coat Pharynx and fauces arc red and injected. The tonsils are large and
irregular; no exudate. Neck. — There is no retraction of the neck. The head is
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Francis W. Peabody, George Draper, and A. B. Dochez. 181.
easily held erect. There is no muscular weakness. The child resists anterior
flexion slightly. Superficial lymph nodes,— The cervical, axillary, and inguinal
glands are all easily palpable. Chest. — Well formed, expansion good, both sides
move equally in respiration, diaphragm active. Lungs. — Clear on ausculation and
percussion. Heart. — Action not especially rapid, sounds well heard, regular, no
murmurs. The heart is not enlarged Abdomen. — Soft, moves well with respira-
tion, no masses or tenderness, no bulging. Abdominal muscles are strong.
Extremities. — ^Upper: arm movements are normal, muscles show no weakness.
Lower: the legs can be moved in all directions. The child stands alone and can
walk well. The legs can be fully flexed on the abdomen without causing pain.
The child, however, shows some irritability on being handled in this way.
Reflexes. — Knee jerks, Achilles, and abdominal reflexes are active. Babinsld
and Kemig reflexes arc absent Temperature.— -100.6'* F.
October 4. Spinal fluid: 35 c.c. of clear limpid fluid; pressure definitely in-
creased (child crying somewhat) ; cells, 94 per c.mm. ; mononuclears, 93 per
cent; polymorphonuclears, 7 per cent; globulin, o; sugar, +.
October 5. Blood count: leukocytes, 15,000; differential count of 200 cells:
polymorphonuclears, 52.5 per cent.; lymphocytes, 31.5 per cent; large mono-
nuclears, 13.5 per cent.; transitional s, 1.5 per cent; basophiles, 0.5 per cent;
eosinophiles, 0.5 per cent ; stimulation form, a
October 8. There is no evidence_of paralysis. Reflexes are present and active
in the legs. The child can walk and stand well, but his gait is rather wobbly.
He is irritable and cries a good deal, but it seems to be temper chiefly. His legs
appeared weak, and he fell when first put on the floor, but when he was started
walking towards his sister, he could walk very well.
October 15. The child walked very well this morning, several times up and
down the hall. Both knee jerks and Achilles reflexes are active. The lungs are
clear. The tonsils are both a little enlarged, but not especially red. Moving the
legs (Kemig) seems to be painful still, though it is hard to distinguish the pain
from temper. The child is discharged today.
CASE 33.
Helen B., age, 6 years. Bergenficld, N. J. Admitted, September 2, 191 1. Dis-
charged, September 17, 191 1. Result, much improved. Diagnosis.— Acute polio-
myelitis (abortive form).
Family History. — Negative.
Past History.— The patient has always been a healthy child and was never sick
until July when she had whooping cough. She has always played with Helen K.
(see case 29, page 174, who was taken sick on August 16 with acute poliomye-
litis and died on August 21).
Present Illness.— The child was perfectly well yesterday morning, September
I. She came down to breakfast singing, ate her breakfast well, and played all
the morning. She also ate a hearty lunch and played for a while in the after-
noon. Later in the afternoon she complained of headache, which continued all the
evening. She ate no supper, slept fairly well, was not very restless but seemed
dull. .This morning she ate no breakfast. She has not vomited, but there was no
movement of the bowels yesterday. No weakness of any extremity has been
noticed. She has had some pain in the back of the neck and forehead.
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182 A Clinical Study of Acute Poliomyelitis.
Physical Examination.'^Tht patient is a well developed little girl who lies
quietly in bed and looks acutely sick. The face is flushed, the expression of the
eyes is heavy and the lids are half closed or closed most of the time ; she is very
apathetic Eyes, — ^The pupils are equal and react normally. Sclerse are clear,
ocular motions normal Nose, — No discharge. Face, — ^There is no weakness of
the face muscles. Ears, — Normal. Mouth. — ^Buccal mucous membranes are
clear. The teeth are in fair condition. No Koplik spots. The tongue has a
very light greyish coat Pharynx and tonsils are slightly reddened. The latter
are large, especially the right Superficial lymph nodes, — The posterior cervical,
submental, axillary, and inguinal nodes are palpable. Neck, — Not stiff. Thorax,
— Well formed, respiratory motions are normal. Lungs. — Clear. Heart, — Rapid,
sounds normal, action regular. Abdomen. — Not distended, soft, no tenderness,
no masses. Extremities. — Upper: normal, no tenderness. Lower: there is
good power in all the muscles, no tenderness. Kemig manipulation causes no
pain. Knee jerks are very active on both sides; crossed adductor reflex is
obtained on tapping the left patellar tendon. The Achilles reflex is also active,
the Babinski reflex negative on both sides. Back, — No weakness, no pain or
tenderness. Surface, — There are several fresh bruise marks over the legs.
Temperature,— lOS.S,'' F.
September 2. Blood count: leukocytes, 8,800; differential count of 200 cells:
polymorphonuclears, 77 per cent; lymphocytes, 17.5 per cent; large mono-
nuclears, 0.5 per cent. ; transitionals, 4 per cent ; stimulation form, i per cent
Spinal fluid : 20 c.c of almost clear limpid fluid. There is a faint suggestion of
opalescence ; cells, 5 per cmm. ; polymorphonuclears, 20 per cent ; mononuclears,
80 per cent; globulin, o; sugar, +.
September 3. The patient slept well. Her temperature is 99.1* F. This morn-
ing the temperature has fallen to 99^ F. She is still rather listless but much less
dull than yesterday. She has no headache. The knee jerks are still very active.
The patient says she feels much better. She vomited after taking citrate of
magnesia. In the afternoon the mother came and finding the child's temperature
normal insisted on taking her home. She was advised to leave the patient but
would not The temperature was 98.7® F. The patient showed some unsteadi-
ness on her feet but no definite weakness. About an hour later the mother
returned in a taxicab with the child. On the way to the train she had com-
plained bitterly of her head and vomited. The child begged to be put in bed.
She looks greatly prostrated. There is a distinct tendency to keep the head
back, and she assumes the position on her side so as to facilitate this. The neck
is very slightly stiff, and an attempt to flex it causes pain. The Kemig manipu-
lation causes pain about the knees. The knee jerks are still exaggerated.
Spinal fluid: about 2 c.c,; cell count, 62 per cmm.; polymorphonuclears, 11.3
per cent; mononuclears, 88.7 per cent; globulin, slightly +.
Blood count: leukocytes, 11,200; differential count of 200 cells: polymorpho-
nuclears, 79.S per cent. ; lymphocytes, 14.5 per cent. ; large mononuclears, 0.5 per
cent.; transitionals, 4.5 per cent; basophiles, o; eosinophiles, as per cent;
stimulation form, 0.5 per cent
September 4. Temperature: 99.1** F. The patient seems a little better this
morning. She is still apathetic and prefers to lie on her side. The neck resists
flexion slightly, and the attempt to flex it causes pain in the occipital region.
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Francis W. Pedbody, George Draper, and A. B. Dochez. 183-
Kemig manipulation causes slight pain in the knee. Knee jerks are not quite
so exaggerated as before, but are still very active. No weakness is found in any
muscles. The patient sits up well. The tongue has a heavy yellowish grey^
coating.
p. M. She has been drowsy and sleepy most of the day. When her father
came the child paid hardly any attention to him and showed no signs of pleasure.
She answered his questions only by nods and shakes of the head. As soon as he
left the room she became drowsy again. At 3:00 p. m. the knee jerks arc found
to be so much less active than before that several blows of the hammer are
required to elicit the jerk. They are fairly active when they do respond. No-
weakness is found The neck is a little less stiff.
10:20 P. M. The patient is sleeping, but half waked during the process of
eliciting knee jerks. They are less easily obtained than when last noted. When
they respond it is with about normal activity. The stiffness of the neck late this,
afternoon (about 5 :20 p. m.) had almost entirely gone.
September 5. The patient slept well this morning. She seems brighter, though
still not very communicative. She has no headache. The neck is not stiff.
Both knee jerks are active. She still prefers to lie in bed and does not feel
energetic. The von Pirquet reaction made two days ago is positive, a raised
urticarial-like area about i cm. in diameter, and red. The temperature dropped
to normal last night This morning it is 99** F. again.
p. M. The patient continues to be somnolent and takes very little interest in
her surroundings. There is no change in her physical condition. It is possible-
that the right palpebral fissure is somewhat narrower than the left Examination
of the eye grounds reveals no abnormality.
September 6. The patient is a little brighter this morning but still prefers to-
lie in bed The tongue has almost entirely cleared. The neck is a little stiff.
"Signe de la nuque" is present The left knee jerk is obtained on reinforce-
ment only, right knee jerk normal.
Spinal fluid : about 8 c.c. of not quite clear, slightly opalescent fluid with faintly
yellowish tinge; cells, 59 per cmm., mostly mononuclears; globulin, slightly +;
sugar, 4~* In the wet preparation for counting, a large phagocytic cell was seen>
containing Ave small mononuclears. Blood count: leukoc3rtes, 5,600; differ-
ential count of 200 cells: polymorphonuclears, 68.5 per cent; lymphocytes, 22-
per cent ; large mononuclears, 1.5 per cent ; transitionals, 6 per cent ; basophiles,.
o; eosinophiles, i per cent.; stimulation form, i per cent
This evening the patient is somewhat brighter but continues to answer ques-
tions by shakes or nods and occasionally a monosyllabic reply. She is still drowsy.
There is no change in her physical condition.
September 7. The patient seems better this morning. She sits in a chair
easily, and also walks well, though perhaps with a little uncertainty. She con-
tinues to be most unresponsive. Her appetite is better, however, and she ate her
supper last night, and breakfast this morning with a relish. There is still slight
rigidity of the neck and " signe dc la nuque." The knee jerks are the same as
yesterday.
September 11. The patient is considerably better. She talks more and
is losing her apathy. She still does not fed much like sitting up. The knee jerks
are active. Spinal fluid : 20 c.c. of clear limpid fluid ; pressure not increased ; cell
count, 4 per cmm. ; globulin, very slight haziness (normal) ; sugar, +.
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184 A Clinical Study of Acute Poliomyelitis,
September 13. Blood count: leukocytes, 11,800; diflfercntial count of 200
cells: polymorphonuclears, 78.5 per cent.; lymphocytes, 14.5 per cent; large
mononuclears, 4.5 per cent ; transitionals, 3.5 per cent ; eosinophiles, 0.5 per cent ;
basophiles, o; stimulation form, 0.5 per cent
September 15. While the patient is better in every way, she still gives the
impression of being a little apathetic. Her appetite is poor. Besides the un-
steadiness that one would expect on first getting up, her manner of walking
gave distinctly the impression of spasticity. This was quite in accord with the
generally increased tone of the legs throughout her illness and with the exag- .
gerated knee jerks. This morning the knee jerks are very much exaggerated.
September 17. The patient has been up in a chair for the past two days and
was walking yesterday. She walks much more steadily. On physical examination
nothing abnormal can be found but the still somewhat exaggerated knee jerks.
The neck has no trace of stiffness and the ''signe de la nuque" is gone. She
feels well and is discharged.
CASE 34.
Clara T., age, 8 months. New York City. Admitted, August 22, 191 1. Dis-
charged, August 24, 191 1. Result, not improved. Diagnosis, — ^Acute poliomyelitis.
Family History, — Mother and father arc living and well. There is one other
child in the family, a twin sister of the patient, who now has poliomyelitis in
this hospital.
Past History. — The child has had no illness previous to the onset of the
present trouble.
Present Illness. — The child was perfectly well until yesterday evening, August
21. At this time the mother noticed that she was rather irritable and objected
to being handled. She vomited several times, and had a slight cough. Today she
has again vomited several times and at four o'clock this afternoon her tempera-
ture was 102*" F. When the child was examined in the receiving ward, hancMing
of the right leg caused loud screaming.
Physical Examination.— Tht patient is a well nourished baby with good color,
bright alert expression, and does not look sick. She lies quietly, and is sometimes
playful. During examination she regurgitated suddenly and without effort
Occasionally she coughs. Eyes, — Pupils are equal and react normally. Ocular
motions are normal, no squints. Ears. — Normal. Nose, — Normal. Mouth. —
Buccal mucous membrane is clear. Tonsils are a little enlarged, pharynx slightly
reddened, ^^c*.— Distinct rigidity. Superficial lymph nodes,-— Tht posterior
cervical and left axillary nodes are palpable. Thorax, — Well formed, respiratory
motions normal. Heart, — Normal. Lungs. — Normal. Abdomen.— WeU. rounded
and prominent, soft, moves properly with respiration. The spleen is easily felt
Extremities. — Upper : there is possibly a shade less strength in the right shoulder
than in the left, but this is very indefinite. At times there is a distinct stiff
shaking of the arms. Lower: knee 'jerks absent on the right, very faint reac-
tion on the left; Achilles reflex absent on the right, present on the left;
Babinski test negative on both sides; Kemig's sign: on the right side no
resistance but some distress, on the left slight resistance. The left 1^ is moved
about in a very active manner. The right, however, is not moved nearly so
much, practically not at all spontaneously* When prodded, there is some move-
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Fromqis W. Peabody, George Draper, and A. B, Dochez. 185
ment to withdraw the extremity, but this is chiefly in the lower leg muscles, and
very little or not at all in the thigh. Surface. — ^There is a faint erythema over
the upper part of the chest anteriorly. Over the inner end of the right eyebrow
is a small superficial moist ulceration, sharply circumscribed and looking much
like a collapsed water blister. T emperature, -^loa.^* F.
August 22. Spinal fluid : 30 c.c. of slightly greyish opalescent fluid ; pressure at
first much increased (child crying) ; later, slightly increased ; cells, 990 per cmm. ;
95 per cent, polymorphonuclears. Smear: polymorphonuclears, 85.5 per cent;
transitionals, 4 per cent. ; mononuclears, 10.5 per cent, (including probably both
endothelial and lymphocytes, these cells being destroyed beyond recognition) ;
globulin, +; sugar, + +. Blood count: leukocytes, 35.6oo; differential count of
200 cells: polymorphonuclears, 32 per cent; lymphocytes, 55.5 per cent; large
mononuclears, i per cent; transitionals, 9 per cent.; basophiles, o; eosinophiles,
I per cent. ; stimulation form, 1.5 per cent.
August 23. Spinal fluid : about 7 cc. The first cubic centimeter was clear
and slightly opalescent. This was used for cell count and smear. The smear con-
tained a few red blood corpuscles, with great excess of mononuclears. Cell count,
627 per cmm. ; polymorphonuclears, 20 per cent. ; mononuclears, 80 per cent. ; no
test for globulin, nor for sugar. On admission the child was irritable and cried
a great deal. The knee jerks and Achilles jerks on each side were exaggerated.
Both lower extremities were strong and active. This evening the left knee jerk
is gone. The left Achilles jerk is very faintly present. The child cannot move
the left thigh now, so that both lower extremities are affected. The flexors and
extensors of the feet are still acting, but are weak. The child is rather more
fretful this evening.
August 24. This morning there is no further advance of the paralysis, but
both lower extremities are flaccid, save for some slight motion in the flexors
and extensors of the feet and toes. The Achilles jerk on the left is gone. The
arms are active and strong. The temperature has risen again to 102.8* F. The
child looks bright, but is perhaps too alert and nervous. She is still inclined to
be irritable if handled. If a sudden noise occurs, she blinks rapidly for several
seconds and starts. Blood count: leukocytes, 23,200; differential count of 200
cells : polymorphonuclears, 49 per cent ; lymphocytes, 33.5 per cent. ; large mono-
nuclears, 5 per cent; transitionals, 9.5 per cent; basophiles, 0.5 per cent;
eosinophiles, as per cent. ; stimulation form, 2 per cent.
This afternoon the child seems to be in about the same condition. It is
possible that the patient is slightly mpre somnolent and does not show the
nervous activity of the upper extremities that she did yesterday. Spinal fluid : a
few cubic centimeters of slightly turbid, opalescent fluid were obtained ; cell count,
1,221 per cmm. In the wet count there are many very large phagocytic mono-
nuclear cells with vacuoles; mononuclears, 92 per cent.; globulin, + (moderate
flocculent precipitate) ; no test made for sugar. The father insisted on taking
the child home this afternoon.
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186 A Clinical Study of Acute Poliomyelitis.
EXPLANATION OF PLATES.
Plate i.
Fig. I. Interstitial meningitis in the anterior fissure of the cord, with begin-
ning perivascular infiltration of the gray matter (human).
Fig. 2. Infiltration with small round cells in the perivascular lymph spaces
< monkey).
Plate 2.
Fig. 3. Diffuse areas of hemorrhage in the gray matter of the cord (human).
Plate 3,
Fig. 4. Neurophages in nerve cells of the anterior horn (monkey).
Fig. 5. Extensive infiltration of the gray matter of the cord (human).
Plate 4.
Fig. 6. The inflammatory process is seen extending throughout the whole
anterior horn (monkey). Low power.
Fig. 7. Drawing of the lumbar cord of a monkey showing extensive intcr-
rstitial meningitis and beginning perivascular infiltration.
Plate 5.
Fig. 8. Perivascular and diffuse round cell infiltration in the medulla
< monkey).
Plate 6.
Fig. 9. Cervical ganglion, showing advanced inflammatory reaction.
Pi-ATE 7.
Fig. 10. A spinal ganglion showing diffuse inflammatory process and begin-
ning necrosis of the nerve cells (human).
Plate a
Fig. II. Neurophages in a spinal ganglion (monkey).
Fig. 12. Human lymph node. The pale centres of the nodules are formed
hy large endothelial cells. Low power.
Plate 9.
Fig. 13. Human liver. Drawing showing necrosis of the liver cells and
accumulation of lymphoid and polynuclear cells. High power.
Fia 14. Electrocardiogram of the arrhythmia r^ularly seen in the fatal
<ases.
Plate la
Fig. 15. Photograph of a case with profound stupor, showing irritated ex-
pression. The paralyzed left arm has been flung over by the shrugging of the
shoulder. The retraction of the neck is also apparent
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Francis W. Peabody, Oeorge Draper, and A, B. Dochez. 187
Fig. i6. A case of intercostal paralysis, showing protrusion of the abdomen
by contraction of the diaphragm and concomitant retraction of the thorax.
Fig. 17. Front view of patient shown in figure 2 with intercostal paralysis.
Plate ii. •
Fig. 18. Paralysis of the lateral abdominal muscles. Bulging is produced
by crying.
Fig. 19. Paralysis of the lateral abdominal muscles and right rectus. Bulg-
ing is caused by the attempt to sit up.
Plate 12.
Fig. 20. The only evidence of paralysis is in the upper distribution of the
seventh nerve. This was a profoundly stuporous case.
Plate 13.
Fig. 21. Residual facial palsy in a case with profound stupor.
Fig. 22. The same as figure 21.
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MONOGRAPH NO. 4.
Fig. I.
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MONOGRAPH NO. 4.
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MONOGRAPH NO. 4. PLATE 3
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MONOGRAPH NO. 4. PLATE 4.
Fig. 6.
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MONOGRAPH NO. 4. PLATE 5.
Fig. 8.
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MONOGRAPH NO. 4. PLATE 6.
Fig. 9.
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MONOGRAPH NO. 4. PLATE 7
Fig. 10.
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MONOGRAPH NO. 4. PLATE
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MONOGRAPH NO. 4. PLATE 9.
Fig. 13.
F'iG. 14.
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MONOGRAPH NO. 4.
Fig. i6.
Fig. 15.
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MONOGRAPH NO. 4. PL^TE 11.
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MONOGRAPH NO. 4. PLATE 12.
Fig. 20.
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MONOGRAPH NO. 4. PLATE 13.
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Reprinted from Turn Journal of -Biolooxoal Cbbmutbt, Vol. XII, No. 1. 1012
PICROLONATES OF THE MONOAMINO-ACmS.
By p. a. LEVENE and DONALD D. VAN SLYKE.
(From the Laboratories of the Rockefeller Institute for Medical Research,
t^ew York.)
(Received for publication, May 29, 1912.)
N0«-CeH4-N
Picrolonic acid N COH was first introduced by
II II
CHs-C CNO,
Knorr* as a precipitant for organic bases. SteudeP applied it
to the hexone bases obtained by hydrolysis of proteins. Later
Mayeda* described also the picrolonates of the aromatic amino-
acids, tryptophane and phenylalanine. The latter was partic-
ularly distinguished by itg slight solubility in water. In the
course of a hydrolysis we found this picrolonate of so much
assistance in the isolation of phenylalanine that we attempted
to make the picrolonates of some of the other monoamino-acids,
with the idea that they also might prove useful in the separa-
tions that are necessary in carrying out protein hydrolyses. We
found that all the natural monoamino-acids, with the exception
of the pyrrollidine a«ids, proline, and oxyproline, gave beau-
tiful crystalline, definite salts with picrolonic acid, most of them
being fairly insoluble in cold water. When this work had been
completed and the report sent in to the Secretary of the Society
for Experimental Biology and Medicine for the meeting of May
15, an article by Abderhalden and Weil* appeared describing
picrolonates of alanine, glycocoU, and inactive leucine. This
' Ber. d. deutsch. chem. Gesellsch., xxx, p. 909, 1897.
» Zeitschr. /. physioL Chem., xxxvii, p. 219.
»/Wd., li, p. 261.
* Ibid,, Ixxviii, p. 150.
127
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128 Picralonates of the Monoamino-Acids
paper antedates our report in demonstrating that the ordinary
monoamino-acids form crystalline picrolonates. As, however,
our technique was somewhat different from that of Abderhalden
and Weil, yielded products of constant molecular composition,
and our work included the preparation and study of a larger series
of picrolonates, we decided to pubhsh it in the present paper.
Abderhalden and Weil added an alcoholic solution of pic-
rolonic acid to the concentrated water solution of the amino-
acids. Crystalline products were obtained, but, in the case of
glycocoU and alanine, when an excess of the amino-acid was pres-
ent the product contained more than 1 molecule of amino-acid.
We never met this diflSculty. Our procedure is as follows: The
amino-acid and picrolonic acid in molecular proportions, or with
amino-acid in excess, are dissolved in a minimum amount of
boiling water. On cooling, and usually while the solution is still
warm, the picrolonate crystallizes. The product obtained was
of normal composition, containing one molecule each of amino-
acid and picrolonic acid, in every case except those of d-alanine,
dZ-serine, and d-glutaminic acid. These salts showed a tendency
to carry down an excess of picrolonic acid. The latter, however,
was readily removed by shaking out the pulverized salt with