after transplantation and of even longer survival on
hemodialysis is an invaluable gift of life to those
who are otherwise doomed to die. To the physician,
burdened with the distasteful task of assigning
priorities for the limited resources presently avail
able, the answer is similarly clear. To those not
directly concerned, the answer does not come so
readily. Looking to the physician for information
and to their collective conscience for guidance, so
ciety is also weighing the balance of priorities and
assessing available resourcesa particularly trying
task for countries less affluent than ours. If, how
ever, history can be relied upon as a dependable
guide, our society's traditional acceptance of finan
cial burdens in preservation of the elderly and the
handicapped is an indication that life-bestowing
treatment for those who need it will not for long
remain a debatable issue.
Cost relates to value. To a large extent our at
titude toward the cost of life will be fixed by the
value we set upon it.
1. Kidney Disease Program Analysis: A Report to the Surgeon General,
publication 1745, US Dept of Health, Education, and Welfare, Public
Health Service, 1968.
2. Report of the Committee on Chronic Kidney Disease, Gottschalk,
C.W., chm, Chapel Hill, NC: University of North Carolina, September
1967.
COLD PANNICULITIS IN CHILDREN
In this day of highly technical reports of
conditions, it is both surprising and perversely
satisfying to find a common ailment which has
seldom been reported and is rarely diagnosed. Every
pediatrician practicing in an area where there is
a cold encounters at least once or twice
season
each winter an infant or young child who, after ex-
posure to the elements, has developed erythema
and induration of the cheeks or submental fat pad
or both. He has learned, by experience, that these
lesions require no treatment and undergo spon-
taneous involution within a few weeks, and that
after several months or years, his patients outgrow
their tendencies to react to cold exposure in this
way. Until he has seen this course of events a few
times, he may consider cellulitis or a peculiar
lymphadenopathy in his differential diagnosis. He
is unlikely to know that application of ice for two
or three minutes to the volar surface of the fore-
arm will reproduce the lesion in 24 to 48 hours.
This condition was first described in 1902 in a
German pdiatrie journal,1 but has since been de
scribed in English only in the dermatologie journals,
no mention of it appearing in the pdiatrie litera
ture. The term cold panniculitis was coined for it
when biopsy of a lesion revealed necrosis, fibrosis,
and inflammatory infiltration of the subcutaneous
fat. Similar lesions have been reported in adults,
but only after either extremely severe or extremely
prolonged exposure to cold. Some infants and chil
dren apparently possess unique susceptibility to
the development of subcutaneous panniculitis after
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exposure to cold in no way extraordinary.
In a recent communication in the American
Journal of Diseases of Children,2 histochemical
studies are reported which suggest that the subcu
taneous fat of affected children may contain ex
cessive amounts of saturated fatty acids, and
hence be more easily solidified at low temperatures
than normally. This increased proportion of sat
urated fatty acids is well documented in the sub
cutaneous fat of newborn infants, but adult levels
of unsaturation are usually reached in the first
few months of life. The normally increased propor
tion of saturated fatty acids in neonatal subcu
taneous fat has frequently been proposed as an
etiologic factor in subcutaneous fat necrosis of the
newborn, which bears some resemblance to cold
panniculitis, both clinically and histopathologically.
Prolonged persistence of infantile fat composi
tion, perhaps related to dietary content of saturated
as opposed to unsaturated fats, may be an etiolog
ic factor in cold panniculitis. Confirmation of this
hypothesis however, will depend upon biochemi
cal analysis of the subcutaneous fat from patients
with cold panniculitis.
1. Hochsinger, C.: Ueber eine akute kongelative Zellgewebsverh\l=a"\rtung
in der Submentalregion bei Kindern, Mschr Kinderheilk 1:323, 1902.
2. Lowe, L.B., Jr.: Cold Panniculitis in Children, Amer J Dis Child
115:709-713 (June) 1968.
rare
OSWALD SCHMIEDEBERG (1838-1921)
EXPERIMENTAL PHARMACOLOGIST
O Schmiedeberg,
Germany, the
successful reformer of experi-
pharmacology,
mental was born in Kurland,
son of a forester. Schmiedeberg spent
his youth in Dorpat where he attended the Gym-
nasium. He received his medical training from the
University faculty, which included as members K.
Schmidt in chemistry, F. Bidder in physiology, and
R. Buchheim, director of the little known Pharma-
cology Institute.1 In 1866, Schmiederberg present-
ed his inaugural thesis, Determination and Con-
centration of Chloroform in the Blood, and received
the MD degree. He assisted Buchheim until 1869,
when his chief was called to Giessen, and he was
advanced to the professorship of pharmacology, di-
etetics, and the history of medicine. Sensing the
importance of the physiologic approach to drug in-
vestigation in man and animals for the advance-
ment of basic and practical pharmacology, he spent
a year in Leipzig with Carl Ludwig. Here he stud-
ied the pharmacologic action of nicotine and atro-
pine on the heart of the frog and the dog, one
of his most important scientific contributions.
Schmiedeberg published a monograph with R.
Koppe on the alkaloids of poisonous mushrooms.
In 1872, he was called to Strassburg to the recently
founded university; there he built an institute that
was recognized as the most important center for
experimental pharmacology in Europe, comparable
 in stature to similar great institutes in Germany
devoted to one of the other medical sciences.
Schmiedeberg attracted a remarkable number of
students throughout his long and productive career
and enriched the pharmacologie literature, as well
as establishing with Bhm, Klebs, and Naunyn the
Archiv fr experimentelle Pathologie und Pharma
kologie. This was subsequently identified in con
versational pharmacology as Schmiedeberg's
Archiv. Schmiedeberg's name was carried on the
masthead as professor of pharmacology from Bad
en-Baden after retirement from Strassburg and was
not removed until his death. He received honorary
degrees from Edinburgh and Bologna, and member
ship in the Academy of Medicine of Paris and the
Ecclesiastical Academy of Science of Rome. In
1883, the first edition of his Fundamentals of Drugs
appeared.2 This was translated into English by
Dixson in 1887, under the author's supervision, and
was published in Edinburgh. The title of the fourth
edition (1902) was changed to Fundamentals of
Pharmacology and was revised in 1906, 1909, and
1913, evidence of its reputation as the basic trea
tise for his generation of pharmacologists.
Schmiedeberg's influence in developing theoreti
cal medicine in Germany through pupils and pub
lished reports or monographs encompassed such
diverse subjects as heavy metals and their effect
on the organism, identification and naming of gly-
curonic acid, selected aspects of carbohydrate me
tabolism, the synthesis of hippuric acid by the kid
ney, the identification of sinistrin and histozyme,
investigation of ferratin and digitalis compounds,
the chemical composition of cartilage, the dietetic
value of wines, diuretics, nucleic acid, chicory,
methyl alcohol poisoning, mucoid, mucin and chon-
droitin metabolism, collagen, and amyloid. Excerpts
from the initial studies of the effect of muscarin
and atropine on the frog's heart are given below.3
Experiments performed with Koppe on Muscarin pois
oning have shown among other features that the smallest
amounts of the poison produced standstill in diastole with
out decreasing irritability. Cardiac arrest persists if coun-
termeasures are not taken. Only a small fraction of a
milligram of atropine, if injected subcutaneously, can com
pletely abolish cardiac arrest in animals and nullify the
effect of additional quantities of Muscarin. The action of
small doses of atropine on the heart is apparent since
neither electrical stimulation of the vagus nor stimulation
of the venous sinus can produce cessation or slowing of the
heart rate, and conduction fibers which respond to electri
cal stimulation are paralyzed by this poison. We conclude
that Muscarin is an antagonist; it stimulates the structures
that are paralyzed by atropine and which otherwise would
lead to diastolic cardiac arrest if excited.
The stimulating action of nicotine on the endings of the
vagus appears only when small amounts of the poison are
applied. Immediately after the injection of Vs to V nig,
the heart rate begins to decrease and soon reaches diastolic
standstill which persists not longer than 60 or 90 seconds,
when pulsations appear and soon reach the same frequen
cy as before the injection. If traces of atropine are admin
istered to the animal before the application of nicotine,
cardiac arrest does not appear; after small doses the rate is
unchanged; after larger doses, gradual slowing of the heart
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rate appears, as without the administration of atropine.
If Muscarin is administered to an animal after nicotine,
which blocks the inhibiting action of the vagus, cardiac
arrest appears even following the strongest electrical stimu
lation, and persists for a considerable time, but again, it
can be interrupted by atropine.
In acomprehensive discussion of the digitalin
group botanicals, Schmiedeberg described neriin,
of
oleandrin, and neriantin.4 Following a short his
torical review of the therapeutic value of digitalis
and the digitalein group, he listed more than a doz
en compounds including antiarin, helleborein, thev-
etin, digitoxin, strophanthin, apocynin, scillain,
adonidin, oleandrin, digitalein, apocynein, conval-
lamarin, erythrophleine, phyrnin, and other sub
stances not belonging to the digitalis group but
endowed with a similar action. The physiologic
and pharmacologie actions of drugs that are mem
bers of the group are summarized as follows.2
A number of non-nitrogenous botanicals, which mainly
belong to the glucosides, act in so uniform a manner upon
the heart of many animals, irrespective of quantitative
differences, that each of the agents seems, as regards this
action, quite similar.
The action of these substances consists almost exclusive
ly in the fact that they alter, in a peculiar way, the elas
ticity of the cardiac muscle, without at first modifying the
contractility of it. The immediate effect of this alteration
is the increase of the volume of the pulse, with prolonga
tion of diastole. At this stage of the action of digitalis, the
absolute capacity of the heart experiences neither an in
crease nor a decrease. On the other hand, the quantity of
blood which, at this time, is propelled into the aorta is
greater than before, not only at every beat, but even in a
given unit of time, although the rate may have diminished.
These active substances therefore produce better filling of
the arteries, as a reflection of the relative efficiency of the
heart. As a result, the blood-pressure increases, irrespective
of its previous level, such as very low in deep chloral nar
cosis. Together with an increase of pressure, which we can
prove indirectly in man, the pulse slows, dependent upon
stimulation of the inhibitory mechanism of the heart,
partly through vagus action and partly through local ef
fects. This slowing is absent if the inhibitory apparatus
has been paralysed by atropine previously, a paralysis
which shows no effect upon the increase of pressure.
Of these actions, the first stagethat is, the rise of
blood-pressure, and the usually concurrent slowing of the
pulsecan be brought about in man, and maintained for a
long time, by small doses, without threat to life. Essential
therapeutic benefit can be ascribed to the blood-pressure-
elevating property and especially the slowing of the pulse,
upon which so much stress is laid in the use of digitalis;
they are either the results of the high arterial pressure, or
appear as the inflammatory process at the point of sup
puration as little more than disturbing factors.
If improved filling of the arteries and subsequent rise of
arterial pressure are the changes produced by these agents
in the healthy and the sick, then the indication for rational
employment follows.
1. Meyer, H.H.: The Contributions of Schmiedeberg (Ger), Arch Exp
Path 92:III-XVII, 1922.
2. Schmiedeberg, O.: Fundamentals of Drugs (Ger), Leipzig: F.C.W.
Vogel, 1883.
3. Schmiedeberg, O.: Investigations of Poisons on the Frog's Heart
(Ger), Arb Physiol Anst 5:41-52, 1871, excerpt translated by Z. Danile-
vicius.
4. Schmiedeberg, O.: The Pharmacology of the Digitalins (Ger), Arch
Exp Path 16:149-187, 1883.