STUDIES ON TRICHINOSIS, WITH ESPECIAL REF- 
ERENCE TO THE INCREASE OF THE EOSINO- 
PHILIC CELLS IN THE BLOOD AND MUSCLE, 
THE ORIGIN OF THESE CELLS AND THEIR 
DIAGNOSTIC IMPORTANCE 
by * 
THOMAS R. BROWN, M. D. 
(From the Clinical Laboratory of the Johns Hopkins University 
and Hospital) 
From 
THE JOURNAL OF EXPERIMENTAL MEDICINE 
Vol. Ill, No. 3, 1898 STUDIES ON TRICHINOSIS, WITH ESPECIAL REFERENCE 
TO THE INCREASE OE THE EOSINOPHILIC CELLS IN 
THE BLOOD AND MUSCLE, THE ORIGIN OF THESE 
CELLS AND THEIR DIAGNOSTIC IMPORTANCE. 
By THOMAS K. BEOWN, M. D. 
(From the Clinical Laboratory of the Johns Hopkins University and Hospital.) 
Plates XXV-XXVII. 
INTRODUCTION. 
Since the discovery by Zenker of the Trichina spiralis as a lethal 
agent in the human being, and the placing of the disease trichinosis 
or trichiniasis on a firm clinical basis, the subject has been studied 
with great care from many points of view. Indeed, the fact that 
with the study of this affection—its aetiology, symptomatology, patho- 
logy and prophylaxis—such names as those of Virchow (70), Leuckart 
(40), Cohnheim (13) and Zenker (74) are intimately connected, 
vouches for the completeness of our knowledge regarding many of 
its features. 
Modern methods, however, have given rise to new possibilities in 
the line of more minute histological and pathological study, and it is 
to this fact and to the unusually favorable conditions surrounding the 
present cases that this contribution owes its origin. 
The Trichina spiralis was discovered in the human cadaver in 1835 
by Owen (53); it possessed, however, mainly zoological interest until, 
by the work of Zenker in 1860, a strong stimulus was given to the 
study of the trichina and of trichinosis. The various German epi- 
demics (13, 57, 42) occurring since then have furnished abundant 
material for investigators, and as a result of their observations and 
experiments it is now known that the main source of infection in 
man is incompletely cooked pork, which in a certain percentage of 
instances contains encapsulated trichinae in the muscle fibres. 
After trichinotic flesh has been eaten the capsules are dissolved off 
by the gastric juice; the worms pass into the small intestine, where 316 
Trichinosis with Increase of Eosinophiles 
they reach their sexual maturity; copulation then takes place, and on 
the 6 th or 7th day after the ingestion of the meat the first embryos 
appear. From the intestine the embryos pass to the muscular tissues. 
Some, especially Leuckart (40), regard this passage as taking place by 
an active boring of the embryos through the loose connective tissue; 
others (14, 2, 21) think that the distribution occurs chiefly through 
the vascular and lymphatic systems, a view which the recent work of 
Cerfontaine (14) and Askanazy (2) seems to favor. These observers 
assert that the female worms, after penetrating the villi, bring forth 
their young directly in the lymph spaces. After the embryos have 
reached the muscles, changes take place in them which will be de- 
scribed a little later. 
CLINICAL HISTORY OF CASE I. 
In the following case which was under observation in the medical 
clinic of the Johns Hopkins Hospital from March 3 until May 13, 1896, 
the blood was examined daily, with a determination of the number of 
leucocytes per cubic millimetre and a differential count of the various 
forms; frequent examinations of the urine and quantitative determina- 
tions of the uric acid, urea and total nitrogen were made, while on 
two different occasions small pieces of muscle were removed and sub- 
jected to careful microscopic examination. 
Eohert T., aged 23 years, an Englishman by birth, was admitted to 
the hospital on March 3, complaining of general pains. His past his- 
tory was of no especial interest excepting that for the last three months 
he had been living the life of a tramp, with continual exposure to the 
weather and with insufficient nourishment. 
Six weeks before entering the hospital he began to complain of gen- 
eral pains, as he expressed it, in the joints, hones and muscles. For the 
last two weeks he had been much worse, scarcely able to move about. 
On entrance he complained of a feeling of fulness in his head. Ho 
diarrhoea; no cough; no oedema at any time. 
Physical examination showed the patient to be rather pale; tongue 
thickly coated; the temperature at time of admission was 102° F.; pulse 
104; respirations 24. Examination of the thorax was negative, except 
for a soft systolic murmur heard all over the cardiac area; very faintly 
heard in the mid-axilla. Patient complained of general soreness in the 
limbs. Pressure on the muscles almost everywhere caused great pain, 
particularly in the right biceps. There was no tenderness apparent in 
the hones or in the skin. Spleen not palpable; no rose spots. Hrine: Thomas R. Brown 
317 
color normal; acid; 1028; albumin, trace; sediment, slight, showing 
mucous cylindroids, hyaline and granular casts. Diazo-reaction was 
not present. 
Examination of the blood on March 5 showed 17,000 leucocytes with 
37 per cent of eosinophiles. The absence of rose spots and of any 
palpable enlargement of the spleen, as well as the presence of a leuco- 
cytosis and the extraordinary increase in eosinophilic cells, rendered the 
diagnosis of typhoid fever, which was at first considered, improbable. 
The extreme muscular tenderness on pressure and on voluntary or pas- 
sive motion, and the irregular temperature, suggested rather a myositis, 
and a diagnosis of trichinosis was made. 
On further questioning the patient stated that six or seven weeks 
previously he began to have vague pains and heavy feelings in the 
muscles of his legs, and that he had repeatedly eaten raw or incom- 
pletely cooked pork during this period. 
To confirm the diagnosis, on March 12 a small piece of muscle was 
removed under cocaine from the right biceps, where the pain was 
greatest at that time. A teased specimen of this showed, on micro- 
scopic examination, trichinae, the majority actively motile, a few appar- 
ently non-motile; none were encapsulated, but many were surrounded 
by a finely granular material. During the remainder of the patient’s 
stay in the hospital the symptoms gradually abated; the temperature, 
which had run a very irregular course, slowly descended to the normal 
point, and the sensitiveness of the muscles to pressure decreased. 
(Edema of the ankles appeared on two occasions in April after walking 
about the ward for several days, but both times quickly disappeared 
after rest in bed. 
On May 13 the patient was discharged, the following note being 
made: “ For from two to three weeks there has been no pain in the mus- 
cles; the stiffness has wholly disappeared and the patient feels perfectly 
well in every way, excepting that violent exertion is not readily borne.” 
Thus it will be seen that in many respects onr case showed the clas- 
sical picture of trichinosis. The pain in the muscles, aggravated hy 
pressure or motion, the similarity of the early symptoms to those of 
typhoid fever, the oedema of the ankles after exercise, and the rather 
irregular fever, were characteristic. The absence of any history of 
gastro-intestinal symptoms, usually so marked, was probably due 
partly to the fact that this was not a case of extreme severity and 
partly to the incoherence of the patient on admission. 318 
Trichinosis with Increase of Eosinophiles 
THE BLOOD. 
Although it was known to the older pathologists that there were 
various kinds of white cells in the blood, it is only since the demon- 
stration by Ehrlich (19) of their varied reactions to different dyes that 
we have possessed an adequate means of differentiating the various 
forms and of studying their relative proportions, one to another, in 
health and disease. 
Morphologically, and by means of these tinctorial reactions, the leu- 
cocytes may, as is well known, he divided into five classes: 
(1) Small mononuclear cells. 
(2) Large mononuclear cells. 
(3) Transitional cells. 
(4) Polymorphonuclear neutrophilic cells. 
(5) Eosinophilic cells. 
In the first two divisions—the small and large mononuclear cells (the 
classification being determined by the fact that they are smaller or 
larger, respectively, than the ordinary polymorphonuclear neutrophiles) 
—the protoplasm shows no evidence of specific granulation and the 
nucleus is round or oval. 
In the cells of the third division—the transitional—the nucleus be- 
comes notched or indented and the protoplasm shows sometimes a slight 
tendency to neutrophilic granulation. 
In the last two varieties, the polymorphonuclear neutrophiles and the 
eosinophiles, the granulations are well marked, in the former being fine 
and neutrophilic, in the latter coarse, highly refractive and acidophilic. 
The nucleus of the former is polymorphous; of the latter usually also 
polymorphous, although sometimes round or oval. 
Many of the English school, notably Kanthack and Hardy (36), and 
Gulland (24), regard the so-called neutrophilic granulations as slightly 
acidophilic, and for, this reason call the cells containing them the 
finely granular oxyphiles or acidophiles or eosinophiles. In the present 
work, however, the name polymorphonuclear neutrophiles (or cells with 
the £ granulation) will he used in describing them. 
The percentage of these various forms in the blood differs quite 
markedly within normal limits. The usual proportions in the adult as 
given by Kanthack are: 
Small mononuclears 15-25 per cent. 
Large mononuclears and transitional forms.... 6 “ 
Polymorphonuclear neutrophiles 70-75 
Eosinophiles 1-5 Thomas R. Brown 
319 
Concerning the proportion of the cells about which we are especially 
interested, the eosinophiles, various observers have given slightly dif- 
ferent figures; Ehrlich (19c) regards it as from 2-4 per cent usually, 
although sometimes normally reaching 10 per cent; Hayem (31) as 7 
per cent; Gabritschewsky (25), 1-3 per cent; Muller and Rieder (476), 
1-4 per cent; Canon (15), 1-3 per cent; v. Limbeck (41), 2-8 per cent; 
Uskov (quoted in 58), 6 per cent; Zappert (73), 0.67-11 per cent; while 
Weichselbaum (64) and Gollasch (26) each gives 5 per cent, including 
the transitional forms. 
In this study the average number of leucocytes per cmm. has been 
taken to be 6500, of which 74 per cent (4810) should be polymorpho- 
nuclear neutrophiles, 18 per cent (1170) small mononuclears, 6 per 
cent (390) large mononuclears and transitionals, 2 per cent (130) 
eosinophiles. 
Ever since the discovery of the specific cell granulations the eosino- 
philic cells have attracted the attention of many investigators who 
have studied the changes in the blood, especially in reference to the 
increase or decrease of this particular form in various pathological 
conditions. Much greater diagnostic significance than would seem to 
be warranted has, in many instances, been ascribed to this increase or 
decrease. Nevertheless, in certain diseases, chief among which are 
bronchial asthma and spleno-myelogenous leukaemia, a constant in- 
crease in these cells has been noted. 
In the latter disease, as noted by Schwarze (60), Spilling (61), and 
Muller and Rieder (476), the increase is more absolute than relative, 
owing to the enormous increase in the total number of leucocytes per 
cmm. In bronchial asthma an increase, both relative and absolute, has 
been described by Gollasch (26), Fink (20) and Gabritschewsky (25). 
In certain affections of the skin, especially pemphigus, prurigo, psoriasis 
and chronic eczema, a marked increase in eosinophiles has been noted 
by Canon (15) and Neusser (51). Kotschetkoff (37) describes an increase 
in scarlet fever, and Zappert (73) and Muller and Rieder (476) in 
anchylostomiasis. Besides these, many isolated reports of an increase 
are to be found, although in many cases this has been too slight to be 
of significance. An increased percentage of eosinophiles has been noted 
in syphilis (4), malaria (1, 17, 27a), diseases of the genital organs and 
bones (51), mental diseases (51), during childhood (29), and after the 
injection of tuberculin (276, 69, 5). 320 
Trichinosis with Increase of Eosinophiles 
The largest percentages of eosinophiles hitherto reported have been 
22.40 per cent in bronchial asthma (25), 33.02 per cent and 29.28 per 
cent in two cases of pemphigus, 27.9 per cent in anchylostomiasis (73), 
and 21.1 per cent in anterior poliomyelitis (475). In a case of chronic 
eczema attending the Johns Hopkins Hospital, three different counts 
of the blood gave 22.6, 24 and 22.6 per cent of eosinophiles. 
In the present case an examination of the blood on March 5 showed 
that the eosinophiles constituted 37 per cent of all the leucocytes— 
so striking an increase above the normal that from that time until the 
patient’s discharge the blood was examined daily, and a determina- 
tion of the number of leucocytes per cubic millimetre and a differential 
count of the various forms were made. 
As a routine proceeding in making the differential estimate 500 
leucocytes were counted daily, the stain employed being Ehrlich’s 
triple stain (orange G., acid fuchsin and methylene green). In the 
case of the larger percentages an additional 500 stained in a different 
mixture (haematoxylin and eosin, methylene blue and eosin, Chenzin- 
sky’s solution, Huber’s or YVeichselbaum’s modification of Ehrlich’s 
triacid stain, Heusser’s modification of the triple stain) were counted 
as a control. 
The cover-glass preparations from which these counts were made 
were fixed either by Ehrlich’s method of heating at 110° C. for from 
1 to 1-| hours, or by Hikiforov’s method of immersion in a mixture of 
equal parts of absolute alcohol and ether for two hours. The Zeiss 
mechanical stage was employed in studying the preparations. 
In determining the number of leucocytes per cubic millimetre the 
Thoma-Zeiss hsemocytometer was used, the diluting agent being 
either Toison’s mixture or an per cent solution of acetic acid. 
The red blood corpuscles, counted at various intervals during the 
disease, showed a gradual increase from 4,200,000 per cubic milli- 
metre, three days after the patient’s admission, to 4,900,000 per cubic 
millimetre on the day of his discharge. 
AY hen we consider the changes which the blood underwent during 
the two months of the patient’s stay (see Table I, p. 322, and the 
Chart (Plate XXYT)), some very interesting facts are brought out. Thomas R. Brown 
321 
From their original percentage of 37, the eosinophiles gradually fell 
to between 10 and 15 per cent, where they remained for about two 
weeks, the number of leucocytes per cubic millimetre during this 
period ranging between 15,000 and 20,000. On March 26 the per- 
centage of eosinophiles began to rise, this rise continuing steadily and 
gradually until April 23, when it reached 68.2 per cent; this means 
that more than two-thirds of all the white blood cells ivere eosinophiles. 
During this time an absolute increase in the leucocytes was also noted, 
the number per cubic millimetre averaging 27,500 between April 8 
and April 22. From April 23 the percentage of eosinophiles de- 
creased, and there was also a decrease in the total number of leucocytes, 
and on May 12, the day previous to the patient’s discharge, 16.8 per 
cent and 11,000 were found respectively. 
During the whole time the character of the eosinophiles was appar- 
ently perfectly normal—their nuclei were almost exclusively poly- 
morphous, and they were slightly larger than the polymorphonuclear 
neutrophiles (Plate XXVI). As was to be expected, the percentage 
of these latter (always quite normal in character) varied inversely with 
that of the eosinophiles, reaching as high as 80.4 per cent and sinking 
as low as 6.6 per cent. The striking nature of this inverse relation- 
ship may be better appreciated if one studies the accompanying table 
and the chart (Plate XXV). 
The small mononuclear leucocytes, scanty at first, soon increased to 
between 10 and 20 per cent, where they subsequently remained; in 
fact the percentage of both small and large mononuclear and transi- 
tional forms showed very slight fluctuations. 
It is interesting to note that after about two weeks the percentage 
of small mononuclears kept fairly constant, being about that normally 
found in the blood. When we consider the very marked leucocytosis, 
this indicates that the total number of small mononuclears was much 
increased. When and how this increase takes place, however, must 
be left open to conjecture. 
A few typical myelocytes were seen, averaging less than 0.3 per 
cent, probably no more than one would expect with so marked a 
leucocytosis. 322 
Trichinosis with Increase of Eosinophiles 
Date. 
Leucocytes 
per cram. 
Percentage 
of Various Forms of Leucocytes. 
Number 
of the Various Forms per cmm. 
P. M. Neut. 
S. Monos. 
L. M. and T. 
Eos. 
P. M. Neut. 
S. Monos. 
L. M. and T. 
Eos. 
March 5.... 
17000 
55.0 
3.0 
5.0 
37.0 
9350 
510 
850 
6300 
6 
16500 
50.0 
5.0 
7.0 
38.0 
8250 
825 
1120 
6120 
7 
17500 
53.0 
3.0 
7.4 
36.4 
9275 
525 
1200 
6300 
8 
25300 
60.9 
1.9 
5.9 
31.4 
15000 
500 
1500 
7750 
9 
22300 
70.8 
2.0 
4.5 
22.7 
15300 
440 
900 
5060 
10 
16500 
74.7 
3.1 
8.0 
15.1 
12000 
480 
1280 
2400 
11 
21167 
75.1 
2.8 
2.4 
18.6 
15800 
630 
500 
3700 
12 
17500 
77.8 
4.4 
3.0 
15.1 
13600 
770 
510 
2625 
13 
18833 
77.6 
2.1 
3.7 
16.6 
13860 
380 
710 
3000 
14 
13800 
74.6 
4.3 
4.0 
14.9 
10300 
580 
560 
2100 
15 
13750 
74.0 
7.6 
3.2 
13.6 
10300 
1000 
420 
1720 
16 
13250 
78.7 
5.3 
2.1 
13.8 
10400 
680 
270 
1700 
17 
16000 
73.2 
11.3 
1.9 
13.5 
11700 
1770 
310 
2160 
18 
17750 
77.4 
10.9 
1.7 
10.0 
13800 
1970 
300 
1775 
19 
20400 
71.1 
13.1 
2.3 
13.1 
14200 
2600 
460 
2600 
20 
15700 
76.5 
10.1 
2.2 
11.2 
12100 
1570 
340 
1760 
21 
16800 
72.9 
13.2 
1.8 
12.1 
12400 
1210 
320 
2040 
22 
14000 
79.2 
10.8 
1.7 
8.3 
11200 
1540 
240 
1130 
23 
16800 
73.6 
10.4 
1.6 
13.5 
12400 
1700 
270 
2200 
24 
19600 
74.6 
11.2 
1.8 
11.2 
14800 
2200 
360 
2200 
25 
17600 
80.4 
8.9 
1.6 
8.7 
14400 
1600 
290 
1560 
26 
24000 
69.2 
12.7 
2.0 
15.4 
16800 
3120 
480 
3700 
27 
20300 
69.9 
11.2 
2.2 
16.0 
14000 
2240 
440 
3200 
28 
24100 
68.3 
10.1 
2.4 
18.9 
16300 
2400 
580 
4560 
29 
20700 
69.4 
5.7 
1.4 
22.9 
14000 
1180 
300 
4600 
TABLE I. CASE I.—SHOWING TOTAL NUMBER AND PERCENTAGE OF VARIOUS KINDS OF LEUCOCYTES. Thomas K. Brown 
323 
Date. 
Leucocytes 
per cmm. 
Percentage oe Various Forms oe Leucocytes. 
Number of the Various Forms per cmm. 
P. M. Neut. 
S. Monos. 
L. M. and T. 
Eos. 
P. M. Neut. 
S. Monos. 
L. M. and T. 
Eos. 
March 30. ... 
22300 
60.7 
9.6 
3.0 
26.0 
13400 
2200 
670 
5720 
31 
22200 
57.4 
11.2 
3.2 
27.8 
12600 
2500 
680 
6160 
April 1.... 
24300 
60.7 
7.9 
3.4 
27.8 
14400 
1920 
840 
6720 
2 
23800 
59.3 
11.6 
3.0 
25.0 
14100 
2760 
710 
5950 
3 
25200 
53.3 
13.3 
2.8 
30.0 
13300 
3S00 
700 
7500 
4 
23400 
49.9 
13.3 
3.0 
32.8 
11700 
3200 
710 
7590 
5 
24300 
48.8 
13.2 
4.0 
33.8 
10100 
3150 
960 
7160 
6 
24700 
51.2 
14.0 
3.6 
31.6 
12700 
3500 
650 
7900 
7 
25100 
48.4 
14.5 
2.5 
33.7 
12100 
3600 
625 
8600 
8 
29600 
45.2 
11.6 
4.0 
38.8 
13500 
3450 
1180 
11600 
9 
28900 
45.0 
13.3 
3.2 
38.3 
13000 
3850 
930 
11000 
10 
24500 
45.8 
12.2 
3.8 
38.0 
11300 
3100 
900 
9300 
11 
29800 
42.2 
14.0 
4.0 
39.8 
12600 
4150 
1180 
11900 
12 
28000 
44.0 
14.8 
2.5 
38.7 
12300 
4150 
700 
10800 
13 
24200 
42.0 
11.8 
1.4 
44.2 
10000 
2880 
340 
10700 
14 
33300 
38.6 
13.2 
3.8 
44.0 
12800 
4400 
1300 
14700 
15 
28100 
34.8 
19.6 
1.6 
44.0 
8600 
5550 
450 
12300 
16 
25400 
30.4 
16.8 
3.0 
49.6 
7600 
4200 
750 
12400 
17 
27000 
31.8 
13.2 
3.4 
51.2 
8600 
3500 
920 
13700 
18 
35700 
27.2 
14.4 
3.8 
54.6 
9700 
5140 
360 
19500 
19 
29000 
26.6 
12.0 
3.6 
58.2 
7700 
3480 
1040 
16900 
20 
19200 
22.2 
12.4 
4.2 
61.0 
4200 
2350 
800 
11600 
21 
23000 
16.6 
16.0 
3.8 
63.6 
3800 
3680 
870 
14600 
22 
26600 
10.4 
18.8 
7.4 
63.4 
2700 
4900 
1950 
16500 
23 
17700 
6.6 
19.6 
5.2 
68.2 
1170 
3400 
880 
11070 
TABLE I.—Continued. Trichinosis with Increase of Eosinophiles 
Date. 
Leucocytes 
per cmm. 
Percentage 
of Various Forms of Leucocytes. 
Number of the Various Forms per cmm. 
P. M. Neut. 
S. Monos. 
L. M. and T. 
Eos. 
P. M. Neut. 
S. Monos. 
L. M. and T. 
Eos. 
April 24.... 
18800 
7.2 
23.4 
4.4 
64.8 
1370 
4400 
840 
12200 
25 
15600 
8.8 
19.2 
7.2 
64.8 
1370 
2990 
1020 
10400 
26 
17000 
12.4 
14.2 
6.0 
67.4 
2100 
2410 
1020 
11400 
27 
12000 
20.0 
8.6 
7.4 
64.0 
2400 
1030 
890 
7700 
28 
11100 
18.2 
17.6 
7.2 
57.0 
2020 
1950 
800 
6330 
29 
12800 
19.4 
19.4 
6.8 
54.4 
2470 
2480 
870 
6990 
30 
13200 
20.8 
17.2 
8.2 
53.8 
2750 
2270 
1080 
7020 
May 1.... 
11000 
21.8 
16.0 
12.0 
50.2 
2400 
1760 
1320 
5520 
2 
8900 
27.4 
17.8 
8.4 
46.4 
2440 
1580 
740 
5160 
3 
10700 
36.8 
15.0 
6.8 
41.4 
3940 
1600 
710 
4430 
4 
10700 
34.8 
20.8 
6.4 
38.0 
3720 
2120 
680 
4070 
5 
11000 
45.6 
19.0 
6.6 
28.6 
5020 
2090 
710 
3150 
6.. . 
10300 
41.0 
20.2 
4.8 
33.6 
4220 
2080 
490 
3460 
7 
12300 
50.8 
20.2 
6.0 
23.0 
6250 
2480 
740 
2830 
8 
11500 
54.0 
18.0 
4.0 
24.0 
6210 
2070 
460 
2760 
9 
11500 
59.8 
17.6 
6.2 
16.4 
6850 
2020 
710 
1890 
10 
15700 
51.0 
12.8 
5.6 
20.4 
7990 
2010 
880 
3200 
11 
13500 
62.4 
14.2 
4.8 
18.8 
8420 
1920 
650 
3540 
12 
11000 
64.0 
14.4 
4.8 
16.8 
7040 
1580 
530 
1850 
TABLE I.—Continued. Thomas R. Brown 
325 
If one estimate the total number of these various forms per cubic 
millimetre (see Table I, p. 322) by multiplying the percentage of 
the individual variety by the total number of leucocytes per cmm., 
it will be found that, for a period of two weeks, the polymorphonu- 
clear neutrophiles were absolutely decreased in amount—a very strik- 
ing fact when one considers the marked leucocvtosis. This tends to 
show even more clearly the remarkable relationship ..which exists be- 
tween the neutrophiles and the eosinophiles, the latter cells being 
greatly increased in number during the same period. 
Plate XXYI shows a typical microscopic field of the blood of Case 
T. The three most striking points furnished by the study of the 
blood are: 
(1) The remarkable increase in the number of the eosinophiles, 
which amounted to 68.2 per cent of all the leucocytes present, 35 per 
cent more than has ever hitherto been reported. 
(2) The coincident diminution in the number of the neutrophiles, 
these cells and the eosinophiles being at all times in inverse propor- 
tion. 
(3) The marked leucocytosis. 
The presence of such great quantities of eosinophiles in the blood 
in this case is a point of especial interest. If further observation 
shows this change to be characteristic we shall be furnished with a 
symptom of the greatest diagnostic value in this disease, and one 
which, perhaps, may help to clear up some of the cases which are 
regarded intra vitarn as rheumatic in nature, the true diagnosis being 
revealed only years afterwards upon the autopsy table. 
As an association has for a long time been noted between the eosin- 
ophiles and the Charcot-Leyden crystals, occurring so commonly in 
the spleen and marrow in leukaemia (526) and in the sputum in bron- 
chial asthma (20, 45, 46, 54), it was regarded as interesting to see 
whether from the blood in this case, containing as it did such large 
quantities of eosinophiles, the crystals might be obtained. 
For this purpose blood was withdrawn on nine occasions, placed 
sometimes in sterilized, at other times in unsterilized vessels, some 
kept in the thermostat at 37.5° C., others at room temperature; but, 326 
Trichinosis with Increase of Eosinophiles 
although repeated and careful microscopical examinations were made 
at frequent intervals during a period of several weeks, in none of the 
specimens were any Charcot-Leyden crystals to be found. 
This completely harmonizes with the conclusions reached by H. E. 
Muller (47a), who earned on investigations of a like nature upon 
the contents of fresh pemphigus vesicles, which also contain great 
quantities of eosinophilic cells. Thus it seems highly probable that the 
Charcot-Leyden crystals are, at least, not direct crystallization pro- 
ducts of the eosinophiles and that something besides the presence of 
these cells is necessary for their formation. 
THE URINE. 
The urine, as has been mentioned, showed a trace of albumin, 
hyaline and finely granular casts and a small number of pus cells. 
TTo sugar was found. Ehrlich’s diazo-reaction was never present, 
A systematic quantitative study of the nitrogenous elements of the 
urine was carried on chiefly in connection with the ideas of Horbac- 
zewski (30). This observer, as is well known, believes that the uric 
acid excreted by the animal organism is derived from the destruction 
of nuclein-holding material and mainly from the destruction of leu- 
cocytes. 
This view is based on the following assumptions: 
(1) That outside the body we may obtain uric acid from nuclein- 
liolding substances. 
(2) That in leukaemia and leucocytosis, where there is a greater 
destruction of leucocytes, there is a distinct increase in the uric acid 
excretion. 
(3) That in many pathological conditions where nuclein-holding 
substances are destroyed, as in fevers, conditions of inanition, phos- 
phorus-poisoning and cachexia, the increase in uric acid is also noted. 
(4) That in the experimental leucopenias, produced by quinine and 
atropine, a diminution in the uric acid excretion may be shown. 
The quantitative work was carried on in this case mainly with a 
view to control the second of the above statements, that is that a 
parallelism exists between the extent of the leucocytosis and the Thomas R. Brown 
327 
amount of uric acid excreted, a parallelism which has, however, been 
denied by Mares (48), who regards the uric acid as a by-product in 
leucocyte formation. 
To determine this question in the present case the total quantity of 
uric acid excreted during the 24 hours was determined on 23 different 
occasions; on four of these days the total nitrogen and on four others 
the total urea per 24 hours was also estimated. 
The uric acid was determined by the Hopkins method—precipitation 
of the uric acid from 100 cc. of the urine by saturation with ammonium 
chloride, filtration, solution of the uric acid, reprecipitation with strong 
hydrochloric acid and final titration with potassium permanganate. The 
total nitrogen was estimated by the Kjeldahl method, t. e. conversion 
of all the nitrogen into ammonia and titration with a standard solution 
of oxalic acid. The urea was determined by oxidation with sodium 
hypobromite, and measurement of the nitrogen given off. 
TABLE II. CASE I.—URINE CHART. 
Date. 
Total Quantity per 24 Hours of 
Katio op 
Uric Acid. 
Urea. 
Total Nitrogen. 
Uric Acid: 
Urea. 
Nitrogen in 
Uric Acid: 
Total Nitrogen 
March 15. ... 
.2423 
gram. 
16 
.2092 
U 
• 
17 
.5722 
U 
18 
.7800 
u 
19 
.8180 
11 
20 
.3869 
u 
21 
.4053 
u 
22 
.2088 
u 
23 
.7935 
u 
24 
.3119 
u 
25 
.4579 
“ 
26 
.4542 
u 
27 
.1975 
“ 
28 
.5882 
u 
April 3. ... 
.3685 
t t 
7.9497 grams. 
1 : 64.7 
4 
.2829 
C l 
7.2300 “ 
1 : 76.6 
5 
.2753 
u 
4.6725 “ 
1 : 50.9 
6 
.3619 
“ 
4.8027 “ 
1 : 39.8 
7. . . . 
.3971 
< c 
24 
.2905 
u 
10.79 grams. 
1 : 37.1 
28 
.3716 
(( 
19.22 “ 
1 : 51.7 
29 
.4893 
11 
29.11 “ 
1 : 59.4 
30 
.2946 
u 
17.21 “ 
1 : 58.4 328 
Trichinosis with Increase of Eosinophiles 
By examination of Table II it will be seen that on no occasion did 
the total uric acid excretion, the ratio of uric acid to urea excretion, 
or the ratio of nitrogen in the uric acid to the total nitrogen in the 
urine, rise to any extent above the limits usually regarded as normal. 
The normal quantity of uric acid and the normal ratio of this to the 
urea is given somewhat differently by different authors; by Ilammar- 
sten (32) as 0.7 gramme and 1:50-70; by Halliburton (33), 0.55 
gramme and 1:60; by Vierordt (71), 0.67 gramme and 1:45; and 
by v. Jaksch (35), 0.21 gramme and 1:60 respectively. Hammar- 
sten (32) gives the normal ratio of nitrogen excreted in the form of 
uric acid to the total nitrogen as 1:69.3. 
Thus the results obtained in this case show such a slight, if in fact 
any, relative or absolute increase in the uric acid excretion that they 
speak against the Hews of Ilorbaczewski; for if this author’s results 
are universally correct we should expect a decided increase—absolute 
or at least relative—in the uric acid excretion in a case where the 
leucocytes were as markedly increased as they were in our case. It 
is an interesting fact, however, that here the eosinophiles and not the 
neutrophiles, as is usually the case in a marked leucocytosis, were the 
elements especially increased. 
THE MUSCLES. 
The changes in the muscles in trichinosis have, of course, been 
repeatedly and carefully studied; in the early sixties by Virchow (70), 
Zenker (74), Fiedler (21), Cohnheim (13) and many others; more 
recently by Soudakewitch (62), Lewin (43), Geisse (28) and Finger (22). 
All of these observers describe the presence of the parasites in the 
primitive muscle bundles and the granular degeneration which takes 
place about them; they further speak of the great proliferation of the 
muscle nuclei, so that in some places, especially in the region of the 
invaded fibre, there may be great masses or clumps of nuclei situated in 
undifferentiated sarcoplasm. In other places swelling and degeneration 
of the nuclei have been described. The method of formation of the 
capsule or cyst wall which surrounds the parasite after it lias been in 
the muscle a certain length of time is still undecided. Many ideas have 
been held. It has been suggested that it arises from a thickening of the 
sarcolemma (70a, b, d, 6); from the interfascicular connective tissue 
(16); from the finely granular degenerative detritus (74a); or partly Thomas R. Brown 
329 
from secretion from the worm itself and partly from inflammatory 
changes in the surrounding connective tissue (7). The more modern 
observers have described further changes not mentioned by the older 
pathologists. 
Finger (22) notes the presence of great numbers of small round cells 
about the vessels and capsules and in the interfibrillar connective tissue, 
and the splitting up of the contents of the sarcolemma sheaths into 
small irregular bits, in most of which the cross striation has been lost. 
Soudakewitch (62), besides this breaking up of the muscle fibre into 
little bits, notes also the presence of great numbers of leucocytes which 
he regards as phagocytes of the degenerated fibres. This phagocytic 
action is also shared by elements which he regards as muscle-cells, and 
which arise by the separation from the rest of the muscle fibre of the 
nucleus with some of the muscle substance about it. These structures 
appear to maintain for a while an independent existence, but soon 
undergo destruction. 
Lewin (43) has devoted himself more especially to the cell changes. 
He describes the proliferation and great hypertrophy of the muscle 
nuclei in the fibres containing trichinae, with a degeneration of many 
of these nuclei as shown by the affinity of the nucleoli for the acid 
stain; the splitting up of the muscle fibre into separate cells; the forma- 
tion of separate cells of the kind regarded by Soudakewitch as phago- 
cytic muscle cells, and the local oedema of many of the fibres. 
The portions of muscle removed in this case, both of which came 
from the right biceps, were hardened immediately, the specimen of 
March 12 in alcohol, that taken two weeks later in bichloride of 
mercury. On microscopic examination many of the above described 
changes are to be noted (Plate XXVII). 
In the first specimen the reaction is especially marked in a few foci; 
in some places the fibre containing the parasite has become converted 
into a finely granular, faintly staining material, containing many 
large, swollen nuclei—the proliferated muscle nuclei—the nucleoli 
here taking the usual deep blue haematoxylin stain. The sarcolemma 
shows slight thickening, but there is no very marked heaping up of 
cells outside of it except in a very few places. Elsewhere absolutely 
no change in the muscle fibre is to be seen, excepting a small layer 
not thicker than the diameter of a red blood corpuscle, surrounding 
the parasite, which is very small; in fact, the whole picture points 
conclusively to a very recent infection. 330 
Trichinosis with Increase of Eosinophiles 
In many of the fibres not containing parasites marked nuclear pro- 
liferation is seen; in some this is found in conjunction with granular 
degeneration of the muscle substance, in others with no apparent 
changes; about the nuclei, especially of the former, a distinct but 
rather small vacuole may be made out, a sign, probably, of lowered 
vitality of the nucleus. 
A peculiar fragmentation of the muscle is sometimes to be noted. 
At times it takes place in the direction of the long axis of the fibres, 
which break up into separate fibrillse or bunches of fibrillse; at other 
times it occurs in an irregular manner. In a few places a peculiarly 
interesting picture is observed, the fragmentation being transverse 
and the axis of the proliferated nuclei running also in a transverse 
direction, thus splitting the muscle into distinct disks. Whether in 
this latter mode of fragmentation the division had occurred at the 
membrane of Krause or the plane of Hensen could not be made out, 
owing to the obscuring of the field by the great number of prolifer- 
ated muscle nuclei. 
Throughout the specimens there are to be seen cells whose proto- 
plasm shows a marked affinity for the eosin stain. These cells contain 
one nucleus or sometimes two or three, generally of rather large size. 
The fact that some of these elements are still in part connected with 
the muscle fibre, and that in the protoplasm of some there are still 
evidences of striation, points at once to their origin by the separation 
of a certain amount of muscle substance, containing one or several 
nuclei from the primitive muscle bundle. 
These cells, together with bits of degenerating muscle, some pale 
and granular, others taking on a deep eosin stain, but both showing 
a total or almost complete loss of striation, and many pale and swollen 
muscle nuclei, are seen in quite large numbers in certain scattered 
foci of degeneration present in the muscle. 
What is of especial interest, however, is that all through the muscle, 
between and within the fibres, but especially in those areas made up 
largely of cells and debris, many polymorphonuclear cells are seen; 
some of these are ordinary pus cells, neutrophiles; others show large 
red refractive acidophilic granules in the cell body, i. e. they are Thomas R. Brown 
331 
eosinophiles; in some again the protoplasm, though finely granular, 
shows a distinct affinity for the eosin stain; in other words, the char- 
acter of the cells appears to be half-way between that of the neutro- 
philes and that of the eosinophiles. 
These cells would appear to be phagocytic in nature, for they are 
especially abundant in the more degenerated areas, and in many 
places are seen in little bays or inlets or lakes in the degenerating 
muscle, as if gnawing it away. It was thought at first that perhaps 
these cells might ingest bodily the little rod-shaped bits or fragments 
which are found especially at the ends of the degenerating muscle 
fibres and which with the hmmatoxylin and eosin stain show consid- 
erable resemblance to the granules in the eosinophilic cells; but stain- 
ing with other double stains and with the triple stain showed that this 
supposition is hardly tenable, since the staining properties of the two 
are markedly different. The degenerated substance if taken up by 
the leucocytes must undergo a rapid disintegration within the cell 
body or possibly may be taken up in a soluble form. 
In the second specimen, taken two weeks later, more advanced 
stages of the same processes are seen. The trichinae are larger, and 
in some cases two or three parasites are found in the same cyst; about 
the cysts there is a marked increase in the number of nuclei; in some 
cases true giant cells are formed, a number of nuclei lying in a mass 
of undifferentiated protoplasm, probably sarcoplasm, while throughout 
the whole specimen the nuclear proliferation is more marked. The 
transverse splitting of the fibres into disks and the transverse prolifera- 
tion of the contained nuclei is more marked than in the preceding 
specimen, as well as the longitudinal and irregular breaking up of 
the fibres. 
The vacuoles about the proliferating and degenerating nuclei are 
more marked; the muscle cells, mentioned above, show less affinity for 
the eosin stain and in some cases give evidence of granular degenera- 
tion; besides the slight thickening of the sarcolemma there is no dis- 
tinct capsule about the parasites. Of the polymorphonuclear cells, the 
eosinophiles are much more common, the neutrophiles much less 
numerous; the former are present everywhere, but are found especially 332 
Trichinosis with Increase of Eosinophiles 
in the scattered foci of more marked degeneration and about the ends 
of degenerating fibres (Plate XXVII). 
That these were typical eosinophiles was shown not only by the 
character and size of their granules, but also by the fact that they 
showed the typical staining properties with acid fuchsin, orange G., 
picrate of ammonium and other acid stains, and the Biondi-Haidenhain 
triple stain for tissues as well as with the ordinary hsematoxylin and 
eosin stain (Plate XXVII). 
In the interfibrillary connective tissue there was a slight prolifera- 
tion of the cells, while the changes in the interfascicular connective 
tissue were barely evident. In the blood-vessels in the latter, counts 
of the white blood cells showed that the neutrophiles and eosinophiles 
were present in about the same ratio (never differing more than 3 or 4 
per cent) as in the blood count of the corresponding day, thus sug- 
gesting that the eosinophiles were not attracted to the part to a greater 
extent than the neutrophiles. 
The presence of such great numbers of eosinophiles was so striking 
that two specimens of trichinotic muscle, found in the Pathological 
Museum of the Johns Ilopkins Hospital, were examined to see whether 
like changes were present. 
In the first, a ease of carcinoma mammae in which trichinae were 
found in the pectoral muscle, the capsules and parasites were for the 
most part calcified, although some showed fatty and fibrous change; 
in the muscle no especial changes were noted. This, of course, wras 
a case of old standing, discovered by chance, probably years after the 
original infection. 
The second specimen, fortunately, was from a case of acute trichi- 
nosis which had caused the death of the patient, a Xew York butcher, 
six weeks after the onset of the disease. Here the muscle is studded 
with cysts, each containing from one to six trichinae, while about these, 
and in fact all through the muscle, great quantities of nuclei are seen, 
about many of which there are distinct vacuoles; in some cases the 
nucleoli take the eosin stain. The muscle cells, mentioned before, 
here show still further degeneration; the protoplasm is granular and 
takes a yellowish color, while the nuclei stain very slightly with hanna- Thomas R. Brown 
333 
toxylin. But what is most interesting is that here again numbers of 
typical eosinophiles are to be seen scattered everywhere throughout 
the specimen, but congregated more especially in the areas of more 
marked degeneration, side by side with the degenerating bits of 
muscle and the muscle cells. 
Thus these two cases, both acute and both studied shortly after the 
infection, besides the marked changes in the muscles, characterized by 
the great proliferation of nuclei, the formation of muscle cells and 
their subsequent degeneration, the formation of distinct vacuoles about 
the proliferating and degenerating muscle nuclei, and the granular 
degeneration of many of the fibres, show an interesting and hitherto 
undescribed condition, namely, the presence of large numbers of 
eosinophilic cells. This fact, coupled with their coincident marked 
increase in the circulating blood, suggests one way at least in which 
these cells may arise in the body. 
Concerning the nature of the eosinophilic granules and the origin 
of the cells containing them, many widely divergent views have been 
held, some founded entirely upon staining reactions, others built on 
a somewhat firmer basis, all more or less hypothetical, some very far- 
fetched and bizarre. 
Until the introduction of the Ehrlich stains, these coarse, refractive 
granules were regarded as fat droplets by Wharton Jones (34), who 
first described them in 1846, by Forster (23) and Biesiadecki (8), who 
saw them in the blood in leukaemia, and by Neumann (52), Bizzozero 
(9), Budge (10) and Hosier (49), who noted them in the bone-marrow 
in the same disease. The cells containing these granules are the 
coarsely granular leucocytes of Max Schultze (63). 
The work of Ehrlich (19) and Schwarze (60) showed, however, that 
these large refractive granules are not fat droplets, but bodies possessing 
a chemical nature not clearly understood. Ehrlich first demonstrated 
the affinity of this granulation for the acid coloring matters. These 
eosinophilic granules, as they are now generally termed, are regarded 
by him and his school as a sort of nutritive reserve, built up by the 
cell for its own use or for excretion. Thus, according to Schwarze (60), 
they resemble somewhat the aleuron granules or crystalloids of plants 
THE INCREASE IN THE EOSINOPHILIC CELLS. 334 
Trichinosis ivith Increase of Eosinophiles 
in being the products of a specific cell activity, and are probably not 
proteid in nature. Zappert (73) and Przewoski (56), however, insist 
that these granules are of the nature of proteid, the latter showing that 
their solubilities and chemical reactions correspond in many respects 
to this form of matter. 
Many investigators, among whom may he mentioned Pouchet (55), 
Bannwarth (11) and Przewoski (56), basing their arguments upon the 
similarity in the reaction of these granules towards the acid aniline 
dyes, have regarded them as related to or identical with haemoglobin, 
though Ehrlich (19) and Schwarze (60) deny this and show that there 
are quite marked tinctorial differences between the eosinophilic granules 
and haemoglobin. 
The demonstration of the presence of iron in these granules by 
Barker (12) is of especial interest in this connection. 
Sherrington (65), who states that he demonstrated phosphorus in 
them by the Lilienfeld-Monti (44) method, regards them as a form of 
nucleo-albumin, while Kanthack and Hardy (36) consider them to he 
secretory products containing a zymogen, giving rise to alexines or other 
substances of great activity in phagocytosis and in conditions of in- 
flammation and intoxication. 
In all the above views the granules are regarded as paraplastic in 
nature. Gulland (24), on the other hand, holds that they are plas- 
matic; or, in other words, that they represent an altered condition of 
the microsomes and are connected by a mitoma. 
As a consequence of this diversity of opinion regarding the nature of 
the granules, the mode of origin of the cells is still an unsolved problem. 
The view most generally held is that they are derived from the poly- 
morphonuclear neutrophiles by a kind of ripening process, a view which 
was advanced by Max Schultze (63) and which is now held by Ehrlich 
(19), Gulland (24), Zappert (73) and many others. Muller and Rieder 
(475, c) and van der Stricht (66) think that, besides this mode of forma- 
tion, some eosinophiles are derived by mitosis from pre-existing cells 
of the same kind. Renaut (59), Denys (18) and Arnold (3) describe 
amitotic division of these elements. 
Max Schultze (63) and Muller and Rieder (476, c) hold that this 
change takes place mainly in the circulating blood; according to Ehrlich 
(19) the bone-marrow is the only place where this transition occurs; 
while van der Stricht (66) and Zappert (73) think that blood and 
haematopoietic organs both play a part in this process. 
Kanthack and Hardy (36) regard these elements as wandering cells 
whose home is normally the connective tissue; Saxer (68) thinks that all Thomas R. Brown 
335 
leucocytes are derived from pre-existing primary wandering cells, while 
Gollasch (26), Heusser (51) and Weiss (72) believe that they are derived 
directly from the tissue elements. 
Of those who think they can trace a relationship between eosinophiles 
and the red blood corpuscles, Przewoski (56) regards the eosinophiles as 
incompletely developed erythrocytes, i. e. derived from haematoblasts, 
while Sacharoff (67) believes that they are formed through the engulf- 
ing by leucocytes of nucleoli cast out by haematoblasts (nucleated red 
corpuscles) at the' time when the latter are converted into erythrocytes. 
The study of the blood and the tissues of our cases of trichinosis 
furnishes us with important evidence bearing upon the origin of the 
eosinophilic cells. The constant inverse relationship existing between 
eosinophiles and neutrophiles, the increase of the former being invari- 
ably coupled with a coincident decrease of the latter, so that the neu- 
trophiles on some occasions were absolutely subnormal in number not- 
withstanding the marked leucocytosis, as well as the similarity in size 
and the character of the nuclei of the two varieties of cells, both point 
strongly toward some very close connection between the two forms. 
Indeed, the striking and constant inverse relationship between the 
neutrophiles and eosinophiles would appear to be strong evidence in 
favor of the view that the latter cells arise, in some instances at least, 
by direct transformation of the former. There is much also to sug- 
gest that this transformation may have occurred here in the muscles. 
The presence in the first piece of muscle of many neutrophiles, to- 
gether with many typical eosinophiles and cells which might be re- 
garded as transitional forms between the two, and the finding in the 
second specimen two weeks later of a greatly increased number of 
eosinophiles, harmonize with this idea, especially when we consider that 
on both of these occasions the ratio of the neutrophiles to the eosin- 
ophiles in the peripheral blood and in the vessels of the interfascicular 
connective tissue was between four and five to one, a very much larger 
ratio than that which exists between these cells in the muscle. 
How such a transformation might take place one can only con- 
jecture. One may imagine that the trichinae on reaching the muscle 
act as a strong irritant or poison, giving rise to many tissue changes, 
and probably producing either primarily or secondarily chemotactic 336 
Trichinosis xuith Increase of Eosinophiles 
substances which attract large numbers of leucocytes to the muscles, 
causing a marked leucocytosis, especially in the more degenerated por- 
tions. In these regions the polymorphonuclear neutrophiles wander- 
ing out of the vessels act as phagocytes upon the degenerating or 
degenerated bits of muscle. It is in these phagocytes apparently 
that the change in the character of the granules takes place. 
By this it is not meant that the eosinophilic granules are bits of 
ingested material, but that they are elaborated by the cell itself. May 
not this result perhaps be due to the ingestion of some material origin- 
ating from the degeneration of the muscle fibres, which may bring 
about some essential change in the character and chemismus of the 
cell? 
Finally, we may well suppose that these cells wander or are swept 
back into the general circulation, giving us the marked increase in 
eosinophiles. Such a theory would not seem unreasonable, particu- 
larly when we consider the amount of muscle tissue in the body. The 
fact that practically no atypical neutrophiles or eosinophiles, i. e. evi- 
dences of transition, were seen in the blood itself speaks against the 
probability that such a change may have taken place in the circula- 
tion. Again, these small polymorphonuclear cells are certainly very 
different in appearance from the large, often mononuclear eosinophiles 
which we find in the blood and know to come from the marrow in 
leukaemia. 
It is interesting to note that during the course of this investigation 
an article appeared by Kischensky (39), in which he comes to the 
same conclusion regarding the origin of the eosinophiles in the sputum 
of asthmatics, in which these cells are present in very large quanti- 
ties, namely, that they are derived from neutrophiles. 
xkfter the completion of the above work and the publication of a 
preliminary note thereon in the Johns Hopkins Hospital Bulletin of 
April, 1897, a second ease entered the Johns Hopkins Hospital, which 
in almost all respects tended to confirm the results obtained in the 
preceding investigations. Thomas R. Brown 
337 
The patient, E. B., a sailor, age 29, white, of German nationality, was 
admitted, April 15, 1897, complaining of fever, chills, muscular pains 
and weakness. 
His past history shows that he has always enjoyed very good health; 
he gives no history of rheumatism nor of oedema, and has been only a 
moderate drinker. During his voyages his ship has often stopped at 
Cuba, hut the sailors have never been allowed to go on shore, and he 
said there had been no sickness whatever amongst the crew. It was 
later found, however, that two members had malarial fever of the 
aestivo-autumnal type. 
The present sickness dates from the first week in April. The onset 
was quite insidious; loss of appetite and general muscular weakness were 
noted, with occasional heavy painful sensations in the epigastrium. 
Headache set in for the first time on Friday, April 9, and continued until 
admission, the pain being especially marked in the frontal region. 
There had been considerable pain in the muscles of the hack and espec- 
ially in the calves of the legs since April 11. The bowels were regular 
until April 15, when the patient had two fluid stools, but no tenesmus. 
On April 10 the patient noticed a rather sudden oedema, of the eyelids 
and face, causing him much discomfort and some pain in opening and 
closing the lids. He had had pain in the facial muscles during mastica- 
tion for the last three days, while on deep inspiration there had been 
a slight pain through the chest. There had been no epistaxis. On 
board the ship the patient ate mostly salted meats and had frequently 
eaten raw sausage, though never raw ham. He had had shaking chills 
at times. 
The physical examination showed heart and lungs negative; good 
color of lips and mucous membranes; gums normal; slight pain and 
stiffness in the masseters on opening and closing the mouth, and slight 
puffmess of the eyelids. Pressure on larynx is slightly painful, but no 
pain on pressure of calf muscles. Ho pain in arms and thighs. Spleen 
is just palpable; abdomen is a little full hut not tender, and has upon it 
one or two spots somewhat suggestive of rose spots. There is no 
glandular enlargement; no tenderness or nodes on the long bones. 
The temperature at first was of an intermittent type, rising each 
evening to between 103° and 105.5° F. and sinking to normal by the 
following morning. After April 24 the temperature continued normal 
until the time of the patient’s discharge. 
The stools, which continued to be of fluid consistence for some time, 
on frequent examinations showed no parasites or ova of parasites. 
CLINICAL HISTORY OF CASE II. 338 
Trichinosis with Increase of Eosinophiles 
The urine was negative. The examination of the blood was made very 
frequently and carefully on many occasions, but no malarial parasites 
were ever obtained, nor were they obtained from the spleen, which was 
aspirated for this purpose. 
The blood, however, showed other marked changes, chief among 
which was a great increase of the eosinophile cells, reaching 42.8 per 
cent on one occasion, accompanied by a moderate leucocytosis. This 
very marked eosinophilia, coupled with other points in the clinical his- 
tory of the case, but mainly the eosinophilic increase, suggested the 
possibility that the case might be one of trichinosis. On April 28 a 
small piece of muscle from the calf was removed, and the diagnosis was 
confirmed by the demonstration in it of young non-encapsulated 
trichinge. These were not present in such large numbers as in Case I, 
as might have been expected from the fact that the present patient 
complained of much less pain and in general showed less marked 
symptoms. 
The subsequent history of the case was, as in the previous instance, 
a gradual cessation of all the symptoms, a disappearance of the mus- 
cular pain and a slow decrease in the percentage of eosinophiles, there 
being 17.6 per cent when he left the hospital, still a considerable increase 
above the normal. 
THE BLOOD. 
The blood in this case showed in many respects the same features 
as in the previous one (Table III). Both eosinophilia and leucocytosis, 
however, were less marked, as one would naturally have expected, since 
we were here dealing with a much less severe infection, if one may 
judge from the much milder clinical symptoms and the discovery of 
fewer parasites in the portion of muscle removed. As the patient 
was under observation a much shorter time, the table is not so com- 
plete as that belonging to Case I. The eosinophiles, which on admis- 
sion made up 42.8 per cent of the total leucocytes of the blood, 
gradually sank to between 14 and 17 per cent, while in the correspond- 
ing period the polymorphonuclear neutrophiles rose from 43.1 to be- 
tween 58 and 67 per cent (see Table III). 
The leucocytosis varied between 6,000 and 13,000 during the 
patient’s stay in the hospital, averaging about 10,000 and not varying 
markedly. The small mononuclears showed at first a tendency to be 
much decreased, as in the previous case; but, as was also seen before, 
showed later only slight fluctuations. Thomas R. Brown 
339 
Date. 
Leucocytes 
per cmm. 
Percentage oe the Various Forms of Leucocytes. 
Total Number of Various Forms per cmm. 
P. M. Neut. 
L. M. and T. 
S. Monos. 
Eos. 
P. M. Neut. 
S. Monos. 
L. M. and T. 
Eos. 
April 15.... 
13000 
43.1 
6.5 
1.4 
42.8 
5600 
180 
840 
5560 
16 
47.7 
4.7 
4.5 
39.1 
17 
52.0 
2.8 
7.6 
37.6 
18 
8000 
19 
57.2 
2.8 
8.0 
32.0 
20 
8900 
55.2 
3.8 
11.2 
31.8 
4900 
1000 
340 
2830 
21 
8700 
22 
10700 
58.0 
2.7 
11.7 
27.7 
6200 
1250 
290 
2960 
23 
6000 
56.2 
2.0 
15.2 
26.2 
3370 
910 
120 
1570 
24 
11000 
60.4 
4.0 
13.2 
22.4 
6640 
1450 
440 
2460 
25 
11000 
57.2 
4.2 
18.6 
20.0 
6290 
2050 
460 
2200 
26 
9600 
60.7 
5.3 
12.3 
21.7 
5830 
1180 
510 
2080 
27 
11300 
63.0 
5.0 
17.0 
14.7 
7120 
1920 
560 
1660 
28 
12700 
62.7 
4.0 
17.0 
16.3 
7960 
2160 
510 
2070 
29 
12000 
67.0 
3.25 
15.25 
14.0 
8040 
1830 
390 
1680 
May 1.... 
10700 
58.3 
4.0 
22.0 
15.7 
6240 
2350 
430 
1680 
3 
13000 
64.3 
4.0 
16.0 
15.7 
8360 
2080 
520 
2040 
5 
12000 
64.7 
4.0 
16.0 
15.3 
7760 
1920 
480 
1840 
7 
9300 
62.8 
4.0 
16.4 
16.8 
6140 
1530 
370 
1560 
10 
10700 
60.4 
2.8 
16.4 
20.0 
6460 
1750 
300 
2140 
12 
11000 
60.4 
3.3 
16.6 
19.6 
6640 
1820 
360 
2160 
14 
12000 
58.8 
2.8 
18.8 
19.6 
7060 
2260 
340 
2350 
17 
9000 
58.8 
3.6 
20.0 
17.6 
5290 
1800 
320 
1580 
TABLE III. CASE II.—BLOOD CHART. 340 
Trichinosis with Increase of Eosinophiles 
When one considers the morphological structure of the different 
white blood cells one is again struck by the fact that mononuclear 
eosinophiles are almost entirely wanting, the nucleus of these cells 
being almost exclusively polymorphous and resembling in every way 
that of the neutrophiles. Here also, as in Case I, extremely few 
myelocytes were seen (averaging 0.03 per cent), and but few forms 
which could be regarded as transitional forms. 
The number of red blood corpuscles per cmm. varied between 
5,000,000 and 5,120,000. 
THE MUSCLE. 
The changes in the muscle in this case, although some of the 
features described before were lacking, resemble in many respects 
those seen in the first case. They were, however, by no means so 
well marked. 
There is proliferation of the muscle nuclei, especially in the fibres, 
which show by their loss of staining properties a beginning degenera- 
tion. The number of degenerating fibres, however, is small, and these 
are entirely confined to the neighborhood of the trichinae. The nuclei 
of the fibre containing the trichina are pale and greatly swollen, the 
nucleoli large and deeply staining; a few karyokinetic figures are 
seen. 
Surrounding the large typically curved trichina in its muscle fibre, 
which shows granular degeneration, we have many small round cells, 
“muscle cells,” muscle nuclei, polymorphonuclear cells (mostly neu- 
trophilic, a few eosinophilic) and bits of muscles containing many 
swollen proliferated nuclei. 
The striation of some of the degenerated fibres is entirely lacking; 
in others the peculiar granular degeneration noted in the first case is 
seen. 
There are some eosinophiles scattered throughout the specimen, 
though not comparable in number to those noted in the first case; 
here more of the polymorphonuclear cells are neutrophiles. 
There is no evidence of transition from neutrophiles to eosinophiles 
in this specimen. In fact the whole picture is one of a much less 
violent infection than in the first case. In all probability the trichinae Thomas R. Brown 
341 
had been in the muscle fibre a longer time than in the first case, since 
when the bit of muscle was removed the number of eosinophiles per 
cmm. had fallen to a comparatively low point, nor did they rise again, 
a point which suggested, as did the clinical history, that the infection 
had almost run its course. 
Decently, since the preceding pages were placed in the hands of the 
editor, a. third case of trichinosis has come under our observation, 
which tends still further to establish our belief in the conclusions 
arrived at from the study of the first two cases. 
In this, as in the second case, the discovery of a largely increased 
number of eosinophiles in the peripheral circulation led to the idea 
that the case was one of trichinosis, and an examination of an excised 
bit of muscle again proved the correctness of this idea. 
Case III.—The patient, J. Y., was admitted to the hospital, December 
21, 1897, complaining of headache, pain in the side, chilly sensations 
and swelling of the feet. Six months previously he had been treated 
for typhoid fever in the hospital and still gave the Widal reaction. 
Seven years previously he had had an attack of acute articular rheu- 
matism. 
The patient lived with his German employer and frequently partook of 
sausages and other forms of swine meat, often insufficiently cooked. 
For five weeks he had been feeling unwell, complaining of frontal 
headaches and coughing spells; there had been no herpes, nose-bleed nor 
shaking chills. Five days before entering the hospital the patient had 
had an acute attack of diarrhoea, having 5 to 8 thin, green stools daily, 
associated with severe griping pains in the abdomen. Two days after 
the commencement of the diarrhoea he had noticed that his legs, feet, 
hands and arms seemed numb and cold. The joints were stiff and the 
limbs swollen and his attention was called by his employer to his 
swollen eyelids. 
On admission the physical examination showed an absence of rose 
spots, spleen not palpable, puffiness of the eyelids, great tenderness of 
the muscles of the arms and of the calf, with swelling of the former 
and a bluish mottling of the skin of the limbs. 
The temperature reached 103° for the first few days and then gradu- 
ally fell to normal; shortly after this the pain in the limbs and the 
intestinal symptoms decreased, and on January 16, 1898, the patient 
was discharged, apparently quite well except for slight soreness of the 
right leg. 342 
Trichinosis with Increase of Eosinophiles 
The blood (Table IY) on admission showed 45 per cent of eosino- 
philes, and this, from the study of the two previous cases, led to the 
diagnosis of trichinosis and the subsequent confirmation of that diag- 
nosis by the removal of a portion of muscle and the discovery of 
trichinae therein. 
TABLE IV. CASE III.—BLOOD CHART. 
Date. 
Number per cmm. 
Percentage op 
Red blood 
corpuscles. 
Leucocytes. 
Polymorpho- 
nuclear 
neutrophlles. 
Large mono- 
nuclears and 
transitional. 
Small 
mono- 
nuclears. 
Eosino- 
pbiles. 
Dec. 22.. 
48.4 
4.7 
1.5 
45.4 
23.. 
17,000 
52.7 
3.6 
3.1 
40.4 
27.. 
4,700,000 
15,300 
42.4 
4.0 
5.6 
45.0 
Jan. 3.. 
4,300,000 
12,000 
42.2 
4.2 
4.6 
49.0 
7.. 
14,700 
31.6 
4.4 
19.0 
44.6 
10. . 
4,546,000 
32.4 
3.0 
21.8 
42.8 
14.. 
13,700 
35.2 
4.0 
23.4 
37.2 
22.. 
9,000 
45.5 
2.0 
17.7 
34.7 
During the stay of the patient in the hospital the proportion of 
eosinophiles varied very slightly, reaching 49 per cent on January 3 
and sinking to 34.7 per cent on January 22. As in the other cases, 
the nuclei of practically all these cells were polymorphous; yet, as 
before, no forms were seen in the blood suggesting transitional stages 
between neutrophiles and eosinophiles. At first there was a smaller 
percentage than normal of the small mononuclears, which, however, 
increased later up to practically the normal, a condition which was 
noted in both the preceding cases. On one occasion, and only one, 
two typical myelocytes were seen. The leucocytosis was not marked, 
being 17,000 on December 23 and 9,000 on January 22 (see Table 
IV). 
As in the preceding cases, it was impossible to determine how long 
the eosinophilia lasted, as in all three cases the patients left town and 
were lost from observation. Thomas R. Brown 
343 
The stools, although examined repeatedly, showed no intestinal 
trichinae. 
The piece of muscle removed during the first week of the patient’s 
presence in the hospital showed in almost all respects the same changes 
noted in the two previous cases, except in this case the specimens of 
the parasite found in the muscle were younger, smaller and less 
abundant than in the first case. In the muscle fibre in which the 
trichinae were found there was a complete loss of striation and a 
tendency to take on a faint bluish stain. In these fibres the prolifer- 
ated and greatly swollen muscle nuclei with their deeply staining 
nucleoli were seen arranged circularly about the trichinae lying in the 
finely granular, faintly staining, degenerated muscular substance. 
Hear the infested fibres were found degenerating areas made up of 
disintegrating bits of muscle fibre, muscle nuclei, small round cells, 
and polymorphonuclear cells, a great many of whose granules were 
eosinophilic. These eosinophilic cells were especially prevalent 
about the bits of degenerating muscle and were certainly as numerous 
as in the first case. 
There was the peculiar granular degeneration of the muscle fibres 
noted before, and the proliferation of the muscle nuclei in the neigh- 
borhood of the parasite. 
The trichinae were young, only slightly curled up and of course 
non-encapsulated. 
In severity, clinically, this case lies midway between the first and 
second cases, and this position is borne out by the number of parasites 
found in the muscle excised, by the leucocytosis and by the grade of 
eosinophilia. 
SUMMARY. 
To summarize, we have been able to demonstrate: 
(1) In a case of acute trichinosis an extensive leucocytosis, with 
great absolute and relative increase in the number of eosinophilic cells 
in the blood, associated with a coincident decrease in the quantity of 
neutrophilic elements. * 
(2) From the examination of specimens of muscle removed during 
life, besides the peculiar degenerations of the muscle, a longitudinal 344 
Trichinosis with Increase of Eosinophiles 
splitting of some of the fibres; a remarkable transverse splitting of 
others; a great proliferation of nuclei, about many of which vacuoles 
are seen; and large numbers of polymorphonuclear eosinophilic cells, 
which are especially prevalent in the more degenerated areas. 
(3) In a second case (after death), besides similar changes in the 
muscle, large numbers of eosinophiles throughout the infested portion. 
(4) In two other cases, during life, a great increase of the eosino- 
philic cells in the blood, with a coincident decrease of the polymor- 
phonuclear neutrophiles, associated with leucocvtosis, though of less 
extent than in the first case. 
(5) In pieces of muscle removed in these last two cases changes in 
most respects similar to those cited in the first case, but of less degree. 
(6) The similar character of the nuclei of the eosinophiles and the 
neutrophiles both in the blood and in the muscle, and the presence 
in the first case of certain cells which might be regarded as forms 
transitional between neutrophiles and eosinophiles, suggesting the 
possibility that the increase in the latter elements may, in these in- 
stances, take place in the muscles by direct transition from the neu- 
trophiles. 
CONCLUSIONS. 
From these observations it is fair to conclude: 
1st. That there is a marked increase in the percentage of eosino- 
philic cells in the blood in trichinosis. 
2nd. That this increase may be used as a diagnostic sign in this 
disease. 
3rd. That this disease in its sporadic form is more common than 
has hitherto been supposed, as shown by the discovery of the three 
cases above described, within a comparatively short period, at the 
Johns Hopkins Hospital. 
4th. That a systematic examination of the blood should be under- 
taken in cases with indefinite intestinal, muscular or articular symp- 
toms, in the hope that in some, at least, of the hitherto doubtful cases 
a diagnosis may be reached. 
In conclusion I wish to express to Professor William Osier my 
sincere appreciation of his kindness in giving me the opportunity of Thomas R. Brown 
345 
studying these cases, and to Dr. William Sidney Thayer my hearty 
thanks for his help during the course of this investigation. 
DESCRIPTION OF PLATES XXV-XXVII. 
Plate XXV. 
Chart showing graphically the total number and percentages of the 
various kinds of leucocytes. 
From the blood of Case I, showing a typical field, containing six eosino- 
philes, with polymorphous nuclei, one polymorphonuclear neutrophile, one 
large mononuclear leucocyte and many erythrocytes. 
Plate XXYI. 
Plate XXYII. 
Showing degenerating area in muscle in neighborhood of trichina, demon- 
strating beginning loss of striation in two fibres, complete loss in a third, 
and in the rest of the specimen, muscle nuclei, bits of degenerating muscle 
tissue and many polymorphonuclear eosinophiles. Haidenhain-Biondi triple 
stain. 
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74c. Ibid., viii (1870-1), 387. THE JOURNAL OF EXPERIMENTAL MEDICINE. VOL. III. 
LEUCOCYTIC CHART OR CASK I. 
Showing Total Number of Leucocytes, of Polymorphonuclear Neutrophiles and of Eosinophiles, and also the Percentage of Polymorphonuclear Neutrophiles and of Eosinophiles. 
PLATE XXV. THE JOURNAL OF EXPERIMENTAL MEDICINE. VOL. III. 
PLATE XXVI 
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PLATE XXVII. 
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