The Russell Sage Institute of Pathology IN AFFILIATION WITH The Second Medical Division of Bellevue Hospital CLINICAL CALORIMETRY PAGE I. A RESPIRATION CALORIMETER FOR THE STUDY OF DISEASE 793 GRAHAM LUSK Scientific Director, Russell Sage Institute of Pathology ' - II. THE RESPIRATION CALORIMETER OF THE RUSSELL SAGE INSTITUTE OF PATHOLOGY IN BELLEVUE HOSPITAL 805 J. A. RICHE 'AND G. F. SODERSTROM IIJ. THE ORGANIZATION OF A SMALL METABOLISM WARD 829 FRANK C. GEPHART, A.B., and EUGENE F. DuBOIS, M.D. IV. THE DETERMINATION OF THE BASAL METABOLISM OF NORMAL MEN AND THE EFFECT OF FOOD 835 FRANK C. GEPHART, A.B., and EUGENE F. DuBOIS, M.D. V. THE MEASUREMENT OF THE SURFACE AREA OF MAN 868 DELAFIELD DuBOIS, B.S>, and EUGENE F. DuBOIS, M.D. VI. NOTES ON THE ABSORPTION OF FAT AND PROTEIN IN TYPHOID FEVER 882 WARREN COLEMAN, M.D., and EUGENE F. DuBOIS, M.D. VII. CALORIMETRIC OBSERVATIONS ON THE METAB- OLISM OF TYPHOID PATIENTS WITH AND WITH- OUT FOOD 887 WARREN COLEMAN, M.D., and EUGENE F. DuBOIS, M.D. Vin. ON THE DIABETIC RESPIRATORY QUOTIENT 939 GRAHAM LUSK Reprinted from the Archives of Internal Medicine, Vol. 15, Part II, May. 15, 1915 CHICAGO American Medical Association, Five Hundred and Thirty-Five N. Dearborn St. 1915 S^ »- o <^ x^ c • lij o 04 1-03^ EO_ K DC--- ^ o.e-_; c^fe'-' Ui ^ •> < ■S?o o , Lh CO a 73— CO ffi O S /. A. RICHE—G. F. SODERSTROM 19 The braces of the wooden frame divide the dead air space between the walls into compartments about 30.48 cm. square and 6.35 cm. thick. In the center of each compartment is placed a thermopile with four thermocouples in thermal but not in electrical contact with each copper wall. The inner end of this thermopile fits in a brass thimble 25.4 mm. deep soldered to the outer side of the inner wall. The outer end (with its four thermocouples) fits in a brass tube which passes through the outer wall and is closed off from the outside air by P. B. Compound and electric tape. Fig. 8. — Calorimeter with front closed. In Figure 13 the large opening at the head of the box, measuring 76 by 70 cm., is closed by two glass plates 7.5 mm. thick, each sealed after the subject has entered the calorimeter by means of a mixture of 5 parts bees-wax and I3/2 parts Venice turpentine. The small window in Figure 6 is permanently closed by glass plates fastened to the copper walls. There are numerous pipes and electric cables entering the box as will be described later. On the surface of the outer copper wall are attached the wires connecting the thermopiles. The pipes for cold water are swung on brass angles attached to this surface and the enameled "Therlo'* resis- tance wire is bound on insulators to the same surface, very much as described by Benedict and Carpenter. 20 CLINICAL CALORIMETRY INSULATING WALL Completely surrounding the outer copper wall and separated from it by a space of 7 cm. is the thick wall intended to protect the calorim- eter from fluctuations in the room temperature. This is constructed of a layer of pressed cork 2.54 cm. thick, between two layers of "Com.po Board," a patented building material made of strips of wood glued between layers of stout paper. This is supported by a framework of white-wood, making panels which are light, yet very effective as heat insulators. The head of the wooden box is provided with a glass window and furnished with handles so that it can be easily removed when the experiment is over and placed on a small shelf on the right of the calorimeter. The frame of this outer box is stained to resemble oak, and the "Compo Board" panels are painted with white enamel. Every effort has been made to make the room and the calorimeter pleasing to the eye, with the result that patients are attracted by the beauty of the apparatus rather than by its resemblance to a coffin. THE ABSORBER TABLE The absorber table is so arranged that the air current is switched from one set of absorbers to the other by means of a three-way valve. This works satisfactorily and is much quicker than the old style seat- valves. The sulphuric bottles are larger models of the form described by Williams and hold about 1)4 liters of acid, which will remove every trace of moisture until more than 100 grams has been absorbed. The soda-lime bottles resemble those devised by Benedict,^ except for a modification of the tube which carries the entering air. This is divided in such a manner that the soda-lime can be packed about a brass pipe, the lower end of which is perforated and the upper end of which reaches almost to the top of the bottle, where it fits snugly in an elbow attached to the stopper. The Crowell blower is the same as the ones used by Williams and Benedict, but a safety device has been attached to prevent accidental reversal of the blower which would have dis- astrous effects. The two small bicarbonate cans next to the last sul- phuric bottle did not remove entirely the acid vapors and it was neces- sary to place a long cylinder in the vertical pipe which carries the air from the absorber table. This contains about 340 grams of bicarbonate of soda packed between layers of cotton and catches all traces of acid fumes. The air enters the box in a pipe which ends in a single opening directed just above the subject's head and leaves through a number of small openings in a pipe which runs across the foot of the box. A small electric fan at the lower end of the calorimeter keeps the air well stirred. /. A. RICHE—G. F. SODERSTROM 21 Fig. 9. — Modified soda-lime bottle. A, Brass tube with perforated bottom and top which fits in brass elbow, B. The bottle is filled with A in position and the rubber stopper D with elbows B and C is then forced into neck of bottle. G and F, Brass couplings. R and Ri, heavy rubber tubing. X and Y, Binding wires. Fig. 10. — Safety device to prevent blower from being reversed. P, Pulley for belt to motor. S, Shaft of blower. H, Hub of wheel. K, Key 1, 2, 3, 4, 5, hardened steel rollers which engage when pulley is running in right direction, but disengage when pulley starts in opposite direction. ■"■S'S ?i .^-o " " « s S i^ 3 ts " si >3 c 5 E„t;(uS« !«r°'SboE C3 «:e « c >'>j"S > .Or" ^ nl . -— Oi) cu a S bot/2 ^ — , ^ v« o . , b X r " 5, oH - 3 1 &' o 3 C t«0 •§ o.~ ti §".2 "- ii " " _ <" OOOu'-' -cO^-S bo I- ^ bjo^ ^ Qj .ii o t- o i-O tn-i-tP'O-*-' •«'^ P .,13 ^ a. »,§ S M >.S rt 3 en P- O ^ ba '- bo .c/i.'"^-^-^ >, i(^ M.2 'C ■5CL, .-^^ri-?: ^ .-P =_ g.;2:H^ii-E < ov'^" o_^w boo S?£-a C3 bo ,-^ CJ ^_ lU "^ -' r- > — •-x^=u3M-,:=:go ■"n— — 3-^u>>pSS V "J=(uO>t" •i'5'>i' PT « "^ l~ ^ > ^ o'-'-^'o'S ». sii fe s„„ •!: . S 3-g-" 3 S g Pi^ u t/5 o, , ■" ^-O rt « " ^ ■-•= su- u o ". & ■" g"0 rt . _ c c bo ui C^ >J3 ■ ' in J) 1-. •- -a M g-n " n c - ^ (L) O OJ tn ^ 3 Q.i; 4J G rt (U O dj (U ■^ S o g » B •S° bb_c o JS *-* r ^ .S i! „ O -*-' "i:^ 5- (u o o ■« e-5 o ^H-i p p p P ill ^ oj ^^ 5^ 5 c :t2 _5 ti y Williams, the Gouy regulator and Williams' water heating resistance and current regulator giving very satisfactory results. The water coil suspended from the roof of the calorimeter has, however, been wound with brass "jack chain" to increase its absorbing surface. From this coil the water runs to the weighing tank on the platform of a "silk scale" /. A. RICHE—G. F. SODERSTROM 27 which is sensitive within 10 grams. The flow of water was formerly cut off by hand at the end of each period, but this is now done by a pair of solenoids controlled by the operator at the observer's table, thus reducing the staff by one man. The stream of water runs constantly through a can which has the capacity of 10 liters, and is provided at its lowest point with a valve that is opened and shut by the pair of solenoids above mentioned. At the end of a period the valve is shut and the water collects in the can while the tank is being weighed. After the weighing is finished the valve is opened and the water runs once more into the tank. RHEOSTAT BOARD AND OBSERVER'S TABLE The marble rheostat board and the observer's table resemble closely those described by Williams. This rheostat board, the panel box, charging panel for the storage batteries, conduits, wires, etc., were installed by the Electric Construction Supply Company after specifica- tions kindly drawn up for us by the Department of Water Supply, Gas and Electricity of New York City. Directly above the rheostat board is mounted a galvanometer of the d'Arsonval type, provided with prisms so that the ascending ray of light from the lamp below is reflected from the mirror of the galvanometer downward to a scale just above the table. (Siemans and Halske.) This vertical mounting with scale that can be read by daylight saves a great deal of room. The galvanometer is braced securely and does not vibrate. To protect it from the dust it is covered with a thin copper hood. The resistance of the moving system is 45 ohms and there is a ballast resistance of 200 ohms in series, which, however, is not used. Most of the precision switches used were furnished by Siemans and Halske, Catalogue Number 17327. One of similar design was made in our own shop. A new device which has given great satisfaction has been introduced into the switch connecting thermopiles with galvan- ometer. At the start of the experiment, or at any other time when the temperature differences between outer and inner walls are large, a resistance ,of 300 ohms is kept in series. As soon as the calorimeter is in balance a button on the switch is turned and the resistance short- circuited, making the adiabatic control extremely delicate. The Kohl- rausch bridge provided by the Leeds and Northrup Company of Phila- delphia is similar to the one described by Williams. The 60-step rheostat for controlling the temperature of the ingoing water and the four 4S-step rheostats controlling that of the ingoing air, bottom, sides and top of the outer copper wall, were made by the Simplex Heater Company of Cambridge, Mass. They are mounted on the back of the board with their handles projecting through the board to the observer's 28 CLINICAL CALORIMETRY table. Just above them on the back of the marble slab are the five tube rheostats (Siemans and Halske) used to cut dovsm the current to various small pieces of apparatus. On the front of the board are the two relays, one for the Williams water heating resistance and current regulator and the other for the Gouy regulator. The thermopiles between outer and inner copper walls are arranged in three groups, thirty-two on the top, thirty on the sides and twelve on the bottom, the area covered by each group being warmed by a strand of enamelled "Therlo Wire," No. 24 B & S gauge, whose tem- perature is controlled by one of the step rheostats. One thermopile is arranged with one end in the outgoing air current and the other in the ingoing air. The temperature of the latter is adjusted to that of the former by means of a step rheostat and two 55 volt lamps. A similar rheostat controls the temperature of the ingoing water by means of the water heating resistance. THERMOMETERS All thermometers contain 100 ohms resistance in nickel or platinum wire and are made on the three-lead system, being read on the same galvanometer used for the thermopiles. The water thermometers made by Leeds and Northrup are similar to those constructed by them for the automatic calorimeter of the Department of Agriculture. They are described in the Leeds and Northrup catalogue (Bulletin 811) and also by Dickinson and Mueller' of the United States Bureau of Standards. In our hands they have been most satisfactory, since they are more accurate, easier to calibrate, and easier to read than mer- curials. The Leeds and Northrup air thermometer, similar to that used by Williams, is in eight divisions scattered over the inside of the box so as to give the average temperature of the air. They are connected in series by copper wire covered with rubber and a casing of lead, a combination made especially for us which has given good service. The wall thermometer consisting of eight divisions in series was made in this laboratory. Each division was made of No. 38 double silk covered nickel wire wound around a strip of mica and held 2 or 3 .mm. from the inside of the inner copper wall. Over this was soldered a shallow copper box so that the resistance wire would lie in a small air space completely surrounded by metal at the temperature of the wall. The rectal thermometer is of a new design made to respond more rapidly to changes in the temperature than the old type in which the resistance wire was surrounded by a jacket of dead air. The nickel wire with its double silk covering is wound on a small piece of ivory 7. Dickinson and Mueller : New Calorimetric Resistance Thermometers, Bull. Bureau Standards, 1913, ix, 483. /. A. RICHE—G. F. SODERSTROM 29 and dipped in a round ended silver tube filled with molten Wood's fusible alloy at a temperature of 96 C. This is solidified by dipping in water, thus forming direct metallic contact between the outside of the silver tube and the insulated wire. The leads from the thermometer are enclosed in a soft rubber tube. The surface thermometers are made of flat circular buttons of ivory 25 mm. in diameter and 5 mm. thick. One side of the button is hollowed out to a depth of 3 mm., the edges being filleted. On the bottom of this depression is wound con- centrically the resistance wire. On this is poured the molten Wood's metal until it is flush with the original level of the ivory. Two of these units are used in series in each of the two surface thermometers. They are strapped to the skin with adhesive plaster and covered with a pad of cotton wool about 20 cm. in diameter and 4 cm. thick, this also being held in place with adhesive plaster. The air thermometers were calibrated by the makers and the wall thermometers made to contain exactly the same resistance. Since they are used only to denote relative changes in temperature, a more exact calibration is not necessary. The rectal, surface and water ther- mometers are standardized several times a year by means of very accurate mercurials, certified by the Physikalische Technische Reichs- anstalt. When calibrating them one notices that the electric ther- mometers all respond to temperature changes much more quickly than the mercurials. The flexible rubber covered leads from the surface and rectal ther- mometers and the lead covered wires from the wall and air ther- mometers are carried to a ten-wire cable which perforates the calo- rimeter walls and is distributed on a hard rubber plate attached to the calorimeter and thence carried to the switches on the observer's table. The high tension currents from the calorimeter pass to a small hard rubber plate inside the box, thence in a separate strand cable to a slate board outside the calorimeter, and thence to the rheostat board. This cable carries leads for the telephone, electric 'fan and for the resistance coil used in electric checks. ACCESSORY APPARATUS The telephone, which has been made as light as possible, is seldom used, since the muscular work involved in telephoning is enough to affect seriously the results in rest experiments. The small electric fan placed in a corner at the foot of the calorimeter stirs the air thoroughly and allows one to get a good sample by drawing off ten liters through the large Bohr meter attached to the outgoing air pipe. The fan is run by the Edison storage batteries, giving off approximately 4.5 calories an hour, the exact amount being determined once an hour by a voltmeter and ammeter. 30 CLINICAL CALORIMETRY On the right side of the subject is a small glass shelf for the weighed urine bottles which, after each voiding, are placed on a spring balance that can be read through the window. Two small brass tubes are led through the wall of the calorimeter just below the small window. One acts as an emergency vent to prevent a positive or negative pres- sure at the beginning or end of an experiment when the ventilation is stopped. To the other is attached the Bowles stethoscope, which is strapped over the apex of the heart so that an observer outside can count the pulse at frequent intervals. The inside of the calorimeter is formed by the polished tinned copper, the roof being almost hidden by the longitudinal absorber pipes wound with brass "jack chain." The calorimeter is wide enough for a man to turn comfortably from side to side, high enough at the foot to allow him to cross his legs and high enough at the head to allow him to sit upright. THE BED The bed in its present form is the result of much experimentation. The frame is made of varnished oak raised at the head so that the top is 12.7 cm. from the floor of the calorimeter while it is raised only 8.2 cm. at the foot. This allows for the sag of the waterproof canvas laced in the frame and keeps the subject 2 to 3 cm. from the copper floor. At the head is a back-rest with a piece of water-proof canvas, which is usually supplemented by a soft pillow. The bed is mounted on a pair of skids so that it can be pushed from the stretcher into the box. The canvas has proved to be much more comfortable than the springs and blankets formerly employed and has the advantage of absorbing very little water vapor. The varnished wood absorbs some water, the necessary clothing of the patient a great deal more, while the polished walls absorb only a minimum. ELECTRIC AND ALCOHOL CONTROL EXPERIMENTS The calorimeter has been tested repeatedly by dissipating known amounts of heat in resistance coils and by burning known amounts of alcohol. The apparatus and procedure used correspond almost exactly with those described by Williams and are similar to those previously used by Atwater and Benedict and by Benedict, Riche and Emmes.* In calculating the latent heat of the evaporation of water we have adopted the figures of Smith' and have given the latent heat the value of 0.584 large calories per gram of water evaporated at 23 C, the usual experimental temperature. 8. Benedict, Riche and Emmes : Control Tests of a Respiration Calorimeter, Am. Jour. Physiol., 1910, xxvi, 1. 9. Smith, A. W. : Heat of Evaporation of Water, Physical Review, 1907, XXV, 14S. K U 1-1 <; w •* ■* cn ■^ g CO s g i-t in e .gs « c cS «e* 6 d d d d d d d d d d d d d d d d d d d d d d d <1 si So n 00 rH ". ■* "*. la ■* M q q q wt "» q q in »] t-; c» i-i d rH CO ui lA d Ol s f: ^ ^ ^ ^ S r rH d 1-5 d d d a d •* ■^ co' ■* d d d d d C^' eg r-i id IH I-l iH IH TH rH r-t rH rH H "■ iH rH rH 1-t a ll s lA eo iH O W I-l ^ <» '^. ■* M « q rH ■* S s ft s t^ •« 3 ■^ CO ;5 rH s d oq d d d l-H d d S S 00 rH 00 g CO . t» Sa o e» CD Ift s \A Ift CD 00 CD Cl g CO ■W t- o 00 ■* lO rH Ol O CD t- °J t- ^ CO t~ eo (N o CO CN CO rH o og Ol C3l o C4 Ol q q g^ I> t^ t^ d i> "* tti "* "*' ■ni rH t~i d d d ■Hi d d 00 d d l>^ d I-l >H l-H i-i iH Oi (M i-t s rH rH rH ss _j_j «i M e» CD 00 •* M •* ph OS o rH 00 CO OO m o eg eg Ol o t^ t- "* CO s 1 t i t T CO + 7 r-< t ?l f d + 1 d 1 d + t T T T eg T d 1 d + 1 i-i 1 p iH 00 t- en Ol ITJ CO Ol CO t- O (N \a CD N 00 00 "* CO rH CO CO CO o o H o i-i ca lO CO CO CO 00 in GO CO t- Ol eg "* CO m CD q & ci 00 c» t^ 00 d iri d d m Wi d d l> d d d t^ d d d d d r-< tH iH 1-1 rH c5 M rH r-i rH CM CM o eo >i ll S 5! s s s g g CO cS « w :s g s s fe CO s g S s s g TH g OJ C» d 00 d d d d CO CO im' CO J> t^ d d t^ d d d d d ^ rH iH I-l CM ; o lO °o CO Ol lO t- Ol oq w q CO CO CO ^i CO CO ^ in d CO s C-1 rH r-i (m' d d d d d s l> d d CD S ?^ to CD CD CD CO Ift in lO in t- 00 t- t- CO in CO CD CD F- CO +3 fv rH w t^ n_: to CD s (M s ■<*H O "* ■* s t- t* D- f; in in in CD m CD F- CD & s o B y ■5m ■* g la CO N O) ■* S Tfl S* CO OS cs © rH eg Ol ■* IH «3 "* ■w TH 1-i CII bd cs f-l C^ Ol bo as CO bO > 3 ° Ph < < rH <1 <3 ■s t- 1 - ■< 32 CLINICAL CALORIMETRY It has seemed advisable to publish all the electric and alcohol checks made with the calorimeter. In publishing control tests the results are much more striking if one selects only the best and leaves out those in which the agreement is not close. This method expresses only the minimum error while the things we really need to know are the average, maximum and total errors. The total error shows the accuracy of the method, the maximum error may occur in the course of any experi- ment, while the average error is with us always. The minimum error TABLE 2. — Electric Checks Length length ol Calories, Calories, Per Cent. of Calories, Calories, Per Cent. Date Period, Min. Theory Found Error Date Period, Min. Theory Found Error 3/4/13 60 72.2B 73.19 +1.2 11/28/13 60 78.22 77.15 —1.4 60 72.25 72.19 +0.0 60 78.22 77.62 —0.8 Average 72.25 72.69 +0.6 60 78.22 78.67 +0.6 4/5/13 60 60 80.78 80.78 77.26 79.31 —4.4 —1.8 Average 78.22 77.81 —0.5 1/26/14 60 76.92 75.86 —1.4 Average •• 80.78 78.29 —3.1 60 76.92 77.41 +0.6 10/13/13 30 30 30 SO 41.74 41.74 41.74 41.74 42.15 41.66 41.25 41.10 +1.0 —0.4 —1.2 —1.5 Average 60 60 76.92 76.92 76.92 77.88 77.24 77.10 +1.3 +0.4 +0.2 80 41.74 41.35 —0.8 5/11/14 60A 78.71 80.03 • Average 41.74 41.49 —0.6 6CB 78.22 76.18 10/22/13 60 83.98 83.98 ±0.0 300 39.07 41.35 60 83.98 83.83 —0.2 Total.... 150 196.00 196.56 +0.3 60 60 83.98 83.98 84.02 83.84 +0.0 -0.2 Total ol Average 83.98 83.92 —0.1 all checks 1589.02 1583.42 —3.5 • A, B, C. Temperature changes of wall of calorimeter; A, +0.06 C; B, —0.73 C; C, —0.05 C. Test to verify hydrothermal equivalent. is a joy to behold, but it does not occur with the regularity inferred by the prominence it is usually given. If, for instance, we should publish only the electric check of October 22 with an hourly error of 0.2 per cent., and the alcohol check of April 30, in which the total errors in the measurement of heat, oxygen and carbon dioxid are all less than ^ of 1 per cent., we should give a false impression of accuracy. This test shows that the calorimeter is capable of measuring heat, oxygen and carbon dioxid with a maximum error of 1.8 per cent, in three consecutive hours. Even better results could be obtained if greater care were taken to secure an even combustion of alcohol. On the other /. A. RICHE—G. F. SODERSTROM 33 hand, the errors which can occur in hourly periods and in whole experi- ments are shown in Table 3. The average error has been obtained by multiplying each per cent, of error by the number of times it occurs and dividing the total by the number of periods. In the whole series of experiments of three or four hours' duration the average error for heat is 0.9 per cent., for oxygen 1.6 per cent, and for carbon dioxid 0.6 per cent., while for the individual hours the error is 1.2 per cent., 3.2 per cent, and 1.6 per cent., respectively. The total error in all the TABLE 3. — Summary of Errors in Electric and Alcohol Checks Per Cent. Error Average ol Whole Experiment Individual Hours Cal. Oa 002 H2O Gal. O2 1 CO2 H2O 1 2 3 4 5 4 2 1 1 1 2 1 3 1 I 2 1 1-. 1 10 15 9 .1 7 3 1 2 2 1 1 1 5 5 5 3 1 4 2 4 3 5 6 7 S 9 10 1 4 1 Total number of experiments or hours 12 5 5 5 1 39 ! 19 19 19 Average error... 0.9 1.6 0.6 3.2 1.2 3.2 : 1.6 i 3.7 Total error —0.33 - 1.69 —0.68 +3.09 electric and alcohol checks is: heat, — 0.32 per cent., O, — 1.69 per cent., CO„ — 0.68 per cent. The total error in the water is + 3.09 per cent. The electric checks show a smaller error in the measurement of calories than the alcohol, since the dissipation of heat is much more uniform. It is difficult to secure an even flow of alcohol to the burner and the larger errors in the oxygen determination are due to irregu- larities in the flow during the last five minutes of the period. If a slight negative pressure develops within the box toward the end of the period, alcohol is sucked into the burner causing the flame to flare up 34 CLINICAL CALORIMETRY and expand the air before the air thermometers record the rise in temperature. This causes an error in the oxygen calculation which, as the tables show, is usually corrected the next hour. With a trained human subject the production of heat and carbon dioxid and the absorption of oxygen are more regular than in the case of an alcohol check and the error presumably not so large. The cause for the nega- tive total error in the measurement of heat, Og and CO2, is not clear, but one cannot help suspecting that a slight absorption of water by the alcohol and a slight evaporation as the alcohol drops from the bottle into the buret may account for most of the error. In experiments on m,an there is another factor which reduces an error in the measurement of oxygen or carbon dioxid considerably. In calculating the indirect calorimetry the factor by which the oxygen or carbon dioxid is multi- plied changes with the respiratory quotient and it happens that a plus error in measurement of the gas is partially offset by a minus change in the factor. This change reduces the error to an extent varying between one-fifth and three-quarters of its original size, unless the errors in both gases are in the same direction, leaving the quotient unaltered. The accuracy of the calorimeter has also been demonstrated by the close agreement of the methods of direct and indirect calorim- etry. This will be taken up in detail in the paper on normal controls, but at this point it may be said that in a total measurement of 4,577 calories the two methods agreed within 0.17 per cent., and that in 26-hourly periods on the normal control most carefully studied, the agreement was within 5 per cent, in seventeen of the hours. In spite of the fact that some of the errors published in the table are larger than those published in connection with other types of apparatus, we feel justified in believing that the Sage calorimeter is the most accurate and most reliable instrument of its size used in the study of the respiratory metabolism. The table includes all the alcohol and electric checks, good, bad and indifferent, made during the period when the machine was used for experiments. The only ones left out are those made at the beginning of the season while the apparatus was being put in order, and actual work was never begun before obtaining a check good enough to publish. To the best of our knowledge this method of publishing all the tests has never been used in connection with other types of respiration apparatus, and we have no detailed information as to their average, maximum and total errors. It is to be regretted that we have not been able to make long electric tests to determine the hydrothermal equivalent of the calorimeter. The storage batteries are not powerful enough to furnish current for more than four hours in addition to the preliminary period of 30 to 40 minutes, and we have never felt justified in using the house current /. A. RICHE—G. F. SODERSTROM 35 with its variations in voltage. Numerous short tests showed that the hydrothermal equivalent was very close to 19 liters of water, and this figure gave results within 0.3 per cent, in the check of May 11 with a large temperature change in the second hour. Incidentally, the advan- tage of a wooden frame is shown by the rapidity with which the box responded to this temperature variation. DETERMINATION OF WATER ELIMINATION In all types of respiration apparatus the measurement of the water elimination has presented great difficulties. This was studied in detail by Benedict, Riche and Emmes, who found that long experimental periods were required to obtain accurate results. The interior of the Sage calorimeter is tinned and polished and there is very little wood- work and cloth, but still a considerable amount of moisture can be retained within the box. In alcohol checks with a water production of only 10 to 14 grams an hour the air becomes dryer and dryer, and this moisture is given off during the whole test, making uniformly a plus error. In experiments on normal men the water elimination is about twice this amount and the percentage of moisture changes but little from hour to hour. In patients who have a tendency to sweat, the water given off may amount to 35 to 40 grams an hour, and there is a tendency for the percentage in the air to increase steadily and finally reach the point of saturation. We should expect a plus error in the determination as the air becomes dryer, a minus error as the percentage of moisture increases, and no error while equilibrium is being main- tained. After the first hour of an experiment on man it seems fair to expect an error of less than 5 per cent., except in extreme cases of sweating. More accurate results could be obtained only by removing all wood-work, stripping the man naked and increasing the ventilating current. This would involve such artificial conditions that the results would be worthless. ADAPTABILITY OF CALORIMETER By carefully controlling the rate of flow and the temperature of the water in the heat-absorber it is possible to adapt the calorimeter to wide variations in the heat production of the subjects. For example, on April 23, 1914, an experiment was made on a cretin with an average heat production of 26 calories an hour. The next day the subject was a patient with exophthalmic goiter, whose heat production averaged 107 calories. In one case the methods of direct and indirect calorimetry agreed within 0.2 per cent., and in the other within 0.7 per cent. It has also been possible to adapt the calorimeter rapidly to changes in the heat production from hour to hour by changing the temperature of the 36 CLINICAL CALORIMETRY ingoing water and in extreme cases by changing the rate of flow at the beginning of a period. It has been possible in a long series of experiments for two men to take all the readings and make all the calculations in hourly periods. Three men can handle the apparatus with ease during the trying experi- ments, and most of the alcohol checks, which are much more difficult, have been made with only three in the room. As a rule, the staff arrives shortly before nine o'clock in the morning, makes a three-hour experi- ment, gets everything in readiness for the next day and leaves the calorimeter room about three or four o'clock in the afternoon. It has been possible, on occasions, to make six experiments in a week. The calorimeter has been very seldom out of commission. Between October 13, 1913, and May 18, 1914, it was possible to make 113 experiments on man and eight alcohol and electric checks. SUMMARY AND CONCLUSIONS The original Atwater-Rosa respiration calorimeter with the improvements added by Benedict, Williams and others has been adapted for clinical study in Bellevue Hospital. The form of the apparatus makes it perfectly comfortable for patients. The accuracy is such that in observations lasting three or four hours the heat pro- duction, carbon dioxid elimination and oxygen consumption as deter- mined by alcohol and electric tests can be measured with an average error of 0.9 per cent., 0.6 per cent, and 1.6 per cent., respectively. In periods one hour long the average error for heat measurement was 1.2 per cent., for carbon dioxid 1.6 per cent, and for oxygen 3.2 per cent. The calorimeter never needs more than three men for its operation, and two men have repeatedly made all the readings and all the calcula- tions in hourly periods. CnNICAL CALORIMETRY THIRD PAPER THE ORGANIZATION OF A SMALL METABOLISM WARD* FRANK C. GEPHART, A.B., and EUGENE F. DuBOIS, M.D. NEW YORK All investigators who have attempted to carry on metabolism experiments in hospitals have experienced more or less difficulty in the administration of the diets and the collection of the excreta. The necessity for a special metabolism ward became evident as soon as it was decided to build a respiration calorimeter in Bellevue Hospital. Through the generosity of the trustees of the hospital and the attending staff of the Second Medical Division a small ward holding four or five beds was placed in charge of the medical director of the Russell Sage Institute of Pathology,^ who was also one of the junior members of the attending staff of the hospital. He is directly responsible to the attending physician for the welfare of the patients, and there has always been a spirit of^active cooperation between the small metabolism ward and the large medical wards of the service. The calorimeter room described in the preceding paper^ is located on the same floor as the male medical wards of the Second Division in the new Medical Pavilion. The side hall, used as an entrance to the calorimeter room, has been partitioned off to make a small diet kitchen. Next to this is a well lighted ward of four beds used almost exclusively for patients v/hose metabolism is the subject of active investigation. The patients are cared for by three graduate nurses, trained in metabolism work and paid by the Institute. The success of the ward is in large measure due to the faithful and intelligent work of the head nurse. Miss Estelle Magill, and her two assistants. They have used the same care in the preparation of food and the collection of excreta that is used in the laboratory and the effort has constantly been made to keep the error within 1 per cent. In order to maintain a high degree of accuracy and at the same time a high standard of nursing it is necessary for the three nurses to devote their whole time to the ward of only four patients. Orderlies, the greatest source of error in metab- * From the Russell Sage Institute of Pathology in affiliation with the Second Medical Division of Bellevue Hospital, New York. 1. Dr. Eugene F. DuBois. 2. Riche and Soderstrom : See p. 13. 38 CLINICAL CALORIMETRY olism work, are excluded from the ward and patients are never allowed in the hospital dining room or kitchen, and only the most trusted are permitted to leave the room at all. These precautions are necessary in order to afford the certainty that the twenty-four-hour specimens of urine are complete and that the patients have not smuggled in outside food. Patients are not allowed out of sight of the nurse in charge for more than a couple of minutes at a time. The food supplied to patients in the metabolism ward is all pre- pared by the special nurses, who have become so skilled in the prep- aration of the various dishes that they can even make one-sided diets attractive. In fact, the patients enjoy the cooking so much that they are sent to their homes or to the general hospital ward with difficulty This is a matter of importance when one desires to keep interest- ing cases under observation. The foods are prepared as often as pos- sible from raw materials whose composition is determined from time to time. Milk and cream have been of fairly constant composition, as the analyses over a period of several years have shown. By applying some of the principles of business efficiency, the work has been made a great deal easier. The dry cereals, eggs, bacon, etc., are weighed in white enamel dishes and bowls of known weight marked with serial numbers. Milk and cream are measured in measuring cylinders and added to these dishes in which the food is baked, fried or boiled. The dishes with the cooked food are then taken directly to the patient and if by any chance he should leave some of the food it is an easy matter to weigh it back. Egg whites and yolks are weighed separately. Sugars, salt, cocoa, butter, etc., are put up in packages of known weight by the night nurse to save time during the day. When a patient first enters the ward the nurses spend a couple days in investigating his dietetic limitations and his dislikes, a matter of great importance. A diet such as the following, for example, is then ordered: 3,000 calories, 15 grams nitrogen, y^ non-protein calories in fat, J^ in carbohydrate. The nurses then work out a diet which will fulfil the .specifications and at the same time be agreeable to the patient. Often by careful work it is possible to educate a patient to a diet that he could not otherwise tolerate. We cannot too strongly emphasize the need of individualization aided by good cooking in experimental metabolism work. The method of collecting twenty-four-hour specimens is, we believe, a new one, and since it has proved to be very satisfactory, should be given in detail. A large number of 20-ounce, round, wide-mouthed bottles with cork stoppers are kept in the ward. These have been etched on the side so that one can write on them with a pencil. At 5 a. m., the time at which the twenty-four-hour period ends, each FRANK C. GEP HART— EUGENE F. DU BOIS 39 Composition of Foods Used in Metabolism Ward Food Protein Fat Carbo- hydrate Calories per Gram 100 Calory Portion Beef, chopped Beef broth Bread, white Chicken, minced Cabbage, thrice boiled *. . . . Cauliflower, thrice boiled * Cocoa, powdered Cheese, cottage Crackers, soda Crackers, sugar Cream Cream Custard Custard, hospital diabetic Farina, dry Flour, hospital diabetic . . . Ice cream, vanilla Ice cream, chocolate Jelly, lemon Junket Macaroni, dry Mammala Mammala (separated milk) Mammala (full cream).. . . Milk, hospital Oatmeal, dry Potatoes, mashed Pudding, rice Pudding, tapioca Rice, dry Rice, cooked Tapioca Special Articles — Cane sugar Corn sirup — glucose Corn sirup — glucose Gelatin Lactose Olive oil Sherry Vinegar Whisky 22.1-48.6 2.1 9.8 18.S 1.7.=; 23.1-23.2 14.9-19.2 8.3 6.2 2.1- 2.9 2.1-2.9 5.4 5.7 18.9 23.2 3.4- 4.8 3.7 2.1 2.1 13.7 26.8 31.7 10.2 3.09- 3.1 15.1 2.2 4.1 5.7 7.0 1.4 2.4-12.8 0.2 0.3 7.2 19.4-25.2 0.2- 1.9 9.3 10.7 17.1-19.8 17.1-19.8 3.5 5.7 0.9 1.3 1.7- 6.9 5.5 0.2 2.1 1.2 9.6 5.4 28.2 3.3- 4.67 5.6 0.2 3.0 2.3 0.5 0.3 53.5 0.24 0.12 48.3-54.0 73.2 80.1 4.0-5.2 4.0-5.2 21.6 7.3 68.2 68.2 12.2-23.4 12.3 17.1 16.6 77.5 4.10- 4.7 71.2 18.0 24.8 14.8 81.9 13.1 91.1 1.3- 2.0 0.1 2.6 l.S- 1.5 4.8- 5.3. 0.6- 0.9 4.3 4.5 1.9-2.1 1.9-2.1 1.4 1.1 3.7 3.9 1.0- 1.6 1.2 0.9 1.0 3.9 4.2 4.0 5.5 0.6 4.1 0.9 1.5 1.1 3.8 0.6 3.7 50- 79 1000 38 69 19-21 118-164 24 22 48- 53 48-53 70 94 27 26 61-99 85 111 104 26 24 26 18 166 24 118 68 94 27 159 27 Sucrose 100 per cent Glucose, 41.3 per cent. ; dextrin, 33.9 per cent. ; sucrose, 2.7 per cent. Glucose, 42.4 per cent. ; dextrin, 44.6 per cent. ; sucrose, 0. Lactose, 98.4 per cent Alcohol by volume, 19.45 per cent. ; Carbohydrate, 1.96 per cent. Acetic acid, 4.07 per cent. Alcohol by volume, 41.76 per cent. 3.96 3.07 37.0 9.52 1.46 2.96 25.2 32.6 27.0 10.5 68.5C.C. 33.8c.c. * Cooked in three changes of water. 40 CLINICAL CALORIMETRY patient is given a bottle and made to empty his bladder. The bottle is then marked with his name, the date, the hour and minute. The volume is estimated for clinical purposes by comparison with a calibrated bottle of the same capacity. The data are then recorded on a special slip of paper to go to the laboratory and also on the diet chart. A little toluene is added to the urine bottle, which is corked and stored in the ice-box along with the previous voidings of that twenty-four- hour period, each voiding being in a separate bottle. At about 9 o'clock in the morning the laboratory man checks up the bottles with the records on the laboratory slip, and with the nurse's notes takes all the bottles to the laboratory, measures the volume accurately, makes up to volume and analyzes a sample. The only disadvantage of this system is the labor of carrying a number of half-filled bottles, although this is not great if suitable carriers are used. The advantages are as follows: 1. There is no chance of a specimen of urine having been poured into another patient's bottle thus spoiling two twenty-four-hour specimens. 2. If a single voiding is lost the urine for the remainder of the day can be accurately analyzed. 3. The urine can be fractionated and the nitrogen elimina- tion determined in hourly periods, as is frequently done in calorimeter experiments. 4. The bottles make excellent urinals, are less apt to spill than the ordinary ward urinal and are not unsightly even when filled with urine. 5. Since the urines are made up to volume in the labora- tory, it is possible to rinse out each bottle with distilled water and collect every drop of urine. 6. The bottles are washed, dried, and, if necessary, sterilized in the laboratory, so that there is no danger of a patient voiding into a urinal containing decomposing urine. 7. The bottles are cheap and can be kept on hand in large numbers, so that the patients need never wait for the urinal. 8. While we have never had occasion to use them in a general ward, there is no reason why they should not be used instead of the common type of expensive and unsightly tirinal. In collecting single specimens for the usual routine analysis the nurse could put a bottle by each bed in the morning and send the desired specimens directly to the ward laboratory without transferring to a special jar. It is surprising how long urines will remain clear if voided into and kept in a clean bottle. The collection of feces is somewhat more difficult. Patients who can get out of bed defecate into a weighed bucket in the commode. This bucket is then weighed again. A Httle formalin is added and the whole sent to the laboratory where the specimen is thoroughly mixed and one-tenth removed to be dried and added to the other aliquot portions of that period and analyzed. Bed-ridden patients use a weighed bed pan from which the feces are transferred to a covered bucket for FRANK C. GEPHART— EUGENE P. DU BOIS 41 transportation. Most of the patients with acute diseases are given every morning an enema of hypertonic salt solution. Oil and soap enemas of course interfere with the accuracy of the fat analyses ; glycerin enemas make it impossible to dry the feces. To divide the periods, powdered carmin (0.3 gm., 5 grains) is given with the first meal of the period and with the first meal after the period is ended. Experience has shown that it is much easier to determine the exact point of appearance of the carmin in the feces than to find the point of disappearance. When patients are being given enemas it is easier to discover traces of carmin than traces of charcoal. Periods are made as long as possible to minimize the errors of division. A special diet sheet has been provided by the hospital on which the nurses record the weights of raw material given to the patient and make the calculations from the table of known composition of the food. On this sheet is a summary column giving carbohydrate, fat and pro- tein grams and calories, total calories, nitrogen of the food, of the urine, of the total excreta and the nitrogen balance; weight of the patient and food calories per kilogram. In another place are columns for recording the time and amount of each voiding and each defecation. Patients are weighed at 9.00 a. m. every day or every other day on a "silk scale" accurate to 10 grams. Bed patients are weighed on a platform resting on these scales in the manner described by Coleman.^ The nurse slides the patient on the smooth platform which is just at the level of the bed, weighs him and then makes, up the bed while he is still on the balance. The whole procedure has been found to be a convenience for the nurse rather than a time-consuming task. Nitrogen determinations are made by the Kjeldahl method, ammonia, uric acid, creatin, creatinin, and indican by Folin's* methods, urea and glucose by the methods of Stanley R. Benedict.' The calorific value of the foods has been determined by means of the Riche° bomb calorimeter. Food fat analyses have been made in a Soxhlet apparatus. Carbohydrates were determined by a difiference using in the later work a new procedure described by Gephart.'' The 3. Coleman: Diet in Typhoid Fever: Journal Am. Med. Assn., 1909, liii, 114S. 4. Folin: Approximately Complete Analysis of Thirty Normal Urines, Am. Jour. Physiol., 1905, xiii, 4S. 5. Benedict : The Detection- and Estimation of Glucose in Urine, Jour. Am. Med. Assn., 1911, Ivii, 1193. The Estimation of Urea in Urine, Jour. Biol. Chem., 1910, viii, 405. 6. Riche : An Improved Type of Calorimeter for use with any Calorimetric Bomb, Jour. Am. Chem. See, 1913, xxxv, 1747. 7. Gephart, Frank C, and Csonka : In the Estimation of Fat in Feces, Jour. Biol. Chem., 1914, xix, 521. 42 CLINICAL CALORIMETRY dried feces were powdered and the fat determined at first by the Kumagawa-Suto method and later by the new saponification procedure described by Gephart/ In calculating food values, Rubner's factors were used, namely : for fat 9.3 calories ; for carbohydrate and protein, 4.1 calories per gram. 8. Kumagawa and Suto: Ein neues Verfahren zur quantitativen Bestim- mungen des Fettes und der unverseifbaren Substanzen in tierschen Material nebst der Kritik einiger gebrauschlischen Material, Biochem, Ztschr., 1908, viii, 212. CLINICAL CALORIMETRY FOURTH PAPER THE DETERMINATION OF THE BASAL METABOLISM OF NORMAL MEN AND THE EFFECT OF FOOD* FRANK C. GEPHART, A.B., and EUGENE F. DuBOIS, M.D.f NEW YORK TABLE OF CONTENTS 1. Introduction. 2. Review of literature on basal metabolism. 3. Review of literature on specific dynamic action of foods. 4. Experimental procedure. 5. Description of subjects and details of experiments. 6. Tables of experimental data. 7. Discussion of results : a. Comparison of direct and indirect calorimetry. b. Comparison of surface and rectal temperature. c. Selection of the average normal standard. d. Variations from this standard found in normal individuals. e. Calories per square meter versus calories per kilogram. f. Increased metabolism following the ingestion of protein and carbo- hydrate. 8. Summary and conclusions. The importance of the normal control has been emphasized so strongly by the serologists and the management of the control has been developed by them to such an art that it has seemed advisable to apply some of their methods of critique to the study of the respiratory metabolism. Serologists insist that a man shall make his own controls with the same apparatus and exactly the same technic as in the experi- ments and they also insist that the controls shall be numerous enough to show individual variations in their true proportions. These precau- tions and many others have been made necessary by the fact that the normal control is usually the point of attack in serological contro- versies. Likewise in the study of metabolism the normal control is coming to be recognized as the weakest part of the experiment. The chemical methods of blanks and duplicates will not suffice; the living organism is the uncertain factor. The literature is notoriously filled with false theories, of which by far the greater part would never have been promulgated if sufficient attention had been given to normal controls. * From the Russell Sage Institute of Pathology, in affiliation with the Second Medical Division of Bellevue Hospital. t With the technical assistance of G. F. Soderstrom and R. H. Harries. 44 CLINICAL CALORIMETRY The three papers immediately preceding have described the Sage respiration calorimeter in Bellevue Hospital and its adjoining metab- olism ward. Before presenting any of the work in pathological con- ditions it has seemed best to study in detail the results obtained on the normal controls. It was the original intention to use a large number of normal subjects and determine the individual variations in metabolism, but this laborious piece of work was gladly abandoned when it was learned that Benedict and his collaborators were engaged in the task. In pathological conditions the work has been confined as ihuch as pos- sible to men between the ages of 20 and 50 who do not depart very markedly from the normal relationship between height and weight. Consequently the normal controls have been selected to comply with these requirements. BASAL METABOLISM As a basis of comparisons between all normal individuals and groups of patients the heat production in the morning from fourteen to eighteen hours after the last meal with the individual at complete rest, was selected. This has been termed the "nuchtern" metabolism by the Germans, the "post-absorptive" by Benedict and Cathcart,^ but the simplest and most satisfactory term is "basal metabolism," a trans- lation of the German Grundumsatz, as used by Lusk and his coworkers^ in the series of papers published under the heading of Animal Calo- rimetry. The literature of the respiratory metabolism of healthy men has been admirably reviewed by Benedict and Carpenter^ in 1910 and Loewy* in 1911. In the former monograph the results of a large number of experiments with the respiration calorimeter of Wesleyan University are gathered in numerous tables. During the so-called rest experim.ents, however, the subjects were allowed to move about the room and indulge in minor muscular activities, something which had 1. Benedict and Cathcart : Muscular Work, Carnegie Institution of Wash- ington, 1913, Pub. 187. 2. Lusk: Caloriraetric Observations, Med. Rec, New York, 1912, Ixxxii, 925 ; Williams, Riche and Lusk : Animal Calorimetry, Second Paper. Meta- bolism of the Dog Following the Ingestion of Meat in Large Quantity, Jour. Biol. Chem., 1912, xii, 349; Lusk: Third Paper, Metabolism After the Inges- tion of Dextrose and Fat, Including the Behavior of Water, Urea and Sodium Chlorid Solutions, Ibid., 1912, xiii, 27; Lusk: Fifth Paper, The Influence of the Ingestion of Amino-Acids upon Metabolism, Ibid., 1912, xiii, 155; Lusk: Sixth Paper, The Influence of Mixtures of Foodstuffs Upon Metabolism, Ibid., 1912, xiii, 185. 3. Benedict and Carpenter : The Metabolism and Energy Transformations of Healthy Man During Rest, Carnegie Institution of Washington, 1910, Pub. 126. 4. Loewy : Oppenheimefs Handbuch der Biochemie der Menschen und der Thiere, Jena, 1908, iv,' 172. FRANK C. GEPHART— EUGENE P. DU BOIS 45 been permitted in practically all the large respiration chambers. Bene- dict and Carpenter measured the increased heat production caused by certain simple movements which their subjects had performed during the experiments. The act of rising from a chair, taking one or two steps, opening the food aperture, removing the food, closing the v/indow and returning to the chair required only 19 to 29 seconds, but involved the expenditure of 1.22 calories. Considering the short time involved in the operation, the heat production was increased from 200 to 300 per cent. They also found the metabolism IS per cent higher when the subject was standing than when he was sitting, and from 8 to 10 per cent, higher when lying awake than when sleeping. The sleeping periods were between 1 a. m. and 7 a. m., and the waking periods followed immediately in the three experiments which were really satisfactory. During the waking periods there was an increase in the oxygen consumption amounting to 1.7, 0.9 and 11.5 per cent., while the heat production was increased 5.8, 15.2 and 13.1 per cent. Some of this increase may be accounted for by difference in the time of day, some by small muscular movements. Johansson^ found that with complete muscular relaxation the carbon dioxid production was the same as during sleep. The two individuals (H. C. K. and H. R. D.) studied by Benedict and Carpenter produced during sleep 35.2 and 36.2 calories per square meter of body surface, whereas only three of the twelve normal men, whose metabolism is recorded in Table 3, pro- duced more than 35.1 calories per square meter per hour. It is obvious that if the metabolism of H. C. K. and H. R. D. were increased 5.8 per cent., 15.2 per cent, and 13.1 per cent., this increase would carry them just so much farther into the zone where it is necessary to assume muscular activity to account for the abnormally high metabolism. In anticipation it may be well to mention that the average basal heat production of the individuals we are reporting is 34.7 calories per square meter per hour, the subjects lying awake, at perfect rest during the morning hours. The average heat production of the nineteen sub- jects of Benedict and Carpenter while asleep between the hours of 1 a. m. and 7 a. m. was 35.3 calories and of fifty-five individuals while awake and moving from time to time in the calorimeter was 49.2 calories per square meter per hour. The fact that their sleeping sub- jects showed a metabolism 3 per cent, higher than our subjects awake may substantiate the conclusions of Johansson. Benedict and Car- penter pointed out at the 'conclusion of their monograph (p. 246) the fact that the figure 49.2 calories per square meter per hour, equaling 5. Johansson : Ueber die Tageschwankungen des Stoffwechsels und der Korpertemperatur in niichternem Zustande und vollsandige Muskelruhe, Skand. Arch. f. Physiol., 1898, viii, 85. 46 CLINICAL CALORIMETRY 36.5 calories per kilogram per day, represented not the condition of true rest, but rather that of a person confined for the day to a small room but allowed to dress and undress, sit in a chair, feed himself, etc. Since the appearance of this monograph Benedict and his coworkers, and also other investigators, have insisted more and more strongly on the necessity of absolute quiet in rest experiments and as a check on muscular activity a graphic record of all movements. This eliminates for our purposes practically all the work done in large respiration chambers before 1910 and leaves us only the work done by means of the small types of apparatus, and especially the Zuntz-Geppert appa- ratus, by Magnus-Levy and Falk,^ and by Loewy. The results of the determinations on nineteen normal individuals have been collected in a table by Loewy' which is reprinted by Benedict and Joslin.' Coleman and DuBois,'' in gathering normal controls to compare with their typhoid patients, grouped these cases of Loewy with twenty-seven normal controls taken from the work of Benedict and Joslin, and with two of their own cases. The average heat production of the total forty-eight normal men was 33.7 calories per square meter of body surface per hour. Very recently Benedict, Emmes, Roth and Smith^" published a brief report of their important work on the basal metab- olism of a total of eighty-nine men and sixty-eight women. The early appearance of these determinations has been of great service to us, and we wish to express our appreciation to these investigators for the publication of the most essential part of their data.* All their deter- m.inations were made on healthy subjects in the morning at least twelve hours after the last meal, with the subject at complete rest. Some of the experiments were made in the bed calorimeter of the Nutrition Laboratory of Boston, but most of them^ were short experiments made with the small Benedict "universal respiration apparatus." The fact that this small machine gives results almost identical with the calorim- eter was amply proved by Benedict^ and his coworkers and confirmed by the limited amount of work done with both types of apparatus by 6. Magnus-Levy and Falk: Der Lungengaswechsel des Menschen in ver- schiedenen Alterstufen, Arch. f. Anat. u. Physiol., 1899, Supp. 314. 7. Loewy: Oppenheimer's Hand, der Biochemie der Menschen und der Thiere, Jena, 1908, iv,' 179. 8. Benedict and Joslin : Metabolism in Diabetes Mellitus, Carnegie Insti- tution of Washington, 1910, Pub. 136; A Study of Metabolism in Severe Dia- betes, ibid., 1912, No. 176. Ueber der Stoff- und Energieumsatz bei Diabetes, Deutsch. Arch. f. klin. Med., 1913, cxi, 333. 9. Coleman and DuBois: The Influence of the High Calory Diet on the Respiratory Exchanges in Typhoid Fever, The Archives Int. Med., 1914, xiv, 168. 10. Benedict, Emmes, Roth and Smith : The Basal, Gaseous Metabolism of Normal Men and Women, Jour. Biol. Chem., 1914, xviii, 139. * A more complete discussion of the work is appearing in the Jour. Biol Chem., March, 1915. FRANK C. GEPHART— EUGENE F. DU BOIS 47 Coleman and Du Bois.^ The average heat production of the eighty- nine men was 34.7 calories per square meter per hour, and of the sixty- eight women, 32.2 calories. The lower heat production of women is in accord with the previous findings of Sonden and Tigerstedt.^^ The work of Magnus-Levy and Falk" showing the diminution of metabolism in old age and the increase in youth is also confirmed. The two men over 50 years of age produced only 28.9 calories per square meter. The eight youths between 17 and 20 averaged 37.1 calories, nine who were 20 years old, 36.6 calories, seven who were 21 years old, 36.1 calories. SPECIFIC DYNAMIC ACTION OF FOODS The subject of the specific dynamic action of foods in increasing metabolism is fully discussed by I.usk^^ in his text-book and in a series of papers on animal calorimetry.''' ^' From his work on dogs, Lusk has concluded that the specific dynamic action of protein is due to the stimulation of the metabolism of the cells by certain of the amino-acids while the action of fat and carbohydrates is due to the mass action of these metabolites in the circulation. He has found marked differences in the action of the various amino-acids and the various carbohydrates. The study of the specific dynamic action of foods on man is not nearly as far advanced as in the case of the dog. Magnus-Levy^* in connection with his work on dogs found that after giving a man 50 to 60 grams of carbohydrate the metabolism was increased in the first hour from 2 to 12 per cent., in the second hour to 7 per cent. After 140 to 160 grams of starch in bread the increase in the first hour averaged 22 per cent., the second hour 14 per cent., the third hour 16 per cent. After 210 grams of bacon and butter the metabolism was increased 5 to 10 per cent, for seven to eight hours, while after 210 to 250 grams of beef the oxygen consumption rose from 3 to 12 per cent, the first hour and then 15 to 34 per cent, in the next six hours. Gigon^' obtained similar results using a Jacquet apparatus. In the period of four to five hours follow- ing the ingestion of 100 grams of dextrose there was an increase of 9.5 per cent, in the oxygen consumption. After 50 grams of casein the oxygen was increased 5.5 per cent, and after 100 grams 16.8 per cent 11. Sonden and Tigerstedt: Untersuchungen iiber die Respiration und den Gesammtestoffwechsel des Menschen, Skand. Arch. f. Physiol., 1895, vi, 99. 12. Lusk: The Science of Nutrition, Philadelphia, 1909, second edition; Stofifwechsel und Ernahrung; Deutsche Uebersetzung von L. Hess, 1910. 13. Lusk : The Cause of the Specific Dynamic Action of Protein, The Archives Int. Med., 1913, xxi, 485. 14. Magnus-Levy: Ueber die Grosse des respiratorische Gaswechsels unter dem Einfluss der Nahrungsaufnahme, Arch. f. d. ges. Physiol. (Pfltiger's), 1894, Iv, 1. 15. Gigon: Ueber den Einfluss der Nahrungsaufnahme auf den Gaswechsel und Energieumsatz, Arch. f. d. ges. Physiol. (Pfliiger's), 1911, cxl, 509. 48 CLINICAL CALORIMETRY EXPERIMENTAL PROCEDURE The normal controls who were kept in the metabolism ward were given a maintenance ration, the last meal of the day being about 5 p. m. At 5 a. m. they were awakened, given an enema, and instead of break- fast, a cup of coffee without cream or sugar. At about half past nine the calorimeter bed was wheeled to the ward on the weighing platform, which is provided with large' casters, and the subject lifted from his bed, weighed, rolled back to the calorimeter room and slid into the calorimeter, bed and all. He was dressed in a night shirt, thick ward pajamas and thick socks, and, as a rule, the legs were covered with a sheet, although some subjects needed a thin blanket and others required no covering. A soft pillow was placed under the head and sometimes one under the knees. Every effort was made to ensure absolute com- fort, a matter of great importance in work on the respiratory metabolism. Those normal controls who lived at home took their evening meal at 6 or 7 o'clock, rose at 6 or 7 a. m., drank a cup of black coffee, took the street car, walked about % mile and arrived at the hospital at 9 o'clock. They then undressed, weighed themselves, dressed in warm pajamas and entered the calorimeter. As soon as the subject was in the calorimeter the rectal ther- mometer was inserted about 12 cm. in the rectum, giving slight discom- fort for a few minutes, but later remaining in position without the man's being conscious of its presence. The surface thermometers were next fastened tightly to the thorax, axillae or abdomen by means of adhesive plaster and the whole covered with a pad of absorbent cotton abottt 20 cm. in diameter and 3 or 4 cm. thick, this being held in place by strips of adhesive. The Bowles stethoscope was next strapped over the apex of the heart and the whole covered with night shirt and pajamas. When this was finished the bed was shoved all the way into the box, the ventilation started, and at about a quarter past 10 the glass plates were sealed in the end of the calorimeter and the heavy front put in position, making it possible to start the preliminary period shortly after half past ten. The actual preparation of the calorimeter had begun long before this. On the previous afternoon all sulphuric bottles, soda-lime con- tainers, etc., had been filled and the oxygen tank weighed so that any leakage over night might be detected. The temperature of the calorim- eter room had been watched every hour by the night nurse and main- tained within 1 degree of the standard experimental temperature of 23 C. At nine in the morning the water circulation through the various cooling coils and the absorber had been started and a lighted 32 candle power electric lamp placed in the box until the subject was ready. If FRANK C. GEPH ART— EUGENE F. DU BOIS 49 these precautions had been carefully followed and if the observer had watched the temperature of the various parts of the apparatus, it was possible to bring the box into perfect equilibrium and control fifteen to twenty minutes after the start of the preliminary period. As we shall see later, there is reason to believe that during the first hour after the box is sealed the wooden frame of the bed may absorb a little heat owing to its proximity to the subject's body. As a rule the preliminary period lasts thirty to forty minutes and the experiment begins shortly after 11 o'clock. Eight minutes before the start a sign is hung in the window telling the subject to remain abso- lutely quiet and the first residual sample of ten liters of air is drawn through U tubes by means of the Bohr meter. At four or five minutes before the start the second residual is begun and a tracing of the spirometer curve made in the manner first used by Benedict and Car- penter. At "time" the various cocks and switches are turned TABLE 1. — The Statistics of the Normal Controls Subject Weight, Kg. Height, Cm. Chest Circumference, Cm. Age, Trs. G. L 78.4 73,6 75.5 56.5 62.0 59.5 51.7 70.9 175.5 178.8 173.9 177.2 170.6 90.5 91.5 80.2 85.3 86.6 47 E. P. D. B. ... 31-32 F. C. G E. H. H L. 0. M 29 21 22 2? 44 as described in the previous article. One or two minutes after "time" the subject is allowed to shift his position, and, if neces- sary, void into a tared urine bottle which he then places on a small spring balance so that the exact weight of urine passed can be read through the calorimeter window. During the remainder of the hour he lies as quiet as possible trying not to turn from back to side and vice versa more than once an hour. The work-adder on the spirometer records each movement and the electrical control of the calorimeter is so delicate that the observer in charge of the thermometers can detect such slight activity as turning the head to look out of the window by the rise in the temperature of the air and wall. At the close of the first and subsequent hours the procedure is the same as at the start, except that only one sample of residual air is analyzed. The statistics of the normal controls are as shown in the accom- panying table (Table 1). so CLINICAL CALORIMETRY DESCRIPTION OF SUBJECTS AND DETAILS OF EXPERIMENTS G. L., physiologist, large frame, slightly adipose. Has taken but little exer- cise during the last few years. Health good, no recent illnesses. Physical examination negative. Experiment 1. — March 11, 1913. Although this was the first experiment on man made with the Sage calorimeter, the accuracy of the machine had been thoroughly tested by means of the alcohol checks described in Paper 2. The temperature of the air in the calorimeter was 24.S C. in this experiment instead of the temperature of 23 C. used later. In addition to a suit of pajamas, the subject wore a heavy sweater. The basal metabolism was determined in the first two hours and at the beginning of the third hour he drank a solution of 115 grams commercial glucose (dextrose 42.37 per cent., dextrin 44.57 per cent., water 13.50 per cent.) in SCO c.c. water and 10 c.c. lemon juice. The commercial glucose was equivalent in calories to 100 grams dextrose. The subject, who had felt somewhat too warm during the first two hours, perspired profusely after the glucose. He remained very quiet during the five hours. E. F. D. B., physician, large frame, moderate adipose. Up to the age of 22 in good athletic condition ; since then has exercised in steadily decreasing amounts. During the winter of 1913 took violent exercise for about half an hour twice a week; in 1914 scarcely exercised at all. General health good; no recent illnesses. Heart, lungs, etc., normal. Experiment 2. — March 13, 1913. The basal metabolism was determined in the first two hours, and at the beginning of the third hour he drank 115 grams commercial glucose in the same solution as in the experiment on G. L. The temperature of the calorimeter was 22 C. and his clothing consisted of thin undershirt and pajamas. He did not perspire but blew his nose several times each hour, spent a good deal of the time looking out of the window and was distinctly more restless than in the subsequent observations. Experiment 25. — May 17, 1913. Basal determination only. Was very quiet during all three hours and dozed from 11:30 to 11:50. Experiment 27. — May 22, 1913. At 8:55 a. m., before entering the calo- rimeter, drank 230 gm. commercial glucose (equivalent to 200 gm. dextrose) in 500 c.c. water and 15 c.c. lemon juice. Six minutes were required to drink the mixture. Dozed at times during the experiment. Experiment 115. — March 30, 1914. Basal metabolism only. This experi- ment was conducted by only two observers, Mr. Soderstrom and Mr. Harries, and the periods were made one and one-half hours long to give them more time for weighings, etc. In the subsequent experiments on this subject these two observers alone were able to make all measurements and keep up with the calculations in hourly periods, a record of which they may well be proud, especially since the agreement between the direct and indirect calorimetry was unusually good. Experiment 116. — April 1, 1914. Just before entering the calorimeter between 9:45 and 10:07 a. m., the subject ate the following meal containing 10.5 gm. nitrogen: fat-free milk, 600; pot cheese (cottage cheese or Schmierkdse), 150; egg-white, 120; egg-yolk, 20. During this experiment the work-adder was out of order and recorded part of the excursions of the spirometer due to the admission of oxygen to the box. The subject was very quiet, much more quiet than the work-adder record would indicate. Experiment 138.— May 8, 1914. Between 10:05 and 10:07 a. m., drank a solution of 200 gm. C. P. Dextrose (Merck) in 400 c.c. water and 35 c.c. lemon juice. No glycosuria resulted in this or any other of the experiments on normal controls. Experiment 141. — May 15, 1914. An attempt was made to raise the respira- tory quotient as high as possible by filling the glycogen stores of the body FRANK C. GEPHART— EUGENE F. DU BOIS 51 before giving the dextrose. At 11 :30 the night before the experiment and again at 6:15 in the morning the subject ate the following carbohydate meal: shredded wheat, SS gm. ; milk, 100 c.c. ; cane sugar, 10 gm. ; in the morning taking an additional 10 gm. cane sugar in coffee. Between 9:50 and 9:53 he drank a solution of 200 gm. C. P. Dextrose in 400 c.c. water and 35 c.c. lemon juice. F. C. G., chemist, thin. At age of 16 had an attack of malaria lasting two weeks. Has not been sick in bed since then and has never weighed over 64 kg. (140 pounds). Has never taken systematic exercise, except baseball from 1900 to 1906. Appetite fair, sleeps well. Physical examination : complexion pale and somewhat sallow; hemoglobin normal; state of nutrition rather poor; heart, lungs and abdomen normal. Experiment 142, May 18, 1914. Basal determin- ation. Experiment 3. — March 17, 1913. The basal metabolism was determined between 9:02 and 12:02, the subject going into a profound sleep in the second and third hours. The calorimeter was then opened and the subject ate the Haferschleim mixture of Schmidt's test diet. This contained 40 gm. dry oat- meal, 10 butter, 200 milk and one egg, or approximately, protein, 13.1, fat, 10.2, carbohydrate, 35.5 gm. At the end of the observation it was apparent that the respiratory quotients were abnormally low and that the apparent oxygen consumption was much higher than was consistent with the direct calorimetry. The cause for this was found in a leak in the oxygen cylinder, making it necessary to omit the oxygen figures from the data and base the calculations on the direct calorimetry alone. Experiment 17. — April 22, 1914. Basal determination. The subject remained very quiet, but took care not to go to sleep. Unfortunately the oxygen cylinder leaked again and the calculation of the indirect calorimetry was not accurate. R. H. H., chemist, tall and spare with long and rather thin bones, very little adipose. At the age of 12 had pneumonia, since then always well. Up to four years ago played semiprofessional baseball or basketball almost every day. Since 1910 his exercise has been limited to four to ten miles of walking a day and in summer a swim of about two miles a day. Physical condition good, heart, lungs and abdomen normal. Experiment 4. — March 13, 1913. Basal determination. During the experi- ment this subject tried to void at the beginning of each hour but was unable to do so and was slightly more nervous and more active than the other sub- jects. He could not void before his first meal after the experiment and it has therefore been necessary to omit the figures for the urinary nitrogen and base the calculations on the tables of Magnus-Levy," assuming that IS per cent, of the calories were derived from protein. Louis M., barber, small frame, short and thin, muscles fairly firm. This subject was in the hospital from September 7 to October 30, 1912, with a moderately severe attack of typhoid fever, and served as a subject of numer- ous observations by means of the Benedict universal respiration apparatus (Coleman and DuBois"). He was born in Germany and came to New Orleans in 1911. There he suffered from a severe attack of malaria but has had no recurrences. His family history shows that one sister is insane. After his attack of typhoid he left the hospital in excellent condition and he has been perfectly well for the last four months, although at first he was somewhat weak and easily tired. Physical examination shows heart, lungs, abdomen, etc., to be normal. Experiment 7. — March 26, 1913. Basal metabolism. Subject remained in the metabolism ward four days. On the evening previous to this experiment 16. Magnus-Levy: Von Noorden's Handbuch der Pathologic des Stoffwech- sels, Ed. 2, 1906. 52 CLINICAL CALORIMETRY at S p. m., ate a dinner containing protein, 35.1 gm., fat, 37.1, carbohydrate, 105.6. During tlie experiment he lay very quiet, dozing most of the time. Experiment 8. — March 28, 1913. March 27 his food contained protein, 80.6; fat, 168.9 ; carbohydrate, 268.7 gm. ; the last meal of the day at 6 p. ra. con- taining protein, 28.9; fat, 61.7; carbohydrate, 82.3 gm. Just before entering the box, between 8 :25 and 9 :25 a. m., he ate 725 gm. chopped beef, fried in butter, the whole containing 23.93 gm. nitrogen and 100 gm. fat. During the experiment he slept from 12 : 26 to 1 : 18 p. m. and from 3 : 22 to 3 : 30. There was a small leak from the absorber pipe into the calorimeter, making the apparent water elimination about 1 gram an hour too high. John L., dentist, medium frame, medium height, well nourished, muscles flabby. This subject, who was born in Sweden, served as a normal control in the metabolism experiments of Dr. R. A. Cooke," who investigated the func- tional powers of the kidneys. Careful tests showed in this subject a slight delay in the excretion of sodium chlorid, but there were no other signs of kidney disease. He gave a history of moderate indulgence in alcohol. In 1904 he was jaundiced; a few months prior to the experiment he suffered from an infected hand after a dog bite. For the last five years he has been nervous. He was admitted to the hospital Jan. IS, 1914, suffering from a few small boils and a pedicular eruption. His ailments were so slight that he was induced to remain in the hospital as a normal control and, being without a home, he was glad to remain. Physical examination showed a thorax with flaring ribs and an increased anteroposterior diameter of the chest with hyperresonant percussion note and breath sounds somewhat distant. The teeth were in poor condition; blood-pressure, systolic 115 to 130, diastolic 75 to 90. Experiment 113. — March 26, 1914. Basal metabolism. During the previous day the diet had contained 11.5 gm. KCl and a minimum of NaCl. The last meal at 6 p. m. had consisted of farina, 25; egg-white, 50; yolk, 50; sugar, 50; cream (20 per cent, fat), 60; KCl, 3.5 gm. Blood-pressure March 25, systolic, 140; diastolic, 95; just before the calorimeter experiment, systolic 135, diastolic 105. L. C. M., laboratory helper, small frame, somewhat short and thin. He was born in Sicily where he lived until the age of 11. Shortly before leaving for this country he suffered from malaria, but since then has been in good health. For the last five years he has worked in the daytime and gone to school at night, consequently has taken but little exercise. Heart, lungs and abdomen normal. Experiment 136. — May 4, 1914. Basal metabolism. Experiment 137. — May 6, 1914. Between 9 :50 and 9 :53 drank a solution of 200 gm. C. P. dextrose in 400 c.c. water and 35 c.c. lemon juice. No glycosuria. The subjects have been described in detail above and particular attention has been given to the athletic history, sirice the recent work in Benedict's laboratory (personal communication) has shov/n a differ- ence in the metabolism of athletes and non-athletic individuals. From a study of the results in previous determinations of the normal metab- oHsm one is led to suspect that a few distinctly abnormal cases have crept in. It has, therefore, been our practice to give the normal con- trols as careful physical examination as the patients. The importance of this is manifest if one considers that the onset of hyperthyroidism is usually accompanied by the symptoms of exuberant good health. 17. Cooke: Unpublished. FRANK C. GEPHART— EUGENE F. DU BOIS 53 The details of the individual experiments are given below. The body- weight at the start of the experiment is determined by weighing the subject shortly before he enters the calorimeter and then making the proper corrections for food, urine and insensible perspiration. All calculations are made from this weight, the surface area being reck- oned from Meeh's" formula 12.312 v wt^. Some actual determinations of the surface area of E. F. D. B. have shown that Meeh's formula is 14.3 per cent, too high in his case, while it is only 7.3 per cent, too high in the case of R. H. H. Calculated from a new formula, Meeh's figures are 14.5 per cent, too high in the case of G. L., 9.3 per cent, too high in the case F. C. G. and 13.4 per cent, too high in the case of L. C. M. These measurements will be given in detail in a subsequent paper. For purposes of uniformity, however, calculations are based on Meeh's formula, since this has been used in all othet metabolism work. The work-adder was not attached to the calorimeter until May 16, 1913, and an exact record of the activity of the subjects was not obtained before this date. After the work-adder as described in Paper 2 was attached it was possible to compare the activity in different periods and in different experiments and express this in terms of the number of centimeters that the plummet was raised by the expansion of air within the box. The excursion of the plummet for certain movements of the subject was roughly calculated as follows: Raising arm to head, 0.3 cm. ; lifting telephone to mouth, 4 cm. ; turning from back to side, 7 cm. In the tables the final calculations of calories per hour have been based on the indirect calorimetry as calculated from the oxygen con- sumption and the respiratory quotient. In the two experiments on F. C. G., where these were inaccurate the direct calorimetry was used, and in one of the hours in the experiment on G. L. where the CO^ measurement was lost the non-protein R. Q. for the purposes of calculation was assumed to be 1.00. In the experiments on E. F. D. B. on May 22 there was an evident error in the division of oxygen between the second and third and the fourth and fifth periods, so these were averaged in the final calcu- lations The methods of calculation have been described in Paper 1, but it may be well to remind the reader that the method of direct calorimetry represents the heat eliminated from the body, plus or minus the heat stored in or lost from the body, when the temperature of the body rises or falls. The calculation of the percentage of calories derived from protein, fat and carbohydrate is based on the urinary nitrogen and the non-protein respiratory quotient. 18. Meeh : Oberflachenmessungen des menschlichen Korpers, Ztschr. f. Biol., 1879, XV, 425. TABLE 2.— Experimental— Subject Date Weight Kg. Period End of Period COa, Gm. 02 Gm. B. Q. H2O, Gm. Drine N Per Hour, Gm. Indirect palo- rimetry, Oal. Heat Elimi- nated, Oal. G. L 3/11/18 78.42 Preliminary 1st Hr A.M. 9:50 10:50 25.26 21.51 0.85 37.03 0.487 72.35 76.77 2d Hr. 1st Hr. P. 0. 11:50 P.M. 12:50 26.56 29.61 25.90 28.57 0.75 0.75 37.84 37.88 0.487 0.404 84.85 94.12 86.10 87.75 2d Hr. P. 0. 1:50 25.75 39.24 0.404 86.76* 92.53 E. P. D. B. 3/13/13 73.6 3d Hr. P. 0. Preliminary IstHr 2:50 A.M. 9:35 10:35 30.33 27.22 23.44 25.27 0.94 0.78 38.98 27.91 0.404 0.554 80.86 83.52 95.67 77.85 2d Hr 1st Hr. P. C. 11:35 P.M. 12:35 25.28 29.51 21.32 23.58 0.86 0.91 26.53 31.19 0.564 0.621 71.75 80.27 71.94 84.87 2d Hr. P. 0. 1:35 31.12 25.50 0.89 30.50 0.621 86.42 82.87 3d Hr. P. 0. 2:35 30.30 24.94 0.88 30.40 0.621 84.41 81.46 E. P. D. B. B/17/13 75.51 4th Hr. P.O. Preliminary 1st Hr 3:35 A.M. 9:30 10:30 29.92 26.41 24.10 22.37 0.90 0.83 32.02 34.22 0.621 0.526 81.92 74.69 86.02 76.83 E. P. D. B. 5/22/13 76.10 2d Hr 3d Hr Preliminary 2d Hr. P. 0. 11:30 P.M. 12:30 A.M. 9:30 19:30 25.45 25.00 31.13 21.95 21.24 23.04 0.84 0.86 0.98 32.00 30.68 36.24 0.526 0.526 0.581 73.60 71.41 79.77 76.67 74.13 84.61 3d Hr. P. 0. 4th Hr. P.O. 11:30 P.M. 12:30 31.53 32.45 25.291 22.49J 0.97 [36.13 135.07 0.581 0.581 165.30 83.21 83.91 E. P. D. B. 3/30/14 74.34 5th Hr. P.O. 6th Hr. P.O. Preliminary l%Hrs 1:30 2:30 A.M. 11:25 P.M. 12:55 31.95 29.73 36.10 28.841 18.18J 32.26 0.95 0.81 36.63 36.78 45.08 0.5811 0.58lJ 0.518 162.04 107.30 84.45 84.96 113.13 l%Hrs 2:25 A.M. 11:27 P.M. 12:27 37.58 34.88 0.78 46.48 0.518 115.24 113.14 E. P. D. B. 4/1/U 74.92 Preliminary 2d Hr. P. 0. 27.47 24.30 0.82 30.51 0.856 80.60 81.65 3d Hr. P. 0. 1:27 29.66 26.17 0.83 31.75 0.830 86.91 81.50 4th Hr. P.O. 2:27 28.13 25.35 0.81 32.87 0.900 83.60 85.98 BthHr. P. 0. 3:27 28.83 25.89 0.81 33.39 0.577 86.11 82.75 6th Hr. P. 0. 4:27 A.M. 11:05 P.M. 12:05 27.12 23.86 0.83 32.98 0.577 79.61 83.6S E. P. D. B. 5/8/14 74.75 Preliminary 2d Hr. P. 0. 30.55 23.41 0.95 32.59 0.604 80.53 76.35 3d Hr. P. 0. 1:05 30.91 24.28 0.93 33.55 0.604 83.08 79.08 4th Hr. P. 0. 2:05 29.37 22.49 0.95 32.48 0.604 77.33 75.63 BthHr. P.O. 3:05 A. M. 30.28 22.06 1.00 32.22 0.604 76.47 76.46 E. P. D. B. 5/15/14 75.02 Preliminary 10:60 2d Hr. P. 0. 11:60 P. M. 29.60, 22.91 0.94 29.06 0.B34 78.74 77.76 Sd Hr. P. 0. 12:50 31.35 22.12 1.03 30.02 0.534 77.26 80.09 4th Hr. P.O. 1:50 31.07 24.04 0.94 30.73 0.534 82.67 80.28 BthHr. P.O. 2:50 29.95 22.21 0.98 30.87 0.534 76.96 79.99 6th Hr. P.O. 3:50 A.M. 28.46 22.57 0.92 30.46 0.534 77.11 75.02 — Data in Hourly Periods Direct Oalo- rlmetry Oal. Beetal Temper- ature, 0. Av. Pulse Work- Adder, Cm. Non- Pro- tein B. Q. Per Cent. Calories from Calories Per Hour Bemarks Prot. Pat Garb. Per Kg. Per Sq.M. 37.26 78.95 37.30 0.87 IS 37 45 0.92 32.07 Basal. 82.80 87.25 62 — 0.74 15 77 8 1.08 37.61 Basal. 94.21 86.51 37.28 37.20 88 0.75 11 12 77 12 1.20 1.11* 41.72 38.46* At 11:63 a. m., 115 gm. commer- cial glucose. 92.88 87.17 36.88 0.96 13 U 76 1.03 35.84 78.09 36.90 0.78 18 62 20 1.13 38.63 Basal. 72.10 36.91 59 0.88 20 33 47 0.98 33.19 Basal. 87.12 83.46 36.84 36.87 57 64 0.94 0.91 21 19 16 25 63 56 1.10 1.18 37.13 39.97 At 11:38 a. m., 115 gm. commer- cial glucose. 85.60 36.98 0.91 19 26 65 1.15 39.04 84.64 36.99 86.96 60 .... 0.93 20 19 61 1.11 37.89 62.89 36.81 57 22 0.83 19 47 34 0.99 33.95 Basal. 77.00 36.80 65 13 0.85 19 41 40 0.97 33.45 Basal. 74.42 36.98 .. 10 0.87 19 36 45 0.95 32.46 Basal. 72.90 36.84 36.75 66 15 1.03 19 81 1.05 36.08 At 8:55 a. m., 230 gm. commer- cial glucose. 82.51 84.53 26.84 36.95 63 60 17 14 1.02 19 81 1.09 37.38 82.50 79.32 37.01 37.00 68 60 16 24 . 0.99 19 2 79 1.07 36.64 36.91 110.72 36.88 54 30— 0.82 19 61 30 0.96 32.86 Basal. 116.62 36.99 56 37— 0.78 18 62 20 1.03 35.29 Basal. 84.05 36.84 36.91 57 24— 0.83 28 42 30 1.07 36.79 At 9:64 a. m., protein meal (10.5 gm. N). 77.92 36.89 57 28— 0.83 25 43 32 1.16 39.72 86.71 36.93 58 30— 0.81 29 46 25 1.12 38.21 81.62 36.94 57 26— 0.81 18 53 29 1.15 39.36 88.88 37.04 36.66 68 33— 0.83 19 46 35 1.06 36.39 75.09 83.22 36.67 36.78 61 61 14.1 23.5 0.99 0.96 20 19 3 11 77 70 1.08 1.11 36.86 38.02 At 10:05-10:07 a. m., 200 gm. dextrose. 73.61 36.78 61 18.8 0.99 21 2 77 1.03 35.39 76.05 36.79 36.69 62 26.0 1.06 21 •• 79 1.02 35.00 78.83 78.30 36.73 36.73 55 58 19.6 22.5 0.97 1.09 :is 18 8 74 82 1.05 1.03 35.95 35.28 At 9:50-9:53 a. m., 200 gm. dextrose. 79.13 81.32 36.73 36.76 59 59 33.1 21.8 0.97 1.03 17 18 8 75 82 1.10 1.03 37.75 35.14 (Carbohydrate breakfast at 6:15 a. m.). 72.36 36.74 57 34.0 0.95 18 15 67 1.03 35.21 * Estimated from CO2. TABLE 2.- Subject Date Weight Kg. Period End ol Period 002, Gm. 02 Gm. 10:50 11:60 P.M. 12: BO A.M. 9:02 23.92 23.85 21.08 21.88 10:02 22.80 11:02 P.M. 12:02 22.92 22.59 1:00 2:00 14.86 41.521 3:00 23.63 21.08J 4:00 A.M. 9:46 22.73 25.27 10:45 21.92 11:45 P.M. 12:45 22.05 21.08 1:46 21.86 2:45 A.M. 9:42 22.03 10:42 26.15 21.59 11:42 A.M. 10:10 27.42 20.98 11:10 P.M. 12:10 20.53 19.95 18.73 17.40 1:10 22.44 20.07 ■ 2:10 18.34 18.05 3:10 22.13 20.71 4:10 A.M. 11:14 P.M. 12:14 19.36 23.43 19.23 22.62 1:14 24.27 22.67 2:14 26.84 25.11 3:14 26.44 25.11 4:14 24.86 23.21 5:14 A.M. 11:20 P.M. 12:20 26.25 21.12 24.79 19,51 1:20 21.37 19.62 2:20 A.M. 11:02 P.M. 12:02 21.07 22.39 19.97 20.71 1:02 A.M. 10:52 22.14 18.98 11:52 P.M. 12:52 29.94 30.30 23.73 22,03 1:52 30.65 21.90 E. Q. H2O, Gm. Urine N Per Hour, Gm. Indirect Oalo- rimetry, Oal. Heat Elimi- nated, Cal. E. F. D. B. 6/18/14 P. C. G. .. 3/17/13 P. C. G. .. 3/17/13 P. C. G. .. 4/22/13 E. H. H. .. 3/19/13 Louis M. . . 3/26/13 Louis M. .. 3/28/13 John L. ... 3/26/14 L. C. M. 5/4/14 L. 0. M. 5/6/14 73.70 64.82 53.49 70.94 60.98 Preliminary 1st Hr 2d Hr Preliminary 1st Hr 2d Hr 3d Hr Preliminary 2d Hr. P. C. 3d Hr. P. C. 4th Hr. P. C. Preliminary 1st Hr 2d Hr 3d Hr 4th Hr 5th Hr Preliminary 1st Hr 2d Hr Preliminary 1st Hr 2d Hr 3d Hr 4th Hr 6th Hr 6th Hr Preliminary 3d Hr. P. C. 4th Hr. P. 0. 6th Hr. P. C. 6th Hr. P. C. 7th Hr. P. C. 8th Hr. P, C. Preliminary 1st Hr 2d Hr 3d Hr Preliminary 1st Hr 2d Hr Preliminary 2d Hr. P. C. 3d Hr. P. C. 4th Hr. P. C. 0.83 0.79 0.85 0.78 0.88 0.95 0.80 0.83 0.81 0.74 0.78 0.73 0.75 0.78 0.78 0.77 0.78 0.77 0.79 0.79 0.77 0.79 0.85 0.92 1.00 1.02 28.03 28.08 17.77 19.69 20.90 23.05 .30.51 26.08 25.40 26.85 26.26 28.59 30.09 27.90 28.93 28.92 26.95 28.10 25.73 27.36 25.85 24.08 29.15 34.80 34.38 35.42 34.71 26.77 24.66 24,01 28.32 27.28 33.43 32.38 32.94 0.530 0.630 0.491 0.491 0.491 0.491 0.491. 0.491 0.522 0.522 0.622 0.622 0.522 0.522 0.703 0.695 0.970 1.014 1.138 1.112 0.363 0.363 0.363 0.634 0.534 0.578 0.678 0.578 70.29 72.38 139.35 69.69 73.54 72.78 61.91 57.99 66.57 58,71 68.20 62.51 73.76 74.44 82.02 81.70 76.38 80.53 64.65 65,10 65,85 68,34 63.67 81.05 76.45 76.21 67.48 69.37 64.43 59.16 60.70 62.52 58.96 61.94 62.60 63.33 68.43 66.50 69.27 64.64 64.44 71.00 66.51 64,89 75.48 79.07 77.18 83,35 81.28 66.00 68.26 66.72 71.73 70.36 73.19 74.95 77.37 — (Continued) Direct Calo- rlmetry Oal: Bectal remper- ature, 0. Av. Pulse Work- Adder, Cm. Non- Pro- tein B.Q. Per Cent. Calories from Calories Per Hour Remarks Prot. Pat Oarb. Per Kg. Per Sq. M. 36.76 67.14 36.76 57 9.8 0.83 20 46 34 0.95 32.48 Basal. 70.23 36.78 37.03 67 18.2 0.79 19 58 23 0.98 33.45 58.83 55.75 37.15 37.11 1.04 0.99 30.75 32.45 Basal. Profound sleep during second and third periods. O2 leak. 66.99 37.06 37.02 1.01 31.43 66.85 60.53 37.17 37.00 0.86 19 39 42 1.18 .1.07 36.87 33.39 At 12 m., plate of oatmeal. O2 leak. 60.83 36.95 37.04 0.78 19 61 20 1.08 33.69 57.28 37.03 74 1.04 32.22 Basal. O2 leak. 62.68 37.07 68 1.14 35.25 60.60 37.04 64 1.10 34.08 68.15 36.94 66 1.06 32.71 64.88 36.87 36.76 70 1.18 36.49 69.22 36.S2 1.19 38.12 Basal. Urine not obtained. 70.31 36.86 37.18 1.19 37.73 58.39 37.07 0.80 22 66 24 1.20 36.23 Basal. 61.88 37.04 0.84 24 40 36 1.12 33.92 76.26 37.15 0.82 21 49 30 1.29 38.95 59.27 37.00 0.72 24 73 S 1.14 34.35 70.95 37.08 0.77 20 63 17 1.32 39.91 62.47 36.98 37.10 0.71 22 77 1 1.21 36.68 74.89 81.49 37.28 37.43 0.74 0.77 25 26 68 69 7 16 1.39 1.40 42.20 42.59 8:25-9:25 a. m., 725 gm. choppea beef = 23.93 gm. N -h lOO gm. fat. 74.67 37.36 0.76 .31 55 14 1.54 46.92 78.43 37.41 0.75 33 68 9 1.54 46.74 30.09 37.38 0.76 40 49 11 1.42 43.12 SI .96 37.39 37-11 0.75 37 54 9 1.51 46.07 52.70 86.89 61 13.04- 0.78 15 62 23 0.91 30.64 Basal. 68.56 36.94 55 13.0-1- 0.79 15 61 24 0.92 30.85 62.04 36.88 36.94 57 38.7 0.76 15 69 16 0.92 31.21 66.95 36.85 74 22.0-1- 0.78 21 69 20 1.15 36.41 Basal, 73.48 36.92 36.84 70 18.2 0.86 22 37 41 1.07 33.87 65.74 36.70 85 19.1 0.95 19 15 66 1.33 42.48 9:50-9:63 a. m., dextrose, 200 gm. 73.60 36.68 82 30.1 1.06 20 80 1.25 40.07 82.69 36.79 79 38.2 1.08 20 80 1.25 39.94 58 CLINICAL CALORIMETRY The results are expressed in terms of grams and calories per hour, since this is the length of period used in the Cornell and Sage calorim- eters and is the nearest unit of the length of the actual experimental period used in most of the modem machines. DISCUSSION OF RESULTS As explained in Paper 1 of this series, the determination of the heat production by the methods of direct and indirect calorimetry have been found to give identical results in the work of Rubner, Atwater and Benedict, Lusk and his coworkers. Rubner demonstrated this on the dog in long periods, Atwater and Benedict on man at rest and at work, Lusk on dogs in hourly periods and Rowland, in Lusk's laboratory, on babies both normal and atrophic. To this list may be added the work of Armsby^^ on cattle in twenty-four-hour experiments and the work of Carpenter and Murlin^" who studied the metabolism of women before and after confinement, in Benedict's laboratory. A comparison of the figures for direct and indirect calorimetry obtained in Benedict's calorimeter shows excellent agreement in the two- and three-hour periods. Out of a total of twenty-eight periods, the two methods were within 5 per cent, of each other in seventeen, while only six showed a disagreement over 10 per cent. Table 3 gives in parallel columns the calories in each of our experi- ments as measured by the methods of direct and indirect calorimetry. The totals of all the experiments show that the two methods come within 0.17 per cent, of each other. Even when we consider periods as short as one hour, the agreement may be striking. On the normal control, E. F. D. B., there were a total of 26 one-hour periods. In 17 of these the methods of direct and indirect calorimetry agreed within 5 per cent., in 6 periods within 6 to 9 per cent., while three isolated periods showed a disagreement of 11, 12 and 16 per cent., respectively. Work with the .Sage calorimeter on normal controls and on patients with a large variety of diseases has shown that in a total measurement of 27,632 calories the direct calorimetry gives a figure only 1.62 per cent, lower than the indirect. There is, therefore, no reason to believe that in long periods, or in the average of a number of short periods, there is any essential difference between the two methods. As will be shown later, there is good reason to believe that indirect calorimetry gives the more accurate results in short periods. There are two methods of calculating the indirect calorimetry, both of which involve factors that change with the respiratory quotient. 19. Armsby: Food as Body Fuel, Pennsylvania State College Agricultural Experiment Station, Bull. 126. 20. Carpenter and Murlin: The Energy Metabolism of Mother and Child Tiist Before and Just After Birth, The Archives Int. Med., 1911, vii, 184. 1 PM fLH PM ^ eg g n A s 1 11 1 11 Ti a CO a CO -a 1=1 03 ^ 1 1 c3 a iz; g a 3 ■3 s M S dj ?3 Pi o a 1 ^ <3S 0) a 1 1 II a D ift a 1 OS taO a o -a *t-i i § S 03 § g t-, s C3 i J3 1 OS 1-1 i 03 i 03 OS OS at OS 03 m 03 as m a ■0 i 03 03 ■3 1 SI 2| ■3 m ca 1 oS OJ 3 » i 1 1 00 5 1 1 ^ &H g r ^■L S rg g w g g tH Metliod of Direct Oalor- imetry Surface Temper- ature CO CO •>* CO 83 iS s r-t S3 -•§ olibad 10 CO f^ r-( S ■^ 00 ■* t- CO CO CO CO 2? s ■i-al s g a i 1 S3 s § Ob CQ CO iH : S i S g s ^ 1 sil' i"«a s in S s g S s Ift r-l S £ §3 s s s "» g i>- a Eg <£) r? ^- ^1 $; Si a-rg w "' ^ '■■' •ai fH IH ■^ ■* ^ * 1 s ^ Varia- tion from Aver- age Normal Basal 34.7 + CO -1- 1 1 10 : 1 01 1 - « : 1 03 + to -1- : 7 + Calo- ries per Sq. M. per Hour 00 s s OS s s 1 S3 CO So & 10 ■* S 00 604^ *S bjn ta CO l> 00 ^- s CO CO S ^ 51 ? S !2 £2 s g s g S s g s 3 CO M CO CO CO CO CO CO CO CO ■-* •V rf CO CO r- cT ID ^ OQ U? 00 J> t- eq dj so s' <£> ■-* «o CO CO CO CO 10 10 CO ^ U3 lA m CO CO "* CO CO CO CO 10 10 *» w ■ 1 'S h4 6 d a a m B Hi a Si d OS 1 w h w H *-> hJ 60 CLINICAL CALORIMETRY The first is the standard method of Zuntz and his associates, based on the liters of oxygen consumed, which are multiplied by a factor that increases about 8 per cent, as the quotient rises from 0.72 to 0.97. The second method is based on the liters of COo produced, the figure for which is multiplied by a factor which decreases 24 per cent, as the TABLE 4. — Heat Production' of Normal Men, Ages 20 to SO. Com- parison OF Calories per Kilogram and per Square Meter Weight, Kg. Calories per Eilogram per Hour Calorics per Sq. Meter per Hour Percentage Variation from Average Calories per Sq. Meter per Hour According to New Surface Area Formula Per Cent. Variation from Average Subject Calories per Kg. Calorics per Sq. Meter F. G. B.* 83.0 1.01 35.8 — 4 + 6 .... G. L 78.4 74.3 1.00 0.95 34.8 32.4 — 5 — 9 -1- 2 — 6 40.7 -f2 F. A. E.* E. P. B. B. .. 74.3 1.00 34.1 — 5 39.8 —0 John L 70.9 0.92 30.9 —12 —10 J. J. C* 67.6 0.96 31.7 — 8 — 7 J. B.* 66.0 1.00 32.8 — 5 -* E. H. H 62.0 1.18 37.9 -1-14 -1-11 40.9 -1-3 L. C. M 69.5 1.11 35.1 -1- 6 + 3 40.5 -1-2 F. C. G 54.8 1.10 34.2 -f 5 37.7 —5 Louis M 51.7 1.21 36.7 -fl6 -1- 7 T. M. C* 49.0 1.13 33.8 ■f 8 — 1 Average 1.06 34.2 ±8.1 ± 4.6 39.9 ±2.4 79 normal men in groupst 8 weights 75-85 1.01 36.2 — 7 + 2 20 weights 66-76 1.02 34.1 — 6 — 2 41 weights — 65-65 1.09 34.7 -1- 1 .... 10 weights 46-66 1.18 35.5 -1- 9 + 2 Average 1.08 34.7 ± 5.8 ± 1.5 * Determinations made by Benedict and Joslin.'^' t Taken largely from work of Benedict, Emmes, Eotb and Smith,!" quotient rises from 0.72 to 0.97. Tables for this latter calculation are given by Benedict and Talbot,^^ who prefer this method in using an apparatus in which they consider that for short periods the determina- tion of the carbon dioxid is more exact than the determination of 21. Benedict and Talbot : Studies in the Respiratory Exchange of Infants, Am. Jour. Dis. Child., 1914, viii, 1 ; The Gaseous Metabolism of Infants, Car- negie Institution of Washington, Pub. 201. FRANK C. GEPHART— EUGENE F. DU BOIS 61 oxygen. It is true that in the closed circuit type of apparatus the measurement of the oxygen is subject to many corrections for changes in the barometer, temperature, moisture, etc., and that it is liable to a plus error in the case of leaks. This error affects the quotient and pro- duces such a change in the CO2 factor that one usually obtains better results by basing the calculations on the oxygen. This is brought out clearly in Table 5, which gives a comparison of the methods of calcu- lating the heat production from the oxygen and from the CO2, showing the errors in the results arising from various assumed errors in the measurements. It will be noted that in the great majority of the cases TABLE S. — Comparison of Methods of Calculation whth Assumed EitRORS IN Measurement of CO2 and O2 COa O2 Calorific Value 1 Liter ol CO2 Calorific Value 1 Liter of O2 Indirect Calorimetry Based on CO2 Indirect Calorimetry Based on O2 R.Q. Liters As- sumed Error % Liters As- sumed Error % Cal. Per Cent. Change Cal. Per Cent. Change Cal. Per Cent. Error Cal. Per Cent. Error 12.94 15.64 0.83 5.829 4.807 75.40 76.17 12.94 17.20 -HO 0.75 6.319 -H8.4 4.708 —2.1 81.74 +8.4 80.98 +7.7 14.23 -HO 15.64 0.91 5.424 -7.0 4.904 +2.0 77.18 +2.4 76.70 +2.0 12.94 16.42 -f-5 0.79 6.062 +i.O 4.768 —1.1 78.44 +4.0 78.13 +3.9 13.59 +5 15.64 0.87 5.617 —3.6 4.855 +1.0 76,33 +1.2 75.93 +1.0 12.29 —5 16.42 +5 0.75 6.319 -f8.4 4.708 —2.1 77.66 +3.0 77.31 +2.8 13.59 H-5 14.86 —5 0.91 5.424 —7.0 4.904 +2.0 73.71 —2.2 72.87 —3.1 12,94 14.86 —5 0.87 5.617 —3.7 4.856 +1.0 72.68 —3.6 72.15 —4.0 cited the error from the use of the oxygen factor is smaller than that from the COv. Even with a plus error of 5 to 10 per cent, in the oxygen and no error in the CO2, the results obtained by using the oxygen are the better, since the minus change in this factor compen- sates for part of the error. In the two instances shown, in which the results obtained by the use of the CO2 factor are closer to the theory than those obtained by the use of the oxygen factor, it will be noted that there is a minus error in the oxygen. This is the least frequent of all the errors. Many investigators in seeking for an index nf the heat production express the results in grams or cubic centimeters of CO2, and compare the elimination of thi.s gas in different individuals, apparently with the impression that they are comparing the actual total metabolism. As we have seen above, a man eliminating, say, 3.13 c.c. CO2 per kg. per min- 62 CLINICAL CALORIMETRY ute might have a heat production 24 per cent, higher than another man eliminating the same amount of COj whose respiratory quotient was at the other end of the scale. If one uses the oxygen consumption the possible error from this source is diminished to 8 per cent. Since it is such an easy calculation to determine the actual calories by using the oxygen figure and the respiratory quotient, it seems inexcus- able to leave the results at a stage which might give false impressions. It is only in special investigations on the ventilation of the lungs, etc., that the amounts of the gases themselves are of any direct interest. In most experiments it is the actual calories that need to be determined. Experience has shown that with careful technic the indirect calorim- etry in hourl;^ periods remains fairly uniform in fasting experiments and shows regular curves in experiments after food. The direct calo- rimetry in hourly periods is a matter of greater technical difficulty on account of the fact that the human body is poorly constructed for accurate thermal measurements. As was shown in Paper 1, a rise or fall of 1 degree centigrade in the average temperature of the body means a storage or loss of about 58 calories af the man weighs 70 kilo- grams. This is based on the assumption that the specific heat of the body is 0.83, a figure which has been accepted for many decades, although without satisfactory experimental support. Rubner^^ has found that the specific heat of lean flesh is 0.828, of fatty tissue 0.53 and of pure fat 0.45. Rosenthal"^ at an earlier date had made the following determinations: compact bone 0.30, spongy bone 0.710, defibrinated blood 0.927, dried muscle 0.330. Using these figures and the figures for the average composition of the body as given by Vierort^* one obtains a specific heat of approximately 0.77. A body rich in fat would, of course, approach the figure 0.45 and one rich in water would approach 1.00. Theoretically, one should change the specific heat each time a subject drinks water or voids. This latter would be a matter of small importance, but in the case of a very obese person one-half of whose weight consisted of fat, the true specific heat would not be far from 0.64. In normal subjects the temperature changes in hourly periods are small and according to the work of Benedict and Slack,^^ the temper- 22. Rubner: Kalorimetrie, Tigerstedt's Handbuch der physiologische Methoden, i, 170. 23. Rosenthal : Ueber die specifische Warme thierische Gewebe, Arch. f. Physiol., 1878, p. 215. 24. Vierort: Daten und Tabellen. Jena, 1893, p. 249. 25. Benedict and Slack: A Comparative Study of the Temperature Fluctua- tion in Different Parts of the Human Body. Carnegie Institution of Wash- ington, 1911, Pub. 155. PRANK C. GEPHART— EUGENE P. DU BOIS 63 ature curves in different parts of the body are nearly parallel. Lusk''* and his coworkers did not find this to be the case in the dog after the ingestion of large amounts of food since this caused a greater rise in surface than in rectal temperature. When one considers the mechan- ism of the regulation of body temperature in fever it becomes evident that the rise in surface temperature follows that of the internal tem- perature. Every clinician has felt in some patients, particularly those seriously ill, the extremities growing colder and colder while the internal temperature is rising and, conversely, has felt the surface grow warmer while the temperature is falling, demonstrating the fact that the two are not always parallel. It was on account of these considerations that the surface ther- mometers described in Paper 2 were used after May, 1913, the two units of the surface thermometer being strapped over the right and left pectoralis major as near as possible to the heart and dome of the liver. They were covered with a thick layer of cotton in an effort to obtain the temperature of the subcutaneous tissue rather than that of the naked skin. After March 12, 1914, a second surface thermometer was added and its two units placed in various parts of the anterior surface of the thorax and abdomen and also in the axillae. The results have been confusing and difificult to interpret, but they have indicated clearly that the different parts of the body do not show parallel tem- perature curves. A fruitless search has been made for some part of the body which will give a true index of the mean temperature change. In the majority of all the experiments the rectal temperature was the more satisfactory, but in typhoid fever the surface gave better results. The method of investigation was as follows : In a total of eighty-five experiments satisfactory rectal and surface temperature measurements were made. Twenty-eight of these experi- ments were on typhoid fever patients. For the reasons above stated the heat production as determined by the method of indirect calorim- etry was considered to be the true heat production, and the results of the direct calorimetry as calculated by three different methods were compared with this as shown in the table below. In all three methods the figure for the heat eliminated from the body was, of course, the same. To obtain the heat produced, the heat stored in or lost from the body, as determined by each of the two measurements, and by a mean of the two, has been added to or subtracted from the heat eliminated. It will be seen from Table 6 that in the total of 85 experiments the rectal temperature gave the best results, approximating the theoretical more closely than either of its competitors in 36 cases, coming within 5 26. Williams, Riche and Lusk: Metabolism of the Dog Following the Inges- tion of Meat in Large Quantity, Jour. Biol. Chem., 1912, xii, 349. 64 CLINICAL CALORIMETRY per cent, in 62 cases and involving a total error of only 0.90 per cent. While the surface temperature gave the best results in 24 cases, it showed an error of over 15 per cent, in 5 cases and did not prove as reliable as the mean of surface and rectal. In typhoid fever the honors were more evently divided and all three methods gave surprisingly good results in spite of the large changes in body temperature sometimes encountered. The surface temperature alone gave the best results in 13 of the 28 experiments and also the lowest total error. TABLE 6.— Comparison of Surface and Rectal Temperatures as an Index of Average Body Temperature; Percentage Differences BETWEEN Indirect Calorimetry and Direct Calorimetry Calculated According to Three Methods Percentage Difference in Individual Experiments to 6 5 to 10 10 to 15 15+ Total difference Number giving results nearest to indirect Number of Experiments Falling in Each Group Twenty-Eight Typhoid Experiments Eectal Tempera- ture Alone 18 » 1 —1.32 8 Surface Tempera- ture Alone 18 9 1 —1.17 13 One-half Bectal, One-half Surface 18 10 —1.24 Eighty-rive Experiments in Various Diseases, Includ- ing the Twenty-Eight Typhoid Observations Rectal Tempera- ture Alone Surface Tempera- ture Alone 62 41 19 28 i 11 5 — 0.9O —1.46 46 24 One-half Bectal, One-half Surface 53 27 4 1 —1.18 15 As a result of the above analysis the rectal temperature has been adopted as the standard indicator of the average body change in hourly periods, but with a full realization of its limitations. In many experi- ments, particularly in those with rapidly changing temperature, better results would be obtained by using the surface temperature, but surface thermometers are more easily displaced than rectal and are not so reHable in the long run. Theoretically, one would obtain the best results by the use of many thermometers placed in the rectum, axillae, groin, on the surface of the body in many areas, giving each measurement an estimated weight, and then calculating the mean temperature change. Our attempt to do this in a small way by giving the rectal and surface equal weights did not lead to better results. For many reasons it seems advisable to attach as little apparatus as possible to the subject, and it is FRANK C. GEP HART— EUGENE F. DU BOIS 65 doubtful if the use of many thermometers at one time will ever become a standard method. There may be several reasons why these results are not in accord with the conclusion of Benedict and Slack. Working with normal sub- jects who showed comparatively small fluctuations in body tempera- ture, they made many measurements at different depths in the rectum and vagina and found that while there was a sharp fall in temperature between a point 7 cm. within the rectum and a point just within the anus, nevertheless the temperature of points at different depths remained parallel, though at a different level. Temperatures taken in the well-closed axilla and groin were also parallel with the rectal. The mouth was found to be an unsatisfactory place to obtain the mean body temperature. Considerable difficulty was experienced in obtaining satisfactory measurements of the surface of the body and of the hands, and the writers speak of the difficulty of devising a ther- mometer that will be shielded so that it may assume the body tem- perature and yet not interfere with the natural liberation of heat. As we have mentioned above, our surface thermometers were covered with a thick layer of cotton wool and represented a subcu- taneous rather than a surface measurement, and therefore not com- parable to the axillary, groin and shallow rectal measurements of Benedict and Slack. All of the latter are in the neighborhood of large blood?-vessels and might be expected to rise and fall simultaneously. All of this brings us back to the desirability of using the method of indirect calorimetry as the standard and checking its accuracy by the level of the respiratory quotient and the agreement with the direct calorimetry. All the evidence of this laboratory shows that the quotient rises and falls in regular curves in rest experiments when hourly periods are used. If, therefore, in any experiment the quotient shows a variation not accounted for by recent food, we suspect an error and usually find it compensated for in the next period. This error is almost always found in the calculation of the residual oxygen in the box at the close of the hour. Luckily there is an automatic correction in the method of calculating the indirect calorimetry. If in the first hour the oxygen estimation be too high, the quotient will be too low, and consequently the factor by which the oxygen is multiplied will be diminished. In the second hour when the error has been com- pensated for, the oxygen estimation will be too low, the quotient too high and the factor increased. This is another reason why the indirect calorimetry is more reliable than the oxygen consumption as an index of metabolism. The method of direct calorimetry serves as an invaluable check, and if in any two- or three-hour experiment during which the body 66 CLINICAL CALORIMETRY temperature changes less than half a degree, the methods of indirect and direct calorimetry do not agree within 5 per cent., one should suspect a defect in the calorimeter. If in the next experiment a similar divergence be found, an alcohol check should be made and the error located. If one can prove that the error was due to any one par- ticular determination, all calculations affected by this must be rejected as in the two experiments on F. C. G. It is by no means necessary to reject the results of the method of calorimetry not affected by the error. There is only one determination that enters into both methods of calculation, but an error in this would cause the two methods to diverge and not to err in the same direction. If through gross careless- ness the first sulphuric acid bottle were allowed to gain so much weight that water vapor passed by into the CO, absorber, the direct calorimetry would be too low and the indirect too high, since both the quotient and the oxygen factor would be increased. DETERMINATION OF THE AVERAGE NORMAL The selection of the proper normal base line is a matter of extreme difficulty. It is also a matter of prime importance in determining whether or not a patient or group of patients shows a total metabolism which is above or below the normal limits. In dealing with patients suffering from acute diseases it is sometimes possible to wait until the patient recovers completely and then determine his normal heat pro- duction. This is not always practicable and even when it can be done one has no guarantee that the metabolism has returned to normal unless several measurements at considerable intervals be made. In the case of patients with chronic diseases this method is out of the question. The method most commonly used is that of selecting groups of normal controls to correspond as nearly as possible to each indi- vidual patient. This of course is the ideal method if many controls be selected, but it is extremely doubtful if any investigator up to the present date has been able to gather enough satisfactory controls for each patient. The recent work of Benedict, Emmes, Roth and Smith" may remedy this, on account of the large number of individuals whose metabolism was determined. Even with this wealth of material one may err if allowed to pick out a small group. The individual variation is large, as one can see from a careful study of the fiotires. It is, perhaps, unfair to draw many deductions before the full descrip- tion of the subjects is published, but we may rely on the statement that all were in presumably good health. The average heat production of the 89 men was 833 calories per square meter per day or 34.7 calories per square meter per hour. The average heat production of the 12 men studied in the bed calorimeters and grouped in Table 4 was 34.2 calories FRANK C. GEPHART— EUGENE F. DU BOIS 67 per square meter per hour. This striking agreement is another proof that the Benedict universal respiration apparatus gives results which are almost identical with the calorimeter. For this reason the 7 sub- jects examined by us have for purposes of calculation been grouped with the 89 of Benedict, Emmes, Roth and Smith. In order to rule out those who were distinctly over- or underweight, the subjects were all plotted in a curve, the height forming the abscissa and the weight the ordinates. All but 9 of the subjects could be grouped between two lines not very far apart. Of the 9, W. S., O. F. M., Prof. C, H. F., F. E. M. and F. A. R. were evidently much heavier in proportion to their height than their fellows, and for this reason excluded from the averages. It is interesting to note that their average heat production was 31.5 calories per square meter. Two of the 9, R. A. C. and B. N. C, were evidently very light in proportion to their height. E. P. C. came just outside the line, but so close to it that he has not been excluded from the averages. All those over 50 years of age were arbitrarily excluded and also those under 20 years. To the remaining 72 were added the normal controls of the present paper. This process of exclusion and addition left a fairly homogeneous total of 79 whose average metabolism was 34.7 calories per square meter per hour, or exactly the same as that of the original 89 before the addition of 7 and the exclusion of 17. These 79 have been divided into four groups according to body weight in Table 4. If we plot the heat production of all the subjects according to surface area, the range of individual variation becomes apparent. Of the total 79 we find 40 within 5 per cent, of the base line drawn at the average figure 34.7, 28 are from 5 to 10 per cent, from the average and 11 are more than 10 per cent, from the average. Of these, 6 were between 10 and 14 per cent, above, and 5 were between 10 and 15 per cent, below. This means that when we speak of a normal average we must remember a normal variation of at least 10 per cent, above and below and realize that in about 14 per cent, of the normal men the variation may be plus or minus 10 to 15 per cent. One cannot help but feel that most of the cases showing a variation of more than 10 per cent, from the average will be found to present some distinct cause for the unusual metabolism, such as an unusual degree of muscular devel- opment or muscular disuse or an unsuspected disturbance of the thyroid secretion, or the ipild infection with tuberculosis which all of us pass through at some time in our lives. At any rate, one can be fairly certain that if the total heat production be 15 per cent, from the average it is distinctly abnormal, and if it be more than 10 per cent, from the average it must be regarded with great suspicion. 68 CLINICAL CALORIMETRY It may be argued that some of the variation may be due to differ- ences in body weight. If we study the 24 normal subjects in the table we have been considering, whose weights are between 60 and 65 kg., the same variation is apparent. Of the 24, only 13 are within 5 per cent, of the average, S are between 5 and 12 per cent, above and 6 are from 5 to 10 per cent, below. If one investigator chanced to select this last group of 6 for his controls his average would be about 15 per cent, lower than if he selected the group of 5 cases with high metabolism. This of course is an extreme instance. It may still be argued that the factor of height must be considered. In the same table we find an exceedingly homogeneous group of 7 men whose weights are between 60.1 and 60.5 kg. and whose heights are between 171 and 175 cm. Even in this group there is a difference of 13 per cent, between the highest and the lowest and a difference of 9 per cent, between the averages of the highest 4 and the lowest 3 in this group. This somewhat lengthy discussion is intended to show the chances of serious error in selecting any small group of normal controls to compare with a pathological case. One cannot say just how large the group should be, but it is safe to say that it must exceed 5, should exceed 10 and if possible, 50. It is obviously much better to use all the normal controls so far studied and let personal selection play no part. This can be done by basing all comparisons on the average heat production per square meter of body surface. In Table 4 we find a comparison of the heat production calculated according to surface area and according to weight. A study of the percentage variation from the average shows clearly that all four weight groups are within 2 per cent, of the mean heat production per square meter of body surface. In other words, one can determine the average normal by this method by using a group of individuals of any weight within ordinary limits. On the other hand, the figures per kilogram of body weight show the customary diminution as weight increases and there is a difference of 16 per cent, between the heavy group and the light group. In other words, there is no such thing as an average calories per kilogram for normal men, but only a normal average for each weight. To iind the normal for a given man by this method one must consult a curve. To find the normal for a given man by the method of surface area one needs only to remember the figure 34.7. Shortly after the experimental work on the normal controls was completed it seemed advisable to investigate the accuracy of Meeh's formula and if possible devise a new formula which could be applied to individuals who depart materially from the average body form. Five subjects were measured and it was found that there was a con- FRANK C. GEPHART— EUGENE F. DU BOIS 69 sistent plus error in Meeh's formula which, in the case of a very fat woman, amounted to 36 per cent. In two of the normal controls whose heat production had been determined, the surface area was actually measured and the errors in Meeh's formula were found to be as follows: E. F. D. B., + 14 per cent., R. H. H., + 7 per cent. In three others, G. L., F. C. G. and L. C. M., the surface area was cal- culated by the new formula and fouijd to be, respectively, 14.5 per cent., 9.3 per cent, and 13.4 per cent, lower than the results obtained by Meeh's formula. Since in all four cases the new surface area figures are lower than the old results obtained from Meeh's forrhula, the heat production per square meter of body surface, according to the new formula, would be about 7 to 15 per cent, higher, the average being 39.9. As will be seen in the last two columns of Table 3, the new results are somewhat more uniform than the old results, but are on a higher level, and it is quite possible that it may be necessary to adopt a higher normal average than 34.7. The general principle of Meeh's formula seems to be correct for individuals of average shape, and for this reason it may be used as the standard in large groups of sub- jects. In the case of very fat individuals, Meeh's formula would give a figure for the calories per square meter which would be much too low. It seems probable that some of the variations from the average normal figure per square meter can be explained by the varia- ble error in the old formula. Future use of the new formula will, it is hoped, clear up this point. The details of the new method will appear in the following paper. There is but little evidence against Rubner's law that metabolism is proportional to surface area. As we have seen there is a plus error in Meeh's formula for determining surface area. Nevertheless, in a group of normal men of approximately average build between the weights of 45 and 85 kilograms the metabolism is, on the whole, pro- portional to the surface area as determined by Meeh's formula. When we come to extend Rubner's law to babies and dogs studied in the modern types of apparatus with the modern scrupulous care to exclude the effect of muscular work, we find the figure for the calories per square meter changed, yet not nearly so much changed as the figure for the calories per kilogram of body weight. Murlin and Hoobler^" have demonstrated that in a group of infants between the ages of 2 and 12 months the metabolism is proportional to weight rather than to surface area, and have pointed out the effect of age, showing that among infants of the same age the metabolism is proportional to the 27. Murlin and Hoobler : The Energy Requirement of Normal and Marasmic Children with Special Reference to the Specific Gravity of the Child's Body, Proc. Soc. Exper. Biol, and Med., 1914, xi, 115. 70 CLINICAL CALORIMETRY surface area. Benedict and Talbot^^ believe that the metaboHsm ' of infants is not proportional to surface area, but is proportional to pro- toplasmic mass. Table 7 shows that comparing babies and dogs with adults the method of surface area gives results much closer to the average for men than the method of comparison by weight. It may seem superfluous at this late date to argue at length in support of Rubner's law of surface area, btit this law is becoming the center of an active discussion. The percentage of calories derived from protein in the fasting experiments is a matter of some interest in the discussion of the subject of the toxic destruction of protein. The average figures for the basal experiments on the various subjects are as follows: G. L., 16.5 per cent. ; E. F. D. B., 19 per cent. ; F. C. G., 18 per cent. ; Louis M., 22 per cent. ; John L., 15 per cent. ; L. C. M., 21.5 per cent. To this list may be added the figures for several normal controls from the work of Benedict and Joslin:^° F. G. B., 17.6 per cent.; J. R., 15.6 per cent. ; J. J. C., 15.7 per cent. ; D. B., 21.6 per cent. ; H. F. T., 19.9 per cent. ; Dr. S., 15.5 per cent. ; V. G., 12.7 per cent. ; T. M. C., 14.8 per cent. These figures represent largely the effect of the amount of protein in the diet of the preceding day. They are by no means the figures that would be obtained had the subjects been maintained on af protein minimum for a few days before the experiments. THE EFFECTS OF FOOD The experiments on the effects of food were intended primarily as controls on the effects of similar meals given to patients with typhoid fever and exophthalmic goiter. While the subject of the specific dynamic action of food is one of great interest and importance it was felt that the chief function of the calorimeter in Bellevue Hospital was the investigation of pathological conditions. Consequently, very simple protein and carbohydrate meals which could be given in typhoid fever were the only ones studied, and the study of the effects of fat was postponed. During the season of 1913 commercial glucose containing dextrose 42.37 per cent., dextrin 44.57 per cent, and water 13.50 per cent, was used. This is one of the cheapest of food-stuffs, is readily soluble in water, is not very sweet and on account of its chemical com- position should be rapidly absorbed. It has been found of great service 28. Benedict and Talbot : Studies in Respiratory Exchange of Infants, Am. Jour. Dis. Child., 1914, viii, 1 ; Gaseous Metabolism of Infants, Carnegie Institution of Washington, 1914, Pub. 201. 29. Benedict and Joslin : A Study of Metabolism in Severe Diabetes, Car- negie Institution of Washington, 1912, Pub. 176, p. 103. PRANK C. GEPHART— EUGENE P. DU BOIS 71 in feeding many of the patients and in some ways is preferable to the less soluble lactose. In the season of 1914 chemically pure dextrose was used in order to compare its effects with that of the mixture. The chief protein meal used in typhoid consisted chiefly of casein in the form of cottage cheese and fat-free milk with the whites of two or three eggs and some tgg yolk. It did not make a very palatable mix- ture, but it was consumed by most of the typhoid patients without much complaint and it certainly did them no harm. While it might have been more satisfactory to give meat, it did not seem justifiable until we had more experience with its effects in fever. TABLE 7. — Comparison of Calories per Kg. and per Square Meters OF Body Surface Investigator Subject Calories per Kg. Calories per Sg. M Per Cent. Variation from Average for Men Accord- ing to Calories per Kg. Accord- ing to Calories per Sp.M. Benedict and collaborators Lusk Lusk Lusk Lusk and McCrudden Howland Howland Murlin and Hoobier Benedict and Talbot 79 men Dogl Dog 2 Dogs Dwarf, Wt. 21.3kg. ... Baby 1., Baby 2 Average 6 infants Average 10 normal in- under 1 month Average 11 normal in- fants between 1 and 10 months 1.08 1.65 1.75 1.45 1.21 2.89 3.45 2.69 1.95 2.21 34 7 31.6 82.7 29.8 32.3 39.5 45.7 36.3 25.6 35.B -1-53 -1-62 -1-35 -1-12 -fl68 -f220 -1-150 -I- SI -1-105 —14 — 7 -H4 -)-31 + 5 —26 -I- 2. Two different methods were used in obtaining a base line to repre- sent the metabolism without food. At first the fasting metabolism was determined in the early morning and the food given while the subject was in the calorimeter. This necessitated a sojourn of three or four hours in the box after the food in addition to the two hours before the food. Even normal individuals become tired after three hours of absolute quiet in a calorimeter and it was evident that patients would be restless in such long experiments. Another disturbing factor was the gradual change in the metabolism with the different hours of the day. The method finally adopted has given great satisfaction. It is the method used so successfully by Lusk^ on the dog. The basal metabolism is determined in a two- or three-hour experiment and two CLINICAL CALORIMETRY days later the food is given before the subject is sealed in the box and the metabolism determined during the same hours studied in the fast- ing experiment. The basal metabolism in our experience does not change rapidly enough to make this method inaccurate. The high metabolism in the first experiment on E. F. D. B. was due to restless- ness, and the low metabolism in the first experiment on F. C. G. was due to profound sleep. Between May 17, 1913, and May 18, 1914, the heat production of E. F. D. B. did not vary 3 per cent, in the three TABLE 8. — Increase in Heat Production Following Ingestion of Dextrose Subject Hours After Glucose Per Cent. Bise Extra Calo- ries Extra Calo- ries Irom Combustion ot Carbo- hydrate Speciflc Dynamic Action, Per Cent. G. L.: 100 glucose 0-1 20 15.52 1-2 10 8.16 2-3 3 2.26 E. P. D. B.: 100 glucose 0-1 3 2.63 24.66 11 1-2 11 8.78 22.38 39 2-3 9 6.77 20.41 39 3-4 6 4.28 23.96 18 Total > .. 22.46 91.31 Av.25 E. P. D. B.: 200 glucose 1-2 13 9.18 41.68 22 2-3 17 11.73 37.83 31 3-4 S 5.98 39.22 15 4-5 7 5.12 40.08 13 Total 32.01 158.81 At. 20 L. C. M.: 200 glucose 1-2 24 15.09 33.37 45 2-3 16 10.49 41.04 26 3-4 16 10.26 40.85 25 Total 35.83 115.26 At. 31 tests made. In some of the ward patients studied the metabolism has remained constant from day to day and even in typhoid fever has changed in gradual curves. Two hundred grams of dextrose or its equivalent caused an average increase of 12.5 per cent, in the first three to six hours after its ingestion. One hundred grams caused an average increase of 9 per cent. The casein meal with lO.S gm. N increased the metabolism 12 per cent., the beef with almost 24 gm. nitrogen increased FRANK C. GEP HART— EUGENE F. DU BOIS 73 it 22 per cent.* A more detailed study of the effects of food is given in Tables 8 and 9, which show the effects in the different periods. The percentage increase in metabolism and the extra calories produced are calculated from the nearest basal determination. The extra protein calories produced are calculated from the increase in the urine nitrogen above the average hourly elimination of the nearest basal determina- tion. The extra grams of urinary nitrogen when multiplied by the factor 26.51 give the extra calories from the combustion of protein during that hour. The extra calories produced when divided by this TABLE 9. — Increase in Heat Production Following Protein Meal Time After Protein Meal, Hours Per Cent. Rise in Metabolism Extra Calories Produced Extra Protein Calories Metabolized. Extra Urine N X 26.51 E. P. D. B.: 10.5 N 1% to 2V4 214 to 3% 3% to Mi »A to S^A 5% to 61^ Total Louis M.: After 23.93 N 2 to 3 3 to 4 4 to 5 5 to 6 6 to 7 7 to 8 Total 5.93 8.96 12.34 8.27 9.03 10.13 11.54 1.56 5.04 1.56 43.88 30.48 9.68 4.80 111.36 4.59 17.94 11.88 17.62 13.04 11.30 16.33 16.45 15.64 ?3.35 66.28 Specific Dynamic Action, Per Cent. 60 140 90 738 300 Av. 144 203 225 151 135 69 loe Av. 126 figure for the extra protein calories metabolized, give the specific d3'namic action in the sense of Rubner (see Note 2, Williams, Riche and Lusk, p. 370), amounting to as much as 144 per cent, and 126 per cent, for the two experiments. The accuracy of this method of cal- culation m.ay be impaired by the lag in the excretion of nitrogen by * Since the completion of this paper two more normal men have been given the test meals. Morris S. on Dec. 18, 1914, showed a rise of 6.5 per cent, after a meal containing 9.6 gm. nitrogen. Albert G. on Jan. 6, 191S, showed an increase of 9 per cent, in his metabolism after 115 gm. commercial glucose (100 gm. dry glucose). 74 CLINICAL CALORIMETRY the kidneys. In the dextrose experiments the method of calculation is slightly different from the method used by Lusk.^ The extra calories produced by the combustion of carbohydrate are reckoned as follows: In the nearest basal determination the average figure for the calories per hour is multiplied by the percentage of calories furnished by the combustion of carbohydrate. A similar calculation is made in each hour of the experiment in which dextrose was administered and the extra carbohydrate calories metabolized in each hour determined. This figure divided into the extra calories produced gives the specific dynamic action of 25, 20 and 31 per cent, in the three experiments. SUMMARY AND CONCLUSIONS Seven normal men were studied with and without food as controls for the observations on patients in the metabolism ward. Their aver- age basal metabolism (at perfect rest, fourteen to eighteen hours after their last meal) was 34.8 calories per hour per square meter of body surface. The average basal metabolism of 89 normal men studied by Benedict, Emmes, Roth and Smith^" was 34.7 calories. The average of the 7 men studied in the Sage bed calorimeter in Bellevue and of the 5 men studied in Benedict's bed calorimeter in Boston was 34.2 calories. As a result we have adopted the figure of 34.7 calories per square meter of the body surface as the average heat production of normal men between the ages of 20 and 50 5'ears. All of the subjects studied in the bed calorimeter were within 11 per cent, of this average. Of the 79 men of normal figure between the ages of 20 and 50 studied by Benedict and collaborators, 86 per cent, were within 10 per cent, of the average and the remainder between 11 and IS per cent. If, therefore, the heat production of a given subject suffering from some pathological condition is more than 10 per cent, above or below the average it may be regarded as abnor- mal, but cannot be proved abnormal unless the departure from the average is at least 15 per cent. Groups of men of weights between 45 and 85 kilograms show a mean heat production within 2 per cent, of the average according to surface area. According to calories per kilogram of body weight the group weighing between 75 and 85 kg. produces 7 per cent, less than the average figure and the group between 45 and 55 kg. produces 9 per cent, more than the average. The conclusion is therefore drawn that among groups of men of varying weights metabolism is proportional to surface area according to Rubner's law and is not proportional to body weight. By using the surface area as a basis one can refer all individuals to a single average normal figure, 34.7. If one uses the body weight as a basis a different normal figure is required for each weight. FRANK C. GEPH ART— EUGENE F. DU BOIS 75 The methods of direct and indirect calorimetry in disease agree in two- and three-hour periods ; and in health may be found to agree in hourly periods. In the total measurement of 4,577 calories in the experiments reported in this paper the two methods have agreed within 0.17 per cent. In a total of thirty one-hour periods on one normal subject the two methods have agreed within 5 per cent, in twenty-one individual hours and within 10 per cent, in twenty-sevep of the periods. The method of indirect calorimetry using the oxygen consumption as a basis gives the best results in hourly periods. The method of direct calorimetry in short periods is made difficult by uncertainty as to the correct specific heat of the body and also by the fact that the differ- ent parts of the body do not always change their temperatures at the same rate. On the average one obtains the best results by considering that the rectal temperature change indicates the mean temperature change of the body, but in typhoid fever the surface thermometers often give a better indication of the mean body change. The most satisfactory method of determining the effect of food in increasing heat production in normal subjects and patients is to deter- mine the basal metabolism at frequent intervals, and on days shortly after a basal determination administer the food before the subject is sealed in the calorimeter. It has been found that 200 gm. of dextrose or its equivalent in commercial glucose or a casein meal with 10.5 gm. of nitrogen increase the heat production by about 12 per cent, over a period of three to six hours. The basal metabolism of patients with various diseases and the effects of this same food will be discussed in subsequent publications. 477 First Avenue. CLINICAL CALORIMETRY FIFTH TAPER THE MEASTJrEMENT OF THE SURFACE AREA OF MAN* DELAFIELD DuBOIS, B.S., and EUGENE F. DuBOIS, M.D. NEW YORK Recent work on the basal metabolism of infants and adults has revived interest in Rubner's law that heat production in different indi- viduals and species of animals is proportional to the surface area. This law was first definitely formulated by Rubner^ in 1883, although sug- gested by Bergman'^ many years before. At the time the experimental work in support of this theory was done no record was kept of body movements and men and animals were allowed to move during the periods of investigation. The average heat production per square meter of body surface was about 1,000 calories per day. In modern work, where the influence of muscular activity is absolutely excluded, the figure is in the neighborhood of 830 calories per square meter per day, as has been shown in Paper 4 of this series. With these new- figures it is not unnatural that many investigators have felt that the whole question must be studied anew. Very recently Murlin and Hoobler^ in New York and Benedict and Talbot^ in Boston have all concluded that among infants metabolism is more nearly proportional to body weight than to surface area. If this is true for adults, it is a matter of great theoretical and practical importance. It is obvious tliat the whole question rests on the accuracy of the determinations of the basal metabolism and of the surface area. The methods of determining the metabolism have been greatly improved, leaving the surface area the doubtful factor. The number of formulas for surface area determination is large, the number of individuals * From the Russell Sage Institute of Pathology, in affiliation with the Second Medical Division of Bellevue Hospital. 1. Rubner : Ueber den Einfluss der Korpergrosse auf Stoflf- und Kraft- wechsel, Ztschr. f. Biol., 1883, xix, S4S. 2. Bergman : Warraeokonomie der Thiere, Gottingen, 1848, p. 9. 3. Murlin and Hoobler : The Energy Metabolism of Normal and Marasmic Children with Special Reference to the Specific Gravity of the Child's Body, Proc. Soc. Exper. Biol, and Med., 1914, xi, IIS. 4. Benedict and Talbot : Studies in the Respiratory Exchange of Infants, Am. Jour. Dis. Child., 1914, viii, 1 ; The Gaseous Metabolism of Infants, Car- negie Institution of Washington, 1914, Pub. 201. DELAFIELD DU BOIS— EUGENE F. DU BOIS 77 whose area has been measured is small. In 1879 Meeh° finished his painstaking and time-constiming work which has remained the standard ever since. He measured six adults and ten children, using a variety of methods. Some parts of the body were marked out in geometrical patterns, which were then traced on transparent paper. The areas of these were then determined by geometry, or, if the pieces of paper were very irregular, by weighing. Some of the cylindrical parts of the body were wound with strips of millimeter paper like a bandage. Funke** in one case covered the skin of a cadaver with adhesive material and pasted over this squares of paper. Fubini and Ronchi'^ measured one man by marking out the anatomical regions of the body and determining the areas geometrically. Bouchard^ used this same method in measur- ing a number of adults. He speaks of a plan of clothing the body in tights made of some thin, flexible, inelastic sort of paper, the area of which could be determined by weighing. Apparently, he was not able to find the right material. He mentions the fact that M. Bergonie measured surface area by means of plates of lead, and that M. Roussy used a very ingenious cylinder with a revolution counter which he passed over the whole .surface of the body. Bouchard also states that D'Arsonval determined the surface area electrically by clothing the man in silk tights and charging him as one would charge a Ley den jar, calculating the surface by applying a ■ metal plate of known area. Lissauer^ measured twelve dead babies by covering the skin with colored adhesive material and then applying silk paper and measuring the area of the paper geometrically or with a planimeter. Meeh^ as a result of his own measurements, based his formula for determining surface area on the fundamental mathematical law that the surfaces of similar solids are proportional to the % power of their volumes. Using the body weight to represent volume he determined that the constant 12.312 when multiplied by the cube root of the square of the weight in kilograms gave results which came within 7 per cent, of all his measurements of adults and older children. The constant for infants was 11.9 and for various species of animals still different. Miwa and Stoltzner^" felt the need of introducing linear measurements 5. Meeh : Oberflachenmessungen des menschlichen Korpers, Ztschr. f. Biol., 1879, XV, 425. 6. Funke: Moleschott's Untersuchungen, z. Naturlehre, 1858, iv, 36. 7. Fubini and Ronchi : Ueber die Perspiration der CO2 beim Menschen Moleschott's Untersuchungen, z. Naturlehre, 1881, xii. 8. Bouchard, Ch. : Traite de Pathologie generate, Paris, 1900, iii', 200, 384. 9. Lissauer, W. : Ueber Oberflachenmessungen an Sauglingen und ihre Bedeutung fiir den Nahrungsbedarf, Jahrb. f. Kinderh., 1902, Iviii, 392. 10. Miwa and Stoltzner: Bestimmung der Korperoberfiache des Menschen. Ztschr. f. Biol., 1898, xxxvi, 314. 78 CLINICAL CALORIMETRY and chose the height (L) and the circumference of the chest (U) at the level of the nipples in men and just above the breasts in viromen, retain- ing the weight (G) as a factor. Using Meeh's measurements they determined by means of the following formula, K UGL Surface = o using an average constant (K) of 4.S33S. This formula, which might have been simplified to Surface = kvipgl has never been much used, although its originators have shown that it comes closer to Meeh's cases than Meeh's own formula. Lissauer from the measurement of babies, almost all of whom were atrophic, retained the principles of Meeh's formula, but found that the constant 10.3 gave better results than the constant 11.9. This indicated that Meeh's figure was about 16 per cent, too high. The formula of Miwa and Stoltzner, according to Lissauer, gave no better results than that of Meeh. Rowland and Dana,^^ using the measurements of Meeh and Lissauer, have devised a simple formula in which the surface area (y) of the child equals the weight in grams (x) multiplied by a constant 0.483 (m) plus 730 (b). This is expressed in the terms y = mx + b. Bouchard found a consistent plus error in Meeh's formula as given in Table 1. In his own formula, which requires twenty-five pages of tables for its application, he uses the body weight, the height and the diagonal circumference of the abdomen from the hollow of the back to a point somewhere above the umbilicus according to the degree of obesity. Bouchard states that a measuring tape passed around the abdomen and moved back and forth will of itself find the right circum- ference, which he calls the "tour de taille." Bouchard's formula has been very little used, as it seems to be difficult to understand and apply. Recently Dreyer, Ray and Walker"^ have made many measurements of birds and small mammals and have found that the surface area, blood volume, cross sections of the aorta and trachea are all nearly proportional to the ^ power of the weight. The formula which applies to all these measurements is S == k W", in which S is the sur- face, blood volume, etc. ; k is a constant which varies with the species ; W is the weight, and n is approximately 0.70-0.72 instead of 0.666 which would be the % power. Benedict and Talbot* have suggested that the active mass of protoplasmic tissue develops normally on this ratio. They are convinced that metabolism is determined, not by the body 11. Howland and Dana: A Formula for the Determination of the Surface Area of Infants, Am. Jour. Dis. Child., 1913, vi, 33. 12. Dreyer and Ray: Phil. Trans., 1909-10, cci, Series B, p. 133. Dreyer, Ray and Walker : The Size of the Aorta in Warm-Blooded Animals and its Relationship to Body Weight and to Surface Area, Expressed in a Formula, Proc. Roy. Soc, 1912-1913, Ixxxvi, Series B, pp. 39 and 56. DELAFIELD DU BOIS— EUGENE F. DU BOIS 79 surface, but by the active mass of protoplasmic tissue. If both are assumed proportional to the same thing, it will be a difficult matter to prove which is the more important factor. As shown in Paper 4 of this series, the metabolism of the normal and pathological subjects studied in the Sage respiration calorimeter in Bellevue Hospital has been expressed in terms of calories per square TABLE 1. — Determination of Error in Meeh's Formula as Applied to Measured Individuals Subject Observer Weight, Kg. Surface Area as Meas- ured, Sq. Cm. Constant for Meeh's ronnula. Area Divided by Wt.% Error in Meeh's Formula Age, Trs. Height, Cm. 24.2 8,473 10.13 +21 36 110.3 28.30 ' 11,883 12.80 — 4 13.1 137.5 31.8 12,737 12.69 -3 35.38 14,988 13.17 — 7 15.7 152 60.00 17,415 12.96 — 5 36 158 50.00 16,067 11.84 + 4 51.75 18,158 12.96 — 5 45 160 55.75 19,206 13.16 — 6 17.7 169 59.50 18,695 12.27 + ... 170 61.6 18,930 12.13 + 2 ... 62.25 19,204 12.01 + 2 26.2 162 64.0 16,720 10.45 +17 21 164.3 64.08 18,375 11.49 + 7 22 178 65.50 20,172 12.48 — 1 66 172 74.05 19,000 10.55 +14 32 179.2 76.5 19,484 10.81 +14 78.25 22,435 12.26 + 36 171 88.6 21,925 11.03 +12 ... 93.0 18,692 9.06 +36 149.7 140.0 24,966 9.26 +33 Body Form Benny L Hagenlocher Very thin woman Eorner Schncck Adult man Nagel Pr. Brotbeck ... Naser Normal man Pr. Haug Morris S E. H. H Porstbauer E. P. D. B Normal woman.. Kehrer Large man Mrs. McK Very fat man... D.B. and D.B Meeh Bouchard Meeh Meeh Pobini and Bonchi Meeh Meeh Meeh Bouchard Meeh D.B. and D.B D.B. and D.B Meeh D.B. and D.B Bouchard Meeh Bouchard D.B. and D.B Bouchard Cretin. Short and fat. Medium strong. Very thin. Muscular. ■ Very thin. ? Somewhat thin. Very strong and muscular. Somewhat thin, but wen pro- portioned. Normal man. Strong. Short and rather stout. TaU and thin. StiU very strong. Tall, average build. Normal woman. Corpulent. Large strong man. Very short and very fat. Very fat man. meter per hour. The work had progressed but a short distance when it was obvious that no formula based on weight could give the surface area of all the patients with any great degree of accuracy. Among the patients studied were men emaciated from typhoid fever and hyper- thyroidism, men of normal shape and men with acromegaluy, hypo- physial dystrophy and cretinism. Eventually, it is hoped every con- ceivable shape will be studied. A formula such as Meeh's is accurate only for objects of different size, but of similar shape. 80 CLINICAL CALORIMETRY The obvious method for determining surface area is to multiply the length by the average width. An attempt has been made to measure a characteristic length and an average or characteristic circumference of each part of the body and determine the area of the part by multiplying the two and correcting by a constant factor. The sum of the parts will then give the total surface area of the body. When the proper meas- urements have been selected and the constants for each part deter- mined, it is evident that the method can be applied to individuals of varying shape no matter what disproportion may exist between the different parts of the body. Fig. 16. — The cretin, Benny L., with mold of his surface area. INDIVIDUALS MEASURED The five individuals whose surface area was measured differed from each other in bodily form to a marked degree. All of them had served as the subjects of observations in which the basal metabolism was deter- mined. Benny L. was a cretin 36 years old with the general mental and physical development of a boy of 8. As his photograph (Fig. 16) shows, he was short and stocky, with prominent abdomen, short thick extremities and rather small head. Morris S., 21 years old, was meas- ured three months after he was discharged from the hospital, where he DELAFIELD DU BOIS— EUGENE F. DU BOIS 81 had been confined three and one-half months with a severe attack of typhoid fever. He had recovered even more than his usual weight in the hospital and during the subsequent stay in the country. At the time he was measured he was of well rounded figure, almost stout. He was short and of small frame, with small hands and feet. R. H. H., a cheinist, 22 years old, was tall and thin, with long, slim bones, sinewy muscles and very little subcutaneous fat. E. F. D. B., 32 years old, was tall, but of average build. Mrs. McK. was a very short and very fat woman whose metabolism had been studied in great detail by Dr. David TABLE 2. — Measurements Used in Formula Index Letter ot Part Measured Benny L. Morris S. E. H. H. E. P. D. B. Mrs. McK. A 67.5 63.9 65.0 67.0 68.0 B 50.2 54.1 56.6 67.8 66.6 P 37.2 56.7 65.0 67.3 65.0 G 20.2 29.5 27.5 32.5 33.0 H 18.7 24.6 26.0 27.5 27.0 I 12.8 16.7 16.3 16.2 16.5 J 13.6 20.0 21.6 20.2 17.0 K 15.2 20.4 20.6 20.5 17.6 L 36.6 65.0 55.0 51.5 56.0 M ; 62.0 76.2 72.5 77.0 111.0 N 63.5 87.2 85.8 96.0 100.0 26.4 41.7 47.0 46.3 40.0 P 35.5 55.5 54.0 59.0 60.0 \ 117.0 Q 61.0 96.0 93.2 96.5 E 29.3 41.7 47.0 49.4 36.8 S 23.7 35.7 33.8 37.0 41.0 T 17.7 24.8 26.2 28.3 21.5 U 16.8 22.5 22.2 23.5 19.3 V 15.7 21.2 21.2 23.5 22.0 Edsall and Dr. James H. Means in Boston. We are greatly indebted to Dr. Means for taking the measurements of this subject and for taking the mold of the surface and sending it to us to be measured. MEASUREMENTS OF THE BODY The individual to be measured was undressed, weighed and placed on a flat table with a vertical foot-board about 30 cm. high. All the measurements were made with the subject flat on his back with his feet against the foot-board. A steel tape was used for all the linear meas- 82 CLINICAL CALORIMETRY urements and a cloth tape for the circumferences. The measurements actually used are given in Table 2 ; those not used are given in Table 3 in case other investigators wish to apply different formulas. THE MOLD OF THE BODY The method of determining the surface area finally adopted con- sisted in making a thin mold of the body, cutting this up in pieces which would lie flat, printing the patterns of these pieces on photo- TABLE 3. — Measurements Not Used in Formula Index Number ol Part Measured Benny L. Morris S. R. H. H. E. P.TD. B. Mrs. McK. I •. 24.2 kg. 64.0 kg. 64.08 74.49 93.0 II 110.5 cm. 164.3 em. 178.0 179.2 149.7 Ill 88.3 135.5 148.0 147.2 125.0 IV 81.1 83.6 124.6 124.4 136.5 139.0 135.5 141.2 V 125.4 VI 76.5 115.2 130.0 125.5 107.0 VII 65.7 83.4 94.0 95.7 76.8 VIII 46.2 72.3 84.5 85.5 60.2 IX 65.1 83.5 80.7 84.5 92.0 X 40.0 60.2 81.5 67.5 65.5 XI 29.6 43.6 48.0 49.0 40.0 XII 8.2 11.3 11.7 15.8 XIII 17.0 24.5 27.0 28.0 21.0 XIV 21.2 33.1 38.6 38.6 32.0 XV 18.6 17.8 27.5 26.0 25.3 25.0 30.0 29.0 XVI 30.0 XVII 35.5 50.3 48.0 56.5 56.0 XVIII 23.2 34.7 32.7 37.5 39.0 XIX 22.6 43.2 31.0 62.0 31.5 48.0 33.5 52.5 30 6 XX 35.5 XXI 28.6 38.0 36.0 87.0 34.2 XXII 74.5 108.0 99.0 107.0 106.0 graphic paper (Fig. 17) and finding the area of the printed patterns by cutting them out and weighing them. The subject was dressed in a tight-fitting suit of thin union underwear, which covered the body, arms and legs. Socks were put on the feet, thin cotton gloves on the hands, while over the head and neck was slipped a section of the leg of a knitted undersuit held in place by means of bandages. On this ground- work strips of paper were pasted until a flexible inelastic mold of the DELAFIELD DU BOIS— EUGENE F. DU BO IS 83 body was completed. The material used was strong manila paper, about \y2 inches broad, gummed on one side. It is manufactured in large rolls and is used by stores as a substitute for string in doing up small pack- ages and also by some tailors in making models of their customers. For our purposes it was wound in small rolls and placed in a small brass holder which moistened the gummed side as it was applied to the cloth covering the body. It could be applied so quickly that very little Fig. 17. — Reduced photograph of the patterns printed from the mold of the head and neck of one of the subjects measured. The patterns of the head marked with one punch were cut out and weighed separately from the pieces of the neck marked with two punches. The dark areas were also weighed as control. time was required to cover the body. The head presented no difficulty until the nose was reached. This region was the last to which the paper was applied and a couple of holes were left for the person to breathe through. The mold of the face was then quickly opened by means of curved bandage scissors. In most cases only one arm and one leg were measured. « o to i-i (J ►J < u m o w 9 -""S M □ (3 j> OS q rH q rH CO OD 00 1% h 00 ft ra CO M OS lA C ;=l oi 03 id ^ ■4J iH i-i i-l r-l i-l r-t 7-K rH rH rH lil c3 OS la 10 ■* IN ift 10 CO q CO CQ M '*. ® Oi 00 s N 06 ei CO ^ 06 CJ oi CO ■^ CO id c< CO t- oi <© «a 1= S S s s s ^ ^ ?S g s S8 B 5; So ^ s s °i>- so rH W tH M N IH i-^ ej rJ 1- rH rH '-' rH fH d CO oiga g •^ * (-* fiB DO « ^1 ^"a s g S S S S § s g g g e g g g CO ^ ^ PhCJ t^ t^ CO CO CD CO pH OS S Sa 0; q q q 01 CO rH CD -* CO q q M to th ir: M ift id -i v. id id CO id id li: id oa "* id .■§* iH iH -H rH T-\ rH rH rH rH r-i rH rH rH CQ S bo tan fl od lis sa -* I-H t- g § tH c- S S g § ^ S s 5 s ■^^"^ lilffl 05 (M (M rH M rH If^ Pm - ■ia (M CO i-< "* -* 01 t- i 1 ^ 01 t- CO a 03 oc S S «3 t- \r. CO r- -* 00 50 1H -* iH -.* PH -* a.a=< r5 iH rH T^ "T^ T^ rH rH SD CW d. 6 3 4 3 3 . CO la c3 . S 53 % t- %. to IM C> ? ?3 S e s u t^ ail J=]§S g §£-§ t^i;5s3s 6a§3 Ss % sSs ^9 g ir^ssS t- a as +;^4J S ^'S^^S 'i'k^ ^^t ii.^^t^t 4.t^t -n S i^ o^c c CQ OQ CQ CQ OS -^- o-§- C OS CQ a G P< >> Q. t»» « ^ 03 -H cu t: t* tu (h gS is f-- ^ 03 +S ? p o CQ 4J to QJ S Ph TJ ■D g- 2 1) H OJ ca S o ■g S > o« -S % <0 « OS > £ S "5 > OJ -g l > t- Relapi Temp, curve, and p. ^ F- s ^ c 3 t ? c g CI c H 1 t £ 1 £? M S i3 « « A 03 .t ta « w ea s 03 OQ W 1.^ < W Q |x H 1^ % ^ W h^ ^ W ft B ■a d.».2 tH C^ CO ■* »H fis c^ r* ^ r ^ ' _ — ■\ _ y ., \ H u a J '& u - = - - - - - - - >^ - - - - H f~ VI 1 T n V ^ -^ - - - — - - - ~ - - ~ -!.. - - ifil ^ _ _i _ _ ^ ^ _ ^ .^ORRIS S. NOV 17 Morris S. Dec 10 MORRIS S. Dec 23 ^ ^ X ^ ■-■'^ w ^^ _--= ^7 ^ ^ "■' ....-• — — ^ . .. _ . ■• IT J Hr °C sae 39,2 38.8 38.+ 380 Cau 80 70 60 Chart 1. — Curves showing the relationship of heat production and heat elim- ination in fever. Rising temperature. The uppermost line shows the rectal temperature as measured every twenty minutes. The heavy continued line represents the heat production in hourly periods as determined by the method of indirect calorimetry. The dotted line gives the heat elimination as deter- mined by the measurement of the calories of radiation, conduction and vapor- ization. The difference between the levels of these two lines represents the heat stored in the body as the temperature rises. Note the fact that in every case except one the heat elimination increases with a rising temperature. no specific dynamic action as usually induced by ingested food. In like manner if the metabolism be raised in fever, food ingestion may cause no increase. He also stated that since protein metabolism in fever 9. Lusk: Jour. Am. Med. Assn., 1914, Ixiii, 831, foot of page. WARREN COLEMAN— EUGEXE F. DU BOIS 109 can never be reduced to as low a level as is present in the normal organism, therefore protein ingestion in fever often merely serves to replace the protein already breaking up in increased quantity, and such protein ingestion would not then serve to increase the heat production. The Regulation of Body Temperature. — The study of the regulation of body temperature is one that demands the utmost accuracy of technic. The question at issue is whether a rise in temperature is due to an increase in heat production or a decrease in heat elimination. Previous investigators have tried to solve this problem on data obtained from the direct calorimetry alone, or from the indirect calorimetry accompanied by measurements of body temperature. In either of these two methods the whole calculation would depend on the exact Morris 5 OCT 2 9 Morris S. NOV. 5 Howard Nov, 20 F Karl 3 Jan. 5 HR 1 ? 1 7 7, 1 . ? 7i i z To ^ 39.6 '^■— ^ .^ / 392 — ■^ ~~ s "^Rfi "* 384 38.0 ^ ^ ^ _ C/^L .- .. _'■ ,_. .. .. ~' 90 - - ^ - "^ 80 „ . _ _ ._ — _ _ _ — _ _ 70 - - - - ■ - = — ^ = ^:7 — - - - - - — -■ V— - 60 _ . _ _ — — _ _ •1. " ■\ *T ^ -.- ■ Pin - - - - ■ - - -- — '■^ ^ — - - — ^ ^ _. _ _ ^ ^ ^^ ^ ^ ■- 1 Chart 2. — Curves showing the relationship of heat production and heat elimination in fever. (See legend Chart 1.) Temperature level or falling. In the last two experiments it will be noted that the heat elimination rises above the production. measurement of the average change in body temperature, the exact calculation of specific heat of the body and the amount of heat stored in or lost from the body. It has been shown in this and preceding papers that these measurements and calculations are the weakest points in the science of calorimetry and it is only very recently that the technic has been so developed that investigators have attempted a comparisun of the methods of direct and indirect calorimetry in periods shorter than six to twelve hours, periods obviously too long for the study of the problem in question. If, in a period of experimentation, the results obtained by the method of indirect calorimetry and by the method of 110 CLINICAL CALORIMETRY direct calorimetry, using either the rectal or the surface temperature, do not agree within 5 per cent., we must suspect some error, probably in the measurement of the average body temperature change. For this reason we have eliminated from the discussion all experiments in which the two methods do not agree within 5 per cent. It is also pref- erable to eliminate all experiments after the taking of food and all experiments in which the subject was not quiet. This gives us eleven experiments during the febrile period in which the technic left nothing to be desired. In Chart 1 are grouped those experiments in which there was a rising body temperature. The dotted line shows the total heat elim- inated from the body by means of radiation, conduction and vaporiza- tion. The continued line shows the heat production as determined by the method of indirect calorimetry, which does not use a single factor that affects the dotted line. With a rising body temperature the heat production within the body must be greater than the elimination to provide for the storage of heat in the tissues. Many are of the opinion that the rise in temperature is chiefly due to a decrease in the heat elimination. This we find to be the case only in the last hour of one of the seven observations, there being a sharp drop in both heat pro- duction and elimination towards the end of the experiment on Morris S. on October 24. In all the other periods the rising temperature was accompanied by an increasing heat production which outweighed the increasing heat elimination. In Chart 2 which shows periods in which the body temperatures were fairly level the production and elimination were about equal and constant. In the two observations with falling temperature the heat production remained fairly level while the elimination was increased. Heat Production, Weight and Nitrogen Equilibrium. — In the cases here studied it is possible to make a comparison of the caloric intake and the caloric output. The intake consists of the calories of the food. The output is made up of many factors, but principally of calories lost by radiation, conduction and the evaporation of water. The first and most important consideration is the determination of the basal heat production as measured by the methods of direct and indirect calorim- etry. As has been shown above, the two methods agree within 2 per cent. The actual heat production during the different hours of the day can depart from the basal as a result of various factors. We have shown above that the ingestion of large amounts of food causes but a slight increase in metabolism, averaging less than 5 per cent, in the case of protein and only 1 per cent, in the case of carbohydrate. These increases may be considered the maxima since the amounts of foods given were the largest the patient could take and the hours of the WARREN COLEMAN— EUGENE P. DU BOIS 111 observation were the hours of the greatest specific dynamic action. The exact percentage rise caused by the stimulation of the food taken during the whole day is problematical but may be estimated as about 3 per cent. The percentage of calories lost in the feces has been studied in two previous papers and has been found to be practically normal. The calories lost as urea and in the feces are taken into consideration in the calculation of the fuel values of the food. In the one case in which there was alimentary glycosuria (Frank W.)/ the calories lost as dextrose have been subtracted from the intake. In a previous paper the writers have discussed the evidence against an abnormal loss of partially oxidized carbon compounds in the urine and have come to the conclusion that this factor is negligible. The entire absence of abnor- mal respiratory quotients supports this view. The lowest quotient found was 0.72, the highest 1.04, obtained respectively during fasting and high carbohydrate ingestion, and thus exhibiting entirely normal relations. The most uncertain factor is the variation in heat production caused by changes in the muscular activity. It is quite possible that a patient who is very delirious and very restless might produce twice as many calories as when quiet. The total heat production of such patients could be determined only by the Middletown type of experiment in which the subject was kept in a respiration calorimeter for days at a time. Such experiments are obviously impossible in typhoid fever. The question remains as to whether we obtain a fair sample of the day's metabolism by making two or three observations a week between the hours of 11 in the morning and 2 or 3 o'clock in the afternoon. This period includes some of the morning hours when the metabolism is said to be low and some of the afternoon hours when it is said to be high. During the experiment the activity of the patient has been almost the same as the activity observed in the ward during the greater part of the day between the hours of 5 in the morning and 8 in the evening. In the calorimeter the subjects are allowed to turn from side to side several times during the hour and they shift their position often enough to make themselves comfortable, which is exactly what they do in their beds in the ward. Part of the time they doze and part of the time they are awake and are looking out of the calorimeter window. In the ward they are kept flat in bed and are never allowed to sit up untilthe temperature has been normal for several days. They are never given cold tubs and hardly ever given cold sponges. Their food is served on trays and they help themselves with a minimum of exer- tion. In the morning the nurse gives each patient an enema, sponges I u Qfi- i ^ 1: ^3 M ^I i= :^ 1 liili 11 i III 1 Mm m II Uii iil «> og 8 5 8 o O ^ o ^ 1»J M — c s i >.'S'2 W) C a-o ^ rt oJ «i j= S ■■a J= w P rt Q^ OJ t=I u Ph 1 u cu H ■- o csCQ 3 ° m OJ 3 • r^ w I- cl^ O "^ c.^:§^ o g ° o~ ."" ^ . — ^ C\J CO U -«-> ., rt tJ t, rH O o « .■t: ° en 3 " '^ _ bc'Cr* b o G ° >.— ,° o a tn lU 5 "O o -M ~ ^ 2 o "*"*. 'T3 a ^ O O w 3 ra O O*^ .§5 1- ^^ 3 1) 3 O . ■> -u-G 5.™ ?f r! O -^ '^2 G £ nj botrj I-* rt OJ tu OJ •■ -4-J O C. U m O G rt •O 3 O G 1-1 rt ai— . 114 CLINICAL CALORIMETRY him off with warm water, slides him from his bed to the weighing platform, makes up his bed and slides him back again. During the rest of the day he is seldom disturbed and he spends his time dozing, reading or talking with his neighbors. A few of the patients have been mildly irrational for a few days at a time and such occurrences have been noted in detail in the histories. Subsultus tendinum and jactita- tion have rarely been observed. On the other hand, there must be a reduction of the metabolism at night since the patients sleep soundly and are seldom disturbed. In a previous paper we have estimated that the bodily activity increases the metabolism during the whole day to an average of 10 per cent, above its basal metabolism. Since that time we have had the opportunity of making two observations on patients who were irrational and restless. November 3 Morris .S. was in the calorimeter for three hours. During the first hour he was unusually quiet, during the second hour he was restless and tossed about the bed, during the third hour he was evidently irrational, tossed about and wrote three or four long notes which he held up to the calo- rimeter window to tell us about the animals that were biting him with their sharp teeth. In spite of this unusual activity his metabolism during the three hour period was only 43 per cent, above the normal and was only 5 per cent, higher than during the quiet basal observation made two days later, when the temperature was lower. Edward B. on Nov. 10, 1914, was in the calorimeter with a temperature of 40.3 C, and during the second and third hours was restless and mildly irrational. His heat production was only 51 per cent, above the average normal. These two observations, which are fair samples of the severest symptoms observed in the typhoid patients presented in this paper, do not indicate any unusual degree of increase of heat production from the moderate activity. There may be an uneconomical expenditure of energy in typhoid in the performance of a certain task but even so the total expenditure is not great in these cases. It is hoped that at a later date the question of muscular efficiency in fever may be solved by having typhoid patients and normal controls do a stated amount of work on an ergometer while in the calorimeter. A detailed consideration of all the factors is of importance when one attempts to draw conclusions from a discrepancy between the calculated intake and the calculated output. It is necessary to consider the possible errors in the various determinations and it is necessary to select somewhat arbitrary average percentages for the various factors. The measurement of the food intake is unusually accurate. Most of WARREN COLEMAN— EUGENE F. DU BOIS lis the foods such as cereals, bread, sugars, egg white and egg yolk, butter and crackers vary but slightly from the samples analyzed. The other foods given, such as milk, cream, and dried apples are not subject to large enough variations to afi'ect the results. Foods subject to signifi- cant variations are carefully avoided. The methods of preparation and weighing have been described in another paper and they are believed to be accurate within 2 per cent. It is doubtful if this error combined with the error in the variation of the individual foods exceeds plus or minus 5 per cent, and there is no factor to throw the error on one side of the scale more often than on the other. The heat production of the patients as determined by the method of indirect calorimetry is not subject to an error of more than 1 or 2 per cent, on the average, although it is possible that some individual observations may show an error of 5 per cent. The collec- tion of the twenty-four hour specimens of urine and the estimation of M«vrMi>f» Olc. r, ■' i T l a^ jg g» ?tT?7 gi» ga ^a ^s^^^i^l, 98 = .^-^- d = ^ i'A ^^^ 5 ;^ t?S Chart 4. — Charles F. Temperature curve. the nitrogen are so carefully controlled by duplicate analyses and checks in the collection of specimens and in the calculations that there is no chance for an error greater than 1 per cent. In the cases in which the feces were not analyzed the method of estimating the feces nitrogen as 10 per cent, of the food nitrogen gives a plus or minus error of less than half a gram a day while there is possibly as great an error in the fact that we do not take into account the nitrogen losses through the skin. In order to estimate the caloric output of typhoid patients on whom respiration experiments were made, one can add to the basal metabo- lism on average 3 per cent, for the specific dynamic action of the food and 10 per cent, for muscular activity. We can, therefore, calculate with reasonable accuracy the heat production for the day by adding 13 per cent, to the figures obtained in the febrile basal experiments and 10 per cent, to the figures obtained in the experiments after food. In the cases in which several observations were made it seems fair to plot a smooth curve and consider that the heat production of the non-experi- 116 CLINICAL CALORIMETRY - mental days was the same as on the days in which actual determina- tions were made. If we look now at Table 4 and Charts 3, 6 and 8, it hecomes evident that three of the patients reported in this paper and one reported in a previous paper^ showed a distinct negative nitrogen balance when they were receiving cofisiderably more ■calories than were sufficient to cover the calculated heat produc- tion. A glance at the food charts will show that the typhoid patients were given 12 to 16 grams of nitrogen a day and that the proportions of fat and carbohydrate were well balanced. The only criticism of the manner of feeding is that on the days of the basal determinations it v/as necessary for the patient to fast sixteen to twenty hours. One might expect a slight negative nitrogen balance at such times, but this should be offset by a positive balance the next day. As a matter of fact the negative balance is not much greater on the experi- MoVFMFjFI? li " 11 i^-:3:\ tf ^~-. lZ 4E = = - = =-<^ £'-£ — = = = = 4E= = i»^ :; F-- 1 _^ i^--fc J---" ^ i^ ^..-Y f— T — -1 ^] 1 h 1^1 -B r \ ' ^ PK ,^ 21 i:^ I==-r ^ — m "S ^ - - ^1 ^1 I==-L_ H ^ 3 Z;! l^'l ' 4§ ^ Z ' ' ^ ^Z> 3^=3__ ____jg J. ' " C'^ -EE IE T* 2 1 E^ dE=_^_, JB ^ S it 5 ^5 4i :; IT ^^ -. _-£3 ni <; 1' t — Tk ^^■^ " n 1==, 1 jg 4 ^ 4 j==i d ig ^ S \ 0^ 3 = =i ^ 4B i si V ^5 -EI i ° ^> ^ :: :-: ■. :i ~ ^» ^ •" ~~ Q -- 3 ^ =: :5 5^ 22^ :.±^__,§ ^ > - ^ -'zri: ---I < t^'' e ^ tv ^~-^^ ■ JC EV-. -^ C ^ 1 "^1 lb ^^ _c( H^ X * a ,> - _:; 1 1 h' u| \ III! |>j °* t -^^ ^ -t -=== :i ^t -,U T ^ -tt -SL • > -■ L -r- -5e- ^ n CM — bo u c.S ^ -^ o< > o 6 "2 rt o a> . n P c to T3 i> Sr rt rt oJ ft u !'« .Ma S jj &5 E 00 P >. ■» 13 - o J=-a -°^ j: iH CJ O 3^ I) -(_. J- '-' rt C ^ J- a o m t; ji £.sij:n£j' t' ^r_ ^=3E-----=----E^S£-£b£-^ - 98"-------"---"-=^"^-"----= ^4k^ ISi^LLiji:' DTf'S; ~— -I _!._ 'Oc. -trXC1tinn~l*7 lC-/LK,-fi— IJ- ^jJ sj ~ iOTrtv^rlv J — '"^ ^= , ^^ ^ -2 c lliriinJ^... f) u . . ■ ■ Ar\rsoc&i -.^ TT - quuubssi.. j2aD. ■ tt"" ' ' " 3000 IJ --■-■-■■-:;;=;;;; ii > • ^^ B •< zooo 1 /^A/^ 1 ooo j^x^^§§liiiiliii Chart 8.— John K. Temperature, body weight, food and excreta nitrogen. Food calories and dot-dash line showing estimated heat production. sions of metabolism in fever. The results of the large number of investigations made on lower animals, while important, cannot with certainty be transferred to man. The question of the toxic destruction of protein took on a new aspect when in 1909 Shaffer and Coleman^ showed that it was possible 120 CLINICAL CALORIMETRY to obtain nitrogen balance in typhoid patients, even during the second and third weeks of the disease. This they accomplished only by making the total caloric value of the food very high, from 60 to 90 calories per kilogram, and the food nitrogen from 9 to 15 grams. In their discussion of the results they expressed the opinion that "... .it is perhaps improbable that the total heat production reached the values represented by the larger amounts of food." This work proved that there was no toxic destruction in the sense of a nitrogen loss which could not be counterbalanced by the nitrogen intake. The question of the average heat production of typhoid patients was fully discussed in last year's paper^ and attention was drawn to the fact that typhoid patients did not come into nitrogen equilibrium until their theoretical caloric requirement was exceeded by from 50 to 110 per cent. Grafe^° in 1911 had shown that his typhoid patients when studied in a respiration chamber, ten to sixteen hours after their last meal, derived about 10 to 20 per cent, of their calories from pro- tein, a percentage usually found in normal men. From this Grafe con- cluded that he had shown that the protein metabolism in fever was not abnormal. The percentage of calories derived from protein on the first eighteen hours after food ingestion depends largely on the previous level of the protein ' metabolism. Normal individuals who have been taking 15 to 19 grams of nitrogen a day will naturally derive about 15 to 20 per cent, of their calories from protein as is shown in Paper 4 of this series. Normal individuals who have been maintaining them- selves in nitrogen balance on 4 to 5 grams a day will derive only 5 per cent, of their calories from protein. The comparison should have been made between normal men and typhoid patients while both were on their nitrogen minima. This will be shown later in a discussion of Kocher's work. RoUand"^^ working under Grafe's direction brought several fever patients into nitrogen balance by means of a caloric intake which she believed to be equal to the heat production as estimated from the aver- ages of other patients. Respiration experiments were not made on the patients themselves. Our reasons for believing that the food intake was above the requirement have been set forth in another place^ (p. 38). Recent work from Friedrich Muller's clinic has thrown important light on the subject. Graham and Poulton" established themselves 10. Grafe E. : Untersuchungen iiber den Stoff- und Kraftwechsel im Fieber, Deutsch. Arch. f. klin. Med., 1911, ci, 209. 11. RoUand, Anne: Zur Frage des toxogenen Eiweisszerfalls im Fieber des Menschens, Deutsch. Arch. f. klin. Med., 1912, cvii, 440. 12. Graham and Poulton : Influence of Temperature on Protein Metabolism, Quart. Jour. Med., 1912, vi, 82. WARREN COLEMAN— EUGENE F. DU BOIS 121 on a minimal nitrogen elimination of 4 to 5 grams a day and found no increase in the elimination when they raised their temperatures to about 40 C. by means of a steam bath. Kocher^^ in two normal sub- jects established a nitrogen minimum at a similar level and found no increase when he raised the heat production by means of a 60 kilometer walk. All of these experiments were made on a caloric intake calcu- lated to cover the requirement. They indicate that rise in temperature alone or increase in heat production alone will not cause an increased protein metabolism, at least when applied for a portion of one day. Kocher then attempted by means of a diet amply sufficient to cover the calculated requirement to bring down the nitrogen elimination of fever patients to the low level obtained in normal men. This he found to be impossible until the active stage of the disease was passed. Grafe^* in a recent paper has criticized these experiments. To all of the patients in Table 4 food was given which had an energy content much greater than the amount required by the patients as measured directly when they were in the calorimeter. Although the protein content of the diet, as represented by an intake of 15 grams of nitrogen, was ample to establish nitrogen equilibrium had the diet been given to normal men, it did not accomplish this in typhoid fever. It is difficult to see in this anything except the proof that there is an abnormal destruction of protein in typhoid fever. In some cases the protein destruction continued several days after the temperature had reached a low level. It is impossible to escape the conclusion that the destruction of protein is caused by the toxins of the disease. SUMMARY AND CONCLUSIONS The heat production of typhoid patients has been measured by the methods of direct and indirect calorimetry in a series of sixty-one experiments. The two methods agreed closely, the total divergence being 2.2 per cent, and the average divergence in the individual experi- ments being 5 per cent. This and the entire absence of abnormal respiratory quotients indicate that in typhoid fever protein, fat and carbohydrate are oxidized to the same or approximately the same end products as in health, and in their oxidation give off the standard 13. Kocher, Rudolph A.: Ueber die Grosse des Eiweisszerfalls bei Fieber und bei Arbeitsleitstung, Deutsch. Arch. f. klin. Med., 1914, cxv, 82. 14. Grafe, E. : Zur Genese des Eiweisszerfalls im Fieber, Deutsch. Arch. f. klin. Med., 1914, cvi, 328. TABLE S.— Clinicai^ Subject Date Weight Period End of Period Oarbon- dioxid, Gm. Oxygen, Gm. R.Q. Water, Gm. Drine N per Hour, Gm. Indirect Oalo- rimetry, Oal. Heat EUmi- nated, Oal. Direct Oalo- rimetry (Bectal Temp.) Oal. Bectal Temp. 0. Morris S Oct. 24, '13 51.60 kg. Prelim. 1 11:35 12:35 30.06 30.02 .73 47.84 0.713 97.69 83.41 84.28 89.86 39.93 2 1:35 27.82 26.13 .77 46.72 0.713 85.89 84.68 81.00 39.89 3 2:35 26.20 24.04 .79 39.48 0.713 79.28 74.63 85.72 40.17 Morris S Oct. 25, '13 51.22 kg. Prelim. 1 ll:0O 12:00 29.65 26.82 .80 42.10 0.671 88.95 78.03 90.06 39.21 39.49 2 1:00 28.63 25.87 .81 39.10 0.671 85.77 80.11 88.09 39.69 3 2:00 31.75 25.46 .91 42.82 0.671 86.62 90.07 78.55 39.49 Morris S Oct. 28, '13 51.60 kg. Prelim. 1 11:10 12:10 34.12 28.35 .88 43.31 0.732 95.71 92.00 75.53 39.62 39.27 2 1:10 32.64 24.82 .96 42.41 0.732 85.31 94.67 76.33 38.87 3 2:10 30.25 22.89 .96 39.40 0.732 78.60 86.73 84.65 38.81 4 3:10 29.93 24.33 .90 34.39 0.732 82.34 78.47 93.97 39.20 5 4:10 28.38 22.06 .94 31.75 0.732 74.59 74.35 90.84 39.65 Morris S Oct. 29, '13 49.86 kg. Prelim. 1 11:10 12:10 26.76 23.77 .82 33.11 0.658 79.00 81.19 76.49 39.63 39.60 2 1:10 27.49 26.95 .77 34.03 0.658 86.28 84.48 85.73 39.54 Morris S Oct. 31, '13 60.28 kg. Prelim. 1 11:00 12:00 28.96 25.45 .83 32.13 1.058 84.11 74.09 68.27 39.06 38.94 2 1:00 29.69 24.17 .89 36.41 1.058 81.16 79.19 79.96 39.08 3 2:00 29.57 26.58 .80 36.76 1.058 87.50 77.70 87.13 39.43 Morris S Nov. 3, '13 48.53 kg. Prelim. 1 10:30 11:30 24.91 20.42 .89 28.68 0.499 69.20 66.44 72.99 38.63 39.05 2 12:30 28.70 26.23 .80 33.10 0.499 83.77 74.39 77.80 39.15 3 1:30 27.63 27.90 .72 42.11 0.499 90.92 86.25 71.74 38.81 Morris S Nov. 5, 'IS 48.45 kg. Prelim. 1 11:20 12:20 26.42 23.10 .80 29.99 0.491 76.70 77.98 81.34 38.08 38.19 2 1:20 26.42 23.05 .83 38.62 0.491 77.19 74.76 67.00 38.01 3 2:20 25.60 23.65 .79 39.13 0.491 78.29 72.89 75.34 38.10 Morris S Nov. 17, '13 47.99 kg. Prelim. 1 11:10 12:10 21.90 19.01 .84 24.39 0.336 63.87 67.98 62.77 38.48 38.61 2 1:10 23.68 20.82 .82 24.44 0.336 69.76 60.70 69.71 38.82 3 2:10 23.79 22.28 .78 26.06 0.336 73.79 66.08 72.85 39.00 Morris S Nov. 18, '13 48.77 kg. Prelim. 1 11:00 12:00 24.40 22.01 .81 26.65 0.567 73.01 67.36 64.94 39.72 39.67 2 1:00 26.37 21.38 .90 28.16 0.667 72.56 71.65 82.60 39.98 3 2:00 25.91 23.67 .80 28.88 0.667 78.11 72.05 77.47 40.15 Morris S Nov. 24, '13 46.69 kg. Prelim. 1 11:13 12:13 29.17 26.27 .78 29.24 0.614 83.66 67.60 68.12 39.54 39.59 2 1:13 26.91 24.54 .75 32.68 0.514 85.26 75.16 64.72 39.33 3 2:13 26.41 25.48 .75 35.00 0.514 83.64 80.48 73.52 39.16 — Caloeimetry in Typhoid Fever Suiface Temp., 0. Aver- age Pulse Work Adder., Cm. Non- ProMin, B.Q. Per Cent. Calories Irom Calories Per Hotu- Pro- tein Pat Oarbo- hyd. Per Kg. Per Sq. M. 96(f) 36.0 .71 24 75 1 1.90 67.33 Basal. 96 21.0 .77 28 58 14 1.67 50.40 105 17.0 .79 31 49 20 1.54 46.53 101 96 30.0+ 21.5 .80 .81 20 21 54 52 26 27 1.74 1.68 52.36 50.48 9:30-10:00 a. m., protein meal. 9.0 gm. N. 105 18.0 + + .94 21 17 62 1.69 60.98 119 113 108 35.0 25.0+5? 30.5 .90 1.01 1.02 20 23 25 29 51 77 75 1.88 1.68 1.55 66.70 50.54 46.66 At 10:22, 115 gm. com. glucose = 100 gm. dex- trose. Asleep Irom 3-3:40. 108 18.0 .93 24 19 57 1.62 48.78 107 9.0 .99 26 3 71 1.47 44.19 105 24.0 .82 22 47 31 1.58 47.17 Basal. 106 17.5 .76 20 65 15 1.70 60.91 101 102 10.0 (?) 11.2+ .84 .95 33 35 36 12 31 53 1.68 1.62 50.16 48.39 8:40-9:20, protein meal; 10.3 gm. N. 98 9.5 .81 32 44 24 1.74 62.1fi 106 111 106 11.7 32.0 8.0+ .91 .79 .70 19 16 15 25 69 85 56 26 1.42 1.71 1.86 42.09 50.96 65.30 Basal. 1st. hr. quiet, 2d. hr. restless, 3d. hr. restless; wrote 3 or 4 notes. 98 5.5 .80 17 56 27 1.58 46.89 Basal. 109 8.0 .84 17 45 38 1.59 47.18 112 8.0 .78 17 61 22 1.62 47.86 37.29 37.52 100 11.0 .84 14 45 41 1.33 39.28 Basal. 37.83 113 6.8 .83 13 61 36 1.45 42.90 37.94 112 3.0 .77 12 68 20 1.54 45.38 38.89 38.98 lU 0.3 .81 21 62 27 1.50 44.44 Basal. 39.27 117 14.7 .92 21 20 59 1.49 44.16 39.16 124 13.7 .80 19 55 26 1.60 47.64 12.0 .78 16 64 20 1.77 52.32 Basal. 122 0.0 .74 16 73 11 1.81 53.39 126 0.5 .74 16 73 11 1.78 52.37 TABLE S. — Clinical Calorimetry- Subject Date Weight 1 Period End of Period Carbon- dioxid, Gm. Oxygen. 6m. B.Q. Water, 6m. Urine N per Hour, 6m. Indirect Calo- rimetry, Oal. Heat Elimi- nated, Oal. Direct Calo- rimetry (Bectal Temp.) Oal. Bectal Temp. 0. Morris S Nov. 25, '13 47.24 ]jg. Prelim. 1 11:20 12:20 28.17 24.45 .84 29.86 0.618 81.79 71.86 66.66 39.40 39.30 2 1:20 30.38 26.92 .82 47.61 0.618 89.78 91.51 78.22 38.97 3 2:20 29.26 27.94 .78 48.78 0.618 89.93 88.95 95.35 39.13 Morris S Nov. 26, '13 46.11 kg. Prelim. 1 10:50 11:50 26.29 24.80 .77 27.88 0.329 82.10 69.08 52.60 39.61 39.19 2 12:50 25.68 24.64 .76 34.79 0.329 81.28 79.19 71.14 38.99 3 1:50 25.70 24.85 .75 42.13 0.329 81.84 88.38 79.59 38.77 Morris S Dec. 12, '13 48.61 kg. Prelim. 1 10:56 11:66 23.45 20.22 .84 18.48 0.272 68.20 61.73 53.71 37.01 36.82 2 12:56 23.88 20.96 .SS 21.26 0.272 70.44 64.58 69.48 36.95 3 1:56 24.99 21.42 .85 24.01 0.272 72.36 66.64 69.52 37.03 Morris S Dec. 13, '13 48.07 kg. Prelim. 1 10:36 U:36 18.99 16.89 .82 18.84 0.323 56.39 58.07 50.93 37.07 36.90 2 15:36 20.10 17.29 .85 19.31 0.323 58.16 58.63 63.06 37.02 3 1:36 20.76 - 18.90 .80 20.26 0.323 62.88 61.95 63.59 37.07 Morris S Dee. 15, '13 48.17 kg. Prelim. 1 10:52 11:52 24.51 18.29 .98 18.41 0.384 63.45 58.74 47.60 37.30 37.03 2 12:52 26.76 18.98 1.03 20.90 0.384 66.42 63.52 64.97 37.10 3 1:52 26.83 18.82 1.04 22.07 0.384 65.97 64.19 67.97 37.23 Morris S Dec. 16, 'IS 47.86 kg. Prelim. 1 11:06 12:06 22.51 17.81 .92 20.83 0.299 61.10 63.36 61.62 37.32 37.30 2 1:06 21.91 18.33 .87 21.42 0.299 62.12 62.76 63.36 37.33 3 2:06 22.37 19.33 .84 21.79 0.299 65.08 63.87 60.35 37.25 Morris S Dec. 19, '13 48.74 kg. Prelim. 1 11: 10 12:10 27.38 21.99 .91 22.55 0.493 74.94 70.40 67.95 39.10 39.14 2 1:10 30.04 22.70 .96 25.64 0.493 78.51 75.00 84.00 39.41 3 2:10 29.47 23.61 .91 27.26 0.493 80.32 74.21 87.13 39.75 Morris S Dec. 20, '13 48.52 kg. Prelim. 1 10:40 11:40 23.69 22.51 .77 23.81 0.547 73.93 67.11 76.36 39.29 39.53 2 12:40 25.60 23.42 .80 25.60 0,547 77.57 70.95 78.45 39.70 3 1:40 25.51 23.84 .78 27.47 0.547 78.68 72.88 72.56 39.77 Morris S Dec. 22, '18 48.87 kg. Prelim. 1 11:16 12:36 37.28 28.77 .94 37.28 0.705 98.85 97.57 112.39 38.65 39.05 2 1:36 28.84 22.32 .94 28.28 0.529 76.65 73.08 88.66 39.47 3 2:36 28.86 22.21 .96 29.24 0.529 76.39 74.60 78.88 39.69 Morris S Dec. 23, '13 48.60 kg. Prelim. 1 11:06 12:06 23.51 21.45 .80 26.82 0.428 71.21 68.75 73.19 38.04 38.16 2 1:06 23.94 21.92 .80 26.39 0.428 72.73 70.84 80.86 38.46 3 2:'06 24.35 22.79 .78 25.38 0.428 76.32 69.86 76.84 38.66 Morris S Jan. 2, '14 49.26 kg. Prelim. 1 11:16 12:16 19.10 16.62 .84 19.75 0.386 65.63 68.53 52.15 36.97 36.86 2 1:16 19.27 17.07 .82 20.20 0.386 56.94 57.89 64.93 37.05 3 2:16 1 19.80 18.38 .78 22.05 0.386 60.77 61.64 60.88 37.07 -IN Typhoid Fever — (Continued) 1 Surface Temp., 0. Aver- age Pulse Work Adder., Om. Non- Protein, E.Q. Per Cent. [ Calories from 1 1 Calories Per Hour Remarks Pro- tein Fat 6arbo- hyd. ' Per Kg Per Sq. M. 38.37 .<)8.6(i 38.12 37.76 112 122 119 18.6 12.2 9.5 .85 .83 .78 20 18 18 42 49 62 38 ! 33 20 1.72 1.89 1.90 50.83 65.80 55.89 9.36:10:15, protein meal; 8.7 gm. N. Began to sweat at end of second hour. 38.87 SS.aH 38.18 112 119 5.5 11.0 -h .77 .75 11 11 70 75 19 14 1.79 1.77 51.83 61.31 Basal. Patient restless in second period. 37.53 123 12.0 .75 11 77 12 '. 1.78 51.67 35.60 S5.62 35.69 91 94 3.8 18.6 .85 .83 n 10 46 51 43 39 1.40 1.45 41.59 42.95 9:03-9:30, protein meal; 10.6 gm. N. 35.73 98 14.5 .85 10 45 45 1.49 44.12 35.82 35.64 35.82 74 88 9.0 9.2 .82 .85 15 15 52 43 33 42 1.17 1.21 34.64 35.73 Basal. Asleep in first period. 36.98 87 7.6 .80 14 59 27 1.31 38.62 35.98 36.54 35.72 83 102 6.0 5.1 1.01 1.07 16 IS 84 85 1.32 1.38 38.95 40.77 At 10:13, 115 gm. com- mercial glucose. 35.75 100 1.2 1.09 15 85 1.37 40.50 35.94) 35.93 84 5.7 .94 13 18 69 1.28 37.66 Basal. 35.95 87 2.5 .88 13 35 52 1.30 38.27 .W.OO 93 7.0 .85 12 46 42 1.36 40.10 37.52 37.29 37.64 105 121 0.3 7.3 .93 1.00 17 17 20 1 63 82 1.54 1.61 45.64 47.81 At 10:26, 115 gm. com- mercial glucose. 37.71 121 2.0 .94 16 19 65 1.65 48.92 37.49 1 37.59 108 1.6 .76 20 67 13 1.65 45.13 Basal. 37.87 114 8.1 .79 19 67 24 1.63 47.36 37.91 117 2.2 .77 18 64 18 1.65 48.00 36.85 .37.44 37.67 37.71 109 120 120 9.2 6.5 1.2 .98 .97 .98 19 18 18 6 8 6 75 74 76 1.62 1.57 1.57 45.07 46.61 46.44 At 10:24, 115 gm. com- mercial glucose. First period 1 hr. 20 min. because patientmoved at end of hour. 36.64 .'56.62 99 1.2 .80 16 58 26 1.46 43.42 Basal. .36.80 100 9.2 .79 16 59 25 1.50 44.35 37.07 105 4.0 .77 15 66 19 1.55 45.93 35.49 35.57 69 8.8 .84 18 44 38 ' 1.13 33.63 Basal. 35.57 76 1.6 .83 18 49 33 1.15 34.43 35.71 79 4.6 .78 17 57 26 1.23 36.74 TABLE 5. — Clinical Calorimetry — Subject Date Weight Period End ol Period Carbon- dioxid, Gm. Oxygen Gm. B.Q. Water, Gm. Urine N per Hour, Gm. Indirect Calo- rimetry, Cal. Heat Elimi- nated, Cal. Direct Calo- rimetry (Bectal Temp.) Cal. Bectal Temp. C. Morris S Jan. 27, 'U 57.50 kg. Prelim. 1 11:45 12:45 19.39 17.28 .82 21.44 0.365 57.63 69.67 66.44 87.06 36.79 2 1:45 22.28 19.73 .82 21.96 0.365 65.98 71.20 73.22 36.90 S 2:45 22.21 19.73 .82 22.74 0.366 65.94 70.02 72.00 36.97 Morris S Dec. 17, '14 61.21 kg. Prelim. 1 11:27 12:27 21.46 19.30 .81 25.58 0.381 64.27 70.65 64.61 36.89 36.70 2 1:27 23.26 21.17 .80 27.85 0.381 70.42 72.99 70.69 36.79 3 2:27 23.02 20.62 .82 27.74 0.381 68.53 72.30 68.84 36.81 Morris S Dec. 18, '14 62.81 kg. Prelim. 1 11:00 12:00 27.66 22.40 .90 31.97 0.409 76.31 77.07 71.53 37.02 36.92 2 1:00 29.29 24.39 .87 34.09 1.101 81.43 84.04 82.67 36.94 3 2:00 23.14 19.14 .88 29.33 1.101 63.60 76.85 73.79 36.89 4 3:00 25.29 21.01 .88 31.79 1.101 69.82 78.61 74.47 36.85 Charles P Nov. 10, 13 S7.73 kg. Prelim. 1 11:10 12:10 26.83 24.23 .81 26.28 0.614 80.56 66.11 79.70 38.94 39.21 2 1:10 27.37 25.06 .79 28.78 0.514 83.17 71.87 73.83 39.26 3 2:10 27.91 25.99 .78 43.30 0.514 86.96 88.09 77.90 39.06 Charles F Nov. 11, "13 58.22 kg. Prelim. 1 11:20 12:20 28.97 24.68 .86 26.84 0.930 82.03 67.32 78.05 38.82 39.05 2 1:20 30.21 26.74 .82 31.12 0.930 88.58 77.70 86.96 39.26 S 2:20 31.40 27.66 .83 31.13 0.930 91.78 82.04 99.99 39.63 Charles P. ... Nov. 14, '13 57.94 kg. Prelim. 1 11:10 12.10 S2.69 26.60 .89 32.29 0.813 89.98 83.73 83.31 39.62 39.62 2 1:10 31.92 25.64 .91 32.26 0.813 87.23 81.28 68.87 39.37 3 2:10 32.24 26.33 .89 32.95 0.813 88.98 89.47 91.35 39.49 Charles F Nov. 15, '13 57.03 kg. Prelim. 1 11:16 12:16 28.26 26.44 .78 28.84 0.657 87.09 75.09 82.25 39.77 39.93 2 1:16 28.23 26.08 .79 32.35 0.667 86.12 86.12 74.34 39.88 Charles P Nov. 29, '13 60.36 kg. Prelim. 1 11:26 12:26 21.39 18.31 .85 29.25 0.483 61.69 61.79 59.74 36.71 36.67 2 1:26 22.06 20.15 .80 28.24 0.483 67.01 63.78 75.00 37.00 3 2:26 21.90 19.44 .82 27.10 0.483 66.08 63.75 72.92 37.26 Charles P Dec. 8, '13 50.99 kg. Prelim. 1 11:10 12:10 25.97 19.63 .96 21.83 0.817 66.98 62.72 52.64 36.90 36.67 2 1:10 26.73 21.61 .90 25.30 0.817 72.92 70.29 75.47 36.86 3 2:10 25.97 21.12 .90 29.04 0.817 71.13 74.23 76.85 36.95 Charles P Dec. 9, '13 60.38 kg. Prelim. 1 11:06 12:06 22.60 18.06 .91 19.36 0.380 61.66 58.80 55.10 36.78 36.70 2 1:06 22.10 17.29 .93 22.22 0.380 59.30 64.40 69.90 36.87 3 2:06 21.98 17.63 .91 22.36 0.380 60.16 61.83 61.66 36.88 Charles P Dec. 10, '13 51.09 kg. Prelim. 1 11:10 12:10 26.98 20.24 .97 22.40 0.362 70.28 62.46 58.29 36.89 36.80 2 1:10 27.70 19.45 1.04 24.37 0.362 68.24 68.32 64.48 36.76 3 2:10 25.68 18.90 .99 28.76 0.362 65.28 72.63 60.44 36.60 —IN Typhoid Fever — {Continued) Surface Temp., 0. Aver- age Pulse Work Adder., Cm. Non- Protein, B.Q. Per Cent. Calorics from Calories Per Hour Pro- tein Pat Carbo- hyd. Per Kg. Per Sq. M. 35.61 35.11 60 0.5 .82 17 51 82 1.00 31.29 Basal. 35.15 71 5.6 .82 15 61 34 1.15 35.82 35.37 68 5.2 .82 15 62 33 1.15 35.80 62 4.0 .81 16 56 29 1.06 33.61 Basal. 65 6.0 .80 14 68 28 1.15 36.83 62 6.0 .82 15 62 33 1.12 36.03 74 5.0 6.0 .91 .92 14 36 21 17 66 47 1.22 1.30 39.23 41.87 At 8:40-9:40 a. m., pro- tein meal; 9.6 gm. N. 70 6.0 .95 46 9 46 1.01 32.66 62 6.0 .93 42 14 44 1.11 35.90 76 8.5 .81 17 56 28 1.40 43.81 Basal. 76 2.0 .79 16 60 24 1.44 46.23 82 9.0 .78 16 64 20 1.49 46.74 37.69 38.24 38.25 77 86 3.6 13.0 .88 .83 30 28 28 42 42 30 1.41 1.52 44.34 47.88 9:10-10:10, protein meal; Nitrogen 6.6 gm. 38.34 84 4.0 .83 27 41 32 1.57 49.61 38.79 38.90 38.68 87 96 15.0 8.3 .93 .94 24 25 19 16 67 60 1.56 1.62 48.80 47.31 At 10:21 a. m., 116 gm commercial glucose. 38.79 96 25.0 .92 24 21 66 1.66 48.25 38.92 39.10 90 17.0 .77 20 63 17 1.63 47.75 Basal. 39.04 88 15.5 .78 20 69 21 1.61 47.22 80 13.2 .86 21 37 42 1.23 36.81 Basal. 86(?) 16.5 .79 20 56 24 1.33 39.98 84 18.8 .83 20 47 33 1.30 38.83 38.24 36.54 36.16 36.37 74 72 84(92) 36.6 20.3 15.0 1.05 .94 .94 32 30 30 13 15 68 67 55 1.31 1.43 1.40 39.64 43.06 41.99 9:03-9:46, protein meal; 10.5 gm. N. Work adder too high on ac- count of rapid changes in barometer. 75 22.S .93 16 19 65 1.23 36.72 Basal. 76 23.0 .96 17 12 n 1.18 36.32 84 9.7 .93 17 20 63 1.20 35.83 73 87 10.0 23.5+2? 1.00 1.08 14 14 86 86 1.38 1.34 41.46 40.26 At 10:22, 116 gm. com- mercial glucose. 81 38.0+2? 1.02 15 85 1.29 38.81 TABLE S. — Clinical Calorimetry- Subject Date Weight Period End of 1 Period Carbon- dioxid, 6m. Oxygen Gm. B. Q. Water, Gm. Urine N per Hour, Gm. Indirect Calo- rimetry, Oal. Heat rumi- nated, Cal. 1 i ! Direct 1 Oalo- Bectal rimetry 1 Temp. (Bectal 0. : Temp.) Cal. Charles ¥ Dec. 26, '13 65.87 kg. 1 Prelim. 1 ^ 11:12 12:12 23.76 19.16 .90 26.72 0.275 i 65.56 76.4? 75.27 36.84 36.90 2 l:12 21.98 18.86 .85 26.23 0.275 63.65 69.83 67.08 36.86 3 2:12 22.11 20.10 ..80 25.14 0.275 67.03 70.63 69.23 36.85 Charles F Dec. 31, '13 55.98 kg. Prelim. 1 1:40 2:40 21.85 19.82 .80 22.56 0.403 65.85 66.09 59.70 37.08 36.95 2 3:40 22.81 21.14 .78 26.98 0.403 69.98 69.09 68.75 36.95 Howard F Nov. 7, '13 35.47 kg. Prelim. 1 11: 16 12:16 22.09 20.53 .78 22.79 68.25 67.28 56.71 39.74 39.73 2 1:16 21.02 19.76 .77 24.24 65.63 64.17 63.90 39.73 3 2 :16 20.86 24.06 65.03 ? 64.99 60.30 39.58 Howard F Nov. 12, '13 34.98 kg. Prelim. 1 11:24 12:24 22.06 19.37 .83 20.58 0.612 64.40 68.89 61.38 39.64 39.74 2 1:24 23.23 20.40 .83 23.38 0.612 67.88 63.72 65.61 39.89 3 2:24 22.55 21.27 .77 23.60 0.612 69.78 63.49 70.09 40.15 Howard P Nov. 13, '13 34.19 kg. Prelim. 1 11:00 12:00 19.45 17.76 .80 22.30 0.436 68.81 57.80 69.64 39.76 39.84 2 1:00 19.64 18.48 .77 22.62 0.436 60.86 58.19 57.19 39.82 3 ' 2:00 20.20 19.24 .76 I 23.66 0.436 63.22 63.74 62.17 38.78 Howard F Nov. 20, '13 32.54 kg. Prelim. 1 11:30 12:30 18.43 17.26 .78 27.43 0.354 56.98 55.72 55.87 39.31 39.33 2 1:30 18.27 17.42 .76 27.31 0.354 67.30 63.70 58.16 39.14 3 2:30 17.96 17.42 .75 25.62 0.354 57.10 59.76 53.97 38.94 Howard F Dee. 1, '13 32.93 kg. Prelim. 1 11:06 12:06 19.35 14.68 .97 18.80 0.292 50.60 45.34 42.26 37.03 36.93 2 3 1:06 2:06 I 39.56 29.26 .98 37.03 0.292 101.68 46.88 ■ 60.17 . 97.14 36.96 36.97 Howard F Dec. 2, '13 33.06 kg. Prelim. 1 11:12 12:12 15.46 12.42 .91 ' 17.57 0.234 42.40 44.03 42.30 36.84 36.79 2 1:12 18.09 13.48 .98 18.64 0.234 46.86 60.53 52.20 36.93 Howard F Dec. B, '13 34.74 kg. Prelim. 1 11:06 12:06 22.13 17.28 .93 21.01 0.614 58.86 56.03 51.80 37.07 36.97 2 1:06 24.24 17.61 1.00 21.99 0.614 60.75 61.84 64.82 37.17 3 2:06 24.72 19.43 .93 23.61 0.614 66.21 64.12 66.52 37.25 Howard F Dec. 6, '13 33.78 kg. Prelim. 1 10:56 11:56 18.20 13.44 .98 17.44 0.267 46.71 47.88 46.67 37.02 36.99 2 12:66 19.17 14.84 .94 18.30 0.267 51.14 51.87 51.43 37.06 ■Howard F ! Dec. 18, '13 37.17 kg. Prelim. 1 11:06 12:06 19.11 16.10 .86 18.73 0.314 64.38 63.61 52.94 37.11 37.10 2 1:06 21.42 18.19 .86 20.94 0.314 61.42 58.80 63.36 37.29 3 2:06 20.93 18.62 .81 ■ 23.84 0.314 62.26 65.14 63.04 37.25 -IN Typhoid Fever — {Continued) Surface Temp., 0. Aver- age Pulse Work Adder., Om. Non- Protein, E.Q. Per Gent. Calories from Calories Per Hour Reniarks Pro- tein Fat Oarbo- liyd. Per Kg. Per 8q. M. ^v^rfi^^x tm^ «LD 36.02 86.09 76 23.2 .92 11 26 63 1.18 36.44 Basal 36.38 18.3 .85 11 44 45 1.14 35.38 35.74 .. 10.2 .80 11 61 28 1.20 37.26 36.90 35.98 78 4.0 .80 16 57 27 1.18 36.38 Basal. 36.68 81 .78 15 64 21 1.25 38.66 100 103 10.0 6.0 1.91 1.83 51.35 49.31 Basal. Urine not ob- tained; 02 lost in third period. 106 2.0 1.8S(?) 48.93(?) 39.01 39.13 39.30 105 104 2.5 9.5 .84 .84 25 24 41 42 34 34 1.84 1.94 48.90 51.55 9:10-9:40, protein meal; 6.5 gm. N. Asleep most ol first period. 39.76 105 5.9 .76 23 63 14 2.00 52.99 108 1.0 .79 20 66 24 1.72 45.34 Basal. 108 2.5 .77 19 65 16 1.78 46.92 104 7.7 .75 18 79 IS 1.85 48.74 39.14 38.89 103 9.6 .77 16 65 19 1.75 45.41 Basal. 38.68 102 9.6 .75 16 70 14 1.76 45.66 38.88 92 9.5 .74 16 75 9 1.75 45.60 37.19 37.16 36.63 37.21 98 97 97 2.6 5.1 6.0 1.00 1.02 15 15 1 84 85 1.63 1.55 39.92 40.19 At 10:19, 115 gm. com- mercial glucose; second and third periods aver- aged. 36.92 36.83 36.60 75 76 2.5 15.6 .92 1.01 15 13 22 63 87 1.28 1.42 33.39 36.90 Basal. Asleep most ol first hour. 91 90 7.0 20.5 .99 1.08 28 27 3 69 73 1.70 . 1.75 44.90 46.34 9.00-10:00, protein meal; 10.2 gm. N. Asleep first period. 93 6.6(?) .97 25 3 67 1.91 60.61 73 76 6.6 14.2 1.02 .96 15 14 11 85 75 1.38 1.51 36.31 39.76 Basal. Asleep one-hall first period. 36.61 36.82 37.00 104 112 5.5 13.0 .87 .87 15 14 37 40 48 46 1.46 1.65 39.66 44.79 Basal. Asleep first period. 36.76 105 17.3 .82 13 63 34 1.68 45.40 TABLE S. — Clinical Caloeimetry — Subject Date Weight Period End ol Period Oarbon dioxid, Gm. Oxygen Gm. E.Q. Water, Gm. Urine N Hour, Gm. 1 Indirec" Calo- rimetry Oal. Heat Elimi- nated, 1 Oal. Direct Oalo- rimetry : (Bectal Temp.) ' Oal. Bectal Temp. 0. Howard F Dec. 30, '13 39.40 kg. Prelim. 1 1:30 2:30 19.66 17.18 .83 22.46 0.278 57.68 62.50 ! 65.92 37.29 37.10 2 3:30 20.74 18.62 .81 23.93 0.278 62.21 60.31 61.45 37.17 Karl S Jan. 5, '14 54.64 kg. Prelim. 1 11:50 12:60 30.78 29.50 .76 39.97 0.720 96.73 101.70 : 91.12 40.14 39.92 2 1:60 29.73 28.53 .76 42.23 0.720 93.48 104.45 93.93 39.70 Karl S Jan. 6, '14 54.52 kg. Prelim. 1 12:30 1:30 34.01 29.51 .84 26.77 0.879 98.46 87.72 112.04 39.63 40.08 2 2:30 35.13 31.49 .81 34.31 0.879 104.43 104.39 99.22 40.06 3 3:30 35.32 S1.56 .81 38.70 0.879 104.75 107.68 105.06 40.02 Karl S Jan. 16, '14 52.21 kg. Prelim. 1 10:50 11:50 26.55 25.94 .74 26.51 0.786 84.44 38.29 38.32 2 1:02 32.49 28.88 .82 38.71 0.943 95.01 38.22 3 1:60 21.52 19.72 .80 32.34 0.655 64.72 38.14 Karl S Jan. 19, '14 .^1.19 kg. Prelim. 1 10:50 11:50 20.70 16.34 .92 12.72 0.522 55.62 36.36 36.54 2 12:60 22.08 18.41 .87 28.28 0.522 62.03 38.55 3 1:50 22.63 19.41 .84 32.55 0.622 64.98 36.67 Karl S Jan. 21, '14 51.29 kg. Prelim. 1 12:30 1:30 24.09 19.71 .89 32.46 0.868 66.11 36.72 36.65 2 2:30 23.96 19.57 .89 26.79 0.858 65.65 36.39 3 3:30 26.95 21.45 .91 32.17 0.858 72.55 38.46 Karl S Jan. 22, '14 50.63 kg. Prelim. 1 12:40 1:40 18.66 15.37 .88 16.87 0.428 51.92 36.75 36.54 2 2:40 21.01 16.98 .90 20.51 0.428 67.70 36.40 3 3:40 20.54 17.06 .88 22.17 0.428 57.62 .S8.48 Karl S Peb. 6, '14 53.30 kg. Prelim. 1 11:05 12:05 23.15 20.28 .83 23.98 0.324 68.07 67.32 58.11 37.15 36.95 2 1:05 21.97 18.82 .85 22.85 0.324 63.43 67.46 68.97 36.72 3 2:05 25.49 24.36 .76 27.16 0.324 80.44 74.45 80.28 36.86 Karl S Feb. 7, '14 54.4B kg. Prelim. 1 10:46 11:46 27.92 22.71 .89 32.41 0.581 77.05 77.13 60.51 37.35 36.99 2 12:46 27.33 ■ 21.87 .91 29.12 0.581 74.43 79.33 74.46 36.89 3 1:46 26.23 21.16 .90 32.41 0.581 71.85 79.75 76.71 36.83 Thomas B Oct. 15, '13 73.62 kg. Prelim. 1 10:48 11:48 24.87 22.60 .80 23.50 0.505 75.00 48.97 70.72 36.79 37.13 2 12:48 27.05 22.82 .86 24.88 0.505 76.95 58.97 72.61 37.38 3 1:48 26.46 24.69 .78 26.46 0.505 81.57 63.67 74.67 37.58 4 2:48 28.39 24.58 .84 28.78 0.505 82.49 67.68 79.68 37.78 Thomas B Oct. il. '13 72,56 kg. Prelim. 1 10:24 11:24 22.98 20.14 .83 24.71 0.407 67.43 62.61 36.69 36.71 2 12:24 24.90 19.11 .95 29.65 0.407 65.88 66.03 63.75 36.71 3 1:24 26.13 20.21 .94 30.15 0.407 69.58 68.06 62.32 36.84 -IN Typhoid Fever — (Continued) Surface Temp., C. Aver- age Pulse Work Adder., Om. Non- Protein, K.Q. Per Cent. Calories trom Calories Per Hour Pro- tein Pat Oarbo- hyd. Per Kg. Per Sq.M. 36.57 36.14 86.60 109 107 6.5 8.5 .84 .81 13 12 48 57 39 31 1.47 1.58 40.49 43.67 Basal. Asleep greater part ot both periods. 39.24 38.97 114 8.4 .75 20 69 11 1.77 54.93 Basal. 38.67 109 6.7 .75 20 69 11 1.71 63.08 88.60 39.61 89.39 107 99(?) 8.8 14.6 .85 .81 24 22 39 60 37 28 1.80 1.92 55.62 69.00 9:45-10:12, protein meal! 10.6 gm. N. 39.27 119 13.0 .82 22 49 29 1.92 59.18 92 96 96 12.2 21.0-1-3? 11.0 .72 .82 .77 26 26 26 70 44 67 5 30 17 1.62 1.53 1.65 49.09 46.03 45.15 Basal. Water tier, broken. Second period 72 min. long on ac- count movement. 76 10.6 .96 25 9 66 1.09 82.74 Basal. 76 14.8-1-4 .89 22 28 50 1.21 36.51 78 16.8 .86 21 39 40 1.27 88.26 73 69 9.8 5.7 .94 .94 34 35 14 13 52 52 1.29 1.28 38.89 38.62 9:35-11:36, protein meal; 10.0 gm. N. 74 17.0 .97 31 7 62 1.42 42.68 59 57 4.0 11.7 .91 .93 22 20 25 20 53 60 1.03 1.14 30.81 34.24 Basal. Asleep first period. 68 9.2 .90 20 29 51 1.14 34.20 36.20 36.62 35.86 81 79 15.5 9.4 .84 .86 13 14 49 42 38 44 1.28 1.19 39.0.? 36.37 Basal. A si 6 e p about SO min. in first period and 50 min. in second. 35.97 82 26.2 .76 11 74 15 1.61 46.12 36.40 36.58 35.97 36.24 94 90 86 12.4 7.2 11.0 .92 .94 .93 20 21 21 22 16 19 58 63 60 1.41 1.37 1.32 43.66 42.07 40.62 7:30-7:40, 44.3 gm. pro- tein; 9:35-9:37, 15.6 gm. protein; total, 9.6 gm. N. Asleep most ol the tiipe. 81 8.0 .80 18 66 26 1.02 34.67 Basal. 85 14.0 .88 17 35 48 1.05 35.58 84 7.6 .77 16 65 19 1.11 37.71 91 21.0 .85 16 43 41 1.12 38.14 73(?) 12.0 .84 16 47 87 0.93 .S1.48 Basal. 78 19.0 .98 16 6 78 0.91 30.76 84 .97 16 9 75 0.96 32.48 TABLE 5. — Clinical Calorimetry — Subject Date Weight Period End of Period Oarbon- dioxid, Gm. Oxygen, Gm. R.Q. Water, Gm. Drine N Hour, Gm. Indirect Calo- rimetry, Oal. Heat Elimi- nated, Oal. Direct Calo- rimetry (Bectal Temp.) .Cal. Bectal Temp. C. Richard T Oct. 18, '13 36.49 leg. Prelim. 1 9:48 10:48 20.39 18.59 .80 30.29 0.403 61.65 43.77 67.62 38.18 38.60 2 11:48 21.05 18.24 .84 21.24 0.403 61.12 42.57 66.86 39.50 3 12:48 20.49 18.68 .80 26.61 0.403 61.95 ? 45.94 62.35 39.74 Richard T Oct. 20, '13 3S.37 kg. Prelim. 1 10:16 11: 16 18.98 15.18 .91 31.21 0.499 51.48 42.37 68.44 37.68 38.24 2 12:16 21.25 18.39 .84 31.41 0.499 61.49 47.46 68.51 38.63 3 1:18 19.90 17.96 .81 29.74 0.499 69.49 48.42 46.90 38.64 Anton K Oct. 16, '13 60.56 kg. Prelim. 1 11:16 12:16 22.48 18.64 .88 30.88 0.479 62.98 61.00 61.00 36.99 36.99 2 1:16 21.65 19.08 .83 33.40 0.479 63.64 66.46 72.34 37.14 3 2:16 23.57 19.73 .87 30.29 0.479 66.57 64.84 68.61 37.24 Rose G Nov. 22, '13 30.11 kg. Prelim. 1 11:04 12:04 17.77 16.73 .82 28.24 62.81 51.24 63.76 37.04 37.15 2 12:34 9.28 7.28 .93 17.44 24.98 28.36 24.99 37.02 Edw. B Oct. 23, '14 65.76 kg. Prelim. 1 12:07 1:07 25.02 22.61 .81 30.22 0.187 76.66 62.23 70.20 38.07 38.25 2 2:07 25.51 23.48 .79 28.78 0.187 78.30 64.70 81.43 38.62 3 3:07 27.24 26.69 .77 29.84 0.187 85.03 70.05 71.67 38.88 Edw. B Oct. 26, '14 66.10 Jcg. Prelim. 1 11:24 12:24 23.13 19.68 .86 31.21 0.264 66.36 61.58 66.23 37.54 37.66 2 1:24 24.87 23.79 .76 29.49 0.264 78.72 60.08 67.98 37.83 3 2:24 25.18 22.90 .80 30.36 0.264 76.47 66.46 73.34 38.01 4 3:24 26.12 23.21 .82 31.13 0.264 77.87 70.55 84.46 38.32 Edw. B Oct. 27, '14 56.84 kg. Prelim. 1 11:20 12:20 24.80 21.91 .82 30.89 0.662 73.08 60.09 69.69 37.40 87.46 2 1:20 23.76 22.13 .78 29.26 0.552 73.01 61.33 70.63 37.68 8 2:20 23.24 22.30 .76 28.83 0.552 73.13 63.78 73.06 37.91 Edw. B Nov. 4, '14 68.72 kg. Prelim. 1 11:15 12:15 24.00 19.79 .88 31.79 0.337 67.32 64.06 64.69 37.16 37.18 2 1:15 25.03 21.77 .84 31.06 0.337 73.17 65.16 69.21 37.27 3 2:15 24.89 21.98 .82 31.62 0.337 73.72 70.13 74.19 37.36 Edw. B Nov. 6, '14 69.78 kg. Prelim. 1 11:15 12:15 26.21 23.22 .82 27.40 0.336 77.76 62.39 81.16 38.84 39.28 2 1:15 26.65 23.45 .83 28.17 0.336 78.07 64.20 69.44 39.41 3 2:15 26.61 23.39 .82 30.30 0.336: 78.33 68.49 72.76 39.62 Edw. B Nov. 10. '14 66.87 kg. Prelim. 1 11:15 12:15 30.59 30.14 .74 35.32 0.626 98.74 88.66 86.50 40.32 40.33 2 1:15 29.62 27.49 .78 36.30 0.626 90.99 87.53 91.26 40.43 3 2:15 30.25 39.64 0.625 94.67 86.34 40.26 John K Dec. 15, '14 63.81 kg. Prelim 1 11:56 12:66 30.97 28.17 .80 34.02 1.258 92.29 85.30 94.23 39.00 39.26 2 1:56 30.59 30.08 .74 39.95 1.258 97.14 91.58 87.82 39.22 -IN Typhoid Fever — {Continued) Surface Temp., 0. 35.75 36.05 36.10 Aver- ' Work age ' Adder., Pulse Cm. Non- Protein, B. Q. 81 102 95 76 81 80 79 118 115 116 105 117 126 123 106 109 107 102 104 105 124 124 141 142 140 31.4 16.2 18.5 22.0 30.0 17.0 21.0 19.0 13.0 16.0 9.0 12.0 17.0 24.0 11.0 10.0 10.0 19.0 14.0 22.0 14.0 10.6 14.0 25.0 31.0 5.0 12.0 24.0 30.5 16.0+ + 16.0 14.0 .80 .85 .80 .95 .85 .81 .81 .79 .77 .87 .76 .80 .82 .83 .78 .75 .90 .84 .73 .78 .70 Per Cent. Calories from Pro- tein Pat Carbo- hyd. 17 57 17 43 17 i 57 26 22 22 20 20 19 19 19 19 13 12 12 11 11 11 14 15 36 34 13 40 50 28 46 32 49 67 73 47 61 54 51 64 79 64 43 66 40 26 61 34 49 44 27 21 50 17 29 35 3i 20 12 57 40 37 35 38 36 7 21 21 Calories Per Hour Per Kg. 1.69 1.68 1.70 1.25 1.26 1.32 1.75 1.66 1.36 1.40 1.53 1.18 1.40 1.36 1.39 1.29 1.29 1.29 1.15 1.25 1.26 1.30 1.31 1.31 1.74 1.60 1.45 1.52 Per Sg. M. Bern arks 45.60 45.11 45.72 1.45 38.79 1.74 46.34 1.68 44.83 37.42 37.81 39.55 44.32 41.93 42.10 43.57 47.32 36.78 43.64 42.39 43.17 40.16 40.12 40.18 36.19 39.34 39.64 41.32 41.48 41.62 54.31 50.05 46.94 49.41 Basal. Somewbat rest- Basal. Basal. Basal. Bestless. Second period ^ br. long be- cause patient voided in bed. Basal. 10:25 a. m., 79 gm. olive oil = 760 calories. Basal. Basal. Bising temp. Basal. Very high temp. Mildly delirious. Basal. TABLE 6.— Clinical Data Charles F. Date, Pooa Pood N., Gm. Urine N., Gm. Excreta N., Gm. Nitrogen Bal., Gm. Body Wt., Kg. Urine 1918 Total Calories Carbohy- drate, Gm. Fat, Gm. Vol., O.C. Nov. 6.... 1,465 88.0 96.0 8.3 14.68 16.61t —7.21 58.66 1,270 Nov. 7.... 16.62 1,600 Nov. 8.... 1,866 116.0 123.0 9.1 21.10 22.01 —12.91 2,300 Nov. 9.... 2,066 130.0 136.0 10.8 20.45 21.63 —10.73 1,870 Nov. 10.... 1,088 80.0 69.0 4.4 16.22 16.66 -12.26 67.76 1,205 Nov. 11.... 2,027 214.0 87.0 13.2 22.28 23.60 —10.40 58.25 1,740 Nov. 12.... 2,610 261.0 144.0 9.8 18.92 19.90 —10.10 2,110 Nov. 18.... 2,265 218.0 118.0 10.2 17.37 18.39 —8.19 57.88 1,900 Nov. 14.... 1,399 208.0 60.0 3.8 16.03 16.41 —12.61 67.60 1,236 Nov. 15.... 1,286 148.0 60.0 4.6 18.64 19.00 —14.40 66.86 1,270 Nov. 16. . . . 1,440 161.0 72.0 6.7 18.89 19.46 —13.76 1,960 Nov. 17.... 1,492 128.0 83.0 7.6 17.82 18.58 —10.98 2,110 Nov. 18.... 1,749 133.0 107.0 8.1 20.34 21.15 —13.05 56.01 1,470 Nov. 19.... 1,019 63.0 68.0 5.2 22.13 22.65 —17.45 1,360 Nov. 20.... 1,328 93.0 76.0 8.7 22.41 23.28 —14.58 1,380 Nov. 21. . . . 1,426 74.0 98.0 8.1 22.81 23.62 —16.52 1,380 Nov. 22.... 1,970 122.0 128.0 10.9 20.50 21.69 —10.69 1,900 Nov. 23.... 1,787 112.0 115.0 10.6 18.16 19.22 —8.62 1,680 Nov. 24.... 1,696 117.0 101.0 10.4 18.16 19.20 —8.80 52.02 1,580 Nov. 25.... 2,443 159.0 155.0 13.8 18.95 20.33 —6.53 1,910 Nov. 26.... 2,695 174.0 160.0 15.4 18.92 20.46 —6.06 51.48 20.50 Nov. 27.... 2,345 173.0 142.0 12.3 18.41 19.64 —7.34 1,920 Nov. 28. . . . 2,646 223.0 160.0 13.1 16.65 17.96 —4.86 60.98 2,120 Nov. 29.... * 1,903 129.0 126.0 7.8 13.91 14.69 —6.89 50.29 1,150 Nov. 30.... 2,825 236.0 158.0 16.2 15.68 17.10 —1.90 1,700 Dee. 1.... 3,491 314.0 195.0 14.9 14.12 15.61 —0.71' 60.50 1,760 Dec. 2.... 8,126 310.0 160.0 14.3 12.83 13.76 +0.64 1,480+ Dec. 3.... 2,695 279.0 118.0 ]3.7 11.99 13.36 +0.34 60.79 1,600 Dec. 4.... 3,408 382.0 150.0 17.4 12.69 14.43 +2.96 1,480 Dec. 6 — 2,683 362.0 87.0 15.0 12.05 13.55 +1.45 1,580 Dec. 6. . . . 2,827 390.0 88.0 15.9 12.67 14.26 +1.64 49.83 1.401 Dec. 7.... 8,223 446.0 106.0 16.0 12.72 14.32 +1.68 49.83 1,740 Dec. 8.... 2,182 346.0 94.0 20.0 16.27 18.27 +1.73 61.02 1,220 Dec. 9.... 2,426 308.0 91.0 12.5 12.04 13.29 —0.79 50.41 695 Dec. 10.... 2.906 432.0 88.0 12.3 10.01 11.24 +1.06 ' 50.80 1,100 Dec. 11.... 3,485 603.0 107.0 16.7 9.47 11.14 +6.56 1,640 Dec. 12.... 3,768 656.0 116.0 16.3 9.92 11.55 +4.75 1,600 Dec. IS.... 4,025 619.0 129.0 18.2- 10.48 12.30 +6.90 68.16 1,880 Dec. 14.... 3,660 649.0 105.0 16.8 10.69 12.27 +4.53 1,470 * Estimate heat production 1,726. TABLE 6. — Clinical Data — (Continued) Charles F. — (Continued) Date, Pood Pood N., Gm. Urine N., 6m. 191S Total Calories Carbohy- drate, Gm. Pat, Gm. N., Gm, Dec. 15.... 4.032 585.0 124.0 18.8 9.93 11.81 Deo. 16.... 3.921 573.0 118.0 18.6 11.67 13.53 Dec. 17.... 3,539 510.0 109.0 16.9 11.15 12.84 Dee. 18.... 3,869 572.0 113.0 18.2 11.64 13.36 Dec. 19.... 4,085 630.0 112.0 17.9 10.39 12.18 Dec. 20.... 3,901 699.0 105.0 18.5 11.04 12.89 Dec. 21.... 4.017 620.0 105.0 19.3 11.43 1-3.36 Dec. 22.... 3,361 282.0 189.0 17.1 12.33 14.04 Dec. 23.... 3,722 241.0 249.0 16.4 11.46 13.10 Dec. 24.... 3,739 228.0 254.0 17.5 13.14 14.89 Dec. 25.... 9.28 Dec. 26.... 2,122 163.0 137.0 12.4 9.40 10.64 Dec. 27.... 3,636 254.0 224.0 20.0 12.16 14.16 Dec. 28.... 3,614 247.0 226.0 19.4 12.86 14.80 Dec. 29.... 3,818 221.0 269.0 19.0 12.78 14.66 Dec. 30.... 4,899 256.0 347.0 24.2 11.49 13.91 Dec. SI.... 2,131 202.0 103.0 13.3 11.63 12.86 Jan. 1 — 3,949 S47.0 161.0 18.6 11.54 13.40 Jan. 2.... 3,587 287.0 202.0 22.0 8.10 10.30 Nitrogen Bal., Gm. Body Wt., Kg. Urine Vol., O.c. +6.99 62.81 1,330+ +6.07 54.06 1,280 +4.06 1,470 +4.84 1,800 +6.72 1,600 +6.61 1,760 +5.94 1,860 +3.06 66.43 1,700 +3.30 1,180 +2.61 1,440 1.300 +1.76 65.91 1,940 +5.84 1,600 +4.60 1,640 +4.34 1,820 +10.29 1,480 +0.44 56.43 1,571 +5.20 1,000 +11.70 860 t Excreta nitrogen estimated as urine nitrogen + 10 per cent, of food nitrogen. TABLE 6. — Clinical Data — (Continued) Morris S. Esti- mated Heat Produc- tion per 24Hra. Pood Date, 1913 Total Calories Carbo- hydrate, Gm. Pat, Gm. Pood N., Gm. Urine N., Gm. Feces N., Gm. Excreta N., Gm. Bal., Gm. WeigM Kg. Volume, C.c. Pat Oct. 23 2,962 419.0 76.0 20.8 16.13 3.1* 18.2 H-2.6 49.69 1,280 Oct. 24 2,376 1,2S9 169.0 28.0 11.8 19.56 1.7* 21.3 —9.5 61.60 2,860 Oct. 25 2,299 2,371 364.0 36.0 21.3 13.59 8.2* 16.8 -1-4.5 51.22 1,710 Oct. 26 4,375 471.0 101.0 19.6 20.34 2.9 23.2 -3.7 3,000 Oct. 27 3,194 321.0 152.0 18.2 21.60 2.7 24.3 —6.1 51.26 2,170 Oct. 28 2,200 2,332 242.0 116.0 10.0 17.43 1.5 18.9 —8.9 61.18 1,390 Oct. 29 2,228 2,876 258.0 150.0 16.4 20.38 2.5 22.9 —6.5 60.17 1,465 Oct. 30 8,031 318.0 141.0 16.5 18.72 2.31 21.03 —5.5 49.85 1,680 9.74 Oct. 31 2,225 2,784 224.0 149.0 18.0 22.28 2.31 24.59 —6.6 60.32 1,830 9.74 Nov. 1 3,089 827.0 147.0 14.8 17.48 2.31 19.79 —6.0 49.82 1,600 9.74 Nov. 2 3,039 324.0 142.0 16.2 16.76 2.31 19.07 —3.9 1,600 9.74 Nov. 3 2,206 3,039 324.0 142.0 15.2 17.39 2.31 19.70 —4.6 48.83 1,870 9,74 Nov. 4 8,039 324.0 142.0 15.2 16.86 2.31 18.17 -3.0 49.63 1,220 9.74 Nov. 5 2,104 3,024 324.0 139.0 16.4 16.57 2.31 17.88 —2.5 48.48 1,160 9.74 Nov. 6 3,039 325.0 147.0 15.4 13.51 2.3 16.8 -0.4 49.03 1,310 Nov. 7 3,034 327.0 140.0 15.0 12.39 2.3 14.7 -1-0.3 1,220 Nov. 8 3,018 319.0 142.0 16.0 11.24 2.3 18.6 -H.5 48.73 1,810 Nov. » 3,048 321.0 144.0 15.4 11.71 2.3 14.0 -1-1.4 1,240 Nov. 10 2,969 305.0 144.0 14.9 12.05 2.2 14.3 -^o.6 2,000 Nov. U 3,004 324.0 140.0 14.8 10.23 2.2 12.4 -f2.4 48.05 1,220 Nov. 12 2,998 314.0 142.0 16.2 12.78 2.3 16.1 -fO.1 1,880 Nov. 18 2,998 314.0 142.0 16.2 11.43 2.3 13.7 -1-1.6 1,480 Nov. 14 S,181_ 331.0 142.0 15.4 10.64 2.3 12.8 -1-2.6 1,390 Nov. 15 2,994 313.0 142.0 16.2 10.42 2.3 12.7 H-2.5 2,000 Nov. 16 8,134 841.0 144.0 16.3 11.44 2.8 13.7 -H.6 1,820 Nov. 17 1,875 S,«6 333.0 142.0 15.2 18.82 2.3 15.6 -0.4 48.80 1,690 Nov. 18 2,022 1,987 217.0 95.0 8.0 16.19 1.2 16.4 —8.4 49.06 1,440 Nov. 19 1,355 148.0 61.0 7.7 16.47 1.2 16.7 —9.0 2,280 « Nov. 20 1,727 199.0 79.0 7.0 16.18 1.1 16.2 —9.2 1,300 Nov. 21 1,805 171.0 95.0 8.4 14.74 1.3 16.0 —7.6 900 Nov. 22 2,292 153.0 152.0 10.1 14.86 1.6 16.4 —6.8 800 Nov. 23 2,392 192.0 132.0 10.7 15.69 1.6 17.3 -6.6 840 Nov. 24 2,282 2,016 173.0 117.0 8.5 13.08 1.3 14.4 —6.9 46.98 890 Nov. 25 2,301 2,298 187.0 123.0 15.1 18.66 2.3 16.0 -0.9 47.47 925 Nov. 26 2,217 2,087 172.0 126.0 8.0 10.32 1.2 11.6 —3.5 45.84 780 Nov. 27 2,747 242.0 148.0 14.8 18.58 2.2 20.8 —6.0 820 Nov. 28 2,741 256.0 14O.0 15.0 12.44 2.3 14.7 -fO.S 47.26 980 Nov. 29 3,038 324.0 142.0 15.0 11.82 2.3 14.1 -fO.9 1,370 Nov. 30 3,153 834.0 147.0 16.0 10.76 2.4 18.2 -1-2.8 1,060 Dec. 1 3,091 333.0 142.0 16.7 9.81 2.4 12.2 -1-3.6 47.08 1,180 Dec. 2 8,090 340.0 142.0 15.3 9.69 2.3 12.0 -1-3.3 1,660 -f * Peces analyzed October SO to November 6. Peces nitrogen averaged 14.8 per cent, of food nitrogen. On all other days the feces nitrogen was calculated as 15 per cent, of food nitrogen. TABLE 6. — Clinical Data — (Continued) Morris S. — (Continued) Esti- mated Heat Produc- tion per 24Hrs. Pood Date, 1913 Total Calories Carbo- hydrate, Gm. Fat, Gm. Pood N., Gm. Urine N., Gm. Peces N., Gm.* Excreta N., Gm.* Nitrogen Balance, Gm. Body Weight, Kg. Urine Volume, O.c. Pat Dee 3 3,189 366.0 141.0 16.0 8.52 2.4 10.9 +5.1 47.31 930 Dee. i 3,11S 250.0 180.0 16.0 8.70 2.4 11.1 -1-4.9 1,600 Dec. 5 2,977 156.0 209.0 15.0 8.74 2.3 11.0 -1-4.0 1,520 Dec. 6 2,998 161.0 209.6 15.0 9.75 2.3 12.1 -1-2.9 46.55 1,340 Dec. 7 3,297 202.0 221.0 16.0 9.08 2.4 11.5 +i.5 1,640 Dec. 8 3,914 206.0 289.0 14.9 8.55 2.2 10.8 -1-4.1 1.340 Dec. 9 3,989 219.0 290.0 15.2 7.65 2.3 10.0 -1-5.2 47.63 1,140 Dec. 10 3,989 219.0 290.0 15.2 8.85 2.3 11.2 -1-4.0 1,650 Dec. 11 3,989 219.0 290.0 ■ 15.2 9.31 2.3 11.6 +3.6 48.46 1,850 Dec. 12 1,867 3,652 222.0 226.0 21.3 9.87 3.2 13.1 4-8.2 48.64 1,700 Dec. 13 1,604 2,925 395.0 104.0 13.1 12.64 2.0 14.6 —1.5 48.10 1,935 Dec. U 3,256 475.0 95.0 16.5 9.47 2.5 12.0 -1-4.5 1,100 Dec. 15 1,723 8,117 511.0 74.0 13.0 8.68 2.0 10.7 -f2.3 47.87 1,229 Dec. 16 1,703 2,132 275.0 76.0 11.6 10.24 1.7 11.9 -0.3 47.91 802 Dec. 17 3,985 440.0 193.0 15.5 9.30 2.3 11.6 -f3.9 1,240 Dec. 18 3,499 266.0 224.0 14.4 10.82 2.2 13.0 -H.4 1,670 Dec. 19 2,058 2,868 248.0 173.0 9.6 11.34 1.4 12.7 —3.1 48.34 1,282 Dec. 20 2,081 2,748 150.0 190.0 141 13.41 2.1 15.5 —1.4 48.55 1,343 Dec. 21 3,426 204.0 232.0 16.0 17.32 2.4 19.7 —3.7 48.55 1,560 Dec. 22 2,217 3,034 345.0 140.0 12.2 14.42 1.8 16.2 —4.0 48.60 1,223 Dec. 23 1,982 2,499 121.0 186.0 10.7 11.94 1.6 13.5 —2.8 48.54 883 Dec. 24 3,357 206.0 226.0 16.5 13.06 2.5 15.6 -1-0.9 1,480 Dec. 25 .... 10.90 .... 1,200 Dec. 26 8,560 189.0 263.0 17.1 10.48 2.6 13.1 -f4.0 49.70 1,680 Dec. 27 3,180 159.0 227.0 16.4 11.10 2.5 13.6 -1-2.8 1,930 Dec. 28 3,128 157.0 224.0 15.5 11.43 2.3 13.7 -H.8 1,740 Dec. 29 3,109 157.0 222.0 15.5 11.77 2.3 14.1 -1-1.4 1,380 Dec. 30 3,277 170.0 235.0 15.5 11.72 2.3 .14.0 -1-1.5 1,710 Dec. 31 2,990 293.0 143.0 17.9 12.61 2.7 15.3 -t-2.6 1,600 1914 Jan; 1 2,991 256.0 166.0 15.4 12.11 2.3 14.4 -H.O 2,120 Jan. 2 1,567 2,078 141.0 132.0 10.7 10.01 1.6 11.6 -0.9 49.22 1,340 Jan. 3 3,051 ■158.0 216.0 is'.e 12.27 2.3 14.6 -1-1.0 2,160 Jan. 4 3,070 162.0 216.0 16.7 10.40 2.4 12.8 -f2.9 1,730 Jan. 5 .... 11.21 1,580 Jan. 6 3,044 158.0 215.0 15.5 12.69 2.3 15.0 -fO.5 2,330 Jan. 7 3,045 158.0 215.0 15.5 11.66 2.3 14.0 -1-1.5 1,800 Jan. 8 3,068 162.0 215.0 15.6 11.77 2.3 14.1 -1-1.5 1,460 Jan. 9 3,063 162.0 215.0 15.6 11.66 2.3 14.0 -1-1.6 1,660 Jan. 10 3,475 268.0 208.0 17.3 12.10 2.6 14.7 +2.6 1,460 Jan. 11 3,739 354.0 191.0 19.8 12.22 3.0 15.2 +i.e 1,560 Jan. 12 3,551 344.0 177.0 19.5 12.61 2.9 15.5 -1-4.0 2,350 Jan. 13 4,198 382.0 222.0 22.1 11.49 3.3 14.8 -1-7.3 1,520 * Exei eta nitrog en estimat ed as urin e nitrogen -1- 15P er cent ( )1 food nitrogen . TABLE 6. — Clinical Data — (Continued) Howard F. Date, Food Food N., Gm. Urine N., Gm. Excreta N., Gm. Nitrogen Bal., Gm.* Body Wt., Eg. Urine 1913 Total Calories Carbohy- drate, Gm. Pat, Gm. Vol., O.C. Nov. 6.... 1,264 83.0 81.0 6,7 12.83 13.50 —6.80 36.06 970 Nov. 7.... 918 62.0 59.0 4.4 12.05 12.49 —8.09 35.74 640 Nov. 8.... 1,538 87.0 107.0 7.0 12.75 13.45 —6.45 35.79 840 Nov. 9.... 1,454 106.0 88.0 7.7 12.61 13.38 —5.68 760 Nov. 10.... 1,401 115.0 78.0 8.1 12.67 13.48 —5.38 680 Nov. 11.... 925 93.0 38.0 7.5 13.79 14.54 —7.04 34.60 750 Nov. 12.... 950 98.0 40.0 7.3 13.12 14.15 —6.85 35.01 830 Nov. 13.... 1,260 134.0 60.0 5.8 12.52 13.10 —7.30 34.22 610 Nov. 14.... 580 52.0 30.0 3.4 10.42 10.76 —7.36 500 Nov. 15. . . . 1,162 83.0 69.0 6.6 11.10 11.76 —5.16 33.36 900 Nov. 16.... 1.096 150.0 40.0 4.4 9.98 10.42 —6.02 500 Nov. 17.... 1,462 123.0 83.0 7.2 9.30 10.02 —2.82 33.12 400 Nov. 18. . . . 1,688 128.0 91.0 8.5 10.20 11.05 —2.55 32.93 590 Nov. 19.... 984 63.0 62.0 5.7 10.65 11.22 —5.52 780 Nov. 20. . . . 1,288 74.0 75.0 7.S 10.25 10.98 —3.68 32.57 550 Nov. 21.... 1,466 91.0 95.0 8.1 11.32 12.13 —4.03 700 Nov. 22.... 1,198 73.0 94.0 8.8 11.12 12.00 —3.20 800 Nov. 23.... 1,789 92.0 121.0 11.6 11.15 12.31 —0.71 660 Nov. 24.... 1,846 146.0 145.0 10.6 10.82 11.88 —1.28 820 Nov. 25. . . . 2,060 138.0 129.0 11.4 9.81 10.95 +0.45 32.14 940 Nov. 26.... 2,686 176.0 168.0 15.7 10.42 11.99 +3.71 780 Nov. 27.... 2,240 211.0 118.0 10.9 9.47 10.56 +0.34 570 Nov. 28.... 2,742 245.0 145.0 16.0 9.98 11.48 +3.52 32.25 920 Nov. 29. . . . 2,581 211.0 152.0 11.9 8.62 9.71 +2.19 620 Nov. 30.... 2,922 273.0 153.0 14.8 9.53 11.01 +3.79 1,220 Dec. 1.... 2,681 309.0 . 112.0 10.6 7.77 8.83 +1.77 870 Dec. 2 2,298 247.0 110.0 10.0 7.69 8.69 +1.31 33.09 900 Dec. 3.... 3,689 423.0 163.0 17.2 9.25 10.97 +6.23 900 Dec. 4 3,627 441.0 • 147.0 17.7 9.0O 10.77 +6.93 1.130 Dec. 5.... 2,671 S37.0 81.0 21.0 13.01 15.11 +5.89 34.77 1,500 Dec. 0.... 2,476 333.0 83.0 12.9 9.20 10.49 +2.41 33.81 775 Dec. 7.... 3,621 496.0 119.0 19.0 10.45 12.35 +6.65 1,600 Dec. 8.... 3,391 434.0 112.0 17.8 9.89 11.67 +6.13 1,270+ Dee. 9.... 3,042 386.0 108.0 18.0 10.73 12.53 +6.47 35.51 1,300 Dec. 10.... 2,986 394.0 101.0 16.8 10.51 12.19 +4.61 1.450 Dec. 11.... 3,149 ' 405.0 114.0, 17.8 10.79 12.57 +5.23 35.99 1,450 Dec 12.... 3,100 417.0 101.0 17.5 10.36 12.11 +5.39 1,610 Dec. 13.... 3,544 472.0 122.0 18.5 10.03 11.88 +6.62 36.65 1,280 TABLE 6. — Clinical Data — {Continued) Howard F. — (Continued) I'ood rood N., Gm. Urine N., Gm. Excreta N., Gm. Nitrogen Bal., Gm.' Body Wt., Kg. 1913 Total Calories Carbohy- drate, Gm. Eat, Gm. Vol., C.C. Dec. U.... 3,338 402.0 133.0 17.8 11.01 ' 12.79 +5.01 1,880 Dea. 15.... 3,280 510.0 130.0 19.2 12.98 14.90 +4.30 37.54 1,890+ Dec. 16.... 3,5U 444.0 ■ 129.0 35.2 13.28 15.20 +4.00 1,580 Dec. 17.... 3,170 845.0 139.0 18.0 9.95 11.75 • +6.25 39.10 1,720 Dec. 18.... 2,008 248.0 78.0 10.5 8.57 9.62 +0.88 37.17 1,600 Dec. 19.... 3,550 411.0 144.0 20.3 11.89 13.92 +6.38 2.050 Dee. 20 2,671 110.0 197.0 15.0 8.10 9.60 +5.40 1,540 Dec. 21.... 2,383 104.0 175.0 12.6 10.65 11.91 +0.69 1,250 Dec. 22.... 2,936 159.0 198.0 17.3 13.23 14.96 +2.34 37.21 1,150 Dec. 23.... 3,620 239.0 235.0 13.9 9.19 10.58 +3.32 1,200 Dec 24.... 3,605 219.0 243.0 17.4 10.70 12.44 +4.96 1,700 Dec. 25.... 10.42 1,370 Dee, 26.... 3,152 219.0 199.0 15.6 9.77 11.33 +4.27 39.46 2,100 Dec. 27.... 3,303 257.0 196.0 16.8 10.03 11.71 +5.09 1.600 Dec. 28.... 2,946 20O.0 186.0 15.4 7.51 9.06 +6.35 1.080 Dec. 29.... 4,199 265.0 278.0 20.5 10.87 12.92 +7.68 1,640 Dec. 30.... 2,325 165.0 145.0 11.4 7.81 8.96 +2.45 39.39 987 Dec. 31.... 3,569 317.0 192.0 18.5 11.77 13.62 +4.88 1,500 Jan. 1.... 2,912 236.0 169.0 14.5 9.02 10.47 +4.03 1,600 Jan. 2.... 2,891 224.0 166.0 16.0 8.74 10.34 +5.66 1,540 ■ Excreta nitrogen estimated as urine nitrogen + 10 per cent of iood nitrogen. TABLE 6. — Clinical Data — (Continued) Karl S. Esti- mated Heat Produc- tion per 24 Hrs. Food Nitrogen Balance, Gm. Body Weight, Kg. Urine Volume, O.c. Date, 1914 Total Calories Carbo- hydrate, Gm. Fat, Gm Food N., 6m. N., Gm. N.. Gm. N., Gm.* 10.8 20.62 21.60 —10.80 880 Jan. S 2,038 104.0 146.0 Jan. 4 ... 1,301 113.0 71.0 6.9 21.72 22.41 —15.51 1,240 Jan. 5 2,579 1,119 95.0 64.0 6.4 54.67 726 Jan. 6 2,707 1,332 167.0 32.0 13.6 22.36 23.72 —10.12 64.31 1,010 Jan. 7 1,942 93.2 136.0 11.3 810 Jan. 8 2,331 136.0 156.0 12.5 16.03 17.28 —4.78 860 Jan. 9 1,892 114.0 126.0 9.8 23.84 24.82 —15.02 62.99 1,700 Jan. 10 2,910 223.0 174.0 14.6 Jan. 11 3,018 318.0 • 139.0 16.4 Jan. 12 3,017 322.0 138.0 16.2 18.15 1.6 19.8 -3.6 2,310 Jan. 13 2,966 326.0 128.0 17.2 13.94 1.7 15.6 -1-1.6 1,820 Jan. 14 2,802 313.0 118.0 16.4 17.06 1.6 18.7 —2.3 1,830 Jan. 15 3,129 323.0 149.0 16.2 18.65 1.6 20.3 ^.1 62.74 1,920 Jan. 16 2,208 2,448 226.0 132.0 11.5 19.11 1.2 20.3 —8.8 52.24 1,960 Jan. 17 3,398 340.0 166.0 17.9 19.16 1.8 21.0 —3.1 1,940 Jan. 18 3,138 329.0 146.0 17.1 17.26 1.7 19.0 —1.9 1,920 Jan. 19 1,651 2,795 268.0 145.0 13.6 14.72 1.4 16.1 —2.5 51.21 1,260 Jan. 20 2,965 S13.0 138.0 15.7 14.61 1.6 16.1 -0.4 1,550 Jan. 21 1,798 2,912 S15.0 129.0 16.3 17.67 1.6 19.2 —2.9 S1.52 1,870 Jan. 22 1,612 2,605 253.0 133.0 12.8 13.25 1.3 14.6 -1.8 51.18 1,194 Jan. 2S 3,033 324.0 140.0 15.9 11.99 1.6 13.6 +2.S 1,360 Jan. 24 2,982 315.0 138.0 15.8 13.06 1.6 14.7 -1-1.1 1,960 Jan. 25 2,967 316.0 139.0 15.8 13.17 1.6 14.8 -1-1.0 1,400 Jan. 26 3,641 408.0 155.0 16.7 12.64 1.7 14.3 H-2.4 64.64 1,620 Jan. 27 3,999 439.0 191.0 16.3 13.06 1.6 14.7 -H.6 1,460 Jan. 28 4,025 439.0 194.0 16.3 11.88 1.6 13.5 -f2.8 1,280 Jan. 29 3,975 438.0 190.0 16.1 11.32 1.6 12.9 -1-3.2 52.54 1,460 Jan. 30 3,991 439.0 191.0 16.2 10.65 1.6 12.S -1-3.9 1,600 Jan. 31 3,922 418.0 193.0 16.2 10.93 1.6 12.5 +3.7 1,400 Feb.- 1 3,940 418.0 194.0 16.3 10.63 1.6 12.2 -1-4.1 1,600 I-eb. 2 3,808 419.0 180.0 16.0 11.21 1.6 12.8 +S.2 1,910 Feb. 3 3,808 419.0 180.0 16.0 11.15 1.6 12.8 -1-3.2 1,980 Feb. 4 3,971 442.0 188.0 16.0 10.87 1.6 12.5 -f3.5 1,870 Feb. 5 3,974 438.0 191.0 16.0 9.29 1.6 10.9 -1-6.1 1,640 Feb. 6 1,916 3,232 330.0 165.0 13.3 1U.24 1.3 11.6 -H.8 63.33 1,360 Feb. 7 1,965 3,526 387.0 148.0 22.1 2.2 17.3 -1-4.8 64.48 2,300 Feb. 8 4,018 474.0 178.0 16.3 11.67 1.6 13.3 -1-3.0 1,440 ' Excreta nitrogen estimated as urine nitrogen + 10 per cent, oi food nitrogen. 6. — Clinical Data — {Continued) Thomas B. Food Date Temperature Total Calories Carbo- hy- drate, Gm. Pat, Gm. Food N., Gm. Urine N., Gm. Feces N., Gm. Excreta N., Gm. Nitrogen Balance, Gm. Body Weight, Kg. Urine Volume, C.c. Fat 191S Max. Min. Oct. 7 103.0 101.4 8,052 168.0 212.0 16.0 24.56 2.09 26.64 —11.64 76.08 1,240 9.19 Oct. 8 103.6 101.2 8,010 163.0 210.0 16.0 25.50 2.09 27.59 —12.69 75.61 1,270 9.19 Oct. 9 104.0 101.6 3,010 163.0 210.0 15.0 21.29 2.09 23.38 -8.38 75.73 1,120 9.19 Oct. 10 103.6 101.6 3.030 163.0 212.0 15.0 23.67 2.09 26.76 —10.76 76.02 1,740 9.19 Oct. 11 103.0 101.0 3.014 479.0 71.0 14.9 20.12 1.89 22.01 —7.11 74.85 1,500 5.80 Oct. 12 102.8 101.6 3,018 480.0 71.0 15.0 17.77 1.89 19.66 —4.66 1,960 6.80 Oct. 13 102.4 100.6 3,014 479.0 71.0 14.9 18.77 1.89 20.66 -6.76 74.24 1,980 5.80 Oct. 14 103.0 100.0 3.046 173.0 212.0 14.2 18.21 1.28 19.49 —6.29 74.38 1,220 5.02 Oct. 15 102.2 98.6 2,670 130.0 187.0 U.7 18.61 1.28 19.89 -8.19 1,040 6.02 Oct. 16 101.0 99.4 3,068 168.0 212.0 16.4 21.04. 1,28 22.32 -6.92 1,010 5.02 Oct. 17 101.6 99.4 3,211 484.0 78.0 15.6 17.79 19.35* —3.76 73.10 1,120 Oct. 18 100.6 99.0 2,998 478.0 71.0 16.0 15.69 17.19 —2.19 1,100 Oct. 19 99.6 98.6 3,019 481.0 71.0 15.0 16.30 16.80 —1.80 1,220 Oct. 20 99.6 98.6 3,002 468.0 75.0 15.0 15.24 16.74 —1.74 72.82 1,880 Oct. 21 98.6 99.4 2,675 412.0 68.0 13.0 15.76t 1,610+ (?) Oct. 22 99.6 98.8 2,943 462.0 71.0 15.0 16.32 17.82 —2.82 1,480 Oct. 23 99.6 98.6 3,062 449.0 76.0 21.2 16.76 18.88 +2.32 1,230 Oct. 24 99.6 98.6 3,396 641.0 60.0 20.0 13.34 15.34 +4.66 72.86 1,640 Oct. 25 99.6 98.6 3,211 493.0 71.0 20.0 16.69 18.59 +1.41 1,120 Oct. 26 99.0 98.2 3,066 164.0 215.0 15.5 18.90 20.45 -4.96 1,320 Oct. 27 99.6 98.4 3,159 164.0 219.0 17.5 17.65 19.40 —1.90 2,280 Oct. 28 99.0 98.2 3,277 182.0 220.0 18.5 14.18 16.03 +2.47 73.69 1,220 t This is the total lor 19% hours. * Excreta nitrogen estimated as urine nitrogen + 10 per cent, of food nitrogen. TABLE 6. — Clinical D.^ta — (Continued) Richard T. Food Temperature Total Calories Carbo- hy- drate, Gm. Fat, Gm. N., Gm. N., Gm. N., Gm. N., Gm. Nitrogen Balance, Gm. Body Weight, Kg. Urine Volume, C.c. Feces Fat 1913 Max. Min. Oct. 17 103.6 101.4 1.666 248.0 38.0 11.3 13.95 0.84 14.79 —3.49 36.09 2,290 1.63 Oct. 18 104.2 100.8 1,143 115.0 49.0 8.4 12.48 0.84 13.32 —4.92 1,145 1.63 Oct. 19 103.2 10O.8 2,131 327.0 49.0 13.0 14.40 0.84 15.24 —2.24 1,720 1.63 Oct. 20 104.0 100.0 2,020 280.0 55.0 14.0 14.63 0.84 15.37 —1.37 1,005 1.63 Oct. 21 102.8 100.0 2,369 360.0 61.0 16.0 15.13 0.84 16.97 +0.03 1,320 1.63 Oct. 22 102.4 99.4 2,092 315.0 46.0 14.7 14.74 0.84 15.58 —0.88 35.57 1,200 1.63 Oct. 23 103.0 99.0 2,576 369.0 67.0 17.4 16.30 0.84 17.14 +0.26 35.70 1,670 1.63 Oct. 24 102.0 99.4 2,153 3S3.0 35.0 18.0 15.69 0.84 16.53 +1.47 1,340 1.63 Oct. 25 101.0 ' 98.4 2,619 228.0 125.0 16.0 16.32 0.84 17.16 —1.16 1,260 1.63 Oct. 26 100.6 99.0 2,093 115.0 133.0 15.0 16.53 * 18.03 —3.03 1,100 Oct. 27 100.2 98.6 2,163 121.0 136.0 15.7 16.34 17.91 —2.21 35.30 1,200 Oct. 28 99.6 98.6 2,009 124.0 117.0 16.0 16.47 18.07 —2.07 35.60 1,460 Oct. 29 100.0 98.6 3,276 348.0 157.0 15.2 14.01 16.53 —0.33 1,370 Oct. 30 100.0 99.0 2,969 302.0 144.0 15.1 11.77 13.28 +1.82 35.38 1,195 Oct; 31 101.6 99.2 2,954 310.0 142.0 15.6 12.05 13.60 - +1.90 1,420 Not. 1 102.0 10O.4 3,069 334.0 142.0 14.6 11.32 12.77 +1.73 36.08 1,320 Not. 2 10^.4 99.6 2,996 325.0 138.0 14.6 11.74 13.19 +1.31 1,900 Not. 3 101.0 99.6 2,984 316.0 140.0 15.1 11.99 , 13.60 +1.60 36.27 1,270 Not. 4 100.2 99.4 3,037 320.0 144.0 15.2 12.22 13.74 +1.46 36.42 1,560 ♦ Excreta nitrogen estimated as urine nitrogen + 10 per cent, of food nitrogen. TABLE 6. — Clinical Data — (^Continued) Edward B. Excreta nitrogen estimated as urine nitrogen -I- 10 per cent, ol food nitrogen. TABLE 6. — Clinical Data — {Continued) John K Esti- mated Heat Produc- tion per 24Hrs. Pood ' Date, 1914 Total Calories Carbo- hydrate, Gm. Fat, Gm. Pood N., Gm. Urine N., Gm. Excreta N., Gm.* Nitrogen Balance Gm. Weight, Kg. Volume, Co. Oct. 14 3,901 214.9 284.8 14.5 14.61 15.96 -1.46 56.29 1,180 Oct. 16 4,171 212.9 309.3 16.4 11.39 13.03 -1-3.4 1.415 Oct. 16 4,003 662.0 97.2 15.0 11.49 12.99 -f2.0 56.36 1,665(?) Oct. 17 1,561 236.3 43.8 7.28 8.65 9.37 —2.09 56.94 1,140 Oct. 18 2,976 94.5 236.9 15.0 11.08 12.68 —2.42 56.01 1,690 Oct. 19 4,217 111.0 • 362.1 13.9 16.17 17.56 —3.66 .56.98 2,230 Oct. 20 4,097 114.9 348.9 14.80 10.96 12.44 4-2.36 66.67 1.520 Oct. 21 3,686 518.9 114.7 16.20 9.17 10.69 -h4.51 57.21 1,250 Oct. 22 3,076 579.6 54.2 7.68 7.85 8.61 —0.93 56.60 1,170 Oct. 23 2,160 3,462 152.8 269.1 12.90 8.21 9.60 -1-3.40 65.76 835 Oct. 24 4,072 220.6 299.4 15.0 n.94 13.44 -fl.56 66.84 1,465 Oct. 25 4,114 220.9 303.1 16.1 11.20 12.70 4-2.40 66.73 1,615 Oct. 26 1,976 2,704 161.4 124.1 6.9 6.75 7.44 -^M 663 Oct. 27 1,982 3,844 109.1 334.5 11.1 8.61 9.72 -1-1.38 1,125 Oct. 28 4,056 223.4 295.7 15.2 8.19 9.71 -1-6.49 67.51 2,155 Oct. 29 4,185 314.8 266.7 16.5 8.70 10.35 4-6.15 57.46 1,960 Oct. 30 3,643 364.7 179.0 18.8 10.30 12.18 4-6.62 57.83 2.310 Oct 31 3,893 402.6 191.4 18.0 9.72 11.52 4-6.48 1.656 Nov. 1 4,394 455.7 218.4 19.3 11.05 12.98 4-6.32 68.63 2,450 Nov. 2 4,491 451.6 225.8 21.0 11.80 13.9 4-7.1 68.76 1,770 Nov. 3 4,836 491.9 244.6 21.2 12.20 14.32 4-6.88 59.52 2,406 Nov. 4 1,936 2,209 209.4 119.7 9.2 9.20 10.12 -0.92 979 Nov. 6 3,960 390.6 196.9 17.0 10.69 12.29 4-5.71 1,665 Nov. 6 2,117 1,907 219.6 85.9 8.0 10.96 11.76 —3.76 1,623 Nov. 7 1,006 101.2 49.8 5.05 12.13 12.63 —7.68 69.23 1.076 Nov. 8 398 64.0 11.8 1.08 10.34 10.44 —9.36 665 Nov. 9 617 94.8 20.0 1.68 11.26 11.42 -9.74 67.06 646 Nov. 10 2,632 1,103 104.3 51.2 6.0 14.72 15.32 —9.32 833 Nov. 11 1,646 96.0 84.2 9.7 16.73 17.70 —8.0 57.11 1,230 Nov. 12 2,196 166.9 119.3 10.7 14.79 16.8 —5.1 1,250 Date, 1913 Total Calories Carbohy- drate, Gm. Pat, Gm. Pood N., Gm. Urine N., Gm. Excreta N., Gm. Nitrogen Bal., Gm. Body Wt., Kg. Urine Vol., O.c. Dec. 16.... • 2,194 139.1 148.9 9.3 24.68 26.61 —16.21 63.81 1,152 Dec. 16.... 3,309 145.1 246.8 16.3 21.45 23.08 —6.78 63.55 1,180 Dec. 17.... 3,621 181.9 268.1 14.6 22.37 23.83 —9.23 63.27 3,110 Dec. 18.... 3,205 181.9 223.6 14.8 19.30 20.78 —6.98 63.35 3,040 Dec. 19.... 3,788 251.6 249.6 17.0 19.40 21.10 —4.10 63.05 8,230 Dec. 20 3,916 269.7 267.1 18.0 18.26 20.06 —2.06 62.37 3,460 Dec. 21.... 4,134 342.5 238.4 20.0 19.33 21.33 —1.33 63.04 4,285 Dec. 22.... 4,558 378.4 267.2 20.4 18.00 20.04 4-0.36 62.64 4,265 Dec. 23.... 4,838 393.9 286.8 22.0 17.93 22.13 -0.13 63.26 3,210 Dec. 24.... 4,450 373.1 259.1 19.9 18.78 20.77 —0.87 63.32 3,350 • Estimated heat production, 2,668 calories. 1 Ti TJ 1 _c 1 fl C3 MOO Bas nati lor riso (N s ay ot termi Used ompa ^ en s o S O ci C3 iH OS o ^ O o <1 M « p ^OT P Per Cent. Rise Above Patient's Own Basal Metab- olism OT «5 ■>w CM r-t i-- M t- lO 1 + (M + + 00 + 00 + O + as + Per Cent. Rise Above Normal Aver. Basal ol S4.7 Oal. per Sq. M. 28 ^ (H -1- ■+ + + + + -f 4- -f + + -1- + + it's 53Q-S IH H 00 ■^ rH -tl OT "> aa 9 S S S s s s S 8§ § I— 1 s § 03 O £ s 00 s is g g s 3 Indirect alorimetr Average per Hour S5 s g § g § 5: S S s 3 a s •§ s g ft s s 31 CO S ^ fe A ■ s s (rt S 00 UT- o ^ o . ia ri t^ o o «> ■5? CD a: •^ CO CO ■s« I-t T-i iH iH tH r-l iH tH r-l I-H iH r-t I-H iH T-i iH tH rH iH iH iH r-f tH iH o Aver- age Respir- atory Quo- tient K ;?^ S e -* S S QC f?. s ES S 00 ga s §8 CO CT> S OS e g S S SB '"' Aver- age Pulse Rate S s iH s s 00 S S S "tj< Ot S s ffl tn SR tD o: to s K g g S ""^ S!"39 o lO (N eo tH Ol tH t- OJ -* iH © o oa CO -* w (M Co O CI 00 Ol gM-SSo § OS Ol s ffi ss S a g g g g s CO s CO ^ o: M ss l> § g CO ■< SB ? » r, a> o CL t d p A d 2 P. A -3 ■*■ B 1 1 4^ « H y .^ a ^ a ^ ° m S 5 S S 8 a p< a i i i 3 C3 3 a 1=1 g +3 '^ '.S 8 £ t •a a 1 1 Ol e g p 1 03 w £.s .a 1 1 ^ 1 1 I !=) 3 i7 n el t: a E o □ > ■a a § -a i o C3 -a i3 'd OM o.S > n e g p 1 > i 03 5 a M O d i> Id ^1 p- CS 0. > a K C C c O O o o a M ^ ^ c C C C |i - 00 s S ^ H W F£ ^ C o " a oj o 3 s 4) bo i o 2o| !Z g ^ ^; 'bl bo bo . ^ bj 1 1 c 1 1 K rt 5 ffi f g 61 1 K i ■^ i *£ rt "o "c , a c m ( lO cr lO f: K « ( M w s w ^ (i p: K pa p: a n t: ft '-' PC Ih fC M ft P ft PC =; • ^ CD s f o i U2 o CV CO s 5- > r IT Ir- a If g <> ^ 1-1 a OB'S a CUWS,£3T3r^BfflS 1^ LO CO "* fH + + Si + a ••3'>:S, + : : + + la 00 + + Sol OogO ■SSao, CO c^ CO n I I I I •H CO + I I + I 1 + + rH(X)OC4m09O00IO + I 7 + I + T + 1 C4 91 I I + + w w Wl :^ V g 03 O QOQ S S fe o c t- p. o D to lO a) '^ Tl M lO m < P4 o P. a .s § _ ■a a a " a s s £; 0"^^ CD O O C3 > >> >> >. >> a a a a a a a s s a a a a a a a M h k ^ h o o o o o a a a d a 15 J a J « ffl 3 m n n n a a 40 ^ CO S a a A ^ a ►t> Ha N O n rH OS -* t- 5 CO CO + + + + s sa CO irt t- W OS Hi o CO CO c R + + + 1 + + 1 + -f + + + : + 4 + + + CO efi : ca c^ 1 + : 1 + Ci- e- QC if CC « 'i* \a in (N i> M in cs ^ 1 + : 1 1 I + 1 1 + + 1 1 1 1 1 1 I 3 % S s S 2 F s IT S 3 . S P g S in g s GO S S S s 5 S s IM ? s ss n SS ■^ 5! O ^ Si 5 s S -* oc ^- n o- C 0- l- t? M f^ S t i-i I- r- 1- <.. S S CO V< Ci" rH S S3 S s s S s § §3 § oc « § s e 53 ^ £ s ^ f: US QO O O- M '^ 0> 0» C4 ir IC LT J OS O iH OS O C^ in OS CD N c^ CO N ^ c S 2 : ^ i> c 1. f: 1, p. p. P. p, £? 9 S d i a E 1 1 ; i 1 i 1 a E w a. "5 5 ffit ntinued temper ntinued temper te steep curve < C > c i 11 1 o O t no c 1 1 ■^ 1 Ol > a > > P J a i!.^ O ra a S rt oi .. .. i i I.I. « - ?ass & a s •a a 1 ~i' 8 6^ H ^ fe N Hi ^ Ph Ph Ph a o : 1 O o ;^ :^ ;a o M "3 B til 1 03 1 fi ■5 "rt 15 rt rt * 'm a rt K « « rt us e cc o as o . (-3 cy Ph ^a ^a i ^c iz 2 1 ^ J - ^ s 146 CLINICAL CALORIMETRY amounts of heat. Therefore the law of the conservation of energy applies to fever patients. The rectal temperature does not always give an accurate indication of the average change in body temperature, and better results are often obtained by well covered surface thermometers. The basal heat production rises and falls in a curve roughly parallel with the temperature. At the height of the fever it averages about 40 per cent, above the normal but in some cases rises to more than 50 per cent, above the normal. The specific dynamic action of protein and carbohydrate is much smaller in the febrile period of typhoid than in health and in some cases seems to be absent. In convalescence it may be greater than normal. In a majority of cases a rise in temperature is accompanied by an increasing heat production and an increasing heat elimination. Typhoid patients can store body fat on an abundant diet while losing body weight and body protein. Loss in weight and loss of protein are usually though not necessarily parallel. There is a toxic destruction of protein in typhoid fever. This is shown by the fact that patients have a distinctly negative nitrogen balance on a diet which contains more than enough calories to cover the heat production. The writers wish to express their thanks to their associates, without whose assistance this work would have been impossible. The analyses of food and urine were made by Mr. Frank C. Gephart, with the assistance of Messrs. R. H. Harries, L. C. Mazzola and R. H. Stone ; all the electrical measurements in the calorimeter experiments were made by Mr. G. F. Soderstrom. We are indebted to Mr. R. H. Harries and Dr. A, L. Meyer for making the residual analyses of air in the calorimeter experiments and for making most of the calculations, and to Miss G. W. Sims for the painstaking work in checking all these calcu- lations. We are indebted to Miss Estelle Magill and to her assistants, especially Miss A. Honold and Miss M. M. Fauquier, for their skillful administration of the diets and for the collection of the specimens. We wish also to thank Miss M. Sawyer for her aid in the preparation of the charts. 477 First Avenue. CLINICAL CALORIMETRY EIGHTH PAPER ON THE DIABETIC RESPIRATORY QUOTIENT* GRAHAM LUSK NEW YORK The respiratory quotient, or the ratio of the volume of carbon dioxid expired to the volume of oxygen inspired, in the case of protein oxidation is stated by Loewy^ to be 0.801. This relation depends on the net result of the oxidation of the many amino-acids of which pro- tein is composed. It is apparent that when some of these amino-acids are converted into glucose which is eliminated in the urine, the respira- tory quotient for protein will not hold true. It has been shown^ that the carbon of glycocoll and alanin is completely converted into glucose in the diabetic organism, and that three of the carbon atoms which are contained in aspartic and glutamic acids are similarly convertible into glucose. Dakin^ states that prolin and arginin yield glucose comparable in quantity to that yielded by glutamic acid. According to this author cystin and serin also yield glucose. The reactions involving the conversion of amino-acids into sugar and urea may thus be written :* Glycocoll 6CH2NH2.COOH -I- 3CO2 + 3H..0 = 2CoH,=06 + 3CH.N.0 + 3O2 Alanin 2CH,,CHNH»C00H + CO. + H=0 — CsH^Oc -t- CH4N2O Aspartic Acid 2COOH.CH,.CHNH2.COOH -t- H=0 = CcHisO, -|- CH4N2O + CO2 Glutamic Acid 2COOH.CH2.CH2.CHNH2COOH + 30.= GHi^Oo + CH4N2O + 3CO2 + H2O Prolin 2CH=.CH,.CH2.CH.COOH -|- 50= = GHi^Oc + CH.N.O + 3CO2 -I- H2O Arginin 2NH2.C.NH.CH2.CH2.CH2.CHNH2COOH + 50= = CeHi^Oo + NH 4CH4N2O -I- 2CO2 Osborne and Jones' have reported an analysis of 100 grams of ox meat containing 16.18 per cent, of total nitrogen. This analysis will *From the Russell Sage Institute of Pathology, in Affiliation with the Sec- ond Medical Division of Bellevue Hospital, New York City. 1. Loewy: Handb. d. Biochem., 1911, iv. No. 1, 279. 2. Ringer and Lusk : Ztschr. f. physiol. Chem., 1910, Ixvi, 106. 3. Dakin : Jour. Biol. Chem., 1913, xiv, 321. 4. For more complete theoretical details consult: Lusk, Jour. Am. Chem. Soc, 1910, xxxii, 671 ; and Dakin and Dudley, Proc. Seventeenth Internat. Cong. Med., 1914, Sec. ii. Part H, 127. 5. Osborne and Jones : Am. Jour. Physiol., 1909, xxiv, 438. 148 CLINICAL CALORIMETRY be found below together with the respiratory quotients, both normal and diabetic, of the individual amino-acids. TABLE 1. — Analysis of 100 Grams Ox Meat with Respiratory Quotients In 100 Gm. Meat gm. Respiratory Quotient Normal Diabetic Glycocoll Alanin 2.06 3.72 0.81 11.65 5.82 3.15 4.51 15.49 ? 2.20 7.47 1.76 7.59 1.07 Present 1.00 0.83 0.75 0.73 0.82 0.87 1.17 1.00 6.89 0.73 0.90 0.71 0.87 * Valin Prolin 0.60 Phenylalanin Aspartic acid .... Glutamic acid Serin t 1.00 0.40 Histidin Lysin ... Ammonia Tryptophan Total 67.30 * R. Q. depressed below that of fat if glycocoll or alanin be ingested, t R. Q. increased above that of fat if aspartic acid be given. A glance at the above table shows how the respiratory quotient of 0.801 for protein is based on the sum of the results of the oxidation of many different substances, and also that the respiratory quotients usually tend to fall when certain of the' amino-acids are converted into sugar. A clear idea of this fall in the respiratory quotient can only be obtained if the respiratory metabolism of those amino-acids which are convertible into glucose is contrasted, the normal with the diabetic condition. It will be noted in the foregoing table that only 67 per cent, of the ox protein was recovered as amino-acids. This is explained by the deficiency in the method; for Osborne and Jones^ have analyzed a specially prepared mixture containing known quantities of a large number of amino-acids and have recovered only 66 per cent, of the substances present. As regards those amino-acids which are con- vertible into glucose, the following percentages were recovered from the mixture: Alanin, 46 per cent., prolin 72 per cent., aspartic acid, 42.5 per cent., glutamic acid 69 per cent., arginin 65 per cent. If one assumes that the quantity of glycocoll is at least double that found. 6. Osborne and Jones; Am, Jour. Physiol., 1910, xxvi, 325. GRAHAM LUSK 149 one arrives at values from which one may compute the quantity of sugar which should in theory arise from these acids. This appears in Table 2. Since the 100 gm. of the ox muscle analyzed contained 16.18 gm. of nitrogen, the D:N equals 2.75:1. TABLE 2. — Calculation Showing the Origin of Glucose from Protein Substance Osborne Recalculated , Glucose GlycocoU 2.06 3.72 4.51 15.49 5.82 7.47 4.0 8.1 10.6 22.3 8.0 11.5 64.5 32 Alanin 82 Aspartic acid Glutamic acid Prolin 7.2 13.6 63 Arginin 59 44.4 TABLE 3. — Respiratory Exchange in the Normal and Diabetic Condition of Six Amino-Acids, AS THEY are CONTAINED IN 100 Gm. OF Ox MeAT, AND WHICH ARE CONVERTIBLE INTO 44.4 Gm. of Glucose, D : N = 2.75 Grams Normal Diabetic Oxygen gm. Carbon Dioxid gm. Oxygen Carbon Dioxid Substance Absorbed gm. Elimin- ated in Reaction gm. Absorbed in_ Reaction gm. Elimin- ated gm. GlycocoU . . . Alanin Aspartic acid Glutamic acid Prolin Arginin 4.0 8.1 10.6 22.3 8.0 ll.S 64.5 2.56 8.75 7.65 21.85 12.25 11.63 64.69 3.52 10.01 12.27 30.04 13.77 11.63 81.24 'o'.o' 0.0 7.30 5.57 5.32 18.19 0.85 17.34 0.85 0.85 1.17 2.00 3.17 1.75 10.03 4.59 2.91 19.28 3.17 16.11 R. Q. 0.915 0.675 When the D :N ratio is 3.65, 59 gm. of glucose, or 14.6 gm. more than the quantity above estimated, are eliminated in the urine when 100 gm. of protein are destroyed. These 14.6 gm. represent an additional amount of glucose whose origin is unexplained and which is equal to 24 per cent, of the total maximal production. Such sources of sugar might be cystin, which if all the sulphur in protein were in that form ISO CLINICAL CALORIMETRY might at most yield 2 gm. of glucose and serin whose solubility has prevented any accuracy of determination. Having determined the approximate quantities of the various sugar yielding amino-acids, one may now compute the difference between their oxidation normally and in the diabetic. This is shown in Table 3. This table signifies that when glycocoll, alanin, aspartic acid, glu- tamic acid, prolin and arginin, together aggregating nearly two-thirds by weight of the protein complex, are oxidized in the normal organism in the proportion in which they may exist in meat, the respiratory quo- tient is 0.915, whereas if 44.4 gm. of glucose is formed from them the respiratory quotient sinks to only 0.675. Of those amino-acids which do not yield glucose, three, valin, leucin and lysin, which together aggregate 20 gm. according to Osborne's (uncorrected) analysis of 100 gm. of meat, have respiratory quotients of 0.75, 0.73 and 0.71, respectively, whereas three others, phenylalanin, tyrosin and histidin, together amount- ing to only 7.1 gm., yield respiratory quotients of 0.87, 0.89 and 0.90. Furthermore, the 1.07 gm. of ammonia liberated would tend to reduce the quotient through urea formation. It is therefore obvious that the respiratory quotient for protein in diabetes is made up pre- dominately of the oxidation of the remnants of the sugar forming amino-acids and from the oxidation of other amino-acids having in the main respiratory quotients of 0.75 to 0.71. As actually calculated, the above named mixture of non-sugar producing amino-acids would yield 48.25 gm. of COa and require 45.86 gm. of oxygen for oxidation, showing a respiratory quotient of 0.76. The aggregate quotient of the non-sugar forming amino-acids as . set forth above may be indirectly obtained by deducting the estimated respiratory exchange of the sugar-forming amino-acids from that of the total involved in the normal oxidation of 100 gm. of ox protein, as shown in Table 4. TABLE 4. — Aggregate Quotient of Non-Sugar Forming Amino-Acids Carbon Oxyen Dioxid Resp. gm. gm. Quot. Normal oxidation of 100 grams of beef protein 138.18 152.17 0.801 Estimated oxidation of the sugar forming amino-acids 64.69 81.24 0.915 73.49 70.93 Add CO. for urea formation from 1.07 gm. NHa 1.39 Estimated oxidation of non-sugar forming amino-acids 73.49 72.32 0.716 Although the last respiratory quotient 0.716 closely approximates that of leucin (0.73) and lysin (0.71), the dominant non-sugar forming amino-acids, it is evident that the influence of the other non-sugar GRAHAM LUSK 151 forming amino-acids would tend to raise the quotient to a higher level, to 0.76 in the before mentioned calculation. Therefore, the present figures can only be regarded as an attempted solution of the problem lather than as a precise analysis. When the mixture of six sugar-forming amino-acids, aggregating 64.5 gm., is normally oxidized 02 = 64.69 gm. and C02 = 81.24 gm. and when it is converted into 44.4 gm. of glucose 02=17.34 gm. and C02= 16.11 gm. the difference between these two sets of figures will represent the quantities of respiratory gases which would not be involved in the respiratory exchange in diabetes and would amount to 02 = 47.35 gm. and 00^ = 65.13 gm. If one takes the grams of respired gases in the normal combustion of 100 grams of protein as given by Loewy, and deducts from these the quantity not eliminated according to the above computation, one arrives at the following results for the diabetic respiratory quotient: TABLE 5. — Protein Respiratory Quotient with D : N = 2.75 Carbon Oxygen Dioxid gm. gm. Normal oxidation 100 grams beef protein 138.18 152.17 Deduct for intermediary production of 44.4 grams of glucose 47.35 65.13 90.83 87.04 R. Q. = 0.697. Proceeding now to the consideration of the cases of diabetes in which the D:N is 3.65, calculations have been made the relations of which may be thus presented : TABLE 6. — Protein Respiratory Quotient with D : N = 3.65 (1). Normal oxidation of 100 grams of beef protein. Deduction, if 16.28 grams N X 3.65 = 59.41 glucose. Carbon Oxygen Dioxid gm. gm. 138.18 152.17 63.38 87.15 74.80 65.02 R. Q. = 0.632. The respiratory quotient for fat is 0.707, and since fat forms the main recourse of the diabetic, the respiratory quotient will be found nearer to that of fat than to 0.632 for protein. Thus, in a diabetic dog with a D :N ratio of 3.54 in which 23 per cent, of the total heat production was derived from protein and 77 per cent, from fat, the 152 CLINICAL CALORIMETRY respiratory quotient was 0.687, the non-protein respiratory quotient being 0.704, which closely approximates that of fat. In the case of a diabetic patient with a low protein metabolism whose urinary D :N was 3.6, Du Bois has found during a three hour period a respiratory quotient of 0.697. In another diabetic man with approximately the same D :N ratio but whose protein metabolism was higher (13 per cent, of the total energy) the R. Q. was 0.691. Magnus-Levy' has called attention to a possible reduction in the respiratory quotient when beta-oxybutyric acid is formed from fat. He estimates that the maximal quantity of beta-oxybutyric acid deriv- able from 100 gm. of fat is 36 gm. Under these circumstances, the respiratory quotient for fat would be reduced from 0.707 to 0.669. The case is not so simple, however, for if the 36 gm. of acid formed neutralized sodium bicarbonate, 15.23 gm. of carbon dioxid would be eliminated. These relations are shown in Table 7: TABLE 7. — Theoretical Respiratory Quotient with Beta-Oxybutyric Acid Formed from Fat Oxygen Carbon Dioxid Liters Liters R. Q. 100 gm. fat 201.9 142.73 0.707 36 gm. beta-oxybutyric acid 34.8S 30.96 0.889 167.05 111.77 0.669 Add for 15.23 gm. CO2 from NaHCOs 7.74 Possible end result 167.05 119.51 0.715 Since other bases than sodium bicarbonate may be used for the neutralization of beta-oxybutyric acid, it is apparent that the exact determination of the theoretical respiratory quotient when this acid is produced in large amounts in human diabetes is at present impos- sible. This discussion has been prepared in order to further the under- standing of a forthcoming description of metabolism in diabetes mel- litus. 7. Magnus-Levy: Ztschr. f. Win. Med., 1905, Ivi, 83.