Adaptation
to Cold in the First Three
Days of Life
Paul H. Peristein, M.D., Carol Harsh, M.D., Charles J. Glueck, M.D., and James M.
Sutherland, M.D.
From the Department ofPediatrics, University ofCincinnati College ofMedicine; Crosley Memorial Nursery, Cincinnati General Hospital; and Children’s Hospital Research Foundation, Cincinnati
Compared to infants with minimized heat loss, newborn babies who get cold tend to have higher mortality rates and more metabolic derange-ments.’4 On the other hand, minimization of heat loss can be excessive and, like a cold stress, can stimulate metabolic activity.5 Moreover, sudden reduction of heat loss has been implicated as a cause of apneic spells in susceptible premature in-fants.6’1 Therefore, although there are many arguments for not allowing infants to get cold, there is need for additional studies to define fur-ther the physiologic consequences of preventing heat loss in newborn babies.
Glass and co-workers have responded to this need with their demonstration of an inverse rela-tionship between successful homeothermic adap-tation and two to three week long exposure of newborn infants to protective thermal environ-ments.12 The following report further explores the homeothermic adaptation of term newborn in-fants by examining how constant minimization of heat loss during the first days of life affects an in-fant’s response to a subsequent heat-losing experi-ence.
METHODS
Nineteen healthy, full-term babies were select-ed solely because they were born during the pe-nod of this study. Each of the infants was of nor-mal weight for gestational age and was the prod-uct of an uncomplicated pregnancy and delivery. Five-minute Apgar scores were 9 or 10 in all cases. Each baby was studied after parental con-sent was obtained. Once admitted to the study the infant was randomly assigned to one of three groups.
These groups were identified as group 1, or in-fants who were to be consciously exposed to heat losing experiences during the first three days of
life (the experienced. stressed group); group 2, or infants who were to be protected against heat loss during the first two days of life and cold stressed only on the third day of life (the inexperienced, stressed group); and group 3, or infants who were to be relatively protected during all of the first three days of life (the inexperienced, unstressed group). Except for the study events, infants in all groups were provided the same routine care in the delivery rooms and nurseries.
Routine Care Procedures
Infants born at the Cincinnati General Hospital are swaddled in plastic bags and placed under ra-diant heaters immediately after birth.13 The plas-tic swaddling is not removed until after arrival in the nursery. Nursery admission procedures in-dude a physical examinatiOn, cord reclamping, clothing the infant in a diaper and cotton shirt, and swaddling in one or two loose cotton blankets. Admission bathing with warm water and cotton sponges is routine, but usually is deferred if the in-fant has a rectal temperature below 36 C. The in-fant is briefly unswaddled for diaper changes, reexaminations, and daily warm water baths dur-ing the four- to six-day nursery stay. Infants are fed formula at four-hour intervals.
(Received November 1, 1973; revision accepted for
publica-tion March 18, 1974.)
Supported in part by Children’s Bureau training grant 174
and Public Health Service general clinical research center grant RR-00068-11.
A portion of this work was done during Dr. Glueck’s tenure
as an established investigator of the American Heart Associ-ation, 1971-1976.
ADDRESS FOR REPRINTS: (P.H.P.) Children’s Hospital
5 MEAN RECTAL TEMP CHANGE ISE C ±SE.
-III-
MEAN 4 3 2 01 MEAN 02 PLASMA GLYCEROL CHANGE 03 0 SE.m.moles/litsr
04
05
-9--n
GROUP I GROUP 2 GROUP 3
EXPERIENCED 4 INEXPERIENCED INEXPERIENCED
STRESSED STRESSED UNSTRESSED
N’6 N’6 N’7
p<05
Fi;. 2. Mean rectal temperature change and mean plasma
glycerol change in Groups 1, 2, and 3.
Study Events SUMMARY OF INTERGROUP TEMPERATURE COMPARISONS
The six infants in the first group (experienced, stressed group) were taken to an examination
room at 12, 36, and 60 hours of age. Therefore,
se-rial studies were performed on any one baby at the
same time of day. Each study was performed as
closely as possible to the next scheduled feeding. The infant was undressed and placed chest down
on an examining table. Interscapular, midback, and deltoid skin temperatures, and deep rectal
temperature were measured with matched
ther-mistors (Yellow Springs Instrument Company). A
thermocouple was used to measure tympanic membrane temperature (Radiation Systems
In-corporated). A certified standard mercury ther-mometer and proportional servo-controlled
con-stant-temperature water bath were used to check the calibration of the thermal monitoring equip-ment. These checks agreed with the
manufactur-er’s specifications allowing for a variability of less than 0.05 C between measurements. Capillary heel blood was collected in micro-collection tubes
for plasma glycerol determinations. Plasma glyc-erols were determined using the enzymatic meth-od of Pinter and co-workers.1 The glycerol values reported are accurate to ± 2%.
The examining room temperature was main-tamed between 18.2 and 19.8 C. The infants were offered sugar nipple pacifiers to minimize the amount of muscular activity induced by the van-ous stresses. Immediately after obtaining an initial series of temperature measurements, an initial
blood sample was obtained from each infant. Fol-lowing a 20-minute naked exposure in the cool
ex-amining room, all thermal and chemical
measure-ments were repeated. The infants then were re-swaddled and returned to their nurseries.
Cold exposures was limited to 20 minutes in this
study because of the results in a previous study in which infrared thermography confirmed that a
20-minute mild exposure induced significant
changes in cutaneous thermal patterns on the
backs and extremities of newborn infants.2’ A
20-minute period of stress was also used by Dawkins and Scopes in their report of neonatal glycerol
re-sponses to cold stress.’7
The management of the six infants in the second
group (inexperienced, stressed group) differed
from the group 1 infants by omission of the mild cold stress experience at 12 and 36 hours of age. At 60 hours the infants’ management was the same as described for the group 1 babies.
The seven infants in the third group (inexpe-rienced, unstressed group) were not cold stressed
at all, but were only subjected to blood collections at 20-minute intervals for plasma glycerol
deter-minations on the third day of life.
TEMPERATURE SITES
6 EXPERIENCED GROUP I INFANTS DAY 3 STRESS (MEAN t SE. ‘C)
6 INEXPERIENCED GROUP II INFANTS DAY 3 STRESS
(MEAN ± SE. ‘C) P’
RECTAl. PRECOOLING POSTCOOLING CHANGE
36.9 ± 0.14 36.8 ± 0.16 -0.15 ±0.07
37.0 ± 0.09 36.6 ± 0.08 -0.38 ±0.05
NY NS <0.05 TYMPANIC MEMBRANE PRECOOLING POSTCOOLING CHANGE
36.7 ±0.13 3#{243}.5±0.12 -0.15 ±0.04
36.7 ±0.07 36.3 ±0.09 -0.43 ± 0.09
NS NS <0.05 INTERSCAPULAR SKIN PRECOOLING POSICOOLING CHANGE
35.7 ±0.19 34.2 ±0.31 -1.5 ±0.12
35.6 ± 0.07 34.2 ± 0.03 -1.4 ± 0.07
NS NY NS MIDBACK SKIN PRECOOLING POSTCOOLING CHANGE
35.8 ±0.20 33.9 ±0.12 -1.9 ±0.16
36.0 ± 0.16 33.8 t 0.20 -2.2 ±0.29
NS NY NS DELTOID SKIN PRECOOLING POSTCOOLING CHANGE
34.1 ±0.49 32.7 ±0.52 -1.4 ± 0.22
34.2 t 0.23 32.4 ± 0.25
-1.9 0.18
NY NY
NS
‘NS #{149}NOT SIGNIFICANT AT p ‘ .05
Fic. 1. Summary of intergroup temperature comparisons.
RESULTS
Except for short-lived bursts of muscular
SUMMARY OF INTRAGROUP TEMPERATURE COMPARISONS
Fic. 3. Signfficance levels determined by paired t test corn-parisons of 20-minute changes (ST) in indicated tempera-tures. R = rectal, T = tympanic membrane, I = surface
in-terscapular, B = surface midback, D = surface deltoid.
0- -5-20 MINUTE MEAN CHANGE IN -I .0
TEMPERA-lURE IN
‘C USE. -1.5
DURING
COLD
STRESS -2.0
-2.5
TYMPANIC RECTAL MEMBRANE
El El
DELTOID
INTERSCAP- S.E
ULAR fl
0 ...MEAN
MIDBACK
#{176}A
GROUP EXPERIENCED
-30 . #{149} STRESSED
n‘“#{176}“ 2 INEXPERIENCEDSTRESSED
FiG. 4. Twenty-minute change in temperature during cold stress in groups 1 and 2.
DISCUSSION TABLE I
PLASMA GLYCEROL VALUES IN GROUPS 1, 2, AND 3 ON THE THIRD DAY OF LIFE
PlILSlna Glycerol s‘n millimols/liter ± SE. on Third Day of Life
At 20 20-Minute
N Initial Minutes P#{176} Change P#{176}
Group 1 (experienced, stressed) 6 .285 ± .006 .325 ± .001 < .01 .041 ± .009 <.05
Group 2 (inexperienced, stressed) 6 .306 ± .015 .318 ± .014 N.S.t .012 ± .007 N.S.
Group 3 (inexperienced, unstressed) 7 .338 ± .012 .344 ± .012 N.S. .006 ± .003
OP = Probability value.
tN.S. = Not significant.
spontaneous physical movements during the peri-ods of cold stress in infants of both groups, the ba-bies remained quiet during the study experiences. The mean with standard error fall in rectal tem-peratures measured during the 20 minutes of heat-losing exposure on the first day of life was 0.25 ± 0.O6CandonthethirddayoflifewasO.15 ± 0.07C for the group 1 (experienced, stressed) infants, and
0.38 ± 0.05 C for the group 2 (inexperienced, stressed) infants. The third day of life changes are significantly different from each other (p < . 05)
(Figs. 1 and 2). The mean changes in plasma glyc-erol levels on the third day of life were also differ-ent with an increase of 0.041 ± 0.009
milli-mols/liter in group 1 (experienced, stressed)
in-fants and 0.012 ± 0.007 millimols/liter in the
group 2 (inexperienced, stressed) babies (p < . 05)
(Table I and Fig. 2). The inexperienced, group 2
stressed infants were not different from the
inex-perienced, unstressed group 3 babies in whom plasma glycerol changed 0.006 ± 0.003 milli-mols/liter (Table I). On the third day a significant
rise in plasma glycerol was recorded only in the experienced group 1 infants (Table I). Similarly on the first day of life plasma glycerols in the group 1 infants significantly increased .035 ± .012 milli-mols/liter from .328 ± .016 before to .363 ± .009 millimols/liter after cooling (p< .01).
Other results are summarized in Figures 3 and
4. Mean changes in tymparnc membrane
temper-atures did not differ significantly from rectal tern-perature changes measured in each group. Like
rectal temperature the falls in tympanic mern-brane temperature were significantly different between groups with 0.15 ± 0.04 C in experi-enced group 1 babies being less than the 0.43 ± 0.09 C measured in the inexperienced group 2
in-fants (p < .05). In both groups the mean falls in in-terscapular, midback, and deltoid temperatures were significantly greater than the intragroup mean falls in rectal and tympanic membrane tern-peratures (p < .01). Only in the inexperienced but stressed group 2 infants did interscapular temper-ature fall less than either midback or deltoid
(p < .05).
fall in core body temperature when cold stressed on the third day of life. The ability of cold experi-enced babies to maintain their body temperatures
is associated with an enhanced ability to increase their lipolytic activity as measured by changes in plasma glycerol levels during the period of cold stress. Although these data support a conclusion that an early postnatal adaptation phenomenon has been demonstrated, the mechanisms of this phenomenon are not clearly evident.
An opposite conclusion, that success in lipolytic heat production does not require an adapting preexperience results from finding a cold-induced significant increase in plasma glycerols in the group 1 infants on the first day of life when adap-tation to in utero warmth might be expected. This demonstration of homeothermic competence in the 1-day-old infant is supported by the data of Dawkins and Scopes’7 who found elevations in plasma glycerols in cold stressed infants at less
than
30 hours of age. It is possible that adaptation to the postnatal environment during the first 24 hours oflife is determined by still undetermined inutero mechanisms and is different from the
adap-live phenomenon in the older infant as demon-strated in this study. A difference in cold-induced cutaneous thermal changes in infants younger and older than 1 day of age has
been
previously dem-onstrated.21 But even beyond the age related dif-ferences, in this study there is a paradox in the fact of the greater retention of interscapular heat com-pared to other skin temperature changes in the 3-day-old unadapted babies with the lowest glycerol production.This finding is contrary to what was expected from previous reports in the literature1521 which have used retention of interscapular heat as evi-dence that interscapular brown fat stores may play
an important role in nonshivering thennogenesis by newborn infants. Moreover, using a comparison of the fall in midback temperature to the fall in
deltoid
temperature as a measure of peripheral vasoconstriction has resulted in a conclusion that unadapted infants, in whom deltoid temperatures matched midback temperatures in cooling and who are compromised in their ability to produce heat, have a somewhat enhanced ability to reduce heat loss when compared to the adapted infants in whom deltoid temperatures remained signifi-cantly wanner than midback temperatures duringthe
heat losing experience (Figs. 3 and 4). Therefore, if interpreted correctly, there is a disassociation of the homeothermic mechanisms in the adapting infant so that cold stress is prefer-entially combatted by heat production rather than by reduction of heat loss. On the other hand the unadapted infant apparently relies on hisvasocon-strictive mechanisms which, in turn, seem to be
under controls privileged from the influences of
adaptation.
It is always possible, of course, that these appar-ent dilemmas are due to errors in interpreting the data. For example, heel capillary blood samples were used to measure glycerol levels in this study. The greater extremity cooling as measured by fall
in
deltoid
skin temperature when compared tomidback temperature in the inexperienced, stressed group 2 infants may reflect greater stasis in the vasoconstricted extremities with a resulting blood sample that is noncomparable to the central blood poois. The possibility of this methodologic artifact cannot be dismissed for lack of
compara-ble
central arterial and peripheral plasma sample values in this study. On the other hand, the group 3 infants who were not cold stressed and therefore presumably not peripherally vasoconstrictedcon-firm
that the
group 2 infants’ plasma glycerol1ev-els are compatible with
those
expected from eith-er unstressed or homeothermically unresponsivebabies. Moreover there is no statistical difference between
the
actual
mean deltoid temperatureafter cooling or mean fall in deltoid temperature during cooling of either the experienced or inex-perienced infants. if the physiologic matches the statistical significance of these measurements then an equal degree of vasoconstriction and con-sequently blood stasis can be presumed in the two groups, maintaining their compatibility in inter-preting the plasma glycerol data. However this
comparability decreases the level of speculative
confidence in interpreting the relationship of the comparative intergroup falls in midback tempera-tures to
the falls
in deltoid temperatures. In addi-lion, although there is precedence in using skintemperature as a measure of vasomotor activity in
this
discussion to a degree which was sufficient tojustify additional mechanistic speculations from
this
study.The use of deltoid skin temperatures as a
mea-sure of peripheral vasoconstriction has been
justi-fled
in this study because the postcooling falls below 33 C. Also previous experience with ther-mography measurements in the newborn21 hasre-sulted in a level of confidence that falls in deltoid skin temperatures reflect the thermal status of the more peripheral extremity skin sites.
In any case, neither the data nor reviewed
liter-ature clarified the interpretive paradoxes noted in this discussion to a degree which was sufficient
to justify additional mechanistic speculations from this study.
well
newborn babies in whom adaptation to “nor-mal” room temperature environments could be unintentionally compromised by excessivether-mal protection.
Unfortunately
the
study
design also did not allow for clearly defining what constitutes exces-sive protection. In fact, the infants who are in-cluded in the inexperienced group were not total-ly protected from some mild cold-stressexperi-ences since during routine diaper changes, exam-inations, and baths they were exposed, albeit briefly, to room temperatures. Of course these re-current brief room-temperature exposures were similarly necessitated by the routine care of the study cold experienced infants so that in nonstudy experiences the groups were similar. Nonetheless,
it is somewhat surprising that the two additional
20-minute periods of cold exposure should have resulted in such a remarkable difference between these two groups of infants.
It
is likely that had the inexperienced group been better protected against minor exposures or the period of cold stress prolonged beyond 20 minutes in the experi-enced group, more significant differencesbe-tween
the
groups might have been measured. However, the significance level achieved by corn-paring groups so minimally different in their ther-mal experiences suggests that there may be only a very narrow range of thermal conditions beyond which optimal thermal care crosses a sharp border into the region of excessive protection.SUMMARY
Newborn infants who were exposed to short periods of cold stress during the first two days of life demonstrated an enhanced ability to maintain their core body temperatures when subsequently
challenged
by exposure
to a heat-losing
environ-ment. The relative thermal stability of these cold-experienced infants was associated with
eleva-lions in their plasma glycerol levels suggesting that lipolytic thermogenesis plays a prominent role in this demonstration of homeothennic com-petence. The data are interpreted as a demonstra-lion of early postnatal adaptation to environmen-tal stress.
REFERENCES
1. Silverman, W. A., Fertig, J.W., and Berger, A. P.: The influence of the thermal environment upon the
sur-vival of newly born premature infants. Pediatrics, 22:876, 1958.
2. Buetow, K. C., and Klein, S. W.: Effect of maintenance of “normal” skin temperature on survival of infants of low birth weight. Pediatrics, 34: 163, 1964. 3. Day, R. L., Caliguiri, L., Kamenski, C., et al.: Body
tem-perature and survival of premature infants. Pediat-ric,i, 34:171, 1964.
4. Gandy, G. M., Adamsons, K., Jr., Cunningham, N., et al.:
Thermal environment and acid-base homeostasis in human infants during the first few hours oflife.
J.
Clin. Invest., 43:751, 1964.
5. Adamsons, K., Jr., Gandy, G. M., andJames, L. S.: The in-fluence of thermal factors upon oxygen consump-tion of newborn human infant. J. Pediat., 66:495,
1965.
6. Perlstein, P. H., Edwards, N. K., and Sutherland, J. M.:
Apnea in premature infants and incubator-air-tem-perature changes. New Eng. J. Med., 282:461,
1970.
7. Daily, W. J., Klaus, M., and Meyer, H. B.: Apnea in pre-mature infants: Monitoring, incidence, heart rate changes, and an effect of environmental tempera-ture. Pediatrics, 43:510, 1969.
8. Silverman, W. A. In Thompson, S. G. (ed.): Discussion of thermoregulation of the newly born (Supplement 2, Reports of Ross Conferences on Pediatric
Re-search). Columbus, Ohio: Ross Laboratories, 1964,
p. 31.
9. Karlberg, P.: Discussion: Neonatal Respiratory Adapta-tion. Proceedings of Interdisciplinary Conference on Neonatal Respiratory Adaptation, Princeton, New Jersey, December 6-9, 1963. Washington,
D. C.: Public Health Service Publication No. 1432,
1966, p. 117.
10. Cross, K. W.: Discussion: Neonatal Respiratory Adapta-tion. Proceedings of Interdisciplinary Conference on Neonatal Respiratory Adaptation, Princeton, New Jersey, December 6-9, 1963. Washington,
D. C.: Public Health Service Publication No. 1432, 1966, pp. 117-119.
11. Dawes, G. S.: Discussion: Neonatal Respiratory Adapta-tion. Proceedings of Interdisciplinary Conference on Neonatal Respiratory Adaptation, Princeton, New Jersey, December 6-9, 1963. Washington,
D. C.: Public Health Service Publication No. 1432, 1966, p. 117.
12. Glass, L., Silverman, W. A., and Sinclair, J. C.: Effect of the thermal environment on cold resistance and growth of small infants after the first week of life. Pediatrics, 41: 1033, 1968.
13. Besch, N. J., Perlstein, P. H., Edwards, N. K., Keenan, W.
J., and Sutherland,
J.
M.: The transparent babybag: A shield against heat loss. New Eng.
J.
Med., 284:121, 1971.14. Pinter,
J.
R., Hayashi, J.A., and Watson, J.A.: Title Arch.Biochem. Biophys., 121:404, 1967.
15. Silverman, W. A., Lamelis, A., Sinclair, J.C., and Agate,
F. J.: Warm nape of the newborn. Pediatrics,
33:964, 1964.
16. Hull, D., and Segall, M. J.: The contribution of brown adipose tissue to heat production in the newborn rabbit. J. Physiol., 181:449, 1965.
17. Dawkins, M. J.R., and Scopes,
J.
W.: Non-shivering ther-mogenesis and brown adipose tissue in the humannewborn infant. Nature, 206:201, 1965.
18. Aherne, W., and Hull, D.: Brown adipose tissue and heat production in the newborn infant.
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Path., 91:223,1966.
19. Heim, T., Kellenmayer, M., and Dani, M.: Thermal con-ditions and the mobilization of lipids from brown and white adipose tissue in the human neonate. Acta Paediat. Acad. Sci. Hung., 9:109, 1968. 20. Bolton, D. R., Fox, A. M., and Kennaird, D. L.:
21. Perlstein, P. H., Edwards, N. K., and Sutherland, J. M.:
Age relationships to thermal patterns on the backs of cold stressed infants. Biol. Neonat.,
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ACKNOWLEDGMENT
The authors wish to thank Neil Edwards and his bioengi-neering staff for technical assistance, Richard Prairie and
Marvin Tabor for biochemical analyses, Ms. Laurine
Coch-ran and her staff for nursing assistance, and Ms. Cheryl Bur-ton for manuscript preparation.
HOW
AMERICAN
INDIAN
MOTHERS
CAREDFOR
THEIR
CHILDREN
IN THE
EARLY
1800’S
John D. Hunter as an infant of two or three years was kidnapped about 1797 by Indians and then lived for most of his childhood and young manhood
with the
Kansasand Osage
tribes,
West
of the Mississippi. He returned to white society in 1816 when he was 19 years old. Seven years later, after he had learned to read and write, his Mem-airs of a
Captivity
among
the
Indians of North America was published in Philadelphia (1823). This narrative contains detailed, first-handde-scriptions of many aspects of Indian life in the Midwest during the early part of the nineteenth century.
He
described the infant and child rearing prac-tices of Indian mothers as follows:Their infants, wrapped in skins, are secured with belts to
a small thin piece of board placed along the back. As they
grow older, should the weather be mild, the skins are re-moved altogether, and no other dresses are substituted for them, except in very cold weather, till near the period of puberty.
When traveling, the mother places the board to which the infant is secured on her back, and supports it in this
manner for the whole distance of the journey. While resting, or at work, she suspends it perpendicularly from the side of
her lodge, the arm of a tree, or a post she has erected for the purpose. She administers food to it when she thinks it is
hungry, disregards its crying, and seldom unbinds and soothes it to rest, except when she herself retires for sleep.
When the temperature of the weather is mild, they bathe
their children daily from their birth till they are able to
walk alone, in order to make their skins hardy, and capable of resisting the extreme changes of the weather, to which they are more particularly exposed in early life. When suffi-ciently old and strong, they wean and suffer them to run
about: this is generally between the age of two and three years. They would, no doubt, deviate from this practice
sometimes, did they not apprehend that such conduct would be stigmatized by a pair of bowed legs, which would
bear witness against their parental care and good qualities
to the whole tribe.
Should the child be a boy, this period is to the mother
pe-culiarly interesting. She now takes it with her in all her vis-its, witnesses its playful, impassioned, or vindictive emo-tions and conduct, with its infantile fellows; and feels her
soul bowed down with mortification and grief, or swelled with pride and joy, as she discovers the ignoble traits of
cowardice, or the innate characters of courage, unfold
themselves in the offspring of her hopes. Boys are seldom
long together without quarreling, and pretty generally make a bold fight, though they are not permitted to
con-tinue it. Should the case be otherwise, the disappointed
mother soon returns to her lodge and commences a very
ex-traordinary discipline. She begins by placing a rod in his
hand, assists him to beat and make flee the dog, or anything else that may come in his way, and then encourages him to pursue. An adept in this, she teases and ypes him, creates an irritable temper, submits to the rod, and flees before him with great apparent dread. When skilled in this branch, she strikes him with her hand, pulls his hair, etc., which her
now hopeful boy retaliates in a spiteful and becoming man-ner. Some time having passed in this way, by which her pupil has learned to bear pain without dread, she takes him again on a visit, and I have never known an instance of a
second disappointment in these trials of courage. They are
then permitted to play with the other children of the vii-lage, and to quarrel and make up as well as they can.
After this conceived salutary course of discipline, the
parents bring them back to their accustomed subjection, by a steady and determined course of government.
There is nothing connected with the education of the fe-male part of the children that requires to be noticed, except
it be their early entrance with the boys into sports and
amusements in imitation of the grown people. . .. Those in
which they most frequently engage are the dances, which they soon learn to perform with accuracy, and with the same variety as practiced by the older ones. Running races, wrestling, jumping, and swimming, also engross much of their time. They perform these sports in a manner very
sim-ilar to what is practiced among civilized people and there-fore I shall not attempt their description.
Noted by T. E. C., Jr., M.D.
REFERENCE
