OBSERVATIONS 
ON THE 
DIAGNOSIS OF DIPHTHERIA 
AND 
A STUDY OF ITS LOCAL TREATMENT. 
BY 
FRANCIS H. WILLIAMS, M.D. 
(Reprinted from the Boston City Hospital Medical and Surgical Reports.) 
BOSTON: 
Press of Rockwell and Churchill. 
1 8 9 5. OBSERVATIONS 
ON THE 
DIAGNOSIS OF DIPHTHERIA 
AND 
A STUDY OF ITS LOCAL TREATMENT 
BY 
FRANCIS H. WILLIAMS, M.D. 
(Reprinted from the Boston City Hospital Medical and Surgical Reports.) 
BOSTON: 
Press of Rockwell and Churchill. 
1 8 9 5. OBSERVATIONS ON THE DIAGNOSIS OF DIPHTHERIA 
AND A STUDY OF ITS LOCAL TREATMENT. 
FRANCIS H. WILLIAMS, M.D. 
Presented at a meeting of the Suffolk District Medical Society, 
Boston, April, 1894. 
I shall assume that diphtheria is caused by the Klebs- 
Lceffler bacillus and begins as a local disease. The diph- 
theria bacillus flourishes chiefly in the throat and is not 
a motile bacillus, but must be carried to the healthy indi- 
vidual. This is done principally by direct transferrence 
from mouth to mouth, or hand to mouth or nose. By 
mouth to mouth T mean, for example, a healthy child may 
catch diphtheria by biting from the same apple, putting the 
same toys in the mouth, using the same handkerchief as a 
child in whose throat diphtheria bacilli are present, or by 
kissing such a child ; or a mother may use her own handker- 
chief for a neighbor’s ailing child, and thus unwittingly carry 
the disease to her own children. The closer contact among 
children, and the habit they have of putting things in their 
mouths, shows why the disease is more prevalent among 
them than among adults. The bacilli may get on to the 
hands of those who are taking care of or are about persons 
ill with diphtheria, and unless the hands are carefully washed 
may be transferred to the mouth at the next meal on a piece 
of bread, for instance. Again the bacilli may live for 
months in the garments of a person who has been ill with 
diphtheria. But I need not multiply examples as to the 
mode of contagion. 
The bacilli, once conveyed to the mouth or nose, may 
remain in the throat some days, or more than a week even, 
without showing any sign of their presence, and in some cases 
may produce no symptoms of disease, although during this 4 
THE DIAGNOSIS OF DIPHTHERIA. 
period such individuals may give diphtheria to others ; but 
in the usual course of things the presence of bacilli in the 
throat is followed, probably within a day or two, by conges- 
tion, although this congestion may not be marked, and 
usually the tonsils, palate, or pharynx are first attacked ; 
this congestion is sometimes accompanied by much oedema 
and swelling, and is generally soon followed by the appear- 
ance of false membrane, which may at first cover a small area 
only, but following the spread of the congestion may appear 
in new areas on each day for a few days ; in other words, the 
mucous membrane is, as it were, planted with bacilli, and 
the false membrane results, but the crops may not all appear 
at once. Most of the bacilli are found in the outer portions 
of the false membrane. In a word, the natural history of the 
disease seems to be : bacilli on a most alkaline surface, at a 
temperature favorable to their growth, irritation, congestion, 
false membrane. This membrane may disappear from the 
throat before the bacilli. Therefore in the beginning; and at 
the close of the disease an individual is especially dangerous 
to the community, because in the first case his diseased condi- 
tion is unsuspected or thought of slight consequence, and in 
the second case because the normal appearance of the throat , 
although the bacilli may still be present, leads to the belief 
that the danger of contagion from him is past. The bacterial 
test, therefore, is of special importance in these two stages 
of the disease, as it is the only means of detecting the diph- 
theria bacilli. 
In 1892 I began to employ the bacterial test for my 
patients and initiated its use at the Boston City Hospital. 
Since the beginning of 1893 this test has been carried 
out without interruption in the pathological laboratory of 
the hospital, under the direction of Prof. W. T. Councilman, 
and it has now been applied to a large number of cases, 
among them to more than 500 of my patients. A number 
of bacterial examinations have also been made for my patients 
in the laboratory of the Harvard Medical School. 
As already stated, there are two stages of diphtheria in 
which this test is especially serviceable. 
First. Very early in the disease, before the throat shows 
any trace of false membrane. THE DIAGNOSIS OF DIPHTHERIA. 
5 
Second. Late in the disease,,after the false membrane 
has disappeared ; that is, during convalescence. 
Let me illustrate the first class of cases by giving the 
history of a household in which a case of diphtheria oc- 
curred. A patient of Dr. James J. Minot, a boy of eight 
years, had sore throat with membrane on a certain Sunday ; 
bacterial examination showed on Monday evening that the 
bacilli of diphtheria were present. Dr. Minot then put the 
patient under my care. The throats of the other members 
of the household presented no signs of diphtheria, but it 
seemed to me wise to follow my rule and have swabs taken 
from the throats of all. They were also taken by Dr. 
Minot from the throats of those outside of the household 
who had been much with the patient. In three of the 
members of the household bacilli of diphtheria were found, 
although, as already stated, there was nothing to indicate 
diphtheria to the unaided eye when the swabs were taken for 
diagnosis. One of these three throats was carefully ex- 
amined with the mirror by a laryngologist shortly after the 
swab was taken and he found no sign of diphtheria. Thirty 
hours later there was no indication of membrane in two of 
these throats. Treatment with strong hydrogen-dioxide 
acid solution was begun on all these cases as soon as the 
Klebs-Lcefher bacilli were found, and in one of the adults the 
dioxide made conspicuous the false membrane on the right 
tonsil and anterior pillar which was barely visible just before 
its application. No membrane was seen at any time in the 
throat of the second patient, a boy of two years. After 
three days’ treatment with strong hydrogen-dioxide solution 
the bacilli of diphtheria were not found in cultures from his 
throat. The third member of the household referred to 
above, the nursery-maid of the first patient, had no sign of 
false membrane in her throat twenty-four hours after the 
swab was taken, but within a day or two it spread to nearly 
every part of the throat within sight, or whjch could be 
seen by depressing the tongue strongly. The diagnosis of 
diphtheria could not hate been made in these cases, except 
by these bacterial examinations, at the stage of the disease 
when the swabs were taken. These four cases all recovered. 
The advantages of early diagnosis, of early isolation, and 6 
THE DIAGNOSIS OF DIPHTHERIA. 
early treatment are seen by contrasting the above-mentioned 
household with the following family: 
In this family, a child was taken ill with diphtheria, 
a few days later a second child, who died soon after at home, 
and at short intervals two other children, the mother and 
aunt. Three children, the mother, and aunt came to the 
Boston City Hospital and were under my care. The chil- 
dren came too late to be helped, and all died. The mother 
and aunt were the last members of the family to show signs 
of the disease ; they entered the hospital when they had 
been ill three and four days respectively, and recovered. 
Such experiences show that as soon as a case of diphtheria 
is found in a household, the bacterial test should be applied 
to all its members, though their throats may be normal in 
appearance. This would lessen the spread of the disease 
and give more patients the great advantage of early 
treatment; in some cases this might be begun before any 
other warning had been given than the presence of the bacilli. 
In the second class of cases — that is, during what I may 
call convalescence — we frequently find that although the 
throat of a given patient looks perfectly well, yet it still 
contains bacilli, and isolation has therefore to be continued. 
The safeguard which bacterial examinations of the throats 
during the convalescent stage may be to the community is 
well illustrated by one of my patients (treated locally with 
corrosive sublimate 1 to 10,000, and a weak (10 volume) 
solution of hydrogen dioxide), from whose throat the 
false membrane had disappeared and who had expressed a 
hope to be at home for the Thanksgiving festival. Formerly, 
discharge being determined by the inspection of the throat 
only, she would have been allowed to leave the hospital 
much before the desired date. The bacterial test, however, 
which was made at short intervals for some weeks after the 
date of the festival referred to above, showed the bacilli to 
be present. One shudders to think of what might have fol- 
lowed her contact with the children of the family, and how, 
originating with her, the disease might have spread to other 
families. 
In a former paper 1 I have referred to the persistence of 
1 “ Araex’ican Journal of the Medical Sciences,” November, 1893. THE DIAGNOSIS OF DIPHTHERIA. 
7 
the bacilli in the throat for some weeks, and in one patient 
(treated locally with corrosive sublimate 1 to 10,000) for 
nearly three months, and pointed out the necessity of 
making a bacterial examination of the throats of patients 
before isolation is terminated. 
We now come to another stage of the disease in which 
there are acute appearances in the throat, with false mem- 
brane. In these cases the Klebs-Loeffler bacilli are usually 
found. We may find cases, though they are uncommon, 
in which one, two, or even three examinations fail to find the 
bacilli of diphtheria, although direct examination of the 
membrane itself sometimes shows them to be present. Fur- 
ther, we may have cases in which no bacilli are found in the 
first examination, but subsequent trials show them to be 
present; and, finally, we may have cases in which the bac- 
terial examination during life fails to find them, although a 
post-mortem examination reveals them. On the other hand, 
unless the test is carefully made it is quite possible to mis- 
take some other bacillus for the bacillus of diphtheria. 
I therefore feel called upon to repeat my statement of last 
year, that these examinations are not infallible ; but when all 
precautions have been carefully taken, and more than one 
examination made, I believe that they may usually be relied 
upon, except in cases where the disease is laryngeal, and 
that we are certainly justified in taking a much more favor- 
able view of the recovery of a patient in whose throat the 
bacilli are not found than in those where they are found, 
although the appearances in the throat may be similar in 
both. Failure to find the Klebs-Lcefiler bacilli may mean 
that they have, perhaps become less abundant through the 
more vigorous growth of other and less dangerous organisms. 
It may be that this is one of nature’s ways of limiting diph- 
theria. The diphtheria cases which give a pure or nearly 
pure culture of the bacillus seem to be very fatal1 unless 
efficient treatment is employed, so far as one may infer from 
47 cases in which the mortality was 64 %. A local treat- 
ment, which I shall describe later, is, I think, especially effi- 
1 It is important to realize that if the pulse in diphtheria suddenly changes during 
the acute stage of the disease and takes on the character indicative of a low blood- 
pressure, the prognosis is very grave, no matter how well the. patient may appear to 
be in all other ways. 8 
THE DIAGNOSIS OF DIPHTHERIA. 
cient in cases where the Klebs-Lcefiler bacillus only is found ; 
nine cases giving a pure or almost pure culture of the diph- 
theria bacillus in which this treatment was used early all 
recovered. 
As regards cases with false membrane in which the diph- 
theria bacilli are not found, 50 cases of what may be 
called pseudo-diphtheria, occurring in different years, there 
was a mortality of 28%. As these cases were designated as 
pseudo-diphtheria on account of the absence from the bacte- 
rial test of the Klebs-Loeffler bacillus, we shall do well to 
look into this high mortality of 28%, or 14 out of 50 cases, 
a little more closely. These 14 cases, in about an equal 
number of instances, contained either streptococci or staphy- 
lococci, or both together. 
10 were laryngeal, with 7 intubations, 
1 had typhoid fever, 
1 scarlet fever, 
1 septic, -with nasal discharge, 
1 had nasal discharge. 
14 
Both the cases with nasal discharge were two years old, and 
in wretched condition when they entered the hospital. 
Excluding the case of typhoid fever, there are two features 
which most of these 14 cases had in common ; that is, their 
laryngeal character and their extreme youth — the average 
age was three years. It seems to me that these conditions 
determined the fatal outcome in these cases rather than any 
special coccus, or, what is more probable if we take the 
ground that the laryngeal cases are usually diphtheria, the 
Klebs-Loeffler bacilli probably escaped detection in some of 
them. As autopsies were not obtained, this point could not 
be determined. 
In studying diphtheria one is struck by the large number 
of cases in which the larynx is involved and the high mortal- 
ity among such cases. As we continue to use the bacterial 
test and obtain more autopsies I think we shall find that the 
percentage of fatal cases of membranous throats where the 
bacillus of diphtheria is absent will be smaller. Large num- 
bers of cases of so-called pseudo-diphtheria already reported THE DIAGNOSIS OF DIPHTHERIA. 
9 
by other observers, in which the mortality is very low, point 
to this conclusion. If the bacterial test has been carefully 
made, no bacilli of diphtheria found, and the larynx and 
nose are not involved, the prognosis of cases of membranous 
throats, where no other disease is present, — such as typhoid 
fever, pneumonia, measles, or scarlet fever, — is usually good. 
Of such cases my experience thus far has justified me in 
taking a hopeful view. I recall a case seen in consultation 
where the physician in charge had given a wholly hopeless 
prognosis, but the bacterial examination and the general 
condition of the patient led me to take an opposite view, 
which proved to be the correct one. 
The inferences which may be drawn from suspicious cases 
seem to be these : First, cases which come to the hospital 
looking like diphtheria usually are such; that is, perhaps 
about nine times out of ten. The milder cases of membranous 
throats are not sent to the hospital in such large numbers 
as the severer ones, and thus the proportion of cases of diph- 
theria is smaller in suspicious cases if seen outside of the 
hospital; this has been my experience in private practice. 
Second, cases which look like tonsillitis, for example, usu- 
ally are such, although now and then among such cases the 
bacilli of diphtheria are found. In practice it is well at first 
to regard everything which resembles diphtheria as diph- 
theria, until careful bacterial tests have been made. 
Before leaving the subject of diagnosis, allow me to re- 
mind you again of the importance of recognizing the mixed 
cases of diphtheria and scarlet fever; these are doubly 
dangerous, as they may give rise to either disease in other 
individuals, especially in a hospital for contagious diseases, 
and require special and careful isolation. In 1892, when I 
first saw these mixed cases, that is, found the Klebs-Lcefiler 
bacillus coincidently with scarlet fever in certain patients, 
their presence was denied by most of those, at least in this 
country, who had given the question special study, but now 
their existence has, I think, been generally recognized.1 
1 In scarlet fever it seems to me desirable to prevent the dissemination of the 
epithelial scales, which are often shed abundantly, and to hasten the removal of this 
layer of epithelium in order to free the normal skin. For this purpose I have my 
patients rubbed all over, daily, avoiding the hair, with a mixture containing seven 
parts of a 10-volume solution of hydrogen dioxide with one part of glycerine; if the 10 
THE DIAGNOSIS OF DIPHTHERIA. 
Three cases of typhoid fever with membranous throats in 
which bacilli of diphtheria were found, occurred during my 
service ; one of these has already been referred to in a former 
paper of mine ("American Journal of the Medical Sciences,’’ 
November, 1893), and Dr. John L. Morse has described 
a second of these cases (Isabella N.) in the Boston City 
Hospital Report for 1894. In my above-mentioned paper I 
also referred to the coincidence of diphtheria and measles 
during my service. 
It is not very rare to see patients with syphilis presenting 
appearances in the throat similar to those found in diph- 
theria (of course both diseases may occur together) ; if 
syphilitic patches occur with an acute tonsillitis or pharyn- 
gitis the similarity to diphtheria is more striking. 
Let us now consider the local treatment of diphtheria, first 
from the laboratory, and, second, from the clinical side. 
The micro-organisms, dangerous above all others in the 
throat, are the venomous bacilli of diphtheria, and an early 
attack upon them with a suitable application diminishes the 
amount of the poison and probably prevents the extension 
of the bacilli to less accessible parts. 
A rational step to be taken in our endeavor to destroy the 
bacilli is to ascertain what germicides will find and kill them 
quickly, and also which of the germicides, sometimes used, 
will not do so. I say find and kill, as there are many ap- 
plications which will kill the bacilli in the laboratory, but 
when used in the throat simply wash the surface of the false 
membrane; there is one, however, which is an exception to 
this, as it has the quality of promptly disintegrating certain 
portions of the false membrane. In the plan which I adopted 
in the study of the action of various germicides upon the 
Klebs-Loeffler bacillus and several of the organisms which 
sometimes accompany it, I assumed that the germicide to 
be efficient must act quickly, as the contact in the throat 
between the germicide and the organisms is limited to a 
few seconds. It was, therefore, necessary to ascertain what 
would kill these organisms in live or ten seconds. 
patient finds this too sticky the proportion of glycerine may be reduced. A quarter 
of the body may be done at one time, and some hours later another quarter, and so 
on. As soon as any portion of the skin is normal the application may be there 
dispensed with. THE DIAGNOSIS OF DIPHTHERIA. 
11 
Second, if an agent or agents could be found to kill the 
organisms in five or ten seconds, the next step would be to 
ascertain what harmful effect, if any, they could have upon 
man, and to select one or more of those which would be least 
injurious to him ; many germicides, such as corrosive sub- 
limate, carbolic acid, the cresols, hydrochloric, nitric, phos- 
phoric, and sulphuric acids alone and in efficient strengths 
are either poisonous or irritating, or both. 
The third step in the investigation would be to learn how 
to apply efficiently a substance quickly fatal to the organisms 
and harmless to man, provided such a substance could be 
found. 
Tests with various germicides were made under my 
direction, or by me, in the Biological Laboratory of the 
Massachusetts Institute of Technology upon the bacillus of 
diphtheria, the staphylococcus pyogenes aureus and albus, 
the streptococcus pyogenes, and a diplococcus, and I wish to 
express here my appreciation of Prof. W. T. Sedgwick’s 
kindness in permitting me to use his laboratory, and my 
obligations to his former and present assistants, Messrs. 
McLauthlin, Mathews, and Keith, for carrying out many of 
these tests.1 
1 The following outline taken from a former article will show the method pursued. 
In any of the ordinary methods for the determination of the germicidal action of any 
liquid disinfectant upon a given bacterial species, three distinct and successive processes 
may usually be recognized. These are : first, the mingling for a known period of ,a 
pure culture of the given species with a suitable amount of the germicide ; second, the 
dilution, after the desired interval has elapsed, of this mixture to the extent necessary 
not only to check further bactericidal action, but also to avoid the possibility of any 
future inhibitory effect; and third, the planting of a portion of this dilution in a suit- 
able culture medium, in order to permit the growth and consequent recognition of 
any bacteria which may have survived the action of the germicide. 
As a source of the diphtheria bacillus, we used a pure culture that came originally 
from the laboratory of Dr. Welch, of Johns Hopkins University, or one from Dr. 
Frudden’s laboratory in New York, or from my own cases. From these, plantings 
were made in bouillon, and to ensure greater accuracy, in most of the experiments old 
and fresh bouillon cultures were used side by side, or a mixture of the two was em- 
ployed. 
The following record of a single action experiment with its control will serve to 
illustrate this method. 
Fivec.c. of 50-volume dioxide solution (% $ acid) were placed in a 60c.c.Erlenmeyer 
flask and 0.25 c.c. added of a bouillon culture of the diphtheria bacillus. (In later 
tests, the germicide was poured over the culture.) Ten seconds after, in order to 
stop the action of the dioxide, the mixture was quickly poured into a litre flask con- 
taining 600 c.c. of slightly alkaline normal salt solution. Thirty seconds after this, 
the whole having been well shaken, 0.2 c.c. were transferred to 75 c.c. of alka- 
line normal salt solution in another flask. At the end of three minutes (in the 12 
THE DIAGNOSIS OF DIPHTHERIA. 
All of the tests given in the following tables, besides 
many others, have been made in duplicate, and some have 
been repeated several times. 
TABLE I. — Tests with various Germicides upon the Klebs- 
Lceffler Bacillus. 
Germicide. 
Did not kill all. 
Killed all. 
1 Hydrochloric acid 
3% 
4% 
'Nitric acid 
2% 
1 Sulphuric acid 
5% 
10% 
1 Phosphoric acid ..... 
2% 
Boric acid ...... 
Solution of chlorinated soda (hypochlorite 
4% • 
of sodium), containing of available 
chlorine ...... 
1-2500 
1-1000 
2 Chlorine....... 
1-25000 
1-10000 
Corrosive sublimate .... 
( 1-10,000 
\ (0.01%) 
1-5000 
(0.02%) 
Chloroform (in water) .... 
1-200 
Carbolic acid 
4 5% 
4 5% 
Tricresol in 25% alcohol 
3% 
3Metaci’esol in water .... 
h% 
Paracresol in water 
hi 
Action period, 10 seconds. 
later experiments at the end of thirty seconds), 1 c.c. of the last dilution was planted 
in 6 c.c. of the bouillon. At the end of four and a half minutes 1 c.c. of the dilution 
was added to 6 c.c. of melted glycerine agar at 40° C., and the mixture at once poured 
into a Petri dish. 
In the control experiment, 0.25 c.c. of the bouillon culture of the bacillus were 
mixed with 600 c.c. of alkaline normal salt solution, then 5 c.c. of 50-volume dioxide 
(% # acid) added, and all were shaken. Thirty seconds after the addition of the dioxide, 
0.2 c.c. of the mixture were transferred to 75 c.c. of alkaline normal salt solution in 
another flask. After four and a half minutes, a glycerine-agar plate was made as 
before. 
After a few days’ growth in the incubator, the agar plate from the control experi- 
ment showed 1,600 colonies of the diphtheria bacillus. At the same time, neither the 
agar plate, nor the bouillon tube, prepared from the action experiment, showed any 
growth. 
Evidently the agar plate is of especial advantage when a part only of the bacteria 
are killed, i.e., when the germicide is diluted just beyond its effective limit. The 
bouillon tube gives no precise means of distinguishing between the survival of a part 
and the survival of the whole of the bacteria. 
1 U.S. Pharmacopoeia dilute acid contains 10 per cent, of acid. 
2 Chlorine water contains 0.4 per cent, of chlorine, which diluted with 99 parts of 
water, gives 1-25000. Chlorine water cannot be mixed with hydrogen-dioxide solutions. 
31 have used a solution containing y2 # of metacresol and 25-volume acid hydrogen- 
dioxide in twenty-five cases of diphtheria; objection has been made to the taste 
by some patients, and it seems to me to be less satisfactory than a strong hydrogen- 
dioxide solution alone. 
4 Does not always kill. THE DIAGNOSIS OF DIPHTHERIA. 
13 
TABLE II. — Tests with various Germicides upon the Staphy- 
lococcus Pyogenes Aureus. 
Action period, 10 seconds. 
Germicide. 
Did not kill all. 
Killed all. 
Hydrochloric acid ..... 
2% 
4% 
Nitric acid 
Solution of chloi'inated soda (hypochlorite 
of sodium), containing of available 
i% 
2% 
chlorine ...... 
1-2500 
1-1000 
Corrosive sublimate .... 
1-5000 
Carbolic acid 
1% 
m 
Tricresol in water 
1% 
i% 
Metacresol in water .... 
it 
4% 
Paraeresol in water ..... 
i% 
ht 
Orthocresol in water .... 
i% 
Staphylococcus Pyogenes Albus. 
Germicide. 
Did not kill all. 
Killed all. 
Hydrochloric acid ..... 
2% 
4% 
TABLE III. — Tests with various Germicides upon the Strep- 
tococcus Pyogenes. 
Action period, 10 seconds. 
Germicide. 
Did not kill all. 
Killed all. 
Hydrochloric acid ..... 
1% 
i% 
Nitric acid ...... 
h% 
Solution of chloi’inated soda (hypochlorite 
of sodium), containing of available 
chlorine ...... 
1-2500 
1-1000 
Corrosive sublimate .... 
1-10,000 
1-5000 
Carbolic acid ...... 
1% 
5% 
Metacresol in water .... 
i% 
h% 
Paracresol in water ..... 
i% 
From these tables it will be seen that with the exception 
perhaps of the solution of chlorinated soda (hypochlorite of 
sodium) and the cresols, there is no one germicide that is 
equally active against all of these organisms. In general it 
may be said that the streptococcus pyogenes is the easiest to 
kill, the staphylococcus aureus the most difficult. A few tests 14 
THE DIAGNOSIS OF DIPHTHERIA. 
made upon the staphylococcus pyogenes albus indicate that in 
this respect it is similar to the aureus. A weak solution of 
hydrochloric acid, %%, will kill the streptococcus in ten sec- 
onds, but it takes a 4 % solution to kill the Klebs-Loeffler bacil- 
lus in the same time. It takes about the same strength to 
kill the staphylococcus aureus and albus. The staphylococ- 
cus aureus is more resistent to corrosive sublimate than these 
other organisms; on the other hand, it is more susceptible 
to carbolic acid than they are. 
It should be remembered that in the laboratory tests the 
micro-organisms are presented to the germicides in a liquid 
culture, whereas clinically they are found enveloped in a 
mass of pus or false membrane, or other matter. Hence the 
advantage of using the substance I am about to consider. 
To discuss the action of all the germicides T have studied 
during my work on diphtheria would not be feasible here, 
but I will devote a few words to one of them ; namely, 
hydrogen dioxide. 
The general principle in antiseptics which my studies have 
brought out, and which I believe to be a new one, is the ad- 
vantage of mixing the stronger germicides with hydrogen 
dioxide, a substance which has the special property of disin- 
tegrating some kinds of dead organic matter, such as pus, 
or certain portions of false membranes, thus rendering the 
bacilli more accessible, and so opening the way for the action of 
the stronger germicides. Pure hydrogen-dioxide solutions, 
or rather neutral solutions, are comparatively weak germ- 
icides, but we may put with them any compatible 
germicides, or use them alternately with an incompatible 
one, the choice depending upon the micro-organisms we de- 
sire to kill. For instance, the mineral acids which are found 
in all the 10-volume hydrogen-dioxide solutions sold in the 
market increase the germicidal value of these solutions. A 
20-volume or even a 40-volume neutral solution of hydrogen 
dioxide will not kill all the streptococci in 10 seconds, but a 
Aveak solution of hydrochloric or nitric acid will do so. 
Tests, therefore, of the germicidal value of the hydrogen- 
dioxide solutions should always take into account the kinds 
and amount of free acid present. THE DIAGNOSIS OF DIPHTHERIA. 
15 
TABLE IV. — TestS with Hydrogen-Dioxide neutral and acid 
Solutions upon the Klebs-Lceffler Bacillus. 
Action period, 10 minutes. 
volumes containing 0.05% of acid.1 
This is stronger in acid than a U.S. Pharmacopoeia 10-volume hydro- 
gen-dioxide solution diluted with three parts of water, a strength which 
is frequently used by physicians. 
Did not kill all. 
Action period, 10 seconds. 
Action period, 5 seconds. 
Did not kill all. 
Killed all. 
5 volumes containing 0.1% acid. 
50 volumes containing 0.17% acid. 
510 “ “ 0.2% “ 
100 
“ “ about 0.3% “ 
12| “ “ 0.25% “ 
150 
“ “ 0.45% “ 
3 25 “ “ 0.5% “ 
200 
“ “ 0.6% “ 
50 neutral or slightly alkaline. 
250 
“ “ 0.9% “ 
TABLET.— Tests with Hydrogen-Dioxide neutral and acid 
Solutions upon the Staphylococcus Pyogenes Aureus. 
Action period, 10 seconds. 
Action period, 5 seconds. 
Did not kill all. 
Killed all. 
25 volumes containing 0.5% acid. 
100 volumes containing 1% acid 
50 “ “ 1.1% “ 
110 “ neutral. 
80 “ “ 0.26% “ 
Staphylococcus pyogenes albus 
was also killed by a 100-volum< 
hydrogen-dioxide solution containin 
g 1% acid. 
TABLE VI. — Tests with Hydrogen-Dioxide neutral and 
acid Solutions upon the Streptococcus Pyogenes. 
Action period, 10 seconds. 
Did riot kill all. Killed all. 
10 volumes containing 0.05% acid. 25 volumes containing 
1.1% acid.4 
10 ‘ 
0.10% “ 12* 
0.5% “ 4 
20 ‘ 
‘ neutral or slightly alkaline. 
40 ‘ 
1 “ “ “ “ 
1 The acid was estimated as HC1 with a 1-100 normal NaOH solution and phenol- 
phthalein. 
2 The U.S. Pharmacopoeia 10-volume solution contains not more than 0.036$ 
of acid. 
3 Sometimes a 25-volume solution containing 1-6 per cent, acid will kill, and some- 
times it will not kill. 
* The tests given in Table III., made later than these, show that 0.5 per cent, of 
hydrochloric acid alone “ killed all ” in ten seconds. 16 
THE DIAGNOSIS OF DIPHTHERIA. 
Tests with hydrogen-dioxide acid solutions upon a diplococ- 
cus from the throat of a patient ill with diphtheria showed that 
a 25-volume solution containing 0.1% acid did not kill in ten 
seconds, hut that a 50-volume solution containing 0.1% of 
acid did kill in ten seconds. 
It is not assumed that these bacterial tests have the ac- 
curacy of chemical ones. I have found nothing, however, 
which vitiates the general character of the deductions drawn 
from these tests : First, that neutral hydrogen-dioxide solu- 
tions are comparatively weak germicides; second, that the 
mineral acids, especially nitric acid, are stronger germicides ; 
third, that hydrogen dioxide and hydrochloric acid together 
are more efficient than either alone against the Klebs-Loefiler 
bacillus; and fourth, that the 50-volume (0.2% acid) 
hydrogen-dioxide solution is not a good germicide against 
the staphylococcus, — 100-volume hydrogen dioxide acid 
(1%) solutions are required to kill this organism in five 
seconds. I hope to discuss the more general applications of 
these tests in another paper. 
I observed an interesting correspondence between the 
laboratory tests and clinical experience in several cases, and 
will recur to this point. 
We now come to the clinical side of the local treatment of 
diphtheria, and the treatment to which I wish to direct your 
attention is that with strong hydrogen-dioxide acid solu- 
tions.1 The mortality in this State from diphtheria is 
greatest during October, November, December, and January, 
and my last service at the Boston City Hospital included 
the three latter months, November and December, 1893, 
and January, 1894, but I have permission to consider here 
the cases that were admitted in October, 1893, also. 
On the mild, as well as on the hopeless cases, a 10-volume 
solution of hydrogen dioxide was generally used, alone or in 
connection with a solution of corrosive sublimate (1-5000 
or 1-2500) or a solution of chlorinated soda. On all of 
the severer cases which came in the early days of the disease, 
1 I have found these strong solutions useful in minor surgery; they should not be 
used in closed cavities, as too much oxygen might be set free and cause pressure. 
As a dressing for sores or ulcers, one may use a 10-volume solution of hydrogen 
dioxide containing 0.1—0.2 percent, of hydrochloric acid; when desirable, pepsin 
may be added to this solution. The dioxide does not interfere with the action of the 
pepsin. THE DIAGNOSIS OF DIFHTHERIA. 
17 
and daring my service, I endeavored to use a 50-volume hy- 
drogen-dioxide acid solution at short intervals. 
To illustrate the advantages of using the 50-volume solu- 
tion, let me take four patients who entered the hospital 
about the same time : 
Two cases of diphtheria treated with a 10-volume solution 
of hydrogen dioxide. 
P. H., 21 years old, entered the hospital December 1st. 
Klebs-Loetller bacilli found in the cultures. Thick false 
membrane on both tonsils and on the sides of the pharynx. 
Under treatment of 10-volume hydrogen-dioxide solution 
every four hours the membrane had disappeared on Decem- 
ber 20th, but there were still bacilli of diphtheria present on 
December 20th and 23d. The membrane returned again on 
January 1st. On January 3d no bacilli were found. 
H. N., 6 years old, entered the hospital on December 
2d. Klebs-Lcefher bacilli found in the cultures. Small 
specks of false membrane on right tonsil and right palate. 
Ten-volume solution every three hours. Bacilli still present 
on December 25th ; absent January 5th. 
Two cases of diphtheria: the tirst one treated in part and 
the other wholly with a 50-volume solution of hydrogen di- 
oxide. 
S. M., 10 years old, entered the hospital on December 3d. 
Bacilli of diphtheria found in the cultures. This case 
seemed more severe than either of those above mentioned. 
False membrane on both tonsils, left palate, right anterior 
pillar, right and left wall of pharynx. At first a 10-volume 
solution was used, but as the membrane increased a 50-vol- 
ume solution was substituted. Bacilli of diphtheria present 
December 10th ; absent December lGth. , 
J. AY., 6 years old, entered the hospital December 8th. 
Bacilli of diphtheria found in cultures. A more severe case 
than any of the above. Thick false membrane on both ton- 
sils, and on both anterior pillars. The next day it covered the 
right, left, and posterior pharyngeal wall. The use of fifty- 
volume hydrogen-dioxide acid solution was then begun. 
Bacilli of diphtheria were present on December 11th, throat 
clear on December 16th, bacilli absent December 17th. 
Of these four cases the last two to enter the hospital pre- 18 
THE DIAGNOSIS OF DIPHTHERIA. 
sented more severe local symptoms than the first two, the 
last one especially. The patients who entered the hospital 
December 1st and 2d, respectively, had a l()-volnme hydro- 
gen-dioxide solution applied, and the bacilli were absent Jan- 
uary 3d and 5th respectively. Average duration of bacilli, 
34 days. The patients who entered the hospital December 
3d and 8th, respectively, had 50-volume hydrogen-dioxide 
acid solution and the bacilli were absent December lGth and 
17th respectively. Average duration of bacilli 11 days. 
The three following cases further illustrate this point. 
The patients were adults of about the same age. 
Case No. I. — Membrane on tonsils and posterior pharynx. 
Cultures were made from the throat about every four days 
and bacilli of diphtheria found. On the 53d1 day of the 
disease bacilli of diphtheria still found in the cultures; on 
the 5t5th day none were found. The treatment in this case 
was 10-volume hydrogen-dioxide solution every hour, cor- 
rosive sublimate 1-2500 on a swab every two hours. Fi- 
nally some of the strong hydrogen-dioxide solution was 
used; after this had been applied for about three days the 
bacilli disappeared. 
One case of diphtheria in which a partial use of the strong 
dioxide acid solutions was made. 
Case No. II. entered the hospital more than two weeks 
later than No. I. Membrane on both tonsils. Ivlebs- 
Lcefher bacilli found in the cultures. As there was no 
strong dioxide solution at hand a 10-volume dioxide solution 
was used every two hours, followed by 1-2000 corrosive 
sublimate with 1% citric acid on swab. During the treat- 
ment the membrane spread and covered besides both tonsils, 
the soft palate on both sides, anterior and posterior pillars, 
and the left and posterior wall of the pharynx. As soon as the 
strong dioxide arrived, the above treatment was stopped and 
a 50-volume hydrogen-dioxide solution was applied every 
two hours by day and every three hours by night for three 
days; then the intervals between the treatments were in- 
1 The duration of the bacilli in this case is above the average duration of the bacilli 
in the 23 cases alluded to later, in which the treatment was a 10-volume solution of 
hydrogen dioxide alone, or in connection with corrosive sublimate or chlorinated soda ; 
but in two other of these cases the bacilli were present in the cultures three weeks 
longer than in this case. THE DIAGNOSIS OF DIPHTHERIA. 
19 
creased. After the culture made for diagnosis, no subse- 
quent culture, unfortunately, was made until the 26th day of 
the disease. No bacilli were then found or afterwards. 
This patient was discharged from the hospital two weeks 
earlier than No. I., and entered, as above stated, more than 
two weeks later. 
One case of diphtheria, in which a complete use of the 
strong hydrogen-dioxide acid solutions was made. 
Case No. III.—This case entered the hospital a month 
after No. I. Klebs-Lcether bacilli found in the cultures. 
The membrane was everywhere on tonsils, palate, uvula, 
pharynx, both sides and back, and in nose,—a case which 
justified the old-fashioned term of putrid sore throat. A 50- 
volume hydrogen-dioxide solution was applied in spray 
every three hours during the day and twice during the night 
for five days; a 25-volume solution was then substituted, 
which was applied three times during the day. No bacilli 
were present in a culture made on the 8th day of the disease 
nor at any subsequent examination. The throat of No. III. 
was free from bacilli two weeks earlier than No. I., although 
the patient entered the hospital a month later than No. I. 
An estimate of the advantage in using the 50-volume solu- 
tion, in point of the duration of the bacilli, is shown better 
by comparing the average time during which the bacilli re- 
mained in the throats of the milder cases which were treated 
with a 10-volume solution of hydrogen dioxide alone, or in 
connection with a solution of chlorinated soda or corrosive 
sublimate, with the average time during which the bacilli 
remained in the throats of patients, more severely ill, but 
who on the other hand were treated with 50-volume hydro- 
gen-dioxide solutions. Most of both sets of cases occurred 
during about the same months. 
In the first class of cases, 23 in number, the bacilli were 
found on the average to be present in the cultures on the 
27th day of the disease and absent on the 36th day of the 
disease. No cultures were made between the two periods 
from which these averages were made up. The average age 
of these cases was 17 years.1 In the second set of cases 
1 Since tlie above was written I have used 0.5 per cent, salt solutions in 11 cases. In 
these the bacilli were found to be present on the average on the 26.3 day of the dis- 20 
THE DIAGNOSIS OF DIPHTHERIA. 
(severer ones), namely, those treated with strong hydrogen- 
dioxide acid solutions, 26 in number,1 the bacilli were found 
on the average to be present in the cultures on the 12th day 
of the disease and absent on the 18.8 day of the disease. 
No cultures were made between the two periods from which 
these averages were made up. The average age of these 
cases was 19.4 years. 
It is hardly necessary to point out that the strong dioxide 
would probably have driven the bacilli from the throats of 
the milder cases sooner than it did from the severer ones. 
In two-thirds of the 26 1 cases treated with strong hydro- 
gen-dioxide acid solutions, the bacilli disappeared before the 
membrane; in the remaining third this point was not deter- 
mined. The patients were not discharged from the hospital 
until both bacilli and membrane had disappeared. 
The capacity of a hospital for the treatment of diphtheria 
would be increased by using the local treatment with strong 
hydrogen-dioxide solutions rather than those ordinarily em- 
ployed, as the patients would remain in a diphtheria ward a 
shorter time. 
The diminution of the bacilli in the throat under different 
treatments may be studied by examining a cover-glass prep- 
aration under the microscope made from swabs taken di- 
rectly from the throat. This was done in a few cases only. 
After a patient had had, for example, a lO-volume hydro- 
gen-dioxide solution for ten days, bacilli of diphtheria and 
other organisms were readily found. In cases treated with 
50-volume hydrogen-dioxide solution examined in the same 
way from two to seven days after beginning treatment, very 
few organisms of any kind were found ; bacilli were, how- 
ever, found in cultures in these cases for a longer period 
than in the cover-slips; these examinations show the marked 
and rapid diminution in the number of bacilli under the 
treatment by a 50-volume hydrogen-dioxide solution. 
ease and absent on the average on the 3.">.4 day of the disease. No cultures were 
made between the two periods from which these averages were made up. One of 
these 11 cases had what may be described as a raw-beef throat—a condition which 
lasted nearly as long as the bacilli remained in the throat, which was six weeks. 
1 These cases are 26 of the 30 cases taken up on page 31; of the four remaining 
cases, two died and two had no bacterial test applied before discharge; therefore 
they could not be taken into consideration here. THE diagnosis of diphtheria. 
21 
The following case is one of those which illustrates how 
the 50-volume hydrogen-dioxide acid solution may kill the 
diphtheria bacilli in a wound : 
A patient ill with diphtheria had a contused wound, which 
was incised and the pus let out. A swab wTas taken from 
the wound and the culture made from it was an almost pure 
culture of diphtheria bacilli. The flaps of thick dead skin 
were trimmed off, leaving an open wound about an inch in 
diameter, covered with pus. The wound was cleansed with 
50-volume hydrogen-dioxide acid solution on a mop and 
covered with gauze moistened with a 10-volume solution. 
Four hours later the gauze was removed and a second swab 
taken ; no diphtheria bacilli were found, only staphylococci. 
That the diphtheria bacilli were killed by the 50-volume 
hydrogen-dioxide solution and the staphylococci wTere not, 
is in accord with the laboratory tests. 
Since this paper was read, by the kindness of Dr. H. W. 
Cushing I have used in certain cases in his service (surgical) 
the strong hydrogen-dioxide solutions—usually 25, sometimes 
50 volumes — freely upon large granulating surfaces of burns 
and ulcers ; when they were so situated that the strong dioxide 
solution could be poured into a cuplike depression of the 
granulating surface, this was done, and the dioxide allowed 
to remain some minutes ; it was then washed out and more 
strong dioxide solution poured in ; this was repeated several 
times. The granulating surfaces were cleansed in this way 
daily for weeks without causing the patient any discomfort, 
and were dressed with a dilute solution of hydrochloric acid 
yL or % • All healed well. 
Let us now consider the method of applying the strong 
hydrogen-dioxide solutions.1 
The Strength of the Applications. — This should ordi- 
narily be from 25 to 50 volumes, according to circumstances, 
1 How not to use the solutions of hydrogen dioxide in diphtheria is very well 
illustrated, I think, by some cases that were brought to my attention since this paper 
was read. A solution of hydrogen dioxide in ether, known as pyrozone, was used to 
make the hydrogen-dioxide solution. The manufacturers claim that these solutions 
are nearly neutral; in other words, an important germicidal element, the acid, is left 
out; the special property of the hydrogen dioxide itself being the disintegrating 
power. Second, the air-pressure used in the atomizers was too great. The air was 
pumped up to a pressure of 80 pounds, then allowed to run down to 30 pounds and 
again pumped up to 30 pounds. The pressure should not be more than 6 or 8 pounds. 22 
THE DIAGNOSIS OF DIPHTHERIA. 
containing about to of acid. A stronger solution 
must be used in the throat than in the laboratory on account 
of the dilution by the saliva. If there is much membrane, 
and especially if the case is septic and in the early days 
of the disease, the full 50-volume strength is needed. It 
is well to make the application with a mop so far as 
may be, and the spray should be used gently. One should 
not omit to treat the nose and keep it clear, but a separate 
atomizer should be used for this purpose. In spraying 
the nose, only very weak solutions 1 or 2 to 5 volumes 
should be used. The spray should be directed horizon- 
tally into the nostril and not upwards. In the posterior 
nares the strong solutions may be employed by means 
of an up-spray, or by a spray directed forwards from the 
posterior nares; the formation of much foam after the ap- 
plication of the solution to the latter parts indicates the 
presence of membrane. It is very important to know the 
acidity and strength of the solutions of hydrogen-dioxide, 
and the value of the treatment cannot be properly esti- 
mated unless analyses of the solutions are made. The 
different makes vary in the amount of acid and hydrogen 
dioxide they contain. The 10-volume solutions purchased 
for the hospital, from which the strong solutions were made, 
have been excellent. The most efficient mode of application 
is by means of a gentle spray under an air-pressure of 6 to 
8 pounds, just sufficient to carry the solution to the desired 
spot; this avoids dilution better than when the applica- 
tions are made on a mop, although sometimes a mop answers 
well, and it is easier for the patient. 
The discomfort of all local applications is usually greatest 
during the early days of the disease, when the throat is 
most sensitive and most congested, but at this time treat- 
ment is most serviceable. Later in the disease when the 
false membrane is clearing off, and if a sensitive, raw, 
congested surface is exposed, especial care should be 
taken to avoid these sensitive areas or use the dioxide 
solution on a mop. One should be careful not to cause 
bleeding. The applications, especially in spray, should 
be made most gently. If the mop is used, the solution 
causes much less, sometimes no discomfort. The amount That the 50-volume hydrogen dioxide solutions are harmless when properly 
even if very frequently applied, is illustrated by the following case, although 
before outlining it I should say that I do not consider it justifiable to use 
any local treatment hourly through the night. 
B. R., a girl 15 years old, nursery maid in a family where two children had 
just died of diphtheria, was sent to the hospital, probably about the first day 
of the disease, the family being on the alert for any symptoms of diphtheria. 
Clinically, the appearances in her throat were those of diphtheria, the false 
membrane covering nearly the whole surface of both tonsils. Unfortunately, 
no culture was made from the throat when the patient entered the hospital, 
and the swab taken next morning, after the strong dioxide solution had been 
applied a number of times, gave no bacilli of diphtheria, only staphylococci 
and streptococci; and that taken four days later, only staphylococci. There 
was a trace of albumen in the urine. A new house officer began his service 
on the afternoon of this patient’s arrival, and, through a misunderstanding, 
the 50-volume dioxide solution was applied every hour through the night, and 
until my visit in the morning (making about eighteen successive hourly 
applications) when 1 reduced the frequency of the applications to once in 
three hours by day, and directed that she should be waked once at night for 
an application. The patient made not the slightest objection to the frequent 
treatment, and, so far as I could see, only good had resulted from it. The 
congestion was lessened, and the false membrane covered very much less 
than its original area, and by afternoon — twenty-four hours after entrance 
— was nearly gone; traces of it were then seen for the last time. THE DIAGNOSIS OF DIPHTHERIA 
23 
of discomfort is, in most instances, an indication of 
the want of skill in making the applications. While the 
smart of the strong dioxide is usually greater at the time 
than that of some of the other applications which are made 
to the throat, it is only momentary; patients invariably 
prefer the strong hydrogen-dioxide solutions to chlorinated- 
soda solutions of efficient strength. I recall some patients 
who spoke of the pain the strong dioxide solution caused, 
and I therefore tried, without their knowledge, spraying 
their throats with water, and often they did not distin- 
guish between the two. It is the friction of the spray which 
I think chiefly causes the discomfort, and some throats are 
evidently more sensitive than others, and some patients more 
nervous. The majority of patients do not mind the strong 
dioxide solutions, but many ask to have them applied oftener 
on account of the relief which follows their use. In an adult 
where the nose was closed with false membrane and the ton- 
sils so much swollen and covered with false membrane as 
to cause cyanosis, the throat was cleared in a few moments 
by the use of strong hydrogen-dioxide solutions, and the 
breathing was thus made perfectly easy, although a few 
moments before tracheotomy had been considered. 
The Number of Applications.— The strong hydrogen-diox- 
ide solutions should be applied often during the flrst few days ; 
by often I mean once every two hours by day, and twice 
during the night for the first night or two in severe cases. 
It will be found, after a few days, in some cases after two 
or three, that the diphtheria bacilli are much diminished in 
number or have even disappeared from the throat, although 
much false membrane may remain. Their disappearance can 
only be determined by cultures; false membrane in the 
throat is not a proof of the presence of the bacilli of diph- 
theria ; it may be due to other organisms. No matter how 
much membrane there may be in the throat, we may 
be much relieved when the bacilli have disappeared from the 
cultures. When this has taken place local treatment should 
be omitted, except to give comfort to the patient by clearing 
the throat. 
I am inclined to think that the persistence of the Klebs- 
Lceffler bacilli for more than a week or ten days, under the 24 
THE DIAGNOSIS OF DIPHTHERIA. 
strong hydrogen-dioxide treatment, is due usually to their 
being concealed in the folds of mucous membrane or in 
pockets which have been made by the inflammatory process, 
especially in the tonsils, and that the attention should be 
directed to the application of the solution to these hiding- 
places carefully and thoroughly. 
I observed that in some cases of diphtheria the false mem- 
brane persisted under the use of the 50-volume hydrogen- 
dioxide acid solution for some time after the Klebs-Loeflier 
bacilli had ceased to be present in the cultures; staphylo- 
cocci were, however, present. This led me to study the 
action of the 50-volume solution upon the staphylococcus 
and to find that it would not kill this organism readily in 
the beaker. It will be seen in Table V. that a 100- 
volume hydrogen-dioxide acid (1%) solution is required to 
kill the staphylococcus in five seconds. Further, I found 
that chlorinated soda would kill it in the beaker quickly (10 
seconds), and that clinically the.false membrane that had 
persisted under the use of a 50-volume solution yielded 
under the alternate use of the 50-volume solution and a 
solution of chlorinated soda containing from 1-1000 to 
1-500 available chlorine. I have tried this in a few cases 
only. 
The local treatment of membranous throats may, therefore, 
be best carried on with the microscope and culture tube in 
one hand and the remedies in the other. As soon as the 
bacilli of diphtheria have disappeared the strong dioxide 
should be omitted, except as a cleansing, deodorizing,1 or 
disintegrating agent. If we find that the organisms 
present are chiefly staphylococci we may substitute chlor- 
inated soda for the strong dioxide, or use them alter- 
nately, — they should never be mixed nor used too near 
together,—or we may use hydrogen dioxide and carbolic 
acid mixed together. The 50-volume dioxide does not kill 
the staphylococcus readily in the beaker; it will not, 
therefore, in the throat. 
It follows from what has been just said that in treating 
1A 5 per cent, solution of permanganate of potassium is frequently used as a deo- 
dorizer; a saturated solution contains about 6 per cent, of this substance; this would 
correspond as a source of oxygen to about a 6-volume solution of hydrogen dioxide. THE DIAGNOSIS OF DIPHTHERIA. 
25 
pseudo-diphtheria where staphylococci are present we may 
use hydrogen-dioxide solution as a disintegrating agent, and 
chlorinated soda, or carbolic acid, as germicides. 
In passing let me add a word of caution as 
to the use of alkalies in diphtheria. Many 
practitioners prescribe lime-water in diphthe- 
ria, and many are in the habit of prescribing 
some simple local appli- 
cation containing 
bicarbonate of so- 
da, such as 
Dobell’s 
solution, in a case 
of sore throat. 
Such alkalies 
seem to me disad- 
vanta geous in 
diphtheria, asthey 
favor the growth 
of the bacilli and 
the formation of 
their poison; we 
should, therefore, 
be careful to avoid 
them in this dis- 
e a s e or where 
there is a suspi- 
cion of the dis- 
ease. It seems 
better to have the 
diseased parts 
bathed in acid, 
not alkaline, 
solutions. 
The instru- 
ments which I 
have designed 
and found efficient for applying the hydrogen-dioxide solu- 
tions are, first, three glass atomizers which can be readily ster- 
ilized by boiling. One of these has a down-spray, the second a 
Fig. 1. 
From the thumb to the point the tube is 5 inches 
long. The up-spray is shown in this figure. The top- 
shaped bulb should not be filled more than one-half 
full. The mouth of the bulb may be loosely closed 
with a small roll of gauze (not absorbent cotton) to 
prevent spattering. 26 
THE DIAGNOSIS OF DIPHTHERIA. 
return-spray, and the third an up-spray. The latter (see Fig. 
1) may be used to direct the spray to the side and upper por- 
tion of the pharynx or to either tonsil without taking it out 
of the mouth, simply by turning it in the hand. A spray 
is best applied to the surface of the tonsils if directed at 
right angles to it. This can easily be done with this atomizer, 
which I find indispensable. The rubber bulbs of these 
atomizers have two valves. I also use an atomizer with a 
straight spray. 
The atomizer for spraying the posterior nares from behind 
forwards (return-spray) is made by bending the atomizer, 
shown in Fig. 1, through ninety degrees one-half an inch 
from its tip. 
The mop which I use for swabbing the throat con- 
sists of a small glass rod on which some absorbent cotton 
has been twisted. The rod is about eight inches long and 
one-eighth of an inch in diameter, and is bent at an an«;le of 
about 45 degrees half an inch from the end, in order that the 
sides of the pharnyx may be more easily reached. The end 
of the rod is rounded and thickened a little by heating in a 
flame, as by this device the cotton is held more firmly. 
To make the applications with success we should not only 
have good instruments, but also the cooperation of the 
patient; it is a mistake to use force — I do not mean that 
young children should not be held in a position to let a good 
light fall into the throat, but the mouth should not be forced 
or pried open. One can nearly always gain the cooperation 
of children who are four or more years old (I have used 
this treatment on children two years old who took it satis- 
factorily). If one begins tactfully it is surprising to see 
how soon young children accept the habit of having the 
throat treated. It is not necessary to have the head lifted 
from the pillow. In order to accustom the patient to open 
the mouth properly I sometimes go through the manipula- 
tions of treatment once or twice with water instead of the 
remedy. It is very important to have the part which is to 
be treated well lighted, so that one may see exactly what is 
required and also what is done. If the physician does not 
apply the treatment himself, he should see it done whenever 
he can. At night a very small kerosene lamp with a reflector 27 
THE DIAGNOSIS OF DIPHTHERIA. 
which also shades the eyes of the physician, a necessary con- 
dition to success, is good. I sometimes use a small electric- 
light with a portable battery. It is not easy to apply local 
treatment properly in the throat, and the best results can 
only be obtained when great care is taken. 
In looking over what I have written it seems to me 
necessary to add some details essential to success in carrying 
out the treatment with strong hydrogen-dioxide acid solutions, 
as there seems to be so much misconception about them as 
well as about the ordinary 10-volume solutions. Neutral 
solutions do not keep well, and alkaline ones decompose 
readily. The hydrogen-dioxide solutions which are sold in 
the market all contain some acid which increases their germi- 
cidal value and assists in preserving them. 
The strong solutions of hydrogen dioxide may be made 
by evaporating the 10-volume solution (U.S. Pharmacopoeia, 
1890) in a porcelain dish over a stove or Bunsen burner; 
in this way one may, if one desires it, obtain a liquid con- 
taining 90 odd per cent, of hydrogen dioxide. A 50-volume 
solution (about 10%) of hydrogen dioxide may be readily 
obtained by evaporating a good 10-volume solution to A- of 
its weight; a 25-volume solution, by evaporating a good 
10-volume solution to \ of its weight.1 
1 If there were no loss of hydrogen dioxide during evaporation, this process would 
yield a 60-volume solutidn, but about 20 per cent, of the dioxide is lost; therefore, 
in making a 50-volume solution it is necessary to evaporate a 10-volume to one-sixth 
instead of one-fifth of its weight. In making solutions of greater strength, the loss 
would be rather more; in making those of weaker strength, say 25 volumes, the loss 
would be less than 20 per cent. There is no economy in buying a solution that has 
not been well made, as it does not keep well and loses more on evaporation than a 
good one. The time required to evaporate over a gas stove 190 grammes of a 10- 
volume solution (U.8. Pharmacopoeia, 1890), to 32 grammes (an ounce), of 50-volume 
solution, is half an hour. One may carry on the evaporation at a gentle boil at the 
rate of about 6 grammes (one drachm and one-half) per minute. 
For commercial purposes the strong solution can doubtless be made with a smaller 
amount of loss. I simply suggest how in the emergency of diphtheria one may 
quickly obtain a strong solution. Usually I make some ounces at one time. 
In the solution of the Oakland Chemical Company the free acid seems to be chiefly 
hydrochloric, and this is the acid which I now prefer. It is a better germicide than 
sulphuric acid, although not so good as nitric. Hydrogen-dioxide solutions keep 
better in cool than in warm places; they decompose more rapidly in sunlight. 
1 have lately made twenty-six experiments, extending over periods of from four to 
twenty-six weeks, upon the keeping qualities of hydrogen-dioxide solutions of 
strengths varying from 10 to over 100 volumes, and these tests show that the strong, 
25 and 50 volumes, hydrogen-dioxide solutions of good make are sufficiently- stable to 
be perfectly practicable. 
Hydrogen dioxide is a bleaching agent and should not be brought into contact with 28 
THE DIAGNOSIS OF DIPHTHERIA. 
In making the strong solutions it is not necessary to add 
any acid, as but little of that present in the solution is lost, 
and 10-volume solutions containing 0.030% of acid when 
evaporated to i- of their weight contain about 0.18% of acid, 
and this is as much as is required for use in diphtheria. 
Let me remind you in passing that the gastric juice 
contains 0.20% of hydrochloric acid. As this amount does 
not injure the lining membrane of the stomach, it could 
hardly injure the throat when applied for a short period only. 
Bromide of potassium is of much service to adults during 
the first few nights, as they are very anxious when they find 
they have so severe a disease as diphtheria; children do not 
need it, as they go to sleep directly after treatment, or if 
asleep are frequently not fully awakened by treatment. 
In many cases of retraction much relief follows the inhala- 
tion of steam or calomel fumigations. 
There should be abundant and dry air in the patient’s 
room and abundant and direct sunlight. Sunlight is espe- 
cially advantageous in a diphtheria ward on account of its 
excellent germicidal properties, and every room in a hospital 
for such patients should have this. The simplest construc- 
tion will permit these conditions to be fulfilled. The build- 
ing should run north and south so that every bed may 
have sunshine part of the day. The utmost attention should 
be paid to the nourishment of the patient; if too little food 
is taken by the mouth it should be supplemented by feeding 
in other ways, as by the rectum or by means of a soft cathe- 
ter and a funnel. The catheter may be inserted gently 
through the nose into the oesophagus and liquid food may be 
poured into the funnel. 
Good food, absolute rest, protection from draught, or 
from a temperature that might give the patient a cold, are to 
be insisted upon. In some cases stimulation may be desira- 
ble. Strychnine, digitalis, and iron should be used when 
required. 
the hair or colored fabrics. One should avoid getting it on the skin, as it may, after 
a few minutes, whiten the skin and cause a pricking sensation. It is probable that it 
attacks the dead outer layer of the epidermis, and hence the white appearance; a 
minute portion of the solution may get into some small cavities of the skin, and the 
oxygen gas be there liberated, thus causing pressure on the endings of the sensitive 
nerves. THE DIAGNOSIS OF DIPHTHERIA. 
29 
The mortality from diphtheria differs in different cities (in 
recent years it has been very much higher in Boston than in 
some other cities) and in different institutions, and may 
differ in the same institution during the same period of time. 
These variations, T believe, usually depend not so much 
upon the special medical treatment employed as upon the 
state in which patients are admitted and the conditions which 
surround them after admission ; by this I mean the ventilation 
of the ward, the amount of sunlight, the care taken in regard 
to the cleanliness of the instruments, exposure to other 
diseases, etc. The milder cases recover if no harmful treat- 
ment is employed. 
At the Boston City Hospital there are two buildings for 
the scarlet-fever patients; one belonging to the hospital 
which is used for acute cases of scarlet fever, and the other, 
a wooden building, placed at the disposal of the hospital less 
than a year ago, which is used for the convalescent cases of 
scarlet fever. Diphtheria has developed in both buildings, 
but in the first, the cases have usually been mild in character ; 
in the second, the building for convalescents, they have been 
severe, among the most severe and fatal we have had at the 
hospital. The two buildings are erected on land that is only 
a few feet above high-water mark, but in the building that 
does not belong to the hospital the damp ground is not cov- 
ered with cement as is the case in the other building. 
I have used the strong hydrogen-dioxide acid solutions in 
over 100 cases, which varied in age from 2 to 68 years; 
some were cases of pseudo-diphtheria, and others were 
hopeless cases of diphtheria in which it was used to give 
comfort to the patient by getting out membrane from the 
throat, so that swallowing was made easier, or to keep down 
the septic odor; again, others were cases that came under 
treatment early in the disease. 
These solutions fulfil the conditions sought: they will kill 
the bacilli of diphtheria in the laboratory in five seconds, 
and are not poisonous (they are readily decomposed 
into oxygen and water) ; they prevent the septic odor, 
and take off certain portions of the false membrane better 
than anything else I have employed; under their use the 
congestion and glandular tenderness and enlargement is 30 
THE DIAGNOSIS OF DIPHTHERIA. 
more quickly diminished, and the bacilli remain for a 
shorter time in the throat. Not only is the course of the 
disease shortened, but also the convalescence is conspic- 
uously rapid compared with the cases under my care 
before I used this treatment. The patient is thus for a 
shorter time a menace to those around him, and the danger 
of the spread of the disease is much lessened. There is 
conspicuously less tendency to cardiac weakness. 
In studying the effect of any local treatment upon the 
mortality it seems to me that we should consider chiefly the 
cases in which the treatment has not been delayed too long, 
say not beyond three days. 
I will, therefore, discuss here two series of cases of mem- 
branous throats, occurring in different years, that were 
treated with strong hydrogen-dioxide solutions and comply 
with this condition. There were 18 in the first series, and 
30 in the second series; 48 in all. During the first period 
there were, in all, 23 cases of membranous throats, the 
diagnosis of which was not based on cultures, that entered 
the hospital within the first three days of the disease, so far 
as known. Five of these do not concern us, as they were 
not treated with strong solutions of hydrogen dioxide, but 
being operative cases, were transferred directly from the 
medical to the surgical side of the hospital, were there 
intubed, and died two days after entrance. The remaining 
18 make up the first series of cases treated with strong 
hydrogen-dioxide acid solutions within the first three days of 
the disease. One of these 18 cases died ; this was a laryngeal 
case at entrance. 
During the second period there were, in all, 40 cases of 
diphtheria, the diagnosis of which was based on cultures, that 
came under my care within the first three days of the disease 
so far as known. Ten of these cases do not concern us, for 
the following reasons: Seven were mild or very mild cases 
that recovered and were not treated with strong hydrogen- 
dioxide acid solutions. The eighth was a child who entered 
the hospital on the second day of the disease, but on account 
of extreme homesickness did not have any treatment until 
the fourth day of the disease. She was then treated with the 
strong hydrogen-dioxide acid solutions and recovered. The THE DIAGNOSIS OF DIPHTHERIA. 
31 
ninth and tenth cases were not treated with the strong hydro- 
gen-dioxide solutions until after three days, as there was none 
in the ward at the time, or it was deficient in strength. These 
two cases died. The remaining 30 cases of diphtheria, making 
up the second series of cases under discussion, were treated 
with strong hydrogen-dioxide acid solutions within the first 
three days of the disease, so far as known. Four-fifths 
of these 30 cases entered the hospital during the months in 
which the mortality from diphtheria in Massachusetts is 
greatest. Of these thirty cases two died. One was a 
woman, 24 years of age, who was vaccinated a few days 
before the attack of diphtheria began, and the solution used 
in this case was found to have been much below 50 volumes 
in strength. (In private practice I always test the solutions 
before using them.) The patient some years before had lost 
a brother and sister with diphtheria. The other was a child 
four years of age, who took the treatment well for one day, 
but became delirious the next day, so that further treatment 
was impracticable, and died the following day. 
It gives me pleasure to testify here to the careful manner 
in which the house officers and nurses carried out my in- 
structions in regard to these patients. 
I have used the strong hydrogen-dioxide acid solutions at 
the Boston City Hospital during the years 1892, ’93, and 
January, ’94, six months in all, as well as in private prac- 
tice, and have used them with increasing satisfaction. 
In closing this paper I wish to emphasize the impor- 
tance of the early diagnosis of diphtheria, and, if the treat- 
ment be local, of prompt, gentle, and thorough treatment 
during the early days of the disease with strong hydrogen- 
dioxide solutions of known strength, containing a proper 
amount of acid, applied with efficient instruments. 32 
THE DIAGNOSIS OF DIPHTHERIA. 
Since this paper was written I have used anti-toxin in a few 
cases (“Boston Medical and Surgical Journal,” December 
20, 1894) with excellent results, and initi- 
ated its use at the Boston City Hospital, 
where its administration in this com- 
munity was begun. Under this treatment 
the bacilli often disappear from the throat 
early. In three of the cases an eruption 
appeared several days after the anti-toxin 
was injected ; in three there was pain in 
the bones; one of these had periostitis of 
the ulnar and an extremely painful teno- 
synovitis about the left hand and wrist; 
two had swelling of the joints. 
The syringe which I have designed and 
use to inject the anti-toxin (see Fig. 2) 
is a modification of the one I published 
in 1892 ; it is made of glass and packed 
with asbestos, and is joined to the hypo- 
dermic needle by a short piece of rubber 
tubing. By this device the anti-toxin is 
injected with greater ease into a strug- 
gling child, and the danger of breaking off 
the needle under the skin — an accident 
which may happen when the needle is 
rigidly fixed to the syringe — is avoided. 
This instrument may be sterilized by boil- 
ing in water.1 
In Europe, local treatment is recom- 
mended to be used with anti-toxin. In 
some of my patients I have used anti- 
toxin alone, and in others I have combined 
with it local treatment with a 25-volume 
acid solution of hydrogen dioxide in the 
throat (made from the U.S. Pharmacopoeia 
10-volume solution) ; and in nasal diph- 
theria I have used in the nose a dilute 
(2-volume) solution. These solutions may 
APPENDIX. 
Fig. 2. 
1 To fill the syringe remove the needle, insert the rubber tube into the bottle of The diagnosis of diphtheria. 
33 
be used every three hours in spray. The loosening and 
softening action of the anti-toxin, together with the disinte- 
grating action of the hydrogen-dioxide solution, remove 
the membrane rapidly, and the hydrogen-dioxide solution 
lessens, if it does not obviate, the danger of pieces of false 
membrane getting into the trachea from the pharynx. 
In treating diphtheria I now usually inject anti-toxin, and 
apply a spray of a 25-volume acid solution of hydrogen 
dioxide locally in the throat, and a 2-volume solution 
in the nose once in three or four hours. 
. serum and draw in the required amount; then hold the syringe vertically, with the 
rubber tube up, draw in air enough to fill the conical end of the syringe and put in 
the needle; next hold the syringe horizontally and fill the needle with serum. Insert 
the needle well under the skin, and inject the serum, holding the handle up; the 
bubble of air near the piston allows all the serum in the syringe to be injected. This 
syringe is made by Codman & ShurtlefF, Boston, and is inexpensive.