living at 68 years of age and had always been subject to attacks of rheumatism from childhood up. After a rheumatic attack when 20 years old he had numerous nodules appear beneath the skin of the arms and legs, some of which the patient states have persisted- up to the present time. According to the patient's statement, these nodules would increase in size during an attack of rheumatism and diminish again afterwards. Could not say whether his father had crops to appear and disappear. Most of the nodules were the size of hazel-nuts but were never painful. Patient's paternal grandfather was disabled for 22 years as the result of repeated rheumatic attacks. A paternal aunt was subject to rheumatism, and a second died of apoplexy.
Patient hail had measles, chicken-pox and mumps. When 14 years old he had a severe attack of pain in the lumbar region of the vertebral column, and also in the muscles on each side and over the shoulder-blades. Was confined to the house for 2 weeks, and had to be propped up in a chair. It was 6 to 8 months before he was able to get about properly, and since then he has never been able to do much stooping without causing pain in the back. About the time of this attack the patient notic,ed a lump about the size of a hazel-nut on the dorsal surface of the right forearm about 3 inches above the wrist joint, and a similar one on the palmar surface of the left forearm about the same distance from the wrist. These have persisted up to the present time, never having entirely disappeared. During an attack of pain in the joints, the nodules would become larger and harder and afterwards diminish in size again. Since the attack of pain in the back when 14, patient has had repeated attacks of pain in nearly all the larger joints of the body, which, however, have never been swollen. Has had nodules appear and disappear during these attacks. Two years ago patient had a severe attack of pain in the left ankle, which prevented him from working for;! or4 months. Joint was not swollen. During this attack the patient noticed several nodules appear on the front ami outer aspect of the left thigh, and two between the crest of the ilium and the left costal margin. Three of tliese on the thigh and the two last mentioned ones have persisted to the present time. Several mild attacks of pain in the joints have occurred since two years ago, and several nodules have appeared and disappeared since then.
Had an attack of dysentery when 19, which lasted one year ; malaria when 18; pneumonia 3 years ago. No history obtainable of gonorrhoea or syphilis. Never had chorea or palpitation of the heart.
The symptoms of which the patient complained on admission began Ave days previously with pains in the elbow, shoulder, knee and ankle-joints, and pain in the back. Pain wrs severe, and he had a stabbing pain beneath the right shoulder-blade. Soon after the joint pains began his throat became slightly sore. Those symptoms continued up to the time of admission, previous to which for 24 hours he had had nausea, vomiting and diarrhoja, which he attributed to an indiscretion in diet.
The patient was a large framed, healthy-looking man. Pulse was 100 to the minute, regular, good volume; vessel wall not thick
ened. Throat was slightly reddened, but tonsils were not swollen.
Joints were all slightly painful, but not swollen. The following
were the situations of the nodules :
Right arm : 1 on the outer side of the arm 8 cm. above the external condyle, 2 on the anterior aspect of the forearm over the flexor muscles, and 2 on the posterior surface over the extensors. These varied in size from 1 to 2 cm. in diameter, were strictly subcutaneous and movable, moderately firm, somewhat flattened and not tender.
Left arm : 1 nodule, 1x1.5 cm., about 4 cm. above the wrist on anterior surface of forearm. It was subcutaneous, movable on the deep structures, rather firm and flattened. This was in all probability the one which had been present since the onset of the rheumatism when patient was 14.
Left thigh : I'here were 4 nodules on the outer and anterior aspect of the middle third of the thigh, all of which measured 2x2 cm., and one of which was rather tender on pali)ation.
•Ibout midway between the iliac crest and the left costal margin there were two separate nodules, which were rather deep and measured 3x3 cm. They were rather deep-seated and somewhat tender. Skin was less freely movable over them than i i the other instances.
Lungs were a trifle hyper-resonant on percussion. Few tine, moist rales heard in right axillary region.
The point of maximum cardiac impulse was neither visible nor palpable. Heart-sounds best heard in 4th space, 3 cm. inside the mammillary line. The relative dulness did not begin until the 4th rib was reached. The heart-sounds were clear at apex and base. and of normal intensity. No murmurs were to be made out.
Physical examination was otherwise also negative.
The long standing of the nodules, some having lasted 15 years and others 2 years, the occurrence of nodules in the patient's father, and the absence of any cardiac lesion, makes the case an interesting one.
Case V. — Rheumatic history, subcutaneous fibroid noduks and doubtful carcinoma of the stomach.
Mr. U., set. 57 years, was admitted to the Johns Hopkins Hospital, June 21, 1895, complaining of general weakness and nausea.
There was a distinct history of tuberculosis in the family, his father and two sisters having died of it. No history of rheumatism or malignant disease in the family.
When a child the patient had measles, whooping-cough and mumps. Gave a doubtful history of his having had typhoid at the age of 27. After this attack of fever he had diarrha'a each spring for 6 or 7 successive years. Had gonorrhcca when 21. but there was no history of lues obtainable. He had had frequency of micturition at night for 3 or 4 years. Two years previous to admission he had a mild attack of rheumatism in the ankles. There was no history of chronic stomach trouble. Used tobacco and alcohol in moderation.
The illness for which the patient c^me to the hospital began four months previously with severe pains in the shoulders, arms and, to a less extent, in the knees. The joints were apparently not swollen. During the attack he liad severe nausea and vomiting, which was not specially associated with the taking of food. He did not vomit any blood. His appetite was poor and nausea was constant, being increased by the sight of food. Flatulence was a prominent symptom. Had not had any pain in the epigastrium. Wm gradually losing flesh.
The patient was not aware of the presence of any lumps beneath the skin.
He was rather pale and somewhat emaciated.
In the parasternal line, about 5 cm. below the costal margin, a small nodular thickening, detinitely situated in the abdominal wall, was to be felt on palpation. The mass w.is somewhat lobulated and rather soft. On the exterior surfaces of the forearms several similar ones of a tibro-liix>matous character were to be seen
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and felt. They were freely movable and the skin was not adherent to them. Along the outer margin of the right tibialis anticus tendon there was a very hard subcutaneous fibroid nodule, and another occupied a corresponding position on the left foot.
The heart and lungs were clear throughout.
An Ewald's test-breakfast was given on two occasions, the contents of the stomach when removed showing an absence of free hydrochloric acid on each occasion. There was no reaction for lactic acid, however.
After inflation of the stomach the lower margin did not pass a point 4 cm. above the umbilicus. A slight sense of induration was to be felt in the left parasternal line, which was not to be made out when the stomach was empty.
The patient lost considerably in weight while lie remained in the hospital.
lu the above case we have the two forms of the uodules present iii the same patient, the soft, flat, comparatively large fibro-lipomatous form, and the small, round, very firm variety.
Case VI. — Rheumatiim, subcutaneous fibroid nodules, with cardiac hypertrophy.
The following case was shown by Dr. Toulmin (now of Philadelphia), at the Hospital Medical Society when he was a resident medical officer in the medical service. The case was not reported, and I am indebted to Dr. Toulmin and Dr. Hobach for finding the address of the patient and permitting me to examine him.
Mr. G., set. 55, was seen at his own house.
There was nothing of importance in the family hi.story. The patient had whooping-cough and mumps when a child. When 22 years of age he had his first attack of rheumatism ; both ankles and right hip joint were affected, being very painful, but not swollen. He was laid up for two months, but did not have any subcutaneous nodules at that time. From then until eight years ago he had several mild attacks of rheumatism. Patient had not complained of any heart symptoms up to this time. Eight years ago he had a right-sided hemiplegia, speech being affected, which lasted three- months. Does not remember whether he had any joint involvement at that time or not. It was during this illness that the patient first noticed the presence of lumps beneath the skin on various parts of the body. His physician counted as many as 140 at this time. Quite a number of these occurred over the epigastrium, and the patient states that the one which is still to be seen and felt in this region first appeared at that time. Some of the lumps were as large as walnuts, were all freely movable, and were painful when they were growing or diminishing in size. Other situations where the nodules appeared at that time were : one on the left under eyelid ; several painful ones on the scalp and on the back of the neck at the junction of the cervical and dorsal regions ; others were present on the anterior surfaces of the arms, forearms, thighs ami legs. The patient states that in all the last mentioned situations the nodules varied in size between a pea and a hazel-nut, most of them disappearing within 24 hours, and none lasting longer than three days.
Since eight years ago the patient has had repeated crops of no<iule8, at no time being perfectly free from them.
In October, 1S02, he had a second attack of right-siiled hemiplegia which laid him up eleven weeks. Again he had a profuse crop of noduUs. The right ankle joint was swollen and painful, and he suffered from dyspnoea and slight precordial pain. Since then he has not had any further joint trouble, and has always been able to attend to his work.
The patient was a healthy looking, fairly well nourished man. Pulse was 92 to min., regular, pood volume, vessel wall a trifle thickened. Subcutaneous nodules were present in the following situations: one beneath the costal margin in the left hypochondrial region, 3x3 cm., soft, somewhat lobulated and rather sensitive on palpation. This was of a Bbro-lipomatous nature.
Right arm: One in front of internal condyle .5 x 1 cm.; five on the anterior surface of forearm, varying in size from a bean to a hazelnut.
Left arm : One about the size of a hazel-nut above the external condyle on the outer side of the arm ; four on the ulnar side of the forearm, also varying in size between a bean and a hazel-nut. All the above were rather flat and not extremely hard.
Right leg : Two over the extensor tendons on the dorsum of the foot, and one apparently in the skin about 4 cm. above the ankle. These were in size between a pea and a bean.
Left leg : One about the size of a bean on the inner surface of the tibia about 11 cm. above the ankle. It was very hard, round, quite movable, subcutaneous, and extremely sensitive to the touch. Excepting for the tenderness it presented all the characters of a subcutaneous fibroid nodule. The patient had been forced for years to wear boots, owing to the pain in the nodules produced by wearing laced shoes.
The Lungs. Hyper-resonant on percussion, but otherwise were clear.
T?ie Heart. The point of maximum cardiac impulse was in the sixth space, 1 cm. inside the mammillary line. The relative cardiac dulness began at the third rib and extended from the left sternal margin obliquely outwards to the point of maximum impulse. The first sound at the apex was distinctly prolonged and softened, but there was no definite murmur to be made out. Passing upwards along the left border of the sternum, a very faint systolic murmur was to be heard, the murmur being of maximum intensity over the pulmonary area. Both aortic sounds were quite clear.
This, like the preceding case, shows the association of the two varieties of subcutaneous nodules in the same patient.
Case VII. — Rheumatic neuritis with subcutaneous nodules.
I am indebted to Dr. Osier for the notes of the following interesting case :
Mr. H.,aged 60, seen with Dr. Lockwood, July 1, 1895, complaining of pains in the arms and legs.
Patient is a tall, spare man, who has always enjoyed good health with the exception of dyspepsia, to which he lias been subject at intervals for many years. He has taken very good care of himself, is a moderate drinker, and has an excellent family history ; no gout ; no rheumatism.
Early in March of this year he began to feel pain in the right leg, chiefly about the ankle and instep. It was as though he had a band about these places. The pain was sharp, but never very acute. He has felt at times a little numbness and tingling, and on several occasions there was a little redness of the skin about the ankle. Shortly afterwards the left leg became affected in the same way and the pain in the ankle was sharp. In it he had one day very sharp, stabbing pains down the back of the leg. He describes here, too, the same feelings as if there was a band about the ankle. Patient still experiences this sensation at times. There was no swelling, no special numbness, no enlargement of the joints. It was confined altoeetber to the legs. It did not incapacitate him in any way, but it was a source of a good deal of annoyance and distress. About two months ago the arms began to be affected. Ill-defined iiains from the shoulder, without anything to be seen or localized, but with a good deal of tenderness, particularly of the muscles, when Jie laid the arm on anything. He does not seem to have had any paraesthesiae. The muscular power of the arms has been perfectly good. The chief distress really has been in soreness on pressure ; thus, yesterday there was so much distress in the arms that to get relief he had to sit with them stretched out on jiillows. Early in the attack he noticed the presence of certain nodules on the legs and arms which would appear and disappear. Most of these have now gone except the ones which I describe below.
On the skin, one-third from the elbow of the right arm just along the margin of the ulna, there is a small subcutaneous fibroid
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nodale, very superflcial and very distinct. There have been others which have disappeared. There is no thickening of the ulnar nerve ; there are no trophic changes, no trace of sensitiveness in the muscles themselves, though there is much pain when the arm is resting in a certain position. The blood-vessels are not specially thickened. There is no soreness along the musculo-spiral nerve, no actual soreness on pressure on the muscles. On several occasions there has been a little redness. One of these small nodules was on the edge cf the left tibia, but has disappeared entirely. There is no atrophy of the muscles in the arms or legs ; a little tenderness along some of the cords of the brachial. Knee-jerks are present; perhaps a little plus. Pupils are of medium size, react well to light. No swellin.' of the joints ; no toplii in the ears ; he never ha had gout.
July 8, 1895.— He has not been so well. Has had much soreness, particularly in the arms and about the left wrist, where there has been subcutaneous redness and swelling. There was also tenderness. There is now on the extensor surface of the left arm midway between the elbow and wrist, a raised red region about 3x2 inches. The redness looks fading, but it is distinctly puflfy. It was a patch similar to this, but horizontal, which was on both ankles at the early period of the disease.
The subcutaneous fibroid nodule on the right arm has disappeared. There is one now on the inner surface of the left knee. This feels like a small shotty body beneath the skin. It was a little sensitive. There is another small nodule just on the inner surface of the patella.
The instep is distinctly swollen and red, and it is tender ^ustoutside the outer malleolus. There is a little superficial redness also just above the outer malleolus.
After the shooting pains which he had at first on the outer side of the left foot, there was some numbness. It feels a little numb to-day.
This was nncloubtedly a case of rheumatic neuritis. Had it not been for the presence of the subcutaneous nodules it would have been almost impossible to say that the condition was rheumatic, owing to the very indefinite nature of the joint symptoms. Their occurrence, however, shows somewhat conclusively that the neuritis was rheumatic in origin.
Case VIII. — Subcuianeous fibroid nodules in a case of arthritis deformans.
Mr. C, ajt. — , was admitted to the Johns Hopkins Hospital on September 12, 189.5, complaining of enlargement and deformity of the wrist, finger, knee and ankle juints, with pain in these situations.
A satisfactory history could not be obtained from the patient. There had been a history of gout in the family for several generations back.
The patient had his first attack of joint trouble 24 years ago. It commenced in the great toe joint.
The following note was dictated by Professor Osier :
Mucous membranes pale, face flushed, otherwise the patient looks well nourished.
The hands show very characteristic lesions of arthritis deformans.
Right hand : The right wrist is almost completely ankylosed ; there is thickening about the bases of the metacarpal bones, and the knuckles are large. The interossei muscles are wasted. There is fair mobility of the metacarpal joints. The fingers have a strong ulnar deflection. There is ankylosis of the 1st and middle nietacarpo-phahingeul joints, of the first interphalangeal joint of the index, middle anil little fiuL'ers, and of the distal joint of the ring and little fingers. No Heberden's nodes.
The fingers are thin, and the skin a little rough and somewhat discolored over tho joints. About the knuckles of the middle
finger, chiefly on the extensor tendon as it passes over the joint, are 4 or 5 subcutaneous fibroid nodules. One flat yellowish-looking nodule exists on the extensor tendon passing over the knuckle of the ring finger. The extensor muscles of the forearm are a little atrophied.
Left hand : Ankylosis of the wrist much less marked, as also is the ulnar deflection. Ankylosis not so marked in the fingers. In the little finger Heberden's nodes are extremely well developed, and the juints are ankylosed. Nodes are well developed in the index finger. Flat subcutaneous nodules are present on the extensor tendon of the middle finger. Radial thickening on both sides.
The knees are very much enlarged, particularly the right, which is very much rounded ; outlines of the patella are lost. Probably some exudation into the bursa. Patella not movable. Much less thickening about left knee ; patella movable.
There is very slight flexion in the knees, much more in the left than right.
The ankle joints are uniformly enlarged ; very slight mobility ; obtuse thickness over the tarsus.
No tophi in the ears.
Heart. — Apex beat neither visible nor palpable. Loud, rough systolic murmur at the apex, transmitted towards the axilla. At the base there is a soft systolic, not loud or rough. Second sound audible and not accentuated.
Case IX Chronic vegetative endocarditis tcith subcutaneous fibroid
nodules.
Dr. Osier has kindly given me the full notes of the following interesting case, which was seen in consultation with Dr. J. K. Mitchell, June 7, 1893. Only abstracts from the history will be given.
Martha S , aged 29, a native of Providence, R. I.
When 12 years of age patient had scarlet fever and rheumatism, evidently a severe attack, in which the doctors stated that her heart was affected. She gradually got better, but a year or two subsequently she had a second light attack.
About a year ago she began to have pains in the fingers, and some of the spots to be hereafter described appeared. Last summer she was at her home in Providence not at all well, having occasional attacks of pain in the feet and in the joints, with chilly feelings. About October she began to have more definite fever, preceded by marked chilly sensations, and she has been ill with occasional fever ever since, the temperature rising to 102° to 104°, sometimes with a definite chill. For the past month the temperature range has been from 97° to IOi°. The joints, and particularly the ankles at times, have been red, swollen and painful.
To-day the only complaint she has is of pain in the right ankle, which is a little swollen, and just in front of the inner malleolus, reddened. There is no enlargement of the smaller joints.
The apex beat of the heart is forcible, outside the normal position. There is no thrill. On auscultation there is a loud systolic murmur, rough in quality, propagated beyond the axilla. The sounds at the aortic cartilage are clear, and the pulmonary second is very much accentuated.
There is no enlargement of the spleen or liver.
One of the most remarkable features about the case istheappearance of painful spots in and beneath the skin. These are apparentl}- of three different characters: (a) reddened, elevated sjxits in various parts, resembling closely urticaria, and these appear and disappear. There were only two on the skin at the time of my visit ; (*) local spots of soreness in the skin from two to three lines in diameter, not elevated, usually as Dr. 3. K. Mitchell describes them. " pale pink, not elevated, not hard, exquisitely tender, and painful even without being touched"; (c) definite firm sulvutaneous nodules which have appeared and disappeared, and which are very sensitive to the touch. At the occasion of uiy visit only one of these was present beneath the skin about the eighth rib on the right side. It felt the size of a small pea, was movable and she winced on the slightest pressure.
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The diagnosis was maJe of a chronic vegetative endocarditiswith intermittent fever.
Literature.
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L>. Bar, Louis: Par., 1890, 1 pL 4to, No. 271, 64 pp.
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4. Bertoye: Lyon Med., 1887, LIV, pp. 179-184.
5. Besnier : Diet, encyclop. sc. m^d. (.■Vrt. Rhumat.), 1876, p. 504.
6. Birchard, A. D. : Cincinnati Lancet Clinic, 1890, N. S., XXIV, 684-G89.
7. Bourcy, P. : France medical de 1882, No. 5.
8. Bourcy, P. : Bull. Soc. Clin, de Par. (1881), 18S2, V, 287-291.
9. Brissaud : Revue de medecine, Par., 1885, V, 241-252.
10. Brocq and Troisier : Revue de medecine, 1881, p. 297.
11. Brocq : Journal de medecine de Paris, 1884, p. 466.
12. Brown, C. H. : Journal of Mental and Nervous Diseases, August, 1893.
13. Cavafy : Brit. Med. Journ., March 31st, 1883.
14. Cayley, W. : Clin. Soc. Trans., 1894.
15. Chauffard : Gaz. d. hop. de Toulouse, 1894, VIII, 225. 1(>. Cheadle, W. B. : Lancet, 1889, p. 871.
17. Cliodorowski: Th(>se, Paris, 1882.
18. Chuffard : The.se, Paris, 1886.
19. Coutts, J. A. : Illust. Med. News, Lond., 1889, III, 267-271.
20. Coutts, J. A. : Lancet, London, 1890, II, 873.
21. Davaine, J. A. : 4to, Paris, 1879.
22. Drewitt, F. D. : Brit. Med. Jour., March 31st, 1883.
23. Duckworth, Sir Dyce : Lancet, Dec, 1882, p. 943.
24. Duckwortli, Sir Dyce : Lancet, May 5, 1883, p. 778.
25. Duckworth, Sir Dyce : Pract., Lond., 1892, XLVIII, pp. 161-165.
26. Duckworth, Sir Dyce: Clin. Trans., Vol. XVI, p. 190.
27. Edge, A. M. : Brit. Med. Jour., 1884, Vol. I, 818.
28. Edge, A. M. : Brit. Med. Jour., 1885, Vol. I, p. 737.
29. Edge, A. M. : Brit. Med. Jour., Jan. 21st, 1893.
30. Edwards, W. A. : Univ. Med. Mag., Jan., 1890.
31. Eve : Br'it. Med. Jour., March 3l8t, 1883.
32. Fereol : These, Paris, 1879, 8vo.
33. Fowler, J. K. . (a) Trans. Clin. Soc, Lond., 1884, XVII, 65-67 ;
(b) Brit. Med. Jour., 1884, Vol. I, p. 167 ;
(c) Lancet, 1884, Vol. I, p. 115.
34. Fritz, C. : Union medical, Paris, 1884, 3 8., XXXVII, p. 69 ;
Bull, et mem. soc. m6d. d. hop. de Par., 1883-4, "2 s., XX, 227-229.
35. Gilly : -Marseille medical, 8th Sept.. 1887, p. 518.
36. Guyot : Bull, et Mem. d. hup. de Par., 1886, 3 s.. Ill, 68-72.
37. Hadden, W. B. : Clin. Soc. Trans., Vol. XXIII, 1890.
38. Hershman, C. F. : Internal. Med. Mag., Oct., 1894.
39. 40. 41. 42. 43. 44. 45. 46. 47.
48. 49. 50. 51. 52. .53. 54.
Hillier: Diseases of Children, 1868.
Hirschsprung: Jahrbuch fUr Kinderheilkunde, 1881, 16 B. HoVjbs, J. : Archives cliniqne de Bordeaux, No. 8, p 380. Honnorat, J. : Lyon medical, 1885, XLVIII, p. .561-563. Hutchinson, Mr.': Brit. Med. Jour., March 31st, 1883. Jaccoud : Traitr de pathologic interne, 1871, t. II, p. 546. Jordan, F. A. : Brit. Med. Jour., 1885, Vol. I, p. 889. Lailler: Bull, et mem. soc. d'hOjp. de Paris, 1886, 3 s.. Ill, p. 68. Lindmann, J. : Deutsche med. Wchnschr., Leipz., 1888, XIV, 519-524.
Loysel De La Billardiere, A.': These, Paris, 1889, No. 296. Mackenzie, Stephen: Brit. Med. Jour., March 31st, 1883. Mackenzie, Stephen : Clin. Trans , Vol. XVI, p. 188. Mackay, E. : Lancet, Jan. 20th, 1894. Mahomed, G. : Brit. Med. Jour., 1882, II, 827. Mahomed, G. : Brit. Med. Jour., March 3Ist, 1883. Meusnier: Congrcs de Blois, 1884. Meynet, M. : Lyon medical, 1875.
Middleton, G. S. : Glasg. Path, and Clin. Soc, 1886-91-92, III, 26.
Middleton, G. S. : Am. Jour. Med. Sc, Oct., 1887, Vol. 94, p. 433.
Mitchell, J. K. : Univ. Med. Mag., Vol. I, 1888-9, p. 161. Money, Angel : Brit. Med. Jour., March 31st, 1883. Money, Angel : Lancet, 1891, I, 510.
Nepven : Compt. rend. soc. de biol., Paris, 1890, 9 s., II, 328-331. Osier: On Chorea, 1894.
Parker, R. A. : Brit. Med. Jour., March Slst, 1883. Payne : Brit. Med. Jour., March 31st, 1883. Phillips, S. : Clin. Soc Trans., 1894. Pitt, G. N. : Clin. Soc. Trans., 1894.
Porter, F. E. : Bost. Med. and Surg. Jour , June 30th, 1886. Prior, J. : Miinchen. med. Wchnsch., 1887, XXXIV, .525-528. Rehn, H. : Verhandl. d.Cong. f. innere Med. Wiesb., 1885, IV, 296-298.
Rehn : Traits des maladies de I'enfance de Gerhardt. Reis, Max : " Ueber den rheumatismus nodosus," Bonn, 1890, C. Georgi, 37 p., 8vo.
Riembault: Loire med., St. Etienne, 1884, III, 148-1-52. Troisier and Brocq : Revue de medecine, 1881, I, p. 297. Troisier, E. : Progres myd., Paris, 1883, XI, 947-966. Troisier, E. : ProgrCs mod., Paris, 1884, XII, 3-5. Troisier, E. : Bull, et mem. soc. med. d. hop. de Paris (1883), 1884, 2 8., XX, pt. 2, 45-67.
Troisier, E. : Union mid., Paris, 1884, 3 s., XXXVII, 385, 393.
Wainer and Barlow : Trans. Internat. Med- Cong., Lond., 1881.
, West, S. : St. Barth. Hospl. Reports, Lond., 1886, XXII, 213 215. , Widal, F. : Gazette hebdomadaire, 1883, p. 825 et suiv.
CASES OF AMCEBIC DYSENTERY.
By Cunningham Wilson, M. I)., Birmingham, Alabama.
The following case.s of amndiic dysentery, occurring in my private practice, lack, in careful study, the hospital reports of 8uch cases. Two of them, however (cases 3 and 3), are of more than usual interest ou account of finding the amoebaj while examining the patients for other conditions. The first three cases falling into my hands at such short intervals of time led me to believe that this form of dysentery will be found to make up a large proportion of this disease in this climate. During 181(4, however, only one case came to my
notice, but in some suspicious cases I was unable to use the rectal tube to get the contents of the bowels.
The amcebn? did not differ iu any way, as far as I was able to see, from descriptions given by Councilman and Lafieur and from those I saw from a patient in Dr. Osier's clinic at Johns Hopkins Hospital. There were no symptoms of abscess of the liver in any of the cases.
Case 1. June 1, 1893. I saw for the first time B., white, male, aged forty-nine, married, of very large frame and
September-Octobbe, 1895.] JOHNS HOPKINS HOSPITAL BULLETIN.
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extremely emaciated. Has always lived in the South. About two years ago began to have frequent actions from bowels, consisting largely of mucus and blood. This condition has kept up with more or less severity since ; at the time of my visit was having from one to twenty stools daily. Microscojjic examination of a portion of the stool just passed showed numerous actively moving amcebce. Frequent examinations of the discharges during the next three weeks always showed the ama3bse. At this time he left the city. His condition with rectal injections, milk diet and other remedies improved very little.
Case 2. S., white, male, aged 30; locomotive engineer. In 1890 had an attack of dysentery which lasted him two weeks. Since then has had several similar attacks of less severity. August 15, 1893, came to me complaining of internal hemorrhoids, otherwise feeling well. Examination of rectum with speculum revealed two or three small hemorrhoids and higher up two superficial ulcers. Removing the speculum, a quantity of bloody mucus adhered to it. Placing a small portion of this under the microscope, active amcebag were found. On more careful inquiry it was found that he had beeii having frequent, small and painless bloody discharges from the bowels which he had taken as symptoms of hemorrhoids. He was advised to use rectal injections of quinine solution. A few days later he was attacked with a violent dysentery which confined him to his bed for three weeks. The amoebs were abundant in the dysenteric discharges. Ice-water injections with suppositories of iodoform and opium seemed to give him most relief. During the following winter he had another attack, but has remained well since.
Case 3. W., white, aged twenty-eight, single; telegraph operator. Was born in Ohio; has lived in Alabama three years. His first sickness was a rectal abscess two years ago, which resulted in an anal fistula. During the past year has
had several attacks of diarrhcea with considerable cramping in lower bowels. September 3, 1893, came to me to have an operation for cure of fistula. Examination showed a superficial fistula. On removing the speculum there was adhering to it a quantity of blood and mucus similar to what I had seen in Case 2. Microscopic examination showed numerous active amoebfe. Three days later he was attacked with a moderately severe dysentery which kept up for a week. The amffiba; were constantly found during the attack. His strength was considerably reduced and he remained in poor health until October 1, when he took a vacation East and soon regained his health, which has remained good since. Treatment during attack was cold water injections with iodoform and opium suppositories.
Case 4. P., white, male, Russian. Was seen a few hours before death, September 15, 1894. No history could be obtained. He was having frequent involuntary actions of mucus and blood from bowels. An autopsy was held four hours after death. Nothing of consequence was found in thorax except sclerotic changes in blood-vessels. In the abdomen the entire big gut was prominent, very much thickened and adherent to neighboring structures. The omentum had engrafted itself to the transverse and descending colon, at many points, preventing perforations. The gut was easily torn, tearing by its own weight when lifted. The mucous surface was an area of necrosis, indented with deep ragged ulcers, many of them just ready to break through. Examination of contents of the ulcers showed numerous active amceba?. Sections of the intestinal wall showed, in a marked degree, the hyaline degeneration described by Councilman and Lafleur (Johns Hopkins Hospital Reports, Vol. II), of muscular fibre as well as of the plastic material thrown around the intestine. Sections of the liver showed advanced cirrhosis. Chronic interstitial changes had taken place in the kidneys.
PROCEEDINGS OF SOCIETIES,
THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.
MeeUng of October 7, 1895.
NOTES ON NEW BOOKS.
BOOKS RECEIVED.
BULLETIN
OF
THE JOHNS HOPKINS HOSPITAL.
Vol. Vl.-Nos. 56-57.
BALTIMORE, NOVEMBER-DECEMBER, 1895.
+++
Contents
147
150
Bacillus Pyogenes Filiformis (nov. spec). By Simon FlexNER, M. D.,
A Clinical and Experimental Study of the so-called Oyster Schucker's Keratitis. By Robert L. Randolph, M.D.,
The Clinical Course of forty-seven Cases of Carcinoma of the Uterus subsequent to Hysterectomy. By W. W. Russell, M.D., 154
Notes on Some Cases of Angina treated with Behring's Antitoxine. By George Blujier, M. D., 158
Proceedings of Societies :
Hospital Medical Society,
Pyarthrosis — Discussion [Dr. Halsted] ; — A Case of Congenital Ptosis [Dr. Thomas] ; — Remarks [Dr. Barker].
Notes on New Books, --.
Books Received,
Notice, ------ Index to Volume VI, _ . .
167 168 168 168
BACILLUS PYOGENES FILIFORMIS (NOV. SPEC.).*
By Simon Flexnek, M. I)., Resident Pathologist, The Johns Flopkiiis Hospital ; Associate Professor of Pathology,
Johns Hopkins University.
[From the Puthologieal Laboratory of the Johns Hopkins University and Hospital.]
(Preliminary Communication.)
During the past winter a large healthy female rabhitof the stock of the laboratory gave birth to a litter of young, and about the fifth day following parturition, although it had not appeared ill, was found dead in its cage. Following the rule of the laboratory, which is to make autopsies upon all animals which die, this one was e-\amiued in the usual way. It is necessary to state that the young of this animal were found dead before the death of the mother occurred.
The animal bore its litter on March 13th or 14th, and was found dead on the morning of the 18th. The autopsy was performed in the afternoon of the 18th.
Tile body was well nourished ; there was no evidence of death from violence, the mammary glands were still large, and upon section a lactiferous fluid escaped from their cut surfaces. There was no excess of fluid in the peritoneal cavity, the layers of the serosa appearing normal except as is about to be mentioned.
The condition of the uterus especially arrested attention
- Read before the .Johns Hopkins Hospital Medical Society,
November 4, 1895.
upon the examination of the abdominal viscera. It was several times larger than the normal, although much smaller than the uterus of the rabbit at term, and presented a series of dilatations and contractions which, except for their irregular distribution, might have been mistaken for a pregnancy. This condition was, however, hardly to be considered under the circumstances, and indeed upon inspection the dilated pouches appeared thin and semi-trauslncent. and gave the impression of being quite empty. The serosa over the dilatations was injected ; the vessels of larger size being very prominent and turgidly filled with blood, the intervening tissue presenting a rosy hue. Both coruua of the uterus were similarly affected. Nothing abnormal was observed in connection with the ovaries. On opening the uterus after its removal with the vagina attached, the pallor of the mucous membrane contrasted with the injection of the serous coat. This pallor of the mucosa was of a peculiar opaque quality and unlike the appearance of the velvety membrjiue itself. On gently stroking the mucosa with a knife a thick, opaque material could be removed, which appeared to be only lightly adherent to the surface of the membrane. It was to the pres
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ence of this material that the peculiar opacity was due, and the exudate extended from the vagina throughout the entire estentof the uterus. In the dilatations before mentioned the mucous membrane was of extreme tenuity, and here, as might have been expected, the layer of opaque exudate was thinner than elsewhere. The impression was given that the dilatations were brought about by accumulations of a gas. After the removal of the exudate the underlying mucosa was found to be congested. The other organs of the peritoneal cavity apparently were normal.
The pleural cavities contained fluid which was not in large amount and of a transparent hajmoglobin-red color. The serosa itself was covered with a thick shaggy layer of a fibrin-like material. Both the parietal and visceral layers were covered with this material, which was very thick over the region of the diaphragm. The lungs were in part voluminous, in part collapsed, the expanded portions being of a firm consistence and apparently consolidated. The bronchi contained fibrinous plugs.
The pericardial sac contained a small amount of fluid between layers of a shaggy appearance, due to the presence of a fibrinous-looking exudate similar to that found covering the pleune. It was, however, thinner here than there.
The lymph glands of the body showed no especial enlargement and the other viscera no gross pathological changes.
BdderiologicaJ Examination. Cover-slips made fi;om the exudate in the vagina and uterus showed a surprisingly large number of organisms which were strikingly pleomorphic. These organisms form for the most part thread-like structures ; not a few, however, are much smaller. They vary from bits only a little larger than cocci to thread-like forms as long as the longest anthrax chains. At first sight there would appear to be several kinds of bacilli present ; but the appearance, in both large and small forms, of a striking irregularity of staining makes this improbable. Very few of the bacilli stain regularly, for the most part brightly staining spots appearing between unstained areas. An outer membrane always stains, enclosing the stained dots in a colorless ground. A closer study reveals the stained particles to occur w-ith much regularity, that is, they are about equidistant in the longer forms, where they arc best studied, and in general they are of the same size. The threads are not as a rule straight, but present delicate sinuous and wavy outlines. The short forms are straight with rounded ends. Among these organisms a large number of pus cells and a few larger cells with single vesicular nuclei were scattered. Although many pus cells were present in the exudate, yet from the appearance of the cover-slips no inconsiderable portion of it must have been furnished by the bacilli.
Cover-slips made from the pericardial and pleural exudates, as well as from the consolidated portions of the lungs, showed the same organisms. While they were very numerous in the cover-slips from these situations, they were not as abundant as in the uterus.
Aerobic cultures were made upon various media, Loeflfler's blood serum, sugar-agar, sugar-bouillon, plain agar and bouillon, the agar, urine and serum mixture; anaerobic cultures were made in plain and sugar-agar and bouillon as
well as upon blood serum in Buchner's jars and an atmosphere of hydrogen. All these kept in the thermostat for several days at 37° C. showed no growth whatever.
Fearing that it would not be possible to cultivate the organism upon the usual media, the pleural cavity of a second rabbit was inoculated by breaking up a speck of the pleural exudate from the first one in bouillon and injecting the suspension with a sterilized syringe, after making a small skin incision, into this cavity. This inoculation was positive in its results.
Subsequent experiments were conducted as in the previous one by transplanting small bits of the fibrinous material from the inflamed parts of previous animals, or of the fluid which was also present in the pleural cavities in the other animals. In this way the series was kept continuous and the bacilli alive.
Considerable variations were observed according as the inoculations were made into the pleural cavity, the peritoneal cavity, the subcutaneous tissues, beneath the dura mater, or directly into the circulation.
The inoculations were positive in all cases except a few in which they were made subcutaneously. The death of the animal occurred soonest when inoculation was made beneath the dura mater. A small portion of the skull was trephined, under the usual antiseptic precautious, and a drop of the jjleural fluid or a speck of the fibrinous exudate was introduced beneath this membrane, care being taken not to injure the brain. These animals, which quickly recovered from the effects of the operation, died on an average about twelvehours after the inoculation. The usual appearances were as follows: The external layer of the dura, excepting at the point of puncture, appeared quite normal; the internal layer was injected. Corresponding with the point of puncture, but smaller, a grayish-white area was visible, this being most marked in the case of the introduction of a bit of the fibrin, and doubtless consisted in part of the introduced exudate. The pia was distinctly reddened, the vessels being more prominent than normal, and the meshes of the pia contained a thin but otherwise distinctly turbid fluid. There were no pathological changes to be observed in the cortex of the brain, nor were any found in the ventricles.
Cover-slip preparations made from the point of inoculation showed, besides pus cells, a very large number of the typical bacilli. Similar preparations from the meninges at a distance from the point of inoculation also showed bacilli, but they were fewer in number, and among them more or less leucocytes with amphophilic granulations and polymorphous nuclei were scattered.
The pleural inoculations were followed by death, as before stated, in every instance, the death of the animal occurring upon the third or fourth day. The appearances presented at autopsy were for the most part an exact reproduction of those observed in the animal wliicli had succumbed to the natural disease. Upon the side of inoculation a thick grayishyellow shaggy membrane covered the pleural surfaces, being at times four or five millimeters in thickness. The pleural cavity contained several cubic centimeters of a clear haemoglobin-colored fluid besides, the lung for the most part being compressed. At times smaller or larger areas of lobular pneu
November-December, 1895.] JOHNS HOPKINS HOSPITAL BULLETIN.
149
monia would be present; and as a rule the inflammation was not limited to the serous membrane of the side of inoculation, but extended into the opposite pleural cavity and into the pericardial sac. However, in these situations the process was as a rule less intense, the solid exudate being less considerable, and in the case of the opposite pleural cavity sometimes entirely wanting. The superficial vessels, however, were injected and the serous surfaces of the affected membrane covered with a slimy material. In addition to this, the opposite i^leural cavity always contained a pink serum similar to that described upon the side of inoculation.
The study of the exudate upon the side of inoculation, as well as the fluid contained in the opposite pleural cavity and in the pericardium, showed the same organisms as had been introduced. They were most numerous upon the side of inoculation and in the solid portion of the exudate. So far as could be determined by the use of cover-slip preparations, they were absent from the blood and distant viscera.
The inoculation of the fluid from one of these pleural cavities into the peritoneum did not always succeed in causing the death of the animal. The periods of incubation in these cases, even when the inoculations were successful, were longer than in the previous ones, the animals affected often not dying in less than a week. The results of the peritoneal inoculations were to produce either a general sero-flbrinous peritonitis or a circumscribed fibrinous peritonitis. In several instances where the inoculations were made into the pleural cavity, an extension through the diaphragm with the productions of a localized pseudo-membranous inflammation over the liver was observed. The exudate in all these cases showed large numbers of typical bacilli upon microscopical examination.
In several instances the subcutaneous inoculation of the pleural fluid was successful. Larger and smaller areas of tissue were converted into a rigid fibrinous material in which bacilli were found in large numbers.
Perhaps the most interesting, certainly the most widespread, effects were obtained by the intravenous inoculation of the pleural fluid. The results were uniformly fatal, the animals all succumbing in from two to four days after inoculation. At autopsy abscesses were present in the viscera. These were generally miliary in size, although at times they were larger and spreading. Preferences were exhibited in reference to their localization, certain organs being entirely spared. The abscesses were never absent from the brain and heart muscle. They appeared occasionally in the liver, more rarely still in the voluntary muscles, never in the kidneys or the lungs.
The effects of the intravenous inoculations with respect to the points of localization of the bacilli were in part dcter
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mined by the local conditions; for example, the inoculation into non-pregnant female animals was not followed by the reappearance of the micro-organisms in any of the structures of the genital tract, whereas in the case of pregnant animals the inoculations were followed by the re-localization of the organisms and the inflammatory process in the pregnant uterus.
The appearances first described in the uterus of the animal dead of the natural disease indicated that an accumulation of gas had occurred in this structure. This appearance was again observed in the experimental disease in this situation, and also in several instances in which the inoculations were made into the subcutaneous tissue and in the pleural cavity, in the last instance the gas bubbles appearing in the inflamed mediastinal tissues.
Culthmtion Experiments. From time to time in the course of the transference of this organism from animal to animal, attempts were made to cultivate it. The repeated use of ordinary media in aerobic and anaerobic cultures failed as in the first instance. The use of more concentrated media, as for example five per cent, peptone in solid and fluid forms, also was without success. An attempt was now made to cultivate the organism upon the organs of a healthy rabbit, which were removed with all precautions and transferred to sterile test tubes. Only occasionally did one of these tubes show contamination. Those which were uncontaminated and had shown no growth for several days were inoculated with material from the experimental animals. For the first time a growth was obtained, not, however, upon all the organs. The growth was fairly vigorous upon the lungs, the heart aud the uterus, and perhaps upon the kidney ; no growth occurred either upon the spleen or liver. Transplantations from these growths were successful only to the extent of one or two subsequent generations. The best results were obtained by cultivating the organisms upon several one-third to one-half grown fcetuses obtained from the rabbit, upon which medium transplantations were successful through a series of six of these objects. The inoculations of animals from the sixth generation of the bacilli obtained in this way, either into the pleural cavity or into the circulation, were followed by positive results indistinguisiiable from those obtained by the use of the pleural fluid before mentioned.
Further facts concerning the morphology aud biology of this organism, such as the question of spore formation, thermal death point, the effect of drying, the length of vitality outside the body, as well as the pathological histology of the lesions caused by it, will be given when the full details of this study are published.
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150
JOHNS HOPKINS HOSPITAL BULLETIN.
[Nos. 56-57.
A CLINICAL AND EXPERIMENTAL STUDY OF THE SO-CALLED OYSTER SHUCKER'S KERATITIS.
By Kobert 1.. ItAsuoi.PH, ^1. 1).
The extent of the injury inducing the so-called oyster shucker's keratitis does not explain the violent reaction that follows. This fact seems to have impressed every ophthalmologist who has been brought into frequent contact with the disease. Cinders and small particles of steel or sand, when they lodge on the cornea, often remain in situation for several days without causing apparent infiltration of the surrounding tissue, and not infrequently does one meet with a case where a cinder has been imbedded in the cornea a considerable length of time without giving rise to anything but unpleasant subjective symptoms. The most common foreign bodies removed from the cornea are the filings or chippiugs of iron or copper, or particles of emery, sand and cinders. It is rare that we see an area of infiltration about the foreign body, and when this latter condition exists it usually means that the foreign substance was infected with pathogenic bacteria, or by its continued presence and consequent irritation has brought about conditions favoring the invasion and growth of microorganisms. When we consider the remarkable resources of the eye for nullifying the effects of pathogenic bacteria we may safely say that a foreign body of the nature just mentioned, when it lodges in the cornea, will as a general rule give rise to an appreciable keratitis only after it has remained in situation for a number of days.
What is known as oyster shucker's keratitis is distinctly a traumatic affection, due to an injury from a particle of the oyster shell. The disease is chiefly remarkable for the rapidity with which an area of infiltration appears at the site of the wound, in marked contrast to the history of wounds by other kinds of foreign bodies of the same size and in tlie same location.
The existing evidence indicates that oyster shucker's keratitis is found more frequently in ^klaryland than in any other part of this country. Dr. Jas. A. Spalding, of Portland, Me., writes me that the affection is practically unknown in that part of the United States, and the same Ciui be said of the disease in Charleston, S. C, from information kindly furnished me by Dr. Kollock of that city. The reports of the New York and Philadelphia eye hospitals contain now and tlien a few cases, but Baltimore seems to carry off the palm. In New Orleans the disease as such appears to be unknown. The reports of the eye hospitals in Baltimore contain the records of several hundred cases during the past few years.f The frequency of the disease in Maryland may be explained by the fact that the oyster industry is a more extensive one in that state than it is anywhere else in the world. Cases of the disease do occur no doubt in New Orleans and Portland, Me., 80 that probably latitude has nothing to do with determining
•Read before the thirty-firat annual meeting of the American Ophthalmological Society, in New Lonilon, Conn., July 17 and 18, 1895.
f I have been informed by one of tlie staff of the Presbyterian Eye an<l Ear Hospital that during the past three months twentyfour cases have been treated at that hospital.
its existence, nor is there any reason for supposing that the keratitis is to be traced to some organic or inorganic property peculiar to the oyster shell of the Chesapeake Bay.
Baltimore is the greatest oyster market in this country, and, according to Ingersoll ("The Oyster Industry," by Ernest Ingersoll, Tenth Census of the United States, Washington, 1881), there are at least six thousand shuckers in Maryland, and most of these are found in the shucking houses of Baltimore. In many of the northern cities, as for instance in Portland, Boston and New York, oysters are received in great quantities that have been shucked in Baltimore, so that oyster shucking in those cities evidently does not exist as a trade to the extent that it does in Baltimore. The magnitude, then, of the oyster industry in this city may be said to account for the frequency of oyster shucker's keratitis.
In a large number of the cases reported here the oyster shuckers had been plying their trade for many years and had been struck for the first time. In two cases the men had shucked for eighteen years without being struck, and it is surprising to note the fact that in none of the sixty-five cases reported M'ere there any novices (new hands). It will be seen then that it is possible to shuck oysters for many years and still to escape injury from a particle of shell, and that the great majority of oyster shuckers escape altogether. Hence we cannot regard the disease as a very common one. It is more than probable that long familiarity with the work breeds contempt of its dangers, and this may explain why in neariy all cases it is the veteran who is wounded and not the recruit. It is very much the same kind of danger that surrounds the mechanic at the emery-wheel. Possibly the danger is a little greater in the case of the oyster shucker. Considering then the number of oyster shuckers in jMaryland and the quantity of work done, it may be said that the disease is of exceptional occurrence.
Causes : As I have said, the disease is distinctly of traumatic origin ; that is, a minute particle of the oyster shell is violently chipped off by the hammer* that is used in the shucking process, and it flies into the eye. The particle is generally too small and too light to penetrate toany distance into the cornea. Large pieces, however, are sometimes detached and are driven through the entire thickness of the cornea, and when such a thing happens loss of the eye usually results. This occurrence is happily rare. I'nlike other foreign bodies that lodge in the cornea, the particle of shell can seldom be detected. Thfs I think is due to the fact that in the rapid infiltration that takes place the particle of shell is thrown off. It is no
•The use of the hammer to break off the edge of the shell before introducing the knife-blade constitutes the chief element of danger in oyster shucking as practiced here in Maryland. In other sections, as for instance in the far South and down East, the shucker dispenses with the hammer and sticks in the point of the knife at once in order to pry open the shell. This no doubt explains why the disease is seldom seen in the portions of the country just mentioned.
November-Decejiber, 1895.] JOHNS HOPKINS HOSPITAL BULLETIN.
L51
uncommon thing to see a particle of steel that is surrounded by a necrotic area drop out at the slightest touch, and sometimes we meet with these small points of infiltration where no foreign body can be detected, it evidently having been dislodged or thrown off in the suppurative process. In two or three instances I have succeeded in removing from the centre of one of these areas of infiltration a small jjarticle of what was undoubtedly a piece of shell. My friend, Dr. B. W. Goldsborough, who lives in Cambridge, Md., one of the smaller oyster shucking centres, tells me that he has more than once removed small particles of shell from these infiltrated areas. No doubt in many cases the piece of shell simply strikes and wounds the cornea without lodging in it. The superficial nature of the injury readily explains why the particle of shell would be apt to drop out as soon as infiltration began.
Symptoms: The photophobia in oyster shucker's keratitis is marked. The patient tells us that he has a defined sensation of having been struck in the eye. This sensation is not usually followed by pain until some hours later. Frequently the exposure to artificial light, as for instance the lighting of the gas or lamp the evening of the same day, will mark the time when the unpleasant symptoms begin. From now on the pain is usually intense, and the clinical symptoms resemble those of phlyctenular keratitis somewhat intensified.
In an article which appeared in the Virginia 3Iedii:al Montlihi about fifteen years ago* — which article, by the way, is the only publication known to me on this subject — the writer states that the position of the ulcer is a constant one, that it is always found in one place, and this is the centre of tlie cornea. The most exposed part of the cornea is the point that is usually struck, and as this part represents an area through which the visual line is passing at the time, and as the visual line always passes through the cornea somewhere near the centre, the location of the wound will be here, and for no other reason, though this explanation does not seem to have occurred to the writer of the article referred to, other reasons being given by that writer for the location of tlie keratitis. It may be added that this location of the ulcer is not an invariable one, for I have frequently noticed a peripheral situation.
There is usually more or less circumcorneal liypern'mia. The ulcer is very white, whiter than otiier corneal ulcers. 1 have never seen such an ulcer with blood-vessels running to it, and its size no doubt is dependent more or less upon the size of the particle of shell. The ulcer is sharply circumscribed as to its borders, which, instead of fading off gradually into the adjacent tissue, will be seen to lie adjacent to perfectly transparent cornea. Such an ulcer suggests more strongly a chemical than a parasitic origin. The ulcer does not show the same tendency to spread as do other corneal ulcers, and when the keratitis assumes a diffuse character it is probably an evidence that bacteria have invaded the tissue at this point. Such complications do occur. I have seen such an ulcer remain absolutely localized for two or tliree weeks withoiit any apparent deiiarture from its origiiuil liorders. On
- Oyater Sluicker'a Coineitis, by W. J. Minowell, M. D., Va.
Med. Month., Vol. V, page 883.
this account the prognosis is favorable, though this is largely governed by the size and depth of the wound. A perforating wound of the cornea or a wound involving a large area is usually followed by loss of the eye, and this is especially true when the former condition is present.
Treatment : The yellow salve has proved useless in our hands. The galvauo-cautery was used in a certain number of cases, but it did not seem to exercise any specific influence for good, and the same can be said of eserine. A compress bandage and a mild sublimate solution {f^^ used every four hours, together with an occasional drop of a solution of atropia — 1 per cent. — have given the best results. To this treatment the keratitis responds promptly, and in a week or ten days the subjective phenomena have been so ameliorated that the sliucker can resume work. The opacity can be detected by oblique illumination and is permanent. In several cases where the shuckers had been struck more than once, I found the old nebula?.
The striking point in these cases is the rapidity with which an area of infiltration makes its appearance at the site of the injury. These areas range in size from a pin's head to twice these dimensions, and even larger. The condition differs so entirely from what we are accustomed to see from injuries caused by other kinds of minute foreign bodies that it has occurred to me that the oyster shucker's keratitis might be due to some specific micro-organism. With this idea in view, I made microscopical examinations and inoculations on culture media, using chiefly nutrient agar, from sixty-five cases of oyster shucker's keratitis, of which the following fifteen cases may be taken as a fair sample of wliat the bacteriological examinations disclosed. In making inoculations a sterilized dropper and cocain solution were used for anassthetizing the cornea. The point of the platinum needle was well forced into the necrosed tissue, and in nearly all cases small particles of the wall of the ulcer were brought away and carried into the agar tube. In every case Esmarch tubes Avere uuule. which were promptly placed in the thermostat.
F. II., struck in left eye three clays ago. Central ulcer. Pain anil photophobia intense. There was nothing definite in the coverslips, and after twenty-four hours there was no growth on the agar.
J. R., struck in right eye with particle of shell yesterday. Large ulcer and marked area of infiltration. Eye very painful. Inoculations into three agar tubes. Two cover slips were made, and one stained with methylene blue and the other with gentian violet. In both cover-slips small micrococci were to be seen, occurring as diplococci. In tube A there was a diffuse growth, and at some jioints the colonies looked round and fiat, and an examination of several of the colonies showed the same organism, a short bacillus. There was no growth in tube B (inoculated from J). In a third tube where the inoculation was made directly from the ulcer there was an abundant growth of what was evidently an impurity.
J. H .struck in left eye three weeks ago. At the present time there ia a violent ker.ito-iritis ; the pupil being contracted and pus in anterior chamber. Two ulcers on the cornea. Cover slips from the ulcer showed nothing. In lube -•! there was a round, large and slightly iritlescent colony with reddish centre and yellow halo, which was the only colony in this tube. This turned out to be an enormous micrococcus. In tube B the agar was dotted with a fine growth, the colonies being very numerous and revealing under
152
JOHNS HOPKINS HOSPITAL BULLETIN.
[Kos. 56-51
the microscope bacilli : :..:. l varieties. The inoculations
were made into both tubes directly from the ulcer.
P. S. , large ulcer in centre of left cornea from an injury received yesterday. Cover-slips showed nothing definite. In tube A there was a vigorous growth of several varieties of bacteria. In tube i> (inoculated from A) there were two kinds of bacilli, one staining very deeply and having rounded ends, and the other bacillus being more slender and having sharply cutends. Both these bacilli were present in tube A. Tube 6^ contained nothing.
A. G., struck in left eye yesterday. Small central ulcer. Coverslips negative. In tube A after twenty-four hours there was a small round white colony that turned out to be the staphylococcus pyogenes albus. There was no growth in tubes B and C (representing the first and second dilutions of tube A).
W. H. W., struck in left eye yesterday. Minute ulcer on the nasal side of the centre of the cornea. Cover-slipsshowed nothing. Tubes A and B contained numbers of small white colonies scattered over the surface of the agar, and examination showed them to be bacteria of various kinds and shapes. {B was inoculated from -4.) Tube C was inoculated direct from the eye and contained two colonies of a long slender bacillus.
R. L., left eye, small central ulcer. Was struck yesterday. Cover-slips vague. Tube B inoculated from A contained a bacillus and large micrococcus. Tube C contained nothing.
T. W., struck yesterday. Central ulcer. Pain intense. Struck for the first time, though he has shucked oysters for fifteen years. Cover-slips and cultures negative.
C. L., struck in right eye yesterday. Large ulcer somewhat below the equator of the cornea. The staphylococcus aureus was found in this case. .
G. ,T., struck in left eye six days ago. Small ulcer on periphery of the cornea. On the second day tube A was found to be dotted with small white colonies which turned out to be a short bacillus. This bacillus was also found in tube B. Nothing grew in tube C.
G. B., struck two days ago, and pain did not come on till he went home that evening and faced the lighted lamps in his house. The staphylococcus aureus and two varieties of bacilli were found in the agar, one a short heavy bacillus and the other a short slender bacillus.
J. B., struck three days ago in the left eye. Small central ulcer. .Small colonies of two kinds of bacteria in tube i) (inoculated from A). One of these was the staphylococcus aureus and the other \ias a large bacillus.
A. S., struck in right eye three days ago. Small ulcer nearly central. Struck in same eye a year ago. Has been shucking for eighteen years. Cover-slips vague, but in tube C there grew the staphylococcus albus and a bacillus. Three tubes made, tube C being second dilution of tube A.
F. R., struck three days ago in the left eye. Central ulcer. There was nothing on the cover-slips, and in l)oth tubes A and B there was a large stumpy bacillus. B was inoculated from -1.
W. J., struck in right eye yesterday. Large central ulcer. One of the cover-slips showed a large micrococcus that also was found in tube B. This tube was inoculated from A.
In eleven cases out of the si.xty-five there was absolutely no growth on the agar. This is not surprising when we consider the very small surface or area from which the inoculations were made. I took particular care never to touch any part of the cornea but the ulcer, and as this always occupies a very prominent position on the cornea it is likely that most bacteria would be swept off into the conjunctival sac by the constant movements of the lids. In thirty-nine cases the bacteria were of various kinds, and there were no two cases presenting the same bacteriological conditions. As a rule bacilli were the predominating organisms, and usually they were
large and coarse. In three of the fifteen cases given in full I found the same bacillus, about the size of the bacillus subtills, possibly somewhat shorter. I made a suspension of this organism in sterilized water and injected a few drops into the cornea and conjunctiva of a rabbit's eye, but scarcely any reaction followed. In several of the cases where there appeared to be some similarity between the organisms 1 tried the effect of injecting a suspension of the organism into the cornea, but always with negative results. In five cases the staphylococcus pyogenes aureus or albus w'as found. The injection of a suspension of this organism into the cornea was followed by suppuration, a thing, of course, to be expected. Inasmuch as the pyogenic staphylococci are found in several other external diseases of the eye, and even in the normal conjunctival culde-sac, to say nothing of their association with inflammation in other parts of the body, and moreover the fact that they were found in only five cases out of sixty-five, we are justified in the conclusion that the pus organisms had nothing specifically to do w'ith the inflammation in those cases where they were discovered.
Were oyster sbucker's keratitis a parasitic disease, certainly its specific organism, if recognizable by our present means of investigation, would have been found in several of the cases; but, as I have said, in only three cases did I find the same organism present, and the experiments with this organism seemed to show that it was possessed of slight, if any, pathogenic properties. It may be added that being once struck did not produce immunity, as there were several shnckers among the sixty-five who had been wounded twice in the same eye.
Is the disease of chemical origin? is there an)' chemical substance in the juice or shell that produces this immediate and intense reaction in the human cornea? To test this hyj)othesis I obtained about an ounce of the oyster juice, to which I added about a teaspoonful of the chippiugs from the shell and then passed this mixture through a Pasteur filter. I always made the oyster shucker open the oyster into a vessel so that I could obtain the juice fresh. This fluid after being filtered was injected from a sterilized hypodermic syringe into the cornea and conjunctiva of a rabbit's eye. Fifteen experiments of this character were made and the result in every case was negative, a fact that goes to show that in so far as the rabbit's cornea is concerned the juice of the oyster manifests no pathogenic effect when injected into that part of the eye.* In the first case I obtained a beautiful kerato-iritis in one eye, and in the other eye an ulcer not unlike the ulcer produced by the oyster shell. On examining the filtrate I found that it contained two varieties of bacteria — in other words, that it was infected. The injection, though, of these bacteria (both were bacilli) into the cornea of the rabbit was in no instance followed by a keratitis, so that the iullammation in the first case must have been due to some organism not found in the oyster. In the other fourteen cases I obtained a filtrate free from micro-organisms, and this filtrate was shown to possess no pathogenic properties when injected into the cornea of a rabbit.
• It may be well to state that in only one or two series of experiments did I use the same filtrate. Fresh juice was obtained and filtered for every experiment.
November-December, 1895.] JOHNS HOPKINS HOSPITAL BULLETIN.
153
The bacteriological study of these cases would seem to indicate that the so-called oyster shucker's keratitis is uot of parasitic origin. A number of experiments with the oyster juice after the latter has been freed of its living organisms goes to show that the juice of the oyster probably has nothing to do with the causation of the keratitis seen among oyster shuckers, and furthermore that the injection of this juice, even as much as a syringeful, under the skin of a rabbit was in no case followed by inflammation. Nor when the unfiltered juice was injected into the cornea was it followed by any irritating effect. It remained to be seen whether there was any chemical ingredient in the shell capable of calling forth this inflammation.
Several fresh oysters were procured and the edges were chipped off and ground up fine. The edge of the shell was selected, as it is this part that is chipped off by the shucker. These particles were then sterilized in a test tube. The heat did not seem to alter the size of the particles. The reaction of this substance was decidedly alkaline. I made a very small wound in the cornea of a rabbit with a cataract knife and rubbed in gently with a platinum needle a few particles of the powder. This experiment was performed eighteen times and in every case I succeeded in getting a well defined ulcer. The ulcer was accompanied with little or no circumcorneal injection, and its edges were sharply cut and separated from the healthy cornea. These ex])eriments show beyond a doubt that there is something in the oyster shell that wlien introduced into the cornea will produce keratitis.
It is difficult to imitate successfully all the conditions connected with a foreign body in the cornea. In the first place, the size of the foreign body is problematical, and the most difficult thing to imitate is the manner and force with which it strikes the cornea. I thought that it would be possible to approach this latter condition by using what the boys call a blow-gun or spit-blower. It was seldom that I succeeded in blowing the particles of shell with force sufficient to drive them into the cornea. Twelve experiments of the following character were performed. One long blower was loaded with cinders from a locomotive smoke-box, and another blower was loaded with particles of oyster shells. Both the cinders and shells were sterilized. At a distance of six inches from the cornea the load was blown into the latter. In a few cases a cinder remained sticking in the cornea, but in only one case did a particle of shell stick ; the particles of shell were too fine to be blown with force sufficient to make them lodge on the cornea. It was noticeable, though, that the reaction was more or less intense in the eye into which the shells had been blown, while there was practically no reaction in the eyes into which the cinders had been blown. In the case of the eyes where the shell was used, redness of the conjunctiva and increased secretion were seen, while in the other class of cases the conjunctiva renuiined normal. 'I'he reason that 1 failed to get an ulcer was that I never succeeded in wounding the cornea to any extent.
It could hardly be expected that the reaction in the case of a rabbit's cornea would be as intense as that following similar injuries in man. I have always been impressed with the promptness with which injuries to the ej'es of dogs and rab
bits heal. Injuries that, in the case of human beings, necessitate long and careful treatment, get well readily in rabbits
and dogs. Spontaneous affections of the rabbit's conjunctiva
are comparatively rare. This is not the case to the same extent
with dogs, which, like man, are not infrequently seen with eye
affections. The tissues, too, of a rabbit's eye are certainly
more resistant to infected wounds than those of man. This
fact I have demonstrated elsewhere again and again. It is
not likely then that we would get a keratitis in a rabbit that
resembled exactly what we are accustomed to see in the oyster
shucker. The keratitis in the shucker would be more intense
in its clinical history, simj)ly because it is the human cornea
that is affected; this intensity being due perhaps to the frequent presence in the conjunctival sac of pathogenic bacteria,
and to the feebler resisting powers of the tissues.
It is reasonable to suppose then that any agent that will produce an ulcer in a rabbit's cornea will certainly have the same effect on the human cornea. It has been shown that, with the exception of the pus organisms, none of the organisms found in the sixty-five cases of oystgr shucker's keratitis produced keratitis when injected into the cornea, that is to say, there was no apparent infiltration of the cornea at the point of injection ; and this, added to the fact that no one organism was found constantly present, inclines one to the opinion that the disease is probably not of bacterial origin — this in the light of our present bacteriological knowledge. It has been shown that the oyster shell contains an inorganic material that does produce keratitis when introduced into the corneal tissue.
The analysis of Chatin and iluntz* shows that the shell of the oyster contains considerably over 90 per cent, of calcium carbonate. The analyses show that carbonic acid held in combination wdth calcium and magnesium is present to the extent of 44 to 48 per cent., and that calcium oxide varies from 49 to 53.7 per cent., and magnesium oxide from 0.4 to 0.5 per cent. The tables further show that sulphates, phosphates, silicates, fluorides, bromides and iodides are present, the sulphates forming about IJ per cent., the phosphates ^'^ per cent, and less, the silicates 3 to 3 per cent, and more, the fluorides a few hundredths of 1 per cent, the bromides and iodides some thousandths only of 1 per cent. The bases corresponding are calcium, magnesium, iron and manganese. Organic matter is present to the extent of ] per cent., and remains in the form of a thin membrane or network when the mineral matters are dissolved out of the shell with the help of acids. It will be seen then that the carbonate of lime forms nearly all of the oyster shell.
I obtained some pure carbonate of lime ^^uot the chalk such as is furnished by the druggist), and after making a sterilized wound of the cornea, powdered some of the lime that had been previously sterilized, between the lips of the wound, and in every iust^mce I succeeded in getting an appreciable keratitis. This experiment was repeated with pcf^itive results a number of times. It would seem then that the carbonate of lime is iu itself sufficiently irritating to call forth au iufiammation of the cornea under certain conditions.
•Analyse des cociuilles d'Huitres. par MM. .\. Chatin et A. Miintz, Comptes Rendus, t. CXX, 53.
154
JOHNS HOPKINS HOSPITAL BULLETIN.
[Nos. 56-57.
In this cuMiiL'Liiuii it is interesting to note the fact that on the Eastern Shore of ilaryland, in the hitter part of September and during October, when the winds are very high and the roads dusty, a form of ophthalmia is very common, which is attributed to the fine particles of oyster shell dust that fill the air and get into the eyes of those who drive along the roads. The roads in that section are for the most part shell roads. The ophthalmia is characterized by great redness of the conjunctiva and profuse secretion. Not infrequently both eyes are affected, and it is a very painful affection. I am indebted to Dr. B. W. Goldsborough of Cambridge for information on the subject of this interesting eye disease, which he tells me is often seen in his section of the country at certain seasons. This certainly shows that the oyster shell possesses irritating qualities. Accounts are contradictory as to the irritating effect of the dust on a well-known shell road in the vicinity of Baltimore.
It has been suggested that the mud which covers the oyster probably flies into the eye and causes the trouble. Any one who has visited an oyster shucking establishment will be struck at once with the appearance of the shuckers. Their hats, faces and the upper portions of the body are peppered with fine particles of mud, and I have been told over and over again that the mud frequently flies into the eyes, but other than a little temporary burning no inconvenience follows. The face is often the seat of hundreds of little poinds where a drop of mud has struck and hardened. I am sure that were the injury inflicted in this manner we would meet with the disease far oftener, in fact oyster shuckers keratitis would be a very common affection, but it has been shown that the disease is of exceptional occurrence.
As to any other ingredient of the oyster shell playing a role in the production of the keratitis I am unable to give any evidence at this time. Positive evidence exists to show that the carbonate of lime possesses properties irritating enough to produce keratitis in the cornea of rabbits and dogs, a keratitis of a sluggish character. And though no typical picture of oyster shucker's keratitis was obtained in these animals, it is highly probable that the peculiar asjfect of the disease as seen in man is due to conditions belonging to the human eye alone, conditions which help to intensify the process. It is more than likely that some one or more of the other chemical ingredients of the shell may play a part in the etiology of the keratitis. From the analysis of Chatin and
Muntz it is evident that the oyster shell contains ingredients besides the carbonate of lime which might be irritating to the cornea and conjunctiva.
Conclusions.
1. Oyster shucker's keratitis may be defined as a traumatic keratitis where the injury is produced by a particle of the oyster shell.
3. The disease is chiefly remarkable for the rapidity with which the cornea undergoes necrosis at the site of the injury, this area of necrosis being usually very small, owing no doubt to the small size of the foreign body. Small foreign bodies of copper, steel and sand usually produce no appreciable keratitis; and even when they lodge in the cornea, commonly reqnire several days to cause a noticeable inflammation. On the other hand, the oyster shucker presents a marked infiltration of the cornea at the point of injury within twenty-four hours after the accident.
3. This decided reaction on the part of the cornea makes the injury a peculiarly dangerous one when a large area is wounded, or when entrance has been made into the anterior chamber, such conditions in my experience being invariably followed by loss of the eye through panophthalmitis. How often do we see the cornea injured in the same degree by other kinds of foreign bodies and still the vision not entirely destroyed.
4. Bacteriological investigations failed to discover any specific organism, nor did any of the organisms obtained from cases of oyster shucker's keratitis manifest any pathogenic properties when introduced into the corneae of rabbits, with the exception of the pyogenic cocci. It is not likely then that the disease is of parasitic origin.
5. The carbonate of lime, of which the oyster shell is almost entirely composed, was found to possess qualities irritating enough to call forth a keratitis when introduced into the cornea of a rabbit, and it is more than probable that several other chemical ingredients of the shell w-ould be more or less irritating to the cornea.
6. It is certain that bacteria always play apart in traumatic keratitis, but it is evident that in this variety of traumatic keratitis the cornea is rendered especially susceptible to the effects of micro-organisms, by the irritating chemical ingredients of the oyster shell, notably the carbonate of lime.
THE CLINICAL COURSE OF FORTY-SEVEN CASES OF CARCINOMA OF THE UTERUS
SUBSEQUENT TO HYSTERECTOMY.
By W. W. EussELL, M. D., Associate in Gynecology. {Read before the Johns llopkins Medical Society, Noremher 4, 1895.)
The doubts which have existed as to the ultimate value of complete extirpation of the uterus for carcinomatous growths can be set aside with certainty. From the statistical reports of many operators we are now justified in claiming the possibility of cure in a certain number of cases by removal of the uterus, or a relief from distressing symptoms for months and even years. We obtain then by snch a procedure either a cure or a palliative effect, very often anticijiating a cure where we obtain only cessation for a variable period of the local discharges, hemorrhages and pain.
It is connnonly accepted that these patients live usually not over two years after the appearance of the first local signs.
If we are able theu to free tliem from this terrible affliction
for a louger time than this, even though recurrence does
result in the end, are we not justified iu the jirocedure? The
indication for operation is to obtain a cure, although ultimately there may be only temporary relief.
Our results clearly illustrate this fact, as sixteen of the twenty-one cases still living have passed the limit of two years and are enjoying good health — a period of exemption well worth the trial.
The following forty-seven cases of hysterectomy for carcinoma of the uterus include all those operated upon by Dr. Kelly and myself since the opening of the Gynecological wards in October, 1889, and in Dr. Kelly's private practice up to October, 189.5, thus giving a time limit of from one to five years.
Many of these cases we have seen personally within the past three months, and where they lived at a distance we have obtained our information by writing to the local consultant or to the patients themselves.
Vaginal hysterectomy has been employed iu forty cases, abdominal in four, and the combined operation in three cases.
Grouping them all under one head the results are as follows :
Death from primary effect of operation 5 = 10 per cent.
Patients still living 21 = -ll "
Patients died with recurrence IG = 34 "
Patients not heard from 4=8 "
Died from heart lesion. 1= 2 "
Three of the deaths immediately following the oi^eration were due to peritonitis and two to ligation of the ureters.
Kecurreuce and death took place in the sixteen cases within eighteen months, but the prognosis in eight of these at the time of operation was unfavorable.
One patient of the twenty-one still living was operated upon nearly five years ago for extensive disease springing from the cervix. She presented herself in perfect health about every six months for examination, but we were never able to find any return of the trouble locally. About sixteen months ago there appeared in the left side of the neck above the clavicle a nodule, to which she called our attention. Since then other glands in this region, on the ojiposite side of the neck and in the axillaa, have become similarly affected, some of which have broken down and discharged externally. She is at present in a critical condition. As her home is at a considerable distance, we are compelled to accept this as a metastatic manifestation.
Two cases died within four months after the uterus was removed. One had at time of operation such extensive infiltration on either side of the cervix that the case was considered hopeless. The uterus in the second case was found during the operation converted into a friable carcinomatous mass adherent in every direction to the bowels, so that complete enucleation was impossible.
Carcinoma of the breast developed and was removed in two cases several months after the uterus was extirpated. One of these died of a pre-existing heart lesion without any evidence of a local return, and the other is at present also free from
any pelvic trouble, but the carcinoma has again appeared in the breast.
The Fallopian tube prolapsed iu three cases in which it had not been removed, and during the healing of the vaginal incision was caught so that it protruded into the vagina, greatly reddened and swollen. These upon examination made us suspicious that there had been a return of the disease, but the microscope proved their true character. Two of these patients are still in good health ; the third died from a recurrence.
Another patient returned a year after operation with a note from her physician telling me that he had discovered a mass in the vaginal vault which he believed to be of a malignant character. There had been associated with it a profuse vaginal discharge, and occasionally some bleeding. This mass proved to be a large silk ligature which had been left on the broad ligament and had become imbedded in the granulation tissue. Since the removal of the ligature the patient has been absolutely well.
The most interesting of these cases is a patient who presented herself three mouths after vaginal hysterectomy for carcinoma of the cervix, with a fungus-like growth arising in the vaginal vault along the scar resulting from the operation. Dr. Kelly dissected the mass carefully out and thoroughly cauterized the surrounding area. This took place two and a half years ago, and the patient at present continues to be in excellent health.
Local return occurred in all the cases terminating fatallv, but in none could we elicit any history of metastatic growths in other parts of the body, the single exception being the one case above cited where the patient is still living.
Pneumonia was the cause of death in one instance thirteen mouths after the operation ; here there was an extensive malignant ulcerated area in the vaginal vault, which had appeared a few mouths after she left our care.
Adeno-carcinoma, body of the uterus 9 cases.
Carcinoma, cervix 38 "
KesuUs of hysterectomy for carcinoma of the body:
Patients still living 7 = 77 per cent,
•' died recurrence, operation incomplete 1 = 11
" died primary effect of operation 1 = 11
No. cases still living, 5 yrs. elapsed 1
'^ 3 " •• •• 2
" " 2 " " . . 2
" 1 " " 2
The uterus was removed by supravaginal amputation in three cases. An ordinary vaginal hysterectomy was performed in the remaining six. Kecurrcnce has taken place therefore only in the case where the operation was not completed.
In some of the cases the growth had penetrated the w.nlls of the uterus so that it could be seen just beneath the peritoneal covering, and yet no evidence of involvement of the lymphatics or the parametrium could l>e detected. The three cases in which the cervix was left have proved as satisfactory ivs those iu which the whole uterus was removed.
156
JOHNS HOPKINS HOSPITAL BULLETIN.
[Nos. 56-57.
Kesults in hysterectomy for carcinoma of the cervix :
Patients died from primary effect of the
operation 4 = 10 per cent.
Patients still living 14 = 3G "
Patients died with recurrence 15 = 38 "
Patients not heard from 4 = 10 "
Operations over 4 years ago and patients still living 3
3 " " " 4
" 2 " " " 4
" 1 " " " 3
The uterus was removed in four cases by the combined method. One of these died a few days after the operation from ligation of the ureter, and another in which the disease was associated with pregnancy died several months after operation with a recurrence in the vagina. The remaining two are reported as free from any suspicious signs.
Vaginal hysterectomy was employed in thirty-four cases, three of which died from the operation, and fourteen afterwards from the original disease.
The four cases not accounted for up to the present time were considered at the time of operation favorable for cure. Two of them I have since seen, one two years after operation and the other one year, and both at that time showed no evidence of ulceration or induration by vaginal examination.
The fourteen women who are still living do not giv6 symptoms pointing to metastasis or local recurrence, except the one mentioned with the nodules in the neck and axilla. This single case proves that even after a lapse of four years we are not justified in claiming a cure. We cannot definitely at present fix a period of years through which a patient must live in order to pass the danger limit. Fritsch, Schauta, Hofmeier, Leopold and Boldt have followed their cases from
five to seven years after the removal of the uterus, and even as late as seven years there continues to be a fall in the percent, of cures.
Olshausen, Schauta and Fritsch report over 47 per cent, without recurrence after a lapse of two years. It is a striking fact that in our cases thus far, all recurrences but one have taken place within eighteen months.*
We have not attempted to show the relationship of the different forms of carcinoma to their tendency to recurrence, but the form of disease has undoubtedly a great infiuence upon the ultimate results. This point is clearly demonstrated by our experience, as in not a single one of the seven cases in which the uterus was completely removed for adeno-carcinoma of the body has a recurrence been noted; while in the thirty-eight cases where the cervix was diseased, fifteen have died with a return of the trouble.f
Metastases were found only once beyond the pelvic and retroperitoneal glands, in ten autopsies performed in the pathological laboratory upon patients in whom carcinoma of the uterus was present. This was an adeno-carcinoma of the body of the uterus, and a few nodules were found in the liver. In four others there were carcinomatous deposits in the pelvic and retroperitoneal glands.
This, in conjunction with the fact that by far the greater majority die subsequent to hysterectomy with a continuation of the growth in the vagina and parametrium, proves the possibility of complete eradication.
- Statistics obtained from Winter, Berliner klin. Wochenselirift,
1891, No. 33, and Ztsch. f. Geburtsh. u. Gyn., Vol. XXIV, p. 135 ; also Boldt, American Jour. Obstet., Vol. 26, p. 517.
fKinkenburg (.Ztsch. f. Geburtsh. u. Gyn., Vol. 23) and Hofmeier (same journal. Vol. 32) have made similar observations.
St.vtistics of Forty-seven Cases of Cakcinoma.
Name.
Seat of Disease. | Operation.
Date of
Operation.
Date of Death.
Remote Resllts.
Mrs. L.
Cervix. Fungating mass iiiin.- \ lu'iiial hystcreAomy.
upper portion of vagina.
11-31-89
8-30-91
Local return.
E. C.
Body.
\ affinal bystuiectomy. Uterus
ruptvired dui'ing removal.
1-2-^
Patient continues to be in excellent
health.
C.G.
Cervix. Previous operation, high
amputation.
Vaginal hjsteicctuiny. First use
of ureteral catheter.
6-18-90
Patient last examined 10-3-93. No sign
of return.
D. J. B.
Body.
Vaginal hysterectomy. Bladder
opened. '
8-38-90
Five days after operation.
Death, peritonitis.
Mrs. H.
Cervix. Extensive lateral in 111tratlon.
Vaginal hysterectomy.
3-38-91
Fire mouths after
operation.
Local return in vaginal vault.
M. W.
Cervix. Fungating mass in vagina.
Vaginal hysterectomy.
4-4-i)l
Last examination 10-3-95. No evidence
of return.
J. B.
Portlo vag. Disease extends I cm.
on vaginal walls.
Vaginal bysterectotny.
5-4-91
Discharging gland.s in neck and axilUe.
No local return, )<-15-y5.
E. C.
Cervix. Disease circumscribed.
Vaginal hysterectomy.
7-1-91
Last seen S-9-93. In perfect condition.
M. A. B.
Cervix. Fungating mass in vagina. F.xtenVivc lateral involvement
Vaginal hysterectomy.
11-9-91
9-5-93
Local return in few months.
Dr. Miller's
Patient.
Cervi
Vaginal hysterectomy.
4-23-91
Excellent health. No evidence of return, 9-11-95.
Mrs. W.
Cervi.x. I,:itiriu iinoivuuieut.
Myoma at fundus.
Vaginal hysterectomy.
13-23-91
1-1-93
Local return.
K. K.
Cervix. Exlcusivc lateral inllltratlon.
Vaginal and abdominal.
1-30-93
Died from operation. Ligation of
ureters.
Mrs. M.
Cervix.
Vaginal hysterectomy. Cauterization of left pedicle on account
of inBltrated area. Prognosis
bad.
,.8-18-92
Patient in excellent health. No local
return, 9-1.5-95.
November-December, 1895.] JOHNS HOPKINS HOSPITAL BULLETIN.
157
Name.
Seat of Disease.
Operation.
Date of
Operation.
Date of Death.
Remote Resclts.
Miss B.
Body.
Incomplete vaginal hysterectomy
on account of extensive disease
and inflltration of fundus.
'^-33-93
About three months
after operation.
Disease had brolien through uterine
wall and spread out on intestines.
Mrs. G.
Cervix.
Vaginal hysterectomy.
8-3-92
9-38-92. Portion of tube in incision
removed with cautery. 9-1-95, patient in L'ood li'-iilth.
F. C.
Cervix. Two nodules found in
uterus entirely separate from
cervix.
Vaginal hysterectomy. Bladder
perforated and afterwards closed
with good result. Bad prognosis.
11-37-93
10-18-93
13-12-(iri ised.
Loca;
C. T.
Cervix. Complicated by 4 months'
pregnancy.
Vaginal and abdominal.
11-10-9J
.5-1-94
Patient died in Hospital. Local return
with perforation of bladder and rectum.
R. A.
Body. Associated with myoma.
Supra-vaginal amputation. Cervical canal cauterized.
11-38-93
Patient In good health, 9-13-95.
Z M.S.
Cervix. Fungating mass in vagina.
Vaginal hysterectomy.
12-17-93
5-13-93. Ulcerated area in vaginal
vault dissected out and cauterized. —
9-31-9.1. No sign of local return.
A. E.
Cervix. Fungating mass iilliug
vagina. Invasion of vaginal
mucosa.
Vaginal hysterectomy.
6-25-93
Unable to find patient.
Mrs. D.
Cervix.
Vaginal hysterectomy.
3-6-93
Patient continues in good health,
10-1-95.
Mrs. C.
Cervix.
Vaginal hysterectomy.
4-13-93
Unable to obtain information regarding patient.
Mrs. G.
Cervix.
Vaginal hysterectomy. Impossible to remove all disease laterally.
4-18-93
7-1-93
Local return.
E. B.
Body.
Vaginal hysterectomy. Uterus
ruptured in removing.
5-10-93
Breast removed for cancer about one
year after hysterectomy. 10-1-95, no
return in vagina, but patient under
treatment for some recurrence in
breast.
Mrs. S.
Cervix.
Vaginal hysterectomy.
8-30-93
Died one year later.
Local return.
8. L.
Cervix. Vagina fllied with fungating mass, and inflltration for
a cm. about cervix.
Vaginal hysterectomy. Bladder
perforated. Transfusion of salt
solution in radial artery.
10-10-93
8-15-94
Local return.
P. H.
Cervix. Circumscribed nodule.
Vaginal hysterectomy.
11-8-93
Last heard from S-20-95. Donblful return in cicatrix.
L. W.
Body. Associated with myoma.
Supra- vaginal amputation.
2-1.5-93
Continues in excellent health, 10-5-95.
C.8.
Cervix.
Vaginal hysterectomy.
11-25-93
Died from operation. Peritonitis.
M. F. W.
Portio vaginalis. Disseminated
nodules in vaginal mucosa.
Vaginal hysterectomy. Whole
upper third of vaginal mucosa
removed.
11-25-93
2-1-95
Death from pneumonia. Local retam.
M. G.
Body.
Vaginal hysterectomy.
12-1-93
Continues to be in excellent health,
S.17-95.
M. D.
Cervix. Lateral intiltration so far
advanced that a bad prognosis
given.
Vaginal hysterectomy. Bougie
in ureter.
12-11-93
1 No evidence of local return. Patient in
' excellent health, 9-13-95.
A. R.
Cervix. Post, lip only involved.
Vaginal hysterectomy.
1-31-94
Sent by physician (or examination on
account of suspicions nodule in scar,
which proved to be silk liirature imbedded in granulation tissue. No
evidence of return of disease, 9-13-95.
L W.
Cervix. Fungating mass filling
upper portion of vagina. Mucosa of vagina not diseased.
Vaginal hysterectomy. Bougie
passed into ureter.
2-15-94
About nine months
after operation.
Local return.
N. C. J.
Cervix. Uterus torn olf above internal OS. Lateral infiltration.
Bad prognosis.
Vaginal hysterectomy.
3-17-94
6-8-94
Local return.
E. O.
Cervix. Lips entirely disappeared. Disease far advanced laterally.
Vaginal hysterectomy. Uterus
ruptured during removal.
3-3-94
11-5-94
Local return.
8. B. H.
Cervix. Nodules fell beneath vaginal mucosa. Prognosis bad.
Vaginal hysterectomy. Bougie in
ureter. Pus cavity beside uterus
in abdomen.
8-5-94
Five months after
operation.
Local return. Death sudden.
M. E.
Cervix. Vagina and parametrium involved. Bad prognosis.
Vaginal hysterectomy. Nodule in
broad lig. dissected out.
8-5-94
Eight months after j Local return,
operation. [
M. 11.
Cervix.
Vaginal hysterectomy.
8-7-94
Died from operation.
Death due to pcrltooitis.
M. Q.
Cervix.
Vaginal hysterectomy.
8-21-94
Died from oueratlon.
Death due to peritonitis.
B. Z.
Portio vaginalis. Disease had encroached upon vaginal walls 3
cm.
Vaginal hysterectomy. Ureter
cut.
8-23-94
Ureter dissected out and sutured into
incision in l>ladder. S-1.5-S6. no sign
of return. No urinary diflicalty.
M. P.
Body.
Abdominal hysterectomy.
7-35-94
Perfect health when last soon, 8-18-85.
A. R.
Cervix. I'.iniliiiu .1 oiuiation, vaginal and
- ib.l..iiiinal.
8-8-94
No local induration or ulceration.
Good hoallh, ^16-a5.
8. A.
Cervix. Converted into shell.
Cumbimil operation, vaginal and
abdominal.
0-5-94
Doctor write* that p,itient Is in good
condition, with no sign of recurrence
of disease, l(V-lC>-lVi.
K. A.
Body.
Supra-vaginal amputation. Cervix cMipiu'd out.
6-30-94
No evidence of recurrence, 9-13-»5.
B.C.
Cervix. Vaginal livstcrectomy. Tube
caught in vairinal incision.
3-17-94
Patient in good health and vitbont
symptoms pointing to return. 9-1 i-a5.
Carcinoma of breast removed about one Tear after the vaginal hysterectomy. I'aliont died of hc,»rt lesion.
Mrs. W.
Cervix.
Vaginal hysterectomy.
11-15-91 Died about eighteen
months affcr op1 eration.
158
JOHNS HOPKINS HOSPITAL BULLETIN.
[Nos. 56-57.
NOTES ON SOME OASES OF ANGINA TREATED WITH BEIIRING'S ANTITOXINE.
By George Blumkk, :M. D., Assidant in Pathology, The Johns Ifnph'vs Hospital
The following cases of siugina, either due to the bacillus diphtheriae, or simulating true diphtheria and due to other organisms, have been observed iu the hospital since the intro•ductiou of the antitoxiue treatment.
Some of the cases are of interest as relating to the eilect of the autitoxine on diphtheria; others were not treated by antitoxiue, but present some special point of interest bearing more or less upon diphtheritic or diphtheroid inflammations.
In the cases treated by autitoxine, the preparation prepared under the direction of Behring was exclusively used, the various strengths being indicated according to the severity of the case and regardless of the age of the patient.
The autitoxine was usually injected into the cellular tissue of the back, though occasionally into the musculature of the thigh, the injection being done with a syringe previously sterilized by boiling, the skin of the part to be injected having been prepared by the methods usual before operative procedures.
The cases, which number eighteen, may be grouped under the following heads:
MEMBK.-VNOUS ANGINA DUE TO THE BACILLUS DiPHTHERIAE.
Case 1.— Female, aged 11, white. Admitted to the hospital December 31, 1894, complaining of sore throat.
JJi«/oij/.— The family histor.v is negative. The patient had measles, whooping cough and typhoid fever as a young child.
The present illness began four nights ago, the patient waking up in the middle of the night with an attack of nausea, followed by vomiting and headache. The throat did not feel sore until the following night, and she then noticed pain on swallowing. .-Vt first the soreness was confined to one side, but later both sides became involved.
On admission the general condition was good. There was great swelling of both tonsils, the glands almost meeting in the median lino. The inner surface of each tonsil was lined by a purulent membrane, whicli, on removal, loft a bleeding surface.
January 1. The membrane has extended to the uvula, and soft palate. There is slight glandular swelling on the left side.
.January 2. The child looks rather pale and is dull and apathetic. Bohring's Antitoxine No. 3 was injected into the snl)outaneous tissue of the back.
.Tanuary 3. The child is much brighter, states that s!ie feels better, and voluntarily asks for food. Tlio swelling of the tonsils has diminished, though the uvula is still covered by membrane. The tense oedema of the tonsils and adjacent parts observed yesterday has disappeared.
January 4. The membrane has almost disappeared.
The temperature on admission was 101.5° F., and ranged between this point and 103° F. up to the time of the Inoculation, when it wjis 103° F. Following the inoculation it sank gradually; the morning following It was 100.5° F., but after this never passed above 100° F., the convalescence being uninterrupted.
The pulse was noted to be a little feeble the day on which the inoculation was made; the following morning it was much improved. About six days after the inoculation the patient began to have attacks of urticaria, coming and going over a period of a week. The eruption was not confined to tlie region of the original Injection, but occurred in various parts of tlie body.
BacteriiiUnjical Examination.— Cn\cr-s\\\>a from the throat did not show definite diphtheria bacilli.
Cultures after 24 hours sliowed almost a inire ciilturo of the bacillus diphtheriae.
A guinea-pig inoculated with a 24-hour buuillon culture died 14 days later with characteristic lesions, diphtheria bacilli being obtained from the seat of inoculation.
Case 2.— Female, aged 35, white. Admitted to the hospital January 7, 1S95, complaining of sore throat.
Histonj.—Hev father died of some disease of the liver, her mother of heart disease. No other diseases in the family.
.\s a child she had the usual exanthems. Slie liad an attack of diphtheria at 9 and another at 29, the latter being a severe attack. She has had four attacks of tonsillitis in the last three years.
The present illness began with a feeling of malaise three days ago; the following day she had chilly feelings and pain in the limbs and back. The throat was not noted to be sore till yesterday.
On admission the general condition was good. There was a general reddening of the throat and a large patch of grayishwhite membrane over the left tonsil, which was detached with difficulty and left a bleeding surface.
Behring's Antitoxine No. 1 was injected into the muscles of the back.
January 8. The membrane on the left tonsil remains the same. There is a small patch on the right tonsil which was not noticed yesterday.
January 10. The membrane has completel.v disappeared.
The temperature on admission was 100.5° F. At the time of the inoculation, two hoiu's later, it was 101.5° F., and had risen two hours later to 102° F. The following morning it had fallen to 100° F., but rose again slightly, reaching 100.5° F. at 4 P. M.; from this time on it fell, reaching normal in four hours and never again rising above that point. The pulse was good at all times. No skin eruption was observed.
liactcrinlogical Eraminatinn. — Cover-slips from the throat showed typical diphtheria bacilli. Cultures on blood serum showed many colonies of the bacillus diphtheriae and a few of the streptococcus pyogenes.
An animal inoculated with a 24-hour bouillon culture failed to react either locally or constitutionally.
The organism isolated was certainly not the pseudo-diphtheria bacillus. It acidified litmus bouillon, and grown side by side with a culture of the pseudo-bacillus, could easily be distinguished. The patient was discharged seven days after the disappearance of the membrane, the bacilli still being present in the throat.
Februaiy 17. The patient again comes under observation after a five weeks' holiday. The throat is quite clear. She states tliat during her absence, and about three weeks after the cess;ition of the first attack, she had a second fairly severe attack of sore throat, which was diagnosed tonsillitis by the attending ph.vsician, but without a bacteriological examination.
Cultures were again from the throat, and diphtheria bacilli and streptococci found to be present.
The patient was kept under observation, and three d&ys later cultures were again taken. tl)o patient having used at frequent intervals for the preceding 24 hours a bicliloride spray and a solution of h.vdrogen peroxide as a gargle. Large numbers of diphtheria bacilli were still present.
Two days later a tliird set of i-ultures were made, the patient in the meanwhile liaviug had Lii(Uor"s toluol solution vigorously applied to botli tonsils five or six times. The diphtheria bacilli were still prtksent, though in smaller numbers.
These organisms, like those isolated in the first attack, were harnih'ss for animals, so the patient was allowed to return to her wiu-k. Three weeks later she was again admitted to the ward with a history of having been taken with sore throat. fever and malaise four days previously. She had been attended
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for a time by her own physician, and creosote had been applied locally. On admission there was a glossy white membrane over each tonsil, very tenacious in character. The patient was practically convalescent at this time. The membrane gradually disappeared and had entirely goue seven days froiA admission. There was no fever.
In the interval between the first and last attacks, and in the last attacli, the diphtheria bacillus could always be obtained from the throat. It was on several occasions inoculated into animals and never produced either local or general reaction.
The organisms finally disappeared from the throat three days after the disappearance of the membrane caused by the last attack, or three months and three days from the beginning of the first attack.
Case 3.— Female, aged 8, white. Admitted to the hospital February 1, 1895, complaining of sore throat.
History.— The family history is negative. She has had the usual exanthems and has been treated for some chronic throat disease since August last.
The present illness began five days ago with a shaking chill lasting about half an hour. She felt well the next day until evening, when she had some fever. She complained of sore throat from the first.
On admission the general condition was good. The right tonsil was swollen and covered by a large patch of yellowish-gray membrane; the left tonsil also swollen and shows a smaller patch of membrane; the uvula free.
Behring's Antitoxine No. 2 was injected into the subciitaneuus tissue of the back.
February 2. The membrane is still i)resent, but looks swollen and has a shining translucent appearance.
February 3. The edges of the membrane are curling up. There is a fine pink papular eruption over the face and back, not itchy.
February 5. All the membrane has gone but a small patch over the right tonsil. The eruption has disappeared.
February 8. The child complains of itching of the back. There are ten to twelve urticarial wheals about the seat of inoculation.
February 9. The urticaria has disappeared.
The temperature on admission was 101° F., but had fallen to 99° F. when the inoculation was made; it never again passed 99.3° F. The pulse was always satisfactory.
Back'rioloyical Examination. — Cover-slips from the membrane showed a fair number of typical diphtheria bacilli. Cultures showed the same organism in an almost pure state.
A guinea-pig inoculated with a 21-hour bouillon culture died 76 hours later, the autopsy showing the typical lesions of experimental diphtheria, and the organism being recovered from the seat of inoculation.
The organism disappeared from the throat five days after the disappearance of the membrane.
Case 4.— Female, aged 30, white. Admitted to the hospital February 5, 1895, complaining of sore throat.
Hi.story. — The family history is unimportant. The ijatient h;iil the usual exanthems as a child. She has had two attacks of appendicitis, the last one two years ago. She had right-sideil pleurisy 20 mouths ago. Since the age of 15 she has had nine or ten attacks of tonsillitis, none of them very severe.
The present illness began two days ago witli chilly feelings, which lasted for twenty-four hours. Last night she began to have frontal headache, which persisted up to a short time ago; all day yesterday she had pains through the limbs. The throat felt a little sore from the first.
On admission the general condition was good. The fauces and tonsils were slightly ccmgested, the tonsils quite swollen, especially the right, which was almost covered with a patch of yellowish-gray adherent membrane; a smaller patch was present on the left tonsil.
Behring's Antitoxine No. .T was injected into the subcutaneotis tissue of tlie back. In the afternoon some pain at the seat of Inoculation was complained of.
February (>. The patient fools much better. There is still some pain at the seat of inoculation. The throat Is less swollen,
though the patch on the left tonsil is somewhat increased in size.
February 7. The throat is almost clear; what membrane remains is swollen and pearly looking.
February 8. The membrane has entirely gone.
The temperature on admission at 2 I'. M. was 102° F.; at (! P. II., about two hours after the inoculation, it had risen to 1(12.5° F.; it then fell, reaching 99° F. at 8 the following morning. At 12 noon on the Oth the temperature was 100° F.; it then fell gradually, reaching normal at midnight and never ag.iin going higher than 99.6° F.
The pulse ranged from 76 to 106; it was always strong.
No skin eruption was noted.
liactcrioloyical Examlruition. — Cover-slips from the membrane showed typical diphtheria bacilli. Cultures showed the same organism associated with the staphylococcus aureus and a few St roptococei.
A guinea-pig inoculated with a 24-hour bouillon ciUture showed marked local tumefaction, but did not die.
The diphtheria bacillus disappeared from the throat 22 days after the disappearance of the membrane.
Case 5.— Male, aged 26, white. Admitted to the hospital March 6, 189.5, complaining of sore throat.
History.— Aside from a history of tuberculosis in two sLsters the family history was negative. The patient had the usual exanthems as a child, and malaria and typhoid as an adult. He has been subject to attacks of .sore throat ever since childhood. some of these attacks having been severe enough to confine him to bed.
The present illness began three days ago with dryness and. later on, soreness of the throat. No cliill or fever. He has beadache and pains through the limbs.
On admission the general condition was excellent Both the tonsils were swollen and reddened, and the middle part of each was covered by a thick yellowish membrane, which, on being detached, did not cause bleeding. The neck glands were a trifle enlarged and tender.
Behring's Antitoxine No. 2 was injected into the sulwutaneous tissue of the back.
The membrane gradually disappeared and was entirely gone three days after admission.
The temperature on admission was 99.5° F.. and never again pas.sed above 99° F. The pulse was always strong.
No skin eruiition was noted.
rtncteriological E .ramiMition.— Coyer-slips from the tliroat showed a few typical diplitheria bacilli. Cultures gave an almost pure growth of the same organism.
.\ guinea-pig inoculated with a 24-hour bouillon culture died 48 hours later, the autopsy showin,g typical lesions of exiierimontal diphtheria, and the bacillus being recovered from tie seat of iuocidation
Tlie organism dis.appeared from the throat three days after tlie disappearance of the membrane.
Case 6.— Male, aged 24. white. Admitted to the hospital March 10. 1S95. complaining of sore throat.
History. — The family history is negative. The patient had the ustial exanthems as a child, and la grippe and dengue as an adult. lie has always been subject to attacks of tonsillitis.
The present illness began two days ago with soreness in the region of the left tonsil and chilly sensations. The attack l>eg:in in tlie morning, and b.v evening a small patch of membrane was noticed on the left tonsil. On removing the membrane a bleeding surface was exposed.
C~>u admission the general condition was good. The tonsils were swollen, and over each was a blackish eschar caused by the use of I.ollior's toluol solution; beneath the eschar a gray membrane could be made out. The glands lu the neck were slightl.v enlarged.
Behring's Antitoxine No. 3 was injected into the sulK'Utaneous tissue of the back.
Two days after the inoculation the membrane bad entirely disappeared, though the tonsils still looked a little rod.
The temperature on admission was 104.S» F.: the next morn
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ing it had fallen to 99.5° F., and did not rise alx)ve 100.5° F. all that day. The following day it began to rise at 8 A. M., reaching 103.5° F. at noon, after which it fell gradually, being 99.5° F. at S the ne.xt morning and never again passing the normal. The pulse was always good.
No skin eruption was noted.
Baclcrioloijical Examination.— CoYcr-sUps from the throat showed a fair number of typical diphtheria bacilli. Cultures showed an almost pure growth of the same organism.
A guinea-pig Inoculated with a 24-hour bouillon culture showed a marked local reaction, but did not die.
The bacilli were still present thirteen days after the membrane disappeared, though not virulent
Case 7.— Male, aged 5, white. Admitted to the hospital .Tune 13. 1895.
Hts^rj/.— Could not be obtained.
On admission it was noted that the child was small and iUnourished. The skin was pale. Tlie mucous membranes not cyanotic. The respiration was loud but not stridulous. 'Ihere was a constant purulent discharge from the nostrils, and much muco-pus dribbled from the mouth. Membrane could be made out on the soft palate, but examination of the tonsils and pharynx was not satisfactory. The temperature was 105° F. on admission.
Behring's Antitoxine No. 2 was injected into the muscles of the right thigh. The child was practically moribund on admission and died suddenly eight hours later.
Bacteriological Examination.— CoviM-sUps showed the diphtheria bacillus and cocci in groups or chains. From the cultures the diphtheria bacillus and the streptococcus were isolated.
An autopsy was not permitted.
Case 8.— Female, aged 29 months, white. Admitted to the hospital with dyspnoea August 12, 1895.
His^o/v/.— Family history negative. The patient had measles five weeks ago. She has had a discharge from the right ear for seventeen months.
The present illness began three days ago with cough. The child, however, ran about and played as usual up to last night. This morning about 4 A. M. she woke up with a severe attack of dyspnoea, which has gradually increased.
On admission the child was dull and apathetic. The mucous membranes and finger-tips were slightly cyanotic. There was marked obstruction to inspiration. Both tonsils were swollen and covered with a grayish exudate. Tliere was no exudate on the posterior pharyngeal wall. Temperature 100.5° F.
Behring's Antitoxine No. 3 was injected into the subcutaneous tissue of the back.
The dyspnoea became rapidly worse about three hours after admission, and the patient died during an attempt at' tracheotomy.
liriclrriolof/ical Exami)wtion.—CoysT-s\\ps from the membrane showed many typical diphtheria bacilli. Cultures showed the same organism. An autopsy was not permitted.
Case 9.— Male, aged 2 years and 10 months, white. Admitted September 8, 1895, complaining of sore throat.
History.— The family history was negative. The child has had no previous illness.
The pres(!nt illness began tive days before admission with anorexia. Two days later the child complained of i)ain on swallowing. This morning a membrane was discovered in his throat by his physif'ian and he was brought to the hospital.
On admission the general condition was good. Both tonsils were swollen and covered with patches of grayish-yellow exudate extending on each side Into the uvula. The pharynx is clean. The glands of the neck are not enlarged.
Behring's Antitoxine No. 2 was injected into the subcutaneous tissue of the back.
Seittember !). The membrane seems to have spread slightly. The child Is bright.
September 10. The child Is better; the membrane has ceased spreading.
September 11. The membrane has largely disappeared.
September 13. The throat is entirely clear.
The temperature on admission at 8 P. M. was 100.4° F. At 2 A. M., four hours after the inoculation, it reached 101.8° F.; it then fell gradually, reaching normal 24 hours later and never again jmssing 90.2° F. The pulse was always strong.
Nil skin eruption was noted.
Baclii-Uihtijiciil Bd;omin«<w».— Cover-slips from the throat showed suggestive bacilli, but no typical ones. Streptococci were present in fair numbers. Cultures showed the diphtheria bacillus and the streptococcus.
A guinea-pig inoculated with a 24-hour bouillon culture of the bacillus died 48 hours later with the lesions of experimental diphtheria, the organism being recovered from the seat of inoculation.
Case 10.— Male, aged 2, white. Admitted to the hospital September 20, 1895, with dilBculty in breathing.
Hixtorii. — A satisfactoiy history cannot be obtained, as the mother speaks only Bohemian.
From the mother's account the child lias only been ill twentyfour hours, its only symptoms being irritability and loss of appetite.
On admission the child looked ill. The breathing was rai)id and slightly obstructed. The voice was, however, clear. Over the tonsils and the neighboring parts of the soft palate a thick white membrane was seen.
Behring's Antitoxine No. 2 was injected into the buttock.
The breathing was somewhat more obstructed in the evening and the voice a trifle brassy.
September 22. The membrane has entirely disappeared. The child looks perfectly well.
The temperature remained steadily up about 102° F. until the 23d. when it fell gradually, reaching 99.4° F. at 10 P. M. and not rising again.
Bactcrisloijical Examination. — Cover-slips from the membrane showed a fair number of diphtheria bacilli. The cultures showed an almost pure culture of liaeillus diphtheriae.
Case 11. — Male, aged 7, white. Admitted to the hositital November 4, 1895, complaining of sore throat.
Bifttory. — The family history is unimportant except that he lost one sister from croup. He has had measles but no othei' illness. The present illness began four days ago with pain in the throat, which was increased by swallowing. The pain was at its worst two days ago, and he felt weak at that time. The pain and the weakness are the only symptoms complained of.
On admission the general condition was good. Both tonsils were swollen and showed numerous areas of membrane formation with rather a iiatchy arrangement. There was also a patch of membrane on the soft palate to the right of the uvula. The breathing was somewhat harsh, but there was no great dyspnoea.
Behring's Antitoxine No. 2 was injected into the muscles of the- left thigh.
November 6. The patient is quite comfortable; he has no pain on swallowing.
November 7. Only a small patch of membrane remains.
November 8. The membrane has quite gone.
The temperature on admission was 100° F., and sank following the inoculation to 98.8° V. It was up to 100° F. at noon on the Gth, and then fell gradually, never again reaching above 99.5° F.
Bavtcrioloiiical Bir'«Hniio<iow.— Cover-slips showed a good many typical diphtheria bacilli. Cultures showed the same organism, almost a pure growth.
The cases recorded in this group arc of that class which from a clinical standpoint alone would be regarded as diphtheria, /. e. they are characterized by definite membrane formation. Aside from the question of the influence of the autito.\ine on the progress of the disease they present no special points of interest, with the exception of Case 2. This case is of interest from several points of view : 1. As showing the duration of antitoxine iinmunization and of natural immunization.
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2. As showing the possibility of auto-infection.
3. As demonstrating that the diphtheria bacillus can exist for long periods in the throat.
4. As demonstrating the resistance of the diphtheria bacillus to chemical agents.
That the immunity conferred by the antitoxine (passive immunity) does not protect over as long a period as natural immunity (active immunity) has long been known as far as animals are concerned. Cases showing the duration of this artificial immunity in man are not, however, common. Henach has reported a case in which a recurrence of the disease occurred from 35 to 30 days after the use of the antitoxine, and Wolff-Lewin reports a case where a child who had apj)arently recovered perfectly after the use of antitoxine develojjed symjjtoms of a fresh attack ten days from the beginning of the first one. In our case the patient was immunized on January 7th and contracted a second attack of what was presumably diphtheria about three weeks later; it is true that the patient was not under observation during this second attack, but cultures made only a week later showed the diphtheria bacillus to be present in the throat. During this second attack no antitoxine was used, and yet a third attack occurred thirty-seven days after the beginning of the second. In this case, theu, the period over which active immunity lasted would seem to be about thirty-seven days, whilst that over which passive (antitoxine) immunity lasted was only twenty-one days.
It seems highly probable that auto-infection occurs in most cases of croujjous pneumonia and in many of streptococcus throat; it is also known that virulent diphtheria bacilli are occasionally found in the throats of healthy people. This case would seem to prove definitely that auto-infection does occur in diphtheria, as it was shown that the diphtheria bacilli were constantly present in the throat between the second and third attacks, the throat all this time pi'esenting a perfectly normal appearance. It is only fair to conclude that when the immunity was worn out the individual became infected by the bacilli then present.
Although the patient was not under constant observation from January 7th, when the first attack began, until April 10th, when the diphtheria bacilli finally disappeared from the throat, yet cultures were made frequently enough to warrant the assumption that the bacilli were continuously present over the period between the dates specified. In an observation recorded in the British ^ledical Journal of which Sevestre speaks, the bacilli were obtained from the throat seven months after the disappearance of the membrane; but in this case the cultures were few and far between. The question of the survival of the diphtheria bacilli after the disappearance of the membrane is an important one from a prophylactic point of view, for we must admit the possibility if not the probability of individuals such as our patient transmitting the disease to others. Such a possibility once being estublislied, the isolation of diphtheria cases would not be subject to any fixed law, but would depend on the demonstration of the presence or absence of the bacillus in the throat.
The fact that the bacilli in this case were only in part destroyed by the repeated action of Loffler's toluol solution is
an interesting one, especially as the solution was acting on a throat devoid of membrane. The fact that the bacillus appears so resistant should not, however, deter us from the use of such chemical agents, as clinical experience has amply proved
their value.
Diphtheria Simulating Follicular Toxsillitis.
Case 12.— Female, aged 23, white. Admitted to the hospital .January 17, 1895, complaining of sore throat.
History.— The family history was uuimportaut. The ijatient had the usual exanthems as a child; slio has not been subject to sore throat. The present illness began four days ago with backache, headache, sore throat and pains in the limbs. There was slight pain ou swallowing.
On admission the general condition was good. Both the tonsils were swollen and on both sides covered with numerous yellowish i)atehes, apparently plugging the follicles. No definite areas of membrane were to be made out.
Behriug's Antitoxine No. 2 was injected into the subcutaneous tissue of the back.
.January 18. This morning a small patch of membr-iue about the size of a split pea was noticed on the soft palate; it was quite adherent.
January 19. The membrane is disappearing.
.January 21. The membrane has entirely gone.
The temperature on admission was 100.2° F., and about the same at the time tlie inoculation was made; the following morning it was 99° F., and never passed above this point subsequently. The pulse w^as always strong. There was some itching about the scat of inoculation three days after its performance, but no skin eruption was noticed.
Bacteriological Examination.— Coyer-sWps from the throat showed suspicious bacilli, but nothing definite. Cultures showed the diphtheria bacillus in practically pure culture.
A guinea-pig inoculated with a 24-hour bouillon culture showed marked local i-eaction, but did not die.
This case corresponds to those described by Koplik as acute lacunar diphtheria of the tonsils. It illustrates the necessity, not yet fully appreciated, of a bacteriological diagnosis ju all cases of throat inflammation. It is just such cases as this which would be clinically regarded as a non-infectious tonsillitis, which may give rise to serious epidemics of diphtheria.
Diphtheria Without Membkaxe.
Case 13.— Female, aged 35, white. The patient has been in the hospital for fifteen mouths with progressive muscular atrophy. Ou February 17, 1S95, she complaiued of sore throat. The throat was examined aud found to be a little swollen and reddened, but there were no signs of membnine. On the ISth the throat was again examined and showed the same appearances. Cultures were made at this time aud showed, the following day, many colonies of typical diphtheria Kicilli.
The patient was transferred to the isolation ward .January 19. Her throat then was a little swollen and reddened, but there Avere no signs of memJirane. There was no dyspnoea, no running at the nose. The general condition was excellent. The throat rom;uned reddened and swollen over a period of eight days, the swelling subsitliug duriug this period and the redness decreasing.
The treatment consisted of a bichloride spray locally, and whiskey as a stimulant.
The temperature, which was 100.2 F. on the night of January 17, rose to 101.5° F. l>y noon of the next day. and remained up fill G P. M.; it then gradually fell, reaching normal ou the lOtli and never passing 90.5° F. substMiuently.
BactiTiologinil A'.r(iminur bouillon culture showed a well-marked local reaction, but did not die.
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This case again illustrates the necessity of a bacteriological diagnosis in all suspected throat cases ; cliuically, no feature was present in tliis case to indicate diphtheria.
Multiple Infection with Bacillus Diphtheriae.
Case 14.— Male, aged 4. white. Aduiilted to the hospital March 29, 1S95, on account of fevei- nnd a disohaiiic from tho right ear.
Histori/.—'rhc family history is imitiipurtant. Tlio patient was in the hospital the June previous with malarial fevor. but recovered completely. The present illness began three days ago with pain in tho head. At this time the ehild was noticed to hold his hand constantly to the side of his head. The morning following the onset of the pain he seemed better, but it was noticed that there was a discharge from the right oar, which has eontinued since. His nose has been discharging for a month or two; he has never complained of sore throat.
March 31. On admission to the isolation ward the child looked rather pale and stupid. There was a thick, creamy, odorless discharge from the right ear which was very profuse. From both nostrils there was a thick muco-purulent discharge. There was no sign of memijrane in the nose. The tonsils and pharynx were reddened, but showed no signs of meml)raue. The neck glands were enlarged, hard and tender to the touch. There was a small area of dullness at the base of the left lung over which the breathing was feeble. On tho radial side of the right thumb there was an e.xcoriated area at the root of the nail. This area was covered by a whitish-yellow membrane, which, on being stripped off, left a raw, non-bleeding surface.
Behring's Antitoxine No. 2 was injected into the subcutaneous tissue of the back. >
.\pril 2. The child seems about the same. The ear is still discharging profusely; the nose less so than formerly. A slight nuMubi-ane has reformed over the wound in the right thumb. The throat is perfectly clear. In the afternoon the ehild did not look quite so well.
April 3. The child looks better this morning. About midday the left ear was noticed to be discharging; the patient had not complained of any pain in the ear region. There is still a slight menjbrane f)ver the right thumb.
April 4. The left thumb is excoriated at its base; there is no membrane over the excoriation.
The ehild was taken home against advice this afternoon.
The temperature on admission to the liospital was 104° 1'. It sank in the evening to 101° F., and from March 30 to the time of admis.sion to the isolating ward varied between normal and 101° F. .■Vt the time of the injection of the antitoxine tlje temperature was 100.8° F.; it sank gradually over the next fortyeight hours, the highest point reached after the inoculation being 101° P. at 8 V. .M. on the day following. The pulse was always fah'ly strong.
No reaction about the seat of inoculation and no skin eruption was noted.
Hactcrioloniail nxaminatimi.— Cover-slips from the discharge from the right ear showed the predominating organism to be a bacillus morphologically resembling the diphtheria bacillus; a good many cocci in chains were also present. Cultures showed many typical diphtheria bacilli and a fair number of streptococci.
A guinea-jiig inoculated with a 24-hour bouillon culture showed very marked local reaction and was very ill for two or three days, bnt eventnally recovered.
(Jultures from the nasal cavity, the tonsils and the pharynx all showed the bacillus diphtheriae associated with the streptoioccus pyogenes; in the tub(!s from the nasal cavity a few colonies of the staphylococcus aureus were also present.
Cultures from the right thumb showed the dlplitheri;i l)acillus with the streptococcus pyogenes and the staphylococcus aureus. Cultures from the left thumb showed the diphtheria bacillus and the streptococcus pyogenes.
The organisms were still present when the child was removed from the hospital.
The two main points of interest in this case are the double otitis media and the occurrence of wound diphtheria.
It is possible that many cases of otitis media in which the diphtheria bacillus is concerned are overlooked, the reported cases not being very numerous. Councilman has reported cases in this country, and Kossel and Kutscher in Germany. In Kossel's cases the diphtheria bacillus could not be isolated from the throat, though membrane was present, a fact which Kossel explains by the overgrowth of the diphtheria bacillus in this locality by other organisms. Most of these cases of otitis media have not been pure diphtheria infections, so that it is often impossible to say whether we are dealing with a primary mixed infection, or whether the diphtheria bacillus was the original causal factor and other organisms afterwards crept in.
Cases of wound diphtheria would also seem to be uncommon, that is if the term wound diphtheria be limited to the infection of woitnds with the Klebs-Loffler bacillus.
Abel has reported a case in which the diphtheria bacillus alone was present in the membrane, proving conclusively that this organism is capable of membrane formation per ,se, a fact which had been disputed by many writers.
It is interesting to note in our case, that while the diphthei'ia bacillus was obtained from the wound on each thumb, membrane was only present over the wound of the right thumb.
Angina Caused by the Pseudo-Diphtheria Bacillus.
Case 15.— Female, aged 22, white. The patient had been in tlie hospital for some weeks with chlorosis. On the evening of .January 31, 1895, she complained of slight sore throat, and examination showed a reddened and swollen condition of the tonsils, with a small patch of membrane (?) on the left side. The next morning the membrane could not be seen and the patient felt perfectly well.
The temperature had risen sharply on the evening of the 31st to 100.5° F., but was normal by 8 A. M. the next morning, and no further elevation occurred.
Bactcriolixjical Examination. — Cover-slips showed apparently characteristic diphtheria bacilli. The cultures were overlooked until the second morning after they wore taken, when the meditmi was seen to be thickly studded with white colonies resembling diphtheria colonies. On cover-slips the organism much resembled llie diphtheria bacillus; it was, however, shorter and thicker, and the individual organisms showed a strong tendency to lie in rows parallel to one another. Culturally, the organism also resembled the diphtheria bacillus, but was a much more profuse grower and alkalinized litmus milk.
.V guinea-pig inoculated with a 24-hour bouillon cultm-e showed neither local nor general reaction.
Tho organism could not be recovered from the throat eighteen days after the attack.
The organism isolated in this case corresponds in all its characteristics to that first described by Hofman and subsef|ueutly by Loffler aiul others. Koplik has described cases in which this organism was found, but not associated with membrane. The membrane in our case seems rather doubtful, as the examination at which the membrane was seen was made by candle light, and on the following morning no membrane was to l)e made out.
Mejibiianous Angina simulating Diphtheria hut due to Oro.vnisms other than the Klehs-Lopfler Bacillus. Case IG.— Male, aged 32, white. Admitted to the hospital
.lauuary 24, 1895, complaining of sore throat.
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History. — The family history was unimportant. Th(> putiont had tlie usual exanthems as a cl)ilfl and thiiilvs he liad diphtheria at three years of age.
The present illness began two days ago with severe headache and a violent shaking chill la.sting about twenty minutes and followed by fever. The following day he felt better, but woke, up on the morning of the third day with fever again. The throat has only been slightly sore.
On admission the general condition was good. Both tonsils were swollen and congested and covered with a thick grayyellow membrane, which was quite densely attached. The uvula and soft palate were not invaded.
Behring's Antitoxine No. ?, was injected into the subcutaneous tissue of the back.
.Tanuni-y 2.5. The patient feels nnu-li In-ttcr. 'I^lio membrane lias iiartly disappeared.
.Tanuary 26. The membrane has entirely disappeared.
The temperature on admission was 100° F.; it had risen to 102° F. two hours later, and then fell rapidly, reaching normal in twelve hours. The pulse was always strong.
Bactcriolor/ical £j"rt/«.in«/io;(.— Cover-slips were negative for diphtheria bacilli.
In cultures the predominating organism was a sliort, slim bacillus which grew well on all media, producing a bright green pigment. The organism corresponded in all its culture reactions with the bacillus pyoeyaneus.
Case 17.— Female, aged 41, white. The patient had been in the hospital for several months with acromegaly. She was admitted to the isolating ward January 2.5, 1895.
History. — The evening before admission the temperature rose and she complained of sore throat. The following morning, wlien the patient was seen, she was quite short of lireath and sitting up in bed. Examination of the throat showed both tonsils to be much swollen and reddened. Over the left tonsil was a large grayish-yellow patch the size of- a quarter, which had the appearance of false membrane. By 7..30 in the evening several spots of exudate were seen on both tonsils and the case presented more the appearance seen in follicular tonsillitis.
Behring's Antitoxine No. 3 was injected into the subcutaneous tissue of the back.
January 2G. The throat looks a little better. The patches still remain, but the swelling has subsided somewhat.
January 27. The patches are fewer in number.
January 28. The exudate has almost gone. The patient complains of a little pain and stiffness in the neck and back.
The temperature on admission was 102° F. By the following morning it had fallen to 100° F., but rose again in the evening to 102° F. A similar exacerbation occurred the following day, after which the temperature gradually fell to normal. The pulse was strong all through the course of the illness.
No skin eruption was noted.
Bacteriological Examination. — Cover-slips showed no diphtheria bacilli; a variety of organisms were present, no one apparently predominating.
Cultures showed an almost pure culture of the streptococcvis pyogenes.
Case 18.— Male, aged 31, white. Admitted to tlie hospital March 11, 1895, complaining of sore throat.
History. — The family history was uninijiortant. The patient had the usual exanthems as a cliild; he has not been subject to sore throats.
The present illness began three days ago with soreness of one, and later, of both sides of the throat. He had headache and general aching all over. No chill or chiil.y sensations.
On admission the general condition was good. Tlio throat was congested, and tlie .tonsils were much swollen, almost meeting in the middle line. On the inner side of each tonsil there was a sloughy-l(x>kiug yellow-gray membrane. The neck glands were enlarged and tender.
Behring's Antitoxine No. 2 was iiijccli'd into llic sulicutaiicous tissue of the back.
In the evening of tlie day of admission the throat was so swollen that the patient had ditticulty in swallowing even liquids.
March 12. The swelling Is decreasing; the patient feels better.
Mai'cli It. The swelling is much less.
Marcli 19. The membrane has entirely disappeared.
The temperature on adraissioil was lO.'J.o' F.; bj- 8 A. M. the next morning it was down to 101° F.. but by 8 P. M. was up to 104° F. : it fell in the night, but rose the next afternoon to 102.5° F., after which it gradually .sank to normal.
No skin eruption was noted.
Bacti rioliiiiiral Exiiminatiori.—CoYer-sVips from the membrane showed numerous cocci in chains, but no diphtheria bacilli.
Cultures gave a practically pure growth of streptococcus pyogenes.
These cases again show the necessity of bacteriological examination in all inflammatory throat affections.
Case 16 is interesting from a bacteriological point of view, for, so far as we have been able to make out, a membranous angina due to the bacillus pyoeyaneus has not been described hitherto. This organism, though usually comparatively harmless, has been described as a factor in various diseased conditions, usually in association with other organs; in our case it was apparently in pnre culture, but this may be due to the fact that it had overgrown the organisms with which it was associated. The comparatively frequent presence of the pyoeyaneus in chronic otitis media would lead one to suspect that it may not be an infrequent inhabitant of the nasal or buccal cavities.
The Effect of the Axtitoxixe Treatmext.
Of the eighteen cases above recorded, si.xteen received the antitoxine treatment, three of these cases being non-diphtheritic.
While this of course is too small a number of cases on which to base any statistical conclusions, several facts in connection with the treatment seem worthy of attention.
Two of the cases died, but both of these were moribund on admission, one dying three and the other eight hours after admission, so that the antitoxine was given no chance.
The other thirteen diphtheria cases were most of them mild, in fact none were very severe, but both on the general condition and on the temperature the antitoxine seemed to have a marked effect. It was almost invariably noticed that the day following the injection the patient was much brigiiter, and in the case of children the return of the appetite was the most marked indication of improvement.
Ill looking over the cases it will be noted that in those due to the bacillus diphtheriae the autitoxiue.as a rule, causeda reduction of the temperature to the normal inside of twenty-four hours ; in one or two of the cases there was a slight rise in the temperature eighteen to twenty hours after the inoculation, but in only one case was no effect on the temperature noted. The last two cases afford excellent examples of the effect of the antitoxine on non-diphtheritic cases : both were early cases, so that a spontaneous fall of temperature can be e.xcluded, and in both the temperature was not influenced in the slightest degree by the antitoxine.
Skin eruptions following the antitoxine injections were noted in several of our cases: they have been noted by varions observers since the inauguration of the treatment, but not enough stress has been laid on the fact that these eruptions are iu all probability due to the serum ;x'r sf, and not to the antitoxic agents contained therein. TUe deleterious effects of the serum of one species of animal when injected into a
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member of anotliui . , , i .: ue too well known to be repeated here, but it is interesting to know that Sevestre, by injecting horse-serum in twenty-centimetre doses into children with non-diphtheritic sore throats, was able to produce urticaria and other forms of skin eruption similar to those observed after the use of the autitosine.
The skin eruptions were the only bad effects, if one could so call them, which were observed after the use of the antitoxine. No other appreciable symptoms plainly due to the injection could be observed, nor did the examination of the urine give evidence of any such.
PROCEEDINGS OF SOCIETIES,
THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.
Meeting of October 1, 1895.
Pjartlirosis— Discussion onDr. Finney's paper. (See September-October Bulletin, page 144.)
Dr. Halsted. — In these cases of knee-joint irrigation we do not hope to do more than to greatly inhibit the activity of the micro-organisms — to assist the tissues to destroy the microorganisms. It is rarely necessary to do more than incise an acute abscess ; the tissues do the rest. And yet we know that the tissues about the abscess have been invaded by the pyogenic micro-organisms. In irrigation of the knee-joint we do not expect to reach the micro-organisms outside of the joint.
In the last case reported by Dr. Finney — the one with triple infection — I do not feel at all sure that we could not'have taken care of the joint itself. We amputated because in a few days we found the tissues in the thigh almost up to the hip-joint invaded by the organisms to a shocking extent, with lesions characteristic of the air-producing bacillus.
That solutions of bichloride of mercury are more efficacious than salt solutions in destroying and inhibiting pyogenic organisms outside of the body we have sufficient proof. There is also abundant clinical, if not wholly conclusive experimental evidence that the same is true in the tissue spaces, in joints, etc.
The irrigation of the urethra in the treatment of gonorrbcea furnishes a good clinical example of the benefits to be derived from solutions of corros. sub. Here, too, the specific micro-organisms have been demonstrated in the tissues outside of the urethra.
I speak from a great deal of experience, from daily observations for five years in the Roosevelt Hospital Dispensary, New York. In this work I was very ably assisted by Drs. Itichard Hall and Frank Hartley of New York. The salt -olutions are worse than ineffectual in the treatment of gonorihcta. With them we never succeeded in aborting a case of gonorrhoni, either in private or dispensary practice, but we constantly induced a cystitis and ejjididyniitis. With the bichloride irrigation, not a single case of cystitis or epididymitis occurred in these five years. I think that we have had tlie same exi)erience in the dispensary here. Doctor Brown told me less than a year ago that he had never produced cystitis or ejjididymitis with bichloride irrigation. In private jn-actice it is very common, indeed it is the rule, to abort a gonorrhcea within a week or ten days with bichloride irrigation. Previous to the use of this irrigation I used to dread to have a case of gonorrhcea come to my office; after its
introduction 1 was glad to see them. The treatment became so pojnilar that certain specialists in New York said that they would never use it because it was ruining their practice. Men after a few visits were cured. Nor would they return when a fresh urethritis was contracted. 'Furthermore, they taught their friends h'ow to treat themselves. It would be too much of a digression to give the details of this treatment at this time. But I must ask your permission to say that everything depends upon the intelligent use of the method. The strength of the solution is determined by the use of the microscope and by the tolerance of the particular urethra. The strength to be used varies from 1-200,000 to 1-25,000. A tolerance of the stronger solutions has, usually, to be acquired. ftleu with red hair have, as a rule, sensitive urethras.
The gonococci disappear jiromptly from the ui-ethral discharge after irrigation with solutions of corrosive sublimate, but are uninfluenced, apparently, by irrigation with the salt solution.
A t'ase of Congenital Ptosis.— Dr. Thomas.
The patient, B. L., dispensary No. B 587, whom I wish to show to you to-night, is a boy fourteen years old. He applied at the dispensary a few days ago complaining that he was unable to open his left eye. No similar case had ever occurred in the family so far as was known. The patient was the eighth child and the only son. His birth was natural but difficult. It was noticed soon after birth that he did not open his left eye, and this condition has remained unchanged ever since. In other resj^ects the boy has developed normally.
In looking at him you notice that while his right eye is widely opened, his left eye is nearly closed by the drooping upper lid. The skin of the forehead on the left side is drawn into deep furrows, as if he were trying to lift the eyelid by a strong action of the occipito-frontalis muscle. If the left eye be covered by the hand the forehead becomes smooth. When asked to look up, the patient opens his right eye wider, rolls the eyeball upward and contracts the occipito-frontalis on that side. On the left side the eyeball remains stationary, and the only noticeable change is a still greater contraction of the occipito-frontalis muscle ; if, however, the left eye bo passively opened, the eyeball is moved upward to some extent, but not so far as on the right side. In looking down, the eyes move normally, but the left upjier lid does not follow the movement as does the right.
The lateral movements of the eyes are normal in extent, but there is a curious disassociation ; they appear to move independently of each other. His pupils are equal, moderately
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coatracted ; they react to light and during accommodation. Ophthalmoscopic examination shows the fundus to be normal. The facial muscles and those of mastication act normally.
In this case we have a congenital defect, consisting of a paralysis of the left levator palpebrse superioris, paresis of the superior rectus, and an associated over-action of the occipito frontalis on the same side, forming the common picture of congenital ptosis. The disassociation of the ocular movements is also of interest.
Congenital ptosis is, in our experience, not a common affection, this being the first case which I have had an opportunity of studying. The cause of the trouble is believed to be some abnormality in the nucleus of the third nerve, from which the muscles involved receive their motor nerve fibres. As far as I know, but a single careful anatomical examination of such a case has been made. I refer to the case of Prof. Siemerling, reported in the Archiv f. Psych, u. Nervenkrank.,Y6\. XXIII, p. 764, 189;'. The patient died from general paralysis, but during life he showed no ocular symptoms referable to that disease except the Argyle-Robertson pupils. The congenital ptosis was of the left eye. Siemerling discovered a lesion in the dorsal and ventral parts of the principal group of cells in the nucleus of the third nerve, and what seemed remarkable, the lesion was bilateral, although the left upper lid was alone affected. The nucleus of the third nerve is a complicated structure. It is, however, impossible to go into this question to-night, as I want to call your attention to some other interesting points in connection with congenital ptosis.
In 1883 Ml-. Marcus Gunn exhibited a case before the Ophthalmological Society of London, which showed remarkable associated movements of the paralysed eyelid. When the patient opened his mouth or moved his jaw towards the right, the paralysed left ujjper lid was raised. This case created a great deal of attention, and a committee including Dr. Gowers, Dr. Stephen McKenzie and others was appointed to examine the patient. They confirmed Mr. Gunn's observation and expressed the opinion that in that case the levator palpebrfe "is innervated both from the nucleus of the third nerve and from the external pterygoid portion of the nucleus of the fifth nerve."
Since the publication of this case, a number of cases have been reported, and in May, 1894, Bernhardt {Neurol. CentralblL, Vol. XIII, p. 325) was able to collect twenty-four cases, eighteen of which he used for comparison. In nearly all of those the associated movement of the paralyzed lid occurred, either when the mouth was opened or the jaw moved away from the side on which the ptosis was present, i. e. during the action of muscles supplied by the fifth nerve. In two remarkable cases the fallen lid was raised when the other eye was voluntarily closed, an associated movement between a muscle supplied by the facial nerve on one side and one supplied by the third nerve of the opposite side.
The extent of the associated movement apparently varies in the different cases. The most striking report that I have seen was published in the Arrliiivs of OpJt/kiilmologi/, Vol. XXII, p. 65, 1893, by Dr. A. A. llubbell, in which there are three excellent photographs, illustrating this associated movement. In this case the paralyzed upper lid was raised quite
as much if not more than the normal one when the mouth was opened.
As you see, when the patient whom I have here to-night "opens his mouth wide, or moves the lower jaw strongly towards the right, there is no very evident raising of the left upper lid. If, however, careful measurements are made, it is found that the visual aperture widens two or three mm. The widening is greater when the patient looks down during the movement of the jaws. Voluntary closure of the right eye produces no effect on the left. It is not at all certain that this slight widening of the aperture is due to a contracture of the levator palpebrae and not to other mechanical causes.
The explanation of these associated movements is not clear. Most observers agree with the English committee in the belief that it is due to the third nerve's receiving axis cylinder processes from cells situated in the fifth nucleus. We know that fibres running in motor nerves may arise from cells quite widely separated in the central nervous system. You will see from the diagrams of the nuclei of the motor cranial nerves, which I have placed on the blackboard, the relative positions of the third and fifth nuclei. The third nucleus is under the aqueduct of Sylvius; the principal motor nucleus of the fifth is about the middle of the upper half of the fourth ventricle. The descending root of the fifth extends quite to the level of the third nucleus. There is some doubt as to whether this root should be considered sensory or motor. It is not difficult to believe that nerve cells might send their axis cylinder processes from either the motor nucleus, or from the nucleus from which the descending root arises, to leave the brain by the third nerve. If such a condition underlies the associated movements which occur in congenital ptosis, the question suggests itself whether the condition is a normal one, or whether it only occurs in connection with the abnormality of the third nucleus upon which the ptosis depends. In two cases in which the ptosis was acquired as one of the symptoms of ophthalmoplegia externa due to nuclear disease. Dr. Ilughlings Jackson was unable to demonstrate any associated movements of the paralysed lids, and in the case before you I have not been able to convince either you or myself that there is any actual contraction of the paralysed levator muscle. These cases, so far as they go, would seem to indicate that this connection is not always present. I know of no anatomical investigations that bear on the subject.
Dr. Jackson, in the article referred to above {Lancet, Jan, 6, 1894), suggests another interesting question in connection with cases of congenital ptosis, /. c. whether Muller"s muscle is also paralysed. You may remember that the eyelid contains, besides the levator palpebral smooth muscular fibres, the so-called iliiller's muscle, which help to elevate the lid. This muscle receives its nervous supply from the cervical sympathetic. These nerve fibres leave the spinal cord by the upper four or five dorsal roots. The nerve cells from which they arise have not been localized, but it is believed that they are situated somewhere near the third nucleus. Since we believe that congenital ptosis is due to some central legion, it is important to know whether Midler's muscle is paralysed. Dr. Jackson suggests a method by which this may be determined. It was pointed out by Jessop i^Proctcd. of Royal Soc.,
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Vol. XXXVIII, p. 432, 1885) that if a solution of cocaine be dropped into the eye the pupil dilutes and the visual aperture widens. He demonstrated by experiments that this was due to a stimulation of the endings of the sympathetic nerve, causing contraction of the dilator muscles of the iris and of Jliiller's muscle in the lid. Dr. Jackson urges the importance of applying this test in nervous diseases wherever the sympathetic may be involved, and points out the desirability of testing a ease of congenital ptosis in this manner.
We dropped into both eyes of this patient three or four drops of a four per cent, solution of cocaine. At the end of half an hour both pupils were dilated and the visual apertures of both eyes had widened about two mm. It would appear from this that the cocaine acted equally on the two sides and gave no evidence of paralysis of Miiller's muscle.
Note. — The patient has been examined on several occasions since he was shown to the Society. The observations differ but little from those recorded, but it may be of interest to give the last note of the examination under cocaine.
December 9, 1895. 10.50 a. m., visual aperture, R. eye opened normal, 12.5 mm.
L. eye opened normally, 5 mm. Eye wide open, 5 nun. Pupils equal, about 5 mm. in diameter. One minim of an 8-per cent, solution of cocaine was put into each eye.
11.40 a.m., visual aperture. E. eye opened normajly, 11 mm. Wide open, 15 mm.
L. eye opened normally, 7.5 nun. Eye wide open, 8 nun., and with mouth open, 9 nun. I'ujiils e(iua], diameters about 9 mm.— H. JI. T.
Dr. L. F. Barker. — The case which Dr. Thomas has shown is of more than ordinary interest. As to the connections of the nervus trigeminus and its motor and sensory nuclei with the nucleus nervi oculomotorii, there is little that can be said to have been definitely established. This much is certain, that fibres run from the gray matter connected with the sensory portion of the fifth nerve (t. e. the substantia gelatinosa near the spinal tract of the 5th and the so-called sensory nucleus of the 5th) into the fasciculus longitudinalis medialis, and the intimate relations of the latter bundle to the oculomotorius nuclei have been very definitely proven. Whether or not the motor nuclei of the trigeminus (nucleus princeps and nuclei minores [radicis descendeiitis]) are directly connected with the nuceus n. oculomotorii, does not as yet seem clear. A large amount of work has been done with regard to the various groups of ganglion cells of which the nucleus of the oculomotorius nerve is made up, but up to the present the cells which have to do with individual muscles have not been satisfactorily localized. Neurologists have recently been inspired with new hope as regards this point through the introduction of a new method of investigation. In June of last year Nissl of Frankfurt-am-llain, in an address in Baden-Haden {Ccntrnlblt. fur Nvrnmheilk. u. Psyihiatrie, 1894, Bd. XVII, pp. 337-344), described a procedure which, although of relatively narrow api)lication, has the advantage of establishing exactly the location and relations of many of the nerve cells in the gray masses. For example.
he states that the method will determine for each individual eye-muscle the localization of its corresponding nerve cells in the central nuclei, a result to which the most careful investigators with the use of other methods (c. g. v. Gudden's or llarchi's) have hitherto been iniable to attain.
In an adult or half-grown animal a solution of continuity of the fibre connecting a nerve cell with a peripheral part, be it muscle fibre or epithelial surface, leads to retrogressive changes in the body of the nerve cell. These alterations, though somewhat different in nerve cells of different types, are very characteristic and easily recognizable, Nissl claims, after some experience. Very soon, too, changes occur in the neuroglia cells which are in the neighborhood of the affected neurons. The changes in the cells are recognizable in alcohol tissues sectioned and stained according to the latest directions of Nissl, and his staining reaction has to be looked upon as one of the most delicate we possess for the study of degenerations of the body of the nerve cell. In order to apply the method to the eye muscles, one would either extirimte a given nuiscle or cut the nerve supplying it, and subsequently (the lesions in the rabbit are most characteristic between the 8th and the 15th day) kill the animal and study serial sections of the nucleus of the third nerve. As Nissl points out, the very delicacy of the reaction necessitates the greatest caution in its application. Operations must be done asepticalh', one must be absolute master of the technique and must be familiar with the appearances of the various cell-forms in the normal condition, otherwise the investigator will be led into serious error. Nissl suggests that his method be called "Die Methode der primiiren Reizung." Should this method prove to be as useful as it promises, and already confirmatory work has been done by other investigators, we can hope for a speedy settlement of the much vexed questions regarding the cells of the eye-muscle nuclei. Now that the importance of the gray matter in the anterior corpora quadrigemina as a governing centre for the various movements of the eye muscles is generally recognized, and the connections of the axons of the cells situated there by means of collaterals with the various eye-muscle nuclei have been definitely established, the possibility of an exact localization of the cells in the nuclei concerned directly with the individual muscles comes opjiortunely.
Another point in connection with the case Dr. Thomas has just reported seems to me worthy of remark.
In the formation of an associated movement there has been a marked dissociation of muscular contractions ordinarily assocuited. Dr. Thomas has spoken of the dissociation of movements of the muscles of the two eyes. Usually in contracting the frontalis muscle the fibres on both sides of the forehead are contracted at once. This -boy possesses in an extraordinary degree the power of unilateral contraction of the frontalis ; indeed, when his eyes are open the left frontalis is continually forcibly contracted, while the muscle on the right side is at rest. This is by no means surprising, for we know of many so-called associated movements which, tlirough training and education, can be dissociated, as for example the isolation of finger movements observable in an accomplished pianist.
NOTES ON NEW BOOKS.
BOOKS RECEIVED.
INDEX TO VOLUME VI OF THE JOHNS HOPKINS HOSPITAL BULLETIN.
